FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Singh, A
Corcoran, P
Thomas, M
Lewis, B
Ayares, D
Reimann, K
Horvath, K
Mohiuddin, M
AF Singh, A.
Corcoran, P.
Thomas, M.
Lewis, B.
Ayares, D.
Reimann, K.
Horvath, K.
Mohiuddin, M.
TI Costimulation Blockade With Anti CD40 Antibody Maintains CD4+and Treg
Cell Numbers in Pig To Baboon Cardiac Transplantation Model.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Singh, A.; Corcoran, P.; Horvath, K.; Mohiuddin, M.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Thomas, M.; Lewis, B.] NIH, Bethesda, MD 20892 USA.
[Ayares, D.] Revivicor Inc, Blacksburgh, VA USA.
[Reimann, K.] Mass Biol, Bethesda, MD USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA 1424
BP 30
EP 30
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033300097
ER
PT J
AU Wood, S
Feng, J
He, S
Marquez, V
Bishop, D
Zhang, Y
AF Wood, S.
Feng, J.
He, S.
Marquez, V.
Bishop, D.
Zhang, Y.
TI Inhibition of Histone Methylation Induces Long-Term Survival of
Vascularized Cardiac Allografts and Preserves the Third-Party T Cell
Immunity.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Wood, S.; Feng, J.; Bishop, D.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
[He, S.; Zhang, Y.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Marquez, V.] NIH, Biol Chem Lab, Ctr Canc Res, Frederick, 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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA 2109
BP 35
EP 35
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033300114
ER
PT J
AU Randhawa, P
Pastrana, D
Zeng, G
Berger, M
Hariharan, S
Ron, S
Buck, C
AF Randhawa, P.
Pastrana, D.
Zeng, G.
Berger, M.
Hariharan, S.
Ron, S.
Buck, C.
TI Neutralizing Antibodies For Polyomavirus BK (BKV) in Intravenous
Immunoglobulins: Pre-Clinical Studies.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Randhawa, P.; Zeng, G.; Hariharan, S.; Ron, S.] Univ Pittsburgh, Pittsburgh, PA USA.
[Pastrana, D.; Buck, C.] NCI, Lab Cellular Oncol, Bethesda, MD 20892 USA.
[Berger, M.] CSL Behring, Immunol R&D, King Of Prussia, PA 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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA 727
BP 85
EP 85
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033300263
ER
PT J
AU Nickerson, P
Wiebe, C
Formica, R
Tinckam, K
Poggio, E
Bunnapradist, S
Gibson, I
Rush, D
Samaniego, M
Gaber, O
Ilke, D
Bridges, N
Fairchild, R
Hricik, D
Heeger, P
AF Nickerson, P.
Wiebe, C.
Formica, R.
Tinckam, K.
Poggio, E.
Bunnapradist, S.
Gibson, I.
Rush, D.
Samaniego, M.
Gaber, O.
Ilke, D.
Bridges, N.
Fairchild, R.
Hricik, D.
Heeger, P.
TI Epitope Mismatch Predicts De Novo DSA After CNI Withdrawal in Low-Risk
Kidney Transplant Recipients.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Nickerson, P.; Wiebe, C.; Gibson, I.; Rush, D.] UM, Winnipeg, MB, Canada.
[Formica, R.] Yale, New Haven, CT USA.
[Tinckam, K.] UHN, Toronto, ON, Canada.
[Poggio, E.; Fairchild, R.] Cleveland Clin, Cleveland, OH 44106 USA.
[Bunnapradist, S.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Samaniego, M.] UoM, Ann Arbor, MI USA.
[Gaber, O.] MTC, Houston, TX USA.
[Ilke, D.] Rho, Chapel Hill, NC USA.
[Bridges, N.] NIH, Bethesda, MD 20892 USA.
[Hricik, D.] UHCMC, Cleveland, OH USA.
[Heeger, P.] MSSM, New York, NY USA.
NR 0
TC 0
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA 2888
BP 137
EP 137
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033300423
ER
PT J
AU Olthoff, K
Chang, B
Christie, J
Levitsky, J
Emond, J
Bridges, N
Sledge, T
Shaked, A
AF Olthoff, K.
Chang, B.
Christie, J.
Levitsky, J.
Emond, J.
Bridges, N.
Sledge, T.
Shaked, A.
TI Immediate Post-Reperfusion PBL Activation Associated With Liver Early
Allograft Dysfunction (EAD).
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Olthoff, K.; Chang, B.; Christie, J.; Shaked, A.] Univ Penn, Philadelphia, PA 19104 USA.
[Levitsky, J.] Northwestern Univ, Chicago, IL 60611 USA.
[Emond, J.] Columbia Univ, New York, NY USA.
[Bridges, N.; Sledge, T.] NIDDK, 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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA 1332
BP 224
EP 224
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033301012
ER
PT J
AU Formica, R
Nickerson, P
Poggio, E
Tinckam, K
Rush, D
Gibson, I
Fairchild, R
Bridges, N
Ikle, D
Samaniego, M
Graber, O
Bunnapradist, S
Armstrong, B
Heeger, P
Hricik, D
AF Formica, R.
Nickerson, P.
Poggio, E.
Tinckam, K.
Rush, D.
Gibson, I.
Fairchild, R.
Bridges, N.
Ikle, D.
Samaniego, M.
Graber, O.
Bunnapradist, S.
Armstrong, B.
Heeger, P.
Hricik, D.
TI Immune Monitoring and Tacrolimus (Tac) Withdrawal in Low Risk Recipients
of Kidney Transplants - Results of CTOT09.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Formica, R.] Yale Univ, New Haven, CT USA.
[Nickerson, P.; Rush, D.; Gibson, I.] UM, Winnipeg, MB, Canada.
[Poggio, E.; Fairchild, R.] Cleveland Clin, Cleveland, OH USA.
[Tinckam, K.] UHN, Toronto, ON, Canada.
[Bridges, N.] NIH, Bethesda, MD 20892 USA.
[Ikle, D.; Armstrong, B.] Rho, Chapel Hill, NC USA.
[Samaniego, M.] UoM, Ann Arbor, MI USA.
[Graber, O.] MTC, Houston, TX USA.
[Bunnapradist, S.] Univ Calif Los Angeles, Los Angeles, CA USA.
MSSM, New York, NY USA.
[Heeger, P.] UHCMC, Cleveland, OH USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA 1436
BP 225
EP 225
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033301018
ER
PT J
AU Arron, S
Yankis, E
Raymond, A
McCulloch, C
Engels, E
AF Arron, S.
Yankis, E.
Raymond, A.
McCulloch, C.
Engels, E.
TI Increased Mortality in Transplant Recipients With a History of
Pretransplant Melanoma
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Arron, S.; Raymond, A.; McCulloch, C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Yankis, E.; Engels, E.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA A529
BP 240
EP 240
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033301067
ER
PT J
AU Kalil, R
Lynch, C
Engels, E
AF Kalil, R.
Lynch, C.
Engels, E.
TI Risk of Cancer in Kidney Retransplants Compared To Primary Kidney
Transplants in The Transplant Cancer Match Study
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Kalil, R.; Lynch, C.] Univ Iowa, Iowa City, IA USA.
[Engels, E.] NCI, 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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA A528
BP 240
EP 240
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033301066
ER
PT J
AU Yanik, E
Snyder, J
Clarke, C
Engels, E
AF Yanik, E.
Snyder, J.
Clarke, C.
Engels, E.
TI Cancer Risk Patterns Among End Stage Renal Disease Patients During
Intervals of Kidney Transplant Function and Non-Function
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Yanik, E.] NCI, Rockville, MD USA.
[Snyder, J.] Univ Minnesota, Minneapolis, MN USA.
[Clarke, C.] Canc Prevent Inst Calif, Fremont, CA 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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA A532
BP 241
EP 242
PG 2
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033301070
ER
PT J
AU Yanik, E
Gustafson, S
Kasiske, B
Israni, A
Snyder, J
Engels, E
Segev, D
AF Yanik, E.
Gustafson, S.
Kasiske, B.
Israni, A.
Snyder, J.
Engels, E.
Segev, D.
TI Sirolimus Use and Cancer Incidence Among U. S. Kidney Transplant
Recipients
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Yanik, E.; Engels, E.] NCI, Rockville, MD USA.
[Gustafson, S.; Kasiske, B.; Israni, A.; Snyder, J.] Sci Registry Transplant Recipients, Minneapolis, MN USA.
[Segev, D.] Johns Hopkins Univ, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA A534
BP 242
EP 242
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033301072
ER
PT J
AU Putheti, P
Ding, R
Naqvi, R
Medeiros, M
Sharma, V
Kuchibhotla, S
LeBeau, P
Ikle, D
Muthukumar, T
Dadhania, D
Myers, K
Ingelfinger, J
McDonald, R
Liu, J
Spaneas, L
Williams, N
Bridges, N
Harmon, W
Suthanthiran, M
Strom, T
AF Putheti, P.
Ding, R.
Naqvi, R.
Medeiros, M.
Sharma, V.
Kuchibhotla, S.
LeBeau, P.
Ikle, D.
Muthukumar, T.
Dadhania, D.
Myers, K.
Ingelfinger, J.
McDonald, R.
Liu, J.
Spaneas, L.
Williams, N.
Bridges, N.
Harmon, W.
Suthanthiran, M.
Strom, T.
TI Gene-Expression Profiles of Peripheral Blood Cells and of Allograft
Biopsies Are Associated With Acute Rejection in Pediatric Renal
Allograft Recipients
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Putheti, P.; Kuchibhotla, S.; Ingelfinger, J.; Spaneas, L.; Harmon, W.; Strom, T.] HMS, Boston, MA USA.
[Ding, R.; Naqvi, R.; Medeiros, M.; Sharma, V.; Muthukumar, T.; Dadhania, D.; Suthanthiran, M.] WCMC, New York, NY USA.
[LeBeau, P.; Ikle, D.] Rho, Chapel Hill, NC USA.
[Liu, J.] PPD, Morrisville, NC USA.
[Williams, N.; Bridges, N.] NIAID, Bethesda, MD 20892 USA.
[Myers, K.] CHOP UPenn, Philadelphia, PA USA.
[McDonald, R.] Seattle Childrens UW, Seattle, WA USA.
RI Medeiros, Mara/B-9230-2015
OI Medeiros, Mara/0000-0002-6848-8933
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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA C1528
BP 324
EP 324
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033301383
ER
PT J
AU Li, Z
Xu, X
Feng, X
Farber, J
Young, N
Murphy, P
AF Li, Z.
Xu, X.
Feng, X.
Farber, J.
Young, N.
Murphy, P.
TI Clodronate-Induced Macrophage Depletion of Mice Receiving Bone Marrow
Allotransplantation Enhances Hematopoietic Chimerism and Donor-Specific
Skin Allograft Tolerance
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Li, Z.; Xu, X.; Farber, J.; Murphy, P.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Feng, X.; Young, N.] NHLBI, Hematol Branch, 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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA D2770
BP 395
EP 395
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033301647
ER
PT J
AU Mohiuddin, M
Singh, A
Corcoran, P
Hoyt, R
Thomas, M
Eckhaus, M
Lewis, B
Clark, T
Phelps, C
Ayares, D
Reimann, K
Horvath, K
AF Mohiuddin, M.
Singh, A.
Corcoran, P.
Hoyt, R.
Thomas, M.
Eckhaus, M.
Lewis, B.
Clark, T.
Phelps, C.
Ayares, D.
Reimann, K.
Horvath, K.
TI Long Term GalKO.hCD46. hTBM Pig Cardiac Xenograft Survival in Baboon May
Be Dependent On Dose and Duration of Anti CD40 (2C10R4) Antibody.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Mohiuddin, M.; Singh, A.; Corcoran, P.; Horvath, K.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Hoyt, R.; Thomas, M.; Eckhaus, M.; Lewis, B.; Clark, T.] NIH, Bethesda, MD 20892 USA.
[Phelps, C.; Ayares, D.] Revivicor Inc, Blacksburgh, VA USA.
[Reimann, K.] Mass Biol, Boston, MA USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA D2844
BP 415
EP 415
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033301721
ER
PT J
AU Mohiuddin, M
Singh, A
Corcoran, P
Hoyt, R
Thomas, M
Lewis, B
Clark, T
Klymiuk, N
Wolf, E
Reimann, K
Ayares, D
Horvath, K
AF Mohiuddin, M.
Singh, A.
Corcoran, P.
Hoyt, R.
Thomas, M.
Lewis, B.
Clark, T.
Klymiuk, N.
Wolf, E.
Reimann, K.
Ayares, D.
Horvath, K.
TI Normal Histology and Contractility of a Cardiac Xenograft For 450+Days:
A Case Report.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Mohiuddin, M.; Singh, A.; Corcoran, P.; Horvath, K.] NHLBI, Cardiathorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Hoyt, R.; Thomas, M.; Lewis, B.; Clark, T.] NIH, Bethesda, MD 20892 USA.
[Ayares, D.] Revivicor Inc, Blacksburg, VA USA.
[Reimann, K.] Mass Biol, Boston, MA USA.
[Klymiuk, N.; Wolf, E.] LMU, Munich, Germany.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA D2848
BP 416
EP 416
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033301725
ER
PT J
AU Daly, K
Starling, R
Armstrong, B
Ikle, D
Bridges, N
Chandraker, A
Sayegh, M
Stehlik, J
Heeger, P
Briscoe, D
AF Daly, K.
Starling, R.
Armstrong, B.
Ikle, D.
Bridges, N.
Chandraker, A.
Sayegh, M.
Stehlik, J.
Heeger, P.
Briscoe, D.
TI Changes in Plasma Levels of VEGF-C and Endothelin-1 During the First
Post-Transplant Year Are Predictive of Cardiac Allograft Vasculopathy:
Results From the CTOT-05 Study.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Daly, K.; Briscoe, D.] Boston Childrens Hosp, Boston, MA USA.
[Starling, R.] Cleveland Clin, Cleveland, OH 44106 USA.
[Armstrong, B.; Ikle, D.] Rho, Chapel Hill, NC USA.
[Bridges, N.] NIH, Bethesda, MD 20892 USA.
[Chandraker, A.; Sayegh, M.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Stehlik, J.] Univ Utah, Salt Lake City, UT USA.
[Heeger, P.] Mt Sinai Sch Med, New York, NY USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA A23
BP 878
EP 878
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033304023
ER
PT J
AU Hricik, D
Augustine, J
Poggio, E
Fairchild, R
Nickerson, P
Rush, D
Gibson, I
Formica, R
Goebel, J
Newell, K
Spain, K
Ikle, D
Bridges, N
Heeger, P
AF Hricik, D.
Augustine, J.
Poggio, E.
Fairchild, R.
Nickerson, P.
Rush, D.
Gibson, I.
Formica, R.
Goebel, J.
Newell, K.
Spain, K.
Ikle, D.
Bridges, N.
Heeger, P.
TI Rabbit ATG Induction Overcomes the Negative Influence of Pretransplant
Memory T Cells On Posttransplant GFR: Results From the CTOT01 Kidney
Transplant Trial
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Hricik, D.; Augustine, J.] UH Case Med Ctr, Cleveland, OH USA.
[Poggio, E.; Fairchild, R.] Cleveland Clin, Cleveland, OH 44106 USA.
[Nickerson, P.; Rush, D.; Gibson, I.] Univ Manitoba, Winnipeg, MB, Canada.
[Formica, R.] Yale Univ, New Haven, CT USA.
[Goebel, J.] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Newell, K.] Emory Univ, Atlanta, GA 30322 USA.
[Spain, K.; Ikle, D.] Rho, Chapel Hill, NC USA.
[Bridges, N.] NIAID, NIH, Bethesda, MD 20892 USA.
[Heeger, P.] Mt Sinai Sch Med, New York, NY 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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA B775
BP 892
EP 893
PG 2
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033304077
ER
PT J
AU Chang, B
Christie, J
Olthoff, K
Emond, J
Levitsky, J
Bridges, N
Sledge, T
Ikle, D
Shaked, A
AF Chang, B.
Christie, J.
Olthoff, K.
Emond, J.
Levitsky, J.
Bridges, N.
Sledge, T.
Ikle, D.
Shaked, A.
TI Dynamic Inflammatory Gene Expression Profiles Among Patients With and
Without Acute Cellular Rejection (ACR) During the First Post- Transplant
Year.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Chang, B.; Christie, J.; Olthoff, K.; Shaked, A.] Univ Penn, Philadelphia, PA 19104 USA.
[Emond, J.] Columbia Univ, New York, NY USA.
[Levitsky, J.] Northwestern Univ, Chicago, IL 60611 USA.
[Bridges, N.; Sledge, T.] NIDDK, Bethesda, MD 20892 USA.
[Ikle, D.] RhoFed, Chapel Hill, NC 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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA D2345
BP 901
EP 902
PG 2
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033304110
ER
PT J
AU Shaked, O
Chang, B
Tobias, J
Demetris, A
Suthanthiran, M
Feng, S
Punch, J
Reyes, J
Levitsky, J
Klintmalm, G
Zimmerman, M
DesMarais, M
Kopeskie, H
Priore, A
Morrison, Y
Bridges, N
Sayre, P
Shaked, A
AF Shaked, O.
Chang, B.
Tobias, J.
Demetris, A.
Suthanthiran, M.
Feng, S.
Punch, J.
Reyes, J.
Levitsky, J.
Klintmalm, G.
Zimmerman, M.
DesMarais, M.
Kopeskie, H.
Priore, A.
Morrison, Y.
Bridges, N.
Sayre, P.
Shaked, A.
TI Whole Blood mRNA to Detect Hepatic Inflammation and Fibrosis in
Post-Liver Transplant Patients With HCV.
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT World Transplant Congress
CY JUL 26-31, 2014
CL San Francisco, CA
C1 [Shaked, O.; Chang, B.; Tobias, J.; Shaked, A.] UPenn, Philadelphia, PA USA.
[Demetris, A.] UPMC, Pittsburgh, PA USA.
[Suthanthiran, M.] Cornell, New York, NY USA.
[Feng, S.; DesMarais, M.; Sayre, P.] UCSF, San Francisco, CA USA.
[Punch, J.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Reyes, J.] Univ Wisconsin, Madison, WI 53706 USA.
[Levitsky, J.] Northwestern Univ, Chicago, IL 60611 USA.
[Klintmalm, G.] Baylor Univ, Dallas, TX USA.
[Zimmerman, M.] Univ Colorado, Denver, CO 80202 USA.
[Priore, A.; Morrison, Y.; Bridges, N.] NIAID, Bethesda, MD 20892 USA.
[Kopeskie, H.] RhoFed, Chapel Hill, NC 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 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
SU 3
MA D2356
BP 905
EP 905
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ9LU
UT WOS:000338033304121
ER
PT J
AU Bradley, MC
Motterlini, N
Padmanabhan, S
Cahir, C
Williams, T
Fahey, T
Hughes, CM
AF Bradley, Marie C.
Motterlini, Nicola
Padmanabhan, Shivani
Cahir, Caitriona
Williams, Tim
Fahey, Tom
Hughes, Carmel M.
TI Potentially inappropriate prescribing among older people in the United
Kingdom
SO BMC GERIATRICS
LA English
DT Article
DE Potentially inappropriate prescribing; Older people; Screening tool of
older persons potentially inappropriate Prescriptions (STOPP); CPRD
ID ADVERSE DRUG EVENTS; PROTON PUMP INHIBITORS; STOPP SCREENING TOOL;
MEDICATION USE; BEERS CRITERIA; PRIMARY-CARE; PERSONS PRESCRIPTIONS;
PRIMARY PREVENTION; CONSENSUS PANEL; ELDERLY-PEOPLE
AB Background: Potentially inappropriate prescribing (PIP) in older people is associated with increases in morbidity, hospitalisation and mortality. The objective of this study was to estimate the prevalence of and factors associated with PIP, among those aged >= 70 years, in the United Kingdom, using a comprehensive set of prescribing indicators and comparing these to estimates obtained from a truncated set of the same indicators.
Methods: A retrospective cross-sectional study was carried out in the UK Clinical Practice Research Datalink (CPRD), in 2007. Participants included those aged >= 70 years, in CPRD. Fifty-two PIP indicators from the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria were applied to data on prescribed drugs and clinical diagnoses. Overall prevalence of PIP and prevalence according to individual STOPP criteria were estimated. The relationship between PIP and polypharmacy (>= 4 medications), comorbidity, age, and gender was examined. A truncated, subset of 28 STOPP criteria that were used in two previous studies, were further applied to the data to facilitate comparison.
Results: Using 52 indicators, the overall prevalence of PIP in the study population (n = 1,019,491) was 29%. The most common examples of PIP were therapeutic duplication (11.9%), followed by use of aspirin with no indication (11.3%) and inappropriate use of proton pump inhibitors (PPIs) (3.7%). PIP was strongly associated with polypharmacy (Odds Ratio 18.2, 95% Confidence Intervals, 18.0-18.4, P < 0.05). PIP was more common in those aged 70-74 years vs. 85 years or more and in males. Application of the smaller subset of the STOPP criteria resulted in a lower PIP prevalence at 14.9% (95% CIs 14.8-14.9%) (n = 151,598). The most common PIP issues identified with this subset were use of PPIs at maximum dose for > 8 weeks, NSAIDs for > 3 months, and use of long-term neuroleptics.
Conclusions: PIP was prevalent in the UK and increased with polypharmacy. Application of the comprehensive set of STOPP criteria allowed more accurate estimation of PIP compared to the subset of criteria used in previous studies. These findings may provide a focus for targeted interventions to reduce PIP.
C1 [Hughes, Carmel M.] NCI, Clin & Translat Epidemiol Branch, Rockville, MD 20850 USA.
[Motterlini, Nicola; Fahey, Tom] Royal Coll Surgeons Ireland, Dept Gen Practice, HRB Ctr Primary Care Res, Dublin 2, Ireland.
[Cahir, Caitriona] Univ Dublin Trinity Coll, Dept Pharmacol & Therapeut, Dublin 2, Ireland.
[Padmanabhan, Shivani; Williams, Tim] Med & Healthcare Prod Regulatory Agcy, London, England.
[Bradley, Marie C.] NCI, Clin & Translat Epidemiol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
RP Bradley, MC (reprint author), NCI, Clin & Translat Epidemiol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,4E320, Rockville, MD 20850 USA.
EM marie.bradley@nih.gov
RI Fahey, Tom/C-9367-2012; CPRD, CPRD/B-9594-2017;
OI Fahey, Tom/0000-0002-5896-5783; Cahir, Caitriona/0000-0002-7137-5737
FU Health Research Board, Ireland [HRC-2007-1]
FX The Health Research Board, Ireland, provided financial support for this
study: grant reference HRC-2007-1.
NR 46
TC 23
Z9 24
U1 2
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2318
J9 BMC GERIATR
JI BMC Geriatr.
PD JUN 1
PY 2014
VL 14
AR 72
DI 10.1186/1471-2318-14-72
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AK9KT
UT WOS:000338746700001
PM 24919523
ER
PT J
AU Ma, XF
Adelstein, RS
AF Ma, Xuefei
Adelstein, Robert S.
TI A Point Mutation in Myh10 Causes Major Defects in Heart Development and
Body Wall Closure
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE apoptosis; cell adhesion; double outlet right ventricle; ectopia cordis;
hernia, diaphragmatic; nonmuscle myosin type IIA
ID NONMUSCLE MYOSIN-II; PROXIMAL OUTFLOW TRACT; HEAVY-CHAIN GENE;
CLEFT-LIP; CELL-ADHESION; MYH9-RELATED DISEASE; DOWN-REGULATION;
LIGHT-CHAIN; ROCK-I; PALATE
AB Background-The 3 isoforms of nonmuscle myosin (NM) II (NMII-A, NMII-B, and NMII-C) play various roles during mouse embryonic development. Previous work, using knockout and hypomorphic mice, showed that Myh10 encoding myosin heavy chain II-B is critical for cardiac and brain development. Ablating or decreasing NMII-B by 80% results in cardiac (ventricular septal defect, double outlet of the right ventricle) and brain defects but not midline fusion defects. Neither NMII-A nor II-C seems to play roles in early myocardial development.
Methods and Results-We had previously generated point mutant knock-in mice and now report novel findings as a result of expressing motor-deficient NMII-B at wild-type levels. Homozygous mice die at embryonic day 14.5 in cardiac failure, exhibiting abnormalities not seen in NMII-B null and hypomorphic mice: a failure in midline fusion resulting in a cleft palate, ectopia cordis, and a large omphalocele. Fusion of the sternum and endocardial cushions is impaired in the mutant mice associated with a failure in apoptosis of the mesenchymal cells. Failure to disassemble myocyte cell-cell adhesions during cardiac outflow tract development contributes to impaired outflow tract myocardialization and displacement of the aorta to the right ventricle.
Conclusions-Expression of motor-impaired NMII-B disrupts normal ventral body wall closure because of a dominant-negative effect. This is not because of the loss of NMII-B function but rather a gain-of-function resulting from prolonged cross-linking of NMII-B to actin filaments, thereby interfering with the dynamics of actomyosin cytoskeletal structure. Furthermore, impaired NMII-B motor activity inhibits outflow tract myocardialization, leading to mislocalization of the aorta.
C1 [Ma, Xuefei; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Ma, XF (reprint author), NIH, Bldg 10,Room 6C-104,10 Ctr Dr,MSC 1583, Bethesda, MD 20892 USA.
EM MaX@nhlbi.nih.gov
OI Adelstein, Robert/0000-0002-8683-2144
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute
FX This research was supported by the Division of Intramural Research,
National Heart, Lung, and Blood Institute.
NR 40
TC 5
Z9 5
U1 1
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD JUN
PY 2014
VL 7
IS 3
BP 257
EP 265
DI 10.1161/CIRCGENETICS.113.000455
PG 9
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA AK1VY
UT WOS:000338207300006
PM 24825879
ER
PT J
AU Saxena, R
Bjonnes, A
Prescott, J
Dib, P
Natt, P
Lane, J
Lerner, M
Cooper, JA
Ye, YQ
Li, KW
Maubaret, CG
Codd, V
Brackett, D
Mirabello, L
Kraft, P
Dinney, CP
Stowell, D
Peyton, M
Ralhan, S
Wander, GS
Mehra, NK
Salpea, KD
Gu, J
Wu, XF
Mangino, M
Hunter, DJ
De Vivo, I
Humphries, SE
Samani, NJ
Spector, TD
Savage, SA
Sanghera, DK
AF Saxena, Richa
Bjonnes, Andrew
Prescott, Jennifer
Dib, Patrick
Natt, Praveen
Lane, Jacqueline
Lerner, Megan
Cooper, Jackie A.
Ye, Yuanqing
Li, Ka Wah
Maubaret, Cecilia G.
Codd, Veryan
Brackett, Daniel
Mirabello, Lisa
Kraft, Peter
Dinney, Colin P.
Stowell, Donald
Peyton, Marvin
Ralhan, Sarju
Wander, Gurpreet S.
Mehra, Narinder K.
Salpea, Klelia D.
Gu, Jian
Wu, Xifeng
Mangino, Massimo
Hunter, David J.
De Vivo, Immaculata
Humphries, Steve E.
Samani, Nilesh J.
Spector, Tim D.
Savage, Sharon A.
Sanghera, Dharambir K.
TI Genome-Wide Association Study Identifies Variants in Casein Kinase II
(CSNK2A2) to be Associated With Leukocyte Telomere Length in a Punjabi
Sikh Diabetic Cohort
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE cardiovascular diseases; diabetes mellitus, type 2; genome-wide
association study; telomere length
ID CORONARY-HEART-DISEASE; ASIAN INDIAN SIKHS; WHITE BLOOD-CELLS;
GENETIC-VARIATION; GENOTYPE IMPUTATION; ATHEROSCLEROSIS; LOCUS; RISK;
SHORTER; PROTEIN
AB Background-Telomere length is a heritable trait, and short telomere length has been associated with multiple chronic diseases. We investigated the relationship of relative leukocyte telomere length with cardiometabolic risk and performed the first genome-wide association study and meta-analysis to identify variants influencing relative telomere length in a population of Sikhs from South Asia.
Methods and Results-Our results revealed a significant independent association of shorter relative telomere length with type 2 diabetes mellitus and heart disease. Our discovery genome-wide association study (n=1616) was followed by stage 1 replication of 25 top signals (P<10(-6)) in an additional Sikhs (n=2397). On combined discovery and stage 1 metaanalysis (n=4013), we identified a novel relative telomere length locus at chromosome 16q21 represented by an intronic variant (rs74019828) in the CSNK2A2 gene (beta=-0.38; P=4.5x10(-8)). We further tested 3 top variants by genotyping in UK cardiovascular disease (UKCVD) (whites n=2952) for stage 2. Next, we performed in silico replication of 139 top signals (P<10(-5)) in UK Twin, Nurses Heart Study, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, and MD Anderson Cancer Controls (n=10033) and joint meta-analysis (n=16998). The observed signal in CSNK2A2 was confined to South Asians and could not be replicated in whites because of significant difference in allele frequencies (P<0.001). CSNK2A2 phosphorylates telomeric repeat binding factor 1 and plays an important role for regulation of telomere length homoeostasis.
Conclusions-By identification of a novel signal in telomere pathway genes, our study provides new molecular insight into the underlying mechanism that may regulate telomere length and its association with human aging and cardiometabolic pathophysiology.
C1 [Saxena, Richa; Bjonnes, Andrew; Lane, Jacqueline] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Prescott, Jennifer; Hunter, David J.; De Vivo, Immaculata] Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA 02115 USA.
[Prescott, Jennifer; Hunter, David J.; De Vivo, Immaculata] Harvard Univ, Sch Med, Boston, MA USA.
[Saxena, Richa; Bjonnes, Andrew; Lane, Jacqueline; Hunter, David J.] Massachusetts Inst Technol & Harvard, Broad Ins, Cambridge, MA USA.
[Dib, Patrick; Natt, Praveen; Sanghera, Dharambir K.] Univ Oklahoma, Dept Pediat, Coll Med, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
[Lerner, Megan; Brackett, Daniel; Stowell, Donald; Peyton, Marvin] Univ Oklahoma, Dept Surg, Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
[Prescott, Jennifer; Kraft, Peter; Hunter, David J.; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Dept Epidemiol, Boston, MA 02115 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Cooper, Jackie A.; Li, Ka Wah; Maubaret, Cecilia G.; Salpea, Klelia D.; Humphries, Steve E.] UCL, BHF Labs, Inst Cardiovasc Sci, London, England.
[Ye, Yuanqing; Gu, Jian; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Codd, Veryan; Mangino, Massimo; Samani, Nilesh J.; Spector, Tim D.] Glenfield Hosp, Natl Inst Hlth Res, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England.
[Mirabello, Lisa; Savage, Sharon A.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Dinney, Colin P.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
[Ralhan, Sarju; Wander, Gurpreet S.] Hero DMC Heart Inst, Ludhiana, Punjab, India.
[Mehra, Narinder K.] All India Inst Med Sci & Res, New Delhi, India.
RP Sanghera, DK (reprint author), Univ Oklahoma, Dept Pediat, Coll Med, Hlth Sci Ctr, 940 Stanton L Young Blvd,Rm 317 BMSB, Oklahoma City, OK 73104 USA.
EM Dharambir-sanghera@ouhsc.edu
RI Savage, Sharon/B-9747-2015; mangino, massimo/F-5134-2011;
OI Savage, Sharon/0000-0001-6006-0740; mangino,
massimo/0000-0002-2167-7470; Humphries, Stephen E/0000-0002-8221-6547
FU National Institutes of Health - National Institute of Diabetes and
Digestive and Kidney Diseases [R01DK082766]; National Genome Research
Institute [NOT-HG-11-009]; Vice President for Research Bridge grant from
University of Oklahoma Health Sciences Center, Oklahoma City, OK
FX This work was partly supported by National Institutes of Health
grants-R01DK082766 funded by the National Institute of Diabetes and
Digestive and Kidney Diseases and NOT-HG-11-009 funded by National
Genome Research Institute and Vice President for Research Bridge grant
from University of Oklahoma Health Sciences Center, Oklahoma City, OK.
The genotyping and analysis for UKCVD was supported by the British Heart
Foundation (PG08/008). Study-specific funding sources for the
replication studies are provided in the Material in the Data Supplement.
NR 53
TC 7
Z9 7
U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD JUN
PY 2014
VL 7
IS 3
BP 287
EP 295
DI 10.1161/CIRCGENETICS.113.000412
PG 9
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA AK1VY
UT WOS:000338207300009
PM 24795349
ER
PT J
AU Guan, WH
Steffen, BT
Lemaitre, RN
Wu, JHY
Tanaka, T
Manichaikul, A
Foy, M
Rich, SS
Wang, L
Nettleton, JA
Tang, WH
Gu, X
Bandinelli, S
King, IB
McKnight, B
Psaty, BM
Siscovick, D
Djousse, L
Chen, YDI
Ferrucci, L
Fornage, M
Mozafarrian, D
Tsai, MY
Steffen, LM
AF Guan, Weihua
Steffen, Brian T.
Lemaitre, Rozenn N.
Wu, Jason H. Y.
Tanaka, Toshiko
Manichaikul, Ani
Foy, Millennia
Rich, Stephen S.
Wang, Lu
Nettleton, Jennifer A.
Tang, Weihong
Gu, Xiangjun
Bandinelli, Stafania
King, Irena B.
McKnight, Barbara
Psaty, Bruce M.
Siscovick, David
Djousse, Luc
Chen, Yii-Der Ida
Ferrucci, Luigi
Fornage, Myriam
Mozafarrian, Dariush
Tsai, Michael Y.
Steffen, Lyn M.
TI Genome-Wide Association Study of Plasma N6 Polyunsaturated Fatty Acids
Within the Cohorts for Heart and Aging Research in Genomic Epidemiology
Consortium
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE epidemiology; genome-wide association study; N6 fatty acids;
polyunsaturated fatty acids
ID ACUTE MYOCARDIAL-INFARCTION; FADS GENETIC-VARIANTS; ARACHIDONIC-ACID;
ADIPOSE-TISSUE; DISEASE; POPULATION; ATHEROSCLEROSIS; DIETARY; DESIGN;
GENOTYPES
AB Background-Omega6 (n6) polyunsaturated fatty acids (PUFAs) and their metabolites are involved in cell signaling, inflammation, clot formation, and other crucial biological processes. Genetic components, such as variants of fatty acid desaturase (FADS) genes, determine the composition of n6 PUFAs.
Methods and Results-To elucidate undiscovered biological pathways that may influence n6 PUFA composition, we conducted genome-wide association studies and meta-analyses of associations of common genetic variants with 6 plasma n6 PUFAs in 8631 white adults (55% women) across 5 prospective studies. Plasma phospholipid or total plasma fatty acids were analyzed by similar gas chromatography techniques. The n6 fatty acids linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-GLA, arachidonic acid, and adrenic acid were expressed as percentage of total fatty acids. We performed linear regression with robust SEs to test for single-nucleotide polymorphism-fatty acid associations, with pooling using inverse-variance-weighted meta-analysis. Novel regions were identified on chromosome 10 associated with LA (rs10740118; P=8.1x10(-9); near NRBF2), on chromosome 16 with LA, GLA, dihomo-GLA, and arachidonic acid (rs16966952; P=1.2x10(-15), 5.0x10(-11), 7.6x10(-65), and 2.4x10(-10), respectively; NTAN1), and on chromosome 6 with adrenic acid after adjustment for arachidonic acid (rs3134950; P=2.1x10(-10); AGPAT1). We confirmed previous findings of the FADS cluster on chromosome 11 with LA and arachidonic acid, and further observed novel genome-wide significant association of this cluster with GLA, dihomo-GLA, and adrenic acid (P=2.3x10(-72), 2.6x10(-151), and 6.3x10(-140), respectively).
Conclusions-Our findings suggest that along with the FADS gene cluster, additional genes may influence n6 PUFA composition.
C1 [Guan, Weihua] Univ Minnesota, Div Biostat, Sch Publ Hlth, Minneapolis, MN 55454 USA.
[Steffen, Brian T.; Tsai, Michael Y.] Univ Minnesota, Sch Publ Med, Minneapolis, MN 55454 USA.
[Tang, Weihong; Steffen, Lyn M.] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN 55454 USA.
[Lemaitre, Rozenn N.; McKnight, Barbara; Psaty, Bruce M.; Siscovick, David] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Lemaitre, Rozenn N.; McKnight, Barbara; Psaty, Bruce M.; Siscovick, David] Univ Washington, Dept Med, Seattle, WA USA.
[Psaty, Bruce M.; Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.; Siscovick, David] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Wu, Jason H. Y.; Wang, Lu; Mozafarrian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Nutr, Boston, MA 02115 USA.
[Mozafarrian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Wu, Jason H. Y.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Manichaikul, Ani; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Manichaikul, Ani] Univ Virginia, Div Biostat & Epidemiol, Charlottesville, VA USA.
[Foy, Millennia; Gu, Xiangjun; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
[Bandinelli, Stafania] ASF, Geriatr Rehabil Unit, Florence, Italy.
[King, Irena B.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Djousse, Luc] Harvard Univ, Sch Med, Div Aging, Brigham & Womens Hosp,Dept Med, Cambridge, MA 02138 USA.
[Djousse, Luc] Boston VA Healthcare Syst, Boston, MA USA.
[Chen, Yii-Der Ida] Cedars Sinai Med Ctr, Med Genet Res Inst, Los Angeles, CA 90048 USA.
[Mozafarrian, Dariush] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc Med, Sch Med, Boston, MA 02115 USA.
RP Steffen, LM (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, 1300 South Second St,Suite 300, Minneapolis, MN 55454 USA.
EM steffen@umn.edu
RI Djousse, Luc/F-5033-2017
OI Djousse, Luc/0000-0002-9902-3047
FU National Heart, Lung, and Blood Institute (NHLBI) [HL105756]; NHLBI
[HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C]; National Human Genome Research
Institute (NHGRI) [U01HG004402]; National Institutes of Health (NIH)
[HSN268200625226C]; NIH Roadmap for Medical Research [UL1RR025005];
National Institute of Neurological Disorders and Stroke; National
Institute on Aging (NIA) [AG023629]; National Center for Advancing
Translational Sciences, CTSI [UL1TR000124]; National Institute of
Diabetes and Digestive and Kidney Disease Diabetes Research Center
[DK063491]; NHGRI [U01-HG-004729, U01-HG-004446, U01-HG-004424]; Italian
Ministry of Health [ICS110.1/RF97.71]; US NIA [263 MD 9164, 263 MD
821336]; Intramural research program of the NIA, NIH, Baltimore, MD; K01
from the National Institute of Diabetes and Digestive and Kidney
Diseases (NIKDD) [5K01DK082729-02]; NHLBI. [HL105756, N01HC85086,
HL080295, HL087652, HL085710, N01-HC-95095, N01-HC-48047, N01-HC-48048,
N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205,
N01-HC-45204, R01-HL-084099, N01-HC-95159, N01-HC-95160]; The NHLBI
[HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641,
R01HL59367, R01HL086694]; The NHLBI. [N01-HC-95161, N01-HC-95162,
N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167,
N01-HC-95168, N01-HC-95169, RR-024156, N02HL64278, HHSN268201200036C,
HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081,
N01HC85082, N01HC85083]
FX Infrastructure for the Cohorts for Heart and Aging Research in Genomic
Epidemiology Consortium is supported, in part, by the National Heart,
Lung, and Blood Institute (NHLBI) grant HL105756. The Atherosclerosis
Risk in Communities (ARIC) Study is performed as a collaborative study
supported by NHLBI contracts HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641,
R01HL59367, and R01HL086694; National Human Genome Research Institute
(NHGRI) contract U01HG004402; and National Institutes of Health (NIH)
contract HSN268200625226C. Infrastructure was partly supported by grant
number UL1RR025005, a component of the NIH Roadmap for Medical Research.
The Cardiovascular Health Study (CHS) was supported by contracts
HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and
grants HL080295, HL087652, and HL105756 from the NHLBI, with additional
contribution from the National Institute of Neurological Disorders and
Stroke. Additional support was provided by AG023629 from the National
Institute on Aging (NIA). The provision of genotyping data was supported
in part by the National Center for Advancing Translational Sciences,
CTSI grant UL1TR000124, and the National Institute of Diabetes and
Digestive and Kidney Disease Diabetes Research Center grant DK063491 to
the Southern California Diabetes Endocrinology Research Center. The
fatty acid measurements were supported by grant HL085710 from NHLBI. The
Coronary Artery Risk Development in Young Adults (CARDIA) study is
funded by contracts N01-HC-95095, N01-HC-48047, N01-HC-48048,
N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205,
and N01-HC-45204 from the NHLBI to the CARDIA investigators. Genotyping
of the CARDIA participants was supported by grants U01-HG-004729,
U01-HG-004446, and U01-HG-004424 from the NHGRI and R01-HL-084099 from
the NHLBI to Dr Foy. The Invecchiare in Chianti (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
US NIA Contracts 263 MD 9164 and 263 MD 821336 and was supported, in
part, by the Intramural research program of the NIA, NIH, Baltimore, MD.
The Multi-Ethnic Study of Atherosclerosis (MESA) and MESA SNP Health
Association Resource (SHARe) were supported by contracts N01-HC-95159
through N01-HC-95169 and RR-024156 from the NHLBI. Funding for MESA
SHARe genotyping was provided by NHLBI Contract N02HL64278. Dr Nettleton
was supported by a K01 from the National Institute of Diabetes and
Digestive and Kidney Diseases (NIKDD) (5K01DK082729-02).
NR 49
TC 9
Z9 9
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD JUN
PY 2014
VL 7
IS 3
BP 321
EP 331
DI 10.1161/CIRCGENETICS.113.000208
PG 11
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA AK1VY
UT WOS:000338207300013
PM 24823311
ER
PT J
AU Lin, HH
Wang, M
Brody, JA
Bis, JC
Dupuis, J
Lumley, T
McKnight, B
Rice, KM
Sitlani, CM
Reid, JG
Bressler, J
Liu, XM
Davis, BC
Johnson, AD
O'Donnell, CJ
Kovar, CL
Dinh, H
Wu, YQ
Newsham, I
Chen, H
Broka, A
DeStefano, AL
Gupta, M
Lunetta, KL
Liu, CT
White, CC
Xing, CH
Zhou, YH
Benjamin, EJ
Schnabel, RB
Heckbert, SR
Psaty, BM
Muzny, DM
Cupples, LA
Morrison, AC
Boerwinkle, E
AF Lin, Honghuang
Wang, Min
Brody, Jennifer A.
Bis, Joshua C.
Dupuis, Josee
Lumley, Thomas
McKnight, Barbara
Rice, Kenneth M.
Sitlani, Colleen M.
Reid, Jeffrey G.
Bressler, Jan
Liu, Xiaoming
Davis, Brian C.
Johnson, Andrew D.
O'Donnell, Christopher J.
Kovar, Christie L.
Dinh, Huyen
Wu, Yuanqing
Newsham, Irene
Chen, Han
Broka, Andi
DeStefano, Anita L.
Gupta, Mayetri
Lunetta, Kathryn L.
Liu, Ching-Ti
White, Charles C.
Xing, Chuanhua
Zhou, Yanhua
Benjamin, Emelia J.
Schnabel, Renate B.
Heckbert, Susan R.
Psaty, Bruce M.
Muzny, Donna M.
Cupples, L. Adrienne
Morrison, Alanna C.
Boerwinkle, Eric
TI Strategies to Design and Analyze Targeted Sequencing Data Cohorts for
Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
Targeted Sequencing Study
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE epidemiology; genetics; sampling studies
ID KERNEL ASSOCIATION TEST; WIDE ASSOCIATION; QUANTITATIVE TRAITS; RARE
VARIANTS; ANNOTATION; DISEASE; MUTATIONS; FRAILTY; SAMPLES; MODELS
AB Background-Genome-wide association studies have identified thousands of genetic variants that influence a variety of diseases and health-related quantitative traits. However, the causal variants underlying the majority of genetic associations remain unknown. Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study aims to follow up genome-wide association study signals and identify novel associations of the allelic spectrum of identified variants with cardiovascular-related traits.
Methods and Results-The study included 4231 participants from 3 CHARGE cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, and the Framingham Heart Study. We used a case-cohort design in which we selected both a random sample of participants and participants with extreme phenotypes for each of 14 traits. We sequenced and analyzed 77 genomic loci, which had previously been associated with >= 1 of 14 phenotypes. A total of 52 736 variants were characterized by sequencing and passed our stringent quality control criteria. For common variants (minor allele frequency >= 1%), we performed unweighted regression analyses to obtain P values for associations and weighted regression analyses to obtain effect estimates that accounted for the sampling design. For rare variants, we applied 2 approaches: collapsed aggregate statistics and joint analysis of variants using the sequence kernel association test.
Conclusions-We sequenced 77 genomic loci in participants from 3 cohorts. We established a set of filters to identify high-quality variants and implemented statistical and bioinformatics strategies to analyze the sequence data and identify potentially functional variants within genome-wide association study loci.
C1 [Lin, Honghuang; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Lin, Honghuang; Dupuis, Josee; Johnson, Andrew D.; O'Donnell, Christopher J.; DeStefano, Anita L.; Lunetta, Kathryn L.; Benjamin, Emelia J.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Wang, Min; Reid, Jeffrey G.; Kovar, Christie L.; Dinh, Huyen; Wu, Yuanqing; Newsham, Irene; Muzny, Donna M.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Brody, Jennifer A.; Bis, Joshua C.; Sitlani, Colleen M.; Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[McKnight, Barbara; Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Dupuis, Josee; Chen, Han; DeStefano, Anita L.; Gupta, Mayetri; Lunetta, Kathryn L.; Liu, Ching-Ti; White, Charles C.; Xing, Chuanhua; Zhou, Yanhua; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand.
[Bressler, Jan; Liu, Xiaoming; Davis, Brian C.; Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Broka, Andi] Boston Univ, LinGA Comp Resource, Boston, MA 02118 USA.
[Schnabel, Renate B.] Univ Heart Ctr, Dept Gen & Intervent Cardiol, Hamburg, Germany.
[Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
RP Muzny, DM (reprint author), Baylor Coll Med, Human Genome Sequencing Ctr, Rm N1621, Houston, TX 77030 USA.
EM donnam@bcm.edu; adrienne@bu.edu
RI Johnson, Andrew/G-6520-2013;
OI Lin, Honghuang/0000-0003-3043-3942; Benjamin,
Emelia/0000-0003-4076-2336; Chen, Han/0000-0002-9510-4923
FU National Institutes of Health through the American Recovery and
Reinvestment Act [5RC2HL102419]; NHLBI [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2682011
00009C, HHSN2682011000010C, HHSN2682011000011C, HHSN2682011000012C];
Boston University [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278];
National Investigation Agency [AG-023629, AG-15928, AG-20098,
AG-027058]; the NHLBI [N01-HC-25195, N01-HC-85239, N01-HC-85079,
N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084,
N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222];
NHLBI. [N01-HC-75150, N01-HC-45133, HHSN268201200036C, HL080295,
HL087652, HL105756]; [R01HL087641]; [R01HL59367]; [R01HL086694]
FX Support for Building on genome-wide association studies (GWAS) for the
National Heart, Lung, and Blood Institute (NHLBI) diseases: the US
Cohorts for Heart and Aging Research in Genomic Epidemiology Targeted
Sequencing Study (CHARGE) consortium was provided by the National
Institutes of Health through the American Recovery and Reinvestment Act
of 2009 (5RC2HL102419). Data for Building on GWAS for NHLBI-diseases:
the US CHARGE consortium was provided by Eric Boerwinkle on behalf of
the Atherosclerosis Risk in Communities (ARIC) Study, L. A. Cupples,
principal investigator for the Framingham Heart Study, and Bruce Psaty,
principal investigator for the Cardiovascular Health Study (CHS).
Sequencing was carried out at the Baylor Genome Center (U54 HG003273).
The ARIC Study is performed as a collaborative study supported by the
NHLBI contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN2682011 00009C,
HHSN2682011000010C, HHSN2682011000011C, and HHSN2682011000012C) and
R01HL087641, R01HL59367, and R01HL086694. We thank the staff and
participants of the ARIC study for their important contributions. The
Framingham Heart Study (FHS) is performed and supported by the NHLBI in
collaboration with Boston University (Contract No. N01-HC-25195), and
its contract with Affymetrix, Inc, for genome-wide genotyping services
(Contract No. N02-HL-6-4278), for quality control by FHS investigators
using genotypes in the SNP Health Association Resource (SHARe) project.
A portion of this research was performed using the Linux Cluster for
Genetic Analysis (LinGA) computing resources at Boston University
Medical Campus. This CHS research was supported by NHLBI contracts
N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082,
N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086; N01-HC-35129,
N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
HHSN268201200036C and by NHLBI grants HL080295, HL087652, and HL105756
with additional contribution from National Institute of Neurological
Disorders and Stroke. Additional support was provided through AG-023629,
AG-15928, AG-20098, and AG-027058 from the National Investigation
Agency. See also http://www.chs-nhlbi.org/pi.htm.
NR 38
TC 9
Z9 9
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD JUN
PY 2014
VL 7
IS 3
BP 335
EP 343
DI 10.1161/CIRCGENETICS.113.000350
PG 9
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA AK1VY
UT WOS:000338207300015
PM 24951659
ER
PT J
AU Liu, CT
Young, KL
Brody, JA
Olden, M
Wojczynski, MK
Heard-Costa, N
Li, G
Morrison, AC
Muzny, D
Gibbs, RA
Reid, JG
Shao, YM
Zhou, YH
Boerwinkle, E
Heiss, G
Wagenknecht, L
McKnight, B
Borecki, IB
Fox, CS
North, KE
Cupples, LA
AF Liu, Ching-Ti
Young, Kristin L.
Brody, Jennifer A.
Olden, Matthias
Wojczynski, Mary K.
Heard-Costa, Nancy
Li, Guo
Morrison, Alanna C.
Muzny, Donna
Gibbs, Richard A.
Reid, Jeffrey G.
Shao, Yaming
Zhou, Yanhua
Boerwinkle, Eric
Heiss, Gerardo
Wagenknecht, Lynne
McKnight, Barbara
Borecki, Ingrid B.
Fox, Caroline S.
North, Kari E.
Cupples, L. Adrienne
TI Sequence Variation in TMEM18 in Association With Body Mass Index Cohorts
for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
Targeted Sequencing Study
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE body mass index; genetic association studies
ID EARLY-ONSET OBESITY; LIFE-COURSE; GENE-EXPRESSION; FTO GENE; VARIANTS;
BMI; ADOLESCENTS; MUTATIONS; CHILDREN; DATABASE
AB Background-Genome-wide association studies for body mass index (BMI) previously identified a locus near TMEM18. We conducted targeted sequencing of this region to investigate the role of common, low-frequency, and rare variants influencing BMI.
Methods and Results-We sequenced TMEM18 and regions downstream of TMEM18 on chromosome 2 in 3976 individuals of European ancestry from 3 community-based cohorts (Atherosclerosis Risk in Communities, Cardiovascular Health Study, and Framingham Heart Study), including 200 adults selected for high BMI. We examined the association between BMI and variants identified in the region from nucleotide position 586 432 to 677 539 (hg18). Rare variants (minor allele frequency, <1%) were analyzed using a burden test and the sequence kernel association test. Results from the 3 cohort studies were meta-analyzed. We estimate that mean BMI is 0.43 kg/m(2) higher for each copy of the G allele of single-nucleotide polymorphism rs7596758 (minor allele frequency, 29%; P=3.46x10(-4)) using a Bonferroni threshold of P<4.6x10(-4). Analyses conditional on previous genome-wide association study single-nucleotide polymorphisms associated with BMI in the region led to attenuation of this signal and uncovered another independent (r(2)<0.2), statistically significant association, rs186019316 (P=2.11x10(-4)). Both rs186019316 and rs7596758 or proxies are located in transcription factor binding regions. No significant association with rare variants was found in either the exons of TMEM18 or the 3' genome-wide association study region.
Conclusions-Targeted sequencing around TMEM18 identified 2 novel BMI variants with possible regulatory function.
C1 [Liu, Ching-Ti; Zhou, Yanhua; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Young, Kristin L.; Shao, Yaming; Heiss, Gerardo; North, Kari E.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Young, Kristin L.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
[McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Brody, Jennifer A.; Li, Guo; McKnight, Barbara] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Olden, Matthias; Heard-Costa, Nancy; Fox, Caroline S.; Cupples, L. Adrienne] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Wojczynski, Mary K.; Borecki, Ingrid B.] Washington Univ, Sch Med, St Louis, MO USA.
[Heard-Costa, Nancy] Boston Univ, Dept Neurol, Sch Med, Boston, MA 02118 USA.
[Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Div Epidemiol Human Genet & Environm Sci, Sch Publ Hlth, Houston, TX 77030 USA.
[Muzny, Donna; Gibbs, Richard A.; Reid, Jeffrey G.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Wagenknecht, Lynne] Wake Forest Baptist Med Ctr, Dept Epidemiol & Prevent, Winston Salem, NC USA.
[McKnight, Barbara] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
RP Liu, CT (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave,CT3, Boston, MA 02118 USA.
EM ctliu@bu.edu; adrienne@bu.edu
RI Young, Kristin/B-5792-2008
OI Young, Kristin/0000-0003-0070-6145
FU National Institutes of Health through the American Recovery and
Reinvestment Act [5RC2HL102419]; NHLBI [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2682011
00009C, HHSN2682011000010C, HHSN2682011000011C, HHSN2682011000012C];
Boston University [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278];
Robert Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine; Boston Medical Center; National Institute
on Aging [AG-023629, AG-15928, AG-20098, AG-027058]; National Institute
of Diabetes and Digestive and Kidney Diseases/Baylor Genome Center
[R01-DK-8925601, R01-DK-075681, U54 HG003273]; the NHLBI [N01-HC-25195,
N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081]; NHLBI.
[N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
HHSN268201200036C, HL080295, HL087652, HL105756]; [R01HL087641];
[R01HL59367]; [R01HL086694]
FX Support for Building on Genome-Wide Association Studies (GWAS) for
National Heart, Lung, and Blood Institute (NHLBI) Diseases: The US
CHARGE Consortium was provided by the National Institutes of Health
through the American Recovery and Reinvestment Act of 2009
(5RC2HL102419). Data for Building on GWAS for NHLBI-Diseases: The US
CHARGE Consortium was provided by Eric Boerwinkle on behalf of the
Atherosclerosis Risk in Communities (ARIC) study; L. Adrienne Cupples,
principal investigator for the Framingham Heart Study (FHS); and Bruce
Psaty, principal investigator for the Cardiovascular Health Study (CHS).
The ARIC study is performed as a collaborative study supported by NHLBI
contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN2682011 00009C, HHSN2682011000010C,
HHSN2682011000011C, and HHSN2682011000012C), R01HL087641, R01HL59367,
and R01HL086694. FHS is conducted and supported by the NHLBI in
collaboration with Boston University (contract no. N01-HC-25195) and its
contract with Affymetrix, Inc, for genome-wide genotyping services
(contract no. N02-HL-6-4278), for quality control by FHS investigators
using genotypes in the SNP Health Association Resource project. A
portion of this research was conducted using the Linux Cluster for
Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment
of the Department of Medicine at Boston University School of Medicine
and Boston Medical Center. The CHS research was supported by NHLBI
contracts N01-HC-85239, N01-HC-85079, N01-HC-85080, N01-HC-85081,
N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, 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 National Institute of Neurological
Disorders and Stroke. Additional support was provided through AG-023629,
AG-15928, AG-20098, and AG-027058 from the National Institute on Aging.
See also http://www.chs-nhlbi.org/pi.htm. This work was partially
supported by R01-DK-8925601 and R01-DK-075681 (Ingrid B. Borecki,
principal investigator) from National Institute of Diabetes and
Digestive and Kidney Diseases/Baylor Genome Center (grant no. U54
HG003273).
NR 32
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD JUN
PY 2014
VL 7
IS 3
BP 344
EP 349
DI 10.1161/CIRCGENETICS.13.000067
PG 6
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA AK1VY
UT WOS:000338207300016
PM 24951660
ER
PT J
AU London, SJ
Gao, W
Gharib, SA
Hancock, DB
Wilk, JB
House, JS
Gibbs, RA
Muzny, DM
Lumley, T
Franceschini, N
North, KE
Psaty, BM
Kovar, CL
Coresh, J
Zhou, YH
Heckbert, SR
Brody, JA
Morrison, AC
Dupuis, J
AF London, Stephanie J.
Gao, Wei
Gharib, Sina A.
Hancock, Dana B.
Wilk, Jemma B.
House, John S.
Gibbs, Richard A.
Muzny, Donna M.
Lumley, Thomas
Franceschini, Nora
North, Kari E.
Psaty, Bruce M.
Kovar, Christie L.
Coresh, Josef
Zhou, Yanhua
Heckbert, Susan R.
Brody, Jennifer A.
Morrison, Alanna C.
Dupuis, Josee
TI ADAM19 and HTR4 Variants and Pulmonary Function Cohorts for Heart and
Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted
Sequencing Study
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE Airway Obstruction; genome-wide association study; lung; polymorphism,
genetic; pulmonary disease, chronic obstructive; respiratory function
tests; sequence analysis, DNA
ID NECROSIS-FACTOR-ALPHA; LUNG-FUNCTION; WIDE ASSOCIATION;
EPITHELIAL-CELLS; DISEASE; POPULATION; EXPRESSION; MORTALITY; SEROTONIN;
DATABASE
AB Background-The pulmonary function measures of forced expiratory volume in 1 second (FEV1) and its ratio to forced vital capacity (FVC) are used in the diagnosis and monitoring of lung diseases and predict cardiovascular mortality in the general population. Genome-wide association studies (GWASs) have identified numerous loci associated with FEV1 and FEV1/FVC, but the causal variants remain uncertain. We hypothesized that novel or rare variants poorly tagged by GWASs may explain the significant associations between FEV1/FVC and 2 genes: ADAM19 and HTR4.
Methods and Results-We sequenced ADAM19 and its promoter region along with the approximate to 21-kb portion of HTR4 harboring GWAS single-nucleotide polymorphisms for pulmonary function and analyzed associations with FEV1/FVC among 3983 participants of European ancestry from Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Meta-analysis of common variants in each region identified statistically significant associations (316 tests; P<1.58x10(-4)) with FEV1/FVC for 14 ADAM19 single-nucleotide polymorphisms and 24 HTR4 single-nucleotide polymorphisms. After conditioning on the sentinel GWASs hit in each gene (ADAM19 rs1422795, minor allele frequency=0.33 and HTR4 rs11168048, minor allele frequency=0.40], 1 single-nucleotide polymorphism remained statistically significant (ADAM19 rs13155908, minor allele frequency=0.12; P=1.56x10(-4)). Analysis of rare variants (minor allele frequency <1%) using sequence kernel association test did not identify associations with either region.
Conclusions-Sequencing identified 1 common variant associated with FEV1/FVC independent of the sentinel ADAM19 GWAS hit and supports the original HTR4 GWAS findings. Rare variants do not seem to underlie GWAS associations with pulmonary function for common variants in ADAM19 and HTR4.
C1 [London, Stephanie J.; Hancock, Dana B.] NIEHS, Epidemiol Branch, Div Intramural Res, NIH,US Dept HHS, Res Triangle Pk, NC 27709 USA.
[London, Stephanie J.; House, John S.] NIEHS, Lab Resp Biol, Div Intramural Res, NIH,US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Gao, Wei; Zhou, Yanhua; Dupuis, Josee] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA.
[Gharib, Sina A.] Univ Washington, Dept Med, Ctr Lung Biol, Div Pulm & Crit Care Med, Seattle, WA USA.
[Psaty, Bruce M.; Heckbert, Susan R.; Brody, Jennifer A.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Hancock, Dana B.] Res Triangle Inst, Behav Hlth Epidemiol Program, Res Triangle Pk, NC 27709 USA.
[Wilk, Jemma B.] Pfizer Global Res & Dev, Precis Med, Cambridge, MA USA.
[Gibbs, Richard A.; Muzny, Donna M.; Kovar, Christie L.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand.
[Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Morrison, Alanna C.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA.
RP London, SJ (reprint author), NIEHS, 111 TW Alexander Dr,POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA.
EM london2@niehs.nih.gov
OI Hancock, Dana/0000-0003-2240-3604; House, John S./0000-0002-8447-7871;
London, Stephanie/0000-0003-4911-5290
FU National Institutes of Health (NIH) through the American Recovery and
Reinvestment Act (ARRA) [5RC2HL102419]; NHLBI [HL105756,
HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN2682011 00009C, HHSN2682011000010C,
HHSN2682011000011C, HHSN2682011000012C]; National Human Genome Research
Institute [U01HG004402]; NIH [HHSN268200625226C]; NIH and NIH Roadmap
for Medical Research [UL1RR025005]; Boston University [N01-HC-25195];
Affymetrix, Inc. [N02-HL-6-4278]; National Institute on Aging
[AG023629]; Intramural Research Program of the NIH, National Institute
of Environmental Health Sciences; the NHLBI [N01-HC-25195,
HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080]; NHLBI. [N01HC85081, N01HC85082, N01HC85083, N01HC85086,
HL080295, HL087652]; [R01HL087641]; [R01HL59367]; [R01HL086694];
[U54 HG003273]
FX Funding support for Building on GWAS for National Heart, Lung, and Blood
Institute (NHLBI) diseases: the US CHARGE Consortium was provided by the
National Institutes of Health (NIH) through the American Recovery and
Reinvestment Act of 2009 (ARRA; 5RC2HL102419). Data for Building on GWAS
for NHLBI diseases: the US CHARGE Consortium was provided by Eric
Boerwinkle on behalf of the ARIC study, L. Adrienne Cupples, principal
investigator for the Framingham Heart Study, and Bruce Psaty, principal
investigator for the Cardiovascular Health Study. Infrastructure for the
CHARGE Consortium is supported in part by NHLBI grant HL105756. The ARIC
study is performed as a collaborative study supported by NHLBI contracts
(HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN2682011 00009C, HHSN2682011000010C,
HHSN2682011000011C, and HHSN2682011000012C) R01HL087641, R01HL59367, and
R01HL086694; National Human Genome Research Institute contract
U01HG004402; and NIH contract HHSN268200625226C. Infrastructure was
partly supported by grant No. UL1RR025005, a component of the NIH and
NIH Roadmap for Medical Research. The Framingham Heart Study is
conducted and supported by the NHLBI in collaboration with Boston
University (contract No. N01-HC-25195) and its contract with Affymetrix,
Inc., for genome-wide genotyping services (contract No. N02-HL-6-4278)
and for quality control by Framingham Heart Study investigators using
genotypes in the SNP Health Association Resource (SHARe) project. A
portion of this research was conducted using the Linux Clusters for
Genetic Analysis computing resources at Boston University Medical
Campus. The Human Genome Sequencing Center at Baylor College of Medicine
is supported by U54 HG003273. The research within CHS was supported by
NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222,
N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and
N01HC85086 and NHLBI grants HL080295, HL087652, and HL105756, with
additional contributions from the National Institute of Neurological
Disorders and Stroke. Additional support was provided through AG023629
from the National Institute on Aging. This work was supported in part by
the Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences.
NR 39
TC 3
Z9 3
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD JUN
PY 2014
VL 7
IS 3
BP 350
EP 358
DI 10.1161/CIRCGENETICS.113.000066
PG 9
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA AK1VY
UT WOS:000338207300017
PM 24951661
ER
PT J
AU Bis, JC
White, CC
Franceschini, N
Brody, J
Zhang, XL
Muzny, D
Santibanez, J
Gibbs, R
Liu, XM
Lin, HH
Boerwinkle, E
Psaty, BM
North, KE
Cupples, LA
O'Donnell, CJ
AF Bis, Joshua C.
White, Charles C.
Franceschini, Nora
Brody, Jennifer
Zhang, Xiaoling
Muzny, Donna
Santibanez, Jireh
Gibbs, Richard
Liu, Xiaoming
Lin, Honghuang
Boerwinkle, Eric
Psaty, Bruce M.
North, Kari E.
Cupples, L. Adrienne
O'Donnell, Christopher J.
CA CHARGE Subclinical Atherosclerosis
TI Sequencing of 2 Subclinical Atherosclerosis Candidate Regions in 3669
Individuals Cohorts for Heart and Aging Research in Genomic Epidemiology
(CHARGE) Consortium Targeted Sequencing Study
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE atherosclerosis; carotid artery, common; epidemiology; genetics; plaque,
atherosclerotic; sequence analysis, DNA
ID INTIMA-MEDIA THICKNESS; KERNEL ASSOCIATION TEST; WIDE ASSOCIATION;
TASK-FORCE; METAANALYSIS; VARIANTS; RISK; LOCI; DESIGN; FRAMINGHAM
AB Background-Atherosclerosis, the precursor to coronary heart disease and stroke, is characterized by an accumulation of fatty cells in the arterial intimal-medial layers. Common carotid intima media thickness (cIMT) and plaque are subclinical atherosclerosis measures that predict cardiovascular disease events. Previously, genome-wide association studies demonstrated evidence for association with cIMT (SLC17A4) and plaque (PIK3CG).
Methods and Results-We sequenced 120 kb around SLC17A4 (6p22.2) and 251 kb around PIK3CG (7q22.3) among 3669 European ancestry participants from the Atherosclerosis Risk in Communities (ARIC) study, Cardiovascular Health Study (CHS), and Framingham Heart Study (FHS) in Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Primary analyses focused on 438 common variants (minor allele frequency >= 1%), which were independently meta-analyzed. A 3' untranslated region CCDC71L variant (rs2286149), upstream from PIK3CG, was the most significant finding in cIMT (P=0.00033) and plaque (P=0.0004) analyses. A SLC17A4 intronic variant was also associated with cIMT (P=0.008). Both were in low linkage disequilibrium with the genome-wide association study single nucleotide polymorphisms. Gene-based tests including T1 count and sequence kernel association test for rare variants (minor allele frequency <1%) did not yield statistically significant associations. However, we observed nominal associations for rare variants in CCDC71L and SLC17A3 with cIMT and of the entire 7q22 region with plaque (P=0.05).
Conclusions-Common and rare variants in PIK3CG and SLC17A4 regions demonstrated modest association with subclinical atherosclerosis traits. Although not conclusive, these findings may help to understand the genetic architecture of regions previously implicated by genome-wide association studies and identify variants within these regions for further investigation in larger samples.
C1 [Bis, Joshua C.; Brody, Jennifer; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
[Bis, Joshua C.; Brody, Jennifer; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA.
[White, Charles C.; Zhang, Xiaoling; Lin, Honghuang; Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[White, Charles C.; Cupples, L. Adrienne] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA.
[Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Muzny, Donna; Santibanez, Jireh; Gibbs, Richard; Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Liu, Xiaoming; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Lin, Honghuang] Boston Univ, Dept Med, Sch Med, Boston, MA 02215 USA.
[Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA.
[Liu, Xiaoming; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA.
RP Bis, JC (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA.
EM joshbis@uw.edu
OI Lin, Honghuang/0000-0003-3043-3942
FU National Institutes of Health through the American Recovery and
Reinvestment Act [5RC2HL102419]; National Heart, Lung, and Blood
Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100 008C, HHSN268201100009C,
HHSN2682011000010C, HHSN268 2011000011C, HHSN2682011000012C]; Boston
University [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; National
Institute on Aging (NIA) [AG023629]; National Center for Advancing
Translational Sciences, CTSI [UL1TR000124]; National Institute of
Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC)
[DK063491]; the NHLBI [N01-HC-25195, HHSN268201200036C,
HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081,
N01HC85082, N01HC85083, N01HC85086, N01HC85085, N01HC45133]; NHLBI
[HL080295, HL087652, HL105756, HL103612, HL120393]; [R01HL087641];
[R01HL59367]; [R01HL086694]
FX Funding support for Building on GWAS for NHLBI-Diseases: The US CHARGE
Consortium was provided by the National Institutes of Health through the
American Recovery and Reinvestment Act of 2009 (5RC2HL102419). Data for
Building on GWAS for NHLBI-Diseases: The US CHARGE Consortium were
provided by Eric Boerwinkle on behalf of the Atherosclerosis Risk in
Communities (ARIC) study; L. Adrienne Cupples, principal investigator
for the Framingham Heart Study (FHS); and Bruce Psaty, principal
investigator for the Cardiovascular Health Study. Sequencing was
performed at the Baylor Genome Center (U54 HG003273). The ARIC study is
performed as a collaborative study supported by National Heart, Lung,
and Blood Institute (NHLBI) contracts (HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100 008C,
HHSN268201100009C, HHSN2682011000010C, HHSN268 2011000011C, and
HHSN2682011000012C), R01HL087641, R01HL59367, and R01HL086694. The
authors thank the staff and participants of the ARIC study for their
important contributions. The FHS is conducted and supported by the NHLBI
in collaboration with Boston University (contract no. N01-HC-25195), and
its contract with Affymetrix, Inc, for genome-wide genotyping services
(contract no. N02-HL-6-4278), for quality control by FHS investigators
using genotypes in the SNP Health Association Resource (SHARe) project.
A portion of this research was conducted using the Linux Cluster for
Genetic Analysis (LinGA) computing resources at Boston University
Medical Campus. This Cardiovascular Health Study research was supported
by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222,
N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086,
N01HC85085, N01HC45133; and NHLBI grants HL080295, HL087652, HL105756,
HL103612, and HL120393 with additional contribution from the National
Institute of Neurological Disorders and Stroke (NINDS). Additional
support was provided through AG023629 from the National Institute on
Aging (NIA). A full list of principal CHS investigators and institutions
can be found at CHS-NHLBI.org/. The provision of genotyping data was
supported in part by the National Center for Advancing Translational
Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes
and Digestive and Kidney Disease Diabetes Research Center (DRC) grant
DK063491 to the Southern California Diabetes Endocrinology Research
Center. The content is solely the responsibility of the authors and does
not necessarily represent the official views of the National Institutes
of Health.
NR 31
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U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD JUN
PY 2014
VL 7
IS 3
BP 359
EP 364
DI 10.1161/CIRCGENETICS.113.000116
PG 6
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA AK1VY
UT WOS:000338207300018
PM 24951662
ER
PT J
AU Magnani, JW
Brody, JA
Prins, BP
Arking, DE
Lin, HH
Yin, XY
Liu, CT
Morrison, AC
Zhang, F
Spector, TD
Alonso, A
Bis, JC
Heckbert, SR
Lumley, T
Sitlani, CM
Cupples, A
Lubitz, SA
Soliman, EZ
Pulit, SL
Newton-Cheh, C
O'Donnell, CJ
Ellinor, PT
Benjamin, EJ
Muzny, DM
Gibbs, RA
Santibanez, J
Taylor, HA
Rotter, JI
Lange, LA
Psaty, BM
Jackson, R
Rich, SS
Boerwinkle, E
Jamshidi, Y
Sotoodehnia, N
AF Magnani, Jared W.
Brody, Jennifer A.
Prins, Bram P.
Arking, Dan E.
Lin, Honghuang
Yin, Xiaoyan
Liu, Ching-Ti
Morrison, Alanna C.
Zhang, Feng
Spector, Tim D.
Alonso, Alvaro
Bis, Joshua C.
Heckbert, Susan R.
Lumley, Thomas
Sitlani, Colleen M.
Cupples, Adrienne
Lubitz, Steven A.
Soliman, Elsayed Z.
Pulit, Sara L.
Newton-Cheh, Christopher
O'Donnell, Christopher J.
Ellinor, Patrick T.
Benjamin, Emelia J.
Muzny, Donna M.
Gibbs, Richard A.
Santibanez, Jireh
Taylor, Herman A.
Rotter, Jerome I.
Lange, Leslie A.
Psaty, Bruce M.
Jackson, Rebecca
Rich, Stephen S.
Boerwinkle, Eric
Jamshidi, Yalda
Sotoodehnia, Nona
CA CHARGE Consortium
NHLBIs Exome Sequencing
UK10K
TI Sequencing of SCN5A Identifies Rare and Common Variants Associated With
Cardiac Conduction: Cohorts for Heart and Aging Research in Genomic
Epidemiology (CHARGE) Consortium
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE electrocardiography; genomics
ID SICK SINUS SYNDROME; LONG QT SYNDROME; SODIUM-CHANNEL; QRS DURATION; PR
INTERVAL; DILATED CARDIOMYOPATHY; WIDE ASSOCIATION; CODING VARIANTS;
MUTATIONS; DISEASE
AB Background-The cardiac sodium channel SCN5A regulates atrioventricular and ventricular conduction. Genetic variants in this gene are associated with PR and QRS intervals. We sought to characterize further the contribution of rare and common coding variation in SCN5A to cardiac conduction.
Methods and Results-In Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study, we performed targeted exonic sequencing of SCN5A (n=3699, European ancestry individuals) and identified 4 common (minor allele frequency >1%) and 157 rare variants. Common and rare SCN5A coding variants were examined for association with PR and QRS intervals through meta-analysis of European ancestry participants from CHARGE, National Heart, Lung, and Blood Institute's Exome Sequencing Project (n=607), and the UK10K (n=1275) and by examining Exome Sequencing Project African ancestry participants (n=972). Rare coding SCN5A variants in aggregate were associated with PR interval in European and African ancestry participants (P=1.3x10(-3)). Three common variants were associated with PR and QRS interval duration among European ancestry participants and one among African ancestry participants. These included 2 well-known missense variants: rs1805124 (H558R) was associated with PR and QRS shortening in European ancestry participants (P=6.25x10(-4) and P=5.2x10(-3), respectively) and rs7626962 (S1102Y) was associated with PR shortening in those of African ancestry (P=2.82x10(-3)). Among European ancestry participants, 2 novel synonymous variants, rs1805126 and rs6599230, were associated with cardiac conduction. Our top signal, rs1805126 was associated with PR and QRS lengthening (P=3.35x10(-7) and P=2.69x10(-4), respectively) and rs6599230 was associated with PR shortening (P=2.67x10(-5)).
Conclusions-By sequencing SCN5A, we identified novel common and rare coding variants associated with cardiac conduction.
C1 [Magnani, Jared W.; Lin, Honghuang; Yin, Xiaoyan; Liu, Ching-Ti; Cupples, Adrienne; Newton-Cheh, Christopher; O'Donnell, Christopher J.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Magnani, Jared W.; Lin, Honghuang; Yin, Xiaoyan; Liu, Ching-Ti; Cupples, Adrienne; Newton-Cheh, Christopher; O'Donnell, Christopher J.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Boston, MA 02118 USA.
[Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[Lin, Honghuang] Boston Univ, Sch Med, Sect Computat Biomed, Boston, MA 02118 USA.
[Brody, Jennifer A.; Bis, Joshua C.; Heckbert, Susan R.; Sitlani, Colleen M.; Psaty, Bruce M.; Sotoodehnia, Nona] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA.
[Prins, Bram P.; Zhang, Feng; Jamshidi, Yalda] St Georges Univ London, Human Genet Res Ctr, London, England.
[Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Yin, Xiaoyan; Liu, Ching-Ti; Cupples, Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Zhang, Feng; Spector, Tim D.] Kings Coll London, Dept Twin Res, St Thomas Hosp, London WC2R 2LS, England.
[Zhang, Feng; Spector, Tim D.] Kings Coll London, Genet Epidemiol Unit, St Thomas Hosp, London WC2R 2LS, England.
[Alonso, Alvaro] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand.
[Lubitz, Steven A.; Pulit, Sara L.; Newton-Cheh, Christopher; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Lubitz, Steven A.; Newton-Cheh, Christopher; O'Donnell, Christopher J.; Ellinor, Patrick T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA.
[Soliman, Elsayed Z.] Wake Forest Univ, Bowman Gray Sch Med, Epidemiol Cardiol Res Ctr, Winston Salem, NC USA.
[Pulit, Sara L.; Newton-Cheh, Christopher] Broad Inst, Cambridge, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA.
[Muzny, Donna M.; Gibbs, Richard A.; Santibanez, Jireh; Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Taylor, Herman A.] Univ Mississippi, Med Ctr, Jackson, MI USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
[Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Jackson, Rebecca] Ohio State Univ, Dept Med, Wexner Med Ctr, Columbus, OH 43210 USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, 88 E Newton St, Boston, MA 02118 USA.
EM jmagnani@bu.edu; nsotoo@uw.edu
RI Alonso, Alvaro/A-4917-2010;
OI Alonso, Alvaro/0000-0002-2225-8323; Jamshidi, Yalda/0000-0003-0151-6482;
Lin, Honghuang/0000-0003-3043-3942; Benjamin, Emelia/0000-0003-4076-2336
FU National Institutes of Health (NIH) through the American Recovery and
Reinvestment Act [5RC2HL102419]; NHLBI [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN26820110
0009C, HHSN2682011000010C, HHSN2682011000011C, HHSN2682011000012C];
Boston University [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278];
Boston University School of Medicine Department of Medicine Career
Investment Award; Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine; Boston Medical Center;
National Institute on Aging [AG023629]; Wellcome Trust [WT091310];
ENGAGE project [HEALTH-F4-2007-201413]; Department of Health via the
National Institute for Health Research (NIHR); British Heart Foundation
[PG/12/38/29615]; the NHLBI [N01-HC-25195, HHSN268201200036C,
HHSN268200800007C, N01HC55222, N01HC85079]; NHLBI. [N01HC85080,
N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295, HL087652,
HL105756]; [6R01-NS 17950NIH]; [1RO1HL092577]; [1R01 HL102214l];
[1RC1HL101056]; [5R21DA027021]; [1RO1HL104156]; [K23HL11472];
[1K24HL105780]; [1R03AG045075]
FX Funding support for building on Genome-wide association studies (GWAS)
for National Heart, Lung, and Blood Institute (NHLBI) diseases: the US
Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE)
Consortium Targeted Sequencing Study was provided by the National
Institutes of Health (NIH) through the American Recovery and
Reinvestment Act of 2009 (5RC2HL102419). Data for building on GWAS for
NHLBI diseases: the US CHARGE Consortium was provided by Dr Boerwinkle
on behalf of the Atherosclerosis Risk in Communities (ARIC) Study, Dr
Cupples, principal investigator for the Framingham Heart Study, and Dr
Psaty, principal investigator for the Cardiovascular Health Study. The
ARIC Study is performed as a collaborative study supported by NHLBI
contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN26820110 0009C, HHSN2682011000010C,
HHSN2682011000011C, and HHSN2682011000012C). The Framingham Heart Study
is conducted and supported by the NHLBI in collaboration with Boston
University (contract No. N01-HC-25195) and its contract with Affymetrix,
Inc, for genome-wide genotyping services (contract No. N02-HL-6-4278),
for quality control by Framingham Heart Study investigators using
genotypes in the SNP Health Association Resource (SHARe) project. This
project was supported by 6R01-NS 17950NIH, 1RO1HL092577, 1R01 HL102214l,
1RC1HL101056, 5R21DA027021, 1RO1HL104156, K23HL11472, 1K24HL105780, and
1R03AG045075. Dr Magnani is further supported by a Boston University
School of Medicine Department of Medicine Career Investment Award. A
portion of this research was conducted using the Linux Cluster for
Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment
of the Department of Medicine at Boston University School of Medicine
and Boston Medical Center. Cardiovascular Health Study (CHS): This CHS
research was supported by NHLBI contracts HHSN268201200036C,
HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081,
N01HC85082, N01HC85083, and N01HC85086 and NHLBI grants HL080295,
HL087652, and HL105756 with additional contribution from the National
Institute of Neurological Disorders and Stroke. Additional support was
provided through AG023629 from the National Institute on Aging. A full
list of CHS investigators and institutions can be found at
http://www.chs-nhlbi.org/pi.htm. UK10K: The UK10K project was funded by
the Wellcome Trust award WT091310. Twins UK (TUK): TUK was funded by the
Wellcome Trust and ENGAGE project grant agreement HEALTH-F4-2007-201413.
The study also receives support from the Department of Health via the
National Institute for Health Research (NIHR)-funded BioResource,
Clinical Research Facility and Biomedical Research Centre based at Guy's
and St. Thomas' NHS Foundation Trust in partnership with King's College
London. Dr Spector is an NIHR senior Investigator and ERC Senior
Researcher. Funding for the project was also provided by the British
Heart Foundation grant PG/12/38/29615 (Dr Jamshidi).
NR 46
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U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD JUN
PY 2014
VL 7
IS 3
BP 365
EP 373
DI 10.1161/CIRCGENETICS.113.000098
PG 9
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA AK1VY
UT WOS:000338207300019
PM 24951663
ER
PT J
AU Cornes, BK
Brody, JA
Nikpoor, N
Morrison, AC
Dang, HCP
Ahn, BS
Wang, S
Dauriz, M
Barzilay, JI
Dupuis, J
Florez, JC
Coresh, J
Gibbs, RA
Kao, WHL
Liu, CT
McKnight, B
Muzny, D
Pankow, JS
Reid, JG
White, CC
Johnson, AD
Wong, TY
Psaty, BM
Boerwinkle, E
Rotter, JI
Siscovick, DS
Sladek, R
Meigs, JB
AF Cornes, Belinda K.
Brody, Jennifer A.
Nikpoor, Naghmeh
Morrison, Alanna C.
Huan Chu Pham Dang
Ahn, Byung Soo
Wang, Shuai
Dauriz, Marco
Barzilay, Joshua I.
Dupuis, Josee
Florez, Jose C.
Coresh, Josef
Gibbs, Richard A.
Kao, W. H. Linda
Liu, Ching-Ti
McKnight, Barbara
Muzny, Donna
Pankow, James S.
Reid, Jeffrey G.
White, Charles C.
Johnson, Andrew D.
Wong, Tien Y.
Psaty, Bruce M.
Boerwinkle, Eric
Rotter, Jerome I.
Siscovick, David S.
Sladek, Robert
Meigs, James B.
TI Association of Levels of Fasting Glucose and Insulin With Rare Variants
at the Chromosome 11p11.2-MADD Locus Cohorts for Heart and Aging
Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing
Study
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE genetic epidemiology; glucose; human genetics; insulin; molecular
genetics
ID HUMAN GENE-EXPRESSION; TRANSCRIPTION FACTOR; CARDIOVASCULAR HEALTH; WIDE
ASSOCIATION; GLYCEMIC TRAITS; BETA-CELL; DNA; POPULATION; RISK;
PATHOPHYSIOLOGY
AB Background-Common variation at the 11p11.2 locus, encompassing MADD, ACP2, NR1H3, MYBPC3, and SPI1, has been associated in genome-wide association studies with fasting glucose and insulin (FI). In the Cohorts for Heart and Aging Research in Genomic Epidemiology Targeted Sequencing Study, we sequenced 5 gene regions at 11p11.2 to identify rare, potentially functional variants influencing fasting glucose or FI levels.
Methods and Results-Sequencing (mean depth, 38x) across 16.1 kb in 3566 individuals without diabetes mellitus identified 653 variants, 79.9% of which were rare (minor allele frequency <1%) and novel. We analyzed rare variants in 5 gene regions with FI or fasting glucose using the sequence kernel association test. At NR1H3, 53 rare variants were jointly associated with FI (P=2.73x10(-3)); of these, 7 were predicted to have regulatory function and showed association with FI (P=1.28x10(-3)). Conditioning on 2 previously associated variants at MADD (rs7944584, rs10838687) did not attenuate this association, suggesting that there are >2 independent signals at 11p11.2. One predicted regulatory variant, chr11: 47227430 (hg18; minor allele frequency=0.00068), contributed 20.6% to the overall sequence kernel association test score at NR1H3, lies in intron 2 of NR1H3, and is a predicted binding site for forkhead box A1 (FOXA1), a transcription factor associated with insulin regulation. In human HepG2 hepatoma cells, the rare chr11: 47227430 A allele disrupted FOXA1 binding and reduced FOXA1-dependent transcriptional activity.
Conclusions-Sequencing at 11p11.2-NR1H3 identified rare variation associated with FI. One variant, chr11: 47227430, seems to be functional, with the rare A allele reducing transcription factor FOXA1 binding and FOXA1-dependent transcriptional activity.
C1 [Cornes, Belinda K.; Dauriz, Marco; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Diabet Unit, Boston, MA 02114 USA.
[Cornes, Belinda K.; Dauriz, Marco; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Brody, Jennifer A.; McKnight, Barbara; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[McKnight, Barbara] Univ Washington, Dept Med, Seattle, WA USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Nikpoor, Naghmeh; Huan Chu Pham Dang; Ahn, Byung Soo; Sladek, Robert] McGill Univ, Fac Med, Dept Human Genet, Montreal, PQ, Canada.
[Nikpoor, Naghmeh; Huan Chu Pham Dang; Ahn, Byung Soo; Sladek, Robert] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
[Gibbs, Richard A.; Muzny, Donna; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genome Sequencing Ctr, Baylor Coll Med, Houston, TX 77030 USA.
[Wang, Shuai; Dupuis, Josee; Liu, Ching-Ti; White, Charles C.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Dauriz, Marco] Univ Verona, Div Endocrinol Diabet & Metab, Dept Med, Sch Med, I-37100 Verona, Italy.
[Dauriz, Marco] Hosp Trust Verona, Verona, Italy.
[Barzilay, Joshua I.] Kaiser Permanente Georgia, Div Endocrinol, Atlanta, GA USA.
[Barzilay, Joshua I.] Emory Univ, Sch Med, Atlanta, GA USA.
[Dupuis, Josee; Johnson, Andrew D.] NHLBI, Framingham Heart Study, Cardiovasc Epidemiol & Human Genom Ctr, Framingham, MA USA.
[Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Coresh, Josef] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA.
[Coresh, Josef; Kao, W. H. Linda; Reid, Jeffrey G.] Johns Hopkins Univ, Dept Epidemiol, Johns Hopkins Univ Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Wong, Tien Y.] Duke NUS Grad Med Sch, Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore, Singapore.
[Wong, Tien Y.] Natl Univ Singapore, Dept Ophthalmol, Yong Loo Lin Sch Med, Singapore 117548, Singapore.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr Torrance, Inst Translat Genom & Populat Sci, Los Angeles Biomed Reasearch Inst, Torrance, CA USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr Torrance, Dept Pediat, Torrance, CA USA.
RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM jmeigs@partners.org
RI Johnson, Andrew/G-6520-2013; Dauriz, Marco/S-5843-2016;
OI Dauriz, Marco/0000-0002-5542-5941; Sladek, Robert/0000-0002-2730-1204;
Pankow, James/0000-0001-7076-483X
FU National Institutes of Health (NIH) through the American Recovery and
Reinvestment Act (ARRA) [5RC2HL102419]; Baylor Genome Center [U54
HG003273]; National Heart, Lung, and Blood Institute (NHLBI)
[HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN2682011 00009C, HHSN2682011000010C,
HHSN2682011000011C, HHSN2682011000012C]; Boston University
[N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans
Endowment of the Department of Medicine at Boston University School of
Medicine; Boston Medical Center; American Diabetes Association Mentored
Post Doctoral Fellowship Award; National Institute on Aging (NIA)
[AG023629]; the NHLBI [N01-HC-25195, HHSN268201200036C,
HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080]; NHLBI.
[N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295, HL087652,
HL105756]; [R01DK078616]; [K24 DK080140]
FX Funding support for Building on GWAS for NHLBI-diseases: the US CHARGE
Consortium was provided by the National Institutes of Health (NIH)
through the American Recovery and Reinvestment Act of 2009 (ARRA;
5RC2HL102419). Data for Building on GWAS for NHLBI-diseases: the US
CHARGE Consortium was provided by Dr Boerwinkle on behalf of the ARIC
study, L. Adrienne Cupples, principal investigator for the FHS, and Dr
Psaty, principal investigator for the CHS. Support was also received
from the Baylor Genome Center (U54 HG003273). The ARIC study is
performed as a collaborative study supported by National Heart, Lung,
and Blood Institute (NHLBI) contracts (HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN2682011
00009C, HHSN2682011000010C, HHSN2682011000011C, and HHSN2682011000012C).
The FHS is conducted and supported by the NHLBI in collaboration with
Boston University (contract No. N01-HC-25195), and its contract with
Affymetrix, Inc, for genome-wide genotyping services (contract No.
N02-HL-6-4278) and for quality control by FHS investigators using
genotypes in the SNP Health Association Resource (SHARe) project. A
portion of this research was conducted using the Linux Cluster for
Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment
of the Department of Medicine at Boston University School of Medicine
and Boston Medical Center. This research is also supported by
R01DK078616, K24 DK080140 and an American Diabetes Association Mentored
Post Doctoral Fellowship Award (Dr Meigs). This CHS research was
supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C,
N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083,
N01HC85086; and NHLBI grants HL080295, HL087652, HL105756 with
additional contribution from the National Institute of Neurological
Disorders and Stroke (NINDS). Additional support was provided through
AG023629 from the National Institute on Aging (NIA). A full list of CHS
investigators and institutions can be found at https://chs-nhlbi.org/pi.
NR 46
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U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD JUN
PY 2014
VL 7
IS 3
BP 374
EP 382
DI 10.1161/CIRCGENETICS.113.000169
PG 9
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA AK1VY
UT WOS:000338207300020
PM 24951664
ER
PT J
AU Ward, MM
AF Ward, Michael M.
TI Update on the American College of Rheumatology/Spondyloarthritis
Research and Treatment Network/Spondylitis Association of America axial
spondyloarhtritis treatment guidelines project
SO CLINICAL RHEUMATOLOGY
LA English
DT Article
DE Ankylosing spondylitis; Axial spondyloarthritis; Guidelines
AB The American College of Rheumatology, the Spondyloarthritis Research and Treatment Network, and the Spondylitis Association of America have begun collaborating on a project to develop treatment guidelines for axial spondyloarthritis. The project will use the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method, which is based on systematic literature reviews and quantitative evidence summaries, to develop treatment recommendations for the use of pharmacological interventions, rehabilitation, surgery, preventive care, and disease monitoring in patients with ankylosing spondylitis and axial spondyloarthritis.
C1 NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), NIAMSD, Intramural Res Program, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases,
National Institutes of Health
FX This work was supported by the Intramural Research Program, National
Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institutes of Health.
NR 1
TC 2
Z9 3
U1 0
U2 1
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0770-3198
EI 1434-9949
J9 CLIN RHEUMATOL
JI Clin. Rheumatol.
PD JUN
PY 2014
VL 33
IS 6
BP 739
EP 740
DI 10.1007/s10067-014-2660-9
PG 2
WC Rheumatology
SC Rheumatology
GA AK3KW
UT WOS:000338323800002
PM 24810702
ER
PT J
AU Lanzer, P
Boehm, M
Sorribas, V
Thiriet, M
Janzen, J
Zeller, T
St Hilaire, C
Shanahan, C
AF Lanzer, Peter
Boehm, Manfred
Sorribas, Victor
Thiriet, Marc
Janzen, Jan
Zeller, Thomas
St Hilaire, Cynthia
Shanahan, Catherine
TI Medial vascular calcification revisited: review and perspectives
SO EUROPEAN HEART JOURNAL
LA English
DT Review
DE Vascular calcifications; Monckeberg's media sclerosis; Vascular
molecular biology and genetics; Vascular function
ID SMOOTH-MUSCLE-CELLS; CALCIUM-PHOSPHATE DEPOSITION;
AMERICAN-HEART-ASSOCIATION; CHRONIC KIDNEY-DISEASE; FETUIN-A LEVELS;
ARTERIAL CALCIFICATION; ATHEROSCLEROTIC LESIONS; CARDIOVASCULAR-DISEASE;
MONCKEBERGS SCLEROSIS; CORONARY-ARTERIES
AB Vascular calcifications (VCs) are actively regulated biological processes associated with crystallization of hydroxyapatite in the extracellular matrix and in cells of the media (VCm) or intima (VCi) of the arterial wall. Both patterns of VC often coincide and occur in patients with type II diabetes, chronic kidney disease, and other less frequent disorders; VCs are also typical in senile degeneration. In this article, we review the current state of knowledge about the pathology, molecular biology, and nosology of VCm, expand on potential mechanisms responsible for poor prognosis, and expose some of the directions for future research in this area.
C1 [Lanzer, Peter] Bitterfeld Wolfen gGmbH, Hlth Care Ctr Bitterfeld, Dept Internal Med, Div Cardiovasc Dis, D-06749 Bitterfeld, Germany.
[Boehm, Manfred; St Hilaire, Cynthia] NIH, Ctr Mol Med, Bethesda, MD 20892 USA.
[Sorribas, Victor] Univ Zaragoza, Mol Toxicol Lab, Zaragoza, Spain.
[Thiriet, Marc] Natl Inst Res Comp Sci & Control, Paris, France.
[Janzen, Jan] VascPath, Bern, Switzerland.
[Zeller, Thomas] Univ Heart Ctr Freiburg, Bad Krozingen, Germany.
[Shanahan, Catherine] Kings Coll London, Div Cardiovasc, London, England.
RP Lanzer, P (reprint author), Bitterfeld Wolfen gGmbH, Hlth Care Ctr Bitterfeld, Dept Internal Med, Div Cardiovasc Dis, Friedrich Ludwig Jahn Str 2, D-06749 Bitterfeld, Germany.
EM planzer@gzbiwo.de
OI Sorribas, Victor/0000-0003-3457-323X; St. Hilaire,
Cynthia/0000-0003-1871-6915
FU British Heart Foundation [RG/11/14/29056]
NR 135
TC 54
Z9 63
U1 3
U2 41
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD JUN
PY 2014
VL 35
IS 23
BP 1515
EP U24
DI 10.1093/eurheartj/ehu163
PG 14
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AK0OF
UT WOS:000338112700010
PM 24740885
ER
PT J
AU Guy, GP
Yabroff, KR
Ekwueme, DU
Smith, AW
Dowling, EC
Rechis, R
Nutt, S
Richardson, LC
AF Guy, Gery P., Jr.
Yabroff, K. Robin
Ekwueme, Donatus U.
Smith, Ashley Wilder
Dowling, Emily C.
Rechis, Ruth
Nutt, Stephanie
Richardson, Lisa C.
TI Estimating The Health And Economic Burden Of Cancer Among Those
Diagnosed As Adolescents And Young Adults
SO HEALTH AFFAIRS
LA English
DT Article
ID UNITED-STATES; SURVIVORS; PRODUCTIVITY; PREVALENCE; IMPACT; CHALLENGES;
COSTS; CARE
AB Adolescent and young adult cancer survivors-those who were ages 15-39 at their first cancer diagnosis-have important health limitations. These survivors are at risk for higher health care expenditures and lost productivity, compared to adults without a history of cancer. Using Medical Expenditure Panel Survey data, we present nationally representative estimates of the economic burden among people who were diagnosed with cancer in adolescence or young adulthood. Our findings demonstrate that surviving cancer at this age is associated with a substantial economic burden. Compared to adults without a history of cancer, adolescent and young adult cancer survivors had excess annual medical expenditures of $3,170 per person and excess annual productivity losses of $2,250 per person. Multifaceted prevention strategies, including education and sustained intervention programs to ensure access to lifelong risk-based follow-up care, may be effective ways to improve the economic outcomes associated with cancer survivorship in this population.
C1 [Guy, Gery P., Jr.] Ctr Dis Control & Prevent CDC, Div Canc Prevent & Control, Atlanta, GA 30333 USA.
[Yabroff, K. Robin; Smith, Ashley Wilder] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Ekwueme, Donatus U.] CDC, Div Canc Prevent & Control, Atlanta, GA 30333 USA.
[Dowling, Emily C.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Rechis, Ruth] LIVESTRONG Fdn, Austin, TX USA.
[Nutt, Stephanie] LIVESTRONG Fdn, Res & Evaluat Team, Austin, TX USA.
[Richardson, Lisa C.] CDC, Div Blood Disorders, Atlanta, GA 30333 USA.
RP Guy, GP (reprint author), Ctr Dis Control & Prevent CDC, Div Canc Prevent & Control, Atlanta, GA 30333 USA.
EM irm2@cdc.gov
FU Intramural CDC HHS [CC999999]
NR 31
TC 17
Z9 18
U1 7
U2 14
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD JUN
PY 2014
VL 33
IS 6
BP 1024
EP 1031
DI 10.1377/hlthaff.2013.1425
PG 8
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA AK1PL
UT WOS:000338187200014
PM 24889952
ER
PT J
AU Campbell, MC
Ranciaro, A
Zinshteyn, D
Rawlings-Goss, R
Hirbo, J
Thompson, S
Woldemeskel, D
Froment, A
Omar, SA
Bodo, JM
Nyambo, T
Belay, G
Drayna, D
Breslin, PAS
Tishkoff, SA
AF Campbell, Michael C.
Ranciaro, Alessia
Zinshteyn, Daniel
Rawlings-Goss, Renata
Hirbo, Jibril
Thompson, Simon
Woldemeskel, Dawit
Froment, Alain
Omar, Sabah A.
Bodo, Jean-Marie
Nyambo, Thomas
Belay, Gurja
Drayna, Dennis
Breslin, Paul A. S.
Tishkoff, Sarah A.
TI Limited evidence for adaptive evolution and functional effect of allelic
variation at rs702424 in the promoter of the TAS2R16 bitter taste
receptor gene in Africa
SO JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID SELECTION; SENSITIVITY; INFECTION; HISTORY; PTC
AB Bitter taste perception, mediated by receptors encoded by the TAS2R loci, has important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on the levels of salicin bitter taste perception. Here, we examined alleles at rs702424 for signatures of selection using Extended Haplotype Homozygosity (EHH) and F-ST statistics in diverse populations from West Central, Central and East Africa. We also performed a genotype-phenotype analysis of salicin sensitivity in a subset of 135 individuals from East Africa. Based on our data, we did not find evidence for positive selection at rs702424 in African populations, suggesting that nucleotide position 516 is likely the site under selection at TAS2R16. Moreover, we did not detect a significant association between rs702424 alleles and salicin bitter taste recognition, implying that this site does not contribute to salicin phenotypic variance. Overall, this study of African diversity provides further information regarding the genetic architecture and evolutionary history of a biologically-relevant trait in humans.
C1 [Campbell, Michael C.; Ranciaro, Alessia; Rawlings-Goss, Renata; Hirbo, Jibril; Thompson, Simon; Woldemeskel, Dawit; Tishkoff, Sarah A.] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
[Zinshteyn, Daniel; Tishkoff, Sarah A.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA.
[Woldemeskel, Dawit; Belay, Gurja] Univ Addis Ababa, Dept Biol, Addis Ababa, Ethiopia.
[Froment, Alain] IRD MNHN, UMR 208, Paris, France.
[Omar, Sabah A.] Kenya Govt Med Res Ctr, Ctr Biotechnol & Allied Sci, Nairobi, Kenya.
[Bodo, Jean-Marie] Minist Sci Res & Innovat, Yaounde, Cameroon.
[Nyambo, Thomas] Muhimbili Univ Hlth & Allied Sci, Dept Biochem, Dar Es Salaam, Tanzania.
[Drayna, Dennis] NIDCD, NIH, Rockville, MD USA.
[Breslin, Paul A. S.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA.
[Breslin, Paul A. S.] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA.
RP Tishkoff, SA (reprint author), Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
EM tishkoff@mail.med.upenn.edu
FU US National Science Foundation [BCS-0552486, BCS-0827436]; US National
Institutes of Health [R01GM076637, 5DP1ES022577 05, RO1 DC02995]
FX We thank Fathya Abdo, Eva Aluvalla, Godfrey Lema, Birhanu Mekaunintie,
Alemayehu Moges, Hussein Musa, Lilian Nyindodo and Solomon Taye who
helped with the field work, and the various institutions in West
Central, Central and East Africa for their generous support. We thank
Dongbo Hu and Wen-Ya Ko for useful discussions. We also offer our
deepest appreciation to the many Africans who generously donated their
DNA and time so that we can learn more about African genetic diversity.
This work was supported by the US National Science Foundation (grant
numbers BCS-0552486, BCS-0827436), US National Institutes of Health
(grant numbers R01GM076637, 5DP1ES022577 05) to SAT and US National
Institutes of Health (grant number RO1 DC02995) to PASB.
NR 15
TC 0
Z9 0
U1 3
U2 20
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1434-5161
EI 1435-232X
J9 J HUM GENET
JI J. Hum. Genet.
PD JUN
PY 2014
VL 59
IS 6
BP 349
EP 352
DI 10.1038/jhg.2014.29
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA AK1PC
UT WOS:000338186000011
PM 24785689
ER
PT J
AU Shimizu, N
Ueno, K
Kurita, E
Shin, SW
Nishihara, T
Amano, T
Anzai, M
Kishigami, S
Kato, H
Mitani, T
Hosoi, Y
Matsumoto, K
AF Shimizu, Natsumi
Ueno, Kimihiro
Kurita, Ena
Shin, Seung-Wook
Nishihara, Takuji
Amano, Tomoko
Anzai, Masayuki
Kishigami, Satoshi
Kato, Hiromi
Mitani, Tasuku
Hosoi, Yoshihiko
Matsumoto, Kazuya
TI Possible Role of ZPAC, Zygote-specific Proteasome Assembly Chaperone,
During Spermatogenesis in the Mouse
SO JOURNAL OF REPRODUCTION AND DEVELOPMENT
LA English
DT Article
DE Spermatogenesis; Ubiquitin-proteasome system; Zygote-specific proteasome
assembly chaperone (ZPAC)
ID GERM-CELL APOPTOSIS; EXPERIMENTAL CRYPTORCHIDISM; TESTIS; MICE;
ACTIVATION; EXPRESSION; CLEARANCE; HISTONES; INSIGHTS; REMOVAL
AB In the mammalian testis, the ubiquitin-proteasome system plays important roles in the process that promotes the formation of mature sperm. We recently identified zygote-specific proteasome assembly chaperone (ZPAC), which is specifically expressed in the mouse gonads and zygote. ZPAC mediates a unique proteasome assembly pathway in the zygote, but the expression profile and function of ZPAC in the testis is not fully understood. In this study, we investigated the possible role of ZPAC during mouse spermatogenesis. First, we analyzed the expression of ZPAC and 20S proteasome subunit alpha 4/PSMA7 in the adult mouse testis. ZPAC and alpha 4 were expressed in spermatogonia, spermatocytes, and round spermatids. In elongating spermatids, ZPAC was expressed until step 10, whereas expression of alpha 4 persisted until step 12. We then examined the expression profile of ZPAC and alpha 4 in a mouse model of experimental unilateral cryptorchidism. Consistent with appearance of morphologically impaired germ cells following cryptorchidism, the ZPAC protein level was significantly decreased at 4 days post induction of experimental cryptorchidism (D4) compared with the intact testis, although the amount of alpha 4 protein persisted at least until D10. Moreover, intense ZPAC staining was co-localized with staining of annexin V, an early indicator of apoptosis in mammalian cells, in germ cells of cryptorchid testis, but ZPAC was also expressed in germ cells showing no detectable expression of annexin V. These results suggest that ZPAC plays a role during spermatogenesis and raises the possibility that 20S proteasome mediated by ZPAC may be involved in the regulation of germ cell survival during spermatogenesis.
C1 [Shimizu, Natsumi; Nishihara, Takuji; Amano, Tomoko; Anzai, Masayuki; Kishigami, Satoshi; Kato, Hiromi; Mitani, Tasuku; Hosoi, Yoshihiko; Matsumoto, Kazuya] Kinki Univ, Grad Sch Biol Oriented Sci & Technol, Lab Mol Dev Biol, Wakayama 6496493, Japan.
[Ueno, Kimihiro; Kurita, Ena] Kinki Univ, Fac Biol Oriented Sci & Technol, Lab Mol Dev Biol, Wakayama 6496493, Japan.
[Shin, Seung-Wook] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Anzai, Masayuki; Kato, Hiromi; Mitani, Tasuku] Kinki Univ, Inst Adv Technol, Wakayama 6420017, Japan.
RP Matsumoto, K (reprint author), Kinki Univ, Grad Sch Biol Oriented Sci & Technol, Lab Mol Dev Biol, Wakayama 6496493, Japan.
FU Japan Society for the Promotion of Science [25292189]; INAMORI
Foundation
FX This study was supported in part by a Grant-in-Aid for Scientific
Research from the Japan Society for the Promotion of Science 25292189
(to KM), and a grant from the INAMORI Foundation (to KM).
NR 34
TC 2
Z9 2
U1 4
U2 5
PU SOCIETY REPRODUCTION & DEVELOPMENT-SRD
PI TSUKUBA
PA C/O KAZUHIRO KIKUCHI, PHD DVM, NATL INST AGROBIOLOGICAL SCIENCES
KANNONDAI 2-1-2, TSUKUBA, IBARAKI 305-8602, JAPAN
SN 0916-8818
J9 J REPROD DEVELOP
JI J. Reprod. Dev.
PD JUN
PY 2014
VL 60
IS 3
BP 179
EP 186
PG 8
WC Agriculture, Dairy & Animal Science; Reproductive Biology
SC Agriculture; Reproductive Biology
GA AK2TF
UT WOS:000338271700002
PM 24583807
ER
PT J
AU Wittig, JH
Richmond, BJ
AF Wittig, John H., Jr.
Richmond, Barry J.
TI Monkeys rely on recency of stimulus repetition when solving short-term
memory tasks
SO LEARNING & MEMORY
LA English
DT Article
ID INFERIOR TEMPORAL CORTEX; VISUAL WORKING-MEMORY; RECOGNITION MEMORY;
LONG-TERM; FAMILIARITY; MACAQUE; MECHANISMS; ANTERIOR; REPRESENTATION;
NEURONS
AB Seven monkeys performed variants of two short-term memory tasks that others have used to differentiate between selective and nonselective memory mechanisms. The first task was to view a list of sequentially presented images and identify whether a test matched any image from the list, but not a distractor from a preceding list. Performance was best when the test matched the most recently presented image. Response rates depended linearly on recency of repetition whether the test matched a sample from the current list or a distractor from a preceding list, suggesting nonselective memorization of all images viewed instead of just the sample images. The second task was to remember just the first image in a list selectively and ignore subsequent distractors. False alarms occurred frequently when the test matched a distractor presented near the beginning of the sequence. In a pilot experiment, response rates depended linearly on recency of repetition irrespective of whether the test matched the first image or a distractor, again suggesting nonselective memorization of all images instead of just the first image. Modification of the second task improved recognition of the first image, but did not abolish use of recency. Monkeys appear to perform nonspatial visual short-term memory tasks often ( or exclusively) using a single, nonselective, memory mechanism that conveys the recency of stimulus repetition.
C1 [Wittig, John H., Jr.; Richmond, Barry J.] NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bldg 9, Bethesda, MD 20892 USA.
EM bjr@ln.nimh.nih.gov
FU Intramural Research Program of the National Institute of Mental Health
FX We thank Adin Horovitz and Evan Masseau for assisting with data
collection, and Mark Eldridge and Brian Scott for their critical
comments that helped improve the manuscript. The views expressed in this
article do not necessarily represent the views of the NIMH, NIH, or the
US Government. This study was supported by the Intramural Research
Program of the National Institute of Mental Health.
NR 34
TC 3
Z9 3
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 1072-0502
EI 1549-5485
J9 LEARN MEMORY
JI Learn. Mem.
PD JUN
PY 2014
VL 21
IS 6
BP 325
EP 333
DI 10.1101/lm.034181.113
PG 9
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA AK5ZM
UT WOS:000338506200004
PM 25171424
ER
PT J
AU Bugreev, DV
Huang, F
Mazina, OM
Pezza, RJ
Voloshin, ON
Camerini-Otero, RD
Mazin, AV
AF Bugreev, Dmitry V.
Huang, Fei
Mazina, Olga M.
Pezza, Roberto J.
Voloshin, Oleg N.
Camerini-Otero, R. Daniel
Mazin, Alexander V.
TI HOP2-MND1 modulates RAD51 binding to nucleotides and DNA
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DOUBLE-STRAND BREAK; COLI RECA PROTEIN; MEIOTIC RECOMBINATION;
HOMOLOGOUS RECOMBINATION; COMPLEX-FORMATION; ATP HYDROLYSIS; HOP2
PROTEIN; MEIOSIS; REPAIR; DMC1
AB The HOP2-MND1 heterodimer is required for progression of homologous recombination in eukaryotes. In vitro, HOP2-MND1 stimulates the DNA strand exchange activities of RAD51 and DMC1. We demonstrate that HOP2-MND1 induces changes in the conformation of RAD51 that profoundly alter the basic properties of RAD51. HOP2-MND1 enhances the interaction of RAD51 with nucleotide cofactors and modifies its DNA-binding specificity in a manner that stimulates DNA strand exchange. It enables RAD51 DNA strand exchange in the absence of divalent metal ions required for ATP binding and offsets the effect of the K133A mutation that disrupts ATP binding. During nucleoprotein formation HOP2-MND1 helps to load RAD51 on ssDNA restricting its dsDNA-binding and during the homology search it promotes dsDNA binding removing the inhibitory effect of ssDNA. The magnitude of the changes induced in RAD51 defines HOP2-MND1 as a 'molecular trigger' of RAD51 DNA strand exchange.
C1 [Bugreev, Dmitry V.; Huang, Fei; Mazina, Olga M.; Mazin, Alexander V.] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA.
[Pezza, Roberto J.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Dept Cell Biol, Oklahoma City, OK 73104 USA.
[Voloshin, Oleg N.; Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Camerini-Otero, RD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
EM camerini@mail.nih.gov; amazin@drexelmed.edu
FU NIH [CA100839, DA033981, MH097512, GM103636]; Leukemia and Lymphoma
Society Scholar Award [1054-09]; W.M. Keck Foundation Award; National
Institute of Diabetes and Digestive and Kidney Diseases
FX We thank P. Sung (Yale) for the hRAD51 expression vector. We thank
members of the Camerini-Otero and Mazin labs for comments and
discussion. This work was supported by the NIH grants CA100839,
DA033981, MH097512, the Leukemia and Lymphoma Society Scholar Award
1054-09, W.M. Keck Foundation Award (to A. V. M.), the Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases (to R.D.C.-O.), and the NIH grant GM103636 (to R.J.P.).
NR 57
TC 12
Z9 12
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUN
PY 2014
VL 5
AR 4198
DI 10.1038/ncomms5198
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL0TC
UT WOS:000338838700023
PM 24943459
ER
PT J
AU Cammas, A
Sanchez, BJ
Lian, XJ
Dormoy-Raclet, V
van der Giessen, K
de Silanes, IL
Ma, J
Wilusz, C
Richardson, J
Gorospe, M
Millevoi, S
Giovarelli, M
Gherzi, R
Di Marco, S
Gallouzi, IE
AF Cammas, Anne
Sanchez, Brenda Janice
Lian, Xian Jin
Dormoy-Raclet, Virginie
van der Giessen, Kate
Lopez de Silanes, Isabel
Ma, Jennifer
Wilusz, Carol
Richardson, John
Gorospe, Myriam
Millevoi, Stefania
Giovarelli, Matteo
Gherzi, Roberto
Di Marco, Sergio
Gallouzi, Imed-Eddine
TI Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is
required for muscle fibre formation
SO NATURE COMMUNICATIONS
LA English
DT Article
ID BINDING PROTEIN HUR; AU-RICH ELEMENTS; EMBRYONIC-DEVELOPMENT; CELL
DIFFERENTIATION; GENE-EXPRESSION; HEAT-SHOCK; DECAY; STABILIZATION;
DEGRADATION; PHOSPHORYLATION
AB HuR promotes myogenesis by stabilizing the MyoD, myogenin and p21 mRNAs during the fusion of muscle cells to form myotubes. Here we show that HuR, via a novel mRNA destabilizing activity, promotes the early steps of myogenesis by reducing the expression of the cell cycle promoter nucleophosmin (NPM). Depletion of HuR stabilizes the NPM mRNA, increases NPM protein levels and inhibits myogenesis, while its overexpression elicits the opposite effects. NPM mRNA destabilization involves the association of HuR with the decay factor KSRP as well as the ribonuclease PARN and the exosome. The C terminus of HuR mediates the formation of the HuR-KSRP complex and is sufficient for maintaining a low level of the NPM mRNA as well as promoting the commitment of muscle cells to myogenesis. We therefore propose a model whereby the downregulation of the NPM mRNA, mediated by HuR, KSRP and its associated ribonucleases, is required for proper myogenesis.
C1 [Cammas, Anne; Sanchez, Brenda Janice; Lian, Xian Jin; Dormoy-Raclet, Virginie; van der Giessen, Kate; Ma, Jennifer; Di Marco, Sergio; Gallouzi, Imed-Eddine] McGill Univ, Dept Biochem, Goodman Canc Ctr, Montreal, PQ H3G 1Y6, Canada.
[Cammas, Anne; Millevoi, Stefania] Ctr Rech Cancerol Toulouse, INSERM, UMR 1037, F-31432 Toulouse, France.
[Lopez de Silanes, Isabel] Spanish Natl Canc Res Ctr CNIO Telomeres & Telome, Mol Oncol Program, Madrid 28029, Spain.
[Wilusz, Carol] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[Richardson, John] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada.
[Gorospe, Myriam] NIA, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Giovarelli, Matteo; Gherzi, Roberto] Ist Nazl Ric Cancro IST, Lab Gene Express Regulat, I-16132 Genoa, Italy.
RP Gallouzi, IE (reprint author), McGill Univ, Dept Biochem, Goodman Canc Ctr, McIntyre Bldg Room 915B, Montreal, PQ H3G 1Y6, Canada.
EM imed.gallouzi@mcgill.ca
RI CAMMAS, Anne/M-7238-2014; Millevoi, Stefania/M-7244-2014; Giovarelli,
Matteo/K-1573-2016; Lopez de Silanes, Isabel/K-4962-2015;
OI Millevoi, Stefania/0000-0003-1659-3552; Lopez de Silanes,
Isabel/0000-0001-6762-9792; Di Marco, Sergio/0000-0002-4039-0600
FU Canderal scholarship for PDFs; Peter Quinlan Fellowship in Oncolgy;
Canadian Cancer Society; CIHR [MOP-89798]; NIA-IRP, NIH; AIRC [IG
2010-2012]; AICR [10-0527]
FX We thank Dr C. von Roretz for critical review of this manuscript and
insightful discussion. We are grateful to Veronique Sauve and Dr Kalle
Gehring for their help with the BIACORE experiments. A. C. is a
recipient of the Canderal scholarship for PDFs (2010-2011) as well as
the Peter Quinlan Fellowship in Oncolgy (2011-2012). V.D.-R. is a
Research Fellow of the Terry Fox foundation through an award from the
Canadian Cancer Society (former National Cancer Institute of Canada).
This work was supported by a CIHR (MOP-89798) operating grant to I.-E.
G. M. G. is supported by the NIA-IRP, NIH. R. G. is supported by grants
from AIRC (IG 2010-2012) and AICR (No. 10-0527). I.-E. G. is a recipient
of a TierII Canada Research Chair.
NR 59
TC 9
Z9 9
U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUN
PY 2014
VL 5
AR 4190
DI 10.1038/ncomms5190
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL0TC
UT WOS:000338838700015
PM 24969639
ER
PT J
AU Wang, HC
DeRose, EF
London, RE
Shears, SB
AF Wang, Huanchen
DeRose, Eugene F.
London, Robert E.
Shears, Stephen B.
TI IP6K structure and the molecular determinants of catalytic specificity
in an inositol phosphate kinase family
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DIPHOSPHOINOSITOL POLYPHOSPHATE PHOSPHOHYDROLASE; HEXAKISPHOSPHATE
KINASE; CRYSTAL-STRUCTURE; 1,3,4,5,6-PENTAKISPHOSPHATE 2-KINASE;
1,4,5-TRISPHOSPHATE 3-KINASE; GENE DELETION; CELL-SURVIVAL;
PYROPHOSPHATES; MULTIKINASE; METABOLISM
AB Inositol trisphosphate kinases (IP3Ks) and inositol hexakisphosphate kinases (IP6Ks) each regulate specialized signalling activities by phosphorylating either InsP(3) or InsP(6) respectively. The molecular basis for these different kinase activities can be illuminated by a structural description of IP6K. Here we describe the crystal structure of an Entamoeba histolytica hybrid IP6K/IP3K, an enzymatic parallel to a 'living fossil'. Through molecular modelling and mutagenesis, we extrapolated our findings to human IP6K2, which retains vestigial IP3K activity. Two structural elements, an alpha-helical pair and a rare, two-turn 3(10) helix, together forge a substrate-binding pocket with an open clamshell geometry. InsP(6) forms substantial contacts with both structural elements. Relative to InsP(6), enzyme-bound InsP(3) rotates 55 degrees closer to the a-helices, which provide most of the protein's interactions with InsP(3). These data reveal the molecular determinants of IP6K activity, and suggest an unusual evolutionary trajectory for a primordial kinase that could have favored efficient bifunctionality, before propagation of separate IP3Ks and IP6Ks.
C1 [Wang, Huanchen; Shears, Stephen B.] NIEHS, Inositol Signaling Grp, NIH, Res Triangle Pk, NC 27709 USA.
[DeRose, Eugene F.; London, Robert E.] NIEHS, Nucl Magnet Resonance Grp, NIH, Res Triangle Pk, NC 27709 USA.
RP Shears, SB (reprint author), NIEHS, Inositol Signaling Grp, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM shears@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences
FX This research was supported by the Intramural Research Programme of the
NIH, National Institute of Environmental Health Sciences. We thank T. M.
Hall and L. C. Pedersen for discussions and critical reading of the
manuscript, the NIEHS Collaborative crystallography group, the Advanced
Photon Source (APS) Southeast Regional Collaborative Access Team
(SER-CAT) 22-ID and 22-BM beam lines for assistance with
crystallographic data collection.
NR 55
TC 9
Z9 10
U1 4
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUN
PY 2014
VL 5
AR 4178
DI 10.1038/ncomms5178
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA AL0TC
UT WOS:000338838700003
PM 24956979
ER
PT J
AU Buchanan, ND
Block, R
Smith, AW
Tai, E
AF Buchanan, Natasha D.
Block, Rebecca
Smith, Ashley Wilder
Tai, Eric
TI Psychosocial Barriers and Facilitators to Clinical Trial Enrollment and
Adherence for Adolescents With Cancer
SO PEDIATRICS
LA English
DT Article
DE adherence; adolescent; cancer survivors; clinical trial; enrollment;
psychosocial
ID EDUCATION SHARE PROGRAM; YOUNG-ADULT CANCER; CHILDHOOD-CANCER;
LYMPHOBLASTIC-LEUKEMIA; SURVIVOR HEALTH; CONSENT FORMS; PARTICIPATION;
CHILDREN; ISSUES; EXPERIENCES
AB Adolescents (aged 15-19 years) have not experienced the same survival gains as children and older adults diagnosed with cancer. Poor clinical trial enrollment and adherence rates among adolescents may account for some of this disparity. Although biological, regulatory, systemic, and practice-related challenges to clinical trial enrollment and adherence have been examined, studies of psychosocial factors, which can serve as barriers or facilitators to enrollment and adherence, are limited. To bring attention to these psychological factors, we reviewed existing literature on psychosocial barriers and facilitators that can affect an adolescent's decision to enroll and adhere to a clinical trial. We also provide potential strategies to address psychosocial factors affecting clinical trial accrual and adherence.
C1 [Buchanan, Natasha D.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Epidemiol & Appl Res Branch, Atlanta, GA 30341 USA.
[Tai, Eric] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Comprehens Canc Control Branch, Atlanta, GA 30341 USA.
[Block, Rebecca] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Smith, Ashley Wilder] NCI, Outcomes Res Branch, Bethesda, MD 20892 USA.
RP Buchanan, ND (reprint author), Ctr Dis Control & Prevent, 4770 Buford Highway NE,MS K-55, Atlanta, GA 30341 USA.
EM nbuchanan@cdc.gov
NR 64
TC 3
Z9 3
U1 1
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 JUN
PY 2014
VL 133
SU 3
BP S123
EP S130
DI 10.1542/peds.2014-01221
PG 8
WC Pediatrics
SC Pediatrics
GA AK3TG
UT WOS:000338347000008
PM 24918211
ER
PT J
AU Zhang, XX
Chen, L
Dang, X
Liu, JL
Ito, Y
Sun, WJ
AF Zhang, Xinxin
Chen, Lin
Dang, Xuan
Liu, Jianli
Ito, Yoichiro
Sun, Wenji
TI Neuroprotective Effects of Total Steroid Saponins on Cerebral Ischemia
Injuries in an Animal Model of Focal Ischemia/Reperfusion
SO PLANTA MEDICA
LA English
DT Article
DE Dioscorea zingiberensis; Dioscoreaceae; steroid saponins; middle
cerebral artery occlusion; ischemia-reperfusion; anti-edema;
anti-oxidative
ID NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; ARTERY OCCLUSION; ACTIVATION; STROKE;
RATS; REPERFUSION; ERK1/2; BLOOD
AB Total steroid saponins isolated from Dioscorea zingiberensis are a unique traditional Chinese medicine known for its potential usage in various types of diseases. However, there is little evidence about its neuroprotective effect in transient focal ischemia-reperfusion cerebral injury. Therefore, the current study was carried out to investigate the effect of total steroid saponins on neuroprotection and its potential mechanisms in the rat ischemia-reperfusion model by middle cerebral artery occlusion for 90 min. The rats were each treated with total steroid saponins (30 mg/kg, 10 mg/kg, and 3 mg/kg) or nimodipine (20 mg/kg) daily for 6 days before middle cerebral artery occlusion. Then, the neurological deficit score, cerebral infarct volume, and brain water content were measured at 24 h after reperfusion. Meanwhile, the histopathological changes and AQP-4 protein activities were examined in hippocampal CA1 and the cortex of ipsilateral ischemic cerebral hemisphere by hematoxylin-eosin staining and immunohistochemistry, respectively. The indices of oxidative stress in the serum were also obtained, and NF-kappa B and ERK 1/2 protein expressions in the injured brain were evaluated by Western blotting. The results indicated that the pre-treatment with these drugs not only significantly reduced cerebral infarct volume, brain water content and improved neurological deficit score, but also restored neuronal morphology and decreased the AQP-4 positive cells in CA1 and the cortex. Moreover, it markedly restored the level of oxidant stress markers (CAT, SOD, MDA, NO and iNOS) to their normal range in serum. In addition, the increased NF-kappa B and ERK 1/2 protein expressions were alleviated as compared with the ischemia-reperfusion group. These findings demonstrate that total steroid saponins exhibit promising neuroprotection effects against the transient focal ischemia-reperfusion cerebral injury in the rat experimental model and the underlying mechanisms might be mediated through inhibition of anti-edema as well as anti-oxidative effects by inactivation of NF-kappa B and ERK 1/2 signalling pathway.
C1 [Zhang, Xinxin; Chen, Lin; Dang, Xuan; Liu, Jianli; Sun, Wenji] NW Univ Xian, Biomed Key Lab Shaanxi Prov, Xian 710069, Peoples R China.
[Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA.
EM itoy@nhlbi.nih.gov; cxbml@nwu.edu.cn
FU Intramural NIH HHS [Z99 HL999999]
NR 28
TC 5
Z9 6
U1 2
U2 9
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0032-0943
EI 1439-0221
J9 PLANTA MED
JI Planta Med.
PD JUN
PY 2014
VL 80
IS 8-9
BP 637
EP 644
DI 10.1055/s-0034-1368584
PG 8
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA AJ9NX
UT WOS:000338039800006
PM 24963614
ER
PT J
AU Ellis, TC
Jain, S
Linowski, AK
Rike, K
Bestor, A
Rosa, PA
Halpern, M
Kurhanewicz, S
Jewett, MW
AF Ellis, Tisha Choudhury
Jain, Sunny
Linowski, Angelika K.
Rike, Kelli
Bestor, Aaron
Rosa, Patricia A.
Halpern, Micah
Kurhanewicz, Stephanie
Jewett, Mollie W.
TI In Vivo Expression Technology Identifies a Novel Virulence Factor
Critical for Borrelia burgdorferi Persistence in Mice (vol 9, e1003567,
2013)
SO PLOS PATHOGENS
LA English
DT Correction
ID LYME-DISEASE SPIROCHETE; VLSE ANTIGENIC VARIATION; LINEAR PLASMIDS 1P25;
GENE-EXPRESSION; BACTERIAL VIRULENCE; MAMMALIAN HOST; INFECTIOUS CYCLE;
TICK VECTOR; IMMUNO-PCR; T-CELLS
AB Analysis of the transcriptome of Borrelia burgdorferi, the causative agent of Lyme disease, during infection has proven difficult due to the low spirochete loads in the mammalian tissues. To overcome this challenge, we have developed an In Vivo Expression Technology (IVET) system for identification of B. burgdorferi genes expressed during an active murine infection. Spirochetes lacking linear plasmid (lp) 25 are non-infectious yet highly transformable. Mouse infection can be restored to these spirochetes by expression of the essential lp25-encoded pncA gene alone. Therefore, this IVET-based approach selects for in vivo-expressed promoters that drive expression of pncA resulting in the recovery of infectious spirochetes lacking lp25 following a three week infection in mice. Screening of approximately 15,000 clones in mice identified 289 unique in vivo-expressed DNA fragments from across all 22 replicons of the B. burgdorferi B31 genome. The in vivo-expressed candidate genes putatively encode proteins in various functional categories including antigenicity, metabolism, motility, nutrient transport and unknown functions. Candidate gene bbk46 on essential virulence plasmid lp36 was found to be highly induced in vivo and to be RpoS-independent. The bbk46 gene was dispensable for B. burgdorferi infection in mice. Our findings highlight the power of the IVET-based approach for identification of B. burgdorferi in vivo-expressed genes, which might not be discovered using other genome-wide gene expression methods. Further investigation of the novel in vivo-expressed candidate genes will contribute to advancing the understanding of molecular mechanisms of B. burgdorferi survival and pathogenicity in the mammalian host.
C1 [Ellis, Tisha Choudhury; Jain, Sunny; Linowski, Angelika K.; Rike, Kelli; Halpern, Micah; Kurhanewicz, Stephanie; Jewett, Mollie W.] Univ Cent Florida Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32827 USA.
[Bestor, Aaron; Rosa, Patricia A.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Jewett, MW (reprint author), Univ Cent Florida Coll Med, Burnett Sch Biomed Sci, Orlando, FL 32827 USA.
EM Mollie.Jewett@ucf.edu
FU NIAID NIH HHS [K22 AI081730, R01 AI099094]
NR 84
TC 1
Z9 1
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUN
PY 2014
VL 10
IS 6
AR e1004260
DI 10.1371/journal.ppat.1004260
PG 18
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AK1SV
UT WOS:000338197400058
PM 24950221
ER
PT J
AU Magadan, JG
Altman, MO
Ince, WL
Hickman, HD
Stevens, J
Chevalier, A
Baker, D
Wilson, PC
Ahmed, R
Bennink, JR
Yewdell, JW
AF Magadan, Javier G.
Altman, Meghan O.
Ince, William L.
Hickman, Heather D.
Stevens, James
Chevalier, Aaron
Baker, David
Wilson, Patrick C.
Ahmed, Rafi
Bennink, Jack R.
Yewdell, Jonathan W.
TI Biogenesis of Influenza A Virus Hemagglutinin Cross-Protective Stem
Epitopes
SO PLOS PATHOGENS
LA English
DT Article
ID STALK-SPECIFIC ANTIBODIES; MEMORY B-CELLS; MONOCLONAL-ANTIBODIES;
INTRACELLULAR-TRANSPORT; RECEPTOR-BINDING; IMMUNE-RESPONSE;
GLYCOPROTEIN; NEUTRALIZATION; VACCINATION; TRIMERIZATION
AB Antigenic variation in the globular domain of influenza A virus (IAV) hemagglutinin (HA) precludes effective immunity to this major human pathogen. Although the HA stem is highly conserved between influenza virus strains, HA stem-reactive antibodies (StRAbs) were long considered biologically inert. It is now clear, however, that StRAbs reduce viral replication in animal models and protect against pathogenicity and death, supporting the potential of HA stem-based immunogens as drift-resistant vaccines. Optimally designing StRAb-inducing immunogens and understanding StRAb effector functions require thorough comprehension of HA stem structure and antigenicity. Here, we study the biogenesis of HA stem epitopes recognized in cells infected with various drifted IAV H1N1 strains using mouse and human StRAbs. Using a novel immunofluorescence (IF)-based assay, we find that human StRAbs bind monomeric HA in the endoplasmic reticulum (ER) and trimerized HA in the Golgi complex (GC) with similar high avidity, potentially good news for producing effective monomeric HA stem immunogens. Though HA stem epitopes are nestled among several N-linked oligosaccharides, glycosylation is not required for full antigenicity. Rather, as N-linked glycans increase in size during intracellular transport of HA through the GC, StRAb binding becomes temperature-sensitive, binding poorly to HA at 4 degrees C and well at 37 degrees C. A de novo designed, 65-residue protein binds the mature HA stem independently of temperature, consistent with a lack of N-linked oligosaccharide steric hindrance due to its small size. Likewise, StRAbs bind recombinant HA carrying simple N-linked glycans in a temperature-independent manner. Chemical cross-linking experiments show that N-linked oligosaccharides likely influence StRAb binding by direct local effects rather than by globally modifying the conformational flexibility of HA. Our findings indicate that StRAb binding to HA is precarious, raising the possibility that sufficient immune pressure on the HA stem region could select for viral escape mutants with increased steric hindrance from N-linked glycans.
C1 [Magadan, Javier G.; Altman, Meghan O.; Ince, William L.; Hickman, Heather D.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Stevens, James] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
[Chevalier, Aaron; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Wilson, Patrick C.] Univ Chicago, Knapp Ctr Lupus & Immunol Res, Dept Med, Sect Rheumatol,Comm Immunol, Chicago, IL 60637 USA.
[Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
RP Magadan, JG (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
EM jyewdell@niaid.nih.gov
RI Altman, Meghan/J-2975-2015
OI Altman, Meghan/0000-0002-8910-9074
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases
FX This work was supported by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 62
TC 2
Z9 2
U1 2
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUN
PY 2014
VL 10
IS 6
AR e1004204
DI 10.1371/journal.ppat.1004204
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AK1SV
UT WOS:000338197400038
PM 24945804
ER
PT J
AU Sully, EK
Malachowa, N
Elmore, BO
Alexander, SM
Femling, JK
Gray, BM
DeLeo, FR
Otto, M
Cheung, AL
Edwards, BS
Sklar, LA
Horswill, AR
Hall, PR
Gresham, HD
AF Sully, Erin K.
Malachowa, Natalia
Elmore, Bradley O.
Alexander, Susan M.
Femling, Jon K.
Gray, Brian M.
DeLeo, Frank R.
Otto, Michael
Cheung, Ambrose L.
Edwards, Bruce S.
Sklar, Larry A.
Horswill, Alexander R.
Hall, Pamela R.
Gresham, Hattie D.
TI Selective Chemical Inhibition of agr Quorum Sensing in Staphylococcus
aureus Promotes Host Defense with Minimal Impact on Resistance
SO PLOS PATHOGENS
LA English
DT Article
ID GLOBAL GENE-EXPRESSION; NADPH OXIDASE; LYTTR DOMAIN; VIRULENCE; SKIN;
ANTIBIOTICS; IDENTIFICATION; INFECTION; DISCOVERY; DISEASE
AB Bacterial signaling systems are prime drug targets for combating the global health threat of antibiotic resistant bacterial infections including those caused by Staphylococcus aureus. S. aureus is the primary cause of acute bacterial skin and soft tissue infections (SSTIs) and the quorum sensing operon agr is causally associated with these. Whether efficacious chemical inhibitors of agr signaling can be developed that promote host defense against SSTIs while sparing the normal microbiota of the skin is unknown. In a high throughput screen, we identified a small molecule inhibitor (SMI), savirin (S. aureus virulence inhibitor) that disrupted agr-mediated quorum sensing in this pathogen but not in the important skin commensal Staphylococcus epidermidis. Mechanistic studies employing electrophoretic mobility shift assays and a novel AgrA activation reporter strain revealed the transcriptional regulator AgrA as the target of inhibition within the pathogen, preventing virulence gene upregulation. Consistent with its minimal impact on exponential phase growth, including skin microbiota members, savirin did not provoke stress responses or membrane dysfunction induced by conventional antibiotics as determined by transcriptional profiling and membrane potential and integrity studies. Importantly, savirin was efficacious in two murine skin infection models, abating tissue injury and selectively promoting clearance of agr+ but not Delta agr bacteria when administered at the time of infection or delayed until maximal abscess development. The mechanism of enhanced host defense involved in part enhanced intracellular killing of agr+ but not Delta agr in macrophages and by low pH. Notably, resistance or tolerance to savirin inhibition of agr was not observed after multiple passages either in vivo or in vitro where under the same conditions resistance to growth inhibition was induced after passage with conventional antibiotics. Therefore, chemical inhibitors can selectively target AgrA in S. aureus to promote host defense while sparing agr signaling in S. epidermidis and limiting resistance development.
C1 [Sully, Erin K.; Alexander, Susan M.; Gray, Brian M.; Gresham, Hattie D.] New Mexico Vet Affairs Med Ctr, Res Serv, Albuquerque, NM 87108 USA.
[Sully, Erin K.; Gresham, Hattie D.] Univ New Mexico, Sch Med, Div Infect Dis, Dept Internal Med, Albuquerque, NM 87131 USA.
[Malachowa, Natalia; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Elmore, Bradley O.; Gray, Brian M.; Hall, Pamela R.] Univ New Mexico, Coll Pharm, Albuquerque, NM 87131 USA.
[Femling, Jon K.] Univ New Mexico, Dept Emergency Med, Albuquerque, NM 87131 USA.
[Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
[Cheung, Ambrose L.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Microbiol, Hanover, NH 03756 USA.
[Edwards, Bruce S.; Sklar, Larry A.] Univ New Mexico, Sch Med, Ctr Mol Discovery, Albuquerque, NM 87131 USA.
[Edwards, Bruce S.; Sklar, Larry A.] Univ New Mexico, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA.
[Horswill, Alexander R.] Univ Iowa, Dept Microbiol, Carver Coll Med, Iowa City, IA 52242 USA.
RP Sully, EK (reprint author), New Mexico Vet Affairs Med Ctr, Res Serv, Albuquerque, NM 87108 USA.
EM phall@salud.unm.edu
RI Hall, Pamela/O-5402-2016;
OI Hall, Pamela/0000-0003-2367-3382; DeLeo, Frank/0000-0003-3150-2516;
Otto, Michael/0000-0002-2222-4115
FU Department of Veterans Affairs; Intramural Research Program of the
NIAID, NIH; NIH [X01MH078952, R01 AI091917, U54MH084690, U54MH074425,
AT007052]; Infectious Diseases and Inflammation Training grant [T32
AI007538]; IRACDA [5K12 GM088021]
FX This work was supported by the Department of Veterans Affairs (HDG), the
Intramural Research Program of the NIAID, NIH (FRD, MO), and NIH grants
X01MH078952 (HDG), R01 AI091917 (PRH), U54MH084690 (LAS), U54MH074425
(LAS), and AT007052 (ARH). EKS was supported by T32 AI007538 Infectious
Diseases and Inflammation Training grant, and BMG was supported by
IRACDA training grant 5K12 GM088021. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 50
TC 57
Z9 58
U1 11
U2 56
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUN
PY 2014
VL 10
IS 6
AR e1004174
DI 10.1371/journal.ppat.1004174
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA AK1SV
UT WOS:000338197400017
PM 24945495
ER
PT J
AU Slugina, MA
Boris, KV
Kakimzhanova, AA
Kochieva, EZ
AF Slugina, M. A.
Boris, K. V.
Kakimzhanova, A. A.
Kochieva, E. Z.
TI Intraspecific polymorphism of the sucrose synthase genes in Russian and
Kazakh potato cultivars
SO RUSSIAN JOURNAL OF GENETICS
LA English
DT Article
ID SOLANUM-TUBEROSUM; PLANTS
AB In 12 different Russian and Kazakh potato cultivars, the polymorphism of the glucosyltransferase domain of the sucrose synthase gene was first examined, as well as the polymorphism of the sucrose synthase domain fragment of the same gene in the potato cultivars of Kazakh breed. It was demonstrated that the examined sequences contained point mutations, as well as insertions and deletions, including those not described earlier. Amino acid substitutions specific to heat- and drought-tolerant varieties were also identified and could be associated with the development of abiotic stress resistance.
C1 [Slugina, M. A.; Boris, K. V.; Kochieva, E. Z.] Russian Acad Sci, Bioengn Ctr, Moscow 117312, Russia.
[Boris, K. V.] Russian Acad Sci, Vavilov Inst Gen Genet, Moscow 119991, Russia.
[Kakimzhanova, A. A.] Natl Biotechnol Ctr, Astana 010000, Kazakhstan.
[Kochieva, E. Z.] Moscow MV Lomonosov State Univ, Dept Biotechnol, Fac Biol, Moscow 119991, Russia.
RP Slugina, MA (reprint author), Russian Acad Sci, Bioengn Ctr, Moscow 117312, Russia.
EM docboris@mail.ru
OI Kakimzhanova, Almagul/0000-0002-7797-6867
FU Russian Foundation for Basic Research [12-04-32291]; Program of the
Presidium of the Russian Academy of Sciences (Molecular and Cellular
Biology)
FX This study was supported by the Russian Foundation for Basic Research
(grant no. 12-04-32291) and the Program of the Presidium of the Russian
Academy of Sciences (Molecular and Cellular Biology).
NR 14
TC 2
Z9 2
U1 0
U2 4
PU MAIK NAUKA/INTERPERIODICA/SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA
SN 1022-7954
EI 1608-3369
J9 RUSS J GENET+
JI Russ. J. Genet.
PD JUN
PY 2014
VL 50
IS 6
BP 593
EP 597
DI 10.1134/S1022795414060118
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA AK2VT
UT WOS:000338278400007
ER
PT J
AU Zhang, Y
Chang, YCE
Louis, JM
Wang, YF
Harrison, RW
Weber, IT
AF Zhang, Ying
Chang, Yu-Chung E.
Louis, John M.
Wang, Yuan-Fang
Harrison, Robert W.
Weber, Irene T.
TI Structures of Darunavir-Resistant HIV-1 Protease Mutant Reveal Atypical
Binding of Darunavir to Wide Open Flaps
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID RESOLUTION CRYSTAL-STRUCTURES; CLINICAL INHIBITORS; DRUG-RESISTANCE;
IN-VITRO; TMC114; GENERATION; STABILITY; VARIANTS; SITES
AB The molecular basis for high resistance to clinical inhibitors of HIV-1 protease (PR) was examined for the variant designated PRP51 that was selected for resistance to darunavir (DRV). High resolution crystal structures of PRP51 with the active site D25N mutation revealed a ligand-free form and an inhibitor-bound form showing a unique binding site and orientation for DRV. This inactivating mutation is known to increase the dimer dissociation constant and decrease DRV affinity of PR The PRP51-D25N dimers were in the open conformation with widely separated flaps, as reported for other highly resistant variants. PRP51-D25N dimer bound two DRV molecules and showed larger separation of 8.7 angstrom between the closest atoms of the two flaps compared with 4.4 angstrom for the ligand-free structure of this mutant. The ligand-free structure, however, lacked van der Waals contacts between Ile50 and Pro81' from the other subunit in the dimer, unlike the majority of PR structures. DRV is bound inside the active site cavity; however, the inhibitor is oriented almost perpendicular to its typical position and exhibits only 2 direct hydrogen bond and two water-mediated interactions with atoms of PRP51-D25N compared with 11 hydrogen bond interactions seen for DRV bound in the typical position in wild-type enzyme. The atypical location of DRV may provide opportunities for design of novel inhibitors targeting the open conformation of PR drug-resistant mutants.
C1 [Zhang, Ying; Weber, Irene T.] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA.
[Chang, Yu-Chung E.; Wang, Yuan-Fang; Harrison, Robert W.; Weber, Irene T.] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA.
[Harrison, Robert W.] Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA.
[Louis, John M.] NIDDK, Chem Phys Lab, NIH, DHHS, Bethesda, MD 20892 USA.
RP Weber, IT (reprint author), Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA.
EM iweber@gsu.edu
FU National Institute of General Medical Sciences of the National
Institutes of Health [U01GM062920]; Georgia State University Center for
Diagnostics and Therapeutics Doctoral Fellowship; NIDDK; Intramural
AIDS-Targeted Antiviral Program of the Office of the Director, NIH; U.S.
Department of Energy, Basic Energy Sciences, Office of Science
[W-31-109-Eng-38]
FX This work was supported in part by the National Institute of General
Medical Sciences of the National Institutes of Health under Award Number
U01GM062920 (I.T.W. and R.W.H.) and by the Georgia State University
Center for Diagnostics and Therapeutics Doctoral Fellowship (Y.Z.) and
by the Intramural Research Program of the NIDDK and the Intramural
AIDS-Targeted Antiviral Program of the Office of the Director, NIH. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health. X-ray data were collected at the Southeast Regional
Collaborative Access Team (SER-CAT) beamline 22BM at the Advanced Photon
Source, Argonne National Laboratory. Use of the Advanced Photon Source
was supported by the U.S. Department of Energy, Basic Energy Sciences,
Office of Science, under Contract No. W-31-109-Eng-38. Darunavir was
obtained through the NIH AIDS Research and Reference Reagent Program,
Division of AIDS, NIAID, NIH.
NR 34
TC 7
Z9 7
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
EI 1554-8937
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD JUN
PY 2014
VL 9
IS 6
BP 1351
EP 1358
DI 10.1021/cb4008875
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AJ7IN
UT WOS:000337870500017
PM 24738918
ER
PT J
AU Nikolaidis, NM
White, MR
Allen, K
Tripathi, S
Qi, L
McDonald, B
Taubenberger, J
Seaton, BA
McCormack, FX
Crouch, EC
Hartshorn, KL
AF Nikolaidis, Nikolaos M.
White, Mitchell R.
Allen, Kimberly
Tripathi, Shweta
Qi, Li
McDonald, Barbara
Taubenberger, Jeffery
Seaton, Barbara A.
McCormack, Francis X.
Crouch, Erika C.
Hartshorn, Kevan L.
TI Mutations flanking the carbohydrate binding site of surfactant protein D
confer antiviral activity for pandemic influenza A viruses
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE collectin; innate immunity; mouse
ID LECTIN DOMAINS; HEMAGGLUTININ; COLLECTINS; MICE; RECOGNITION;
INHIBITION; INFECTION; EMPHYSEMA; LIGANDS
AB We recently reported that a trimeric neck and carbohydrate recognition domain (NCRD) fragment of human surfactant protein D (SP- D), a host defense lectin, with combinatorial substitutions at the 325 and 343 positions (D325A + R343V) exhibits markedly increased antiviral activity for seasonal strains of influenza A virus (IAV). The NCRD binds to glycan- rich viral envelope proteins including hemagglutinin (HA). We now show that replacement of D325 with serine to create D325S + R343V provided equal or increased neutralizing activity compared with D325A + R343V. The activity of the double mutants was significantly greater than that of either single mutant (D325A/S or R343V). D325A + R343V and D325S + R343V also strongly inhibited HA activity, and markedly aggregated, the 1968 pandemic H3N2 strain, Aichi68. D325S + R343V significantly reduced viral loads and mortality of mice infected with Aichi68, whereas wild- type SP- D NCRD did not. The pandemic H1N1 strains of 1918 and 2009 have only one N- linked glycan side on the head region of the HA and are fully resistant to inhibition by native SP- D. Importantly, we now show that D325A + R343V and D325S + R343V inhibited Cal09 H1N1 and related strains, and reduced uptake of Ca109 by epithelial cells. Inhibition of Cal09 was mediated by the lectin activity of the NCRDs. All known human pandemic strains have at least one glycan attachment on the top or side of the HA head, and our results indicate that they may be susceptible to inhibition by modified host defense lectins.
C1 [Nikolaidis, Nikolaos M.; McCormack, Francis X.] Univ Cincinnati, Div Pulm & Crit Care Med, Cincinnati, OH USA.
[White, Mitchell R.; Tripathi, Shweta; Hartshorn, Kevan L.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Seaton, Barbara A.] Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA.
[Allen, Kimberly; McDonald, Barbara; Crouch, Erika C.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA.
[Qi, Li; Taubenberger, Jeffery] NIAID, Bethesda, MD 20892 USA.
RP Hartshorn, KL (reprint author), Boston Univ, Sch Med, EBRC 414,650 Albany St, Boston, MA 02118 USA.
EM khartsho@bu.edu
OI McCormack, Francis/0000-0001-7168-9464
FU National Institutes of Health [PO1-AI-083222, RO1-HL-069031]; National
Institute of Allergy and Infectious Diseases
FX This work was supported by National Institutes of Health Grants
PO1-AI-083222 to B. A. Seaton, K. L. Hartshorn, and F. McCormack; and
RO1-HL-069031 to K. L. Hartshorn; and by National Institute of Allergy
and Infectious Diseases intramural research support to L. Qi and J.
Taubenberger.
NR 29
TC 2
Z9 2
U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
EI 1522-1504
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD JUN
PY 2014
VL 306
IS 11
BP L1036
EP L1044
DI 10.1152/ajplung.00035.2014
PG 9
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA AJ7SE
UT WOS:000337896600009
PM 24705721
ER
PT J
AU Stober, VP
Szczesniak, C
Childress, Q
Heise, RL
Bortner, C
Hollingsworth, JW
Neuringer, IP
Palmer, SM
Garantziotis, S
AF Stober, Vandy P.
Szczesniak, Christopher
Childress, Quiana
Heise, Rebecca L.
Bortner, Carl
Hollingsworth, John W.
Neuringer, Isabel P.
Palmer, Scott M.
Garantziotis, Stavros
TI Bronchial epithelial injury in the context of alloimmunity promotes
lymphocytic bronchiolitis through hyaluronan expression
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE endoplasmic reticulum stress; lung rejection
ID ENDOPLASMIC-RETICULUM STRESS; HUMAN LUNG TRANSPLANTATION; AIRWAY; CELLS;
DISEASE; INFLAMMATION; NAPHTHALENE; FIBROSIS; CYTOTOXICITY; METABOLITES
AB Epithelial injury is often detected in lung allografts, however, its relation to rejection pathogenesis is unknown. We hypothesized that sterile epithelial injury can lead to alloimmune activation in the lung. We performed adoptive transfer of mismatched splenocytes into recombinant activating gene 1 (Rag1)-deficient mice to induce an alloimmune status and then exposed these mice to naphthalene to induce sterile epithelial injury. We evaluated lungs for presence of alloimmune lung injury, endoplasmic reticulum (ER) stress, and hyaluronan expression, examined the effect of ER stress induction on hyaluronan expression and lymphocyte trapping by bronchial epithelia in vitro, and examined airways from patients with bronchiolitis obliterans syndrome and normal controls histologically. We found that Rag1deficient mice that received mismatched splenocytes and naphthalene injection displayed bronchial epithelial ER stress, peribronchial hyaluronan expression, and lymphocytic bronchitis. Bronchial epithelial ER stress led to the expression of lymphocyte-trapping hyaluronan cables in vitro. Blockade of hyaluronan binding ameliorated naphthalene- induced lymphocytic bronchitis. ER stress was present histologically in > 40% of bronchial epithelia of BOS patients and associated with subepithelial hyaluronan deposition. We conclude that sterile bronchial epithelial injury in the context of alloimmunity can lead to sustained ER stress and promote allograft rejection through hyaluronan expression.
C1 [Stober, Vandy P.; Szczesniak, Christopher; Childress, Quiana; Heise, Rebecca L.; Bortner, Carl; Garantziotis, Stavros] NIEHS, Res Triangle Pk, NC 27709 USA.
[Hollingsworth, John W.; Palmer, Scott M.] Duke Univ, Med Ctr, Durham, NC USA.
[Neuringer, Isabel P.] Univ North Carolina Hosp, Chapel Hill, NC USA.
RP Garantziotis, S (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM garantziotis@niehs.nih.gov
RI Heise, Rebecca/N-7797-2016; Garantziotis, Stavros/A-6903-2009
OI Heise, Rebecca/0000-0002-6602-6700; Garantziotis,
Stavros/0000-0003-4007-375X
FU Division of Intramural Research of the National Institutes of Health
(NIH); National Institute of Environmental Health Sciences; NIH
[ES-016126, ES-020350, HL-091140]
FX Research was supported in part by the Division of Intramural Research of
the National Institutes of Health (NIH), National Institute of
Environmental Health Sciences. J. W. Hollingsworth appreciates support
provided by the NIH, including Grants ES-016126 and ES-020350. S. M.
Palmer receives support by the NIH, including Grant HL-091140.
NR 33
TC 7
Z9 7
U1 1
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
EI 1522-1504
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD JUN
PY 2014
VL 306
IS 11
BP L1045
EP L1055
DI 10.1152/ajplung.00353.2013
PG 11
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA AJ7SE
UT WOS:000337896600010
PM 24748604
ER
PT J
AU Friesen, MC
Locke, SJ
Tornow, C
Chen, YC
Koh, DH
Stewart, PA
Purdue, M
Colt, JS
AF Friesen, Melissa C.
Locke, Sarah J.
Tornow, Carina
Chen, Yu-Cheng
Koh, Dong-Hee
Stewart, Patricia A.
Purdue, Mark
Colt, Joanne S.
TI Systematically Extracting Metal- and Solvent-Related Occupational
Information from Free-Text Responses to Lifetime Occupational History
Questionnaires
SO ANNALS OF OCCUPATIONAL HYGIENE
LA English
DT Article
DE cadmium; chlorinated solvents; exposure assessment methodology; lead
ID RENAL-CELL CARCINOMA; DECISION RULES; EXPOSURE; WHITE
AB Objectives: Lifetime occupational history (OH) questionnaires often use open-ended questions to capture detailed information about study participants' jobs. Exposure assessors use this information, along with responses to job-and industry-specific questionnaires, to assign exposure estimates on a job-by-job basis. An alternative approach is to use information from the OH responses and the job-and industry-specific questionnaires to develop programmable decision rules for assigning exposures. As a first step in this process, we developed a systematic approach to extract the free-text OH responses and convert them into standardized variables that represented exposure scenarios.
Methods: Our study population comprised 2408 subjects, reporting 11 991 jobs, from a case-control study of renal cell carcinoma. Each subject completed a lifetime OH questionnaire that included verbatim responses, for each job, to open-ended questions including job title, main tasks and activities (task), tools and equipment used (tools), and chemicals and materials handled (chemicals). Based on a review of the literature, we identified exposure scenarios (occupations, industries, tasks/tools/chemicals) expected to involve possible exposure to chlorinated solvents, trichloroethylene (TCE) in particular, lead, and cadmium. We then used a SAS macro to review the information reported by study participants to identify jobs associated with each exposure scenario; this was done using previously coded standardized occupation and industry classification codes, and a priori lists of associated key words and phrases related to possibly exposed tasks, tools, and chemicals. Exposure variables representing the occupation, industry, and task/tool/chemicals exposure scenarios were added to the work history records of the study respondents. Our identification of possibly TCE-exposed scenarios in the OH responses was compared to an expert's independently assigned probability ratings to evaluate whether we missed identifying possibly exposed jobs.
Results: Our process added exposure variables for 52 occupation groups, 43 industry groups, and 46 task/tool/chemical scenarios to the data set of OH responses. Across all four agents, we identified possibly exposed task/tool/chemical exposure scenarios in 44-51% of the jobs in possibly exposed occupations. Possibly exposed task/tool/chemical exposure scenarios were found in a nontrivial 9-14% of the jobs not in possibly exposed occupations, suggesting that our process identified important information that would not be captured using occupation alone. Our extraction process was sensitive: for jobs where our extraction of OH responses identified no exposure scenarios and for which the sole source of information was the OH responses, only 0.1% were assessed as possibly exposed to TCE by the expert.
Conclusions: Our systematic extraction of OH information found useful information in the task/chemicals/tools responses that was relatively easy to extract and that was not available from the occupational or industry information. The extracted variables can be used as inputs in the development of decision rules, especially for jobs where no additional information, such as job-and industry-specific questionnaires, is available.
C1 [Friesen, Melissa C.; Locke, Sarah J.; Chen, Yu-Cheng; Koh, Dong-Hee; Stewart, Patricia A.; Purdue, Mark; Colt, Joanne S.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Tornow, Carina] WESTAT Corp, Rockville, MD 20850 USA.
[Stewart, Patricia A.] Stewart Exposure Assessments LLC, Arlington, VA 22207 USA.
RP Friesen, MC (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8106,MSC 7240, Bethesda, MD 20892 USA.
EM friesenmc@mail.nih.gov
RI Friesen, Melissa/A-5362-2009
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health [Z01
CP10122-19, Z01 CP010136-19]
FX Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, National Institutes of Health (Z01
CP10122-19; Z01 CP010136-19).
NR 14
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Z9 1
U1 1
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0003-4878
EI 1475-3162
J9 ANN OCCUP HYG
JI Ann. Occup. Hyg.
PD JUN
PY 2014
VL 58
IS 5
BP 612
EP 624
DI 10.1093/annhyg/meu012
PG 13
WC Public, Environmental & Occupational Health; Toxicology
SC Public, Environmental & Occupational Health; Toxicology
GA AK0MN
UT WOS:000338107300008
PM 24590110
ER
PT J
AU Skuladottir, H
Wilcox, AJ
Ma, C
Lammer, EJ
Rasmussen, SA
Werler, MM
Shaw, GM
Carmichael, SL
AF Skuladottir, Hildur
Wilcox, Allen J.
Ma, Chen
Lammer, Edward J.
Rasmussen, Sonja A.
Werler, Martha M.
Shaw, Gary M.
Carmichael, Suzan L.
TI Corticosteroid Use and Risk of Orofacial Clefts
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Article
DE orofacial clefts; cleft lip and palate; corticosteroids; birth defects;
pregnancy
ID BIRTH-DEFECTS PREVENTION; TOPICAL CORTICOSTEROIDS; ORAL CLEFTS;
DRUG-USE; PREGNANCY; PALATE; EXPOSURE; LIP
AB Background: Maternal use of corticosteroids during early pregnancy has been inconsistently associated with orofacial clefts in the offspring. A previous report from the National Birth Defect Prevention Study (NBDPS), using data from 1997 to 2002, found an association with cleft lip and palate (odds ratio, 1.7; 95% confidence interval [CI], 1.1-2.6), but not cleft palate only (odds ratio, 0.5, 95% CI, 0.2-1.3). From 2003 to 2009, the study population more than doubled in size, and our objective was to assess this association in the more recent data. Methods: The NBDPS is an ongoing multi-state population-based case-control study of birth defects, with ascertainment of cases and controls born since 1997. We assessed the association of corticosteroids and orofacial clefts using data from 2372 cleft cases and 5922 controls born from 2003 to 2009. Maternal corticosteroid exposure was based on telephone interviews. Results: The overall association of corticosteroids and cleft lip and palate in the new data was 1.0 (95% CI, 0.7-1.4). There was little evidence of associations between specific corticosteroid components or timing and clefts. Conclusion: In contrast to the 1997 to 2002 data from the NBDPS, the 2003 to 2009 data show no association between maternal corticosteroid use and cleft lip and palate in the offspring. (C) 2014 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc.
C1 [Skuladottir, Hildur] Haukeland Hosp, Dept Plast Surg, N-5021 Bergen, Norway.
[Skuladottir, Hildur] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5020 Bergen, Norway.
[Wilcox, Allen J.] NIEHS, NIH, Durham, NC USA.
[Ma, Chen; Shaw, Gary M.; Carmichael, Suzan L.] Stanford Univ, Dept Pediat, Div Neonatol & Dev Med, Sch Med, Stanford, CA 94305 USA.
[Lammer, Edward J.] Childrens Hosp Oakland Res Inst, Oakland, CA USA.
[Rasmussen, Sonja A.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Werler, Martha M.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
RP Skuladottir, H (reprint author), Haukeland Hosp, Dept Plast Surg, Jonas Lies Vei 67, N-5021 Bergen, Norway.
EM hildur.skuladottir@gmail.com
OI Wilcox, Allen/0000-0002-3376-1311
FU NCBDD CDC HHS [U01-DD-001033, U01-DD-000489]
NR 24
TC 12
Z9 12
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD JUN
PY 2014
VL 100
IS 6
BP 499
EP 506
DI 10.1002/bdra.23248
PG 8
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA AJ9MU
UT WOS:000338036300006
PM 24777675
ER
PT J
AU Lionakis, MS
Netea, MG
Holland, SM
AF Lionakis, Michail S.
Netea, Mihai G.
Holland, Steven M.
TI Mendelian Genetics of Human Susceptibility to Fungal Infection
SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
LA English
DT Article
ID CHRONIC GRANULOMATOUS-DISEASE; HYPER-IGE SYNDROME; CHRONIC MUCOCUTANEOUS
CANDIDIASIS; POLYENDOCRINE SYNDROME TYPE-1; HEREDITARY MYELOPEROXIDASE
DEFICIENCY; ANHIDROTIC ECTODERMAL DYSPLASIA; ACUTE MYELOID-LEUKEMIA;
SYNDROME TYPE-I; AUTOSOMAL-DOMINANT; ASPERGILLUS-FUMIGATUS
AB A recent surge in newly described inborn errors of immune function-related genes that result in susceptibility to fungal disease has greatly enhanced our understanding of the cellular and molecular basis of antifungal immune responses. Characterization of single-gene defects that predispose to various combinations of superficial and deep-seated infections caused by yeasts, molds, and dimorphic fungi has unmasked the critical role of novel molecules and signaling pathways in mucosal and systemic antifungal host defense. These experiments of nature offer a unique opportunity for developing new knowledge in immunological research and form the foundation for devising immune-based therapeutic approaches for patients infected with fungal pathogens.
C1 [Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 ED Nijmegen, Netherlands.
[Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Nijmegen Inst Infect Inflammat & Immun N4i, NL-6525 ED Nijmegen, Netherlands.
[Holland, Steven M.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Lionakis, MS (reprint author), NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
EM lionakism@niaid.nih.gov
RI Netea, Mihai/N-5155-2014
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; ERC Consolidator
Grant [310372]
FX This work is supported by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. M. G. N. is supported by an ERC Consolidator Grant
(No. 310372).
NR 120
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U1 1
U2 6
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 2157-1422
J9 CSH PERSPECT MED
JI Cold Spring Harb. Perspect. Med.
PD JUN
PY 2014
VL 4
IS 6
AR a019638
DI 10.1101/cshperspect.a019638
PG 21
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AJ9IC
UT WOS:000338021000008
ER
PT J
AU Voorspoels, W
Storms, G
Longenecker, J
Verheyen, S
Weinberger, DR
Elvevag, B
AF Voorspoels, Wouter
Storms, Gert
Longenecker, Julia
Verheyen, Steven
Weinberger, Daniel R.
Elvevag, Brita
TI Deriving semantic structure from category fluency: Clustering techniques
and their pitfalls
SO CORTEX
LA English
DT Article
DE Category fluency; Similarity; Schizophrenia; Semantic deficits; Sampling
ID VERBAL FLUENCY; SCHIZOPHRENIC-PATIENTS; INSTANTIATION PRINCIPLE;
HEALTHY-ADULTS; MEMORY; ORGANIZATION; DEFICITS; RECALL; ALZHEIMERS;
RETRIEVAL
AB Assessing verbal output in category fluency tasks provides a sensitive indicator of cortical dysfunction. The most common metrics are the overall number of words produced and the number of errors. Two main observations have been made about the structure of the output, first that there is a temporal component to it with words being generated in spurts, and second that the clustering pattern may reflect a search for meanings such that the 'clustering' is attributable to the activation of a specific semantic field in memory. A number of sophisticated approaches to examining the structure of this clustering have been developed, and a core theme is that the similarity relations between category members will reveal the mental semantic structure of the category underlying an individual's responses, which can then be visualized by a number of algorithms, such as MDS, hierarchical clustering, ADD-TREE, ADCLUS or SVD. Such approaches have been applied to a variety of neurological and psychiatric populations, and the general conclusion has been that the clinical condition systematically distorts the semantic structure in the patients, as compared to the healthy controls. In the present paper we explore this approach to understanding semantic structure using category fluency data. On the basis of a large pool of patients with schizophrenia (n = 204) and healthy control participants (n = 204), we find that the methods are problematic and unreliable to the extent that it is not possible to conclude that any putative difference reflects a systematic difference between the semantic representations in patients and controls. Moreover, taking into account the unreliability of the methods, we find that the most probable conclusion to be made is that no difference in underlying semantic representation exists. The consequences of these findings to understanding semantic structure, and the use of category fluency data, in cortical dysfunction are discussed. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Voorspoels, Wouter; Storms, Gert; Verheyen, Steven] Katholieke Univ Leuven, Dept Psychol, B-3000 Louvain, Belgium.
[Longenecker, Julia; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Elvevag, Brita] Univ Tromso, Dept Clin Med, Psychiat Res Grp, N-9001 Tromso, Norway.
[Elvevag, Brita] Univ Hosp North Norway, Norwegian Ctr Integrated Care & Telemed NST, Tromso, Norway.
RP Storms, G (reprint author), Katholieke Univ Leuven, Dept Psychol, Tiensestr 102, B-3000 Louvain, Belgium.
EM Gert.Storms@ppw.kuleuven.be
FU Intramural Research Program of the National Institutes of Health,
National Institute of Mental Health; Northern Norwegian Regional Health
Authority
FX WV and SV are postdoctoral fellows at the Research Foundation -
Flanders. This research was supported by the Intramural Research Program
of the National Institutes of Health, National Institute of Mental
Health. BE was supported by the Northern Norwegian Regional Health
Authority (Helse Nord RHF). None of the funding agencies had any further
role in study design, data analysis and interpretation, or in the
writing of the report and decision to submit for publication.
NR 57
TC 11
Z9 12
U1 6
U2 15
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 0010-9452
EI 1973-8102
J9 CORTEX
JI Cortex
PD JUN
PY 2014
VL 55
SI SI
BP 130
EP 147
DI 10.1016/j.cortex.2013.09.006
PG 18
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA AJ5ZY
UT WOS:000337770700012
PM 24275165
ER
PT J
AU Rosenstein, M
Diaz-Asper, C
Foltz, PW
Elvevag, B
AF Rosenstein, Mark
Diaz-Asper, Catherine
Foltz, Peter W.
Elvevag, Brita
TI A computational language approach to modeling prose recall in
schizophrenia
SO CORTEX
LA English
DT Article
DE Episodic memory; Wechsler memory scale; Text analysis; Latent semantic
analysis
ID LATENT SEMANTIC ANALYSIS; COGNITIVE IMPAIRMENTS; MEMORY IMPAIRMENT;
RELATIVE RISK; VERBAL MEMORY; DISORDER; POLYMORPHISM; METHODOLOGY;
MEDICATIONS; MECHANISMS
AB Many cortical disorders are associated with memory problems. In schizophrenia, verbal memory deficits are a hallmark feature. However, the exact nature of this deficit remains elusive. Modeling aspects of language features used in memory recall have the potential to provide means for measuring these verbal processes. We employ computational language approaches to assess time-varying semantic and sequential properties of prose recall at various retrieval intervals (immediate, 30 min and 24 h later) in patients with schizophrenia, unaffected siblings and healthy unrelated control participants. First, we model the recall data to quantify the degradation of performance with increasing retrieval interval and the effect of diagnosis (i.e., group membership) on performance. Next we model the human scoring of recall performance using an n-gram language sequence technique, and then with a semantic feature based on Latent Semantic Analysis. These models show that automated analyses of the recalls can produce scores that accurately mimic human scoring. The final analysis addresses the validity of this approach by ascertaining the ability to predict group membership from models built on the two classes of language features. Taken individually, the semantic feature is most predictive, while a model combining the features improves accuracy of group membership prediction slightly above the semantic feature alone as well as over the human rating approach. We discuss the implications for cognitive neuroscience of such a computational approach in exploring the mechanisms of prose recall. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Rosenstein, Mark; Foltz, Peter W.] Pearson Knowledge Technol, Boulder, CO USA.
[Diaz-Asper, Catherine] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Foltz, Peter W.] Univ Colorado, Inst Cognit Sci, Boulder, CO 80309 USA.
[Elvevag, Brita] Univ Tromso, Dept Clin Med, Psychiat Res Grp, N-9001 Tromso, Norway.
[Elvevag, Brita] Univ Hosp North Norway, Norwegian Ctr Integrated Care & Telemed NST, Tromso, Norway.
RP Rosenstein, M (reprint author), Pearson, 4940 Pearl East Circle,Suite 200, Boulder, CO 80301 USA.
EM mark.rosenstein@pearson.com
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health, USA; Northern Norwegian Regional Health
Authority, Helse Nord RHF
FX We gratefully acknowledge Daniel R. Weinberger M.D., for making the data
available, which were collected via the Clinical Brain Disorders (NIMH)
Schizophrenia Sibling Study (D.R. Weinberger, PI). This research was
supported by the Intramural Research Program of the National Institute
of Mental Health, National Institutes of Health, USA. We are also
thankful for assistance from Julia Longenecker M. Phil. and Krista
Wisner B.A. Brita Elvevag was funded by the Northern Norwegian Regional
Health Authority, Helse Nord RHF, and Peter Foltz and Mark Rosenstein
are employees of Pearson, the publisher of the Wechsler test utilized in
the paper, which partially supported their work as part of their
employment. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 69
TC 2
Z9 2
U1 0
U2 8
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 0010-9452
EI 1973-8102
J9 CORTEX
JI Cortex
PD JUN
PY 2014
VL 55
SI SI
BP 148
EP 166
DI 10.1016/j.cortex.2014.01.021
PG 19
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA AJ5ZY
UT WOS:000337770700013
PM 24709122
ER
PT J
AU Nicodemus, KK
Elvevag, B
Foltz, PW
Rosenstein, M
Diaz-Asper, C
Weinberger, DR
AF Nicodemus, Kristin K.
Elvevag, Brita
Foltz, Peter W.
Rosenstein, Mark
Diaz-Asper, Catherine
Weinberger, Daniel R.
TI Category fluency, latent semantic analysis and schizophrenia: a
candidate gene approach
SO CORTEX
LA English
DT Article
DE Cognition; Verbal learning and recall; Gene; Latent semantic analysis;
Schizophrenia
ID NEUROCOGNITIVE PHENOTYPES; INTERMEDIATE PHENOTYPES; PSYCHIATRIC
GENETICS; SUSCEPTIBILITY GENE; COGNITIVE-PROCESSES; ZNF804A;
ASSOCIATION; DISC1; RISK; VARIANTS
AB Background: Category fluency is a widely used task that relies on multiple neurocognitive processes and is a sensitive assay of cortical dysfunction, including in schizophrenia. The test requires naming of as many words belonging to a certain category (e.g., animals) as possible within a short period of time. The core metrics are the overall number of words produced and the number of errors, namely non-members generated for a target category. We combine a computational linguistic approach with a candidate gene approach to examine the genetic architecture of this traditional fluency measure.
Methods: In addition to the standard metric of overall word count, we applied a computational approach to semantics, Latent Semantic Analysis (LSA), to analyse the clustering pattern of the categories generated, as it likely reflects the search in memory for meanings. Also, since fluency performance probably also recruits verbal learning and recall processes, we included two standard measures of this cognitive process: the Wechsler Memory Scale and California Verbal Learning Test (CVLT). To explore the genetic architecture of traditional and LSA-derived fluency measures we employed a candidate gene approach focused on SNPs with known function that were available from a recent genome-wide association study (GWAS) of schizophrenia. The selected candidate genes were associated with language and speech, verbal learning and recall processes, and processing speed. A total of 39 coding SNPs were included for analysis in 665 subjects.
Results and discussion: Given the modest sample size, the results should be regarded as exploratory and preliminary. Nevertheless, the data clearly illustrate how extracting the meaning from participants' responses, by analysing the actual content of words, generates useful and neurocognitively viable metrics. We discuss three replicated SNPs in the genes ZNF804A, DISCI. and KIAA0319, as well as the potential for computational analyses of linguistic and textual data in other genomics tasks. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Nicodemus, Kristin K.] Univ Dublin Trinity Coll, St Jamess Hosp, Trinity Ctr Hlth Sci, Neuropsychiat Genet Res Grp,Dept Psychiat, Dublin 8, Ireland.
[Elvevag, Brita] Univ Tromso, Dept Clin Med, Psychiat Res Grp, N-9001 Tromso, Norway.
[Elvevag, Brita] Univ Hosp North Norway, Norwegian Ctr Integrated Care & Telemed NST, Tromso, Norway.
[Foltz, Peter W.; Rosenstein, Mark] Pearson Knowledge Technol, Boulder, CO USA.
[Foltz, Peter W.] Univ Colorado, Inst Cognit Sci, Boulder, CO 80309 USA.
[Diaz-Asper, Catherine; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Weinberger, Daniel R.] Lieber Inst Brain Dev, Baltimore, MD USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA.
[Weinberger, Daniel R.] Johns Hopkins Sch Med, Inst Genom Med, Baltimore, MD USA.
RP Nicodemus, KK (reprint author), Univ Dublin Trinity Coll, St Jamess Hosp, Trinity Ctr Hlth Sci, Neuropsychiat Genet Res Grp,Dept Psychiat, Dublin 8, Ireland.
EM nicodemk@tcd.ie
FU Science Foundation Ireland; Marie-Curie Action COFUND [11/SIRG/B2183];
Northern Norwegian Regional Health Authority (Helse Nord RHF);
Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health, USA
FX This publication has emanated from research conducted with the financial
support of Science Foundation Ireland and the Marie-Curie Action COFUND
under Grant Number 11/SIRG/B2183 to Dr. Nicodemus. Dr. Elvevag was
supported by the Northern Norwegian Regional Health Authority (Helse
Nord RHF). All calculations were performed on the Lonsdale cluster
maintained by the Trinity Centre for High Performance Computing. This
cluster was funded through grants from Science Foundation Ireland. This
research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health, USA.
NR 58
TC 13
Z9 14
U1 1
U2 8
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 0010-9452
EI 1973-8102
J9 CORTEX
JI Cortex
PD JUN
PY 2014
VL 55
SI SI
BP 182
EP 191
DI 10.1016/j.cortex.2013.12.004
PG 10
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA AJ5ZY
UT WOS:000337770700015
PM 24447899
ER
PT J
AU Kane, A
Deenick, EK
Ma, CS
Cook, MC
Uzel, G
Tangye, SG
AF Kane, Alisa
Deenick, Elissa K.
Ma, Cindy S.
Cook, Matthew C.
Uzel, Gulbu
Tangye, Stuart G.
TI STAT3 is a central regulator of lymphocyte differentiation and function
SO CURRENT OPINION IN IMMUNOLOGY
LA English
DT Review
ID HYPER-IGE SYNDROME; SECRETING PLASMA-CELLS; CD4(+) T-CELLS; SIGNAL
TRANSDUCER; B-CELLS; ANTIBODY-RESPONSES; HYPERIMMUNOGLOBULINEMIA-E;
STAT3-DEPENDENT MANNER; IL-21 RECEPTOR; JOBS SYNDROME
AB Signalling in lymphocytes through cytokine receptors is critical for their development, activation and differentiation into effector cells that mediate protection against pathogens and provide the host with protective immunological memory. The essential role of cytokine signalling has been established not only by the generation and examination of gene-targeted mice, but also 'Experiments of Nature' whereby monogenic mutations cause primary immunodeficient conditions characterised by impaired immunity to infectious diseases due to compromised lymphocyte function. Mutations in STAT3 cause autosomal dominant hyper-IgE syndrome. Here, we will review how the study of STAT3-deficient individuals has revealed non-redundant functions of STAT3 and specific cytokines in human lymphocyte biology, and have delineated mechanisms underlying the distinct clinical features of autosomal dominant hyper-IgE syndrome.
C1 [Kane, Alisa; Deenick, Elissa K.; Ma, Cindy S.; Tangye, Stuart G.] St Vincents Hosp, Garvan Inst Med Res, Immunol Res Program, Immunol & Immunodeficiency Grp, Darlinghurst, NSW 2010, Australia.
[Kane, Alisa; Deenick, Elissa K.; Ma, Cindy S.; Tangye, Stuart G.] Univ New S Wales, St Vincents Clin Sch, Darlinghurst, NSW, Australia.
[Cook, Matthew C.] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 0200, Australia.
[Cook, Matthew C.] Canberra Hosp, Dept Immunol, Canberra, ACT, Australia.
[Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Tangye, SG (reprint author), St Vincents Hosp, Garvan Inst Med Res, Immunol Res Program, Immunol & Immunodeficiency Grp, Darlinghurst, NSW 2010, Australia.
EM s.tangye@garvan.org.au
OI Deenick, Elissa/0000-0002-9271-0004; Cook, Matthew/0000-0002-3331-9363
FU National Health and Medical Research Council of Australia
FX Research performed in the authors' labs is supported by grants and
fellowships awarded by the National Health and Medical Research Council
of Australia.
NR 59
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U1 0
U2 20
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0952-7915
EI 1879-0372
J9 CURR OPIN IMMUNOL
JI Curr. Opin. Immunol.
PD JUN
PY 2014
VL 28
BP 49
EP 57
DI 10.1016/j.coi.2014.01.015
PG 9
WC Immunology
SC Immunology
GA AJ7BX
UT WOS:000337853300010
PM 24594518
ER
PT J
AU Kruse, AC
Hu, JX
Kobilka, BK
Wess, J
AF Kruse, Andrew C.
Hu, Jianxin
Kobilka, Brian K.
Wess, Juergen
TI Muscarinic acetylcholine receptor X-ray structures: potential
implications for drug development
SO CURRENT OPINION IN PHARMACOLOGY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; ALLOSTERIC MODULATION; CRYSTAL-STRUCTURE;
TIOTROPIUM; MICE; LIGANDS
AB Muscarinic acetylcholine receptor antagonists are widely used as bronchodilating drugs in pulmonary medicine. The therapeutic efficacy of these agents depends on the blockade of M-3 muscarinic receptors expressed on airway smooth muscle cells. All muscarinic antagonists currently used as bronchodilating agents show high affinity for all five muscarinic receptor subtypes, thus increasing the likelihood of unwanted side effects. Recent X-ray crystallographic studies have provided detailed structural information about the nature of the orthosteric muscarinic binding site (the conventional acetylcholine binding site) and an 'outer' receptor cavity that can bind allosteric (non-orthosteric) drugs. These new findings should guide the development of selective M-3 receptor blockers that have little or no effect on other muscarinic receptor subtypes.
C1 [Kruse, Andrew C.; Kobilka, Brian K.] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
[Hu, Jianxin; Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, Bethesda, MD USA.
RP Kruse, AC (reprint author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA.
EM akruse@stanford.edu; jurgenw@helix.nih.gov
FU National Science Foundation Graduate Research Fellowship; National
Science Foundation [CHE-1223785]; National Institutes of Health
[U19GM106990]; Intramural Research Program of the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK); NIH
FX The structural studies summarized in this review were supported by a
National Science Foundation Graduate Research Fellowship to ACK and by
National Science Foundation grant CHE-1223785 and National Institutes of
Health grant U19GM106990 to BKK. The work of JH and JW was supported by
the Intramural Research Program of the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK), NIH. We thank all of our
coworkers and collaborators for their invaluable contributions to the
work summarized in this chapter.
NR 26
TC 10
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U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4892
EI 1471-4973
J9 CURR OPIN PHARMACOL
JI Curr. Opin. Pharmacol.
PD JUN
PY 2014
VL 16
BP 24
EP 30
DI 10.1016/j.coph.2014.02.006
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AK0HU
UT WOS:000338094300006
PM 24662799
ER
PT J
AU Sepeta, LN
Berl, MM
Theodore, WH
Xu, B
Roopchansingh, V
Shih, S
Barrett, L
Terwilliger, V
Emery, E
Germeyan, S
Suthana, N
Bookheimer, SY
Gaillard, WD
AF Sepeta, L. N.
Berl, M. M.
Theodore, W. H.
Xu, B.
Roopchansingh, V
Shih, S.
Barrett, L.
Terwilliger, V
Emery, E.
Germeyan, S.
Suthana, N.
Bookheimer, S. Y.
Gaillard, W. D.
TI LATERALIZATION OF HIPPOCAMPAL ACTIVATION FOR SURGICAL GUIDANCE IN
REFRACTORY PEDIATRIC EPILEPSY
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 11th European Congress on Epileptology
CY JUN 29-JUL 03, 2014
CL Stockholm, SWEDEN
C1 [Sepeta, L. N.; Berl, M. M.; Terwilliger, V; Emery, E.; Gaillard, W. D.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Theodore, W. H.; Xu, B.; Roopchansingh, V; Germeyan, S.; Gaillard, W. D.] NIH, Bethesda, MD 20892 USA.
[Barrett, L.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
[Suthana, N.; Bookheimer, S. Y.] Univ Calif Los Angeles, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
EI 1528-1167
J9 EPILEPSIA
JI Epilepsia
PD JUN
PY 2014
VL 55
SU 2
SI SI
MA p467
BP 152
EP 152
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA AJ8TA
UT WOS:000337979300454
ER
PT J
AU O'Reilly, M
Federoff, HJ
Fong, YM
Kohn, DB
Patterson, AP
Ahmed, N
Asokan, A
Boye, SE
Crystal, RG
De Oliveira, S
Gargiulo, L
Harper, SQ
Ikeda, Y
Jambou, R
Montgomery, M
Prograis, L
Rosenthal, E
Sterman, DH
Vandenberghe, LH
Zoloth, L
Abedi, M
Adair, J
Adusumilli, PS
Goins, WF
Gray, J
Monahan, P
Popplewell, L
Sena-Esteves, M
Tannous, B
Weber, T
Wierda, W
Gopal-Srivastava, R
McDonald, CL
Rosenblum, D
Corrigan-Curay, J
AF O'Reilly, Marina
Federoff, Howard J.
Fong, Yuman
Kohn, Donald B.
Patterson, Amy P.
Ahmed, Nabil
Asokan, Aravind
Boye, Shannon E.
Crystal, Ronald G.
De Oliveira, Satiro
Gargiulo, Linda
Harper, Scott Q.
Ikeda, Yasuhiro
Jambou, Robert
Montgomery, Maureen
Prograis, Lawrence
Rosenthal, Eugene
Sterman, Daniel H.
Vandenberghe, Luk H.
Zoloth, Laurie
Abedi, Mehrdad
Adair, Jennifer
Adusumilli, Prasad S.
Goins, William F.
Gray, Jhanelle
Monahan, Paul
Popplewell, Leslie
Sena-Esteves, Miguel
Tannous, Bakhos
Weber, Thomas
Wierda, William
Gopal-Srivastava, Rashmi
McDonald, Cheryl L.
Rosenblum, Daniel
Corrigan-Curay, Jacqueline
TI Gene Therapy: Charting a Future Course-Summary of a National Institutes
of Health Workshop, April 12, 2013
SO HUMAN GENE THERAPY
LA English
DT Review
ID LEBER CONGENITAL AMAUROSIS; CHIMERIC ANTIGEN RECEPTOR; HEMATOPOIETIC
STEM/PROGENITOR CELLS; MODIFIED T-CELLS; ADENOASSOCIATED VIRUS;
CANCER-IMMUNOTHERAPY; HEMOPHILIA-B; EFFICACY; SAFETY; EXPRESSION
AB Recently, the gene therapy field has begun to experience clinical successes in a number of different diseases using various approaches and vectors. The workshop Gene Therapy: Charting a Future Course, sponsored by the National Institutes of Health (NIH) Office of Biotechnology Activities, brought together early and mid-career researchers to discuss the key scientific challenges and opportunities, ethical and communication issues, and NIH and foundation resources available to facilitate further clinical advances.
C1 [O'Reilly, Marina; Patterson, Amy P.; Gargiulo, Linda; Jambou, Robert; Montgomery, Maureen; Rosenthal, Eugene; Corrigan-Curay, Jacqueline] Off Director, Off Sci Policy, Bethesda, MD 20892 USA.
[Prograis, Lawrence] NIAID, Bethesda, MD 20892 USA.
[Gopal-Srivastava, Rashmi; Rosenblum, Daniel] Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[McDonald, Cheryl L.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Federoff, Howard J.] Georgetown Univ, Med Ctr, Washington, DC 20057 USA.
[Fong, Yuman; Popplewell, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Kohn, Donald B.; De Oliveira, Satiro] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Ahmed, Nabil] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Asokan, Aravind; Monahan, Paul] Univ N Carolina, Chapel Hill, NC 27599 USA.
[Boye, Shannon E.] Univ Florida, Gainesville, FL 32605 USA.
[Crystal, Ronald G.] Weill Cornell Med Coll, Dept Med Genet, New York, NY 10065 USA.
[Harper, Scott Q.] Ohio State Univ, Coll Med, Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.
[Ikeda, Yasuhiro] Mayo Clin, Rochester, MN 55905 USA.
[Sterman, Daniel H.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA.
[Vandenberghe, Luk H.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA.
[Vandenberghe, Luk H.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
[Zoloth, Laurie] Northwestern Univ, Evanston, IL 60208 USA.
[Abedi, Mehrdad] Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA 95817 USA.
[Adair, Jennifer] Fred Hutchinson Canc Res Ctr, Seattle, WA 98102 USA.
[Adusumilli, Prasad S.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Goins, William F.] Univ Pittsburgh, Pittsburgh, PA 15219 USA.
[Gray, Jhanelle] H Lee Mofitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA.
[Tannous, Bakhos] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
[Weber, Thomas] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Wierda, William] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
RP Corrigan-Curay, J (reprint author), NIH, Off Biotechnol Act, 6705 Rockledge Dr,Suite 750, Bethesda, MD 20892 USA.
EM corrigaja@od.nih.gov
RI Weber, Thomas/A-2363-2008; De Oliveira, Satiro/D-8860-2014; Kohn,
Donald/N-5085-2016
OI Weber, Thomas/0000-0002-0494-0484; De Oliveira,
Satiro/0000-0002-8181-7316; Kohn, Donald/0000-0003-1840-6087
FU Foundation Fighting Blindness; Massachusetts Eye and Ear Infirmary
(Boston, MA); Genelux; Roche; Asklepios Biopharmaceutical; Baxter
Biologics
FX N.A. has patent applications in the field of T-cell and gene-modified
T-cell therapy for cancer. The Center for Cell and Gene Therapy (CAGT)
has research collaboration with Celgene Inc. to develop CAR-based
therapeutics that is administered by Baylor College of Medicine. L. H.
V. is inventor on gene therapy-related patents that are licensed to
various pharmaceutical and biotechnological companies, holds equity in
GenSight Biologics, consults for Novartis and GenSight Biologics, and
receives funding from the Foundation Fighting Blindness and the
Massachusetts Eye and Ear Infirmary (Boston, MA). He has been employed
by the University of Pennsylvania and the Massachusetts Eye and Ear
Infirmary. Y.F. is a paid advisor for Genelux and consultant to Roche.
H.F. is a founder and advisor to MedGenesis. P.M.'s university receives
or has received funding to support basic science research work in the
author's laboratory from Asklepios Biopharmaceutical and Baxter
Biologics. He has received remuneration for consulting work and for
speaking from Asklepios Biopharmaceutical and Baxter Biologics.
NR 47
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U1 1
U2 17
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
EI 1557-7422
J9 HUM GENE THER
JI Hum. Gene Ther.
PD JUN
PY 2014
VL 25
IS 6
BP 488
EP 497
DI 10.1089/hum.2014.045
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA AJ8JR
UT WOS:000337949900004
PM 24773122
ER
PT J
AU Zhang, H
Kathawala, RJ
Wang, YJ
Zhang, YK
Patel, A
Shukla, S
Robey, RW
Talele, TT
Ashby, CR
Ambudkar, SV
Bates, SE
Fu, LW
Chen, ZS
AF Zhang, Hui
Kathawala, Rishil J.
Wang, Yi-Jun
Zhang, Yun-Kai
Patel, Atish
Shukla, Suneet
Robey, Robert W.
Talele, Tanaji T.
Ashby, Charles R., Jr.
Ambudkar, Suresh V.
Bates, Susan E.
Fu, Li-Wu
Chen, Zhe-Sheng
TI Linsitinib (OSI-906) antagonizes ATP-binding cassette subfamily G member
2 and subfamily C member 10-mediated drug resistance
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Article
DE Linsitinib; Multi-drug resistance; ABCG2; ABCC10; Tyrosine kinase
inhibitor
ID MULTIDRUG-RESISTANCE; ACQUIRED MUTATIONS; ABC TRANSPORTERS; PROTEIN
ABCG2; CANCER; INHIBITOR; CELLS; QUANTITATION; EFFLUX; SPECIFICITY
AB In this study we investigated the effect of linsitinib on the reversal of multidrug resistance (MDR) mediated by the overexpression of the ATP-binding cassette (ABC) subfamily members ABCB1, ABCG2, ABCC1 and ABCC10. Our results indicate for the first time that linsitinib significantly potentiate the effect of anti-neoplastic drugs mitoxantrone (MX) and SN-38 in ABCG2-overexpressing cells; paclitaxel, docetaxel and vinblastine in ABCC10-overexpressing cells. Linsitinib moderately enhanced the cytotoxicity of vincristine in cell lines overexpressing ABCB1, whereas it did not alter the cytotoxicity of substrates of ABCC1. Furthermore, linsitinib significantly increased the intracellular accumulation and decreased the efflux of [H-3]-MX in ABCG2-overexpressing cells and [H-3]-paclitaxel in ABCC10-overexpressing cells. However, linsitinib, at a concentration that reversed MDR, did not significantly alter the expression levels of either the ABCG2 or ABCC10 transporter proteins. Furthermore, linsitinib did not significantly alter the intracellular localization of ABCG2 or ABCC10. Moreover, linsitinib stimulated the ATPase activity of ABCG2 in a concentration-dependent manner. Overall, our study suggests that linsitinib attenuates ABCG2- and ABCC10-mediated MDR by directly inhibiting their function as opposed to altering ABCG2 or ABCC10 protein expression. Published by Elsevier Ltd.
C1 [Zhang, Hui; Kathawala, Rishil J.; Wang, Yi-Jun; Zhang, Yun-Kai; Patel, Atish; Talele, Tanaji T.; Ashby, Charles R., Jr.; Chen, Zhe-Sheng] St Johns Univ, Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Queens, NY 11439 USA.
[Zhang, Hui; Fu, Li-Wu] Sun Yat Sen Univ, State Key Lab Oncol South China, Collaborat Innovat Ctr Canc Med, Canc Ctr, Guangzhou 510060, Guangdong, Peoples R China.
[Shukla, Suneet; Ambudkar, Suresh V.] NCI, Lab Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Robey, Robert W.; Bates, Susan E.] NCI, Canc Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Chen, ZS (reprint author), St Johns Univ, Dept Pharmaceut Sci, Jamaica, NY 11439 USA.
EM fulw@mail.sysu.edu.cn; chenz@stjohns.edu
RI Wang, Yi-Jun/K-3218-2016; Patel, Atish/J-4699-2014
OI Patel, Atish/0000-0002-5549-9166
FU NIH [1R15CA143701]; St. John's University Research Seed Grant
[579-1110-7002]; Major Science and Technology Project of The National
Natural Sciences Foundation of China [81072669, 81061160507]; Intramural
Research Program, National Institutes of Health, National Cancer
Institute, Center for Cancer Research
FX This work was supported by funds from NIH (No. 1R15CA143701) and St.
John's University Research Seed Grant (No. 579-1110-7002) to Z.S. Chen,
The Major Science and Technology Project of The National Natural
Sciences Foundation of China Grant (No. 81072669 and No. 81061160507) to
L.W. Fu. Drs. S. Shukla, R.W. Robey, S.V. Ambudkar and S.E. Bates were
supported by the Intramural Research Program, National Institutes of
Health, National Cancer Institute, Center for Cancer Research. We are
grateful to late Dr. Gary Kruh (University of Illinois at Chicago) for
providing ABCC10 plasmid. We thank Dr. Mark F. Rosenberg (University of
Manchester, Manchester, UK) and Dr. Zsolt Bikadi (Virtua Drug Ltd.,
Budapest, Hungary) for providing coordinates of ABCG2 homology model.
NR 34
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U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1357-2725
EI 1878-5875
J9 INT J BIOCHEM CELL B
JI Int. J. Biochem. Cell Biol.
PD JUN
PY 2014
VL 51
BP 111
EP 119
DI 10.1016/j.biocel.2014.03.026
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AJ6BL
UT WOS:000337774600016
PM 24726739
ER
PT J
AU Chew, EY
AF Chew, Emily Y.
TI Vitamins and Minerals, for Eyes Only?
SO JAMA OPHTHALMOLOGY
LA English
DT Editorial Material
ID MACULAR DEGENERATION; CLINICAL-TRIAL; BETA-CAROTENE; SUPPLEMENTATION;
ZINC
C1 [Chew, Emily Y.] NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Chew, EY (reprint author), NEI, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
NR 9
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U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD JUN
PY 2014
VL 132
IS 6
BP 665
EP 666
DI 10.1001/jamaophthalmol.2014.643
PG 2
WC Ophthalmology
SC Ophthalmology
GA AJ7PQ
UT WOS:000337889000001
PM 24651887
ER
PT J
AU Zhang, R
Cairelli, MJ
Fiszman, M
Rosemblat, G
Kilicoglu, H
Rindflesch, TC
Pakhomov, SV
Melton, GB
AF Zhang, Rui
Cairelli, Michael J.
Fiszman, Marcelo
Rosemblat, Graciela
Kilicoglu, Halil
Rindflesch, Thomas C.
Pakhomov, Serguei V.
Melton, Genevieve B.
TI Using semantic predications to uncover drug-drug interactions in
clinical data
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Drug-drug interactions; MEDLINE; SemRep; SemMedDB; Natural language
processing; Semantic predication
ID BIOMEDICAL TEXT; DISCOVERY; INHIBITION; KNOWLEDGE; CYP; IDENTIFICATION;
INFORMATION; PERSPECTIVE; SYSTEM; MODEL
AB In this study we report on potential drug-drug interactions between drugs occurring in patient clinical data. Results are based on relationships in SemMedDB, a database of structured knowledge extracted from all MEDLINE citations (titles and abstracts) using SemRep. The core of our methodology is to construct two potential drug-drug interaction schemas, based on relationships extracted from SemMedDB. In the first schema, Drug1 and Drug2 interact through Drug1's effect on some gene, which in turn affects Drug2. In the second, Drug1 affects Gene1, while Drug2 affects Gene2. Gene1 and Gene2, together, then have an effect on some biological function. After checking each drug pair from the medication lists of each of 22 patients, we found 19 known and 62 unknown drug-drug interactions using both schemas. For example, our results suggest that the interaction of Lisinopril, an ACE inhibitor commonly prescribed for hypertension, and the antidepressant sertraline can potentially increase the likelihood and possibly the severity of psoriasis. We also assessed the relationships extracted by SemRep from a linguistic perspective and found that the precision of SemRep was 0.58 for 300 randomly selected sentences from MEDLINE. Our study demonstrates that the use of structured knowledge in the form of relationships from the biomedical literature can support the discovery of potential drug-drug interactions occurring in patient clinical data. Moreover, SemMedDB provides a good knowledge resource for expanding the range of drugs, genes, and biological functions considered as elements in various drug-drug interaction pathways. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Zhang, Rui; Pakhomov, Serguei V.; Melton, Genevieve B.] Univ Minnesota, Inst Hlth Informat, Minneapolis, MN USA.
[Cairelli, Michael J.; Fiszman, Marcelo; Rosemblat, Graciela; Kilicoglu, Halil; Rindflesch, Thomas C.] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20892 USA.
[Pakhomov, Serguei V.] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA.
[Melton, Genevieve B.] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA.
RP Cairelli, MJ (reprint author), BG 38A Rm 9N912A,8600 Rockville Pike, Bethesda, MD 20892 USA.
EM zhan1386@umn.edu; cairellimj@mail.nih.gov; fiszmanm@mail.nih.gov;
grosemblat@mail.nih.gov; kilicogluh@mail.nih.gov;
trindflesch@mail.nih.gov; pakh0002@umn.edu; gmelton@umn.edu
FU Intramural Research Program of the NIH, National Library of Medicine
FX This research was supported in part by an appointment to the NLM
Research Participation Program, which is administered by the Oak Ridge
Institute for Science and Education through an inter-agency agreement
between the U.S. Department of Energy and the National Library of
Medicine. This project was supported in part by the Intramural Research
Program of the NIH, National Library of Medicine.
NR 44
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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 1532-0464
EI 1532-0480
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD JUN
PY 2014
VL 49
BP 134
EP 147
DI 10.1016/j.jbi.2014.01.004
PG 14
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA AJ6AN
UT WOS:000337772200014
PM 24448204
ER
PT J
AU Dufresne, SF
Marr, KA
Sydnor, E
Staab, JF
Karp, JE
Lu, K
Zhang, SAX
Lavallee, C
Perl, TM
Neofytos, D
AF Dufresne, Simon F.
Marr, Kieren A.
Sydnor, Emily
Staab, Janet F.
Karp, Judith E.
Lu, Kit
Zhang, Sean X.
Lavallee, Christian
Perl, Trish M.
Neofytos, Dionysios
TI Epidemiology of Candida kefyr in Patients with Hematologic Malignancies
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID INVASIVE FUNGAL-INFECTIONS; KLUYVEROMYCES-MARXIANUS; NEUTROPENIC
PATIENTS; EMERGING PATHOGEN; SPOILAGE YEASTS; FUNGEMIA; ALBICANS; PCR;
COLONIZATION; LEUKEMIA
AB Candida kefyr is an emerging pathogen among patients with hematologic malignancies (HM). We performed a retrospective study at Johns Hopkins Hospital to evaluate the epidemiology of C. kefyr colonization and infection in HM patients between 2004 and 2010. Eighty-three patients were colonized and/or infected with C. kefyr, with 8 (9.6%) having invasive candidiasis (IC). The yearly incidence of C. kefyr colonization and candidemia increased over the study period (P < 0.01), particularly after 2009. In 2010, C. kefyr caused 16.7% of candidemia episodes. The monthly incidence of C. kefyr was higher during the summer throughout the study. In a cohort of patients with acute myelogenic leukemia receiving induction chemotherapy, risks for C. kefyr colonization included the summer season (odds ratio [OR], 3.1; P = 0.03); administration of an azole (OR, 0.06; P < 0.001) or amphotericin B (OR, 0.35; P = 0.05) was protective. Fingerprinting of 16 isolates by repetitive sequence-based PCR showed that all were different genotypes. The epidemiology of C. kefyr candidemia was evaluated in another hospital in Montreal, Canada; data confirmed higher rates of C. kefyr infection in the summer. C. kefyr appears to be increasing in HM patients, with prominent summer seasonality. These findings raise questions about the effect of antifungal agents and health care exposures (e.g., yogurt) on the epidemiology of this yeast.
C1 [Dufresne, Simon F.; Marr, Kieren A.; Sydnor, Emily; Staab, Janet F.; Perl, Trish M.; Neofytos, Dionysios] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
[Dufresne, Simon F.; Lavallee, Christian] Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada.
[Marr, Kieren A.; Karp, Judith E.; Lu, Kit] Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Ctr, Baltimore, MD USA.
[Sydnor, Emily] Univ Utah, Div Infect Dis, Salt Lake City, UT USA.
[Lu, Kit] NIH, Dept Hematol, Bethesda, MD 20892 USA.
[Zhang, Sean X.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Perl, Trish M.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
RP Marr, KA (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
EM kmarr4@jhmi.edu
FU Astellas Pharma Inc.; Pfizer Inc. [WS297422]; National Institutes of
Health grant K24 [AI085118]; National Cancer Institute [2P30-06973-48];
drug development grant [U01 CA70095]; Universite de Montreal and Hopital
Maisonneuve-Rosemont; Astellas; Merck; Pfizer; Sigma Tau; Medimmune;
CDC; VA; IBIS Biosciences/Abbott Molecular; AdvanDx Corporation;
University of Montreal, Maisonneuve-Rosemont Hospital
FX This work was partly supported by a grant from Astellas Pharma Inc., a
grant from Pfizer Inc. (WS297422), the National Institutes of Health
grant K24 (AI085118, to K. A. M.), a National Cancer Institute grant
(2P30-06973-48, to J.E.K.), a drug development grant (U01 CA70095, to
J.E.K.), and fellowship grants from Universite de Montreal and Hopital
Maisonneuve-Rosemont (to S. F. D.).; K. A. M. has been a
consultant/advisor for Astellas, Merck, and Pfizer and has received
research grants from Astellas, Merck, Pfizer, and Sigma Tau. T. M. P.
has received research grants from Medimmune, Merck, CDC, and VA and has
been an advisor for Pfizer. S. X. Z. has received research contract
funds from IBIS Biosciences/Abbott Molecular and AdvanDx Corporation. S.
F. D. has received research funding from University of Montreal,
Maisonneuve-Rosemont Hospital, and Pfizer; has consulted for Merck; and
has moderated a conference for Pfizer. D. N. has received research
grants from Pfizer and has served on advisory boards or as a consultant
for Roche and Astellas.
NR 42
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U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD JUN
PY 2014
VL 52
IS 6
BP 1830
EP 1837
DI 10.1128/JCM.00131-14
PG 8
WC Microbiology
SC Microbiology
GA AJ7YZ
UT WOS:000337919500005
PM 24622105
ER
PT J
AU Drame, PM
Fink, DL
Kamgno, J
Herrick, JA
Nutman, TB
AF Drame, Papa M.
Fink, Doran L.
Kamgno, Joseph
Herrick, Jesica A.
Nutman, Thomas B.
TI Loop-Mediated Isothermal Amplification for Rapid and Semiquantitative
Detection of Loa loa Infection
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID SERIOUS ADVERSE EVENTS; DIAGNOSTIC SENSITIVITY; COLORIMETRIC DETECTION;
MANSONELLA-PERSTANS; MASS TREATMENT; LOIASIS; IVERMECTIN; MALARIA;
FILARIASIS; BLUE
AB Rapid and accurate tests are currently needed to identify individuals with high levels of Loa loa microfilaria (mf), so that these individuals may be excluded from mass ivermectin administration campaigns against onchocerciasis and lymphatic filariasis being conducted in areas where Onchocerca volvulus, Wuchereria bancrofti, and L. loa are coendemic. To address this need, colorimetric loop-mediated isothermal amplification (LAMP) assays targeting the L. loa-specific gene sequences LLMF72 and LLMF342 were developed for the detection and quantification of L. loa microfilaremia. Both LAMP assays were highly specific (100%) for L. loa infection compared to the absence of infection or infection with related filarial pathogens. The LLMF72-based LAMP assay showed greater analytic sensitivity (limit of detection, 0.1 pg/ml of genomic DNA [gDNA] and/or 5 mf/ml) than the LLMF342-based LAMP assay (10 pg/ml of gDNA and/or 50 mf/ml), and its analytic sensitivity was similar to that of LLMF72-based quantitative PCR (qPCR). A high level of correlation was observed between microfilaria counts as determined by LLMF72-based qPCR and time to positivity by the LAMP assay, and performance measures of sensitivity, specificity, and positive and negative predictive values were similar for both assays when applied to field-collected clinical samples. By simply varying the run time, the LAMP assay was able to accurately distinguish individuals at risk for serious adverse events (SAEs) after exposure to ivermectin, using thresholds of >5,000 mf/ml and >30,000 mf/ml as indicators of increasing levels of risk. In summary, LLMF72 LAMP represents a new molecular diagnostic tool that is readily applicable as a point-of-care method for L. loa microfilarial detection and quantification in resource-limited countries where L. loa infection is endemic.
C1 [Drame, Papa M.; Fink, Doran L.; Herrick, Jesica A.; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Kamgno, Joseph] Ctr Res Filariasis & Trop Dis, Yaounde, Cameroon.
[Kamgno, Joseph] Univ Yaounde, Fac Med & Biomed Sci, Yaounde, Cameroon.
RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
EM TNUTMAN@niaid.nih.gov
FU Division of Intramural Research (DIR) of the NIAID
FX The Division of Intramural Research (DIR) of the NIAID provided all of
the funds for this study.
NR 45
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U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD JUN
PY 2014
VL 52
IS 6
BP 2071
EP 2077
DI 10.1128/JCM.00525-14
PG 7
WC Microbiology
SC Microbiology
GA AJ7YZ
UT WOS:000337919500036
PM 24696020
ER
PT J
AU Taylor, G
Wyld, S
Valarcher, JF
Guzman, E
Thom, M
Widdison, S
Buchholz, UJ
AF Taylor, Geraldine
Wyld, Sara
Valarcher, Jean-Francois
Guzman, Efrain
Thom, Michelle
Widdison, Stephanie
Buchholz, Ursula J.
TI Recombinant bovine respiratory syncytial virus with deletion of the SH
gene induces increased apoptosis and pro-inflammatory cytokines in
vitro, and is attenuated and induces protective immunity in calves
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID SMALL HYDROPHOBIC PROTEIN; INFLUENZA-VIRUS; MEMBRANE-PERMEABILITY;
MONOCLONAL-ANTIBODIES; CELL-CULTURE; INFECTION; RESPONSES; VACCINE;
DISEASE; INTERLEUKIN-1
AB Bovine respiratory syncytial virus (BRSV) causes inflammation and obstruction of the small airways, leading to severe respiratory disease in young calves. The virus is closely related to human (H)RSV, a major cause of bronchiolitis and pneumonia in young children. The ability to manipulate the genome of RSV has provided opportunities for the development of stable, live attenuated RSV vaccines. The role of the SH protein in the pathogenesis of BRSV was evaluated in vitro and in vivo using a recombinant (r)BRSV in which the SH gene had been deleted. Infection of bovine epithelial cells and monocytes with rBRSV Delta SH, in vitro, resulted in an increase in apoptosis, and higher levels of TNF-alpha and IL-1 beta compared with cells infected with parental, wildtype (WT) rBRSV. Although replication of rBRSV Delta SH and WT rBRSV, in vitro, were similar, the replication of rBRSV Delta SH was moderately reduced in the lower, but not the upper, respiratory tract of experimentally infected calves. Despite the greater ability of rBRSV Delta SH to induce proinflammatory cytokines, in vitro, the pulmonary inflammatory response in rBRSV Delta SH-infected calves was significantly reduced compared with that in calves inoculated with WT rBRSV, 6 days previously. Virus lacking SH appeared to be as immunogenic and effective in inducing resistance to virulent virus challenge, 6 months later, as the parental rBRSV. These findings suggest that rBRSV Delta SH may be an ideal live attenuated virus vaccine candidate, combining safety with a high level of immunogenicity.
C1 [Taylor, Geraldine; Wyld, Sara; Valarcher, Jean-Francois; Guzman, Efrain; Thom, Michelle; Widdison, Stephanie] Pirbright Inst, Woking GU24 0NF, Surrey, England.
[Buchholz, Ursula J.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Taylor, G (reprint author), Pirbright Inst, Woking GU24 0NF, Surrey, England.
EM geraldine.taylor@pirbright.ac.uk
RI Institute, Pirbright/K-4476-2014;
OI Guzman, Efrain/0000-0002-1583-2964
FU European Commission [EC 5th FP-RSV Vac QLK2-CT-1999-00443]; Department
for Environment, Food and Rural Affairs, UK; BBSRC Institute Strategic
Programme on Livestock Viral Diseases at the Pirbright Institute;
Intramural Research Program of the NIH, NIAID
FX This work was supported by the European Commission (EC 5th FP-RSV Vac
QLK2-CT-1999-00443), the Department for Environment, Food and Rural
Affairs, UK and the BBSRC Institute Strategic Programme on Livestock
Viral Diseases at the Pirbright Institute. U. J. B. was supported by the
Intramural Research Program of the NIH, NIAID. We thank Animal Services
at the Pirbright Institute for all their help and Dr Simon Gubbins,
Pirbright Institute, for statistical advice.
NR 45
TC 9
Z9 10
U1 2
U2 9
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
EI 1465-2099
J9 J GEN VIROL
JI J. Gen. Virol.
PD JUN
PY 2014
VL 95
BP 1244
EP 1254
DI 10.1099/vir.0.064931-0
PN 6
PG 11
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA AK1LN
UT WOS:000338176700005
PM 24700100
ER
PT J
AU Yeager, DS
Johnson, R
Spitzer, BJ
Trzesniewski, KH
Powers, J
Dweck, CS
AF Yeager, David Scott
Johnson, Rebecca
Spitzer, Brian James
Trzesniewski, Kali H.
Powers, Joseph
Dweck, Carol S.
TI The Far-Reaching Effects of Believing People Can Change: Implicit
Theories of Personality Shape Stress, Health, and Achievement During
Adolescence
SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY
LA English
DT Article
DE implicit theories; stress; health; ostracism; psychological
interventions
ID SOCIAL-PSYCHOLOGICAL INTERVENTIONS; SELF-AFFIRMATION; STEREOTYPE THREAT;
MIDDLE SCHOOL; POWER; STUDENTS; AGGRESSION; IDENTITY; VICTIMIZATION;
INTELLIGENCE
AB The belief that personality is fixed (an entity theory of personality) can give rise to negative reactions to social adversities. Three studies showed that when social adversity is common-at the transition to high school-an entity theory can affect overall stress, health, and achievement. Study 1 showed that an entity theory of personality, measured during the 1st month of 9th grade, predicted more negative immediate reactions to social adversity and, at the end of the year, greater stress, poorer health, and lower grades in school. Studies 2 and 3, both experiments, tested a brief intervention that taught a malleable (incremental) theory of personality-the belief that people can change. The incremental theory group showed less negative reactions to an immediate experience of social adversity and, 8 months later, reported lower overall stress and physical illness. They also achieved better academic performance over the year. Discussion centers on the power of targeted psychological interventions to effect far-reaching and long-term change by shifting interpretations of recurring adversities during developmental transitions.
C1 [Yeager, David Scott] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA.
[Johnson, Rebecca] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[Spitzer, Brian James] NYU, Steinhardt Sch Culture Educ & Human Dev, New York, NY 10003 USA.
[Trzesniewski, Kali H.] Univ Calif Davis, Dept Human Dev, Davis, CA USA.
[Powers, Joseph] Stanford Univ, Grad Sch Educ, Stanford, CA 94305 USA.
[Dweck, Carol S.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA.
RP Yeager, DS (reprint author), 108 East Dean Keeton Stop A8000, Austin, TX 78712 USA.
EM dyeager@utexas.edu
OI Yeager, David/0000-0002-8522-9503
NR 101
TC 26
Z9 27
U1 12
U2 86
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-3514
EI 1939-1315
J9 J PERS SOC PSYCHOL
JI J. Pers. Soc. Psychol.
PD JUN
PY 2014
VL 106
IS 6
BP 867
EP 884
DI 10.1037/a0036335
PG 18
WC Psychology, Social
SC Psychology
GA AJ7SN
UT WOS:000337897500001
PM 24841093
ER
PT J
AU Sayah, R
Farah, J
Donadille, L
Herault, J
Delacroix, S
De Marzi, L
De Oliveira, A
Vabre, I
Stichelbaut, F
Lee, C
Bolch, WE
Clairand, I
AF Sayah, R.
Farah, J.
Donadille, L.
Herault, J.
Delacroix, S.
De Marzi, L.
De Oliveira, A.
Vabre, I.
Stichelbaut, F.
Lee, C.
Bolch, W. E.
Clairand, I.
TI Secondary neutron doses received by paediatric patients during
intracranial proton therapy treatments
SO JOURNAL OF RADIOLOGICAL PROTECTION
LA English
DT Article
DE proton therapy; passive scattering; stray neutron doses; pediatric and
adult patients; intracranial treatments
ID MONTE-CARLO SIMULATIONS; RADIATION-THERAPY; STRAY RADIATION; 2ND CANCER;
EQUIVALENT; RADIOTHERAPY; PHANTOMS; FIELD; RISK; IRRADIATION
AB This paper's goal is to assess secondary neutron doses received by paediatric patients treated for intracranial tumours using a 178 MeV proton beam. The MCNPX Monte Carlo model of the proton therapy facility, previously validated through experimental measurements for both proton and neutron dosimetry, was used. First, absorbed dose was calculated for organs located outside the clinical target volume using a series of hybrid computational phantoms for different ages and considering a realistic treatment plan. In general, secondary neutron dose was found to decrease as the distance to the treatment field increases and as the patient age increases. In addition, secondary neutron doses were studied as a function of the beam incidence. Next, neutron equivalent dose was assessed using organ-specific energy-dependent radiation weighting factors determined from Monte Carlo simulations of neutron spectra at each organ. The equivalent dose was found to reach a maximum value of similar to 155 mSv at the level of the breasts for a delivery of 49 proton Gy to an intracranial tumour of a one-year-old female patient. Finally, a thorough comparison of the calculation results with published data demonstrated the dependence of neutron dose on the treatment configuration and proved the need for facility-specific and treatment-dependent neutron dose calculations.
C1 [Sayah, R.; Farah, J.; Donadille, L.; Clairand, I.] PRP HOM SDE, IRSN, F-92262 Fontenay Aux Roses, France.
[Herault, J.] CAL Cyclotron Biomed, F-06200 Nice, France.
[Delacroix, S.; De Marzi, L.; De Oliveira, A.] Inst Curie, Ctr Protontherapie Orsay ICPO, F-91898 Orsay, France.
[Vabre, I.] IPN, F-91406 Orsay, France.
[Stichelbaut, F.] IBA, B-1348 Louvain, Belgium.
[Lee, C.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
[Bolch, W. E.] Univ Florida, Dept Nucl & Radiol, Gainesville, FL 32611 USA.
[Bolch, W. E.] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA.
RP Sayah, R (reprint author), PRP HOM SDE, IRSN, BP17, F-92262 Fontenay Aux Roses, France.
EM jad.farah@irsn.fr
RI Lee, Choonsik/C-9023-2015
OI Lee, Choonsik/0000-0003-4289-9870
NR 40
TC 4
Z9 4
U1 0
U2 8
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0952-4746
EI 1361-6498
J9 J RADIOL PROT
JI J. Radiol. Prot.
PD JUN
PY 2014
VL 34
IS 2
BP 279
EP 296
DI 10.1088/0952-4746/34/2/279
PG 18
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA AJ7US
UT WOS:000337904600009
PM 24704989
ER
PT J
AU Lee, E
Lamart, S
Little, MP
Lee, C
AF Lee, Eunah
Lamart, Stephanie
Little, Mark P.
Lee, Choonsik
TI Database of normalised computed tomography dose index for retrospective
CT dosimetry
SO JOURNAL OF RADIOLOGICAL PROTECTION
LA English
DT Article
DE computed tomography dose index; CT dose survey; dose reconstruction
ID CANCER-RISK; SCANS; SCANNERS
AB Volumetric computed tomography dose index (CTDIvol) is an important dose descriptor to reconstruct organ doses for patients combined with the organ dose calculated from computational human phantoms coupled with Monte Carlo transport techniques. CTDIvol can be derived from weighted CTDI (CTDIw) normalised to the tube current-time product (mGy/100 mAs), using knowledge of tube current-time product (mAs), tube potential (kVp), type of CTDI phantoms (head or body), and pitch. The normalised CTDIw is one of the characteristics of a CT scanner but not readily available from the literature. In the current study, we established a comprehensive database of normalised CTDIw values based on multiple data sources: the ImPACT dose survey from the United Kingdom, the CT-Expo dose calculation program, and surveys performed by the US Food and Drug Administration (FDA) and the National Lung Screening Trial (NLST). From the sources, the CTDIw values for a total of 68, 138, 30, and 13 scanner model groups were collected, respectively. The different scanner groups from the four data sources were sorted and merged into 162 scanner groups for eight manufacturers including General Electric (GE), Siemens, Philips, Toshiba, Elscint, Picker, Shimadzu, and Hitachi. To fill in missing CTDI values, a method based on exponential regression analysis was developed based on the existing data. Once the database was completed, two different analyses of data variability were performed. First, we averaged CTDI values for each scanner in the different data sources and analysed the variability of the average CTDI values across the different scanner models within a given manufacturer. Among the four major manufacturers, Toshiba and Philips showed the greatest coefficient of variation (COV) (=standard deviation/mean) for the head and body normalised CTDIw values, 39% and 54%, respectively. Second, the variation across the different data sources was analysed for CT scanners where more than two data sources were involved. The CTDI values for the scanners from Siemens showed the greatest variation across the data sources, being about four times greater than the variation of Toshiba scanners. The established CTDI database will be used for the reconstruction of CTDIvol and then the estimation of individualised organ doses for retrospective patient cohorts in epidemiologic studies.
C1 [Lee, Eunah; Lamart, Stephanie; Little, Mark P.; Lee, Choonsik] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
RP Lee, E (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA.
EM leechoonsik@mail.nih.gov
RI Lee, Choonsik/C-9023-2015;
OI Lee, Choonsik/0000-0003-4289-9870; Little, Mark/0000-0003-0980-7567
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute, Division of Cancer Epidemiology and Genetics
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, the National Cancer Institute, Division
of Cancer Epidemiology and Genetics.
NR 14
TC 6
Z9 6
U1 0
U2 6
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0952-4746
EI 1361-6498
J9 J RADIOL PROT
JI J. Radiol. Prot.
PD JUN
PY 2014
VL 34
IS 2
BP 363
EP 388
DI 10.1088/0952-4746/34/2/363
PG 26
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA AJ7US
UT WOS:000337904600016
PM 24727361
ER
PT J
AU Han, EY
Lee, C
Mcguire, L
Bolch, WE
AF Han, Eun Young
Lee, Choonsik
Mcguire, Lynn
Bolch, Wesley E.
TI A practical guideline for the release of patients treated by I-131 based
on Monte Carlo dose calculations for family members
SO JOURNAL OF RADIOLOGICAL PROTECTION
LA English
DT Article
DE guideline; I-131; Monte Carlo
ID THERAPY; EXPOSURE; POINT; LINE
AB We recently published effective doses per time-integrated activity (mSv MBq(-1) s(-1)) for paediatric and adult family members exposed to an adult patient released from hospital following I-131 therapy. In the present study, we intend to provide medical physicists with a methodology to estimate family member effective dose in daily clinical practice because the duration of post-radiation precautions for the patient-family member exposure scenario has not been explicitly delineated based on the effective dose. Four different exposure scenarios are considered in this study including (1) a patient and a family member standing face to face, (2) a patient and a family member lying side by side, (3) an adult female patient holding a newborn child to her chest and (4) a one-year-old child standing on the lap of an adult female patient following her I-131 therapy. The results of this study suggest that an adult female hyperthyroidism (HT) patient who was administered with 740 MBq should keep a distance of 100 cm from a 15-year-old child for six days and the same distance from other adults for seven days. The HT female patient should avoid holding a newborn against her chest for at least 16 days following hospital discharge, and a female patient treated with 5550 MBq for differentiated thyroid cancer should not hold her newborn child for at least 15 days following hospital discharge. This study also gives dose coefficients allowing one to predict age-specific effective doses to family members given the measured dose rate (mSv h(-1)) of the patient. In conclusion, effective dose-based patient release criteria with a modified NRC two-component model provide a site medical physicist with less restrictive and age-specific radiation precaution guidance as they fully consider a patient's iodine biokinetics and photon attenuation within both the patient and the exposed family members.
C1 [Han, Eun Young] Univ Arkansas Med Sci, Dept Radiat Oncol, Little Rock, AR 72205 USA.
[Lee, Choonsik] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Mcguire, Lynn] Univ Arkansas Med Sci, Dept Radiol, Div Nucl Med, Little Rock, AR 72205 USA.
[Bolch, Wesley E.] Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32611 USA.
RP Han, EY (reprint author), Univ Arkansas Med Sci, Dept Radiat Oncol, Little Rock, AR 72205 USA.
EM eyhan@uams.edu
RI Lee, Choonsik/C-9023-2015
OI Lee, Choonsik/0000-0003-4289-9870
NR 16
TC 3
Z9 3
U1 0
U2 6
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0952-4746
EI 1361-6498
J9 J RADIOL PROT
JI J. Radiol. Prot.
PD JUN
PY 2014
VL 34
IS 2
BP N7
EP N17
DI 10.1088/0952-4746/34/2/N7
PG 11
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA AJ7US
UT WOS:000337904600003
PM 24705486
ER
PT J
AU Yoo, SS
Jorgensen, TJ
Kennedy, AR
Boice, JD
Shapiro, A
Hu, TCC
Moyer, BR
Grace, MB
Kelloff, GJ
Fenech, M
Prasanna, PGS
Coleman, CN
AF Yoo, Stephen S.
Jorgensen, Timothy J.
Kennedy, Ann R.
Boice, John D., Jr.
Shapiro, Alla
Hu, Tom C-C
Moyer, Brian R.
Grace, Marcy B.
Kelloff, Gary J.
Fenech, Michael
Prasanna, Pataje G. S.
Coleman, C. Norman
TI Mitigating the risk of radiation-induced cancers: limitations and
paradigms in drug development
SO JOURNAL OF RADIOLOGICAL PROTECTION
LA English
DT Review
DE radiation-induced cancer; radiation mitigator; radioprotector; radiation
risk
ID PERIPHERAL-BLOOD LYMPHOCYTES; DICENTRIC CHROMOSOME ASSAY; GRADE
PROSTATE-CANCER; BOWMAN-BIRK INHIBITOR; PHOSPHORIBOSYL TRANSFERASE
LOCUS; NUTRITION INTERVENTION TRIALS; SPORADIC COLORECTAL ADENOMAS;
DISEASE-SPECIFIC MORTALITY; BLOCK MICRONUCLEUS ASSAY; ATM-DEFICIENT MICE
AB The United States radiation medical countermeasures (MCM) programme for radiological and nuclear incidents has been focusing on developing mitigators for the acute radiation syndrome (ARS) and delayed effects of acute radiation exposure (DEARE), and biodosimetry technologies to provide radiation dose assessments for guiding treatment. Because a nuclear accident or terrorist incident could potentially expose a large number of people to low to moderate doses of ionising radiation, and thus increase their excess lifetime cancer risk, there is an interest in developing mitigators for this purpose. This article discusses the current status, issues, and challenges regarding development of mitigators against radiation-induced cancers. The challenges of developing mitigators for ARS include: the long latency between exposure and cancer manifestation, limitations of animal models, potential side effects of the mitigator itself, potential need for long-term use, the complexity of human trials to demonstrate effectiveness, and statistical power constraints for measuring health risks (and reduction of health risks after mitigation) following relatively low radiation doses (< 0 :75 Gy). Nevertheless, progress in the understanding of the molecular mechanisms resulting in radiation injury, along with parallel progress in dose assessment technologies, make this an opportune, if not critical, time to invest in research strategies that result in the development of agents to lower the risk of radiation-induced cancers for populations that survive a significant radiation exposure incident.
C1 [Yoo, Stephen S.; Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Jorgensen, Timothy J.] Georgetown Univ, Sch Med, Dept Radiat Med, Washington, DC USA.
[Kennedy, Ann R.] Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA.
[Boice, John D., Jr.] Vanderbilt Univ Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med, Div Epidemiol, Nashville, TN USA.
[Boice, John D., Jr.] Natl Council Radiat Protect & Measurements, Bethesda, MD USA.
[Shapiro, Alla] US FDA, Ctr Drug Evaluat & Res, Off Counter Terrorism & Emergency Coordinat, Silver Spring, MD USA.
[Hu, Tom C-C; Moyer, Brian R.; Grace, Marcy B.] BARDA, Dept Hlth & Human Serv, Div CBRN Countermeasures, Off Assistant Secretary Preparedness & Response,O, Washington, DC USA.
[Kelloff, Gary J.] NCI, Canc Imaging Program, Div Canc Treatment & Diag, NIH, Bethesda, MD USA.
[Fenech, Michael] Commonwealth Sci & Ind Res Org, Adelaide, SA, Australia.
RP Coleman, CN (reprint author), NCI, Radiat Res Program, Div Canc Treatment & Diag, NIH, 9609 Med Ctr Dr 3W102, Bethesda, MD 20892 USA.
FU NCI's Radiation Research Program
FX NCI's Radiation Research Program supported this work. The views
expressed are those of the authors; no endorsement by NCI or other
agencies has been given or inferred. This article has been reviewed by
FDA and determined not to be consistent with Agency's views or policies.
It reflects only the views and opinions of the author. Authors would
like to acknowledge and thank the critical reading and review of the
manuscript by Drs Rosemary Roberts and Joanne Holmes, Center for Drug
Evaluation and Research, FDA, Silver Spring, MD, USA.
NR 172
TC 3
Z9 3
U1 0
U2 16
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0952-4746
EI 1361-6498
J9 J RADIOL PROT
JI J. Radiol. Prot.
PD JUN
PY 2014
VL 34
IS 2
BP R25
EP R52
DI 10.1088/0952-4746/34/2/R25
PG 28
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA AJ7US
UT WOS:000337904600002
PM 24727460
ER
PT J
AU Tempero, M
AF Tempero, Margaret
TI Embracing Team-Based Oncology Care
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Editorial Material
C1 [Tempero, Margaret] Univ Calif San Francisco, Pancreas Ctr, San Francisco, CA 94143 USA.
[Tempero, Margaret] ASCO, Alexandria, VA USA.
[Tempero, Margaret] NCI, Clin Oncol Study Sect, Bethesda, MD 20892 USA.
[Tempero, Margaret] Mayo Clin, Rochester, MN USA.
[Tempero, Margaret] UAB Minnesota, Birmingham, AL USA.
[Tempero, Margaret] Univ Arizona, GI SPORE, Tucson, AZ 85721 USA.
[Tempero, Margaret] Alberta Canada Canc Board, Lustgarten Fdn, Pancreat Canc Act Network, Fdn 5, Edmonton, AB, Canada.
[Tempero, Margaret] EORTC, Brussels, Belgium.
[Tempero, Margaret] Univ Calif San Francisco, Div Med Oncol, San Francisco, CA 94143 USA.
[Tempero, Margaret] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
RP Tempero, M (reprint author), Univ Calif San Francisco, Pancreas Ctr, San Francisco, CA 94143 USA.
NR 2
TC 0
Z9 0
U1 0
U2 1
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
EI 1540-1413
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD JUN
PY 2014
VL 12
IS 6
BP 845
EP 845
PG 1
WC Oncology
SC Oncology
GA AJ5GF
UT WOS:000337710000001
PM 24925194
ER
PT J
AU Noguchi, S
Ogawa, M
Kawahara, G
Malicdan, MC
Nishino, I
AF Noguchi, Satoru
Ogawa, Megumu
Kawahara, Genri
Malicdan, May Christine
Nishino, Ichizo
TI Allele-specific Gene Silencing of Mutant mRNA Restores Cellular Function
in Ullrich Congenital Muscular Dystrophy Fibroblasts
SO MOLECULAR THERAPY-NUCLEIC ACIDS
LA English
DT Article
DE allele-specific; autosomal dominant inheritance; Co16a1; gene silencing;
muscular dystrophy; siRNA
ID COLLAGEN-VI DEFICIENCY; DISEASE; COMMON; SARCOLEMMA; MUTATIONS;
SECRETION; SEQUENCE; CHAINS
AB Ullrich congenital muscular dystrophy (UCMD) is an inherited muscle disorder characterized clinically by muscle weakness, distal joint hyperlaxity, and proximal joint contractures. Sporadic and recessive mutations in the three collagen VI genes, COL6A1, COL6A2, and COL6A3, are reported to be causative. In the sporadic forms, a heterozygous point mutation causing glycine substitution in the triple helical domain has been identified in higher rate. In this study, we examined the efficacy of siRNAs, which target point mutation site, on specific knockdown toward transcripts from mutant allele and evaluated consequent cellular phenotype of UCMD fibroblasts. We evaluated the effect of siRNAs targeted to silence-specific COL6A1 alleles in UCMD fibroblasts, where simultaneous expression of both wild-type and mutant collagen VI resulted in defective collagen localization. Addition of mutant-specific siRNAs allowed normal extracellular localization of collagen VI surrounding fibroblasts, suggesting selective inhibition of mutant collagen VI. Targeting the single-nucleotide COL6A1 c.850G>A (p.G284R) mutation responsible a sporadic autosomal dominant form of UCMD can potently and selectively block expression of mutant collagen VI. These results suggest that allele-specific knockdown of the mutant mRNA can potentially be considered as a therapeutic procedure in UCMD due to COL6A1 point mutations.
C1 [Noguchi, Satoru; Ogawa, Megumu; Kawahara, Genri; Malicdan, May Christine; Nishino, Ichizo] Natl Ctr Neurol & Psychiat, Dept Neuromuscular Res, Natl Inst Neurosci, Translat Med Ctr, Kodaira, Tokyo 1878502, Japan.
[Noguchi, Satoru; Nishino, Ichizo] Natl Ctr Neurol & Psychiat, Translat Med Ctr, Dept Clin Dev, Kodaira, Tokyo 1878502, Japan.
[Kawahara, Genri] Childrens Hosp Boston, Div Genet, Program Genom, Boston, MA USA.
[Malicdan, May Christine] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Noguchi, S (reprint author), Natl Ctr Neurol & Psychiat, Dept Neuromuscular Res, Natl Inst Neurosci, 4-1-1 Ogawahigashi Cho, Kodaira, Tokyo 1878502, Japan.
EM noguchi@ncnp.go.jp
OI Nishino, Ichizo/0000-0001-9452-112X
FU Intramural Research Grant for Neurological and Psychiatric Disorders of
NCNP [25-5]; Research on Rare and intractable disease from the Ministry
of Health, Labour and Welfare, Japan; JSPS KAKENHI [23390236, 26293214]
FX We thank Takahiro Yonekawa (NCNP) for helpful discussion. This study was
partially supported by Intramural Research Grant (25-5) for Neurological
and Psychiatric Disorders of NCNP to S.N., by Research on Rare and
intractable disease from the Ministry of Health, Labour and Welfare to
I.N., Japan and by JSPS KAKENHI (23390236, 26293214) to S.N. The authors
declared no conflict of interest.
NR 25
TC 2
Z9 2
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2162-2531
J9 MOL THER-NUCL ACIDS
JI Mol. Ther.-Nucl. Acids
PD JUN
PY 2014
VL 3
AR e171
DI 10.1038/mtna.2014.22
PG 7
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AK0BA
UT WOS:000338076400005
PM 24959844
ER
PT J
AU Ahsan, S
Raabe, E
Haffner, M
Warren, K
Quezado, M
Ballester, L
Nazarian, J
Eberhart, C
Rodriguez, F
AF Ahsan, Sama
Raabe, Eric
Haffner, Michael
Warren, Katherine
Quezado, Martha
Ballester, Leomar
Nazarian, Javad
Eberhart, Charles
Rodriguez, Fausto
TI INCREASED 5-HYDROXYMETHYLCYTOSINE AND DECREASED 5-METHYLCYTOSINE ARE
INDICATORS OF GLOBAL EPIGENETIC DYSREGULATION IN DIFFUSE INTRINSIC
PONTINE GLIOMA
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 16th International Symposium on Pediatric Neuro-Oncology (ISPNO)
CY JUN 28-JUL 02, 2014
CL Singapore, SINGAPORE
C1 [Ahsan, Sama] Johns Hopkins Dept Pediat Hematol Oncol, Baltimore, MD USA.
[Raabe, Eric] Johns Hopkins Dept Pediat Oncol, Baltimore, MD USA.
[Haffner, Michael] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA.
[Warren, Katherine] NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Quezado, Martha; Ballester, Leomar] NIH, Pathol Lab, Bethesda, MD 20892 USA.
[Nazarian, Javad] Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA.
[Eberhart, Charles; Rodriguez, Fausto] Johns Hopkins Univ Hosp, Div Neuropathol, Baltimore, MD 21287 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 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2014
VL 16
SU 1
MA HG-044
BP 50
EP 51
PG 2
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA AJ8AK
UT WOS:000337924200191
ER
PT J
AU Grasso, C
Truffaux, N
Berlow, N
Liu, LN
Debily, MA
Davis, L
Huang, E
Woo, P
Tang, YJ
Ponnuswami, A
Chen, S
Huang, YL
Hutt-Cabezas, M
Warren, K
Dret, L
Meltzer, P
Mao, H
Quezado, M
van Vuurden, D
Abraham, J
Fouladi, M
Svalina, MN
Wang, N
Hawkins, C
Raabe, E
Hulleman, E
Li, XN
Keller, C
Spellman, PT
Pal, R
Grill, J
Monje, M
AF Grasso, Catherine
Truffaux, Nathalene
Berlow, Noah
Liu, Lining
Debily, Marie-Anne
Davis, Lara
Huang, Elaine
Woo, Pamelyn
Tang, Yujie
Ponnuswami, Anitha
Chen, Spenser
Huang, Yulun
Huett-Cabezas, Marianne
Warren, Katherine
Dret, Ludivine
Meltzer, Paul
Mao, Hua
Quezado, Martha
van Vuurden, Dannis
Abraham, Jinu
Fouladi, Maryam
Svalina, Matthew N.
Wang, Nicholas
Hawkins, Cynthia
Raabe, Eric
Hulleman, Esther
Li, Xiao-Nan
Keller, Charles
Spellman, Paul T.
Pal, Ranadip
Grill, Jacques
Monje, Michelle
TI FUNCTIONALLY-DEFINED THERAPEUTIC TARGETS IN DIFFUSE INTRINSIC PONTINE
GLIOMA: A REPORT OF THE CHILDREN'S ONCOLOGY GROUP DIPG PRECLINICAL
CONSORTIUM
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 16th International Symposium on Pediatric Neuro-Oncology (ISPNO)
CY JUN 28-JUL 02, 2014
CL Singapore, SINGAPORE
C1 [Grasso, Catherine; Wang, Nicholas; Spellman, Paul T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Truffaux, Nathalene; Debily, Marie-Anne; Dret, Ludivine; Grill, Jacques] Inst Gustave Roussy, Villejuif, France.
[Truffaux, Nathalene; Debily, Marie-Anne; Dret, Ludivine; Grill, Jacques] Univ Paris 11, Villejuif, France.
[Berlow, Noah] Texas Tech Univ, Lubbock, TX 79409 USA.
[Liu, Lining; Woo, Pamelyn; Tang, Yujie; Ponnuswami, Anitha; Chen, Spenser; Pal, Ranadip; Monje, Michelle] Stanford Univ, Stanford, CA 94305 USA.
Univ Evry Val dEssone, Evry, France.
[Davis, Lara; Huang, Elaine; Abraham, Jinu; Svalina, Matthew N.; Keller, Charles] Pape Family Pediat Res Inst, Portland, OR USA.
[Huang, Yulun; Mao, Hua; Li, Xiao-Nan] Texas Childrens Canc Ctr, Houston, TX USA.
Soochow Univ, Affiliated Hosp 1, Suzhou, Peoples R China.
[Huett-Cabezas, Marianne; Raabe, Eric] Johns Hopkins Univ, Baltimore, MD USA.
[Warren, Katherine; Meltzer, Paul; Quezado, Martha] NCI, Bethesda, MD 20892 USA.
[van Vuurden, Dannis; Hulleman, Esther] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Fouladi, Maryam] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Hawkins, Cynthia] Univ Toronto, Toronto, ON, Canada.
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 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2014
VL 16
SU 1
MA HG-047
BP 51
EP 51
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA AJ8AK
UT WOS:000337924200194
ER
PT J
AU Shandilya, S
McCully, C
Murphy, R
Akshintala, S
Cole, D
Macallister, RP
Cruz, R
Widemann, B
Warren, K
AF Shandilya, Shaefali
McCully, Cynthia
Murphy, Robert
Akshintala, Srivandana
Cole, Diane
Macallister, Rhonda Pung
Cruz, Rafael
Widemann, Brigitte
Warren, Katherine
TI INTRANASAL DELIVERY OF CHEMOTHERAPEUTIC AGENTS IN A NON-HUMAN PRIMATE
MODEL
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 16th International Symposium on Pediatric Neuro-Oncology (ISPNO)
CY JUN 28-JUL 02, 2014
CL Singapore, SINGAPORE
C1 [Shandilya, Shaefali; McCully, Cynthia; Murphy, Robert; Akshintala, Srivandana; Cole, Diane; Macallister, Rhonda Pung; Cruz, Rafael; Widemann, Brigitte; Warren, Katherine] 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 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2014
VL 16
SU 1
MA HG-052
BP 53
EP 53
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA AJ8AK
UT WOS:000337924200199
ER
PT J
AU Fouladi, M
Bartels, U
Warren, K
Hassal, T
Baugh, J
Kirkendall, J
Doughman, R
Leach, J
Jones, B
Miles, L
Hawkins, C
Bouffet, E
Hargrave, D
Grill, J
Jones, C
Jacques, T
Savage, S
Goldman, S
Leary, S
Packer, R
Saunders, D
Wesseling, P
Varlet, P
van Vuurden, D
AF Fouladi, Maryam
Bartels, Ute
Warren, Kathy
Hassal, Tim
Baugh, Joshua
Kirkendall, Jenavieve
Doughman, Renee
Leach, James
Jones, Blaise
Miles, Lili
Hawkins, Cynthia
Bouffet, Eric
Hargrave, Darren
Grill, Jacques
Jones, Chris
Jacques, Thomas
Savage, Sharon
Goldman, Stewart
Leary, Sarah
Packer, Roger
Saunders, Dawn
Wesseling, Peter
Varlet, Pascale
van Vuurden, Dannis
TI ESTABLISHMENT OF AN INTERNATIONAL DIFFUSE INTRINSIC PONTINE GLIOMA
(DIPG) REGISTRY
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 16th International Symposium on Pediatric Neuro-Oncology (ISPNO)
CY JUN 28-JUL 02, 2014
CL Singapore, SINGAPORE
C1 [Fouladi, Maryam; Baugh, Joshua; Kirkendall, Jenavieve; Doughman, Renee; Leach, James; Jones, Blaise; Miles, Lili] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Bartels, Ute; Hawkins, Cynthia; Bouffet, Eric] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Warren, Kathy; Savage, Sharon] NIH, Bethesda, MD 20892 USA.
[Hassal, Tim] Royal Childrens Hosp, Brisbane, Qld, Australia.
[Hargrave, Darren; Saunders, Dawn] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[Grill, Jacques] Inst Gustave Roussy, Villejuif, France.
[Jones, Chris] Inst Canc Res, Sutton, Surrey, England.
[Jacques, Thomas] UCL, Child Hlth, London, England.
[Goldman, Stewart] Lurie Childrens Hosp, Chicago, IL USA.
[Leary, Sarah] Seattle Childrens Hosp, Seattle, WA USA.
[Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Wesseling, Peter] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Varlet, Pascale] Hop St Anne, F-75674 Paris, France.
[van Vuurden, Dannis] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
RI Wesseling, P./H-8114-2014; Jacques, Thomas/C-2209-2008
OI Wesseling, P./0000-0001-5453-5201; Jacques, Thomas/0000-0002-7833-2158
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 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2014
VL 16
SU 1
MA HG-074
BP 58
EP 59
PG 2
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA AJ8AK
UT WOS:000337924200221
ER
PT J
AU Fisher, MJ
Widemann, BC
Dombi, E
Wolters, P
Cantor, A
Vinks, A
Parentesis, J
Ullrich, N
Gutmann, D
Viskochil, D
Tonsgard, J
Korf, B
Packer, R
Weiss, B
AF Fisher, Michael J.
Widemann, Brigitte C.
Dombi, Eva
Wolters, Pamela
Cantor, Alan
Vinks, Alexander
Parentesis, John
Ullrich, Nicole
Gutmann, David
Viskochil, David
Tonsgard, James
Korf, Bruce
Packer, Roger
Weiss, Brian
TI PHASE 2 STUDY OF THE MTOR INHIBITOR SIROLIMUS FOR PROGRESSIVE
NF1-ASSOCIATED PLEXIFORM NEUROFIBROMAS (PN): A NEUROFIBROMATOSIS
CLINICAL TRIALS CONSORTIUM STUDY
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 16th International Symposium on Pediatric Neuro-Oncology (ISPNO)
CY JUN 28-JUL 02, 2014
CL Singapore, SINGAPORE
C1 [Fisher, Michael J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Widemann, Brigitte C.; Dombi, Eva; Wolters, Pamela] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Cantor, Alan; Korf, Bruce] Univ Alabama Birmingham, Birmingham, AL USA.
[Vinks, Alexander; Parentesis, John; Weiss, Brian] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Ullrich, Nicole] Childrens Hosp, Boston, MA 02115 USA.
[Gutmann, David] Washington Univ, St Louis, MO USA.
[Viskochil, David] Primary Childrens Med Ctr, Salt Lake City, UT USA.
[Tonsgard, James] Univ Chicago, Chicago, IL 60637 USA.
[Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 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 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2014
VL 16
SU 1
MA RTU-009
BP 129
EP 129
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA AJ8AK
UT WOS:000337924200493
ER
PT J
AU Fisher, MJ
Marcus, L
Weiss, B
Kim, A
Dombi, E
Baldwin, A
Whitcomb, P
Martin, S
Gillespie, A
Doyle, A
Widemann, BC
AF Fisher, Michael J.
Marcus, Leigh
Weiss, Brian
Kim, AeRang
Dombi, Eva
Baldwin, Andrea
Whitcomb, Patricia
Martin, Staci
Gillespie, Andrea
Doyle, Austin
Widemann, Brigitte C.
TI SELUMETINIB (AZD6244) HYDROGEN SULFATE, A MEK1/2 INHIBITOR, IN CHILDREN
WITH NEUROFIBROMATOSIS TYPE 1 (NF1) AND INOPERABLE PLEXIFORM
NEUROFIBROMAS (PNS): A PHASE I STUDY
SO NEURO-ONCOLOGY
LA English
DT Meeting Abstract
CT 16th International Symposium on Pediatric Neuro-Oncology (ISPNO)
CY JUN 28-JUL 02, 2014
CL Singapore, SINGAPORE
C1 [Dombi, Eva; Baldwin, Andrea; Whitcomb, Patricia; Martin, Staci; Gillespie, Andrea; Doyle, Austin; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Fisher, Michael J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Marcus, Leigh; Kim, AeRang] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Weiss, Brian] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
NR 0
TC 0
Z9 0
U1 3
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD JUN
PY 2014
VL 16
SU 1
MA RTU-010
BP 129
EP 129
PG 1
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA AJ8AK
UT WOS:000337924200494
ER
PT J
AU Okoli, T
Traba, J
Sack, M
AF Okoli, Tracy
Traba, Javier
Sack, Michael
TI Acetylation in the control of the NLRP3 inflammasome
SO PHARMACOTHERAPY
LA English
DT Meeting Abstract
CT Virtual Poster Symposium of the American-College-of-Clinical-Pharmacy
CY MAY 20-21, 2014
CL ELECTR NETWORK
SP Amer Coll Clin Pharm
C1 [Okoli, Tracy] Belmont Univ, Coll Pharm, Nashville, TN USA.
[Traba, Javier; Sack, Michael] NHLBI, Ctr Mol Med, NIH, 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 0277-0008
EI 1875-9114
J9 PHARMACOTHERAPY
JI Pharmacotherapy
PD JUN
PY 2014
VL 34
IS 6
MA 141
BP E113
EP E113
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AJ5BV
UT WOS:000337696600144
ER
PT J
AU Martin, A
Simmons, WK
Beauchamp, MS
Gotts, SJ
AF Martin, Alex
Simmons, W. Kyle
Beauchamp, Michael S.
Gotts, Stephen J.
TI Is a single 'hub', with lots of spokes, an accurate description of the
neural architecture of action semantics? Comment on "Action semantics: A
unifying conceptual framework for the selective use of multimodal and
modality-specific object knowledge" by van Elk, van Schie and Bekkering
SO PHYSICS OF LIFE REVIEWS
LA English
DT Editorial Material
ID ANATOMY; NETWORKS; CORTEX; BRAIN
C1 [Martin, Alex; Gotts, Stephen J.] NIMH, NIH, Bethesda, MD 20892 USA.
[Simmons, W. Kyle] Laureate Inst Brain Res, Tulsa, OK USA.
[Simmons, W. Kyle] Univ Tulsa, Tulsa, OK 74104 USA.
[Beauchamp, Michael S.] Univ Texas Houston, Sch Med, Dept Neurobiol & Anat, Houston, TX 77225 USA.
RP Martin, A (reprint author), NIMH, NIH, Bethesda, MD 20892 USA.
RI Simmons, William/K-8925-2015
OI Simmons, William/0000-0002-0399-9003
NR 16
TC 8
Z9 8
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1571-0645
EI 1873-1457
J9 PHYS LIFE REV
JI Phys. Life Rev.
PD JUN
PY 2014
VL 11
IS 2
BP 261
EP 262
DI 10.1016/j.plrev.2014.01.002
PG 2
WC Biology; Biophysics
SC Life Sciences & Biomedicine - Other Topics; Biophysics
GA AJ8UH
UT WOS:000337982800021
PM 24461375
ER
PT J
AU Rynes, KN
Rohrbaugh, MJ
Lebensohn-Chialvo, F
Shoham, V
AF Rynes, Kristina N.
Rohrbaugh, Michael J.
Lebensohn-Chialvo, Florencia
Shoham, Varda
TI Parallel Demand-Withdraw Processes in Family Therapy for Adolescent Drug
Abuse
SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS
LA English
DT Article
DE demand-withdraw interaction; adolescent substance abuse; family therapy;
BSFT; process-outcome research
ID SUBSTANCE USE; EXTERNALIZING BEHAVIORS; MARITAL INTERACTION; PROBLEM
DRINKING; COMMUNICATION; GENDER; CHILD; ALCOHOLISM; CONFLICT; EFFICACY
AB Isomorphism, or parallel process, occurs in family therapy when patterns of therapist-client interaction replicate problematic interaction patterns within the family. This study investigated parallel demand-withdraw processes in brief strategic family therapy (BSFT) for adolescent drug abuse, hypothesizing that therapist-demand/adolescent-withdraw interaction (TD/AW) cycles observed early in treatment would predict poor adolescent outcomes at follow-up for families who exhibited entrenched parent-demand/adolescent-withdraw interaction (PD/AW) before treatment began. Participants were 91 families who received at least four sessions of BSFT in a multisite clinical trial on adolescent drug abuse (Robbins et al., 2011). Prior to receiving therapy, families completed videotaped family interaction tasks from which trained observers coded PD/AW. Another team of raters coded TD/AW during two early BSFT sessions. The main dependent variable was the number of drug-use days that adolescents reported in timeline follow-back interviews 7 to 12 months after family therapy began. Zero-inflated Poisson regression analyses supported the main hypothesis, showing that PD/AW and TD/AW interacted to predict adolescent drug use at follow-up. For adolescents in high PD/AW families, higher levels of TD/AW predicted significant increases in drug use at follow-up, whereas for low PD/AW families, TD/AW and follow-up drug use were unrelated. Results suggest that attending to parallel demand-withdraw processes in parent-adolescent and therapist-adolescent dyads may be useful in family therapy for substance-using adolescents.
C1 [Rynes, Kristina N.] Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87106 USA.
[Rohrbaugh, Michael J.; Lebensohn-Chialvo, Florencia; Shoham, Varda] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA.
[Shoham, Varda] NIMH, Bethesda, MD 20892 USA.
RP Rynes, KN (reprint author), Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, 2650 Yale Blvd SE,MSC11-6280, Albuquerque, NM 87106 USA.
EM krynes@unm.edu
FU NIAAA NIH HHS [T32-AA0018108-01A1, T32 AA018108]; NIDA NIH HHS
[U10-DA13720, U10 DA013720, U10-DA15815, R01-DA17539-01, R01 DA017539,
U10 DA015815]
NR 58
TC 1
Z9 1
U1 5
U2 11
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0893-164X
EI 1939-1501
J9 PSYCHOL ADDICT BEHAV
JI Psychol. Addict. Behav.
PD JUN
PY 2014
VL 28
IS 2
BP 420
EP 430
DI 10.1037/a0031812
PG 11
WC Substance Abuse; Psychology, Multidisciplinary
SC Substance Abuse; Psychology
GA AJ7XW
UT WOS:000337915800012
PM 23438248
ER
PT J
AU Bhutani, M
Landgren, O
AF Bhutani, M.
Landgren, O.
TI Imaging in smoldering (asymptomatic) multiple myeloma. Past, present and
future
SO RADIOLOGE
LA German
DT Article
DE Skeletal survey; Computed tomography; Magnetic resonance imaging;
Positron-emission tomography; Survival
ID STEM-CELL TRANSPLANTATION; WHOLE-BODY MRI; APPARENT
DIFFUSION-COEFFICIENT; HIGH-RISK MYELOMA; BONE-MARROW; F-18-FDG PET/CT;
PROGNOSTIC-SIGNIFICANCE; EMISSION-TOMOGRAPHY; PRECURSOR DISEASE;
SKELETAL SURVEY
AB Emerging clinical trial data support treatment of high-risk smoldering multiple myeloma (SMM) upon diagnosis, and not only at the time of progression to symptomatic complications (multiple myeloma). Early detection of bone and/or bone marrow involvement by sensitive imaging modalities may help define SMM patients at a high risk of progression.
Current (2011) consensus guidelines recognize skeletal survey as a cornerstone modality for assessment of bone involvement at initial diagnosis and during follow-up of SMM. Skeletal survey has severe limitations related to underdetection of bone lesions and also provides no information on bone marrow abnormalities.
Modern imaging strategies such as fluorodeoxyglucose positron-emission tomography/CT (FDG PET/CT) and MRI, in conjunction with functional innovations, provide improved estimates of global abnormalities in the bone marrow and bone compartments. These methods have the potential to objectively quantify early transformation from SMM to multiple myeloma.
Although frequently used for staging and risk prognostication in multiple myeloma, modern imaging techniques have only been evaluated to a limited extent in SMM. Scant data in SMM indicate the prognostic value of two or more MRI-detected focal bone marrow abnormalities, which, if present, predict rapid progression to multiple myeloma. Data evaluating the role of FDG PET/CT in detecting early bone marrow abnormalities as an aid to predicting risk or directing treatment in SMM is currently lacking.
The superior specificity and sensitivity of modern imaging techniques compared to skeletal survey suggest that these should have a place in standard practice management of patients at a high risk of SMM progression. The model imaging of the future should be an all-in-one strategy offering high diagnostic performance for bone marrow abnormalities and low-volume bone lesions, as well as allowing monitoring by minimizing radiation exposure and the need for contrast agents.
Newer imaging techniques need to be validated in prospective clinical trials assessing the SMM to multiple myeloma transition, with the aim of enabling appropriate management decisions. Efforts are also needed to improve the costs and availability of whole-body MRI and/or FDG PET/CT, in order to facilitate their widespread adoption as first-line detection modalities. Future clinical trials of therapeutic agents using earlier detection strategies will have to be carefully designed and take into consideration the risk of lead-time and length-time biases, which might falsely demonstrate longer overall survival.
The English full text version of this article is available at SpringerLink (under "Supplemental").
C1 [Bhutani, M.; Landgren, O.] NCI, Multiple Myeloma Sect, Lymphoid Malignancies Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Landgren, O (reprint author), NCI, Multiple Myeloma Sect, Lymphoid Malignancies Branch, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 10 Room 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
NR 54
TC 4
Z9 4
U1 1
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-832X
EI 1432-2102
J9 RADIOLOGE
JI Radiologe
PD JUN
PY 2014
VL 54
IS 6
BP 572
EP +
DI 10.1007/s00117-014-2694-7
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AJ6GM
UT WOS:000337789000007
PM 24927659
ER
PT J
AU Liu, SH
Moayeri, M
Leppla, SH
AF Liu, Shihui
Moayeri, Mahtab
Leppla, Stephen H.
TI Anthrax lethal and edema toxins in anthrax pathogenesis
SO TRENDS IN MICROBIOLOGY
LA English
DT Review
DE anthrax; capillary morphogenesis protein 2; edema toxin; lethal toxin;
tumor endothelial marker 8
ID CAPILLARY MORPHOGENESIS PROTEIN-2; KINASE 1/2 ACTIVITY;
BACILLUS-ANTHRACIS; INHALATION ANTHRAX; SYSTEMIC ANTHRAX; BARRIER
FUNCTION; IN-VIVO; RECEPTOR; INTERNALIZATION; HOST
AB The pathophysiological effects resulting from many bacterial diseases are caused by exotoxins released by the bacteria. Bacillus anthracis, a spore-forming bacterium, is such a pathogen, causing anthrax through a combination of bacterial infection and toxemia. B. anthracis causes natural infection in humans and animals and has been a top bioterrorism concern since the 2001 anthrax attacks in the USA. The exotoxins secreted by B. anthracis use capillary morphogenesis protein 2 (CMG2) as the major toxin receptor and play essential roles in pathogenesis during the entire course of the disease. This review focuses on the activities of anthrax toxins and their roles in initial and late stages of anthrax infection.
C1 [Liu, Shihui; Moayeri, Mahtab; Leppla, Stephen H.] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Liu, SH (reprint author), NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shliu@niaid.nih.gov; nimoayeri@niaid.nih.gov; sleppla@niaid.nih.gov
FU intramural research programs of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the intramural research programs of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 98
TC 47
Z9 53
U1 5
U2 48
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0966-842X
EI 1878-4380
J9 TRENDS MICROBIOL
JI Trends Microbiol.
PD JUN
PY 2014
VL 22
IS 6
BP 317
EP 325
DI 10.1016/j.tim.2014.02.012
PG 9
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA AJ7JR
UT WOS:000337873500005
PM 24684968
ER
PT J
AU Friend, DM
Kravitz, AV
AF Friend, Danielle M.
Kravitz, Alexxai V.
TI Working together: basal ganglia pathways in action selection
SO TRENDS IN NEUROSCIENCES
LA English
DT Editorial Material
ID NEURONS; EXPECTATION; DISORDERS; STRIATUM; MOVEMENT
AB Jin, Tecuapetla, and Costa combined in vivo electrophysiology with optogenetic-identification to examine firing in multiple basal ganglia nuclei during rapid motor sequences. Their results support a model of basal ganglia function in which co-activation of the direct and indirect pathways facilitate appropriate, while inhibiting competing, motor programs.
C1 [Friend, Danielle M.; Kravitz, Alexxai V.] NIDDK, Bethesda, MD 20814 USA.
[Kravitz, Alexxai V.] NIDA, Baltimore, MD USA.
RP Kravitz, AV (reprint author), NIDDK, NIH, Bldg 10,Room 5-5932 10 Ctr Dr, Bethesda, MD 20814 USA.
EM lex.kravitz@nih.gov
FU Intramural NIH HHS [Z99 DK999999]
NR 15
TC 13
Z9 14
U1 1
U2 17
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD JUN
PY 2014
VL 37
IS 6
BP 301
EP 303
DI 10.1016/j.tins.2014.04.004
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA AJ7ML
UT WOS:000337880700001
PM 24816402
ER
PT J
AU Cuthbert, BN
AF Cuthbert, Bruce N.
CA NIMH RDoC Workgrp
TI The RDoC framework: continuing commentary
SO WORLD PSYCHIATRY
LA English
DT Editorial Material
C1 [Cuthbert, Bruce N.; NIMH RDoC Workgrp] NIMH, Bethesda, MD 20892 USA.
RP Cuthbert, BN (reprint author), NIMH, 6001 Execut Blvd, Bethesda, MD 20892 USA.
NR 4
TC 9
Z9 9
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1723-8617
EI 2051-5545
J9 WORLD PSYCHIATRY
JI World Psychiatry
PD JUN
PY 2014
VL 13
IS 2
BP 196
EP 197
DI 10.1002/wps.20140
PG 2
WC Psychiatry
SC Psychiatry
GA AJ3SS
UT WOS:000337588300023
PM 24890074
ER
PT J
AU Afonin, KA
Kasprzak, WK
Bindewald, E
Kireeva, M
Viard, M
Kashlev, M
Shapiro, BA
AF Afonin, Kirill A.
Kasprzak, Wojciech K.
Bindewald, Eckart
Kireeva, Maria
Viard, Mathias
Kashlev, Mikhail
Shapiro, Bruce A.
TI In Silico Design and Enzymatic Synthesis of Functional RNA Nanoparticles
SO ACCOUNTS OF CHEMICAL RESEARCH
LA English
DT Review
ID SECONDARY STRUCTURE PREDICTION; RNA/DNA HYBRID DUPLEXES; SPLIT
FUNCTIONALITIES; BUILDING-BLOCKS; EMERGING FIELD; DNA HYBRIDS;
POLYMERASE; DELIVERY; SIRNA; ELONGATION
AB CONSPECTUS: The use of RNAs as scaffolds for biomedical applications has several advantages compared with other existing nanomaterials. These include (i) programmability, (ii) precise control over folding and self-assembly, (iii) natural functionalities as exemplified by ribozymes, riboswitches, RNAi, editing, splicing, and inherent translation and transcription control mechanisms, (iv) biocompatibility, (v) relatively low immune response, and (vi) relatively low cost and ease of production. We have tapped into several of these properties and functionalities to construct RNA-based functional nanoparticles (RNA NPs). In several cases, the structural core and the functional components of the NPs are inherent in the same construct. This permits control over the spatial disposition of the components, intracellular availability, and precise stoichiometry.
To enable the generation of RNA NPs, a pipeline is being developed. On one end, it encompasses the rational design and various computational schemes that promote design of the RNA-based nanoconstructs, ultimately producing a set of sequences consisting of RNA or RNA DNA hybrids, which can assemble into the designed construct. On On the other end of the pipeline is an experimental component, which takes the produced sequences and uses them to initialize and characterize their proper assembly and then test the resulting RNA NPs for their function and delivery in cell culture and animal models. An important aspect of this pipeline is the feedback that constantly occurs between the computational and the experimental parts, which synergizes the refinement of both the algorithmic methodologies and the experimental protocols. The utility of this approach is depicted by the several examples described in this Account (nanocubes, nanorings, and RNA DNA hybrids). Of particular interest, from the computational viewpoint, is that in most cases, first a three-dimensional representation of the assembly is produced, and only then are algorithms applied to generate the sequences that will assemble into the designated three-dimensional construct. This is opposite to the usual practice of predicting RNA structures from a given sequence, that is, the RNA folding problem. To be considered is the generation of sequences that upon assembly have the proper intra- or interstrand interactions (or both). Of particular interest from the experimental point of view is the determination and characterization of the proper thermodynamic, kinetic, functionality, and delivery protocols. Assembly of RNA NPs from individual single-stranded RNAs can be accomplished by one-pot techniques under the proper thermal and buffer conditions or, potentially more interestingly, by the use of various RNA polymerases that can promote the formation of RNA NPs cotransciptionally from specifically designed DNA templates. Also of importance is the delivery of the RNA NPs to the cells of interest in vitro or in vivo. Nonmodified RNAs rapidly degrade in blood serum and have difficulties crossing biological membranes due to their negative charge. These problems can be overcome by using, for example, polycationic lipid-based carriers. Our work involves the use of bolaamphiphiles, which are amphipathic compounds with positively charged hydrophilic head groups at each end connected by a hydrophobic chain. We have correlated results from molecular dynamics computations with various experiments to understand the characteristics of such delivery agents.
C1 [Afonin, Kirill A.; Viard, Mathias; Shapiro, Bruce A.] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Kasprzak, Wojciech K.; Bindewald, Eckart; Viard, Mathias] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 21702 USA.
[Kireeva, Maria; Kashlev, Mikhail] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Shapiro, BA (reprint author), NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM shapirbr@mail.nih.gov
FU Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]; National Institutes of Health, Center for
Cancer Research
FX This publication has been funded in part with federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health, under Contract HHSN261200800001E. This research was supported
in part by the Intramural Research Program of the National Institutes of
Health, Center for Cancer Research. 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 75
TC 18
Z9 18
U1 2
U2 32
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0001-4842
EI 1520-4898
J9 ACCOUNTS CHEM RES
JI Accounts Chem. Res.
PD JUN
PY 2014
VL 47
IS 6
BP 1731
EP 1741
DI 10.1021/ar400329z
PG 11
WC Chemistry, Multidisciplinary
SC Chemistry
GA AJ4KL
UT WOS:000337645100011
PM 24758371
ER
PT J
AU Leeds, PR
Yu, FS
Wan, ZF
Chiu, CT
Zhang, YM
Leng, Y
Linares, GR
Chuang, DM
AF Leeds, Peter R.
Yu, Fengshan
Wan, Zhifei
Chiu, Chi-Tso
Zhang, Yumin
Leng, Yan
Linares, Gabriel R.
Chuang, De-Maw
TI A New Avenue for Lithium: Intervention in Traumatic Brain Injury
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Review
DE Anti-inflammation; behavioral deficits and cognitive improvements;
combined therapy treatment; controlled cortical impact; functional
recovery; GSK-3 (glycogen synthase kinase-3) inhibitor; lithium; mood
stabilizer; neuroprotection; neuroregeneration; preclinical model; TBI
(traumatic brain injury)
ID GLYCOGEN-SYNTHASE KINASE-3; ENDOTHELIAL GROWTH-FACTOR; AMYLOID PRECURSOR
PROTEIN; MOOD STABILIZERS LITHIUM; FOCAL CEREBRAL-ISCHEMIA; NEURAL
PROGENITOR CELLS; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM;
N-ACETYL-ASPARTATE; RAT DENTATE GYRUS
AB Traumatic brain injury (TBI) is a leading cause of disability and death from trauma to central nervous system (CNS) tissues. For patients who survive the initial injury, TBI can lead to neurodegeneration as well as cognitive and motor deficits, and is even a risk factor for the future development of neurodegenerative disorders such as Alzheimer's disease. Preclinical studies of multiple neuropathological and neurodegenerative disorders have shown that lithium, which is primarily used to treat bipolar disorder, has considerable neuroprotective effects. Indeed, emerging evidence now suggests that lithium can also mitigate neurological deficits incurred from TBI. Lithium exerts neuroprotective effects and stimulates neurogenesis via multiple signaling pathways; it inhibits glycogen synthase kinase-3 (GSK-3), upregulates neurotrophins and growth factors (e.g., brain-derived neurotrophic factor (BDNF)), modulates inflammatory molecules, upregulates neuroprotective factors (e.g., B-cell lymphoma-2 (Bcl-2), heat shock protein 70 (HSP-70)), and concomitantly downregulates pro-apoptotic factors. In various experimental TB1 paradigms, lithium has been shown to reduce neuronal death, microglial activation, cyclooxygenase-2 induction, amyloid-beta (A beta), and hyperphosphorylated tau levels, to preserve blood-brain barrier integrity, to mitigate neurological deficits and psychiatric disturbance, and to improve learning and memory outcome. Given that lithium exerts multiple therapeutic effects across an array of CNS disorders, including promising results in preclinical models of TB!, additional clinical research is clearly warranted to determine its therapeutic attributes for combating TBI. Here, we review lithium's exciting potential in ameliorating physiological as well as cognitive deficits induced by TBI.
C1 [Leeds, Peter R.; Yu, Fengshan; Wan, Zhifei; Chiu, Chi-Tso; Leng, Yan; Linares, Gabriel R.; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Yu, Fengshan; Zhang, Yumin; Chuang, De-Maw] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Yu, Fengshan; Zhang, Yumin; Chuang, De-Maw] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA.
RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, 10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA.
EM chuang@mail.nih.gov
FU Department of Defense in the Center for Neuroscience and Regenerative
Medicine (CNRM); Intramural Research Program of the National Institute
of Mental Health, National Institutes of Health, Department of Health
and Human Services (IRP-NIMH-NIH-DHHS)
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health,
Department of Health and Human Services (IRP-NIMH-NIH-DHHS), and the
Department of Defense in the Center for Neuroscience and Regenerative
Medicine (CNRM).
NR 174
TC 16
Z9 18
U1 1
U2 42
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD JUN
PY 2014
VL 5
IS 6
BP 422
EP 433
DI 10.1021/cn500040g
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
& Neurology
GA AJ5KF
UT WOS:000337720400004
PM 24697257
ER
PT J
AU Rapoport, SI
AF Rapoport, Stanley I.
TI Lithium and the Other Mood Stabilizers Effective in Bipolar Disorder
Target the Rat Brain Arachidonic Acid Cascade
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Review
DE Lithium; bipolar disorder; arachidonic acid; carbamazepine; mood
stabilizers; valproic acid; rat; brain; antidepressant; antipsychotics;
biotype
ID POSTMORTEM FRONTAL-CORTEX; ACYL-COA SYNTHETASES; PHOSPHOLIPASE A(2);
DOCOSAHEXAENOIC ACID; UNANESTHETIZED RAT; VALPROIC ACID; DOUBLE-BLIND;
IMAGING NEUROINFLAMMATION; CYCLOOXYGENASE-1 AND-2; TREATMENT DECREASES
AB This Review evaluates the arachidonic acid (AA, 20:4n-6) cascade hypothesis for the actions of lithium and other FDA-approved mood stabilizers in bipolar disorder (BD). The hypothesis is based on evidence in unanesthetized rats that chronically administered lithium, carbamazepine, valproate, or lamotrigine each downregulated brain AA metabolism, and it is consistent with reported upregulated AA cascade markers in post-mortem BD brain. In the rats, each mood stabilizer reduced AA turnover in brain phospholipids, cyclooxygenase-2 expression, and prostaglandin E-2 concentration. Lithium and carbamazepine also reduced expression of cytosolic phospholipase A, (cPLA(2)) IVA, which releases AA from membrane phospholipids, whereas valproate uncompetitively inhibited in vitro acyl-CoA synthetase-4, which recycles AA into phospholipid. Topiramate and gabapentin, proven ineffective in BD, changed rat brain AA metabolism minimally. On the other hand, the atypical antipsychotics olanzapine and clozapine, which show efficacy in BD, decreased rat brain AA metabolism by reducing plasma AA availability. Each of the four approved mood stabilizers also dampened brain AA signaling during glutamatergic NMDA and dopaminergic D-2 receptor activation, while lithium enhanced the signal during cholinergic muscarinic receptor activation. In BD patients, such signaling effects might normalize the neurotransmission imbalance proposed to cause disease symptoms. Additionally, the antidepressants fluoxetine and imipramine, which tend to switch BD depression to mania, IVA increased AA turnover and cPLA, A expression in rat brain, suggesting that brain AA metabolism is higher in BD mania than depression. The AA hypothesis for mood stabilizer action is consistent with reports that low-dose aspirin reduced morbidity in patients taking lithium, and that high n-3 and/or low n-6 polyunsaturated fatty acid diets, which in rats reduce brain AA metabolism, were effective in BD and migraine patients.
C1 NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA.
RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA.
EM sir@mail.nih.gov
FU Intramural Program of the National Institute on Aging
FX This work was entirely supported by the Intramural Program of the
National Institute on Aging.
NR 100
TC 21
Z9 21
U1 4
U2 22
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD JUN
PY 2014
VL 5
IS 6
BP 459
EP 467
DI 10.1021/cn500058v
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
& Neurology
GA AJ5KF
UT WOS:000337720400008
PM 24786695
ER
PT J
AU Liu, ZH
Smith, CB
AF Liu, Zhonghua
Smith, Carolyn Beebe
TI Lithium: A Promising Treatment for Fragile X Syndrome
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Review
DE Fragile X syndrome; FMR1; FMRP; intellectual disability; autism;
dendritic spines; glycogen synthase kinase-3 (GSK-3)
ID MENTAL-RETARDATION PROTEIN; LONG-TERM POTENTIATION; FMR1 KNOCKOUT MICE;
MEDIAL FRONTAL-CORTEX; MOUSE MODEL; SYNAPTIC PLASTICITY; INCREASED
RATES; MESSENGER-RNAS; DROSOPHILA; MEMORY
AB Fragile X syndrome (FXS) is an inherited disorder that results in intellectual disability and a characteristic behavioral profile that includes autism spectrum disorder, attention deficit hyperactivity disorder, sensory hypersensitivity, hyperarousal, and anxiety. The epigenetic silencing of FMR1 and the consequent absence of its protein product, FMRP, is the most common cause of fragile X. The development of animal models of fragile X syndrome 20 years ago has produced a considerable increase in our understanding of the consequences of the absence of FMRP on the structure and function of the nervous system. Some of the insights gained have led to proposals of treatment strategies that are based on cellular and molecular changes observed in animals lacking FMRP. One such proposal is treatment with lithium, a drug with a long history of clinical efficacy in psychiatry and a drug with newly described uses in degenerative disorders of the nervous system. Lithium treatment has been studied extensively in both mouse and fruit fly models of FXS, and it has been shown to reverse numerous behavioral, physiological, cellular, and molecular phenotypes. A report of a pilot clinical trial on a limited number of adult FXS patients indicated that measurable improvements in behavior and function were seen after 2 months of lithium treatment. A double-blind clinical trial of lithium treatment in FXS patients is now needed.
C1 [Liu, Zhonghua; Smith, Carolyn Beebe] NIMH, Sect Neuroadaptat & Prot Metab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Smith, CB (reprint author), NIMH, NIH, Bldg 10,Room 54,10 Ctr Dr,MSC 1298, Bethesda, MD 20892 USA.
EM beebe@mail.nih.gov
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health, Department of Health and Human Services
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health,
Department of Health and Human Services.
NR 77
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Z9 5
U1 2
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD JUN
PY 2014
VL 5
IS 6
BP 477
EP 483
DI 10.1021/cn500077p
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
& Neurology
GA AJ5KF
UT WOS:000337720400010
PM 24814569
ER
PT J
AU Blough, BE
Landavazo, A
Partilla, JS
Baumann, MH
Decker, AM
Page, KM
Rothman, RB
AF Blough, Bruce E.
Landavazo, Antonio
Partilla, John S.
Baumann, Michael H.
Decker, Ann M.
Page, Kevin M.
Rothman, Richard B.
TI Hybrid Dopamine Uptake Blocker-Serotonin Releaser Ligands: A New Twist
on Transporter-Focused Therapeutics
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Dopamine uptake inhibitors; serotonin releasers; serotonin receptor;
cocaine; methamphetamine
ID BIOGENIC-AMINE TRANSPORTERS; IN-VITRO; BUPROPION; HYDROXYBUPROPION;
METHCATHINONE; METABOLITES
AB As part of our program to study neurotransmitter releasers, we report herein a class of hybrid dopamine reuptake inhibitors that display serotonin releasing activity. Hybrid compounds are interesting since they increase the design. potential of transporter related compounds and hence represent a novel and unexplored strategy for therapeutic drug discovery. A series of N-alkylpropiophenones was synthesized and assessed for uptake inhibition and release activity using rat brain synaptosomes. Substitution on the aromatic ring yielded compounds that maintained hybrid activity, with the two disubstituted analogues (PAL-787 and PAL-820) having the most potent hybrid activity.
C1 [Blough, Bruce E.; Landavazo, Antonio; Decker, Ann M.; Page, Kevin M.] RTI Int, Ctr Drug Discovery, Discovery Sci Technol, Res Triangle Pk, NC 27709 USA.
[Partilla, John S.; Baumann, Michael H.; Rothman, Richard B.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Blough, BE (reprint author), RTI Int, Ctr Drug Discovery, Discovery Sci Technol, 3040 Cornwallis Rd, Res Triangle Pk, NC 27709 USA.
EM beb@rti.org
FU National Institute on Drug Abuse [DA12970]; National Institute on Drug
Abuse, NIH
FX Funding was provided by the National Institute on Drug Abuse (DA12970).
Aspects of this work were supported by the Intramural Research Program,
National Institute on Drug Abuse, NIH.
NR 17
TC 13
Z9 13
U1 0
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD JUN
PY 2014
VL 5
IS 6
BP 623
EP 627
DI 10.1021/ml500113s
PG 5
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AJ2OM
UT WOS:000337497200004
PM 24944732
ER
PT J
AU Kumar, V
Banala, AK
Garcia, EG
Cao, JJ
Keck, TM
Bonifazi, A
Deschamps, JR
Newman, AH
AF Kumar, Vivek
Banala, Ashwini K.
Garcia, Erick G.
Cao, Jianjing
Keck, Thomas M.
Bonifazi, Alessandro
Deschamps, Jeffery R.
Newman, Amy Hauck
TI Chiral Resolution and Serendipitous Fluorination Reaction for the
Selective Dopamine D3 Receptor Antagonist BAK2-66
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE DAST; asymmetric catalysis; enantioselectivity; dopamine
ID D-3; PERSPECTIVE; SUBTYPE; BINDING
AB The improved chiral synthesis of the selective dopamine D3 receptor (D3R) antagonist (R)-N-(4-(4-(2,3-dichlorophenyl)piperazin- I -yl) -3-hydroxybutyl)1H-indole-2carboxamide ((R)-PG648) is described. The same chiral secondary alcohol intermediate was used to prepare the enantiomers of a 3-F-benzofuranyl analogue, BAK 2-66. The absolute configurations of the 3-F enantiomers were assigned from their X-ray crystal structures that confirmed retention of configuration during fluorination with N,N-diethylaminosulfur trifluoride (DAST). (R)-BAK2-66 showed higher D3R affinity and selectivity than its (S)-enantiomer; however, it had lower D3R affinity and enantioselectivity than (R)-PG648. Further, importance of the 4-atom linker length between the aryl amide and 4-phenylpiperazine was demonstrated with the 4-fluorobutylproduct (8).
C1 [Kumar, Vivek; Banala, Ashwini K.; Garcia, Erick G.; Cao, Jianjing; Keck, Thomas M.; Bonifazi, Alessandro; Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Deschamps, Jeffery R.] Naval Res Lab, Washington, DC 20375 USA.
RP Newman, AH (reprint author), NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
RI Kumar, Vivek/F-6183-2016; Keck, Thomas/G-9798-2012
OI Keck, Thomas/0000-0003-1845-9373
FU NIDA Intramural Research Program, National Institutes of Health,
Department of Health and Human Services; NIH Visiting Fellowship; NIH
Postdoctoral Intramural Research Training Award (IRTA) Fellowship; NIDA
[Y1-DA1101]; Naval Research Laboratory (NRL)
FX This research was funded by the NIDA Intramural Research Program,
National Institutes of Health, Department of Health and Human Services.
V.K. was supported by an NIH Visiting Fellowship, and T.M.K. was
supported by an NIH Postdoctoral Intramural Research Training Award
(IRTA) Fellowship. The X-ray crystallographic studies were supported by
NIDA through Interagency Agreement #Y1-DA1101 with the Naval Research
Laboratory (NRL).
NR 22
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Z9 8
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD JUN
PY 2014
VL 5
IS 6
BP 647
EP 651
DI 10.1021/ml500006v
PG 5
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AJ2OM
UT WOS:000337497200009
PM 24944737
ER
PT J
AU Kumar, V
Rahbek-Clemmensen, T
Billesbolle, CB
Jorgensen, TN
Gether, U
Newman, AH
AF Kumar, Vivek
Rahbek-Clemmensen, Troels
Billesbolle, Christian B.
Jorgensen, Trine Nygaard
Gether, Ulrik
Newman, Amy Hauck
TI Novel and High Affinity Fluorescent Ligands for the Serotonin
Transporter Based on (S)-Citalopram
SO ACS MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Fluorescent ligand; SERT; citalopram; rhodamine
ID DOPAMINE TRANSPORTER; ANALOGS; PROBES; DESIGN
AB Novel rhodamine-labeled ligands, based on (S)citalopram, were synthesized and evaluated for uptake inhibition at the human serotonin, dopamine, and norepinephrine transporters (hSERT, hDAT, and hNET, respectively) and for binding at SERT, in transiently transfected COS7 cells. Compound 14 demonstrated high affinity binding and selectivity for SERT (K-i; = 3 nM). Visualization of SERT, using confocal laser scanning microscopy, validated compound 14 as a novel tool for studying SERT expression and distribution in living cells.
C1 [Kumar, Vivek; Newman, Amy Hauck] NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Rahbek-Clemmensen, Troels; Billesbolle, Christian B.; Jorgensen, Trine Nygaard; Gether, Ulrik] Univ Copenhagen, Fac Hlth & Med Sci, Mol Neuropharmacol Lab, DK-2200 Copenhagen N, Denmark.
[Rahbek-Clemmensen, Troels; Billesbolle, Christian B.; Jorgensen, Trine Nygaard; Gether, Ulrik] Univ Copenhagen, Fac Hlth & Med Sci, Ctr Pharmacogen, Dept Neurosci & Pharmacol, DK-2200 Copenhagen N, Denmark.
RP Newman, AH (reprint author), NIDA, Med Chem Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM anewman@intra.nida.nih.gov
RI Kumar, Vivek/F-6183-2016;
OI Rahbek-Clemmensen, Troels/0000-0003-2067-5411; Gether,
Ulrik/0000-0002-0020-3807
FU NIDA Intramural Research Program; National Institute of Health [P01 DA
12408]; Danish Medical Research Council; Lundbeck Foundation Center for
Biomembranes in Nanomedicine; NIH Visiting Fellowship
FX This research was funded by the NIDA Intramural Research Program and by
the National Institute of Health Grants P01 DA 12408 (to U.G.), the
Danish Medical Research Council (to U.G.), and the Lundbeck Foundation
Center for Biomembranes in Nanomedicine (to U.G.). V.K. was supported by
an NIH Visiting Fellowship.
NR 15
TC 5
Z9 5
U1 0
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-5875
J9 ACS MED CHEM LETT
JI ACS Med. Chem. Lett.
PD JUN
PY 2014
VL 5
IS 6
BP 696
EP 699
DI 10.1021/ml5000806
PG 4
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA AJ2OM
UT WOS:000337497200018
PM 24944746
ER
PT J
AU Miller, RA
Harrison, DE
Astle, CM
Fernandez, E
Flurkey, K
Han, M
Javors, MA
Li, XN
Nadon, NL
Nelson, JF
Pletcher, S
Salmon, AB
Sharp, ZD
Van Roekel, S
Winkleman, L
Strong, R
AF Miller, Richard A.
Harrison, David E.
Astle, Clinton M.
Fernandez, Elizabeth
Flurkey, Kevin
Han, Melissa
Javors, Martin A.
Li, Xinna
Nadon, Nancy L.
Nelson, James F.
Pletcher, Scott
Salmon, Adam B.
Sharp, Zelton Dave
Van Roekel, Sabrina
Winkleman, Lynn
Strong, Randy
TI Rapamycin-mediated lifespan increase in mice is dose and sex dependent
and metabolically distinct from dietary restriction
SO AGING CELL
LA English
DT Article
DE aging; caloric restriction; glucose; IGF-1; insulin; longevity; mouse;
mTOR; rapamycin; xenobiotic metabolism
ID GENETICALLY HETEROGENEOUS MICE; INTERVENTIONS TESTING PROGRAM; AMES
DWARF MICE; INSULIN SENSITIVITY; EXTENSION; LONGEVITY; TOR; RESISTANCE;
PATHWAY; GENES
AB Rapamycin, an inhibitor of mTOR kinase, increased median lifespan of genetically heterogeneous mice by 23% (males) to 26% (females) when tested at a dose threefold higher than that used in our previous studies; maximal longevity was also increased in both sexes. Rapamycin increased lifespan more in females than in males at each dose evaluated, perhaps reflecting sexual dimorphism in blood levels of this drug. Some of the endocrine and metabolic changes seen in diet-restricted mice are not seen in mice exposed to rapamycin, and the pattern of expression of hepatic genes involved in xenobiotic metabolism is also quite distinct in rapamycin-treated and diet-restricted mice, suggesting that these two interventions for extending mouse lifespan differ in many respects.
C1 [Miller, Richard A.; Han, Melissa; Li, Xinna; Van Roekel, Sabrina; Winkleman, Lynn] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Miller, Richard A.; Han, Melissa; Li, Xinna; Pletcher, Scott; Van Roekel, Sabrina; Winkleman, Lynn] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA.
[Harrison, David E.; Astle, Clinton M.; Flurkey, Kevin] Jackson Lab, Bar Harbor, ME 04609 USA.
[Fernandez, Elizabeth; Strong, Randy] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA.
[Fernandez, Elizabeth; Strong, Randy] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA.
[Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Nadon, Nancy L.] NIA, Div Aging Biol, Bethesda, MD 20892 USA.
[Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Nelson, James F.; Salmon, Adam B.; Sharp, Zelton Dave; Strong, Randy] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Pletcher, Scott] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Sharp, Zelton Dave] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78245 USA.
RP Miller, RA (reprint author), Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
EM millerr@umich.edu
FU NIH [AG022303, AG031736, AG022307, AG013319, AG022308, CA034196];
Department of Veterans Affairs
FX This work was supported by NIH grants AG022303, AG031736 (RAM),
AG022307, AG013319 (RS), and AG022308 (DEH), with important facilities
supported by CA034196 (DEH) and the Department of Veterans Affairs (RS),
We thank Lili Deng and Andrzej Galecki for statistical assistance, Jeff
Halter for comments on an early draft of the paper, and Lisa Burmeister,
Vivian Diaz, Nelson Durgin, Vicki Ingalls, Amanda Keedle, and Pam J
Krason for technical assistance.
NR 46
TC 103
Z9 105
U1 4
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD JUN
PY 2014
VL 13
IS 3
BP 468
EP 477
DI 10.1111/acel.12194
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA AJ2VV
UT WOS:000337523400009
PM 24341993
ER
PT J
AU Tapocik, JD
Schank, JR
Mayo, CL
Damazdic, R
Pincus, A
King, C
Koenig, JI
Heilig, M
Elmer, GI
AF Tapocik, J. D.
Schank, J. R.
Mayo, C. L.
Damazdic, R.
Pincus, A.
King, C.
Koenig, J. I.
Heilig, M.
Elmer, G. I.
TI A RAT MODEL OF PTSD LEADS TO NEURONAL ACTIVATION OF THE LATERAL
SUBREGION OF THE LATERAL HABENULA AND ESCALATED CONTEXT-INDUCED ALCOHOL
CONSUMPTION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
Univ Maryland, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA.
NR 0
TC 0
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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J9 ALCOHOL CLIN EXP RES
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PD JUN
PY 2014
VL 38
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SI SI
MA 0055
BP 14A
EP 14A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700056
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PT J
AU Vatsalya, V
Schwandt, M
Ramchandani, VA
George, DT
AF Vatsalya, V.
Schwandt, M.
Ramchandani, V. A.
George, D. T.
TI CHARACTERIZATION OF POLYUNSATURATED FATTY ACIDS WITH IMMUNE AND HEPATIC
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SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Vatsalya, V.; Schwandt, M.; Ramchandani, V. A.; George, D. T.] NIAAA, Lab Clin & Translat Sci, NIH, Bethesda, MD 20892 USA.
NR 0
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U1 0
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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J9 ALCOHOL CLIN EXP RES
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PD JUN
PY 2014
VL 38
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SI SI
MA 0087
BP 22A
EP 22A
PG 1
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GA AJ2VX
UT WOS:000337523700088
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PT J
AU Vatsalya, V
Ramchandani, VA
Leggio, L
AF Vatsalya, V.
Ramchandani, V. A.
Leggio, L.
TI CARDIOVASCULAR ASSESSMENT BETWEEN TITRATION AND MAINTAINENCE DOSE OF
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SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Vatsalya, V.; Ramchandani, V. A.; Leggio, L.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
RI Leggio, Lorenzo/M-2972-2016
NR 0
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PU WILEY-BLACKWELL
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PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
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J9 ALCOHOL CLIN EXP RES
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PY 2014
VL 38
SU 1
SI SI
MA 0190
BP 48A
EP 48A
PG 1
WC Substance Abuse
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GA AJ2VX
UT WOS:000337523700191
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PT J
AU Vatsalya, V
Umhau, J
Schwandt, M
Phillip, M
Ramchandani, VA
George, DT
AF Vatsalya, V.
Umhau, J.
Schwandt, M.
Phillip, M.
Ramchandani, V. A.
George, D. T.
TI METABOLIC VARIABILITY IN PLASMA FATTY ACIDS CONCENTRATION COULD SERVE AS
POTENTIAL BIOMARKER IN HCV COMORBID ALCOHOL DEPENDENT PATIENTS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Vatsalya, V.; Umhau, J.; Schwandt, M.; Phillip, M.; Ramchandani, V. A.; George, D. T.] NIAAA, Lab Clin & Translat Sci, NIH, Bethesda, MD 20892 USA.
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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J9 ALCOHOL CLIN EXP RES
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PY 2014
VL 38
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SI SI
MA 0189
BP 48A
EP 48A
PG 1
WC Substance Abuse
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GA AJ2VX
UT WOS:000337523700190
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PT J
AU Breslow, RA
Dong, C
White, A
Chen, CM
Yoon, YH
Yi, H
AF Breslow, R. A.
Dong, C.
White, A.
Chen, C. M.
Yoon, Y-H.
Yi, H.
TI ALCOHOL-INTERACTIVE PRESCRIPTION DRUG USE: PREVALENCE BY DRINKING STATUS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Breslow, R. A.; Dong, C.; White, A.; Chen, C. M.; Yoon, Y-H.; Yi, H.] NIAAA, NIH, Bethesda, MD 20892 USA.
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TC 0
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U1 0
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PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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J9 ALCOHOL CLIN EXP RES
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PY 2014
VL 38
SU 1
SI SI
MA 0246
BP 62A
EP 62A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700247
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PT J
AU Pickering, RP
Chou, P
Grant, BF
AF Pickering, R. P.
Chou, P.
Grant, B. F.
TI ALCOHOL DEPENDENCE INCIDENCE BY BEVERAGE PREFERENCE: RESULTS OF THE
NATIONAL EPIDEMIOLOGIC SURVEY ON ALCOHOL AND RELATED CONDITIONS (NESARC
I&II)
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Pickering, R. P.; Chou, P.; Grant, B. F.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD 20892 USA.
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PU WILEY-BLACKWELL
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PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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J9 ALCOHOL CLIN EXP RES
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VL 38
SU 1
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MA 0255
BP 64A
EP 64A
PG 1
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GA AJ2VX
UT WOS:000337523700256
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PT J
AU Saha, TD
Grant, BF
AF Saha, T. D.
Grant, B. F.
TI DIMENSIONALITY AND SCALE PROPERTIES OF DSM-5 ALCOHOL USE DISORDER
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Saha, T. D.; Grant, B. F.] NIAAA, LEB, Bethesda, MD USA.
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TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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J9 ALCOHOL CLIN EXP RES
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PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0256
BP 64A
EP 64A
PG 1
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GA AJ2VX
UT WOS:000337523700257
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PT J
AU Barbier, E
Tapocik, J
Johnstone, A
Schank, J
Zhou, Z
Yuan, Q
Goldman, D
Wahlestedt, C
Heilig, M
AF Barbier, E.
Tapocik, J.
Johnstone, A.
Schank, J.
Zhou, Z.
Yuan, Q.
Goldman, D.
Wahlestedt, C.
Heilig, M.
TI ROLE OF HISTONE MODIFYING ENZYMES PRDM2 AND KDM6B IN ALCOHOL-RELATED
BEHAVIORS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Barbier, E.; Tapocik, J.; Schank, J.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA.
[Zhou, Z.; Yuan, Q.; Goldman, D.] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA.
[Johnstone, A.; Wahlestedt, C.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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J9 ALCOHOL CLIN EXP RES
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VL 38
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MA 0317
BP 80A
EP 80A
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GA AJ2VX
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PT J
AU Carlson, VCC
Carlson, TL
Lovinger, DM
AF Carlson, V. C. Cuzon
Carlson, T. L.
Lovinger, D. M.
TI DIFFERENT ACUTE ETHANOL EFFECTS ON GABAERGIC-MEDIATED POSTSYNAPTIC
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SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Carlson, V. C. Cuzon; Carlson, T. L.] Oregon Hlth & Sci Univ, Oregon Natl Primate Ctr, Beaverton, OR USA.
[Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
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PU WILEY-BLACKWELL
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PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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J9 ALCOHOL CLIN EXP RES
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MA 0352
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GA AJ2VX
UT WOS:000337523700353
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PT J
AU Carlson, VCC
Grant, KA
Lovinger, DM
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Grant, K. A.
Lovinger, D. M.
TI AGE OF ONSET AND GENDER AFFECTS ETHANOL INTAKE AND SYNAPTIC TRANSMISSION
ONTO MEDIUM SPINY NEURONS IN THE PUTAMEN OF THE RHESUSMONKEY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Carlson, V. C. Cuzon; Grant, K. A.] Oregon Hlth & Sci Univ, Oregon Natl Primate Ctr, Beaverton, OR USA.
[Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 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
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MA 0351
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GA AJ2VX
UT WOS:000337523700352
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PT J
AU Augier, E
Dulman, RS
Heilig, M
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Dulman, Russell S.
Heilig, Markus
TI A NEW MODEL OF COMPULSIVE ALCOHOL INTAKE IN RATS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
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CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
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MA 0396
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PT J
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Song, BJ
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Abdelmegeed, M. A.
Jang, S. H.
Song, B. J.
TI LEPTIN INDUCED HIGHER HEPATIC STEATOSIS AND INFLAMMATION IN BINGE
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SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
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PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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MA 0412
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GA AJ2VX
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PT J
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Yun, JW
Yoo, SH
Song, BJ
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Banerjee, A.
Jang, S.
Yun, J. W.
Yoo, S. H.
Song, B. J.
TI THE ROLE OF CYTOCHROME P450 2E1 (CYP2E1) IN THE DEVELOPMENT OF HIGH FAT
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SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20892 USA.
Seoul Natl Univ, Coll Med, Seoul 110, South Korea.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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MA 0413
BP 104A
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UT WOS:000337523700414
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PT J
AU Feng, DC
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Wang, H
Wang, Y
Gao, B
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Li, Yongmei
Xu, Ming-Jiang
Wang, Hua
Wang, Yan
Gao, Bin
TI AGING AGGRAVATES ALCOHOLIC LIVER INJURY IN MICE BY DOWNREGULATING
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SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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CY JUN 21-25, 2014
CL Bellevue, WA
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NR 0
TC 0
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U1 1
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PU WILEY-BLACKWELL
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PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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J9 ALCOHOL CLIN EXP RES
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VL 38
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MA 0423
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GA AJ2VX
UT WOS:000337523700424
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PT J
AU Yun, JW
Son, MJ
Abdelmegeed, MA
Banerjee, A
Morgan, TR
Yoo, SH
Song, BJ
AF Yun, J. W.
Son, M. J.
Abdelmegeed, M. A.
Banerjee, A.
Morgan, T. R.
Yoo, S. H.
Song, B. J.
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alpha-DEPENDENT APOPTOSIS PATHWAY IN MICE AND HUMANS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
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International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 NIAAA, Lab Memb Biochem & Biophys, Rockville, MD 20892 USA.
Seoul Natl Univ, Coll Med, Seoul 151, South Korea.
VA Long Beach Hosp, Long Beach, CA 90701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0426
BP 107A
EP 107A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700427
ER
PT J
AU N'Gouemo, P
Allard, JS
Lovinger, DM
AF N'Gouemo, P.
Allard, J. S.
Lovinger, D. M.
TI UPREGULATION OF CAV1.2 L-TYPE CHANNELS PRECEDES THE ONSET OF ALCOHOL
WITHDRAWAL SEIZURE SUSCEPTIBILITY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [N'Gouemo, P.] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20057 USA.
[Allard, J. S.] Howard Univ, Col Med, Dept Physiol & Biophys, Washington, DC 20059 USA.
[Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0435
BP 109A
EP 109A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700436
ER
PT J
AU Schuebel, KE
Blackistone, K
Mordi, I
Yuan, Q
Idrus, N
Thomas, JD
Goldman, D
AF Schuebel, K. E.
Blackistone, K.
Mordi, I.
Yuan, Q.
Idrus, N.
Thomas, J. D.
Goldman, D.
TI WHOLE GENOME DNA CYTOSINE METHYLATION PROFILING IN A RAT MODEL OF FASD
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Schuebel, K. E.; Blackistone, K.; Mordi, I.; Yuan, Q.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
[Idrus, N.; Thomas, J. D.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0460
BP 115A
EP 115A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700461
ER
PT J
AU Yan, J
Schwandt, ML
Cho, SB
Stangl, BL
Kwako, LE
Dick, DM
Kendler, KS
Leggio, L
Momenan, R
Heilig, M
Ramchandani, VA
AF Yan, J.
Schwandt, M. L.
Cho, S. B.
Stangl, B. L.
Kwako, L. E.
Dick, D. M.
Kendler, K. S.
Leggio, L.
Momenan, R.
Heilig, M.
Ramchandani, V. A.
TI LATENT CLASS ANALYSIS OF NON-TREATMENT SEEKING SOCIAL DRINKERS REVEAL 3
EMPIRICAL CLASSES WITH DIFFERENCES IN RISK FOR ALCOHOL-RELATED
PHENOTYPES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Yan, J.; Schwandt, M. L.; Stangl, B. L.; Kwako, L. E.; Leggio, L.; Momenan, R.; Heilig, M.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, LCTS, NIH, Bethesda, MD 20892 USA.
[Yan, J.; Cho, S. B.; Dick, D. M.; Kendler, K. S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA.
RI Leggio, Lorenzo/M-2972-2016
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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0495
BP 124A
EP 124A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700496
ER
PT J
AU Falk, DE
Litten, Z
Ryan, ML
Fertig, JB
AF Falk, D. E.
Litten, Z.
Ryan, M. L.
Fertig, J. B.
CA Natl Inst Alcohol Abuse Alcoholism
TI A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL ASSESSING THE EFFICACY OF
VARENICLINE TARTRATE FOR ALCOHOL DEPENDENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Falk, D. E.; Litten, Z.; Ryan, M. L.; Fertig, J. B.; Natl Inst Alcohol Abuse Alcoholism] NIAAA, Div Treatment & Recovery Res, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0554
BP 139A
EP 139A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700555
ER
PT J
AU Sanjuan, PM
Rice, SL
Witkiewitz, K
Mandler, RN
Crandall, C
Bogenschutz, MP
AF Sanjuan, P. M.
Rice, S. L.
Witkiewitz, K.
Mandler, R. N.
Crandall, C.
Bogenschutz, M. P.
TI ALCOHOL, TOBACCO, AND DRUG USE AMONG EMERGENCY DEPARTMENT PATIENTS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 UNM, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87106 USA.
UNM, Hlth Sci Ctr, Albuquerque, NM 87106 USA.
NIDA, Clin Trials Network, NIH, 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0562
BP 141A
EP 141A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700563
ER
PT J
AU Hingson, RW
Zha, W
White, A
AF Hingson, R. W.
Zha, W.
White, A.
TI MAGNITUDE OF AND TRENDS IN ALCOHOL-RELATED MORTALITY AND MORBIDITY AMONG
US COLLEGE STUDENTS, 1998-2010
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Hingson, R. W.; Zha, W.; White, A.] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0579
BP 145A
EP 145A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700580
ER
PT J
AU Spagnolo, PA
Schwandt, ML
Momenan, R
Ramchandani, VA
Heilig, M
George, DT
AF Spagnolo, P. A.
Schwandt, M. L.
Momenan, R.
Ramchandani, V. A.
Heilig, M.
George, D. T.
TI EFFECTS OF FAAH RS324420 SNP IN CO-MORBID ALCOHOL DEPENDENCE AND
POSTTRAUMATIC STRESS DISORDER
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Spagnolo, P. A.; Schwandt, M. L.; Momenan, R.; Ramchandani, V. A.; Heilig, M.; George, D. T.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0585
BP 147A
EP 147A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700586
ER
PT J
AU Enoch, MA
Hodgkinson, C
Gorodetsky, E
Marietta, C
Roy, A
Goldman, D
AF Enoch, M. -A.
Hodgkinson, C.
Gorodetsky, E.
Marietta, C.
Roy, A.
Goldman, D.
TI VARIATION IN GENES IMPLICATED IN GABA SYNTHESIS, SYNAPTIC TRANSMISSION
AND RE-UPTAKE ARE PREDICTORS FOR ALCOHOLISM
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Enoch, M. -A.; Hodgkinson, C.; Gorodetsky, E.; Marietta, C.; Roy, A.; Goldman, D.] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0592
BP 148A
EP 148A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700593
ER
PT J
AU Lee, MR
Oot, EN
Schwandt, ML
Hodgkinson, CA
Goldman, D
Heilig, M
Ramchandani, VA
Leggio, L
AF Lee, M. R.
Oot, E. N.
Schwandt, M. L.
Hodgkinson, C. A.
Goldman, D.
Heilig, M.
Ramchandani, V. A.
Leggio, L.
TI ON THE LINK BETWEEN OXYTOCIN SIGNALING AND ALCOHOL REWARD: POSSIBLE ROLE
OF THE CD38 RS3796863 POLYMORPHISM IN ALCOHOL-INDUCED BRAIN DOPAMINE
RELEASE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Lee, M. R.; Oot, E. N.; Schwandt, M. L.; Hodgkinson, C. A.; Goldman, D.; Heilig, M.; Ramchandani, V. A.; Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIDA,NIH, Bethesda, MD 20892 USA.
RI Leggio, Lorenzo/M-2972-2016
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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0593
BP 149A
EP 149A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700594
ER
PT J
AU Gowin, JL
Vatsalya, V
Momenan, R
Schwandt, ML
Bartlett, S
Heilig, M
Ramchandani, VA
AF Gowin, J. L.
Vatsalya, V.
Momenan, R.
Schwandt, M. L.
Bartlett, S.
Heilig, M.
Ramchandani, V. A.
TI ATTENUATION OF AMYGDALA RESPONSE TO ALCOHOL CUES BY VARENICLINE IN HEAVY
DRINKERS: ASSOCIATION WITH SELF-ADMINISTRATION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Gowin, J. L.; Vatsalya, V.; Momenan, R.; Schwandt, M. L.; Bartlett, S.; Heilig, M.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0620
BP 155A
EP 155A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700621
ER
PT J
AU Zywiak, WH
Swift, RM
McGeary, JE
Leggio, L
Kenna, GA
AF Zywiak, W. H.
Swift, R. M.
McGeary, J. E.
Leggio, L.
Kenna, G. A.
TI DETECTING MEDICATION EFFECTS BY EXAMINING PRECURSORS OF RECENT HEAVY
DRINKING
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 Pacific Inst Res & Eval, Pawtucket, RI 02860 USA.
Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
Providence VA, Providence, RI 02912 USA.
NIAAA, Bethesda, MD 20892 USA.
NIDA, Bethesda, MD 20892 USA.
RI Leggio, Lorenzo/M-2972-2016
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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0638
BP 160A
EP 160A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700639
ER
PT J
AU Zhang, L
Xiong, W
Homanics, GE
Lovinger, DM
AF Zhang, Li
Xiong, Wei
Homanics, Gregg E.
Lovinger, David M.
TI INVOLVEMENT OF GLYCINE RECEPTORS IN LOW DOSE ETHANOL AND THC INDUCED
MOTOR IMPAIRMENT IN MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Zhang, Li; Xiong, Wei; Lovinger, David M.] NIAAA, NIH, Bethesda, MD USA.
[Homanics, Gregg E.] Univ Pittsburgh, Pittsburgh, PA USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0648
BP 162A
EP 162A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700649
ER
PT J
AU Jury, NJ
Holmes, A
AF Jury, N. J.
Holmes, A.
TI EFFECTS OF CHRONIC INTERMITTENT ETHANOL VAPOR EXPOSURE IN ADOLESCENT AND
FEMALE MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Jury, N. J.; Holmes, A.] NIAAA, Lab Behav & Genom Neurosci, NIH, Rockville, MD 20852 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0670
BP 168A
EP 168A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700671
ER
PT J
AU Karlsson, C
Schank, JR
Rehman, F
Barbier, E
Salomon, M
Tapocik, J
Thorsell, A
Heilig, M
AF Karlsson, C.
Schank, J. R.
Rehman, F.
Barbier, E.
Salomon, M.
Tapocik, J.
Thorsell, A.
Heilig, M.
TI PROINFLAMMATORY SIGNALING REGULATES VOLUNTARY ALCOHOL INTAKE AND
ESCALATION OF CONSUMPTION AFTER EXPOSURE TO SOCIAL DEFEAT STRESS IN MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Karlsson, C.; Schank, J. R.; Rehman, F.; Barbier, E.; Salomon, M.; Tapocik, J.; Heilig, M.] NIAAA, Lab Clin & Transl Studies, NIH, Bethesda, MD USA.
[Karlsson, C.] KI, Dept Clin Neurosci, Stockholm, Sweden.
[Thorsell, A.] LiU, Dept Clin & Exp Med, Linkoping, Sweden.
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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0669
BP 168A
EP 168A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700670
ER
PT J
AU Hisada, M
Zhang, X
Ota, Y
Gao, B
Williams, GM
Sun, Z
AF Hisada, M.
Zhang, X.
Ota, Y.
Gao, B.
Williams, G. M.
Sun, Z.
TI CHRONIC ALCOHOL CONSUMPTION INDUCED MITOCHONDRIAL DAN DAMAGES TO BONE
MARROW STEM CELLS RESULTS IN FIBROSIS OF REDUCED SIZE LIVER GRAFTS IN
RATS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
NIAAA, Lab Liver Dis, 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0680
BP 170A
EP 170A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700681
ER
PT J
AU Bertola, A
Xu, MJ
Deng, C
Gao, B
AF Bertola, A.
Xu, M. J.
Deng, C.
Gao, B.
TI HEPATOCYTE- AND MYELOID CELL-SPECIFIC DELETION OF SIRTUIN-6 PREVENTS
ALCOHOL-INDUCED HEPATOCELLULAR DAMAGE IN MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Bertola, A.; Xu, M. J.; Deng, C.; Gao, B.] NIAAA, Lab Liver Dis, NIH, 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0682
BP 171A
EP 171A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700683
ER
PT J
AU Zhai, R
Wesson, R
Wang, Y
Lin, Q
Munivenkatappa, RB
Gao, B
Sun, Z
AF Zhai, R.
Wesson, R.
Wang, Y.
Lin, Q.
Munivenkatappa, R. B.
Gao, B.
Sun, Z.
TI DELAYED LIVER REGENERATION AND INCREASED CD133 STEM CELLS AFTER 85%
PARTIAL HEPATECTOMY IN A RAT MODEL OF CHRONIC PLUS BINGE ETHANOL FEEDING
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
NIAAA, Lab Liver Dis, NIH, Bethesda, MD 21085 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0681
BP 171A
EP 171A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700682
ER
PT J
AU Mathews, S
Feng, D
Gao, B
AF Mathews, S.
Feng, D.
Gao, B.
TI INVARIANT NATURAL KILLER T CELLS CONTRIBUTE TO CHRONIC PLUS BINGE
ETHANOL-MEDIATED LIVER INJURY BY PROMOTING HEPATIC NEUTROPHIL
INFILTRATION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Mathews, S.; Feng, D.; Gao, B.] NIAAA, NIH, Rockville, MD 20852 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0686
BP 172A
EP 172A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700687
ER
PT J
AU Wang, H
Bertola, A
Xu, MJ
Feng, D
Yin, S
Wang, Y
Li, J
Gao, B
AF Wang, H.
Bertola, A.
Xu, M. J.
Feng, D.
Yin, S.
Wang, Y.
Li, J.
Gao, B.
TI LONG-TERM PLUS MULTIPLE BINGE ETHANOL FEEDING INDUCES STEATOHEPATITIS
AND FIBROSIS IN AGED MICE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Wang, H.; Li, J.] Anhui Med Univ, Inst Liver Dis, Hefei 230032, Peoples R China.
[Wang, H.; Bertola, A.; Xu, M. J.; Feng, D.; Yin, S.; Wang, Y.; Gao, B.] NIAAA, Lab Liver Dis, NIH, 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0699
BP 175A
EP 175A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700700
ER
PT J
AU Grodin, EN
Kerich, MJ
Heilig, M
Schumann, G
Momenan, R
AF Grodin, E. N.
Kerich, M. J.
Heilig, M.
Schumann, G.
Momenan, R.
TI ADOLESCENTS WITH AND WITHOUT ALCOHOL PROBLEMS: RESPONSE TO REWARD
ANTICIPATION AND FEEDBACK
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Grodin, E. N.; Kerich, M. J.; Heilig, M.; Momenan, R.] NIAAA, LCTS, NIH, Bethesda, MD USA.
[Schumann, G.] MRC Social Genet & Dev Psychiat Ctr, London, England.
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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0741
BP 186A
EP 186A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700742
ER
PT J
AU Stangl, BL
Zametkin, M
Ramchandani, VA
AF Stangl, B. L.
Zametkin, M.
Ramchandani, V. A.
TI CHARACTERIZATION OF OPERANT INTRAVENOUS ALCOHOL SELF-ADMINISTRATION IN
HUMANS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Stangl, B. L.; Zametkin, M.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, Bethesda, MD 20814 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0746
BP 187A
EP 187A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700747
ER
PT J
AU Huang, B
Grant, BF
Chou, SP
Smith, SM
Saha, TD
Ruan, WJ
Goldstein, RB
Jung, J
Zhang, H
Pickering, RP
AF Huang, B.
Grant, B. F.
Chou, S. P.
Smith, S. M.
Saha, T. D.
Ruan, W. J.
Goldstein, R. B.
Jung, J.
Zhang, H.
Pickering, R. P.
TI PROSPECTIVE ASSOCIATION BETWEEN ALCOHOL CONSUMPTION AND MAJOR
DEPRESSION: NATIONAL EPIDEMIOLOGIC SURVEY ON ALCOHOL AND RELATED
CONDITIONS, 2001-2005
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Huang, B.; Grant, B. F.; Chou, S. P.; Smith, S. M.; Saha, T. D.; Ruan, W. J.; Goldstein, R. B.; Jung, J.; Zhang, H.; Pickering, R. P.] NIAAA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0785
BP 197A
EP 197A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523700786
ER
PT J
AU Hagman, BT
Schonfeld, L
AF Hagman, B. T.
Schonfeld, L.
TI COLLEGE STUDENTS WHO ENDORSE A SUB-THRESHOLD NUMBER OF DSM-5 ALCOHOL USE
DISORDER CRITERIA: THE NEW DIAGNOSTIC ORPHAN
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Hagman, B. T.; Schonfeld, L.] NIAAA, Div Treatment & Recovery Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0810
BP 203A
EP 203A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701010
ER
PT J
AU Suchankova, P
Yan, J
Schwandt, ML
Stangl, BL
Jerlhag, E
Engel, JA
Hodgkinson, CA
Goldman, D
Heilig, M
Ramchandani, VA
Leggio, L
AF Suchankova, P.
Yan, J.
Schwandt, M. L.
Stangl, B. L.
Jerlhag, E.
Engel, J. A.
Hodgkinson, C. A.
Goldman, D.
Heilig, M.
Ramchandani, V. A.
Leggio, L.
TI GENETIC VARIATION AT THE GLUCAGON-LIKE PEPTIDE-1 RECEPTOR GENE LOCUS IS
ASSOCIATED WITH ALCOHOL USE DISORDER
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Suchankova, P.; Yan, J.; Schwandt, M. L.; Stangl, B. L.; Jerlhag, E.; Engel, J. A.; Hodgkinson, C. A.; Goldman, D.; Heilig, M.; Ramchandani, V. A.; Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIDA,NIH, Bethesda, MD 20892 USA.
RI Leggio, Lorenzo/M-2972-2016
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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0879
BP 220A
EP 220A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701079
ER
PT J
AU Suchankova, P
Oot, EN
Dias, AA
Yan, J
Schwandt, ML
Stangl, BL
Jerlhag, E
Engel, JA
Hodgkinson, CA
Goldman, D
Ye, T
Kleinman, J
Heilig, M
Ramchandani, VA
Leggio, L
AF Suchankova, P.
Oot, E. N.
Dias, A. A.
Yan, J.
Schwandt, M. L.
Stangl, B. L.
Jerlhag, E.
Engel, J. A.
Hodgkinson, C. A.
Goldman, D.
Ye, T.
Kleinman, J.
Heilig, M.
Ramchandani, V. A.
Leggio, L.
TI GENETIC VARIATIONS IN THE GHRELIN SYSTEM ARE ASSOCIATED WITH ALCOHOL
DEPENDENCE AND ALCOHOL DRINKING BEHAVIORS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Suchankova, P.; Oot, E. N.; Dias, A. A.; Yan, J.; Schwandt, M. L.; Stangl, B. L.; Jerlhag, E.; Engel, J. A.; Hodgkinson, C. A.; Goldman, D.; Ye, T.; Kleinman, J.; Heilig, M.; Ramchandani, V. A.; Leggio, L.] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIDA,NIH, Bethesda, MD 20892 USA.
RI Leggio, Lorenzo/M-2972-2016
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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0878
BP 220A
EP 220A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701078
ER
PT J
AU Zhu, X
Mathur, K
Cortes, CR
Momenan, R
AF Zhu, X.
Mathur, K.
Cortes, C. R.
Momenan, R.
TI CHANGES IN BRAIN NETWORKS IN ALCOHOLICS: A RESTING-STATE FMRI STUDY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Zhu, X.; Mathur, K.; Cortes, C. R.; Momenan, R.] NIAAA, Sect Brain Electrophysiol & Imaging, Lab Clin & Translat Studies, 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0935
BP 234A
EP 234A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701135
ER
PT J
AU Collins, MA
Tajuddin, N
Moon, KH
Nixon, K
Neafsey, EJ
Kim, HY
AF Collins, M. A.
Tajuddin, N.
Moon, K. -H.
Nixon, K.
Neafsey, E. J.
Kim, H. -Y.
TI PARP-1 AND OXIDATIVE STRESS GOVERN BINGE ETHANOL-DEPENDENT
NEUROINFLAMMATION AND NEURODEGENERATION IN ADULT RAT BRAIN
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Collins, M. A.; Tajuddin, N.; Moon, K. -H.; Neafsey, E. J.] Loyola Univ, Sch Med, Dept Mol Pharmacol, Maywood, IL 60153 USA.
[Nixon, K.] Univ Kentucky, Dept Pharmaceut Sci, Lexington, KY 40536 USA.
[Kim, H. -Y.] NIAAA, Lab Mol Signaling, NIH, 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 0980
BP 245A
EP 245A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701180
ER
PT J
AU Vatsalya, V
Stangl, B
Schmidt, V
Ramchandani, VA
AF Vatsalya, V.
Stangl, B.
Schmidt, V.
Ramchandani, V. A.
TI CHARACTERIZATION OF HANGOVER SYMPTOMS FOLLOWING ACUTE INTRAVENOUS
ALCOHOL ADMINISTRATION: PREDICTORS AND CLINICAL CONSEQUENCES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Vatsalya, V.; Stangl, B.; Schmidt, V.; Ramchandani, V. A.] NIAAA, Sect Human Psychopharmacol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 1086
BP 272A
EP 272A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701285
ER
PT J
AU McGinnis, K
Tate, J
Bryant, K
Fiellin, D
Justice, A
AF McGinnis, K.
Tate, J.
Bryant, K.
Fiellin, D.
Justice, A.
TI SENSITIVITY TO ALCOHOL INTOXICATION EFFECTS BY HIV STATUS AND TREATMENT
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
CT VA Healthcare Syst, Vet Aging Cohort Study, West Haven, CT USA.
Yale Univ, New Haven, CT USA.
NIAAA, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 1131
BP 283A
EP 283A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701330
ER
PT J
AU Aziz, A
Brothers, S
Cameron, M
Heilig, M
Mittapalli, G
Roberts, E
Wahlestedt, C
Thorsell, A
AF Aziz, A.
Brothers, S.
Cameron, M.
Heilig, M.
Mittapalli, G.
Roberts, E.
Wahlestedt, C.
Thorsell, A.
TI A NOVEL, BRAIN PENETRANT NPY-Y2R ANTAGONIST IN ANIMAL MODELS OF
ALCOHOL-INTAKE AND ANXIETY
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Aziz, A.; Thorsell, A.] Linkoping Univ, S-58183 Linkoping, Sweden.
[Brothers, S.; Wahlestedt, C.] Univ Miami, Miami, FL USA.
[Cameron, M.] Scripps Res Inst, Trans Res Inst, Jupiter, FL USA.
[Heilig, M.] NIAAA, NIH, Bethesda, MD USA.
[Mittapalli, G.; Roberts, E.] Scripps Res Inst, La Jolla, CA 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 016
BP 296A
EP 296A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701383
ER
PT J
AU Kenna, G
Columbo, G
Zywiak, W
Caputo, F
Swift, R
Addolorato, G
Fricchione, S
Brickley, M
Haass-Koffler, C
Leggio, L
AF Kenna, G.
Columbo, G.
Zywiak, W.
Caputo, F.
Swift, R.
Addolorato, G.
Fricchione, S.
Brickley, M.
Haass-Koffler, C.
Leggio, L.
TI METADOXINE FOR ACUTE ALCOHOL TOXICITY, ALCOHOLISM AND ALCOHOLIC LIVER
DISEASE: PRECLINICAL AND CLINICAL FINDINGS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Kenna, G.; Columbo, G.; Zywiak, W.; Caputo, F.; Swift, R.; Addolorato, G.; Fricchione, S.; Brickley, M.; Haass-Koffler, C.; Leggio, L.] Brown Univ, NIAAA, Providence, RI 02912 USA.
[Kenna, G.; Columbo, G.; Zywiak, W.; Caputo, F.; Swift, R.; Addolorato, G.; Fricchione, S.; Brickley, M.; Haass-Koffler, C.; Leggio, L.] Brown Univ, NIDA, Providence, RI 02912 USA.
[Kenna, G.; Columbo, G.; Zywiak, W.; Caputo, F.; Swift, R.; Addolorato, G.; Fricchione, S.; Brickley, M.; Haass-Koffler, C.; Leggio, L.] Univ Cagliari, Catholic Univ Rome, SS Annunziata Hosp, Cento, IT, Italy.
RI Leggio, Lorenzo/M-2972-2016
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 072
BP 310A
EP 310A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701439
ER
PT J
AU Enoch, MA
AF Enoch, M. -A.
TI GENETIC INFLUENCES ON THE LEVEL OF RESPONSE TO ALCOHOL: IMPLICATIONS FOR
NEW TREATMENT APPROACHES FOR ALCOHOL USE DISORDERS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Enoch, M. -A.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 103
BP 318A
EP 318A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701470
ER
PT J
AU Heilig, M
Thorsell, A
Rice, KC
Malanga, CJ
Robinson, JE
AF Heilig, M.
Thorsell, A.
Rice, K. C.
Malanga, C. J.
Robinson, J. E.
TI A DUAL MECHANISM FOR NEUROKININ 1 (NK1) RECEPTOR ANTAGONISM AS A
THERAPEUTIC TARGET IN ADDICTIVE DISORDERS
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Heilig, M.; Thorsell, A.; Rice, K. C.; Malanga, C. J.; Robinson, J. E.] NIAAA, Intramural Res Program, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 183
BP 338A
EP 338A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701550
ER
PT J
AU Heilig, M
Sommer, W
Thorsell, A
Malanga, CJ
Bilbao, A
Robinson, JE
AF Heilig, M.
Sommer, W.
Thorsell, A.
Malanga, C. J.
Bilbao, A.
Robinson, J. E.
TI A HUMANIZED MOUSE MODEL OF THE MU-OPIOID RECEPTOR (OPRM1) GENE A118G
POLYMORPHISM: DEMONSTRATION OF ALTERED ALCOHOL AND OPIOID RESPONSES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Heilig, M.] NIAAA, Bethesda, MD USA.
[Heilig, M.; Thorsell, A.] Linkoping Univ, Linkoping, Sweden.
[Sommer, W.; Bilbao, A.] Cent Inst Mental Hlth, Mannheim, Germany.
[Malanga, C. J.; Robinson, J. E.] Univ N Carolina, Chapel Hill, NC 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 211
BP 345A
EP 345A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701578
ER
PT J
AU Lovinger, DM
AF Lovinger, D. M.
TI ETHANOL INDUCED HABIT FORMATION IN MICE AND MONKEYS: ROLE OF STRIATAL
GABAERGIC TRANSMISSION
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Lovinger, D. M.] NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 222
BP 348A
EP 348A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701589
ER
PT J
AU Kwako, LE
Schwandt, ML
Grodin, EN
Momenan, R
Heilig, M
Hommer, DW
George, DT
Ramchandani, VA
AF Kwako, L. E.
Schwandt, M. L.
Grodin, E. N.
Momenan, R.
Heilig, M.
Hommer, D. W.
George, D. T.
Ramchandani, V. A.
TI EARLY LIFE STRESS, ALCOHOL DEPENDENCE, AND POST-TRAUMATIC STRESS
DISORDER: EVIDENCE FOR DISRUPTIONS IN PHYSIOLOGIC OUTCOMES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Kwako, L. E.; Schwandt, M. L.; Grodin, E. N.; Momenan, R.; Heilig, M.; Hommer, D. W.; George, D. T.; Ramchandani, V. A.] NIAAA, Lab Clin & Translat Studies, 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 251
BP 355A
EP 355A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701618
ER
PT J
AU Schwandt, ML
Stangl, B
Huang, MC
Kwako, L
Heilig, M
Hommer, DW
George, DT
Ramchandani, VA
AF Schwandt, M. L.
Stangl, B.
Huang, M. -C.
Kwako, L.
Heilig, M.
Hommer, D. W.
George, D. T.
Ramchandani, V. A.
TI EARLY LIFE STRESS AND TRAUMA: PREVALENCE IN ALCOHOL DEPENDENT AND
NON-DEPENDENT DRINKERS, AND ASSOCIATIONS WITH ALCOHOL-RELATED PHENOTYPES
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Schwandt, M. L.; Stangl, B.; Huang, M. -C.; Kwako, L.; Heilig, M.; Hommer, D. W.; George, D. T.; Ramchandani, V. A.] NIAAA, Lab Clin & Translat Studies, 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
MA 250
BP 355A
EP 355A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701617
ER
PT J
AU Adinoff, B
Gu, H
Merrick, C
McHugh, M
Devous, MD
Briggs, R
Sunderajan, P
Yang, Y
Stein, EA
AF Adinoff, B.
Gu, H.
Merrick, C.
McHugh, M.
Devous, M. D.
Briggs, R.
Sunderajan, P.
Yang, Y.
Stein, E. A.
TI LOCALIZED AND FUNCTIONALLY CONNECTED NEURAL PREDICTORS OF RELAPSE IN
COCAINE DEPENDENCE
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Meeting Abstract
CT 37th Annual Scientific Meeting of the Research-Society-on-Alcoholism
(RSA) / 17th Congress of the
International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
CY JUN 21-25, 2014
CL Bellevue, WA
SP Res Soc Alcoholism, Int Soc Biomed Res Alcoholism
C1 [Adinoff, B.] VA North Texas Hlth Care Syst, Dallas, TX USA.
[Adinoff, B.; Sunderajan, P.] UT Southwestern Med Ctr, Dept Psychiat, Dallas, TX USA.
[Gu, H.; McHugh, M.] NIDA, Intramural Res Program, Neuroimaging Res Branch, Baltimore, MD USA.
[Merrick, C.] UT Dallas, Dept Cognit Neurosci, Dallas, TX USA.
[Devous, M. D.; Yang, Y.; Stein, E. A.] UT Southwestern Med Ctr, Dallas, TX USA.
[Briggs, R.] UT Southwestern Med Ctr, Dept Radiol, Dallas, TX 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 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
SU 1
SI SI
BP 385A
EP 385A
PG 1
WC Substance Abuse
SC Substance Abuse
GA AJ2VX
UT WOS:000337523701644
ER
PT J
AU Li, HH
Tyburski, JB
Wang, YW
Strawn, S
Moon, BH
Kallakury, BVS
Gonzalez, FJ
Fornace, AJ
AF Li, Heng-Hong
Tyburski, John B.
Wang, Yi-Wen
Strawn, Steve
Moon, Bo-Hyun
Kallakury, Bhaskar V. S.
Gonzalez, Frank J.
Fornace, Albert J.
TI Modulation of Fatty Acid and Bile Acid Metabolism By Peroxisome
Proliferator-Activated Receptor Protects Against Alcoholic Liver Disease
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Ppara-Null Mice; Fibrogenesis; Metabolic Pathways; Transcriptomics;
Metabolomics
ID HEPATIC STELLATE CELLS; HEPATOCYTE PROLIFERATION; LIPID-METABOLISM;
BINDING PROTEIN; GROWTH-FACTOR; PPAR-ALPHA; EXPRESSION; METABOLOMICS;
OXIDATION; PATHWAYS
AB Background Chronic alcohol intake affects liver function and causes hepatic pathological changes. It has been shown that peroxisome proliferator-activated receptor (PPAR)-null mice developed more pronounced hepatic changes than wild-type (WT) mice after chronic exposure to a diet containing 4% alcohol. The remarkable similarity between the histopathology of alcoholic liver disease (ALD) in Ppara-null model and in humans, and the fact that PPAR expression and activity in human liver are less than one-tenth of those in WT mouse liver make Ppara-null a good system to investigate ALD. Methods In this study, the Ppara-null model was used to elucidate the dynamic regulation of PPAR activity during chronic alcohol intake. Hepatic transcriptomic and metabolomic analyses were used to examine alterations of gene expression and metabolites associated with pathological changes. The changes triggered by alcohol consumption on gene expression and metabolites in Ppara-null mice were compared with those in WT mice. Results The results showed that in the presence of PPAR, 3 major metabolic pathways in mitochondria, namely the fatty acid -oxidation, the tricarboxylic acid cycle, and the electron transfer chain, were induced in response to a 2-month alcohol feeding, while these responses were greatly reduced in the absence of PPAR. In line with the transcriptional modulations of these metabolic pathways, a progressive accumulation of triglycerides, a robust increase in hepatic cholic acid and its derivatives, and a strong induction of fibrogenesis genes were observed exclusively in alcohol-fed Ppara-null mice. Conclusions These observations indicate that PPAR plays a protective role to enhance mitochondrial function in response to chronic alcohol consumption by adaptive transcriptional activation and suggest that activation of this nuclear receptor may be of therapeutic value in the treatment for ALD.
C1 [Li, Heng-Hong; Tyburski, John B.; Wang, Yi-Wen; Strawn, Steve; Moon, Bo-Hyun; Fornace, Albert J.] Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA.
[Kallakury, Bhaskar V. S.] Georgetown Univ, Dept Pathol, Med Ctr, Washington, DC 20057 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Li, HH (reprint author), Georgetown Univ, Dept Biochem & Mol & Cellular Biol, Washington, DC 20057 USA.
EM hl234@georgetown.edu
FU NIEHS, NIH [U01ES016013]; NIAAA, NIH [R01AA018863]
FX This study was funded by grant U01ES016013 from NIEHS, NIH, and grant
R01AA018863 from NIAAA, NIH.
NR 40
TC 9
Z9 9
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
IS 6
BP 1520
EP 1531
DI 10.1111/acer.12424
PG 12
WC Substance Abuse
SC Substance Abuse
GA AJ2SI
UT WOS:000337511400005
PM 24773203
ER
PT J
AU Kenna, GA
Zywiak, WH
Swift, RM
McGeary, JE
Clifford, JS
Shoaff, JR
Vuittonet, C
Fricchione, S
Brickley, M
Beaucage, K
Haass-Koffler, CL
Leggio, L
AF Kenna, George A.
Zywiak, William H.
Swift, Robert M.
McGeary, John E.
Clifford, James S.
Shoaff, Jessica R.
Vuittonet, Cynthia
Fricchione, Samuel
Brickley, Michael
Beaucage, Kayla
Haass-Koffler, Carolina L.
Leggio, Lorenzo
TI Ondansetron Reduces Naturalistic Drinking in Nontreatment-Seeking
Alcohol-Dependent Individuals with the LL 5-HTTLPR Genotype: A
Laboratory Study
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE 5-HTTLPR; Alcoholism; Genotype; Ondansetron; Sertraline
ID SEROTONIN TRANSPORTER GENE; SERTRALINE TREATMENT; CONTROLLED-TRIAL;
ASSOCIATION; ABUSE; PHARMACOTHERAPY; POLYMORPHISM; VALIDATION;
INSTRUMENT; DISORDERS
AB Background One hypothesis suggests that the differential response to ondansetron- and serotonin-specific re-uptake inhibitors (SSRIs) may be due to a functional polymorphism of the 5-HTTLPR promoter region in SLC6A4, the gene that codes for the serotonin transporter (5-HTT). The LL 5-HTTLPR genotype is postulated to be specifically sensitive to the effects of ondansetron with SS/SL 5-HTTLPR genotypes sensitive to SSRIs. This study tests this hypothesis by matching nontreatment-seeking alcohol-dependent (AD) individuals with LL genotype to ondansetron and SS/SL genotypes to the SSRI sertraline, and mismatching them assessing naturalistic and bar-laboratory alcohol drinking. Methods Seventy-seven AD individuals were randomized to 1 of 2 counterbalanced arms to receive sertraline 200mg/d or ondansetron 0.5mg/d for 3weeks followed by an alcohol self-administration experiment (ASAE) and then received placebo for 3weeks followed by a second ASAE. Individuals then received the alternate drug for 3weeks followed by a third ASAE. Drinks per drinking day (DDD with drinks in standard drinking units) for 7days prior to each ASAE and milliliters consumed during each ASAE were the primary outcomes. Results Fifty-five participants completed the study. The genotypexorder interaction was significant, F(1, 47)=8.42, p=0.006, for DDD. Three analyses of covariance were conducted for DDD during the week before each ASAE. Ondansetron compared to sertraline resulted in a significant reduction in DDD during the week before the first, F(1, 47)=7.64, p=0.008, but not the third ASAE. There was no difference in milliliters consumed during each ASAE. Conclusions This study modestly supports the hypothesis that ondansetron may reduce DDD in AD individuals with the LL genotype as measured naturalistically. By contrast, there was no support that ondansetron reduces drinking during the ASAEs or that sertraline reduces alcohol use in individuals who have SS/SL genotypes. We provide limited support that ondansetron may reduce drinking in nontreatment-seeking individuals with the LL genotype.
C1 [Kenna, George A.; Zywiak, William H.; Swift, Robert M.; McGeary, John E.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
[Kenna, George A.; Zywiak, William H.; Swift, Robert M.; McGeary, John E.; Shoaff, Jessica R.; Fricchione, Samuel; Brickley, Michael; Haass-Koffler, Carolina L.; Leggio, Lorenzo] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
[Zywiak, William H.] Pacific Inst Res & Evaluat, Decis Sci Inst, Pawtucket, RI USA.
[Swift, Robert M.; McGeary, John E.; Beaucage, Kayla] Providence VA Med Ctr, Providence, RI USA.
[Clifford, James S.] Virginia Commonwealth Univ, Richmond, VA USA.
[Vuittonet, Cynthia] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Leggio, Lorenzo] Brown Univ, Dept Behav & Social Sci, Providence, RI 02912 USA.
RP Kenna, GA (reprint author), Brown Univ, Ctr Alcohol & Addict Studies, Box G-S121-5, Providence, RI 02912 USA.
EM George_Kenna@Brown.edu
RI Leggio, Lorenzo/M-2972-2016
FU National Institute on Alcohol Abuse and Alcoholism [R01-AA016079];
Medical Research Service Department of Veteran Affairs; CT Laboratories;
[1S10RR023457-01A1]
FX This work was supported by the National Institute on Alcohol Abuse and
Alcoholism grant R01-AA016079 (PI: Kenna), Shared Equipment grants
(ShEEP) from the Medical Research Service Department of Veteran Affairs,
and 1S10RR023457-01A1 (PI: McGeary). Dr. Swift has received travel and
honorarium from D&A Pharma, and Drs. Kenna and Swift have received
consultant fees from CT Laboratories. The other authors report no
financial interests or potential conflicts of interest to declare.
NR 35
TC 8
Z9 9
U1 3
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
IS 6
BP 1567
EP 1574
DI 10.1111/acer.12410
PG 8
WC Substance Abuse
SC Substance Abuse
GA AJ2SI
UT WOS:000337511400010
PM 24773166
ER
PT J
AU Lovallo, WR
Enoch, MA
Yechiam, E
Glahn, DC
Acheson, A
Sorocco, KH
Hodgkinson, CA
Kim, B
Cohoon, AJ
Vincent, AS
Goldman, D
AF Lovallo, William R.
Enoch, Mary-Anne
Yechiam, Eldad
Glahn, David C.
Acheson, Ashley
Sorocco, Kristen H.
Hodgkinson, Colin A.
Kim, Bojeong
Cohoon, Andrew J.
Vincent, Andrea S.
Goldman, David
TI Differential Impact of Serotonin Transporter Activity on Temperament and
Behavior in Persons with a Family History of Alcoholism in the Oklahoma
Family Health Patterns Project
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Serotonin Transporter; Family History of Alcoholism; Anxiety; Depression
ID RISK TASK BART; SUBSTANCE USE DISORDERS; PSYCHOPATHIC TRAITS; IMPULSIVE
BEHAVIOR; PREFRONTAL CORTEX; ALLELIC VARIATION; POLYMORPHISM; 5-HTTLPR;
GENE; MEN
AB Background Central serotonergic (5-HT) function is implicated in pathways to alcohol dependence, including dysphoria manifested by symptoms of anxiety and depression. However, little is known about genetic variation in central 5-HT function and its potential impact on temperament and behavior in persons with a family history of alcoholism (FH+). Methods We tested 314 healthy young adults (23.5years of age, 57% female; 193 FH- and 121 FH+) enrolled in the Oklahoma Family Health Patterns project, a study of alcoholism risk in relation to temperament and behavioral dyscontrol. Dysphoria was assessed using the Eysenck neuroticism and Beck depression scales, and Cloninger's Tridimensional Personality Questionnaire. Risk taking was assessed with the Iowa Gambling Task (IGT) and Balloon Analogue Response Task (BART). All subjects were genotyped for a functional polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4). Results FH+ subjects with the gain-of-function 5-HTTLPR genotype scored higher in neuroticism, harm avoidance, and symptoms of depression (p-values0.03). No effect of 5-HTTLPR genotype was seen in FH-. FH+ carriers of the gain-of-function 5-HTTLPR genotype played to minimize their frequency of losses in the IGT, whereas FH- carriers played a balanced strategy (p<0.003). No 5-HTTLPR effects were seen in the BART. Results were unaffected by sex, education, drug use, and antisocial characteristics. Conclusions The functional 5-HTTLPR polymorphism predicted significant variation in negative moods and poorer affect regulation in FH+ persons, with possible consequences for behavior, as seen in a simulated gambling task. This pattern may contribute to a drinking pattern that is compensatory for such affective tendencies.
C1 [Lovallo, William R.] Univ Oklahoma, Hlth Sci Ctr, Dept Psychiat & Behav Sci, Oklahoma City, OK 73190 USA.
[Lovallo, William R.; Sorocco, Kristen H.; Cohoon, Andrew J.] Vet Affairs Med Ctr, Behav Sci Labs, Oklahoma City, OK 73104 USA.
[Enoch, Mary-Anne; Hodgkinson, Colin A.; Kim, Bojeong; Goldman, David] NIAAA, Neurogenet Lab, Bethesda, MD USA.
[Yechiam, Eldad] Technion Israel Inst Technol, Haifa, Israel.
[Glahn, David C.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Glahn, David C.] Olin Neuropsychiat Res Ctr, Inst Living, Hartford, CT USA.
[Acheson, Ashley] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Acheson, Ashley] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA.
[Sorocco, Kristen H.] Univ Oklahoma, Hlth Sci Ctr, Donald W Reynolds Dept Geriatr Med, Oklahoma City, OK USA.
[Vincent, Andrea S.] Univ Oklahoma, Cognit Sci Res Ctr, Norman, OK 73019 USA.
RP Lovallo, WR (reprint author), Vet Affairs Med Ctr, Behav Sci Labs 151A, 921 NE 13th St, Oklahoma City, OK 73104 USA.
EM bill@mindbody1.org
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU Department of Veterans Affairs Medical Research Service [M01 RR014467];
National Council on Research Resources [R01AA019691, R01 AA012207];
National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health; Israel Science Foundation [199/12]
FX This work was supported in part by the Department of Veterans Affairs
Medical Research Service, grant M01 RR014467; National Council on
Research Resources, grants R01AA019691 and R01 AA012207; and the
Intramural Research Program of the National Institute on Alcohol Abuse
and Alcoholism, National Institutes of Health. The content is solely the
view of the authors and does not necessarily represent the official view
of the National Institutes of Health or the Department of Veterans
Affairs. The involvement of EY was made possible by grant 199/12 from
the Israel Science Foundation.
NR 53
TC 5
Z9 5
U1 3
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
IS 6
BP 1575
EP 1581
DI 10.1111/acer.12412
PG 7
WC Substance Abuse
SC Substance Abuse
GA AJ2SI
UT WOS:000337511400011
PM 24796636
ER
PT J
AU Bolnick, JM
Karana, R
Chiang, PJ
Kilburn, BA
Romero, R
Diamond, MP
Smith, SM
Armant, DR
AF Bolnick, Jay M.
Karana, Rita
Chiang, Po J.
Kilburn, Brian A.
Romero, Roberto
Diamond, Michael P.
Smith, Susan M.
Armant, D. Randall
TI Apoptosis of Alcohol-Exposed Human Placental Cytotrophoblast Cells is
Downstream of Intracellular Calcium Signaling
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Trophoblast; Alcohol; Apoptosis; Calcium; Intracellular Signaling;
Intrauterine Growth Restriction; Fetal Alcohol Spectrum Disorder
ID INTRAUTERINE GROWTH-RETARDATION; PHOSPHOLIPASE-C INHIBITOR;
PREIMPLANTATION DEVELOPMENT; BETA-CATENIN; ETHANOL; TRANSIENT; RELEASE;
DEATH; NEURONS; U73122
AB Background Apoptosis is induced by ethanol (EtOH) in human placental trophoblast cells, possibly disrupting placentation and contributing to intrauterine growth restriction in fetal alcohol spectrum disorder (FASD). EtOH induces programmed cell death in several embryonic tissues by raising intracellular Ca2+. Therefore, the role of Ca2+ signaling in EtOH-induced apoptosis was examined using human first trimester cytotrophoblast cell lines, examining the hypothesis that apoptosis is dependent on intracellular Ca2+ signaling. Methods Using HTR-8/SVneo and SW.71 cytotrophoblast cell lines, real-time intracellular Ca2+ concentration was monitored by fluo-4 epifluorescence microscopy and apoptosis was assessed by flow cytometry of cells fluorescently labeled for DNA fragmentation (TUNEL) and annexin V binding. Results Intracellular Ca2+ concentrations increased synchronously in all cells within 10seconds of exposure to 50mM EtOH, but not at lower EtOH concentrations (10 to 25mM) incapable of inducing apoptosis. Trophoblast cells treated with inhibitors of Ca2+ signaling (BAPTA-AM, U73122, xestospongin D, BAPTA, SKF-96365) produced no intracellular Ca2+ transients after exposure to 50mM EtOH and were protected from cell death induced by EtOH. Conclusions EtOH-induced apoptosis in human cytotrophoblast cells, identified by DNA fragmentation and externalized phosphatidylserine, was dependent upon Ca2+ signaling. Both intracellular Ca2+ mobilization and extracellular Ca2+ influx were required, as well as phosphatidylinositol signaling. Inhibition by SKF-96365 suggests that the capacitative Ca2+ entry mechanism that utilizes TRPC channels was activated by EtOH. Apoptosis occurs downstream of Ca2+ signaling in trophoblasts and may contribute to placental insufficiency and poor fetal growth associated with FASD.
C1 [Bolnick, Jay M.; Karana, Rita; Chiang, Po J.; Kilburn, Brian A.; Romero, Roberto; Armant, D. Randall] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Diamond, Michael P.] Georgia Regents Univ, Dept Obstet & Gynecol, Augusta, GA USA.
[Smith, Susan M.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA.
[Armant, D. Randall] Wayne State Univ, Dept Anat & Cell Biol, CS Mott Ctr Human Growth & Dev, Detroit, MI 48201 USA.
[Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD USA.
RP Armant, DR (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Mott Ctr Human Growth & Dev, 275 East Hancock St, Detroit, MI 48201 USA.
EM D.Armant@wayne.edu
OI Diamond, Michael/0000-0001-6353-4489; Armant, D.
Randall/0000-0001-5904-9325
FU NIH [R37AA11085, R21HD071408]; NICHD, NIH
FX This research was supported by NIH grant R37AA11085 to SMS, R21HD071408
to DRA, and the Intramural Research Program of the NICHD, NIH.
NR 40
TC 9
Z9 10
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUN
PY 2014
VL 38
IS 6
BP 1646
EP 1653
DI 10.1111/acer.12417
PG 8
WC Substance Abuse
SC Substance Abuse
GA AJ2SI
UT WOS:000337511400019
PM 24889927
ER
PT J
AU Samuels, J
Shugart, YY
Wang, Y
Grados, MA
Bienvenu, OJ
Pinto, A
Rauch, SL
Greenberg, BD
Knowles, JA
Fyer, AJ
Piacentini, J
Pauls, DL
Cullen, B
Rasmussen, SA
Stewart, SE
Geller, DA
Maher, BS
Goes, FS
Murphy, DL
McCracken, JT
Riddle, MA
Nestadt, G
AF Samuels, Jack
Shugart, Yin Yao
Wang, Ying
Grados, Marco A.
Bienvenu, O. Joseph
Pinto, Anthony
Rauch, Scott L.
Greenberg, Benjamin D.
Knowles, James A.
Fyer, Abby J.
Piacentini, John
Pauls, David L.
Cullen, Bernadette
Rasmussen, Steven A.
Stewart, S. Evelyn
Geller, Dan A.
Maher, Brion S.
Goes, Fernando S.
Murphy, Dennis L.
McCracken, James T.
Riddle, Mark A.
Nestadt, Gerald
TI Clinical Correlates and Genetic Linkage of Social and Communication
Difficulties in Families with Obsessive-Compulsive Disorder: Results
From the OCD Collaborative Genetics Study
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE obsessive-compulsive disorder; OCD; pragmatics; genetic linkage
ID BROAD AUTISM PHENOTYPE; PSYCHIATRIC-DISORDERS; ASPERGER-SYNDROME;
CHILDREN; PARENTS; INDIVIDUALS; PERSONALITY; BEHAVIORS; TRAITS; SCAN
AB Some individuals with obsessive-compulsive disorder (OCD) have autistic-like traits, including deficits in social and communication behaviors (pragmatics). The objective of this study was to determine if pragmatic impairment aggregates in OCD families and discriminates a clinically and genetically distinct subtype of OCD. We conducted clinical examinations on, and collected DNA samples from, 706 individuals with OCD in 221 multiply affected OCD families. Using the Pragmatic Rating Scale (PRS), we compared the prevalence of pragmatic impairment in OCD-affected relatives of probands with and without pragmatic impairment. We also compared clinical features of OCD-affected individuals in families having at least one, versus no, individual with pragmatic impairment, and assessed for linkage to OCD in the two groups of families. The odds of pragmatic impairment were substantially greater in OCD-affected relatives of probands with pragmatic impairment. Individuals in high-PRS families had greater odds of separation anxiety disorder and social phobia, and a greater number of schizotypal personality traits. In high-PRS families, there was suggestive linkage to OCD on chromosome 12 at marker D12S1064 and on chromosome X at marker DXS7132 whereas, in low-PRS families, there was suggestive linkage to chromosome 3 at marker D3S2398. Pragmatic impairment aggregates in OCD families. Separation anxiety disorder, social phobia, and schizotypal personality traits are part of a clinical spectrum associated with pragmatic impairment in these families. Specific regions of chromosomes 12 and X are linked to OCD in high-PRS families. Thus, pragmatic impairment may distinguish a clinically and genetically homogeneous subtype of OCD. (C) 2014 Wiley Periodicals, Inc.
C1 [Samuels, Jack; Wang, Ying; Grados, Marco A.; Bienvenu, O. Joseph; Cullen, Bernadette; Goes, Fernando S.; Riddle, Mark A.; Nestadt, Gerald] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Shugart, Yin Yao] NIMH, Genom Res Branch, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA.
[Pinto, Anthony; Fyer, Abby J.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Pinto, Anthony; Fyer, Abby J.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Rauch, Scott L.; Geller, Dan A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Greenberg, Benjamin D.; Rasmussen, Steven A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA.
[Knowles, James A.] Univ So Calif, Dept Psychiat, Sch Med, Los Angeles, CA USA.
[Piacentini, John; McCracken, James T.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Pauls, David L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Pauls, David L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Pauls, David L.] Harvard Univ, Sch Med, Boston, MA USA.
[Stewart, S. Evelyn] Univ British Columbia, Fac Med, Dept Psychiat, Vancouver Fac Med, Vancouver, BC, Canada.
[Maher, Brion S.] Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA.
RP Samuels, J (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 550 N Broadway 901, Baltimore, MD 21205 USA.
EM jacks@jhmi.edu
RI Pinto, Anthony/D-2718-2017;
OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905;
Stewart, S. Evelyn/0000-0002-0994-6383
FU National Institutes of Health [R01-MH-50214, R01MH071507, K23-MH-64543,
NIH/NCRR/OPD-GCRC RR00052]; James E. Marshall OCD Foundation
FX Grant sponsor: National Institutes of Health; Grant numbers:
R01-MH-50214, R01MH071507, K23-MH-64543, NIH/NCRR/OPD-GCRC RR00052;
Grant sponsor: James E. Marshall OCD Foundation.
NR 57
TC 3
Z9 3
U1 3
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4841
EI 1552-485X
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUN
PY 2014
VL 165
IS 4
BP 326
EP 336
DI 10.1002/ajmg.b.32235
PG 11
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA AJ4UX
UT WOS:000337674600006
PM 24798771
ER
PT J
AU Mirzaa, GM
Paciorkowski, AR
AF Mirzaa, Ghayda M.
Paciorkowski, Alex R.
TI Introduction: Brain malformations
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
LA English
DT Article
DE brain malformations; genetics; review
ID MENTAL-RETARDATION; MUTATIONS; CONFIRMATION; HETEROTOPIA; HYPOPLASIA;
PHENOTYPE; DISORDER; DISEASE; MODEL; LIS1
AB This issue of the American Journal of Medical Genetics Seminar Series Part C is dedicated to congenital brain malformations with a special focus on the molecular mechanisms underlying this fascinating, and often complex, group of developmental brain disorders. As with most genetic disorders, the past few years have witnessed a dramatic leap in our understanding of the molecular basis of these malformations that include both constitutional and post-zygotic (or mosaic) genetic aberrations. This is best exemplified by the recent identification of mutations within components of the PI3K-AKT-mTOR pathway in hemimegalencephaly and megalencephaly syndromes, and the rapidly increased identification of mutations within the tubulin family in a broad range of cortical and non-cortical brain malformations. These discoveries, particularly of the emerging tubulinopathies spectrum, have not only expanded our knowledge of these disorders but challenge our existing, and perhaps overly simplistic, classification of these malformations based on the primary neuronal stage at which the abnormality occurs. It is our hope that this series will facilitate a deeper understanding of these malformations beyond their clinical and neuroimaging features and syndromic associations to their molecular and pathway underpinnings. We believe this knowledge will most certainly be instrumental as we move into the era of delineating genotype-phenotype correlations and, ultimately, pathway-based therapies. (c) 2014 Wiley Periodicals, Inc.
C1 [Mirzaa, Ghayda M.] Seattle Childrens Hosp, Dept Human Genet, Seattle, WA USA.
[Mirzaa, Ghayda M.] Seattle Childrens Res Inst, Seattle, WA USA.
[Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
[Paciorkowski, Alex R.] NINDS, Ctr Neural Dev & Dis, Supported Res Program Genet Causes Dev Brain Diso, Bethesda, MD 20892 USA.
RP Paciorkowski, AR (reprint author), Univ Rochester, Med Ctr Neurol, 601 Elmwood Ave, Rochester, NY 14642 USA.
EM alex_paciorkowski@urmc.rochester.edu
FU NINDS
FX Dr. Paciorkowski is a clinical neurogeneticist at the University of
Rochester Medical Center, and principal investigator at the Center for
Neural Development & Disease with a NINDS-supported research program in
the genetic causes of developmental brain disorders.
NR 24
TC 5
Z9 5
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4868
EI 1552-4876
J9 AM J MED GENET C
JI Am. J. Med. Genet. C
PD JUN
PY 2014
VL 166
IS 2
SI SI
BP 117
EP 123
DI 10.1002/ajmg.c.31404
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA AJ4HF
UT WOS:000337633800001
PM 24853778
ER
PT J
AU Seltzer, LE
Paciorkowski, AR
AF Seltzer, Laurie E.
Paciorkowski, Alex R.
TI Genetic disorders associated with postnatal microcephaly
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
LA English
DT Review
DE postnatal microcephaly; Angelman syndrome; MECP2-related disorder;
Christianson syndrome; CASK; CDKL5; FOXG1; Pitt-Hopkins syndrome;
Rubinstein-Taybi syndrome; Warburg MICRO syndrome; Cockayne syndrome;
Cerebral-oculo-facial skeletal syndrome
ID RUBINSTEIN-TAYBI-SYNDROME; PITT-HOPKINS-SYNDROME; WARBURG MICRO
SYNDROME; SEVERE MENTAL-RETARDATION; OF-FUNCTION MUTATIONS;
FACIO-SKELETAL SYNDROME; PRADER-WILLI SYNDROMES; SYNDROME GROUP-B;
RETT-SYNDROME; COCKAYNE-SYNDROME
AB Several genetic disorders are characterized by normal head size at birth, followed by deceleration in head growth resulting in postnatal microcephaly. Among these are classic disorders such as Angelman syndrome and MECP2-related disorder (formerly Rett syndrome), as well as more recently described clinical entities associated with mutations in CASK, CDKL5, CREBBP, and EP300 (Rubinstein-Taybi syndrome), FOXG1, SLC9A6 (Christianson syndrome), and TCF4 (Pitt-Hopkins syndrome). These disorders can be identified clinically by phenotyping across multiple neurodevelopmental and neurobehavioral realms, and enough data are available to recognize these postnatal microcephaly disorders as separate diagnostic entities in their own right. A second diagnostic grouping, comprised of Warburg MICRO syndrome, Cockayne syndrome, and Cerebral-oculo-facial skeletal syndrome, share similar features of somatic growth failure, ophthalmologic, and dysmorphologic features. Many postnatal microcephaly syndromes are caused by mutations in genes important in the regulation of gene expression in the developing forebrain and hindbrain, although important synaptic structural genes also play a role. This is an emerging group of disorders with a fascinating combination of brain malformations, specific epilepsies, movement disorders, and other complex neurobehavioral abnormalities. (c) 2014 Wiley Periodicals, Inc.
C1 [Seltzer, Laurie E.; Paciorkowski, Alex R.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
[Paciorkowski, Alex R.] NINDS, Ctr Neural Dev & Dis, Supported Res Program Genet Causes Dev Brain Diso, Bethesda, MD 20892 USA.
RP Paciorkowski, AR (reprint author), Univ Rochester, Med Ctr, 601 Elmwood Ave, Rochester, NY 14642 USA.
EM alex_paciorkowski@urmc.rochester.edu
FU National Institute of Neurological Disorders and Stroke (NINDS) of the
National Institutes of Health (NIH) [K12NS066098, K08NS078054]
FX We wish to thank our research families for their participation and
support of our work. Dr. Seltzer is supported by the National Institute
of Neurological Disorders and Stroke (NINDS) of the National Institutes
of Health (NIH) award number K12NS066098 and Dr. Paciorkowski by award
number K08NS078054. The authors have no financial disclosures.
NR 131
TC 10
Z9 10
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4868
EI 1552-4876
J9 AM J MED GENET C
JI Am. J. Med. Genet. C
PD JUN
PY 2014
VL 166
IS 2
SI SI
BP 140
EP 155
DI 10.1002/ajmg.c.31400
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA AJ4HF
UT WOS:000337633800003
PM 24839169
ER
PT J
AU Mirzaa, GM
Poduri, A
AF Mirzaa, Ghayda M.
Poduri, Annapurna
TI Megalencephaly and hemimegalencephaly: Breakthroughs in molecular
etiology
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
LA English
DT Article
DE megalencephaly; hemimegalencephaly; polymicrogyria; somatic mosaicism;
overgrowth; PI3K-AKT-mTOR pathway; Ras; MAPK pathway
ID AUTISM SPECTRUM DISORDERS; MARMORATA TELANGIECTATICA CONGENITA;
RILEY-RUVALCABA-SYNDROME; ACTIVATING MUTATIONS; CUTIS MARMORATA; PTEN
GENE; CYCLIN D2; BEHAVIORAL ABNORMALITIES; CAPILLARY MALFORMATION;
GERMLINE MUTATIONS
AB Megalencephaly (MEG) is a developmental disorder characterized by brain overgrowth that occurs due to either increased number or size of neurons and glial cells. The former may be due to either increased neuronal proliferation or decreased apoptosis. The degree of brain overgrowth may be extensive, ranging from generalized MEG affecting the entire cortex-as with mutations in PTEN (phosphatase and tensin homolog on chromosome ten)-to unilateral hemispheric malformations-as in classic hemimegalencephaly (HME). On the other hand, some lesions are more focal or segmental. These developmental brain abnormalities may occur in isolation in some individuals, whereas others occur in the context of a syndrome involving dysmorphic features, skin findings, or other organ system involvement. Brain overgrowth disorders are often associated with malformations of cortical development, resulting in increased risk of epilepsy, intellectual disability, and autistic features, and some are associated with hydrocephalus. The past few years have witnessed a dramatic leap in our understanding of the molecular basis of brain overgrowth, particularly the identification of mosaic (or post-zygotic) mutations in core components of key cellular pathways such as the phosphatidylinositol 3-kinase (PI3K)-vakt murine thymoma viral oncogene homolog (AKT)-mTOR pathway. These molecular insights have broadened our view of brain overgrowth disorders that now appear to span a wide spectrum of overlapping phenotypic, neuroimaging, and neuropathologic features and molecular pathogenesis. These molecular advances also bring to light the possibility of pathway-based therapies for these often medically devastating developmental disorders. (c) 2014 Wiley Periodicals, Inc.
C1 [Mirzaa, Ghayda M.] Seattle Childrens Hosp, Dept Human Genet, Seattle, WA USA.
[Mirzaa, Ghayda M.] Seattle Childrens Res Inst, Seattle, WA USA.
[Poduri, Annapurna] Boston Childrens Hosp, Div Epilepsy & Clin Electrophysiol, Dept Neurol, Hosp Epilepsy Genet Program, Boston, MA USA.
[Poduri, Annapurna] NINDS, Supported Ctr, Bethesda, MD 20892 USA.
RP Mirzaa, GM (reprint author), Univ Washington, Div Med Genet, Dept Pediat, Ctr Integrat Brain Res,Seattle Childrens Res Inst, 1900 9th Ave, Seattle, WA 98101 USA.
EM gmirzaa@uw.edu; annapurna.poduri@childrens.harvard.edu
FU NINDS [NS069784]
FX The authors thank our patients and their families for their valuable and
ongoing contributions and support of our research. A. P. was supported
by the NINDS (NS069784).
NR 67
TC 22
Z9 24
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4868
EI 1552-4876
J9 AM J MED GENET C
JI Am. J. Med. Genet. C
PD JUN
PY 2014
VL 166
IS 2
SI SI
BP 156
EP 172
DI 10.1002/ajmg.c.31401
PG 17
WC Genetics & Heredity
SC Genetics & Heredity
GA AJ4HF
UT WOS:000337633800004
PM 24888963
ER
PT J
AU Engels, EA
Castenson, D
Pfeiffer, RM
Kahn, A
Pawlish, K
Goodman, MT
Nalesnik, MA
Israni, AK
Snyder, J
Kasiske, B
AF Engels, E. A.
Castenson, D.
Pfeiffer, R. M.
Kahn, A.
Pawlish, K.
Goodman, M. T.
Nalesnik, M. A.
Israni, A. K.
Snyder, J.
Kasiske, B.
TI Cancers Among US Organ Donors: A Comparison of Transplant and Cancer
Registry Diagnoses
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Cancer; donor evaluation; organ donation
ID MALIGNANT-MELANOMA; DISEASE TRANSMISSION; MULTIORGAN DONOR;
RENAL-ALLOGRAFT; PROSTATE-CANCER; TUMOR; ADENOCARCINOMA; RECIPIENTS;
CARCINOMA; RISK
AB Transmission of cancer is a life-threatening complication of transplantation. Monitoring transplantation practice requires complete recording of donor cancers. The US Scientific Registry of Transplant Recipients (SRTR) captures cancers in deceased donors (beginning in 1994) and living donors (2004). We linked the SRTR (52 599 donors, 110 762 transplants) with state cancer registries. Cancer registries identified cancers in 519 donors: 373 deceased donors (0.9%) and 146 living donors (1.2%). Among deceased donors, 50.7% of cancers were brain tumors. Among living donors, 54.0% were diagnosed after donation; most were cancers common in the general population (e. g. breast, prostate). There were 1063 deceased donors with cancer diagnosed in the SRTR or cancer registry, and the SRTR lacked a cancer diagnosis for 107 (10.1%) of these. There were 103 living donors with cancer before or at donation, diagnosed in the SRTR or cancer registry, and the SRTR did not have a cancer diagnosis for 43 (41.7%) of these. The SRTR does not record cancers after donation in living donors and so missed 81 cancers documented in cancer registries. In conclusion, donor cancers are uncommon, but lack of documentation of some cases highlights a need for improved ascertainment and reporting by organ procurement organizations and transplant programs.
C1 [Engels, E. A.; Pfeiffer, R. M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Castenson, D.] Informat Management Serv Inc, Rockville, MD USA.
[Kahn, A.] New York State Canc Registry, Albany, NY USA.
[Pawlish, K.] New Jersey Dept Hlth, Trenton, NJ USA.
[Goodman, M. T.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Nalesnik, M. A.] Univ Pittsburgh, Med Ctr, Div Transplantat & Hepat Pathol, Pittsburgh, PA USA.
[Israni, A. K.; Snyder, J.; Kasiske, B.] Minneapolis Med Res Fdn Inc, Sci Registry Transplant Recipients, Minneapolis, MN USA.
[Israni, A. K.; Kasiske, B.] Univ Minnesota, Dept Med, Hennepin Cty Med Ctr, Minneapolis, MN 55455 USA.
RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM engelse@exchange.nih.gov
FU Intramural Research Program of the National Cancer Institute; Arbor
Research Collaborative for Health in Ann Arbor, MI [HHSH234200537009C];
National Program of Cancer Registries of the Centers for Disease Control
and Prevention: California [1U58 DP000807-01]; National Program of
Cancer Registries of the Centers for Disease Control and Prevention:
Colorado [U58 DP000848-04]; National Program of Cancer Registries of the
Centers for Disease Control and Prevention: Georgia [5U58DP003875-01];
National Program of Cancer Registries of the Centers for Disease Control
and Prevention: Illinois [5658DP000805-04]; National Program of Cancer
Registries of the Centers for Disease Control and Prevention: Michigan
[5U58DP000812-03]; National Program of Cancer Registries of the Centers
for Disease Control and Prevention: New Jersey [1US58/DP0039311-01];
National Program of Cancer Registries of the Centers for Disease Control
and Prevention: New York [U58DP0038789]; National Program of Cancer
Registries of the Centers for Disease Control and Prevention: North
Carolina [U58DP000832]; National Program of Cancer Registries of the
Centers for Disease Control and Prevention: Texas [5U58DP000824-04];
SEER Program of the National Cancer Institute: California
[HHSN261201000036C, HHSN261201000035C, HHSN261201000034C]; SEER Program
of the National Cancer Institute: Connecticut [HHSN261201000024C]; SEER
Program of the National Cancer Institute: Hawaii [HHSN261201000037C,
N01-PC-35137, N01-PC-35139]; SEER Program of the National Cancer
Institute: Iowa [HSN261201000032C, N01-PC-35143]; SEER Program of the
National Cancer Institute: New Jersey [HHSN261201000027C,
N01-PC-2010-0027]; SEER Program of the National Cancer Institute:
Seattle-Puget Sound [N01-PC-35142]; SEER Program of the National Cancer
Institute: Utah [HHSN261201000026C]; state of California; state of
Colorado; state of Connecticut; state of Illinois; state of Iowa; state
of New Jersey; state of New York (Cancer Surveillance Improvement
Initiative) [14-2491]; state of Texas; state of Washington; Fred
Hutchinson Cancer Research Center in Seattle, WA
FX The authors thank Monica Lin and James Bowman (Health Resources and
Services Administration) and Maureen McBride and Sarah Taranto (United
Network for Organ Sharing) for their thoughtful advice on this study and
comments on the manuscript. We also acknowledge the support and
assistance provided by individuals at the Health Resources and Services
Administration, the SRTR (Paul Newkirk), and the following cancer
registries: the states of California (Tina Clarke), Colorado (Jack
Finch), Connecticut (Lou Gonsalves), Georgia(Rana Bayakly), Hawaii
(Brenda Hernandez), Iowa(Charles Lynch), Illinois (Lori Koch), Michigan
(Glenn Copeland), New Jersey (Xiaoling Niu), New York, North Carolina
(Chandrika Rao), Texas (Beatriz Gutierrez) and Utah (Janna Harrell) and
the Seattle-Puget Sound area of Washington (Margaret Madeleine). We also
thank analysts at Information Management Services for programming
support (Matthew Chaloux, Michael Curry, Ruth Parsons). The views
expressed in this paper are those of the authors and should not be
interpreted to reflect the views or policies of the National Cancer
Institute, Health Resources and Services Administration, SRTR, cancer
registries or their contractors. This research was supported in part by
the Intramural Research Program of the National Cancer Institute. During
the initial period when registry linkages were performed, the SRTR was
managed by Arbor Research Collaborative for Health in Ann Arbor, MI
(contract HHSH234200537009C); beginning in September 2010, the SRTR was
managed by Minneapolis Medical Research Foundation in Minneapolis, MN
(HHSH250201000018C). The following cancer registries were supported by
the National Program of Cancer Registries of the Centers for Disease
Control and Prevention: California (agreement 1U58 DP000807-01),
Colorado (U58 DP000848-04), Georgia (5U58DP003875-01), Illinois
(5658DP000805-04), Michigan (5U58DP000812-03), New Jersey
(1US58/DP0039311-01), New York (U58DP0038789), North Carolina
(U58DP000832) and Texas (5U58DP000824-04). The following cancer
registries were supported by the SEER Program of the National Cancer
Institute: California (contracts HHSN261201000036C, HHSN261201000035C
and HHSN261201000034C), Connecticut (HHSN261201000024C), Hawaii
(HHSN261201000037C, N01-PC-35137 and N01-PC-35139), Iowa
(HSN261201000032C and N01-PC-35143), New Jersey (HHSN261201000027C and
N01-PC-2010-0027), Seattle-Puget Sound (N01-PC-35142) and Utah
(HHSN261201000026C). Additional support was provided by the states of
California, Colorado, Connecticut, Illinois, Iowa, New Jersey, New York
(Cancer Surveillance Improvement Initiative 14-2491), Texas and
Washington, as well as the Fred Hutchinson Cancer Research Center in
Seattle, WA.
NR 32
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUN
PY 2014
VL 14
IS 6
BP 1376
EP 1382
DI 10.1111/ajt.12683
PG 7
WC Surgery; Transplantation
SC Surgery; Transplantation
GA AJ2UP
UT WOS:000337519500019
PM 24712385
ER
PT J
AU Canna, SW
Costa-Reis, P
Bernal, WE
Chu, NS
Sullivan, KE
Paessler, ME
Behrens, EM
AF Canna, Scott W.
Costa-Reis, Patricia
Bernal, William E.
Chu, Niansheng
Sullivan, Kathleen E.
Paessler, Michele E.
Behrens, Edward M.
TI Alternative Activation of Laser-Captured Murine Hemophagocytes
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID MACROPHAGE ACTIVATION; HETEROGENEITY; RESPONSES; ANEMIA
AB Objective. Hemophagocytes (HPCs) are activated macrophages that have engulfed other hematopoietic cells. Although HPCs are rarely identified in normal spleen tissue and bone marrow, an excess of these macrophages characterizes many cytokine storm syndromes, particularly macrophage activation syndrome and hemophagocytic lymphohistiocytosis. This study was undertaken to assess the functions of HPCs and their significance in acute inflammatory conditions.
Methods. HPCs were generated in wild-type mice using repeated stimulation with Toll-like receptor 9 (TLR-9) and interleukin-10 receptor blockade. RNA was extracted from HPCs that had been isolated by laser-captured microdissection. Transcriptional profiles of the HPCs were then compared to those of resting splenic macrophages. In addition, bone marrow samples were obtained from a diverse cohort of patients in whom excess hemophagocytosis was identified by clinical bone marrow biopsy or aspiration. The bone marrow samples were analyzed by immunohistochemistry for markers of classic (CD64) or alternative (CD163 and CD206) macrophage activation.
Results. Differential gene expression and gene set enrichment analyses of murine HPCs identified upregulation of genes and gene sets associated with alternative activation of HPCs. Immunohistochemical analyses of HPCs in human bone marrow samples showed universal staining of HPCs for CD163, but rarely for CD206 or CD64.
Conclusion. Laser-captured murine TLR-9induced HPCs had a transcriptional profile similar to that of alternatively activated macrophages. In addition, HPC expression of CD163 was confirmed in a uniquely diverse cohort of patients with hemophagocytic syndromes. Collectively, these data support the hypothesis that HPCs have both immunoregulatory and clean-up functions.
C1 [Canna, Scott W.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Costa-Reis, Patricia; Chu, Niansheng; Sullivan, Kathleen E.; Paessler, Michele E.; Behrens, Edward M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Bernal, William E.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Sullivan, Kathleen E.; Paessler, Michele E.; Behrens, Edward M.] Univ Penn, Philadelphia, PA 19104 USA.
RP Canna, SW (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, 10 Ctr Dr,Bldg 10,Room 13C103, Bethesda, MD 20892 USA.
EM scott.canna@nih.gov
OI Canna, Scott/0000-0003-3837-5337
FU Histiocytosis Association; NIH [F32-AI-98337, K08-AI-79396];
Rheumatology Research Foundation Scientist Development award; Fundacao
Calouste Gulbenkian; Fundacao para a Ciencia e a Tecnologia; Howard
Hughes Medical Institute Early Career Physician Scientist award;
Arthritis Foundation Innovative Research grant
FX Supported by a grant from the Histiocytosis Association. Dr. Canna's
work was supported by NIH grant F32-AI-98337 and a Rheumatology Research
Foundation Scientist Development award. Dr. Costa-Reis' work was
supported by the Fundacao Calouste Gulbenkian and the Fundacao para a
Ciencia e a Tecnologia. Dr. Behrens' work was supported by NIH grant
K08-AI-79396, a Howard Hughes Medical Institute Early Career Physician
Scientist award, and an Arthritis Foundation Innovative Research grant.
NR 15
TC 7
Z9 7
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD JUN
PY 2014
VL 66
IS 6
BP 1666
EP 1671
DI 10.1002/art.38379
PG 6
WC Rheumatology
SC Rheumatology
GA AJ0SL
UT WOS:000337366200029
PM 24470386
ER
PT J
AU Kim, EJ
Abramowitz, LK
Bond, MR
Love, DC
Kang, DW
Leucke, HF
Kang, DW
Ahn, JS
Hanover, JA
AF Kim, Eun J.
Abramowitz, Lara K.
Bond, Michelle R.
Love, Dona C.
Kang, Dong W.
Leucke, Hans F.
Kang, Dae W.
Ahn, Jong-Seog
Hanover, John A.
TI Versatile O-GlcNAc Transferase Assay for High-Throughput Identification
of Enzyme Variants, Substrates, and Inhibitors
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID INSULIN-RESISTANCE; TETRATRICOPEPTIDE REPEATS; CYTOSOLIC PROTEINS;
GLYCOSYLATION; MECHANISM; PHOSPHORYLATION; GLCNACYLATION; ISOFORMS;
NUCLEAR; DOMAIN
AB The dynamic glycosylation of serine/threonine residues on nucleocytoplasmic proteins with a single N-acetylglucosamine (O-GlcNAcylation) is critical for many important cellular processes. Cellular O-GlcNAc levels are highly regulated by two enzymes: O-GlcNAc transferase (OGT) is responsible for GlcNAc addition and O-GlcNAcase (OGA) is responsible for removal of the sugar. The lack of a rapid and simple method for monitoring OCT activity has impeded the efficient discovery of potent OCT inhibitors. In this study we describe a novel, single-well OGT enzyme assay that utilizes 6 X His-tagged substrates, a chemoselective chemical reaction, and unpurified OCT. The high-throughput Ni-NTA Plate OCT Assay will facilitate discovery of potent OGT-specific inhibitors on versatile substrates and the characterization of new enzyme variants.
C1 [Kim, Eun J.] Daegu Univ, Dept Sci Educ Chem Major, Gyeongbuk 712714, South Korea.
[Abramowitz, Lara K.; Bond, Michelle R.; Love, Dona C.; Hanover, John A.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
[Leucke, Hans F.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Kang, Dong W.] Catholic Univ Daegu, Dept Pharmaceut Sci & Technol, Gyeongbuk 712702, South Korea.
[Kang, Dae W.] Changwon Natl Univ, Coll Nat Sci, Dept Biochem & Hlth Sci, Chang Won 641773, South Korea.
[Ahn, Jong-Seog] Korea Res Inst Biosci & Biotechnol KRIBB, Biotherapeut Res Inst, Chem Biol Res Ctr, Cheongwon 363883, South Korea.
RP Kim, EJ (reprint author), Daegu Univ, Dept Sci Educ Chem Major, Gyeongbuk 712714, South Korea.
EM eunkim@daegu.ac.kr; jah@helix.nih.gov
FU NIDDK intramural funds (NIH); National Research Foundation of Korea
[2011-0027257]
FX This work was supported by NIDDK intramural funds (NIH) and the National
Research Foundation of Korea (2011-0027257).
NR 37
TC 4
Z9 4
U1 2
U2 15
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 JUN
PY 2014
VL 25
IS 6
BP 1025
EP 1030
DI 10.1021/bc5001774
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA AJ5KB
UT WOS:000337720000001
PM 24866374
ER
PT J
AU Lee, JA
Biel, NM
Kozikowski, RT
Siemann, DW
Sorg, BS
AF Lee, Jennifer A.
Biel, Nikolett M.
Kozikowski, Raymond T.
Siemann, Dietmar W.
Sorg, Brian S.
TI In vivo spectral and fluorescence microscopy comparison of microvascular
function after treatment with OXi4503, Sunitinib and their combination
in Caki-2 tumors
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID VASCULAR-DISRUPTING AGENTS; DORSAL WINDOW CHAMBER; COMBRETASTATIN A-4
PHOSPHATE; HUMAN-MELANOMA XENOGRAFTS; BLOOD-FLOW; ANTIANGIOGENIC
THERAPY; INTRAVITAL MICROSCOPY; HEMOGLOBIN SATURATION; COMBINING
AVASTIN; TARGETING AGENTS
AB Vascular targeting agents on their own have been shown to be insufficient for complete treatment of solid tumors, emphasizing the importance of studying the vascular effects of these drugs for their use with conventional therapies in the clinic. First-pass fluorescence imaging combined with hyperspectral imaging of hemoglobin saturation of microvessels in the murine dorsal window chamber model provides an easily implementable, low cost method to analyze tumor vascular response to these agents in real-time. In this study, the authors utilized these methods to spectroscopically demonstrate distinct vessel structure, blood flow and oxygenation changes in human Caki-2 renal cell carcinoma following treatment with OXi4503 alone, Sunitinib alone and both drugs together. We showed that treatment with OXi4503 plus Sunitinib destroyed existing tumor microvessels, inhibited blood vessel recovery and impaired Caki-2 tumor growth significantly more than either treatment alone. (C) 2014 Optical Society of America
C1 [Lee, Jennifer A.] Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32610 USA.
[Biel, Nikolett M.] Univ Florida, Coll Med, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA.
[Kozikowski, Raymond T.] Ventana Med Syst Inc, Tucson, AZ 85755 USA.
[Siemann, Dietmar W.] Univ Florida, Coll Med, Dept Radiat Oncol, Gainesville, FL 32610 USA.
[Sorg, Brian S.] NCI, Canc Diag Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA.
RP Lee, JA (reprint author), Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Biomed Sci Bldg, Gainesville, FL 32610 USA.
EM jalee2@ufl.edu
FU Bankhead-Coley Cancer Research Program of the Florida Department of
Health; National Cancer Institute (US Public Health Service) [R01
CA084408]
FX This work was supported in part by a grant from the Bankhead-Coley
Cancer Research Program of the Florida Department of Health (Brian S.
Sorg) and in part by a grant from the National Cancer Institute (US
Public Health Service grant R01 CA084408; (Dietmar W. Siemann)).
NR 58
TC 6
Z9 6
U1 2
U2 11
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD JUN 1
PY 2014
VL 5
IS 6
BP 1965
EP 1979
DI 10.1364/BOE.5.001965
PG 15
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA AJ2QM
UT WOS:000337503900021
PM 24940553
ER
PT J
AU Chen, BJ
Qin, J
AF Chen, Baojiang
Qin, Jing
TI Test the reliability of doubly robust estimation with missing response
data
SO BIOMETRICS
LA English
DT Article
DE Auxiliary; Doubly robust; Estimating equation; Goodness of fit; Missing
data
ID SURROGATE END-POINTS; CLINICAL-TRIALS; INCOMPLETE DATA; REGRESSION;
MODELS; RESIDUALS; CHECKING
AB In statistical inference, one has to make sure that the underlying regression model is correctly specified otherwise the resulting estimation may be biased. Model checking is an important method to detect any departure of the regression model from the true one. Missing data are a ubiquitous problem in social and medical studies. If the underlying regression model is correctly specified, recent researches show great popularity of the doubly robust (DR) estimates method for handling missing data because of its robustness to the misspecification of either the missing data model or the conditional mean model, that is, the model for the conditional expectation of true regression model conditioning on the observed quantities. However, little work has been devoted to the goodness of fit test for DR estimates method. In this article, we propose a testing method to assess the reliability of the estimator derived from the DR estimating equation with possibly missing response and always observed auxiliary variables. Numerical studies demonstrate that the proposed test can control type I errors well. Furthermore the proposed method can detect departures from model assumptions in the marginal mean model of interest powerfully. A real dementia data set is used to illustrate the method for the diagnosis of model misspecification in the problem of missing response with an always observed auxiliary variable for cross-sectional data.
C1 [Chen, Baojiang] Univ Nebraska, Med Ctr, Coll Publ Hlth, Dept Biostat, Omaha, NE 68198 USA.
[Qin, Jing] NIAID, NIH, Bethesda, MD 20892 USA.
RP Chen, BJ (reprint author), Univ Nebraska, Med Ctr, Coll Publ Hlth, Dept Biostat, 600 S 42nd St, Omaha, NE 68198 USA.
EM baojiang.chen@unmc.edu
FU National Institute on Aging [U01AG016976]
FX The authors thank the Editor, associated editor, and two referees for
their constructive comments and suggestions, which have improved this
article greatly. Dr Chen was supported in part by National Institute on
Aging grant U01AG016976.
NR 31
TC 0
Z9 0
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
EI 1541-0420
J9 BIOMETRICS
JI Biometrics
PD JUN
PY 2014
VL 70
IS 2
BP 289
EP 298
DI 10.1111/biom.12150
PG 10
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA AJ4DK
UT WOS:000337621000005
PM 24571677
ER
PT J
AU Falzarano, D
Feldmann, H
AF Falzarano, Darryl
Feldmann, Heinz
TI Possible leap ahead in filovirus therapeutics
SO CELL RESEARCH
LA English
DT Editorial Material
ID EBOLA-VIRUS INFECTION; POSTEXPOSURE PROTECTION; NONHUMAN-PRIMATES;
HEMORRHAGIC-FEVER
C1 [Falzarano, Darryl; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
RP Feldmann, H (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
EM feldmannh@niaid.nih.gov
NR 12
TC 10
Z9 14
U1 0
U2 17
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
EI 1748-7838
J9 CELL RES
JI Cell Res.
PD JUN
PY 2014
VL 24
IS 6
BP 647
EP 648
DI 10.1038/cr.2014.49
PG 2
WC Cell Biology
SC Cell Biology
GA AJ4XL
UT WOS:000337682900004
PM 24732011
ER
PT J
AU Xu, YS
Xu, LL
Zhao, M
Xu, CG
Fan, YL
Pierce, SK
Liu, WL
AF Xu, Yinsheng
Xu, Liling
Zhao, Meng
Xu, ChenGuang
Fan, Yilin
Pierce, Susan K.
Liu, Wanli
TI No receptor stands alone: IgG B-cell receptor intrinsic and extrinsic
mechanisms contribute to antibody memory
SO CELL RESEARCH
LA English
DT Review
DE B-cell receptor; antibody response; B-cell memory; plasma cell; germinal
center
ID RESONANCE ENERGY-TRANSFER; SINGLE-MOLECULE TRACKING; GERMINAL CENTER
REACTION; ANTIGEN RECEPTOR; LYMPH-NODE; TRANSCRIPTION FACTOR;
PLASMA-MEMBRANE; SIGNAL-TRANSDUCTION; SUBCAPSULAR SINUS; SECRETING CELLS
AB Acquired immunological memory is a striking phenomenon. A lethal epidemic sweeps through a naive population, many die but those who survive are never "attacked twice - never at least fatally", as the historian Thucydides observed in 430 BCE. Antibody memory is critical for protection against many human infectious diseases and is the basis for nearly all current human vaccines. Antibody memory is encoded, in part, in isotype-switched immunoglobulin (Ig)G-expressing memory B cells that are generated in the primary response to antigen and give rise to rapid, high-affinity and high-titered antibody responses upon challenge with the same antigen. How IgG-B-cell receptors (BCRs) and antigen-induced IgG-BCR signaling contribute to memory antibody responses are not fully understood. In this review, we summarize exciting new advances that are revealing the cellular and molecular mechanisms at play in antibody memory and discuss how studies using different experimental approaches will help elucidate the complex phenomenon of B-cell memory.
C1 [Xu, Yinsheng; Xu, Liling; Zhao, Meng; Xu, ChenGuang; Fan, Yilin; Liu, Wanli] Tsinghua Univ, Sch Life Sci, MOE Key Lab Prot Sci, Beijing 100084, Peoples R China.
[Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Xu, Yinsheng; Liu, Wanli] Tsinghua Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Beijing 100084, Peoples R China.
RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM spierce@nih.gov; liuwanli@biomed.tsinghua.edu.cn
FU Ministry of Science and Technology of China [2014CB542500-03,
2014AA020527]; National Natural Science Foundation of China
[81361120384, 31270913]; Beijing Natural Science Foundation [5132016];
PhD Programs Foundation of Ministry of Education of China
[20130002110059, 201200021200076]; New Century Excellent Talents program
in University of Ministry of Education of China [NCET-12-0299];
One-Thousand-Youth-Talents program of Chinese Central Government
[2069999-3]; Tsinghua University Initiative Scientifc Research Program
[2013Z1089279]
FX This work was supported by the Ministry of Science and Technology of
China (2014CB542500-03, 2014AA020527), the National Natural Science
Foundation of China (81361120384, 31270913), the Beijing Natural Science
Foundation (5132016), the PhD Programs Foundation of Ministry of
Education of China (20130002110059, 201200021200076), the New Century
Excellent Talents program in University of Ministry of Education of
China (NCET-12-0299), the One-Thousand-Youth-Talents program (2069999-3)
of Chinese Central Government, and Tsinghua University Initiative
Scientifc Research Program (2013Z1089279). Wanli Liu expresses his
heartfelt thanks to Dr Susan K Pierce for her inculcated mentoring in
his postdoctoral trainings.
NR 81
TC 9
Z9 9
U1 4
U2 11
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
EI 1748-7838
J9 CELL RES
JI Cell Res.
PD JUN
PY 2014
VL 24
IS 6
BP 651
EP 664
DI 10.1038/cr.2014.65
PG 14
WC Cell Biology
SC Cell Biology
GA AJ4XL
UT WOS:000337682900006
PM 24839903
ER
PT J
AU Andrade, BB
Kumar, NP
Sridhar, R
Banurekha, VV
Jawahar, MS
Nutman, TB
Sher, A
Babu, S
AF Andrade, Bruno B.
Kumar, Nathella Pavan
Sridhar, Rathinam
Banurekha, Vaithilingam V.
Jawahar, Mohideen S.
Nutman, Thomas B.
Sher, Alan
Babu, Subash
TI Heightened Plasma Levels of Heme Oxygenase-1 and Tissue Inhibitor of
Metalloproteinase-4 as Well as Elevated Peripheral Neutrophil Counts Are
Associated With TB-Diabetes Comorbidity
SO CHEST
LA English
DT Article
ID MYCOBACTERIUM-TUBERCULOSIS; MATRIX METALLOPROTEINASES; PULMONARY
TUBERCULOSIS; OXIDATIVE STRESS; MICE; BIOMARKERS; CELLS;
MATRIX-METALLOPROTEINASE-9; INFLAMMATION; EXPRESSION
AB Background: The increased prevalence of type 2 diabetes mellitus (T2DM) in countries endemic for TB poses a serious complication in the clinical management of this major infectious disease. Understanding the impact of T2DM on TB and the determinants of comorbidity is critical in responding to this growing public health problem with better therapeutic approaches. Here, we performed an exploratory study assessing a series of biologic parameters that could serve as markers of pathogenesis in TB with T2DM.
Methods: Cross-sectional analyses of levels of heme oxygenase-1 (HO-1), acute phase proteins, tissue metalloproteinases, and tissue inhibitors of metalloproteinase (TIMPs) as well as cytokines and chemokines were performed in plasma samples from individuals with active pulmonary TB or with coincident TB and T2DM from South India.
Results: Compared with patients with TB without diabetes, those with coincident T2DM exhibited increased Mycobacterium tuberculosis bacillary loads in sputum. Plasma levels of HO-1 but not of other acute phase proteins were higher in patients with TB and T2DM than in patients without diabetes, independent of bacillary sputum loads. HO-1 concentrations also positively correlated with random plasma glucose, circulating glycosylated hemoglobin, and low-density lipoprotein levels. Moreover, patients with coincident TB and T2DM exhibited increased plasma levels of TIMP-4 and elevated peripheral blood neutrophil counts, which, when considered together with HO-1, resulted in increased power to discriminate individuals with active TB with and without T2DM.
Conclusions: Elevated plasma levels of HO-1 and TIMP-4 and peripheral blood neutrophil counts are potential single and combined markers of pathogenesis in TB and T2DM.
C1 [Andrade, Bruno B.; Sher, Alan] NIH, Immunobiol Sect, Bethesda, MD 20892 USA.
[Nutman, Thomas B.; Babu, Subash] NIH, Helminth Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Kumar, Nathella Pavan; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.] Int Ctr Excellence Res, Madras, Tamil Nadu, India.
[Kumar, Nathella Pavan; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.] Natl Inst Res TB, Madras, Tamil Nadu, India.
[Sridhar, Rathinam] Govt Stanley Med Hosp, Madras, Tamil Nadu, India.
RP Andrade, BB (reprint author), NIH, Parasit Dis Lab, 50 S Dr,Room 6146, Bethesda, MD 20892 USA.
EM andradebd@niaid.nih.gov
RI Andrade, Bruno/J-9111-2012
OI Andrade, Bruno/0000-0001-6833-3811
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.
NR 31
TC 6
Z9 6
U1 0
U2 3
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUN
PY 2014
VL 145
IS 6
BP 1244
EP 1254
DI 10.1378/chest.13-1799
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA AJ0OV
UT WOS:000337355600017
PM 24458266
ER
PT J
AU Demehri, S
Yockey, LJ
Visness, CM
Jaffee, KF
Turkoz, A
Wood, RA
O'Connor, GT
Kattan, M
Gern, JE
Gergen, PJ
Holtzman, M
Bloomberg, G
Kopan, R
AF Demehri, S.
Yockey, L. J.
Visness, C. M.
Jaffee, K. F.
Turkoz, A.
Wood, R. A.
O'Connor, G. T.
Kattan, M.
Gern, J. E.
Gergen, P. J.
Holtzman, M.
Bloomberg, G.
Kopan, R.
TI Circulating TSLP associates with decreased wheezing in non-atopic
preschool children: data from the URECA birth cohort
SO CLINICAL AND EXPERIMENTAL ALLERGY
LA English
DT Article
DE atopy; birth cohort; preschool wheeze; recurrent wheeze; TSLP; URECA
ID THYMIC STROMAL LYMPHOPOIETIN; AGGRAVATES EXPERIMENTAL ASTHMA;
ATOPIC-DERMATITIS; MOUSE SKIN; INFLAMMATION; KERATINOCYTES; EXPRESSION;
VITAMIN-D3; TRIGGER; CELLS
AB Background Mouse models of atopic march suggest that systemic, skin-derived thymic stromal lymphopoietin (TSLP) mediates progression from eczema to asthma. Objective We investigated whether circulating TSLP is associated with eczema, allergic sensitization, or recurrent wheezing in young children. Methods A prospective analysis of the relationship between plasma levels of TSLP to allergic sensitization and recurrent wheezing was conducted in the birth cohort from the Urban Environment and Childhood Asthma (URECA) study. Plasma TSLP levels were measured at 1, 2, and 3years of age and analysed for correlation with clinical parameters in each of the three years. Only those children with consecutive samples for all three years were included in this analysis. Results We detected TSLP in 33% of 236 children for whom plasma samples were available for all three years. Overall, a consistently significant association was not found between TSLP and eczema or allergic sensitization. With regard to recurrent wheezing, children with detectable TSLP at one year of age were significantly less likely to experience recurrent wheezing by 3years compared with those children without detectable TSLP, but this was only seen in children without aeroallergen sensitization at 3years (P<0.01). Conclusions and Clinical Relevance Contrary to our expectations, circulating TSLP was not significantly associated with eczema, allergen sensitization, or recurrent wheezing during the first three years of life. Early presence of circulating TSLP was significantly associated with reduced incidence of recurrent wheeze in those children not sensitized to aeroallergen. These findings suggest a possible underlying distinction between pathogenesis of developing atopic vs. non-atopic recurrent wheeze.
C1 [Demehri, S.; Yockey, L. J.; Turkoz, A.; Holtzman, M.; Bloomberg, G.; Kopan, R.] Washington Univ, Sch Med, St Louis, MO 63110 USA.
[Visness, C. M.; Jaffee, K. F.] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Wood, R. A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[O'Connor, G. T.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Kattan, M.] Columbia Univ, Sch Med, New York, NY USA.
[Gern, J. E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Gergen, P. J.] NIH, Div Allergy Immunol & Transplantat, Bethesda, MD USA.
[Kopan, R.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp, Div Dev Biol,Med Ctr, Cincinnati, OH USA.
RP Bloomberg, G (reprint author), Washington Univ, Sch Med, St Louis Childrens Hosp, Div Allergy & Pulm Med, 5 S 30,One Childrens Pl, St Louis, MO 63110 USA.
EM Bloomberg@kids.wustl.edu; Raphael.kopan@cchmc.org
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [NO1-AI-25496, NO1-AI-25482, HHSN 272200900052C,
HHSN2722010000521]; National Center for Research Resources, National
Institutes of Health [RR00052, M01RR00533, 1UL1RR025771, M01RR00071,
1UL1RR024156]; Lincoln Diagnostics; Children's Discovery Institute of
Washington University; St. Louis Children's Hospital; American Asthma
Foundation [09-0234]
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,
HHSN 272200900052C, and HHSN2722010000521. Additional support was
provided by the National Center for Research Resources, National
Institutes of Health, under Grants RR00052, M01RR00533, 1UL1RR025771,
M01RR00071, and 1UL1RR024156; and from Lincoln Diagnostics (which
provided Multi-Test (R)). Additional funding for this project was
provided by the Children's Discovery Institute of Washington University
and St. Louis Children's Hospital. RK was funded in part by the American
Asthma Foundation (grant 09-0234).
NR 25
TC 4
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0954-7894
EI 1365-2222
J9 CLIN EXP ALLERGY
JI Clin. Exp. Allergy
PD JUN
PY 2014
VL 44
IS 6
BP 851
EP 857
DI 10.1111/cea.12270
PG 7
WC Allergy; Immunology
SC Allergy; Immunology
GA AJ2XT
UT WOS:000337529100007
PM 24397611
ER
PT J
AU Lockett, S
Verma, C
Brafman, A
Gudla, P
Nandy, K
Mimaki, Y
Fuchs, PL
Jaja, J
Reilly, KM
Beutler, J
Turbyville, TJ
AF Lockett, Stephen
Verma, Chrissie
Brafman, Alla
Gudla, Prabhakar
Nandy, Kaustav
Mimaki, Yoshihiro
Fuchs, Philip L.
Jaja, Joseph
Reilly, Karlyne M.
Beutler, John
Turbyville, Thomas J.
TI Quantitative analysis of F-actin redistribution in astrocytoma cells
treated with candidate pharmaceuticals
SO CYTOMETRY PART A
LA English
DT Article
DE fibrillar actin; image analysis; pattern analysis; cytoskeleton;
anti-cancer drugs; artificial neural network; fluorescence microscopy
ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; MICROSCOPY IMAGES; NATURAL-PRODUCTS;
MYOSIN-II; ORGANIZATION; LAMELLIPODIA; CYTOSKELETON; MECHANISMS;
NETWORKS; CALCIUM
AB Actin fibers (F-actin) control the shape and internal organization of cells, and generate force. It has been long appreciated that these functions are tightly coupled, and in some cases drive cell behavior and cell fate. The distribution and dynamics of F-actin is different in cancer versus normal cells and in response to small molecules, including actin-targeting natural products and anticancer drugs. Therefore, quantifying actin structural changes from high resolution fluorescence micrographs is necessary for further understanding actin cytoskeleton dynamics and phenotypic consequences of drug interactions on cells. We applied an artificial neural network algorithm, which used image intensity and anisotropy measurements, to quantitatively classify F-actin subcellular features into actin along the edges of cells, actin at the protrusions of cells, internal fibers and punctate signals. The algorithm measured significant increase in F-actin at cell edges with concomitant decrease in internal punctate actin in astrocytoma cells lacking functional neurofibromin and p53 when treated with three structurally-distinct anticancer small molecules: OSW1, Schweinfurthin A (SA) and a synthetic marine compound 23'-dehydroxycephalostatin 1. Distinctly different changes were measured in cells treated with the actin inhibitor cytochalasin B. These measurements support published reports that SA acts on F-actin in NF1-/- neurofibromin deficient cancer cells through changes in Rho signaling. Quantitative pattern analysis of cells has wide applications for understanding mechanisms of small molecules, because many anti-cancer drugs directly or indirectly target cytoskeletal proteins. Furthermore, quantitative information about the actin cytoskeleton may make it possible to further understand cell fate decisions using mathematically testable models. Published 2014 Wiley Periodicals Inc.
C1 [Lockett, Stephen; Brafman, Alla; Gudla, Prabhakar; Nandy, Kaustav; Turbyville, Thomas J.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res FNLCR, Opt Microscopy & Anal Lab, Frederick, MD USA.
[Verma, Chrissie] VMware Inc, Cambridge, MA USA.
[Mimaki, Yoshihiro] Tokyo Univ Pharm & Life Sci, Sch Pharm, Hachioji, Tokyo 1920392, Japan.
[Fuchs, Philip L.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Jaja, Joseph] Univ Maryland, College Pk, MD 20742 USA.
[Reilly, Karlyne M.] Natl Canc Inst Frederick NCI F, Mouse Canc Genet Program, Frederick, MD USA.
[Beutler, John] NCI F, Mol Targets Lab, Frederick, MD USA.
RP Lockett, S (reprint author), Frederick Natl Lab Canc Res, Rm 104A,POB B, Frederick, MD 21702 USA.
EM locketts@mail.nih.gov
FU National Cancer Institute; National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the National
Institutes of Health, National Cancer Institute; Center for Cancer
Research
FX Grant sponsors: National Cancer Institute and National Institutes of
Health, Grant number: HHSN261200800001E; Grant sponsors: Intramural
Research Program of the National Institutes of Health, National Cancer
Institute and Center for Cancer Research.
NR 42
TC 2
Z9 2
U1 3
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4922
EI 1552-4930
J9 CYTOM PART A
JI Cytom. Part A
PD JUN
PY 2014
VL 85A
IS 6
BP 512
EP 521
DI 10.1002/cyto.a.22442
PG 10
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AJ2WS
UT WOS:000337525900008
PM 24515854
ER
PT J
AU Margolis, KL
O'Connor, PJ
Morgan, TM
Buse, JB
Cohen, RM
Cushman, WC
Cutler, JA
Evans, GW
Gerstein, HC
Grimm, RH
Lipkin, EW
Narayan, KMV
Riddle, MC
Sood, A
Goff, DC
AF Margolis, Karen L.
O'Connor, Patrick J.
Morgan, Timothy M.
Buse, John B.
Cohen, Robert M.
Cushman, William C.
Cutler, Jeffrey A.
Evans, Gregory W.
Gerstein, Hertzel C.
Grimm, Richard H., Jr.
Lipkin, Edward W.
Narayan, K. M. Venkat
Riddle, Matthew C., Jr.
Sood, Ajay
Goff, David C., Jr.
TI Outcomes of Combined Cardiovascular Risk Factor Management Strategies in
Type 2 Diabetes: The ACCORD Randomized Trial
SO DIABETES CARE
LA English
DT Article
ID INTENSIVE BLOOD-PRESSURE; MULTIFACTORIAL INTERVENTION; MICROVASCULAR
OUTCOMES; MELLITUS; THERAPY; RATIONALE; MORTALITY; TARGETS; DISEASE;
DESIGN
AB OBJECTIVE
To compare effects of combinations of standard and intensive treatment of glycemia and either blood pressure (BP) or lipids in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.
RESEARCH DESIGN AND METHODS
ACCORD enrolled 10,251 type 2 diabetes patients aged 40-79 years at high risk for cardiovascular disease (CVD) events. Participants were randomly assigned to hemoglobin A(1c), goals of <6.0% (<42 mmol/mol; intensive glycemia) or 7.0-7.9% (53-63 mmol/mol; standard glycemia) and then randomized a second time to either 1) systolic BP goals of <120 mmHg (intensive BP) or <140 mmHg (standard BP) or 2) simvastatin plus fenofibrate (intensive lipid) or simvastatin plus placebo (standard lipid). Proportional hazards models were used to assess combinations of treatment assignments on the composite primary (deaths due to CVD, nonfatal myocardial infarction [MI], and nonfatal stroke) and secondary outcomes.
RESULTS
In the BP trial, risk of the primary outcome was lower in the groups intensively treated for glycemia (hazard ratio [HR] 0.67; 95% CI 0.50-0.91), BP (HR 0.74; 95% CI 0.55-1.00), or both (HR 0.71; 95% CI 0.52-0.96) compared with combined standard BP and glycemia treatment. For secondary outcomes, MI was significantly reduced by intensive glycemia treatment and stroke by intensive BP treatment; most other HRs were neutral or favored intensive treatment groups. In the lipid trial, the general pattern of results showed no evidence of benefit of intensive regimens (whether single or combined) compared with combined standard lipid and glycemia treatment. The mortality HR was 1.33 (95% CI 1.02-1.74) in the standard lipid/intensive glycemia group compared with the standard lipid/standard glycemia group.
CONCLUSIONS
In the ACCORD BP trial, compared with combined standard treatment, intensive BP or intensive glycemia treatment alone improved major CVD outcomes, without additional benefit from combining the two. In the ACCORD lipid trial, neither intensive lipid nor glycemia treatment produced an overall benefit, but intensive glycemia treatment increased mortality.
C1 [Margolis, Karen L.; O'Connor, Patrick J.] HealthPartners Inst Educ & Res, Minneapolis, MN 55440 USA.
[Morgan, Timothy M.; Evans, Gregory W.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Buse, John B.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Cohen, Robert M.] Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA.
[Cohen, Robert M.] Univ Cincinnati, Cincinnati, OH USA.
[Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA.
[Cutler, Jeffrey A.] NHLBI, Bethesda, MD 20892 USA.
[Gerstein, Hertzel C.] McMaster Univ, Hamilton, ON, Canada.
[Grimm, Richard H., Jr.] Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA.
[Lipkin, Edward W.] Univ Washington, Seattle, WA 98195 USA.
[Narayan, K. M. Venkat] Emory Univ, Atlanta, GA 30322 USA.
[Riddle, Matthew C., Jr.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Sood, Ajay] Louis Stokes Vet Affairs Med Ctr, Cleveland, OH USA.
[Sood, Ajay] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Goff, David C., Jr.] Colorado Sch Publ Hlth, Aurora, CO USA.
RP Margolis, KL (reprint author), HealthPartners Inst Educ & Res, Minneapolis, MN 55440 USA.
EM karen.l.margolis@healthpartners.com
RI Narayan, K.M. Venkat /J-9819-2012
OI Narayan, K.M. Venkat /0000-0001-8621-5405
FU NHLBI [N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181,
N01-HC-95182, N01HC-95183, N01-HC-95184, IAA-Y1-HC-9035,
IAA-Y1-HC-1010]; National Institute of Diabetes and Digestive and Kidney
Diseases; National Institute on Aging; National Eye Institute; NHLBI;
NIH
FX This work was supported by the NHLBI (contracts N01-HC-95178,
N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01HC-95183,
N01-HC-95184, IAA-Y1-HC-9035, and IAA-Y1-HC-1010) and partially
supported by the National Institute of Diabetes and Digestive and Kidney
Diseases, the National Institute on Aging, and the National Eye
Institute and by General Clinical Research Centers at many sites.
Substudies within the ACCORD trial on cost-effectiveness and
health-related quality of life were supported by the Centers for Disease
Control and Prevention. All authors were supported by NIH grant funds
for the ACCORD trial during the study. K.L.M. has NIH studies with funds
going to her institution and assumes all responsibility for the work as
a whole. W.C.C. reports grants from NHLBI and NIH during the conduct of
the study. The following companies provided study medications,
equipment, or supplies: Abbott Laboratories, Amylin Pharmaceuticals,
AstraZeneca, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline, King
Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare,
Sanofi, and Schering-Plough.
NR 23
TC 38
Z9 41
U1 2
U2 9
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUN
PY 2014
VL 37
IS 6
BP 1721
EP 1728
DI 10.2337/dc13-2334
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AJ5RX
UT WOS:000337746100050
PM 24595629
ER
PT J
AU Mejia, E
Buraka, M
Alonso, A
Larraga, V
Kunkel, TA
Bebenek, K
Garcia-Diaz, M
AF Mejia, Edison
Buraka, Matthew
Alonso, Ana
Larraga, Vicente
Kunkel, Thomas A.
Bebenek, Katarzyna
Garcia-Diaz, Miguel
TI Structures of the Leishmania infantum polymerase beta
SO DNA REPAIR
LA English
DT Article
DE DNA repair; Leishmaniasis; DNA polymerase; Family X
ID HUMAN DNA-POLYMERASE; BASE-EXCISION-REPAIR; MURINE TERMINAL
DEOXYNUCLEOTIDYLTRANSFERASE; 5'-DEOXYRIBOSE-5-PHOSPHATE LYASE ACTIVITY;
CRYSTAL-STRUCTURES; CATALYTIC CYCLE; STRAND MISALIGNMENT; POL LAMBDA;
FIDELITY; MECHANISM
AB Protozoans of the genus Leishmania, the pathogenic agent causing leishmaniasis, encode the family X DNA polymerase Li Pol beta. Here, we report the first crystal structures of Li Pol beta. Our pre- and post-catalytic structures show that the polymerase adopts the common family X DNA polymerase fold. However, in contrast to other family X DNA polymerases, the dNTP-induced conformational changes in Li Pol beta are much more subtle. Moreover, pre- and post-catalytic structures reveal that Li Pol beta interacts with the template strand through a nonconserved, variable region known as loop3. Li Pol beta Delta Ioop3 mutants display a higher catalytic rate, catalytic efficiency and overall error rates with respect to WT Li Pol beta. These results further demonstrate the subtle structural variability that exists within this family of enzymes and provides insight into how this variability underlies the substantial functional differences among their members. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Mejia, Edison; Buraka, Matthew; Garcia-Diaz, Miguel] SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA.
[Alonso, Ana; Larraga, Vicente] CSIC, Ctr Invest Biol, E-28040 Madrid, Spain.
[Kunkel, Thomas A.; Bebenek, Katarzyna] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Bebenek, K (reprint author), SUNY Stony Brook, BST 7-120, Stony Brook, NY 11733 USA.
EM bebenek@niehs.nih.gov; miguel.garcia-diaz@stonybrook.edu
FU Offices of Biological and Environmental Research and of Basic Energy
Sciences of the US Department of Energy; National Center for Research
Resources of the National Institutes of Health; Fundacion Ramon Areces;
MICINN [AGL2010-21806-C02-01)]; [R01-GM100021]; [ROD ES015421]
FX We thank the NSLS Protein Crystallography group. NSLS beamlines x25 and
x29 are mainly supported by the Offices of Biological and Environmental
Research and of Basic Energy Sciences of the US Department of Energy,
and the National Center for Research Resources of the National
Institutes of Health. This work was supported by R01-GM100021 and ROD
ES015421 to MGD. AA and VL thank the Fundacion Ramon Areces and MICINN
(AGL2010-21806-C02-01) for funding.
NR 48
TC 1
Z9 1
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD JUN
PY 2014
VL 18
BP 1
EP 9
DI 10.1016/j.dnarep.2014.03.001
PG 9
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA AJ4PP
UT WOS:000337658600001
PM 24666693
ER
PT J
AU Makarova, AV
McElhinny, SAN
Watts, BE
Kunkel, TA
Burgers, PM
AF Makarova, Alena V.
McElhinny, Stephanie A. Nick
Watts, Brian E.
Kunkel, Thomas A.
Burgers, Peter M.
TI Ribonucleotide incorporation by yeast DNA polymerase zeta
SO DNA REPAIR
LA English
DT Article
DE Ribonucleotides; Mutagenesis; DNA polymerase; Translesion synthesis
ID DOUBLE-STRAND BREAK; SACCHAROMYCES-CEREVISIAE; REV1 PROTEIN;
MUTAGENESIS; COMPLEX; REPAIR; DELTA; PCNA
AB During replication in yeast, the three B family DNA replicases frequently incorporate ribonucleotides (rNMPs) into DNA, and their presence in the nuclear genome can affect genome stability. This prompted us to examine ribonucleotide incorporation by the fourth B family member, Pol zeta, the enzyme responsible for the majority of damage-induced mutagenesis in eukaryotes. We first show that Pol inserts rNMPs into DNA and can extend primer termini containing 3'-ribonucleotides. We then measure rNMP incorporation by Pol in the presence of its cofactors, RPA, RFC and PCNA and at normal cellular dNTP and rNTP concentrations that exist under unstressed conditions. Under these conditions, Pol zeta stably incorporates one rNMP for every 200-300 dNMPs incorporated, a frequency that is slightly higher than for the high fidelity replicative DNA polymerases. Under damage-induced conditions wherein cellular dNTP concentrations are elevated 5-fold, Pol zeta only incorporates one rNMP per 1300 dNMPs. Functional interaction of Pol zeta with the mutasome assembly factor Rev1 gives comparable rNMP incorporation frequencies. These results suggest that ribonucleotide incorporation into DNA during Pol zeta-mediated mutagenesis in vivo may be rare. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Makarova, Alena V.; Burgers, Peter M.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
[McElhinny, Stephanie A. Nick; Watts, Brian E.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[McElhinny, Stephanie A. Nick; Watts, Brian E.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Burgers, PM (reprint author), Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
EM burgers@biochem.wustl.edu
RI Makarova, Alena/I-1338-2014
FU National Institutes of Health [GM032431]; Division of Intramural
Research of the National Institutes of Health, National Institute on
Environmental Health Sciences [Z01 ES065089]
FX The authors thank Carrie Stith for help with protein purification. This
work was supported in part by Grant GM032431 from the National
Institutes of Health to P.M.B. and by Project Z01 ES065089 from the
Division of Intramural Research of the National Institutes of Health,
National Institute on Environmental Health Sciences, to T.A.K.
NR 25
TC 5
Z9 5
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD JUN
PY 2014
VL 18
BP 63
EP 67
DI 10.1016/j.dnarep.2014.02.017
PG 5
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA AJ4PP
UT WOS:000337658600007
PM 24674899
ER
PT J
AU Ira, G
Nussenzweig, A
AF Ira, Grzegorz
Nussenzweig, Andre
TI A new Riff: Rif1 eats its cake and has it too
SO EMBO REPORTS
LA English
DT Editorial Material
ID END RESECTION; DNA-REPAIR; REPLICATION
AB Rif1 protein is present in eukaryotic cells from yeast to human. In yeast, Rif1 is important for telomere homeostasis. Despite conservation in its domain organization, human Rif1 is not part of the telomere complex but was recently reported to work at DNA double-strand breaks (DSBs) with 53BP1 to inhibit 50 strand degradation (resection) and stimulate a subset of nonhomologous end-joining (NHEJ) reactions. Martina et al [1] report in this issue of EMBO reports that yeast Rif1 is also recruited to DSBs, but in contrast to its human counterpart, it promotes resection. The authors propose that Rif1 stimulates resection by limiting the access of Rad9, an ortholog of 53BP1, to DSBs.
C1 [Ira, Grzegorz] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Nussenzweig, Andre] NCI, Lab Genome Integr, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ira, G (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
EM gira@bcm.edu
FU NIGMS NIH HHS [R01 GM080600]
NR 10
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1469-221X
EI 1469-3178
J9 EMBO REP
JI EMBO Rep.
PD JUN
PY 2014
VL 15
IS 6
BP 622
EP 624
DI 10.1002/embr.201438825
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AJ0QL
UT WOS:000337360300003
PM 24769453
ER
PT J
AU Hayes, DJ
Jupp, B
Sawiak, SJ
Merlo, E
Caprioli, D
Dalley, JW
AF Hayes, Dave J.
Jupp, Bianca
Sawiak, Steve J.
Merlo, Emiliano
Caprioli, Daniele
Dalley, Jeffrey W.
TI Brain -aminobutyric acid: a neglected role in impulsivity
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Review
DE dopamine; GABA; noradrenaline; nucleus accumbens; prefrontal cortex
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY
DISORDER; REACTION-TIME-TASK; SUBSTANCE-USE DISORDERS; VENTRAL TEGMENTAL
AREA; NUCLEUS-ACCUMBENS CORE; GABA(A) RECEPTOR ACTIVATION; INHIBITORY
RESPONSE CONTROL; MEDIAL PREFRONTAL CORTEX; DECISION-MAKING
AB The investigation of impulsivity as a core marker of several major neuropsychiatric disorders has been greatly influenced by the therapeutic efficacy of drugs that block the reuptake of dopamine and noradrenaline in the brain. As a result, research into the neural mechanisms of impulsivity has focused on the catecholamine systems as the loci responsible for the expression of impulsive behaviour and the primary mechanism of action of clinically effective drugs for attention-deficit hyperactivity disorder (ADHD). However, abnormalities in the catecholamine systems alone are unlikely to account for the full diversity and complexity of impulsivity subtypes, nor can they fully explain co-morbid brain disorders such as drug addiction. Here we review the lesser-studied role of -aminobutyric acid (GABA) in impulsivity, a major target of the dopaminergic and noradrenergic systems in the prefrontal cortex and striatum, and consider how abnormalities in this inhibitory neurotransmitter might contribute to several forms of impulsive behaviour in humans and experimental animals. Our analysis reveals several promising leads for future research that may help inform the development of new therapies for disorders of impulse control.
C1 [Hayes, Dave J.] Toronto Western Hosp, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada.
[Hayes, Dave J.] Univ Toronto, Div Neurosurg, Toronto, ON, Canada.
[Hayes, Dave J.] Univ Ottawa, Mental Hlth Res Inst, Ottawa, ON, Canada.
[Hayes, Dave J.; Jupp, Bianca; Sawiak, Steve J.; Merlo, Emiliano; Dalley, Jeffrey W.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England.
[Sawiak, Steve J.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Wolfson Brain Imaging Ctr, Cambridge CB2 3EB, England.
[Caprioli, Daniele] NIDA, Baltimore, MD USA.
[Dalley, Jeffrey W.] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England.
[Hayes, Dave J.; Jupp, Bianca; Merlo, Emiliano; Dalley, Jeffrey W.] Univ Cambridge, Dept Psychol, Cambridge CB2 3EB, England.
RP Dalley, JW (reprint author), Univ Cambridge, Dept Psychol, Cambridge CB2 3EB, England.
EM jwd20@cam.ac.uk
RI Sawiak, Stephen/I-8944-2012; hayes, dave/C-7809-2013
OI Sawiak, Stephen/0000-0003-4210-9816; hayes, dave/0000-0001-9474-8770
FU Medical Research Council (MRC) [G0701500, G0802729, MRC G1000183, WT
093875/Z/10/Z]; Wellcome Trust (WT) [MRC G1000183, WT 093875/Z/10/Z];
MRC Imperial College-Cambridge University-Manchester University (ICCAM)
strategic cluster [G1000018]; Royal Society; National Health and MRC of
Australia; AXA Research Fund; Canadian Institutes of Health Research
(CIHR)
FX The work was supported by Medical Research Council (MRC) grants to
J.W.D. (G0701500; G0802729) and by a joint core award from the MRC and
Wellcome Trust (WT) in support of the Behavioural and Clinical
Neuroscience Institute at Cambridge University (MRC G1000183; WT
093875/Z/10/Z). We also acknowledge funding support within the MRC
Imperial College-Cambridge University-Manchester University (ICCAM)
strategic cluster (G1000018). E. M. was supported by a Royal Society
Newton International Fellowship. B.J. was supported by Fellowships from
the National Health and MRC of Australia and the AXA Research Fund.
D.J.H. was funded through a Canadian Institutes of Health Research
(CIHR) Postdoctoral Fellowship.
NR 163
TC 16
Z9 17
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0953-816X
EI 1460-9568
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD JUN
PY 2014
VL 39
IS 11
SI SI
BP 1921
EP 1932
DI 10.1111/ejn.12485
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA AJ3BT
UT WOS:000337540800019
PM 24460847
ER
PT J
AU Thakur, SA
Nyska, A
White, KL
Smith, MJ
Auttachoat, W
Germolec, DR
AF Thakur, Sheetal A.
Nyska, Abraham
White, Kimber L., Jr.
Smith, Matthew J.
Auttachoat, Wimolnut
Germolec, Dori R.
TI Immunomodulatory activity of orphan drug Elmiron (R) in female B6C3F1/N
mice
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE Immunotoxicity; Orphan drug; Sodium pentosan polysulfate; Interstitial
cystitis
ID POLYSULFATE-INDUCED THROMBOCYTOPENIA; PHASE-I TRIAL; PENTOSAN
POLYSULFATE; INTERSTITIAL CYSTITIS; DENDRITIC CELLS; DRINKING-WATER;
ANTIBODY; BLADDER; GAVAGE; ELISA
AB Interstitial cystitis (IC) is a chronic disorder characterized by bladder discomfort and urinary urgency in the absence of identifiable infection. Despite the expanding use in IC treatment and other chronic conditions, the effects of Elmiron treatment on immune system remain unknown. Therefore, female B6C3F1/N mice were orally administered Elmiron (R) daily for 28-days at doses of 63, 125, 250, 500 or 1000 mg/kg to evaluate its immunomodulatory effects. Mice treated with Elmiron (R) had a significant increase in absolute numbers of splenic macrophages (63, 500 and 1000 mg/kg) and natural killer (NK) cells (250 and 1000 mg/kg). Elmiron (R) treatment did not affect the humoral immune response or T cell proliferative response. However, innate immune responses such as phagocytosis by liver macrophages (1000 mg/kg) and NK cell activity were enhanced (500 and 1000 mg/kg). Further analysis using a disease resistance model showed that Elmiron (R)-treated mice demonstrated significantly increased anti-tumor activity against B16F10 melanoma cells at the 500 and 1000 mg/kg doses. Collectively, we conclude that Elmiron (R) administration stimulates the immune system, increasing numbers of specific cell populations and enhancing macrophage phagocytosis and NK cell activity in female B6C3F1/N mice. This augmentation may have largely contributed to the reduced number of B16F10 melanoma tumors. (C) 2014 Published by Elsevier Ltd.
C1 [Thakur, Sheetal A.; Germolec, Dori R.] Natl Inst Environm Hlth Sci, Toxicol Branch, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Nyska, Abraham] Integrated Syst Lab, Res Triangle Pk, NC USA.
[White, Kimber L., Jr.; Smith, Matthew J.; Auttachoat, Wimolnut] Virginia Commonwealth Univ, Richmond, VA USA.
RP Germolec, DR (reprint author), Natl Inst Environm Hlth Sci, Div Natl Toxicol Program, 111 TW Alexander Dr,POB 12233,MD K2-15, Res Triangle Pk, NC 27709 USA.
EM thakursa@niehs.nih.gov; germolec@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences
FX This research was supported by the NIH, National Institute of
Environmental Health Sciences. The authors would like to thank William
M. Gwinn, Ph.D. (DNTP/NIEHS) and Kymberly M. Gowdy, Ph.D. (DIR/NIEHS)
for their critical and editorial review.
NR 42
TC 0
Z9 0
U1 1
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-6915
EI 1873-6351
J9 FOOD CHEM TOXICOL
JI Food Chem. Toxicol.
PD JUN
PY 2014
VL 68
BP 196
EP 203
DI 10.1016/j.fct.2014.03.015
PG 8
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA AJ4NL
UT WOS:000337653000021
PM 24657363
ER
PT J
AU Raggi, C
Factor, VM
Seo, D
Holczbauer, A
Gillen, MC
Marquardt, JU
Andersen, JB
Durkin, M
Thorgeirsson, SS
AF Raggi, Chiara
Factor, Valentina M.
Seo, Daekwan
Holczbauer, Agnes
Gillen, Matthew C.
Marquardt, Jens U.
Andersen, Jesper B.
Durkin, Marian
Thorgeirsson, Snorri S.
TI Epigenetic Reprogramming Modulates Malignant Properties of Human Liver
Cancer
SO HEPATOLOGY
LA English
DT Article
ID STEM-CELL FATE; DNA METHYLATION; SELF-RENEWAL; HETEROGENEITY; MODELS;
AGENTS; GENES; CD133; SLUG
AB Reversal of DNA hypermethylation and associated gene silencing is an emerging cancer therapy approach. Here we addressed the impact of epigenetic alterations and cellular context on functional and transcriptional reprogramming of hepatocellular carcinoma (HCC) cells. Our strategy employed a 3-day treatment of established and primary human HCC-derived cell lines grown as a monolayer at various cell densities with the DNMT1 inhibitor zebularine (ZEB) followed by a 3D culture to identify cells endowed with selfrenewal potential. Differences in self-renewal, gene expression, tumorigenicity, and metastatic potential of spheres at generations G1-G5 were examined. Transient ZEB exposure produced differential cell density-dependent responses. In cells grown at low density, ZEB caused a remarkable increase in self-renewal and tumorigenicity associated with long-lasting gene expression changes characterized by a stable overexpression of cancer stem cell-related and key epithelial-mesenchymal transition genes. These effects persisted after restoration of DNMT1 expression. In contrast, at high cell density, ZEB caused a gradual decrease in self-renewal and tumorigenicty, and up-regulation of apoptosis- and differentiation-related genes. A permanent reduction of DNMT1 protein using short hairpin RNA (shRNA)-mediated DNMT1 silencing rendered HCC cells insensitive both to cell density and ZEB effects. Similarly, WRL68 and HepG2 hepatoblastoma cells expressing low DNMT1 basal levels also possessed a high self-renewal, irrespective of cell density or ZEB exposure. Spheres formed by low-density cells treated with ZEB or shDNMT1 displayed a high molecular similarity which was sustained through consecutive generations, confirming the essential role of DNMT1 depletion in the enhancement of cancer stem cell properties. Conclusion: These results identify DNA methylation as a key epigenetic regulatory mechanism determining the pool of cancer stem cells in liver cancer and possibly other solid tumors.
C1 [Raggi, Chiara; Factor, Valentina M.; Seo, Daekwan; Holczbauer, Agnes; Gillen, Matthew C.; Marquardt, Jens U.; Andersen, Jesper B.; Durkin, Marian; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37 Room 4146A,MSC 4262, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
OI Andersen , Jesper B/0000-0003-1760-5244; RAGGI,
Chiara/0000-0003-2473-3535
FU GEO [GSE47932]
FX We thank E.A. Conner for help with animal procedures, B. Taylor and S.
Banerjee for assistance with flow cytometry, and T. Hoang for help with
immunohistochemistry. Transcript profiling: GEO accession number:
GSE47932.
NR 37
TC 18
Z9 20
U1 1
U2 19
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 JUN
PY 2014
VL 59
IS 6
BP 2251
EP 2262
DI 10.1002/hep.27026
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AJ3LF
UT WOS:000337567100026
PM 24449497
ER
PT J
AU Wang, AS
Pfeiffer, RM
Morgan, TR
O'Brien, TR
AF Wang, Alan S.
Pfeiffer, Ruth M.
Morgan, Timothy R.
O'Brien, Thomas R.
TI Hepatitis C Genotype 1 Virus With Low Viral Load and Rapid Virologic
Response to Peginterferon/Ribavirin Obviates a Protease Inhibitorl
SO HEPATOLOGY
LA English
DT Letter
ID IL28B
C1 [Wang, Alan S.; O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA.
[Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA.
RP Wang, AS (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA CP005782-18]
NR 3
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
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD JUN
PY 2014
VL 59
IS 6
BP 2423
EP 2424
DI 10.1002/hep.26771
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AJ3LF
UT WOS:000337567100045
PM 24122888
ER
PT J
AU White, JT
DeSanto, CL
Gibbons, C
Lardner, CK
Panakos, A
Rais, S
Sharp, K
Sullivan, SD
Tidhar, W
Wright, L
Berrigan, D
Heideman, PD
AF White, Jordan T.
DeSanto, Cori L.
Gibbons, Connie
Lardner, Casey K.
Panakos, Andrew
Rais, Salehin
Sharp, Kathy
Sullivan, Shannon D.
Tidhar, Wendy
Wright, Leanne
Berrigan, David
Heideman, Paul D.
TI Insulins, leptin and feeding in a population of Peromyscus leucopus
(white-footed mouse) with variable fertility
SO HORMONES AND BEHAVIOR
LA English
DT Review
DE Genetic variation; Natural population; Leptin; Insulin Insulin-like
growth factor 1; Energetics; Reproduction; Photoperiod; Food intake;
Calorie adjustment
ID GROWTH-FACTOR-I; REPRODUCTIVE PHOTORESPONSIVENESS; PHOTOPERIODIC
CONTROL; GENETIC-VARIATION; ENERGY-BALANCE; BODY-WEIGHT; FOOD-INTAKE;
NEUROENDOCRINE MECHANISMS; NEUROPEPTIDE-Y; MICE
AB Natural populations display a variety of reproductive responses to environmental cues, but the underlying physiology that causes these responses is-largely unknown. This study tested the hypothesis that heritable variation in reproductive traits can be described by heritable variation in concentrations of hormones critical to both energy balance and reproduction. To test this hypothesis, we used mouse lines derived from a wild population and selectively bred for response to short day photoperiod. Reproductive and metabolic traits of Peromyscus leuco pus display heritable variation when held in short photoperiods typical of winter. Our two lines of mice have phenotypes spanning the full range of variation observed in nature in winter. We tested male and female mice for heritable variation in fasted serum concentrations of three hormones involved in energetic regulation: leptin, insulin-like growth factor 1 (IGF-1) and insulin, as well as the effects of exogenous leptin and a high energy diet on reproductive maturation. Exogenous leptin decreased food intake, but protected males from the reduction in testis mass caused by equivalent food restriction in pair-fed, saline-infused controls. A high energy diet resulted in calorie adjustment by the mice, and failed to alter reproductive phenotype. Concentrations of the three hormones did not differ significantly between selection lines but had correlations with measures of food intake, fertility, blood glucose, and/or body mass. There was evidence of interactions between reproductive traits and hormones related to energy balance and reproduction, but this study did not find evidence that variation in these hormones caused variation in reproductive phenotype. (C) 2014 Published by Elsevier Inc.
C1 [White, Jordan T.; DeSanto, Cori L.; Gibbons, Connie; Lardner, Casey K.; Panakos, Andrew; Rais, Salehin; Sharp, Kathy; Sullivan, Shannon D.; Tidhar, Wendy; Wright, Leanne; Heideman, Paul D.] Coll William & Mary, Dept Biol, Williamsburg, VA 23187 USA.
[White, Jordan T.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Berrigan, David] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA.
RP Heideman, PD (reprint author), Coll William & Mary, Dept Biol, POB 8795, Williamsburg, VA 23187 USA.
EM jtwhite@email.wm.edu; desantoc@wusm.wustl.edu; connie.gibbons@gmail.com;
cklardner@email.wm.edu; andrew.panakos@gmail.com; sr5z@virginia.edu;
kathy_r_sharp@yahoo.com; Shannon.D.Sullivan@Medstar.net;
wtidhar@yahoo.co.uk; Lmpina@gmail.com; berrigad@mail.nih.gov;
pdheid@wm.edu
OI White, Jordan/0000-0003-3202-4181; Lardner, Casey/0000-0002-3993-3153
FU National Institutes of Health [R15-HD068962]; ALSAM Foundation; Howard
Hughes Medical Institute Undergraduate Education Program Grant; Charles
Center of the College of William and Mary
FX We thank three anonymous reviewers for helpful comments and suggestions
that improved the manuscript significantly. Thanks to P. Kaseloo, E.
Bradley, P. Zwollo, M. Leu, J. Pittman, and H. Murphy for technical
assistance. M. Crowell assisted with data collection, and L
Wright-Jackson with animal care. Recombinant leptin was provided by
Amgen, Inc. Funding was provided by the National Institutes of Health
(R15-HD068962), from a Howard Hughes Medical Institute Undergraduate
Education Program Grant to the College of William and Mary, by the ALSAM
Foundation, and the Charles Center of the College of William and Mary.
NR 53
TC 3
Z9 3
U1 3
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0018-506X
EI 1095-6867
J9 HORM BEHAV
JI Horm. Behav.
PD JUN
PY 2014
VL 66
IS 1
SI SI
BP 169
EP 179
DI 10.1016/j.yhbeh.2014.02.006
PG 11
WC Behavioral Sciences; Endocrinology & Metabolism
SC Behavioral Sciences; Endocrinology & Metabolism
GA AJ3FB
UT WOS:000337550800015
PM 24583085
ER
PT J
AU Hu, Y
Xiao, HT
Shi, TC
Oppenheim, JJ
Chen, X
AF Hu, Ya
Xiao, Haitao
Shi, Tingchen
Oppenheim, Joost J.
Chen, Xin
TI Progranulin promotes tumour necrosis factor-induced proliferation of
suppressive mouse CD4+Foxp3+regulatory T cells
SO IMMUNOLOGY
LA English
DT Article
DE progranulin; proliferation; regulatory T cells; tumour necrosis factor;
tumour necrosis factor receptor type 2
ID FRONTOTEMPORAL LOBAR DEGENERATION; AUTOIMMUNE-DISEASE; REGULATORY-CELLS;
TNF RECEPTORS; GROWTH-FACTOR; DRUG TARGET; MICE; INFLAMMATION;
INDUCTION; PATHWAY
AB Progranulin (PGRN) is a pleiotropic growth factor with immunosuppressive properties. Recently, it was reported that PGRN was an antagonist of tumour necrosis factor (TNF) receptors, preferentially for TNFR2. However, we and others showed that TNF-TNFR2 interaction was critical for the activation and expansion of functional CD4+Foxp3+ regulatory T (Treg) cells. We therefore examined the effect of PGRN on the proliferation of naturally occurring murine suppressive Treg cells induced by TNF. Consistent with our previous reports, TNF overcame the hyporesponsiveness of highly purified Treg cells to T-cell receptor stimulation. Furthermore, in the presence of interleukin-2, TNF preferentially stimulated proliferation of Treg cells contained in unfractionated CD4 cells. These effects of TNF on suppressive Treg cells were markedly increased by exogenous PGRN. TNF and TNFR2 interactions are required for this effect of PGRN, because the PGRN by itself did not stimulate Treg cell proliferation. The effect of PGRN on Treg cells was abrogated by antibody against TNFR2, and Treg cells deficient in TNFR2 also failed to respond to PGRN. Furthermore, PGRN also enhanced the proliferative responses of effector T cells to TNF, but to a lesser extent than that of Treg cells, presumably caused by the different levels of TNFR2 expression on these two subsets of CD4 cells. Hence, our data clearly show that PGRN promotes, rather than inhibits, the functional consequence of TNF-TNFR2 interaction on Treg cells.
C1 [Hu, Ya; Xiao, Haitao; Shi, Tingchen; Oppenheim, Joost J.; Chen, Xin] NCI, Mol Immunoregulat Lab, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Hu, Ya] Yangtze Univ, Sch Med, Jinzhou, Hubei, Peoples R China.
[Chen, Xin] Leidos Biomed Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Chen, X (reprint author), NCI, LMI, Bldg 560,Rm 31-19,1050 Boyles St,POB B, Frederick, MD 21702 USA.
EM oppenhej@mail.nih.gov; chenxin@mail.nih.gov
RI Chen, Xin/I-6601-2015
OI Chen, Xin/0000-0002-2628-4027
FU National Cancer Institute, National Institutes of Health
[HHSN26120080001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract HHSN26120080001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
This Research was supported (in part) by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. The
authors thank Drs O.M. Zack Howard and Qiong Zhou, Ms Trivett L. Anna
and Ms Czarra T. Kelli for their help in this study. We thank the
NCI-Frederick Cancer Inflammation Program Fluorescence Cytometry core
for expert technical assistance with flow cytometry.
NR 32
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Z9 10
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
EI 1365-2567
J9 IMMUNOLOGY
JI Immunology
PD JUN
PY 2014
VL 142
IS 2
BP 193
EP 201
DI 10.1111/imm.12241
PG 9
WC Immunology
SC Immunology
GA AJ3AC
UT WOS:000337536000004
PM 24383743
ER
PT J
AU Brite, J
Laughon, SK
Troendle, J
Mills, J
AF Brite, J.
Laughon, S. k
Troendle, J.
Mills, J.
TI Maternal overweight and obesity and risk of congenital heart defects in
offspring
SO INTERNATIONAL JOURNAL OF OBESITY
LA English
DT Article
DE prepregnancy BMI; congenital heart defects
ID ADVERSE PREGNANCY OUTCOMES; BODY-MASS INDEX; BIRTH-DEFECTS;
HYPERGLYCEMIA; ANOMALIES
AB OBJECTIVE: Obesity is a risk factor for congenital heart defects (CHDs), but whether risk is independent of abnormal glucose metabolism remains unknown. Data on whether overweight status increases the risk are also conflicting.
RESEARCH DESIGN AND METHODS: We included 121 815 deliveries from a cohort study, the Consortium on Safe Labor (CSL), after excluding women with pregestational diabetes as recorded in the electronic medical record. CHD was identified via medical record discharge summaries. Adjusted odds ratios (ORs) for any CHD were calculated for prepregnancy body mass index (BMI) categories of overweight (25-<30 kgm(-2)), obese (30-<40 kgm(-2)) and morbidly obese (>= 40 kgm(-2)) compared with normal weight (18.5-<25 kgm(-2)) women, and for specific CHD with obese groups combined (>= 30 kgm(-2)). A subanalysis adjusting for oral glucose tolerance test (OGTT) results where available was performed as a proxy for potential abnormal glucose metabolism present at the time of organogenesis.
RESULTS: There were 1388 (1%) infants with CHD. Overweight (OR = 1.15, 95% confidence interval (95% CI): 1.01-1.32), obese (OR = 1.26, 95% CI: 1.09-1.44) and morbidly obese (OR = 1.34, 95% CI: 1.02-1.76) women had greater OR of having a neonate with CHD than normal weight women (P<0.001 for trend). Obese women (BMI >= 30 kgm(-2)) had higher OR of having an infant with conotruncal defects (OR = 1.33, 95% CI: 1.03-1.72), atrial septal defects (OR = 1.22, 95% CI: 1.04-1.43) and ventricular septal defects (OR = 1.38, 95% CI: 1.06-1.79). Being obese remained a significant predictor of CHD risk after adjusting for OGTT.
CONCLUSION: Increasing maternal weight class was associated with an increased risk for CHD. In obese women, abnormal glucose metabolism did not completely explain the increased risk for CHD; the possibility that other obesity-related factors are teratogenic requires further investigation.
C1 [Brite, J.; Laughon, S. k; Mills, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Epidemiol Branch, Bethesda, MD USA.
[Brite, J.] CUNY, Hunter Coll, Sch Publ Hlth, New York, NY USA.
[Brite, J.] CUNY, CIDR, Inst Demog Res, New York, NY USA.
[Troendle, J.] NHLBI, Div Cardiovasc Sci, Off Biostat Res, Bethesda, MD 20892 USA.
RP Laughon, SK (reprint author), NICHD, Epidemiol Branch, NIH, 6100 Executive Blvd,Room 7B03, Rockville, MD 20852 USA.
EM laughonsk@mail.nih.gov
OI Grantz, Katherine/0000-0003-0276-8534
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health [HHSN267200603425C]
FX Institutions involved in the Consortium include, in alphabetical order:
Baystate Medical Center, Springfield, MA; Cedars-Sinai Medical Center
Burnes Allen Research Center, Los Angeles, CA; Christiana Care Health
System, Newark, DE; Georgetown University Hospital, MedStar Health,
Washington, DC; Indiana University Clarian Health, Indianapolis, IN;
Intermountain Healthcare and the University of Utah, Salt Lake City,
Utah; Maimonides Medical Center, Brooklyn, NY; MetroHealth Medical
Center, Cleveland, OH; Summa Health System, Akron City Hospital, Akron,
OH; The EMMES Corporation, Rockville, MD (Data Coordinating Center);
University of Illinois at Chicago, Chicago, IL; University of Miami,
Miami, FL; and University of Texas Health Science Center at Houston,
Houston, Texas. The named authors alone are responsible for the views
expressed in this manuscript, which does not necessarily represent the
decisions or the stated policy of the NICHD. JB, SKL, JT and JM were
supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health & Human Development, National
Institutes of Health. The data included in this paper were obtained from
the Consortium on Safe Labor, which was supported by the Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health,
through Contract No. HHSN267200603425C.
NR 24
TC 12
Z9 12
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0307-0565
EI 1476-5497
J9 INT J OBESITY
JI Int. J. Obes.
PD JUN
PY 2014
VL 38
IS 6
BP 878
EP 882
DI 10.1038/ijo.2013.244
PG 5
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA AJ2PJ
UT WOS:000337499900018
PM 24362506
ER
PT J
AU Braithwaite, RS
Nucifora, KA
Kessler, J
Toohey, C
Li, LF
Mentor, SM
Uhler, LM
Roberts, MS
Galvani, A
Bryant, K
AF Braithwaite, Ronald S.
Nucifora, Kimberly A.
Kessler, Jason
Toohey, Christopher
Li, Lingfeng
Mentor, Sherry M.
Uhler, Lauren M.
Roberts, Mark S.
Galvani, Alison
Bryant, Kendall
TI How Inexpensive Does an Alcohol Intervention in Kenya Need to be in
Order to Deliver Favorable Value by Reducing HIV-Related Morbidity and
Mortality?
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Letter
ID SUB-SAHARAN AFRICAN; ANTIRETROVIRAL THERAPY; SOUTH-AFRICA; INFECTED
PATIENTS; UNPROTECTED SEX; WOMEN; ADHERENCE; MEN; PATTERNS; DRINKING
C1 [Braithwaite, Ronald S.; Nucifora, Kimberly A.; Kessler, Jason; Toohey, Christopher; Li, Lingfeng; Mentor, Sherry M.; Uhler, Lauren M.] NYU, Sch Med, Dept Populat Hlth, New York, NY 10012 USA.
[Roberts, Mark S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA USA.
[Galvani, Alison] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Bryant, Kendall] NIAAA, NIH, Bethesda, MD USA.
RP Braithwaite, RS (reprint author), NYU, Sch Med, Dept Populat Hlth, New York, NY 10012 USA.
FU NIAAA NIH HHS [R01 AA017385]
NR 36
TC 3
Z9 3
U1 4
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD JUN 1
PY 2014
VL 66
IS 2
BP E54
EP E58
DI 10.1097/QAI.0000000000000140
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AJ4YJ
UT WOS:000337685800006
PM 24828269
ER
PT J
AU Moraga, NB
Poma, HR
Amoroso, MJ
Rajal, VB
AF Beatriz Moraga, Norma
Ramiro Poma, Hugo
Julia Amoroso, Maria
Beatriz Rajal, Veronica
TI Isolation and characterization of indigenous Streptomyces and Lentzea
strains from soils containing boron compounds in Argentina
SO JOURNAL OF BASIC MICROBIOLOGY
LA English
DT Article
DE Actinobacteria; Boron-tolerance; Streptomyces, Lentzea; Boron
contaminated soils
ID SP NOV.; BORIC-ACID; BACTERIUM; TOLERANT; IDENTIFICATION; SEQUENCE;
GENE; BIOSYNTHESIS; HALOTOLERANT; BOROMYCIN
AB The Salta Province - in the northwest of Argentina - is the main worldwide producer of hydroboracite and leads in exports of boron mineral and its derivatives in Latin America. In addition to the natural presence of boron compounds in the soils, there are others contaminated due to the boron mining industry. Although some bacteria are known to require boron for their growth or to be capable of storing boron, no studies have been published about Streptomyces or Lentzea genera's capacity to tolerate high boron concentrations, or about their metabolic capacities in boron contaminated environments. The results of this research show the isolation and molecular characterization of eight strains belonging to the actinobacteria phylum collected from different soils contaminated with high boron concentration in Salta state. The boron tolerance assays, which show that three of the strains were able to tolerate up 60-80 mM boron, demonstrate the potential capability of this group of bacteria to grow and maybe to remove boron from the environment. They appear to be promising, considering that these microorganisms are infrequent pathogens, are metabolically versatile and many Streptomyces can synthesize boron containing metabolites.
C1 [Beatriz Moraga, Norma; Ramiro Poma, Hugo; Beatriz Rajal, Veronica] CONICET UNSa, Inst Invest Ind Quim INIQUI, RA-4400 Salta, Argentina.
[Beatriz Moraga, Norma; Beatriz Rajal, Veronica] Univ Nacl Salta, Fac Ingn, Salta, Argentina.
[Julia Amoroso, Maria] Consejo Nacl Invest Cient & Tecn, Planta Proc Ind & Microbiol PROIMI, San Miguel De Tucuman, Argentina.
[Julia Amoroso, Maria] Univ Nacl Tucuman, Fac Bioquim Quim & Farm, San Miguel De Tucuman, Argentina.
[Beatriz Rajal, Veronica] Univ Calif Davis, Fogarty Int Ctr, Davis, CA 95616 USA.
RP Rajal, VB (reprint author), CONICET UNSa, Inst Invest Ind Quim INIQUI, Avda Bolivia 5150, RA-4400 Salta, Argentina.
EM vbrajal@gmail.com
FU National Institute of Health - Fogarty International Center [D43
TW005718]; National Institute of Environmental Health Sciences; Consejo
de Investigaciones de la Universidad Nacional de Salta (Salta,
Argentina) [1669, 1798]; Consejo Nacional de Investigaciones Cientificas
y Tecnicas
FX This project was partially supported by National Institute of Health
Grant # D43 TW005718 funded by the Fogarty International Center and the
National Institute of Environmental Health Sciences. It was also funded
by the Consejo de Investigaciones de la Universidad Nacional de Salta
(Salta, Argentina) through the research projects No 1669 and 1798. Norma
Moraga and Ramiro Poma are recipients of graduate fellowships from
Consejo Nacional de Investigaciones Cientificas y Tecnicas. The authors
would like to thank Dr. Jerold Last for his help with the English
corrections and Oscar Gamboni for his technical assistance.
NR 50
TC 1
Z9 1
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0233-111X
EI 1521-4028
J9 J BASIC MICROB
JI J. Basic Microbiol.
PD JUN
PY 2014
VL 54
IS 6
SI SI
BP 568
EP 577
DI 10.1002/jobm.201200714
PG 10
WC Microbiology
SC Microbiology
GA AJ4TU
UT WOS:000337670000012
PM 23686918
ER
PT J
AU Shacham, R
Steinberg, I
Gandjbakhche, AH
Gannot, I
AF Shacham, Ranit
Steinberg, Idan
Gandjbakhche, Amir H.
Gannot, Israel
TI Monitoring LITT thermal penetration depth using real-time analysis of
backscattered light
SO JOURNAL OF BIOPHOTONICS
LA English
DT Article
DE backscattering; laser interstitial thermal therapy; Monte-Carlo method;
optical properties
ID LASER-INDUCED THERMOTHERAPY; OPTICAL-PROPERTIES; LIVER-TUMORS; TISSUE;
NM; CO2-LASER; SKIN
AB Real-time monitoring of the thermal penetration depth (TPD) is essential in various clinical procedures, such as Laser Interstitial Thermal Therapy (LITT). MRI is commonly used to this end, though bulky and expensive. In this paper, we present an alternative novel method for an optical feedback system based on changes in the diffused reflection from the tissue during treatment. Monte-Carlo simulation was used to deduce the relations between the backscattered pattern and the TPD. Several methods of image analysis are developed for TPD estimation. Each yields a set of parameters which are linearly dependent on the TPD. In order to test these experimentally, tissue samples were monitored in-vitro during treatment at multiple wavelengths. The SNR and coefficient of determination were used to compare the various methods and wavelengths and to determine the preferred method. Such system and algorithms may be used for real-time in-vivo control during laser thermotherapy and other clinical procedures.
[GRAPHICS]
Setup (right) and image analysis (left) preformed on tissue sample for estimation of the Thermal Penetration Depth (TPD).
C1 [Shacham, Ranit; Steinberg, Idan; Gannot, Israel] Tel Aviv Univ, Dept Biomed Engn, IL-69978 Tel Aviv, Israel.
[Gandjbakhche, Amir H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Gannot, I (reprint author), Tel Aviv Univ, Dept Biomed Engn, IL-69978 Tel Aviv, Israel.
EM gannot@eng.tau.ac.il
OI Steinberg, Idan/0000-0002-1592-8026
FU Ela Kodesz Foundation, Tel-Aviv University
FX The authors would like to thank Dr. Moshe Ben-David for his help in
planning the in-vitro experiments and data analysis. In addition, the
authors would like to thank the Ela Kodesz Foundation, Tel-Aviv
University, for their partial support of this research.
NR 18
TC 0
Z9 0
U1 0
U2 5
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1864-063X
EI 1864-0648
J9 J BIOPHOTONICS
JI J. Biophotonics
PD JUN
PY 2014
VL 7
IS 6
BP 381
EP 391
DI 10.1002/jbio.201200082
PG 11
WC Biochemical Research Methods; Biophysics; Optics
SC Biochemistry & Molecular Biology; Biophysics; Optics
GA AJ5CQ
UT WOS:000337699300003
PM 23192946
ER
PT J
AU Persoskie, A
Kaufman, AR
Leyva, B
AF Persoskie, Alexander
Kaufman, Annette R.
Leyva, Bryan
TI Receiving and Adhering to Lifestyle Modification Counseling for
Hypertension: Disparities Between Smokers and Nonsmokers
SO JOURNAL OF CLINICAL HYPERTENSION
LA English
DT Article
ID HIGH BLOOD-PRESSURE; JOINT NATIONAL COMMITTEE; UNITED-STATES; SOCIAL
DESIRABILITY; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; 7TH REPORT; HEALTH;
ADULTS; ADVICE
AB Hypertensive patients who smoke are in particular need of lifestyle modification counseling because they are at increased risk for poorer outcomes. The authors examined whether hypertensive smokers were more or less likely than nonsmokers to report receiving recommendations for diet, salt intake, exercise, alcohol use, and medication and whether receipt of recommendations was differentially associated with lifestyle changes among smokers vs nonsmokers. In an analysis of data from the 2011 Behavioral Risk Factor Surveillance System on a representative sample of hypertensive adults from 9 US states (N=23,093), smokers were less likely than nonsmokers to report being told by a provider to exercise (odds ratio [OR], 0.66; P<.001) and change their diet (OR, 0.83; P<.05). Receiving dietary recommendations was more strongly associated with self-reported dietary improvements among smokers (OR, 7.08; P<.001) compared with nonsmokers (OR, 4.17; P<.001) P<.01. Delivery of counseling may vary by smoking status. When provided, lifestyle counseling may be equally or more effective for smokers compared with nonsmokers.
C1 [Persoskie, Alexander] NCI, Basic Biobehav & Psychol Sci Branch, Bethesda, MD 20892 USA.
[Kaufman, Annette R.] NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA.
[Leyva, Bryan] NCI, Proc Care Res Branch, Bethesda, MD 20892 USA.
RP Persoskie, A (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 3E204,MSC 9761, Bethesda, MD 20892 USA.
EM persoskieai@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 45
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1524-6175
EI 1751-7176
J9 J CLIN HYPERTENS
JI J. Clin. Hypertens.
PD JUN
PY 2014
VL 16
IS 6
BP 429
EP 436
DI 10.1111/jch.12314
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AJ3XE
UT WOS:000337600400010
PM 24713034
ER
PT J
AU Shah, RV
Abbasi, SA
Yamal, JM
Davis, BR
Barzilay, J
Einhorn, PT
Goldfine, A
AF Shah, Ravi V.
Abbasi, Siddique A.
Yamal, Jose-Miguel
Davis, Barry R.
Barzilay, Joshua
Einhorn, Paula T.
Goldfine, Allison
CA ALLHAT Collaborative Res Grp
TI Impaired Fasting Glucose and Body Mass Index as Determinants of
Mortality in ALLHAT: Is the Obesity Paradox Real?
SO JOURNAL OF CLINICAL HYPERTENSION
LA English
DT Article
ID CORONARY-HEART-DISEASE; FAT DISTRIBUTION; RISK; ASSOCIATION; ADULTS;
HYPERTENSION; METAANALYSIS; OVERWEIGHT; WEIGHT; STROKE
AB Emerging literature suggests that obesity may be protective against mortality and cardiovascular outcomes, while dysglycemia may worsen outcomes regardless of obesity. The authors measured the association of weight, smoking, and glycemia with mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Among 5423 ALLHAT participants without established diabetes or cardiovascular disease, 3980 (73%) had normal fasting glucose and 1443 (27%) had impaired fasting glucose (IFG) levels at study entry. After a median of 4.9years follow-up, 554 (10%) had died (37% cardiovascular). IFG was associated with higher all-cause mortality (adjusted hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.02-1.50), while obesity was associated with lower all-cause mortality (adjusted HR, 0.76; 95% CI, 0.60-0.96). However, after excluding underweight individuals (body mass index [BMI] <22kg/m2) and smokers, neither obesity nor IFG was associated with all-cause mortality, but IFG identifies individuals at greater risk in the nonobese population. Although obesity appeared protective against mortality, this association was not significant in never-smokers or after exclusion of BMI <22kg/m2. The obesity paradox may result from confounding by a sicker, underweight referent population and smoking.
C1 [Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Abbasi, Siddique A.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Yamal, Jose-Miguel; Davis, Barry R.] Univ Texas Houston, Sch Publ Hlth, Div Biostat, Houston, TX 77030 USA.
[Barzilay, Joshua] Kaiser Permanente Georgia, Gwinnett Comprehens Med Ctr, Duluth, GA USA.
[Einhorn, Paula T.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Goldfine, Allison] Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Yamal, JM (reprint author), Univ Texas Houston, Sch Publ Hlth, Coordinating Ctr Clin Trials, 1200 Pressler St, Houston, TX 77030 USA.
EM jose-miguel.yamal@uth.tmc.edu
OI Abbasi, Siddique/0000-0002-9601-7565
FU National Heart, Lung, and Blood Institute [NO1-HC-35130,
HHSN268201100036C]; American Heart Association Post-Doctoral Research
Award; Pfizer, Inc.
FX This study was supported by contracts NO1-HC-35130 and HHSN268201100036C
with the National Heart, Lung, and Blood Institute and an American Heart
Association Post-Doctoral Research Award to Dr Shah. The ALLHAT
investigators acknowledge study medications contributed by Pfizer, Inc
(amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and
Bristol-Myers Squibb (pravastatin) and financial support provided by
Pfizer, Inc.
NR 32
TC 8
Z9 8
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1524-6175
EI 1751-7176
J9 J CLIN HYPERTENS
JI J. Clin. Hypertens.
PD JUN
PY 2014
VL 16
IS 6
BP 451
EP 458
DI 10.1111/jch.12325
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AJ3XE
UT WOS:000337600400013
PM 24779706
ER
PT J
AU Kukke, SN
Paine, RW
Chao, CC
de Campos, AC
Hallett, M
AF Kukke, Sahana N.
Paine, Rainer W.
Chao, Chi-Chao
de Campos, Ana C.
Hallett, Mark
TI Efficient and Reliable Characterization of the Corticospinal System
Using Transcranial Magnetic Stimulation
SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Transcranial magnetic stimulation; Recruitment curve; Input-output
curve; Motor threshold
ID HUMAN MOTOR CORTEX; INPUT-OUTPUT PROPERTIES; LOW-FREQUENCY; HUMAN-BRAIN;
MUSCLE; RELIABILITY; PATHWAY; REPRESENTATIONS; POTENTIALS; THRESHOLD
AB Purpose: The purpose of this study is to develop a method to reliably characterize multiple features of the corticospinal system in a more efficient manner than typically done in transcranial magnetic stimulation studies.
Methods: Forty transcranial magnetic stimulation pulses of varying intensity were given over the first dorsal interosseous motor hot spot in 10 healthy adults. The first dorsal interosseous motor-evoked potential size was recorded during rest and activation to create recruitment curves. The Boltzmann sigmoidal function was fit to the data, and parameters relating to maximal motor-evoked potential size, curve slope, and stimulus intensity leading to half-maximal motor-evoked potential size were computed from the curve fit.
Results: Good to excellent test-retest reliability was found for all corticospinal parameters at rest and during activation with 40 transcranial magnetic stimulation pulses.
Conclusions: Through the use of curve fitting, important features of the corticospinal system can be determined with fewer stimuli than typically used for the same information. Determining the recruitment curve provides a basis to understand the state of the corticospinal system and select subject-specific parameters for transcranial magnetic stimulation testing quickly and without unnecessary exposure to magnetic stimulation. This method can be useful in individuals who have difficulty in maintaining stillness, including children and patients with motor disorders.
C1 [Kukke, Sahana N.; Paine, Rainer W.; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Kukke, Sahana N.; de Campos, Ana C.] NIH, Funct & Appl Biomech Lab, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
[Chao, Chi-Chao] Natl Taiwan Univ Hosp, Dept Neurol, Taipei, Taiwan.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 7D3710 Ctr Dr MSC 1428, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
OI Chao, Chi-Chao/0000-0001-6499-5789; Kukke, Sahana/0000-0002-1359-6136
FU NIH, National Institute of Neurological Disorders and Stroke
FX Supported by the Intramural Research Program of the NIH, National
Institute of Neurological Disorders and Stroke.
NR 28
TC 5
Z9 5
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0736-0258
EI 1537-1603
J9 J CLIN NEUROPHYSIOL
JI J. Clin. Neurophysiol.
PD JUN
PY 2014
VL 31
IS 3
BP 246
EP 252
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AJ0OS
UT WOS:000337355300013
PM 24887609
ER
PT J
AU Brown, GT
Patel, V
Lee, CCR
AF Brown, Gregory Thomas
Patel, Vishal
Lee, Chyi-Chia Richard
TI Cutaneous metastasis of prostate cancer: a case report and review of the
literature with bioinformatics analysis of multiple healthcare delivery
networks
SO JOURNAL OF CUTANEOUS PATHOLOGY
LA English
DT Article
DE cutaneous neoplasm; dermatopathology; metastatic carcinoma; cutaneous
metastasis
ID MARY-JOSEPH-NODULE; SKIN METASTASES; CARCINOMA; ADENOCARCINOMA; PENILE;
MANIFESTATION; LESIONS; SCALP; CHEST
AB Distant cutaneous metastases of prostate carcinomas are extremely rare, despite its high incidence and prevalence. Most cases are either a result of local extension, such as into seminal vesicles or distant metastases to bone. Few cases of true cutaneous metastatic prostate carcinoma exist in the literature. Clinically, cutaneous prostate carcinoma has been reported to mimic many other conditions, such as cellulitis, sebaceous cysts, zosteriform lesions, telangectasias and more, resulting in poor recognition. We report a case of distant cutaneous metastasis of prostate carcinoma and recent review of the literature with an analysis of de-identified patient records from multiple healthcare delivery networks. A diagnosis of metastatic prostate carcinoma may have been easily overlooked given the location and nature of the rash. Reviewing case reports and using aggregated electronic health records (EHRs), we find that fewer than 0.1% of all prostate carcinomas result in cutaneous metastases, compared with much higher rates in other types of cancers. Coupled with the low frequency of metastases to skin, careful consideration must be taken when evaluating a rash in a patient with a prior history of cancer. A complete clinical history and strong suspicion would be required to make a diagnosis of cutaneous metastases of the prostate.
C1 [Brown, Gregory Thomas; Lee, Chyi-Chia Richard] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Patel, Vishal] Case Western Reserve Univ, Ctr Prote & Bioinformat, Cleveland, OH 44106 USA.
[Patel, Vishal] MetroHlth Syst, Ctr Clin Informat Res & Educ, Cleveland, OH USA.
RP Lee, CCR (reprint author), NIH, Bldg 10,Rm 2B50,10 Ctr Dr, Bethesda, MD 20814 USA.
EM leechy@mail.nih.gov
RI Lee, Chyi-Chia/I-1938-2013
OI Lee, Chyi-Chia/0000-0002-5306-7781
NR 42
TC 5
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0303-6987
EI 1600-0560
J9 J CUTAN PATHOL
JI J. Cutan. Pathol.
PD JUN
PY 2014
VL 41
IS 6
BP 524
EP 528
DI 10.1111/cup.12296
PG 5
WC Dermatology; Pathology
SC Dermatology; Pathology
GA AJ2VO
UT WOS:000337522600009
PM 24456209
ER
PT J
AU Trifiro, G
Coloma, PM
Rijnbeek, PR
Romio, S
Mosseveld, B
Weibel, D
Bonhoeffer, J
Schuemie, M
van der Lei, J
Sturkenboom, M
AF Trifiro, G.
Coloma, P. M.
Rijnbeek, P. R.
Romio, S.
Mosseveld, B.
Weibel, D.
Bonhoeffer, J.
Schuemie, M.
van der Lei, J.
Sturkenboom, M.
TI Combining multiple healthcare databases for postmarketing drug and
vaccine safety surveillance: why and how?
SO JOURNAL OF INTERNAL MEDICINE
LA English
DT Review
DE claims database; drug monitoring; electronic health records; product
surveillance; postmarketing; vaccine
ID MEDICAL-PRODUCT-SAFETY; ACTIVE SURVEILLANCE; PHARMACOEPIDEMIOLOGY;
NETWORK; PHARMACOVIGILANCE; PROJECT; FOOD
AB A growing number of international initiatives (e. g. EU-ADR, Sentinel, OMOP, PROTECT and VAESCO) are based on the combined use of multiple healthcare databases for the conduct of active surveillance studies in the area of drug and vaccine safety. The motivation behind combining multiple healthcare databases is the earlier detection and validation, and hence earlier management, of potential safety issues. Overall, the combination of multiple healthcare databases increases statistical sample size and heterogeneity of exposure for postmarketing drug and vaccine safety surveillance, despite posing several technical challenges. Healthcare databases generally differ by underlying healthcare systems, type of information collected, drug/vaccine and medical event coding systems and language. Therefore, harmonization of medical data extraction through homogeneous coding algorithms across highly different databases is necessary. Although no standard procedure is currently available to achieve this, several approaches have been developed in recent projects. Another main challenge involves choosing the work models for data management and analyses whilst respecting country-specific regulations in terms of data privacy and anonymization. Dedicated software (e. g. Jerboa) has been produced to deal with privacy issues by sharing only anonymized and aggregated data using a common data model. Finally, storage and safe access to the data from different databases requires the development of a proper remote research environment. The aim of this review is to provide a summary of the potential, disadvantages, methodological issues and possible solutions concerning the conduct of postmarketing multidatabase drug and vaccine safety studies, as demonstrated by several international initiatives.
C1 [Trifiro, G.; Coloma, P. M.; Rijnbeek, P. R.; Romio, S.; Mosseveld, B.; Weibel, D.; Schuemie, M.; van der Lei, J.; Sturkenboom, M.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands.
[Trifiro, G.] Univ Messina, Dept Clin & Expt Med, Messina, Italy.
[Romio, S.] Univ Milano Bicocca, Dept Clin & Prevent Med, Milan, Italy.
[Bonhoeffer, J.] Brighton Collaborat Fdn, Brighton, E Sussex, England.
[Bonhoeffer, J.] Univ Basel, Univ Childrens Hosp Basel, Basel, Switzerland.
[Schuemie, M.] Janssen Res & Dev LLC, Titusville, NJ USA.
[Schuemie, M.] Fdn Natl Inst Hlth, Observat Med Outcomes Partnership, Bethesda, MD USA.
RP Trifiro, G (reprint author), Erasmus Univ, Med Ctr, Dept Med Informat, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands.
EM g.trifiro@erasmusmc.nl
RI Trifiro, Gianluca/K-9744-2016
OI Trifiro, Gianluca/0000-0003-1147-7296
FU AstraZeneca; Pfizer; Lilly; Boehiinger
FX Miriam Sturkenboom is running a research group that occasionally
performs studies for pharmaceutical companies according to unconditional
grants These companies include AstraZeneca, Pfizer, Lilly and
Boehiinger. She has also been a consultant to Pfizer Novartis, Consumer
Health, Servier, Celgene and Lundbeck on issues not related to the
study. The other authors have no conflicts of interest to declare.
NR 33
TC 24
Z9 24
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0954-6820
EI 1365-2796
J9 J INTERN MED
JI J. Intern. Med.
PD JUN
PY 2014
VL 275
IS 6
BP 551
EP 561
DI 10.1111/joim.12159
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA AJ6FY
UT WOS:000337787300002
PM 24635221
ER
PT J
AU Mamais, A
Cookson, MR
AF Mamais, Adamantios
Cookson, Mark R.
TI LRRK2: dropping (kinase) inhibitions and seeking an (immune) response
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Editorial Material
ID ASSOCIATION; DISEASE; ERK5
C1 [Mamais, Adamantios; Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Sect, Neurogenet Lab, NIH, 35 Convent Dr, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov
FU Intramural NIH HHS [Z01 AG000948-01]
NR 14
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD JUN
PY 2014
VL 129
IS 6
BP 895
EP 897
DI 10.1111/jnc.12691
PG 3
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA AJ5WI
UT WOS:000337760500001
PM 24661004
ER
PT J
AU Szalay, KZ
Nussinov, R
Csermely, P
AF Szalay, Kristof Z.
Nussinov, Ruth
Csermely, Peter
TI Attractor Structures of Signaling Networks: Consequences of Different
Conformational Barcode Dynamics and Their Relations to Network-Based
Drug Design
SO MOLECULAR INFORMATICS
LA English
DT Article
DE Adaptation strategies; Attractors; Conformational barcodes; Drug design
strategies; Fuzzy systems; Molecular memory; Network dynamics; Network
plasticity; Network rigidity
ID SELECTION; PROTEINS; DISORDER
AB Conformational barcodes tag functional sites of proteins and are decoded by interacting molecules transmitting the incoming signal. Conformational barcodes are modified by all co-occurring allosteric events induced by post-translational modifications, pathogen, drug binding, etc. We argue that fuzziness (plasticity) of conformational barcodes may be increased by disordered protein structures, by integrative plasticity of multi-phosphorylation events, by increased intracellular water content (decreased molecular crowding) and by increased action of molecular chaperones. This leads to increased plasticity of signaling and cellular networks. Increased plasticity is both substantiated by and inducing an increased noise level. Using the versatile network dynamics tool, Turbine (www.turbine.linkgroup.hu), here we show that the 10% noise level expected in cellular systems shifts a cancer-related signaling network of human cells from its proliferative attractors to its largest, apoptotic attractor representing their health-preserving response in the carcinogen containing and tumor suppressor deficient environment modeled in our study. Thus, fuzzy conformational barcodes may not only make the cellular system more plastic, and therefore more adaptable, but may also stabilize the complex system allowing better access to its largest attractor.
C1 [Szalay, Kristof Z.; Csermely, Peter] Semmelweis Univ, Dept Med Chem, H-1094 Budapest, Hungary.
[Nussinov, Ruth] NCI, Basic Sci Program, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Szalay, KZ (reprint author), Semmelweis Univ, Dept Med Chem, Tuzolto Str 37-47, H-1094 Budapest, Hungary.
EM peter.csermely@med.semmelweis-univ.hu
OI Szalay, Kristof/0000-0001-7876-3516
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Hungarian National Science Foundation [OTKA
K83314]; NIH, National Cancer Institute, Center for Cancer Research
FX Authors thank to the anonymous reviewers of this paper for their
suggestions, and Reviewer 1 highlighting an important conclusion of the
current work on the robustness of the Turbine method, which we inserted
as the concluding two sentences of our paper. Daniel V. Veres's
(Department of Medical Chemistry, Semmelweis University, Budapest,
Hungary, www.linkgroup.hu) contribution to Figure 1 is kindly
acknowledged. This project has been funded in whole or in part with
Federal funds from the National Cancer Institute, National Institutes of
Health, under Contract Number HHSN261200800001E and by a research grant
from the Hungarian National Science Foundation (OTKA K83314). The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U. S. Government. This research was supported (in
part) by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research.
NR 24
TC 3
Z9 3
U1 0
U2 5
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1868-1743
EI 1868-1751
J9 MOL INFORM
JI Mol. Inf.
PD JUN
PY 2014
VL 33
IS 6-7
SI SI
BP 463
EP 468
DI 10.1002/minf.201400029
PG 6
WC Chemistry, Medicinal; Computer Science, Interdisciplinary Applications;
Mathematical & Computational Biology
SC Pharmacology & Pharmacy; Computer Science; Mathematical & Computational
Biology
GA AJ4EO
UT WOS:000337624900010
PM 27485984
ER
PT J
AU Noinaj, N
Buchanan, SK
AF Noinaj, Nicholas
Buchanan, Susan K.
TI FhaC takes a bow to FHA in the two-partner do-si-do
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID GRAM-NEGATIVE BACTERIA; TPSB TRANSPORTER FHAC; FILAMENTOUS
HEMAGGLUTININ; SECRETION; MEMBRANE; DOMAINS; PATHWAY
AB FhaC is an outer membrane transporter from Bordetella pertussis belonging to the two-partner secretion (TPS) pathway with its primary role being the secretion of the virulence factor filamentous haemagglutinin (FHA). FhaC serves as a model transporter of the TPS pathway and significant work has been done to characterize the role of FhaC in FHA secretion. Recent studies characterized interactions between FHA and the POTRA domains of FhaC, suggesting that secretion may involve a successive translocation mechanism mediated by -augmentation and/or electrostatic interactions. Moreover, it was also shown that reconstituted FhaC is necessary and sufficient to transport FHA into proteoliposomes. While the crystal structure of FhaC clearly suggests a role in transport, the putative transport pore is plugged by an N-terminal -helix (H1 helix) that occludes access by FHA. Therefore, it has been proposed that the H1 helix must be expelled from the pore in order for secretion of FHA to occur. However, this has yet to be shown experimentally. Guerin etal. (2014) report the first direct experimental evidence to show that the FhaC H1 helix is quite dynamic and exchanges between closed and open states upon interaction with FHA.
C1 [Noinaj, Nicholas; Buchanan, Susan K.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Buchanan, SK (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM skbuchan@helix.nih.gov
FU Intramural Research Program of the NIH, National Institute of Diabetes
and Digestive and Kidney Diseases
FX NN and SKB are supported by the Intramural Research Program of the NIH,
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 9
TC 0
Z9 0
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0950-382X
EI 1365-2958
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD JUN
PY 2014
VL 92
IS 6
BP 1155
EP 1158
DI 10.1111/mmi.12627
PG 4
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA AJ3TA
UT WOS:000337589100001
PM 24798489
ER
PT J
AU Liu, R
Baird, D
Park, Y
Freedman, ND
Huang, XM
Hollenbeck, A
Blair, A
Chen, HL
AF Liu, Rui
Baird, Donna
Park, Yikyung
Freedman, Neal D.
Huang, Xuemei
Hollenbeck, Albert
Blair, Aaron
Chen, Honglei
TI Female Reproductive Factors, Menopausal Hormone Use, and Parkinson's
Disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE reproductive factors; Parkinson's disease; cohort studies; menopausal
hormone therapy
ID NIGROSTRIATAL DOPAMINERGIC SYSTEM; POSTMENOPAUSAL ESTROGEN USE;
UNDERWENT OOPHORECTOMY; COGNITIVE IMPAIRMENT; GENDER-DIFFERENCES;
INCREASED RISK; WOMEN; PROGESTERONE; DEMENTIA; 17-BETA-ESTRADIOL
AB The objective of this study was to examine the associations of reproductive factors and exogenous hormone use with risk of Parkinson's disease (PD) among postmenopausal women. The study comprised 119,166 postmenopausal women aged 50 to 71 years in the NIH-AARP Diet and Health Study, who completed a baseline questionnaire in 1995-1996 and a follow-up survey in 2004-2006. A total of 410 selfreported PD diagnoses were identified between 1995 and 2006. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models. PD risk was not significantly associated with female reproductive factors including age at menarche, age at first live birth, parity, and age at menopause. For example, compared with women with natural menopause at age 50 to 54 years, the ORs were 1.18, (95% CI, 0.78-1.79) for women with natural menopause aged <45, 1.19 (95% CI, 0.88-1.61) for those aged 45 to 49, and 1.33 (95% CI, 0.91-1.93) for those aged 55 or older. We found that oral contraceptive use for >= 10 years (vs. never used) was associated with lower PD risk (OR, 0.59; 95% CI, 0.38-0.92), but shorter use showed no association. Use of menopausal hormone therapy showed inconsistent results. Compared with non-hormone users at baseline, current hormone users for <5 years showed a higher risk of PD (OR, 1.52; 95% CI, 1.11-2.08). However, no associations were observed for past hormone users or current users of >= 5 years. Overall, this large prospective study provides little support for an association between female reproductive factors and PD risk. Our findings on long-term oral contraceptive use and current hormone therapy warrant further investigations. (C) 2013 International Parkinson and Movement Disorder Society
C1 [Liu, Rui; Baird, Donna; Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Park, Yikyung; Freedman, Neal D.; Blair, Aaron] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA.
[Hollenbeck, Albert] AARP, Washington, DC USA.
RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM chenh2@niehs.nih.gov
RI Freedman, Neal/B-9741-2015; Baird, Donna/D-5214-2017;
OI Freedman, Neal/0000-0003-0074-1098; Baird, Donna/0000-0002-5544-2653;
Chen, Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X
FU NIH, the National Institute Neurological Disorders and Stroke
[R01-NS060722, U01-NS082151]; NIH, National Institute of Environmental
Health Sciences [Z01-ES-101986]; NIH, National Cancer Institute [Z01
CP010196-02]
FX This study was supported in part by the intramural and extramural
research programs of the NIH, the National Institute Neurological
Disorders and Stroke (R01-NS060722, U01-NS082151), the National
Institute of Environmental Health Sciences (Z01-ES-101986), and the
National Cancer Institute (Z01 CP010196-02).
NR 35
TC 10
Z9 10
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD JUN
PY 2014
VL 29
IS 7
BP 889
EP 896
DI 10.1002/mds.25771
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA AJ4TZ
UT WOS:000337670600013
PM 24352877
ER
PT J
AU Savage, SW
Zald, DH
Cowan, RL
Volkow, ND
Marks-Shulman, PA
Kessler, RM
Abumrad, NN
Dunn, JP
AF Savage, Shane W.
Zald, David H.
Cowan, Ronald L.
Volkow, Nora D.
Marks-Shulman, Pamela A.
Kessler, Robert M.
Abumrad, Naji N.
Dunn, Julia P.
TI Regulation of Novelty Seeking by Midbrain Dopamine D2/D3 Signaling and
Ghrelin is Altered in Obesity
SO OBESITY
LA English
DT Article
ID BRAIN DOPAMINE; FOOD REWARD; WEIGHT-LOSS; IN-VIVO; NEURONS; BINDING;
INDIVIDUALS; RECEPTORS; MICE; PERSONALITY
AB Objective To investigate the relationship of novelty seeking traits (NS) with midbrain dopamine (DA) receptors and acyl ghrelin levels (AG) in normal weight (NW) and obese females.NS predict addictive behaviors and are hypothesized to contribute to eating behaviors. In healthy, NS are negatively associated with DA receptors in the substantia nigra (SN). The influence of obesity on the regulation of NS by DA signaling and AG was hypothesized.
Methods PET scanning to measure DA type 2/type 3 receptor (D2/D3R) binding potential (BPND) in the SN was used. Participants completed Tridimensional Personality Questionnaire-Novelty-Seeking Scale (TPQ-NS) and AG were measured.
Results In eight NW and 19 obese (BMI 22 vs 38 kg/m2), TPQ-NS (16 vs 15) and SN D2/D3R BPND (2.48 vs 2.66) were similar, while AG higher (256 vs 60, P<0.01), respectively. D2/D3R BPND and TPQ-NS had a negative relationship in NW (r=-0.7) but not in obese (0.10). AG and TPQ-NS were positively correlated in NW (r=0.9) but not in obese (0.10). D2R BPND and AG were negatively correlated in NW (r=-0.8) but positively in obese (r=0.6).
Conclusion Obese do not maintain posited regulatory relationships for NS to either midbrain D2/D3R availability or AG present in NW. Also opposite relationships exist for NW and obese between SN D2/D3R availability and AG. The altered regulation of NS in obesity needs to be further explored.
C1 [Savage, Shane W.; Zald, David H.; Cowan, Ronald L.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37235 USA.
[Zald, David H.; Cowan, Ronald L.; Kessler, Robert M.] Vanderbilt Univ, Sch Med, Dept Radiol, Nashville, TN 37235 USA.
[Zald, David H.] Vanderbilt Univ, Sch Med, Dept Psychol, Nashville, TN 37235 USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
[Marks-Shulman, Pamela A.; Abumrad, Naji N.] Vanderbilt Univ, Sch Med, Dept Surg, Nashville, TN 37235 USA.
[Dunn, Julia P.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37235 USA.
RP Dunn, JP (reprint author), Vanderbilt Univ, Sch Med, Dept Med, 221 Kirkland Hall, Nashville, TN 37235 USA.
EM julia.dunn@va.gov
FU National Institutes of Health (NIH) from the National Center for
Research Resources (Vanderbilt Clinical and Translational Science Award)
[UL1-RR-024975]; National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) [DK-20593]; NIDDK (Vanderbilt Digestive Disease
Research Center) [DK-058404]; National Institute of Environmental Health
Sciences (Vanderbilt Environmental Health Science Scholars Program)
[K12-ESO15855]; NIDDK [DK-70860]
FX This study was supported by National Institutes of Health (NIH) grants
UL1-RR-024975 from the National Center for Research Resources
(Vanderbilt Clinical and Translational Science Award), DK-20593 from the
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK;
Vanderbilt Diabetes Research and Training Award), DK-058404 from NIDDK
(Vanderbilt Digestive Disease Research Center), K12-ESO15855 from the
National Institute of Environmental Health Sciences (Vanderbilt
Environmental Health Science Scholars Program) to J.P.D., and DK-70860
from the NIDDK to N.N.A.
NR 40
TC 7
Z9 7
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD JUN
PY 2014
VL 22
IS 6
BP 1452
EP 1457
DI 10.1002/oby.20690
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA AJ3AM
UT WOS:000337537000011
PM 24415718
ER
PT J
AU Lafferty, MK
Fantry, L
Bryant, J
Jones, O
Hammoud, D
Weitzmann, MN
Lewis, GK
Garzino-Demo, A
Reid, W
AF Lafferty, Mark K.
Fantry, Lori
Bryant, Joseph
Jones, Odell
Hammoud, Dima
Weitzmann, M. Neale
Lewis, George K.
Garzino-Demo, Alfredo
Reid, William
TI Elevated suppressor of cytokine signaling-1 (SOCS-1): a mechanism for
dysregulated osteoclastogenesis in HIV transgenic rats
SO PATHOGENS AND DISEASE
LA English
DT Article
DE SOCS-1; HIV-1; osteoclast; osteoporosis
ID BONE-MINERAL DENSITY; VIRUS-INFECTED WOMEN; B LIGAND RANKL;
ANTIRETROVIRAL THERAPY; T-CELLS; RECEPTOR ACTIVATOR; IFN-GAMMA;
OSTEOPROTEGERIN LIGAND; INHIBITORY FACTOR; CROSS-TALK
AB Accelerated bone loss leading to osteopenia, osteoporosis, and bone fracture is a major health problem that is increasingly common in human immunodeficiency virus (HIV)-infected patients. The underlying pathogenesis is unclear but occurs in both treatment naive and individuals receiving antiretroviral therapies. We developed an HIV-1 transgenic rat that exhibits many key features of HIV disease including HIV-1-induced changes in bone mineral density (BMD). A key determinant in the rate of bone loss is the differentiation of osteoclasts, the cells responsible for bone resorption. We found HIV-1 transgenic osteoclast precursors (OCP) express higher levels of suppressor of cytokine signaling-1 (SOCS-1) and TNF receptor-associated factor 6 (TRAF6) and are resistant to interferon-gamma (IFN-) mediated suppression of osteoclast differentiation. Our data suggest that dysregulated SOCS-1 expression by HIV-1 transgenic OCP promotes osteoclastogenesis leading to the accelerated bone loss observed in this animal model. We propose that elevated SOCS-1 expression in OCP antagonizes the inhibitory effects of IFN- and enhances receptor activator of NF-kB ligand (RANKL) signaling that drives osteoclast differentiation and activation. Understanding the molecular mechanisms of HIV-associated BMD changes has the potential to detect and treat bone metabolism disturbances early and improve the quality of life in patients.
C1 [Lafferty, Mark K.; Lewis, George K.; Garzino-Demo, Alfredo; Reid, William] Univ Maryland, Sch Med, Inst Human Virol, Div Basic Sci & Vaccine Res, Baltimore, MD 21201 USA.
[Lafferty, Mark K.; Lewis, George K.; Garzino-Demo, Alfredo; Reid, William] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Fantry, Lori] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Fantry, Lori; Bryant, Joseph] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Bryant, Joseph] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA.
[Bryant, Joseph; Jones, Odell] Univ Maryland, Sch Med, Anim Models Div, Inst Human Virol, Baltimore, MD 21201 USA.
[Hammoud, Dima; Reid, William] NIH, Ctr Clin, Baltimore, MD 21201 USA.
[Weitzmann, M. Neale] Emory Univ, Sch Med, Div Endocrinol & Metab & Lipids, Atlanta, GA 30322 USA.
[Weitzmann, M. Neale] Atlanta Vet Affairs Med Ctr, Decatur, GA 30033 USA.
[Weitzmann, M. Neale] Emory Univ, Winship Canc Inst, Sch Med, Atlanta, GA 30322 USA.
RP Reid, W (reprint author), NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Ctr Clin, Baltimore, MD 21201 USA.
EM william.reid@nih.gov
RI Hammoud, Dima/C-2286-2015
FU National Institute of Allergy and Infectious Diseases, NIH [R01A1063171,
R01AI087181]; National Institute of Neurological Disorders And Stroke,
NIH [R01NS066842]
FX We thank Dr Marvin Reitz for his critical reading of this manuscript. We
also thank Dr Bryan Taylor, manager of the Core facility at the
Institute of Human Virology, for his technical assistance. This study
was supported by National Institute of Allergy and Infectious Diseases,
NIH grants R01A1063171 and R01AI087181 and National Institute of
Neurological Disorders And Stroke, NIH grant R01NS066842. The authors
declare no competing financial interests.
NR 63
TC 2
Z9 2
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2049-632X
J9 PATHOG DIS
JI Pathog. Dis.
PD JUN
PY 2014
VL 71
IS 1
BP 81
EP 89
DI 10.1111/2049-632X.12117
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AJ3PB
UT WOS:000337577900009
PM 24376119
ER
PT J
AU Sturdevant, GL
Zhou, B
Carlson, JH
Whitmire, WM
Song, LH
Caldwell, HD
AF Sturdevant, Gail L.
Zhou, Bing
Carlson, John H.
Whitmire, William M.
Song, Lihua
Caldwell, Harlan D.
TI Infectivity of urogenital Chlamydia trachomatis plasmid-deficient,
CT135-null, and double-deficient strains in female mice
SO PATHOGENS AND DISEASE
LA English
DT Article
DE Chlamydiae; plasmid; CT135; mouse infectivity
ID TRANSCRIPTIONAL REGULATOR; MEMBRANE-PROTEIN; VIRULENCE FACTOR;
GENITAL-TRACT; VACCINE; GENES
AB Chlamydia trachomatis is the most common cause of human bacterial sexually transmitted infections and is the world's leading cause of infectious preventable blindness. The chlamydial 7.5-kb plasmid and chromosomal gene CT135 have been shown to be important virulence factors in both nonhuman primate and mouse infection models. Chlamydia trachomatis plasmid-deficient urogenital isolates and a predicted CT135 null mutant have been evaluated independently in the female mouse genital tract model and both have been shown to reduce infectivity and virulence. However, these attenuating phenotypes have not been evaluated collectively in the murine model. Here, we test the infectivity of C.trachomatis serovar D strains in the mouse model that are plasmid-deficient, CT135 disrupted, or possess a combination of these attenuating genotypes. We find that the presence of the plasmid results in infections with higher infectious burdens, whereas CT135 facilitates a more protracted or chronic infection. Not unexpectedly, a combination of these genetic deficiencies resulted in a strain with enhanced infection attenuation characteristics.
C1 [Sturdevant, Gail L.; Zhou, Bing; Carlson, John H.; Whitmire, William M.; Song, Lihua; Caldwell, Harlan D.] NIAID, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA.
[Song, Lihua] Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing, Peoples R China.
RP Caldwell, HD (reprint author), NIAID, NIH, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA.
EM hcaldwell@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX We thank Kelly Matteson, Anita Mora, and Dan Sturdevant for editorial
assistance, graphics preparation, and statistical analyses,
respectively. This work was supported by the Intramural Research Program
of the National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 19
TC 3
Z9 3
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2049-632X
J9 PATHOG DIS
JI Pathog. Dis.
PD JUN
PY 2014
VL 71
IS 1
BP 90
EP 92
DI 10.1111/2049-632X.12121
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AJ3PB
UT WOS:000337577900010
PM 24376189
ER
PT J
AU Miller, AC
Rosati, SF
Suffredini, AF
Schrump, DS
AF Miller, Andrew C.
Rosati, Shannon F.
Suffredini, Anthony F.
Schrump, David S.
TI A systematic review and pooled analysis of CPR-associated cardiovascular
and thoracic injuries
SO RESUSCITATION
LA English
DT Review
DE CPR; Cardiopulmonary resuscitation; Automated compression devices;
Vascular injury; Cardiac injury; Thoracic injury
ID ACUTE MYOCARDIAL-INFARCTION; CHEST CARDIAC MASSAGE; DECOMPRESSION
CARDIOPULMONARY-RESUSCITATION; RIGHT-VENTRICULAR RUPTURE; MAJOR BLEEDING
COMPLICATIONS; 2010 INTERNATIONAL CONSENSUS; BASIC LIFE-SUPPORT;
THROMBOLYTIC THERAPY; PULMONARY-EMBOLISM; ACD-CPR
AB Objective: The incidence of thoracic injuries resulting from cardiopulmonary resuscitation (CPR) is not well characterized. We describe a case in which a CPR-associated atrial rupture was identified with ultrasound and successfully managed in the intensive care unit with a bedside thoracotomy and atrial repair. We then describe a systematic review with pooled data analysis of CPR-associated cardiovascular, pulmonary, pleural, and thoracic wall injuries.
Data sources: PubMed, Scopus, EMBASE, and Web of Science were searched to identify relevant published studies. Unpublished studies were identified by searching the Australian and New Zealand Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform, Cochrane Library, ClinicalTrials.gov, Current Controlled Trials, and Google.
Study selection: Inclusion criteria for the pooled analysis were any clinical or autopsy study in which (a) patients underwent cardiopulmonary resuscitation, (b) chest compressions were administered either manually or with the assistance of active compression-decompression devices, and (c) autopsy or dedicated imaging assessments were conducted to identify complications. Exclusion criteria for the pooled analysis were pre-clinical studies, case reports and abstracts.
Data extraction: Nine-hundred twenty-eight potentially relevant references were identified. Twenty-seven references met inclusion criteria.
Data synthesis: A systematic review of the literature is provided with pooled data analysis.
Conclusions: The incidence of reported CPR-associated cardiovascular and thoracic wall injuries varies widely. CPR with active compression-decompression devices has a higher reported incidence of cardiopulmonary injuries. Bedside ultrasound may be a useful adjunct to assess and risk-stratify patients to identify serious or life-threatening CPR-associated injuries. Published by Elsevier Ireland Ltd.
C1 [Miller, Andrew C.; Suffredini, Anthony F.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Rosati, Shannon F.; Schrump, David S.] NCI, Surg Branch, Thorac Oncol Sect, NIH, Bethesda, MD 20892 USA.
RP Miller, AC (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bldg 10,Rm 2C-145,10 Ctr Dr, Bethesda, MD 20892 USA.
EM Andrew.Miller3@nih.gov
OI Miller, Andrew/0000-0001-8474-5090
FU Intramural Research Program of the Clinical Center; National Cancer
Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Clinical Center and the National Cancer Institute, National Institutes
of Health.
NR 99
TC 27
Z9 27
U1 1
U2 10
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0300-9572
J9 RESUSCITATION
JI Resuscitation
PD JUN
PY 2014
VL 85
IS 6
BP 724
EP 731
DI 10.1016/j.resuscitation.2014.01.028
PG 8
WC Critical Care Medicine; Emergency Medicine
SC General & Internal Medicine; Emergency Medicine
GA AJ0GY
UT WOS:000337329600019
PM 24525116
ER
PT J
AU Bosch-Marce, M
Seetharaman, S
Kurtz, J
Mohan, KVK
Wagner, SJ
Atreya, CD
AF Bosch-Marce, Marta
Seetharaman, Shalini
Kurtz, James
Mohan, Ketha V. K.
Wagner, Stephen J.
Atreya, Chintamani D.
TI Leukoreduced whole blood-derived platelets treated with antimicrobial
peptides maintain in vitro properties during storage
SO TRANSFUSION
LA English
DT Article
ID SIMULATED SHIPPING CONDITIONS; COMBINED IMMUNODEFICIENT MICE; APHERESIS
PLATELETS; 7-DAY STORAGE; AGITATION; PERIODS; VIVO; MECHANISMS;
SURVIVAL; PLASMA
AB Background Bacterial sepsis is still a complication in patients transfused with stored platelets (PLTs). We have recently demonstrated that selected antimicrobial peptides (AMPs) have bactericidal activity in bacteria-spiked PLTs. In a subsequent preclinical study, we have also shown that these AMPs do not elicit antibody response in rabbits and treatment of PLTs before transfusion does not affect their in vivo recovery and survival in severe combined immunodeficient mice. Here we have selected two such AMPs, Arg-Trp (RW) repeats of tri- and tetra-peptides (RW3 and RW4) in combination (i.e., cocktail), and evaluated their effect on the in vitro properties of PLTs. Study Design and Methods Leukoreduced ABO- and D-identical whole blood-derived PLT concentrates were pooled and divided into two 60-mL aliquots in CLX storage bags. On Day 0, one bag received a peptide cocktail of RW3plusRW4 at 0.01mmol/L final concentration (test) and the other bag received only phosphate-buffered saline (PBS), the AMP solvent (control). The treated PLTs were stored for 7 days at 20 to 24 degrees C. Samples were collected on Days 1, 5, and 7 to evaluate the in vitro properties of PLTs with standard assays. Results In vitro properties of the RW3plusRW4 cocktail-treated PLTs were similar to those incubated with PBS only. There were no significant differences between the control and test PLTs during the 7-day storage. Conclusion Leukoreduced whole blood-derived PLTs treated with a mixture of RW3 and RW4 peptides maintain their in vitro properties during 7 days of storage.
C1 [Bosch-Marce, Marta; Mohan, Ketha V. K.; Atreya, Chintamani D.] US FDA, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Sect Cell Biol, Bethesda, MD 20014 USA.
[Seetharaman, Shalini; Kurtz, James; Wagner, Stephen J.] Amer Red Cross, Blood Components Dept, Rockville, MD USA.
RP Atreya, CD (reprint author), Bldg 29A,Room 2C-11,NIH Campus, Bethesda, MD 20892 USA.
EM chintamani.atreya@fda.hhs.gov
FU Center for Biologics Evaluation and Research (CBER)
FX MBM is the recipient of a postdoctoral fellowship at the Center for
Biologics Evaluation and Research (CBER) administered by the Oak Ridge
Institute for Science and Education (ORISE) through an intraagency
agreement between the US Department of Energy and the US Food and Drug
Administration. The authors thank Ms Sandhya Kulkarni for her help with
timely procurement of materials used in this work.
NR 32
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD JUN
PY 2014
VL 54
IS 6
BP 1604
EP 1609
DI 10.1111/trf.12534
PG 6
WC Hematology
SC Hematology
GA AJ3TU
UT WOS:000337591200024
PM 24410697
ER
PT J
AU Valsangkar, B
Chen, C
Wohltjen, H
Mullan, F
AF Valsangkar, Bina
Chen, Candice
Wohltjen, Hannah
Mullan, Fitzhugh
TI Do Medical School Mission Statements Align With the Nation's Health Care
Needs?
SO ACADEMIC MEDICINE
LA English
DT Editorial Material
AB Problem
To quantify the relative prevalence of traditional (education, research, service) and emerging (prevention, diversity, primary care, distribution, cost control) themes in medical school mission statements.
Approach
In 2011, the authors obtained and analyzed the mission statements from 136 MD-granting and 34 DO-granting medical schools. They read each for the presence of traditional and emerging themes and then compared the mission statements by category of school (MD-granting versus DO-granting, level of National Institutes of Health funding, public versus private, date of initial accreditation [before or during/after 2000], and community-based versus non-community-based).
Outcomes
Traditional themes were common in medical school mission statement-seducation (170; 100%), research (146; 86%), and service (150; 88%). Emerging themes were less common-distribution (41; 24%), primary care (32; 19%), diversity (27; 16%), prevention (9; 5%), and cost control (2; 1%). DO-granting and community-based medical school mission statements cited the traditional theme of service and the emerging themes of primary care and distribution more frequently than those of MD-granting and non-community-based schools.
Next Steps
The traditional themes of education, research, and service dominate medical school mission statements. DO-granting and community-based medical schools, however, more often have incorporated the emerging themes of primary care and distribution. Although including emerging themes in a mission statement does not guarantee tangible results, omitting them suggests that the school has not embraced these issues. Without the engagement of established medical schools, the national health care problems represented by these emerging themes will not receive the attention they need.
C1 [Valsangkar, Bina; Mullan, Fitzhugh] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20052 USA.
[Chen, Candice] Natl Inst Minor Hlth & Hlth Dispar, Bethesda, MD USA.
[Chen, Candice; Wohltjen, Hannah; Mullan, Fitzhugh] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
RP Valsangkar, B (reprint author), 2000 L St NW,Suite 500, Washington, DC 20036 USA.
EM bvalsangkar@savechildren.org
FU National Institute of Minority Health and Health Disparities, National
Institutes of Health
FX Dr. Candice Chen is supported through a Disparities Research and
Education Advancing Mission (DREAM) Career Transition Award from the
National Institute of Minority Health and Health Disparities, National
Institutes of Health.
NR 10
TC 1
Z9 1
U1 2
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-2446
EI 1938-808X
J9 ACAD MED
JI Acad. Med.
PD JUN
PY 2014
VL 89
IS 6
BP 892
EP 895
DI 10.1097/ACM.0000000000000241
PG 4
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA AI8NU
UT WOS:000337176300022
PM 24871240
ER
PT J
AU Buckheit, RW
Sexauer, SB
Sedaghat, AR
Wilke, CO
Laeyendecker, O
Basseth, CR
Blankson, JN
AF Buckheit, Robert W., III
Sexauer, Stephen B.
Sedaghat, Ahmad R.
Wilke, Claus O.
Laeyendecker, Oliver
Basseth, Christie R.
Blankson, Joel N.
TI Long-Term Control of Viral Replication in a Group O, Human
Immunodeficiency Virus Type 1-Infected Individual
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Letter
ID HIV-1; INFECTION; EVOLUTION; CAMEROON
C1 [Buckheit, Robert W., III; Sexauer, Stephen B.; Laeyendecker, Oliver; Basseth, Christie R.; Blankson, Joel N.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Sedaghat, Ahmad R.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
[Wilke, Claus O.] Ctr Computat Biol & Bioinformat, Sect Integrat Biol, Austin, TX USA.
[Wilke, Claus O.] Univ Texas Austin, Inst Cell & Mol Biol, Austin, TX 78712 USA.
[Laeyendecker, Oliver] NIAID, Div Intramural Res, NIH, Baltimore, MD USA.
RP Blankson, JN (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, 733 North Broadway,BRB 880, Baltimore, MD 21205 USA.
EM jblanks@jhmi.edu
OI Laeyendecker, Oliver/0000-0002-6429-4760; Wilke,
Claus/0000-0002-7470-9261
FU NIGMS NIH HHS [T32 GM008752]
NR 13
TC 2
Z9 2
U1 0
U2 5
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD JUN
PY 2014
VL 30
IS 6
BP 511
EP 513
DI 10.1089/aid.2014.0054
PG 3
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AI9CE
UT WOS:000337224400001
PM 24798496
ER
PT J
AU Yao, L
Gai, N
Boutin, RD
AF Yao, Lawrence
Gai, Neville
Boutin, Robert D.
TI Axial Scan Orientation and the Tibial Tubercle-Trochlear Groove
Distance: Error Analysis and Correction
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE knee; MRI; patellofemoral instability; tibial tubercle; trochlear groove
ID PATELLAR INSTABILITY; TUBEROSITY; KNEE; CT
AB OBJECTIVE. The tibial tubercle (TT)-trochlear groove (TG) distance is an important metric in the assessment of patellofemoral dysfunction and is routinely measured on axial MRI and CT. This study examines error in measurements of the TT-TG distance related to variance in axial MRI scan orientation.
SUBJECTS AND METHODS. Isotropic 3D turbo spin-echo MRI of the extended knee was performed in 12 healthy subjects. The z-axis of the scanner defines the perpendicular to a routine axial plane, and the anatomic axial plane is parallel to the knee joint. Isotropic MRI was reformatted into routine and anatomic axial planes and in axial planes simulating 5 degrees of femoral adduction and abduction relative to the anatomic plane. A method for correcting the TT-TG distance to account for variable axial scan orientation is presented.
RESULTS. Five degrees of simulated femoral abduction is associated with a mean increase in the TT-TG distance of 38% (SD = 17%), whereas 5 degrees of simulated femoral adduction is associated with a mean decrease in the TT-TG distance of 51% (SD = 39%). The average deviation of the routine axial plane from the anatomic axial plane was 5.0 degrees abduction (SD = 2.3 degrees). The simplest correction method reduced the mean discrepancy in the observed TT-TG distance by 68% and 72% in simulated femoral abduction and adduction, respectively.
CONCLUSION. The TT-TG distance is sensitive to small changes in femoral alignment and should be interpreted with caution if axial image acquisition is not standardized. Knowing the vertical separation of the TT from the TG facilitates a simplified correction of the TT-TG distance, which is as effective as more complex corrections.
C1 [Yao, Lawrence; Gai, Neville] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Boutin, Robert D.] Univ Calif, Dept Radiol, Sacramento, CA USA.
RP Yao, L (reprint author), NIH, Ctr Clin, Dept Radiol & Imaging Sci, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM lyao@cc.nih.gov
FU National Institutes of Health Clinical Center, Intramural Research
Program
FX This study was supported in part by the National Institutes of Health
Clinical Center, Intramural Research Program.
NR 14
TC 3
Z9 3
U1 0
U2 1
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD JUN
PY 2014
VL 202
IS 6
BP 1291
EP 1296
DI 10.2214/AJR.13.11488
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI6DB
UT WOS:000336959000037
PM 24848827
ER
PT J
AU Murphy, RA
Bureyko, TF
Miljkovic, I
Cauley, JA
Satterfield, S
Hue, TF
Klepin, HD
Cummings, SR
Newman, AB
Harris, TB
AF Murphy, Rachel A.
Bureyko, Taylor F.
Miljkovic, Iva
Cauley, Jane A.
Satterfield, Suzanne
Hue, Trisha F.
Klepin, Heidi D.
Cummings, Steven R.
Newman, Anne B.
Harris, Tamara B.
TI Association of total adiposity and computed tomographic measures of
regional adiposity with incident cancer risk: a prospective
population-based study of older adults
SO APPLIED PHYSIOLOGY NUTRITION AND METABOLISM-PHYSIOLOGIE APPLIQUEE
NUTRITION ET METABOLISME
LA English
DT Article
DE obesity; weight; adipose; body fat; cancer incidence; cancer risk; aging
ID BODY-MASS INDEX; WAIST CIRCUMFERENCE; FAT DISTRIBUTION; LUNG-CANCER;
OBESITY; COHORT; HEALTH; WOMEN; OVERWEIGHT; WEIGHT
AB Obesity is associated with increased risk of many types of cancer. Less is known regarding associations between adipose depots and cancer risk. We aimed to explore relationships between adipose depots, risk of cancer, and obesity-related cancer (per NCI definition) in participants initially aged 70-79 years without prevalent cancer (1179 men, 1340 women), and followed for incident cancer for 13 years. Measures included body mass index (BMI), total adipose tissue from dual-energy X-ray absorptiometry, and computed tomography measures of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, thigh intermuscular adipose tissue, and thigh muscle attenuation (Hounsfield unit, HU), where low HU indicates fatty infiltration. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models adjusted for demographics, lifestyle variables, and medical conditions. During follow-up, 617 participants developed cancer of which 224 were obesity-related cancers. Total adipose tissue and VAT were positively associated with cancer risk among women (HR 1.14, 95% CI 1.01-1.30 per SD increase; HR 1.15, 95% CI 1.02-1.30 per SD increase). There were no associations with cancer risk among men. Total adipose tissue was positively associated with obesity-related cancer risk among women (HR 1.23, 95% CI 1.03-1.46 per SD increase). VAT was positively associated with obesity-related cancer risk among men (HR 1.30, 95% CI 1.06-1.60 per SD increase) and remained associated even with adjustment for BMI (HR 1.40, 95% CI 1.08-1.82 per SD increase). These findings provide insight into relationships between specific adipose depots and cancer risk and suggest differential relationships among men and women.
C1 [Murphy, Rachel A.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20814 USA.
[Bureyko, Taylor F.] Univ Alberta, Dept Agr Food & Nutr Sci, Li Ka Shing Ctr 4 126, Edmonton, AB T6G 2E1, Canada.
[Miljkovic, Iva; Cauley, Jane A.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA.
[Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Hlth Sci Ctr, Memphis, TN 38163 USA.
[Hue, Trisha F.; Cummings, Steven R.] Calif Pacific Med Ctr Res Inst, San Francisco, CA 94120 USA.
[Klepin, Heidi D.] Wake Forest Sch Med, Ctr Comprehens Canc, Winston Salem, NC 27157 USA.
RP Murphy, RA (reprint author), NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, 7201 Wisconsin Ave,3C-309, Bethesda, MD 20814 USA.
EM Rachel.murphy@nih.gov
RI Cauley, Jane/N-4836-2015; Newman, Anne B./C-6408-2013;
OI Cauley, Jane/0000-0003-0752-4408; Newman, Anne B./0000-0002-0106-1150;
Miljkovic, Iva/0000-0002-3155-9777
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; NIA [R01-AG028050]; NINR [R01-NR-012459]; National
Institutes of Health, National Institute on Aging; Banting Postdoctoral
Fellowship
FX This research was supported by National Institute on Aging (NIA)
Contracts N01-AG-6-2101; N01-AG-6-2103, N01-AG-6-2106; NIA grant
R01-AG028050, and NINR grant R01-NR-012459. This research was supported
in part by the Intramural Research Program of the National Institutes of
Health, National Institute on Aging. R.A.M. is supported by a Banting
Postdoctoral Fellowship.
NR 19
TC 4
Z9 4
U1 0
U2 5
PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS
PI OTTAWA
PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA
SN 1715-5312
EI 1715-5320
J9 APPL PHYSIOL NUTR ME
JI Appl. Physiol. Nutr. Metab.
PD JUN
PY 2014
VL 39
IS 6
BP 687
EP 692
DI 10.1139/apnm-2013-0360
PG 6
WC Nutrition & Dietetics; Physiology; Sport Sciences
SC Nutrition & Dietetics; Physiology; Sport Sciences
GA AI8KZ
UT WOS:000337164600006
PM 24869972
ER
PT J
AU Williams, JS
Xiao, Y
Brownell, I
AF Williams, Jonathan S.
Xiao, Ying
Brownell, Isaac
TI Low pH reprograms somatic murine cells into pluripotent stem cells A
novel technique with therapeutic implications
SO CANCER BIOLOGY & THERAPY
LA English
DT Editorial Material
DE induced pluripotent stem cells; embryonic stem cells; stimulus-triggered
acquisition of pluripotency; blastocyst complementation assay; tumor
infiltrating lymphocytes
ID FIBROBLASTS; LYMPHOCYTES; GENERATION
AB Induced pluripotent stem cells (iPSCs) are somatic cells that are reprogrammed into a state resembling embryonic stem cells (ESCs). iPSCs represent a promising technology with applications in cancer research, yet current methods used to generate iPSCs limit their translation to clinical use. In a recent Nature article, Obokata et al. detail a novel technique to generate pluripotent murine cells called stimulus-triggered acquisition of pluripotency (STAP). STAP eliminates the need for exogenous expression of reprogramming factors used in previous iPSC technologies, instead transforming somatic cells to pluripotency using physical and chemical stimuli. The authors found that STAP cells are generated at a 10-fold higher efficiency than prior iPSC technologies. STAP cells display several features of pluripotency, namely the expression of pluripotency-related genes (Oct4, Nanog, Sox2, Ecat1, Esg1, and Dax1), the ability to form teratomas in vivo, and the ability to produce viable, fertile mice in blastocyst complementation assays. Here, we review these findings on STAP and contrast it to previous iPSC technologies, while noting the potential of this method to generate autologous anti-tumor immune cells for cancer therapy.
C1 [Williams, Jonathan S.; Xiao, Ying; Brownell, Isaac] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Brownell, I (reprint author), NCI, Dermatol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
EM isaac.brownell@nih.gov
FU Intramural NIH HHS
NR 10
TC 1
Z9 1
U1 0
U2 16
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4047
EI 1555-8576
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD JUN
PY 2014
VL 15
IS 6
BP 675
EP 677
DI 10.4161/cbt.28414
PG 3
WC Oncology
SC Oncology
GA AI8MC
UT WOS:000337169500004
PM 24618709
ER
PT J
AU McAllister, F
Pineda, DM
Jimbo, M
Lal, S
Burkhart, RA
Moughan, J
Winter, KA
Abdelmohsen, K
Gorospe, M
Acosta, AD
Lankapalli, RH
Winter, JM
Yeo, CJ
Witkiewicz, AK
Iacobuzio-Donahue, CA
Laheru, D
Brody, JR
AF McAllister, Florencia
Pineda, Danielle M.
Jimbo, Masaya
Lal, Shruti
Burkhart, Richard A.
Moughan, Jennifer
Winter, Kathryn A.
Abdelmohsen, Kotb
Gorospe, Myriam
Acosta, Ana de Jesus
Lankapalli, Rachana H.
Winter, Jordan M.
Yeo, Charles J.
Witkiewicz, Agnieska K.
Iacobuzio-Donahue, Christine A.
Laheru, Daniel
Brody, Jonathan R.
TI dCK expression correlates with 5-fluorouracil efficacy and HuR
cytoplasmic expression in pancreatic cancer A dual-institutional
follow-up with the RTOG 9704 trial
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE pancreatic cancer; gemcitabine; 5-fluorouracil; HuR; dCK
ID THYMIDYLATE SYNTHASE EXPRESSION; RANDOMIZED CONTROLLED-TRIAL; MISMATCH
REPAIR STATUS; PLUS FOLINIC ACID; ADJUVANT CHEMOTHERAPY; DEOXYCYTIDINE
KINASE; COLORECTAL-CANCER; PREDICTIVE MARKER; COLON-CANCER; CELL-LINES
AB Deoxycytidine kinase (dCK) and human antigen R (HuR) have been associated with response to gemcitabine in small studies. The present study investigates the prognostic and predictive value of dCK and HuR expression levels for sensitivity to gemcitabine and 5-fluorouracil (5-FU) in a large phase III adjuvant trial with chemoradiation backbone in pancreatic ductal adenocarcinoma (PDA). The dCK and HuR expression levels were determined by immunohistochemistry on a tissue microarray of 165 resected PDAs from the Radiation Therapy Oncology Group (RTOG) 9704 trial. Association with overall survival (OS) and disease-free survival (DFS) status were analyzed using the log-rank test and the Cox proportional hazards model. Experiments with cultured PDA cells were performed to explore mechanisms linking dCK and HuR expression to drug sensitivity. dCK expression levels were associated with improved OS for all patients analyzed from RTOG 9704 (HR: 0.66, 95% CI [0.47-0.93], P = 0.015). In a subset analysis based on treatment arm, the effect was restricted to patients receiving 5-FU (HR: 0.53, 95% CI [0.33-0.85], P = 0.0078). Studies in cultured cells confirmed that dCK expression rendered cells more sensitive to 5-FU. HuR cytoplasmic expression was neither prognostic nor predictive of treatment response. Previous studies along with drug sensitivity and biochemical studies demonstrate that radiation interferes with HuR's regulatory effects on dCK, and could account for the negative findings herein based on the clinical study design (i.e., inclusion of radiation). Finally, we demonstrate that 5-FU can increase HuR function by enhancing HuR translocation from the nucleus to the cytoplasm, similar to the effect of gemcitabine in PDA cells. For the first time, in the pre-treatment tumor samples, dCK and HuR cytoplasmic expression were strongly correlated (chi-square P = 0.015). This dual-institutional follow up study, in a multi-institutional PDA randomized clinical trial, observed that dCK expression levels were prognostic and had predictive value for sensitivity to 5-FU.
C1 [McAllister, Florencia; Acosta, Ana de Jesus; Lankapalli, Rachana H.; Iacobuzio-Donahue, Christine A.; Laheru, Daniel] Johns Hopkins Univ, Dept Med Oncol, Baltimore, MD USA.
[McAllister, Florencia; Acosta, Ana de Jesus; Lankapalli, Rachana H.; Iacobuzio-Donahue, Christine A.; Laheru, Daniel] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[McAllister, Florencia] Johns Hopkins Univ, Dept Med, Div Clin Pharmacol, Baltimore, MD USA.
[Pineda, Danielle M.; Jimbo, Masaya; Lal, Shruti; Burkhart, Richard A.; Winter, Jordan M.; Yeo, Charles J.; Brody, Jonathan R.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg,Div Surg Res, Jefferson Pancreas Biliary & Related Canc Ctr, Philadelphia, PA 19107 USA.
[Moughan, Jennifer; Winter, Kathryn A.] RTOG Stat Ctr, Philadelphia, PA USA.
[Abdelmohsen, Kotb; Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Witkiewicz, Agnieska K.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA.
RP Brody, JR (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg,Div Surg Res, Jefferson Pancreas Biliary & Related Canc Ctr, Philadelphia, PA 19107 USA.
EM jonathan.brody@jefferson.edu
OI Lal, Shruti/0000-0002-2091-4307
FU NIGMS [T32GMO66691]; Pancreatic Cancer Action Network-AACR Fellowship
[12-40-25-MCAL]; Conquer Cancer Foundation Young Investigator Award;
American Cancer Society; NIA-IRP, NIH; RTOG Translational Research
Program (seed grant) [78]; RTOG grant [U10 CA21661]; CCOP grant from the
National Cancer Institute (NCI) [U10 CA37422]; Pennsylvania Department
of Health Formula Grant [4100057652]
FX F.M. was supported by NIGMS T32GMO66691, 2012 Pancreatic Cancer Action
Network-AACR Fellowship, in memory of Samuel Stroum, Grant Number
12-40-25-MCAL and Conquer Cancer Foundation Young Investigator Award
2012. J.R.B. was in part supported by resources provided by
AACR-Pancreatic Cancer Action Network and A Research Scholar Grant from
the American Cancer Society. M. G. and K. A. were supported by the
NIA-IRP, NIH. This project was supported by the RTOG Translational
Research Program (seed grant #78), RTOG grant U10 CA21661, CCOP grant
U10 CA37422 from the National Cancer Institute (NCI), and the
Pennsylvania Department of Health Formula Grant 4100057652. No part of
this manuscript has been submitted to any other journal.
NR 51
TC 13
Z9 14
U1 0
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4047
EI 1555-8576
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD JUN
PY 2014
VL 15
IS 6
BP 688
EP 698
DI 10.4161/cbt.28413
PG 11
WC Oncology
SC Oncology
GA AI8MC
UT WOS:000337169500007
PM 24618665
ER
PT J
AU Pastan, I
Hassan, R
AF Pastan, Ira
Hassan, Raffit
TI Discovery of Mesothelin and Exploiting It as a Target for Immunotherapy
SO CANCER RESEARCH
LA English
DT Review
ID MONOCLONAL-ANTIBODY MORAB-009; IMMUNOTOXIN SS1P; PHASE-I; RECOMBINANT
IMMUNOTOXIN; ANTITUMOR-ACTIVITY; OVARIAN-CANCER; EXPRESSING MESOTHELIN;
PLUS CYCLOPHOSPHAMIDE; LUNG ADENOCARCINOMA; POTENTIATING FACTOR
AB We have recently reported that an immunotoxin targeting mesothelin produced durable major tumor regressions in patients with extensive treatment-refractory mesothelioma. These unprecedented tumor responses have prompted us to review how mesothelin was discovered and the advances that led to these tumor responses. This review is not comprehensive but focuses on major developments over the past 20 years since mesothelin was first identified in our laboratory. Mesothelin is a cell-surface glycoprotein whose expression in normal human tissues is restricted to mesothelial cells. Because it is highly expressed by many solid tumors, it is an attractive immunotherapy target. Antibody-based therapies currently in clinical trials include an immunotoxin, a chimeric monoclonal antibody, and an antibody drug conjugate. In addition, a mesothelin tumor vaccine and a mesothelin-chimeric antigen receptor are being evaluated in the clinic. SS1P, an anti-mesothelin immunotoxin, was the first mesothelin-directed therapy to enter the clinic, and its use showed that mesothelin- targeted therapy was safe in patients. More importantly, our recent work has shown that SS1P in combination with pentostatin and cyclophosphamide can result in durable tumor regression in patients with advanced mesothelioma and opens up the possibility that such an approach can benefit patients with many common cancers.
C1 [Pastan, Ira; Hassan, Raffit] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov; hassanr@mail.nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research; CRADA; Roche Pharmaceuticals
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research, and a CRADA with
Roche Pharmaceuticals.
NR 47
TC 43
Z9 43
U1 3
U2 17
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUN 1
PY 2014
VL 74
IS 11
BP 2907
EP 2912
DI 10.1158/0008-5472.CAN-14-0337
PG 6
WC Oncology
SC Oncology
GA AI8ML
UT WOS:000337170600001
PM 24824231
ER
PT J
AU Ekenga, CC
Parks, CG
D'Aloisio, AA
Deroo, LA
Sandler, DP
AF Ekenga, Christine C.
Parks, Christine G.
D'Aloisio, Aimee A.
Deroo, Lisa A.
Sandler, Dale P.
TI Breast Cancer Risk after Occupational Solvent Exposure: the Influence of
Timing and Setting
SO CANCER RESEARCH
LA English
DT Article
ID ORGANIC-SOLVENTS; ENDOCRINE DISRUPTORS; YOUNG-WOMEN; EARLY-LIFE;
CHEMICALS; SMOKING; DISEASE
AB Organic solvents are ubiquitous in occupational settings where they may contribute to risks for carcinogenesis. However, there is limited information on organic solvents as human breast carcinogens. We examined the relationship between occupational exposure to solvents and breast cancer in a prospective study of 47,661 women with an occupational history in the Sister Study cohort. Occupational solvent exposure was categorized using self-reported job-specific solvent use collected at baseline. Multivariable Cox regression analyses were used to assess breast cancer risk, adjusting for established breast cancer risk factors. A total of 1,798 women were diagnosed with breast cancer during follow-up, including 1,255 invasive cases. Overall the risk of invasive breast cancer was not associated with lifetime exposure to solvents [HR, 1.04; 95% confidence interval (CI), 0.88-1.24]. Parous women who worked with solvents before their first fullterm birth had an increased risk of estrogen receptor-positive invasive breast cancer compared with women who never worked with solvents (HR, 1.39; 95% CI, 1.03-1.86). A significantly elevated risk for estrogen receptor-positive invasive breast cancer was associated with solvent exposure among clinical laboratory technologists and technicians (HR, 2.00; 95% CI, 1.07-3.73). Occupational exposure to solvents before first birth, a critical period of breast tissue differentiation, may result in increased vulnerability for breast cancer. Our findings suggest a need for future studies in this area to focus on exposure time windows and solvent types in different occupational settings. (C) 2014 AACR.
C1 [Ekenga, Christine C.; Parks, Christine G.; D'Aloisio, Aimee A.; Deroo, Lisa A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Deroo, Lisa A.] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
RP Ekenga, CC (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM christine.ekenga@nih.gov
OI Parks, Christine/0000-0002-5734-3456; Sandler, Dale/0000-0002-6776-0018
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z1A ES044005]
FX This research was supported by the Intramural Research Program of the
NIH, National Institute of Environmental Health Sciences (Z1A ES044005).
NR 35
TC 6
Z9 6
U1 1
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUN 1
PY 2014
VL 74
IS 11
BP 3076
EP 3083
DI 10.1158/0008-5472.CAN-13-2430
PG 8
WC Oncology
SC Oncology
GA AI8ML
UT WOS:000337170600017
PM 24879566
ER
PT J
AU Layani-Bazar, A
Skornick, I
Berrebi, A
Pauker, MH
Noy, E
Silberman, A
Albeck, M
Longo, DL
Kalechman, Y
Sredni, B
AF Layani-Bazar, Adi
Skornick, Itai
Berrebi, Alain
Pauker, Maor H.
Noy, Elad
Silberman, Alon
Albeck, Michael
Longo, Dan L.
Kalechman, Yona
Sredni, Benjamin
TI Redox Modulation of Adjacent Thiols in VLA-4 by AS101 Converts Myeloid
Leukemia Cells from a Drug-Resistant to Drug-Sensitive State
SO CANCER RESEARCH
LA English
DT Article
ID ACUTE MYELOGENOUS LEUKEMIA; INTEGRIN ACTIVATION; PROTEIN THIOLS; LATE
ANTIGEN-4; EXPRESSION; DOMAIN; ALPHA(IIB)BETA(3); CHEMOTHERAPY;
SURVIVAL; ADHESION
AB Interaction between the integrin VLA-4 on acute myelogenous leukemia (AML) cells with stromal fibronectin is a decisive factor in chemotherapeutic resistance. In this study, we provide a rationale for a drug repositioning strategy to blunt integrin activation in AML cells and restore their sensitivity to chemotherapy. Specifically, we demonstrate that the nontoxic tellurium compound AS101, currently being evaluated in clinical trials, can abrogate the acquired resistance of AML. Mechanistic investigations revealed that AS101 caused redox inactivation of adjacent thiols in the exofacial domain of VLA-4 after its ligation to stromal fibronectin. This effect triggered cytoskeletal conformational changes that decreased PI3K/Akt/Bcl2 signaling, an obligatory step in chemosensitization by AS101. In a mouse xenograft of AML derived from patient leukemic cells with high VLA-4 expression and activity, we demonstrated that AS101 abrogated drug resistance and prolonged survival in mice receiving chemotherapy. Decreased integrin activity was confirmed on AML cells in vivo. The chemosensitizing activity of AS101 persisted in hosts with defective adaptive and innate immunity, consistent with evidence that integrin deactivation was not mediated by heightening immune attack. Our findings provide a mechanistic rationale to reposition the experimental clinical agent, AS101, to degrade VLA-4-mediated chemoresistance and improve clinical responses in patients with AML.
C1 [Layani-Bazar, Adi; Skornick, Itai; Pauker, Maor H.; Noy, Elad; Silberman, Alon; Kalechman, Yona; Sredni, Benjamin] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, CAIR Inst, Safdie AIDS & Immunol Res Ctr, IL-5290002 Ramat Gan, Israel.
[Silberman, Alon; Albeck, Michael] Bar Ilan Univ, Dept Chem, IL-5290002 Ramat Gan, Israel.
[Berrebi, Alain] Kaplan Med Ctr, Dept Hematol, Rehovot, Israel.
[Longo, Dan L.] NIA, Lab Mol Biol & Immunol, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Sredni, B (reprint author), Bar Ilan Univ, Max & Anna Webb St, IL-5290002 Ramat Gan, Israel.
EM srednib@mail.biu.ac.il
FU Israel Cancer Association [20092012, 20080016]; Safdie Institute for
AIDS and Immunology Research; Dr. Tovi Comet-Walerstein Cancer Research
Chair; Dave and Florence Muskovitz Chair in Cancer Research
FX This work was partly supported by grants from the Israel Cancer
Association (20092012 and 20080016), The Safdie Institute for AIDS and
Immunology Research, The Dr. Tovi Comet-Walerstein Cancer Research
Chair, and The Dave and Florence Muskovitz Chair in Cancer Research.
NR 48
TC 16
Z9 16
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUN 1
PY 2014
VL 74
IS 11
BP 3092
EP 3103
DI 10.1158/0008-5472.CAN-13-2159
PG 12
WC Oncology
SC Oncology
GA AI8ML
UT WOS:000337170600019
PM 24699624
ER
PT J
AU Rahman, F
Goldstein, DS
AF Rahman, Faisal
Goldstein, David S.
TI Quantitative indices of baroreflex-sympathoneural function: application
to patients with chronic autonomic failure
SO CLINICAL AUTONOMIC RESEARCH
LA English
DT Article
DE Baroreflex; Chronic autonomic failure; Baroreflex-sympathoneural
function; Sympathetic; Autonomic
ID MULTIPLE SYSTEM ATROPHY; SENSITIVITY; INVOLVEMENT; HYPOTENSION; DISEASE
AB Purpose Chronic autonomic failure syndromes such as Parkinson disease with orthostatic hypotension (PD + OH), multiple system atrophy (MSA), and pure autonomic failure (PAF) typically feature arterial baroreflex failure. Identifying baroreflex-sympathoneural failure from hemodynamic responses to the maneuver usually has been qualitative. We report quantitative methods for evaluating baroreflex-sympathoneural function, based on beatto- beat systolic blood pressure (BPs) responses to the Valsalva maneuver.
Method Using the trapezoid rule, we calculated the area under the curve (baroreflex area, BRA) between baseline systolic blood pressure (BPs) and the BPs for each beat in Phase II (BRA-II) and Phase IV (BRA-IV) in 136 autonomic failure patients and 171 controls. The sum of the areas was defined as total BRA (BRA-T). We compared individual values by the BRA approach with those by other measures.
Results Mean values for log BRA-II, BRA-IV, and BRAT were higher in PD + OH, PAF, and MSA than in controls (p < 0.001 each). The log of BRA-T correlated negatively with the fractional orthostatic change in total peripheral resistance (r = -0.41, p < 0.001), fractional orthostatic change in plasma norepinephrine (r = -0.27, p < 0.001), orthostatic change in BPs (r = -0.62, p < 0.001), fall in BPs in Phase II of the Valsalva (r = 0.58, p < 0.001), and log of baroreflex-cardiovagal slope (r = -0.40, p < 0.001). Areas under receiver operating characteristic curves were 0.85 for BRA-T and 0.89 for BRA-IV (p < 0.001).
Conclusion The BRA approach provides quantitative measures of baroreflex-sympathoneural function. Chronic autonomic failure syndromes entail deficiencies of both the cardiovagal and sympathoneural limbs of the arterial baroreflex.
C1 [Rahman, Faisal; Goldstein, David S.] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC-1620,Bldg 10 Room 5N220, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU Intramural NIH HHS
NR 14
TC 3
Z9 3
U1 0
U2 7
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0959-9851
EI 1619-1560
J9 CLIN AUTON RES
JI Clin. Auton. Res.
PD JUN
PY 2014
VL 24
IS 3
BP 103
EP 110
DI 10.1007/s10286-014-0234-1
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AI9SI
UT WOS:000337275500002
PM 24706176
ER
PT J
AU Thomas, DA
AF Thomas, David A.
TI Virtual Reality Research Continues to Progress at the National
Institutes of Health
SO CYBERPSYCHOLOGY BEHAVIOR AND SOCIAL NETWORKING
LA English
DT Editorial Material
C1 NIDA, Div Clin & Behav Res, NIH, Bethesda, MD 20892 USA.
RP Thomas, DA (reprint author), NIDA, Div Clin & Behav Res, NIH, Bethesda, MD 20892 USA.
EM dthomas1@nida.nih.gov
NR 1
TC 0
Z9 0
U1 1
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2152-2715
EI 2152-2723
J9 CYBERPSYCH BEH SOC N
JI Cyberpsychology Behav. Soc. Netw.
PD JUN
PY 2014
VL 17
IS 6
BP 334
EP 334
DI 10.1089/cyber.2014.1509
PG 1
WC Psychology, Social
SC Psychology
GA AI8QA
UT WOS:000337184600003
PM 24892194
ER
PT J
AU Varadkar, P
Despres, D
Kraman, M
Lozier, J
Phadke, A
Nagaraju, K
Mccright, B
AF Varadkar, Prajakta
Despres, Daryl
Kraman, Matthew
Lozier, Julie
Phadke, Aditi
Nagaraju, Kanneboyina
Mccright, Brent
TI The protein phosphatase 2A B56 regulatory subunit is required for heart
development
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE protein phosphatase 2A regulatory B subunit; PP2A; PR61; ventricular
septal defect; mouse heart development; cardiomyocyte
ID SMOOTH-MUSCLE ACTIN; A-SUBUNIT; PP2A; MICE; EXPRESSION; PHOSPHORYLATION;
DIFFERENTIATION; IDENTIFICATION; ALPHA; LOCALIZATION
AB Background: Protein Phosphatase 2A (PP2A) function is controlled by regulatory subunits that modulate the activity of the catalytic subunit and direct the PP2A complex to specific intracellular locations. To study PP2A's role in signal transduction pathways that control growth and differentiation in vivo, a transgenic mouse lacking the B56 regulatory subunit of PP2A was made. Results: Lack of PP2A activity specific to the PP2A-B56 holoenzyme, resulted in the formation of an incomplete ventricular septum and a decrease in the number of ventricular cardiomyocytes. During cardiac development, B56 is expressed in the nucleus of -actinin-positive cardiomyocytes that contain Z-bands. The pattern of B56 expression correlated with the cardiomyocyte apoptosis we observed in B56-deficient mice during mid to late gestation. In addition to the cardiac phenotypes, mice lacking B56 have a decrease in locomotive coordination and gripping strength, indicating that B56 has a role in controlling PP2A activity required for efficient neuromuscular function. Conclusions: PP2A-B56 activity is required for efficient cardiomyocyte maturation and survival. The PP2A B56 regulatory subunit controls PP2A substrate specificity in vivo in a manner that cannot be fully compensated for by other B56 subunits. Developmental Dynamics 243:778-790, 2014. (c) 2014 Wiley Periodicals, Inc.
C1 [Varadkar, Prajakta; Lozier, Julie; Mccright, Brent] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Despres, Daryl] NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA.
[Kraman, Matthew] Univ Cambridge, Cambridge Res Inst, Cambridge, England.
[Phadke, Aditi; Nagaraju, Kanneboyina] Childrens Natl Med Ctr, Washington, DC 20010 USA.
RP Mccright, B (reprint author), 29 Lincoln Dr,Bldg 29B,Room 2NN08, Bethesda, MD 20892 USA.
EM brenton.mccright@fda.hhs.gov
FU US Department of Defense [W81XWH-09-1-0599]
FX The preclinical phenotyping facility at CNMC is supported by a grant
from US Department of Defense grant no. W81XWH-09-1-0599 to Dr.
Nagaraju.
NR 31
TC 5
Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1058-8388
EI 1097-0177
J9 DEV DYNAM
JI Dev. Dyn.
PD JUN
PY 2014
VL 243
IS 6
BP 778
EP 790
DI 10.1002/dvdy.24111
PG 13
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA AJ3SI
UT WOS:000337587200004
PM 24425002
ER
PT J
AU Fourie, NH
Peace, RM
Abey, SK
Sherwin, LB
Rahim-Williams, B
Smyser, PA
Wiley, JW
Henderson, WA
AF Fourie, Nicolaas H.
Peace, Ralph Michael
Abey, Sarah K.
Sherwin, LeeAnne B.
Rahim-Williams, Bridgett
Smyser, Paul A.
Wiley, John W.
Henderson, Wendy A.
TI Elevated circulating miR-150 and miR-342-3p in patients with irritable
bowel syndrome
SO EXPERIMENTAL AND MOLECULAR PATHOLOGY
LA English
DT Article
DE Irritable bowel syndrome; MicroRNA; hsa-miRNA-150; hsa-miR-342-3p
ID CALCIUM-CHANNELS; PAIN SYNDROME; ACTIVATION; INTESTINE; CELLS; IBS
AB Background and aims: MicroRNAs (miRNAs) are small non-coding RNAs, which regulate gene expression and are thus of interest as diagnostic markers, and as clues to etiology and targets of intervention. This pilot study examined whether circulating miRNAs are differentially expressed in patients with IBS.
Methods: miRNA microarrays (NanoString) were run on the whole blood of 43 participants.
Results: hsa-miR-150 and hsa-miR-342-3p were found to be significantly elevated (FDR adjusted p <= 0.05, >= 1.6 fold change) in IBS patients compared to healthy controls. Neither of these miRNAs showed any relationship to race or sex. hsa-miR-150 is associated with inflammatory bowel disorders and pain, and interacts with a protein kinase (AKT2) through which it may affect inflammatory pathways. hsa-miR-342-3p is predicted to interact with mRNAs involved in pain signaling, colonic motility, and smooth muscle function.
Conclusions: This preliminary study reports the association of two miRNAs, detected in whole blood, with IBS. These miRNAs link to pain and inflammatory pathways both of which are thought to be dysregulated in IBS. Larger sample sizes are needed to confirm their importance and potential as biomarkers. Published by Elsevier Inc.
C1 [Fourie, Nicolaas H.; Peace, Ralph Michael; Abey, Sarah K.; Sherwin, LeeAnne B.; Rahim-Williams, Bridgett; Smyser, Paul A.; Henderson, Wendy A.] Natl Inst Nursing Res, Digest Disorders Unit, NIH, DHHS, Bethesda, MD 20892 USA.
[Peace, Ralph Michael] Howard Hughes Med Inst, Natl Inst Hlth Res Scholar, Chevy Chase, MD 20815 USA.
[Rahim-Williams, Bridgett] Natl Inst Minor Hlth & Hlth Dispar, NIH, DHHS, Bethesda, MD 20892 USA.
[Wiley, John W.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
RP Henderson, WA (reprint author), Natl Inst Nursing Res, Digest Disorders Unit, Div Intramural Res, NIH,DHHS, 10 Ctr Dr,Room 2-1341, Bethesda, MD 20892 USA.
EM hendersw@mail.nih.gov
OI Fourie, Nicolaas/0000-0002-5167-8570; Henderson,
Wendy/0000-0003-3924-7118
FU U.S. Department of Health and Human Services; National Institutes of
Health; National Institute of Nursing Research; Division of Intramural
Research [1ZIANR000018-01-04]; Intramural Research Training Awards;
National Institute on Minority Health and Health Disparities
[1K22MD006143-01]; NIH Research Scholar RMP; Burroughs Wellcome Fund
FX The authors acknowledge funding from the U.S. Department of Health and
Human Services, National Institutes of Health, National Institute of
Nursing Research, Division of Intramural Research to Wendy A. Henderson,
1ZIANR000018-01-04; Intramural Research Training Awards to Nicolaas H.
Fourie, Ralph M. Peace, Sarah K. Abey, Leeanne B. Sherwin, and Paul A.
Smyser; Howard Hughes-NIH Research Scholar RMP; Special support from the
Burroughs Wellcome Fund to Ralph M. Peace. Training award to Bridgett
Rahim-Williams supported by the National Institute on Minority Health
and Health Disparities (1K22MD006143-01).
NR 20
TC 25
Z9 25
U1 2
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4800
EI 1096-0945
J9 EXP MOL PATHOL
JI Exp. Mol. Pathol.
PD JUN
PY 2014
VL 96
IS 3
BP 422
EP 425
DI 10.1016/j.yexmp.2014.04.009
PG 4
WC Pathology
SC Pathology
GA AI8YJ
UT WOS:000337212600022
PM 24768587
ER
PT J
AU Ocean, AJ
Christos, P
Sparano, JA
Shah, MA
Yantiss, RK
Cheng, J
Lin, J
Papetti, M
Matulich, D
Schnoll-Sussman, F
Besanceney-Webler, C
Xiang, J
Ward, M
Dilts, KT
Keresztes, R
Holloway, S
Chen, EX
Wright, JJ
Lane, ME
AF Ocean, Allyson J.
Christos, Paul
Sparano, Joseph A.
Shah, Manish A.
Yantiss, Rhonda K.
Cheng, Jonathan
Lin, Juan
Papetti, Michael
Matulich, Dan
Schnoll-Sussman, Felice
Besanceney-Webler, Christen
Xiang, Jenny
Ward, Maureen
Dilts, Kaili Temple
Keresztes, Roger
Holloway, Shannon
Chen, Eric X.
Wright, John J.
Lane, Maureen E.
TI Phase II trial of bortezomib alone or in combination with irinotecan in
patients with adenocarcinoma of the gastroesophageal junction or stomach
SO INVESTIGATIONAL NEW DRUGS
LA English
DT Article
DE Bortezomib; Proteasome inhibitor; Irinotecan; Gastroesophageal junction;
Adenocarcinoma; Combination therapy; Microarray
ID PROTEASOME INHIBITOR PS-341; FACTOR-KAPPA-B; COLORECTAL-CANCER;
GASTRIC-CANCER; GROWTH; APOPTOSIS; MYELOMA
AB Purpose To determine the effectiveness of bortezomib plus irinotecan and bortezomib alone in patients with advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma. We also sought to explore the effect of these therapeutics on tumor and normal gene expression in vivo. Methods Forty-one patients with advanced GEJ (89 %) or gastric (11 %) adenocarcinoma received bortezomib (1.3 mg/m(2) days 1, 4, 8, 11) plus irinotecan (125 mg/m(2) days 1, 8) every 21 days as first line therapy (N = 29), or bortezomib alone as second line therapy (N = 12). The trial was designed to detect a 40 % response rate for the combination, and 20 % response rate for bortezomib alone. Affymetrix HU133A gene chip arrays were used for gene expression studies. Results Objective response occurred in 3 of 29 patients (10 %, 95 % confidence intervals [CI] 2 %, 27 %) treated with bortezomib plus irinotecan, and in 1 of 12 patients (8 %, 95 % CI 0 %, 39 %) with bortezomib alone. Due to the limited number of responders, there were no significant correlations with response found in the gene expression profiles of 12 patients whose tumors were sampled before and 24 h after therapy with bortezomib alone (N = 2) or the combination (N = 10). Conclusions We conclude that bortezomib is not effective for the treatment of advanced adenocarcinoma of the GEJ or stomach, whether used alone or in combination with irinotecan, in an unselected patient population.
C1 [Ocean, Allyson J.; Christos, Paul; Shah, Manish A.; Yantiss, Rhonda K.; Schnoll-Sussman, Felice; Besanceney-Webler, Christen; Xiang, Jenny; Ward, Maureen; Dilts, Kaili Temple; Holloway, Shannon; Lane, Maureen E.] Weill Cornell Med Coll, New York, NY 10021 USA.
[Sparano, Joseph A.; Papetti, Michael] Montefiore Med Ctr, Bronx, NY 10467 USA.
[Sparano, Joseph A.; Lin, Juan; Papetti, Michael] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Cheng, Jonathan] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Matulich, Dan] Columbia Univ, New York, NY USA.
[Keresztes, Roger] SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA.
[Chen, Eric X.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Wright, John J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Lane, ME (reprint author), Weill Cornell Med Coll, New York, NY 10021 USA.
EM mel2009@med.cornell.edu
FU National Institute of Health, National Cancer Institute [N01-CM-62204,
P30CA013330]
FX The authors acknowledge the late Dr. Scott Wadler, our colleague and
friend, who conceived of and designed this trial and founded the New
York Cancer Consortium. He will be remembered for his skills as
clinician, scholar, and mentor. This work was supported by the National
Institute of Health, National Cancer Institute (N01-CM-62204, PI: Joseph
A. Sparano and P30CA013330, PI: David Goldman, MD).
NR 19
TC 4
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U1 3
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0167-6997
EI 1573-0646
J9 INVEST NEW DRUG
JI Invest. New Drugs
PD JUN
PY 2014
VL 32
IS 3
BP 542
EP 548
DI 10.1007/s10637-014-0070-0
PG 7
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA AI7OU
UT WOS:000337084000017
PM 24526575
ER
PT J
AU Habibi, M
Chahal, H
Opdahl, A
Gjesdal, O
Helle-Valle, TM
Heckbert, SR
McClelland, R
Wu, CL
Shea, S
Hundley, G
Bluemke, DA
Lima, JAC
AF Habibi, Mohammadali
Chahal, Harjit
Opdahl, Anders
Gjesdal, Ola
Helle-Valle, Thomas M.
Heckbert, Susan R.
McClelland, Robyn
Wu, Colin
Shea, Steven
Hundley, Gregory
Bluemke, David A.
Lima, Joao A. C.
TI Association of CMR-Measured LA Function With Heart Failure Development
Results From the MESA Study Results From the MESA Study
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE feature-tracking MRI; heart failure; left atrial function; left atrial
strain
ID LEFT ATRIAL VOLUME; CARDIOVASCULAR MAGNETIC-RESONANCE; SPECKLE TRACKING
ECHOCARDIOGRAPHY; VENTRICULAR SYSTOLIC FUNCTION; PRESERVED EJECTION
FRACTION; MYOCARDIAL FEATURE TRACKING; END-DIASTOLIC PRESSURE;
2-DIMENSIONAL ECHOCARDIOGRAPHY; GREATER-THAN-OR-EQUAL-TO-65 YEARS;
DEFORMATION ANALYSIS
AB OBJECTIVES The goal of this study was to assess the association between left atrial (LA) volume and function measured with feature-tracking cardiac magnetic resonance (CMR) and development of heart failure (HF) in asymptomatic individuals.
BACKGROUND. Whether alterations of LA structure and function precede or follow HF development remains incompletely understood. We hypothesized that significant alterations of LA deformation and architecture precede the development of HF in the general population.
METHODS In a case-control study nested in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA volume and function assessed using CMR feature-tracking were compared between 112 participants with incident HF (mean age 68.4 +/- 8.2 years; 66% men) and 224 age- and sex-matched controls (mean age 67.7 +/- 8.9 years; 66% men). Participants were followed up for 8 years. All individuals were in normal sinus rhythm at the time of imaging, without any significant valvular abnormalities and free of clinical cardiovascular diseases.
RESULTS Individuals with incident HF had greater maximal and minimal LA volume indexes (LAVI(min)) than control subjects (40 +/- 13 mm(3)/m(2) vs. 33 +/- 10 mm(3)/m(2) [p < 0.001] for maximal LA index and 25 +/- 11 mm(3)/m(2) vs. 17 +/- 7 mm(3)/m(2) [p < 0.001] for LAVI(min)). The HF case subjects also had smaller global peak longitudinal atrial strain (PLAS) (25 +/- 11% vs. 38 +/- 16%; p < 0.001) and lower LA emptying fraction (40 +/- 11% vs. 48 +/- 9%; p < 0.001) at baseline. After adjustment for traditional cardiovascular risk factors, left ventricular mass, and N-terminal pro-B-type natriuretic peptide, global PLAS (odds ratio: 0.36 per SD [95% confidence interval: 0.22 to 0.60]) and LAVI(min) (odds ratio: 1.65 per SD [95% confidence interval: 1.04 to 2.63]) were independently associated with incident HF.
CONCLUSIONS Deteriorations in LA structure and function preceded development of HF. Lower global PLAS and higher LAVI(min), measured using CMR feature-tracking, were independent markers of incident HF in a multiethnic population of asymptomatic individuals. (C) 2014 by the American College of Cardiology Foundation
C1 [Habibi, Mohammadali; Chahal, Harjit; Opdahl, Anders; Gjesdal, Ola; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Dept Med, Div Cardiol, Baltimore, MD 21287 USA.
[Opdahl, Anders; Gjesdal, Ola; Helle-Valle, Thomas M.] Univ Oslo, Dept Cardiol, Oslo, Norway.
[Heckbert, Susan R.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[McClelland, Robyn] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Wu, Colin] NHLBI, Off Biostat, Bethesda, MD 20892 USA.
[Shea, Steven] Columbia Univ, Med Ctr, New York, NY USA.
[Hundley, Gregory] Wake Forest Univ, Sch Med, Cardiol Sect, Winston Salem, NC 27109 USA.
[Bluemke, David A.] NIH, Bethesda, MD 20892 USA.
RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, Dept Med, Div Cardiol, Blalock 524D,600 North Wolfe St, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
RI Gjesdal, Ola/C-1941-2015; Opdahl, Anders/I-7580-2015
OI Opdahl, Anders/0000-0002-0599-592X
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95168]; National Center for Research Resources,
National Institutes of Health [UL1-RR-024156, UL1-RR-025005]
FX This research was supported by contracts N01-HC-95159 through
N01-HC-95166 and N01-HC-95168 from the National Heart, Lung, and Blood
Institute and UL1-RR-024156 and UL1-RR-025005 from the National Center
for Research Resources, National Institutes of Health. All authors have
reported that they have no relationships relevant to the contents of
this paper to disclose. Sherif Nagueh, MD, served as Guest Editor for
this paper.
NR 45
TC 27
Z9 28
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
EI 1876-7591
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD JUN
PY 2014
VL 7
IS 6
BP 570
EP 579
DI 10.1016/j.jcmg.2014.01.016
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA AJ0HP
UT WOS:000337331800005
PM 24813967
ER
PT J
AU Shaw, LJ
Berman, DS
Picard, MH
Friedrich, MG
Kwong, RY
Stone, GW
Senior, R
Min, JK
Hachamovitch, R
Scherrer-Crosbie, M
Mieres, JH
Marwick, TH
Phillips, LM
Chaudhry, FA
Pellikka, PA
Slomka, P
Arai, AE
Iskandrian, AE
Bateman, TM
Heller, GV
Miller, TD
Nagel, E
Goyal, A
Borges-Neto, S
Boden, WE
Reynolds, HR
Hochman, JS
Maron, DJ
Douglas, PS
AF Shaw, Leslee J.
Berman, Daniel S.
Picard, Michael H.
Friedrich, Matthias G.
Kwong, Raymond Y.
Stone, Gregg W.
Senior, Roxy
Min, James K.
Hachamovitch, Rory
Scherrer-Crosbie, Marielle
Mieres, Jennifer H.
Marwick, Thomas H.
Phillips, Lawrence M.
Chaudhry, Farooq A.
Pellikka, Patricia A.
Slomka, Piotr
Arai, Andrew E.
Iskandrian, Ami E.
Bateman, Timothy M.
Heller, Gary V.
Miller, Todd D.
Nagel, Eike
Goyal, Abhinav
Borges-Neto, Salvador
Boden, William E.
Reynolds, Harmony R.
Hochman, Judith S.
Maron, David J.
Douglas, Pamela S.
CA ISCHEMIA Trial Investigators
TI Comparative Definitions for Moderate-Severe Ischemia in Stress Nuclear,
Echocardiography, and Magnetic Resonance Imaging
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE cardiac imaging; ischemia; prognosis
ID CORONARY-ARTERY-DISEASE; EMISSION COMPUTED-TOMOGRAPHY; VENTRICULAR
EJECTION FRACTION; INCREMENTAL PROGNOSTIC VALUE; OPTIMAL MEDICAL
THERAPY; MYOCARDIAL-PERFUSION SCINTIGRAPHY; AMERICAN-HEART-ASSOCIATION;
EXERCISE ECHOCARDIOGRAPHY; RISK STRATIFICATION; REVASCULARIZATION
PROCEDURES
AB The lack of standardized reporting of the magnitude of ischemia on noninvasive imaging contributes to variability in translating the severity of ischemia across stress imaging modalities. We identified the risk of coronary artery disease (CAD) death or myocardial infarction (MI) associated with >= 10% ischemic myocardium on stress nuclear imaging as the risk threshold for stress echocardiography and cardiac magnetic resonance. A narrative review revealed that >= 10% ischemic myocardium on stress nuclear imaging was associated with a median rate of CAD death or MI of 4.9%/year (interquartile range: 3.75% to 5.3%). For stress echocardiography, >= 3 newly dysfunctional segments portend a median rate of CAD death or MI of 4.5%/year (interquartile range: 3.8% to 5.9%). Although imprecisely delineated, moderate-severe ischemia on cardiac magnetic resonance may be indicated by >= 4 of 32 stress perfusion defects or >= 3 dobutamine-induced dysfunctional segments. Risk-based thresholds can define equivalent amounts of ischemia across the stress imaging modalities, which will help to translate a common understanding of patient risk on which to guide subsequent management decisions. (C) 2014 by the American College of Cardiology Foundation
C1 [Shaw, Leslee J.; Goyal, Abhinav] Emory Univ, Dept Med, Div Cardiol, Atlanta, GA 30324 USA.
[Berman, Daniel S.] Cedars Sinai Med Ctr, Dept Med, Div Cardiac Imaging Nucl Cardiol, Los Angeles, CA 90048 USA.
[Picard, Michael H.; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Friedrich, Matthias G.] Montreal Heart Inst, Dept Med, Div Cardiol, Montreal, PQ H1T 1C8, Canada.
[Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA.
[Stone, Gregg W.] Columbia Univ, New York Presbyterian Hosp, Med Ctr, Dept Med,Div Cardiol, New York, NY USA.
[Senior, Roxy] Univ London Imperial Coll Sci Technol & Med, Dept Cardiovasc Med, Div Cardiol, London, England.
[Min, James K.] Weill Cornell Med Coll, Dept Cardiovasc Med, Div Radiol, New York, NY USA.
[Hachamovitch, Rory] Cleveland Clin Fdn, Dept Cardiovasc Med, Div Cardiol, Cleveland, OH 44195 USA.
[Mieres, Jennifer H.] North Shore Long Isl Jewish Hosp, Dept Med, Div Cardiol, Manhasset, NY USA.
[Marwick, Thomas H.] Menzies Res Inst Tasmania, Dept Med, Div Cardiol, Hobart, Tas, Australia.
[Phillips, Lawrence M.; Reynolds, Harmony R.; Hochman, Judith S.] NYU, Med Ctr, Dept Med, Div Cardiol, New York, NY 10016 USA.
[Chaudhry, Farooq A.] Icahn Sch Med Mt Sinai, Dept Med, Div Cardiol, New York, NY USA.
[Pellikka, Patricia A.; Miller, Todd D.] Mayo Clin, Dept Med, Div Cardiovasc Med, Rochester, MN USA.
[Slomka, Piotr] Cedars Sinai Med Ctr, Dept Med, Div Imaging, Los Angeles, CA 90048 USA.
[Arai, Andrew E.] NHLBI, Dept Med, Div Cardiovasc Med, NIH, Bethesda, MD 20892 USA.
[Iskandrian, Ami E.] Univ Alabama Birmingham, Dept Radiol, Div Cardiovasc Dis, Birmingham, AL USA.
[Bateman, Timothy M.] St Lukes Mid Amer Heart Inst, Dept Med, Div Cardiol, Kansas City, MO USA.
[Heller, Gary V.] Hartford Hosp, Hartford, CT 06115 USA.
[Nagel, Eike] Kings Coll London, Dept Med, Div Cardiovasc Med, London, England.
[Borges-Neto, Salvador] Duke Clin Res Inst, Dept Nucl Med, Div Radiol, Durham, NC USA.
[Boden, William E.] Samuel S Stratton VA Med Ctr, Dept Med, Div Cardiol, Albany, NY USA.
[Maron, David J.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
[Douglas, Pamela S.] Duke Clin Res Inst, Dept Med, Div Cardiol, Durham, NC USA.
RP Shaw, LJ (reprint author), Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, 1462 Clifton Rd NE,Room 529, Atlanta, GA 30324 USA.
EM lshaw3@emory.edu
RI Nagel, Eike/C-6903-2008;
OI Nagel, Eike/0000-0002-6044-950X; Reynolds, Harmony/0000-0003-0284-0655;
Picard, Michael/0000-0002-9264-3243; Hochman, Judith/0000-0002-5889-5981
FU Astellas; Bracco Diagnostics Inc.; GE Healthcare; Philips Healthcare;
Siemens; Lantheus Medical Imaging; Spectrum Dynamics; Bayer HealthCare;
GlaxoSmithKline
FX Dr. Shaw has received research support from Astellas and Bracco
Diagnostics Inc. Dr. Friedrich is a board member, advisor, and
shareholder for Circle Cardiovascular Imaging. Dr. Senior is a member of
the speaker's bureau for and has received honoraria from Bracco
Diagnostics Inc. and Philips Healthcare. Dr. Min is a member of the
medical advisory board and speaker's bureau for and has received
research support from GE Healthcare; is a member of the medical advisory
board for Arineta Ltd.; has received research support from Philips
Healthcare; and holds equity interest in TC3 and MDDX. Dr. Arai has
received research support from Siemens. Dr. Iskandrian is a member of
the advisory committee for Rapidscan Pharma. Dr. Bateman is a member of
the advisory committee for and receives research support from Astellas,
Lantheus Medical Imaging, GE Healthcare, and Spectrum Dynamics. Dr.
Miller is a consultant for Astellas. Dr. Nagel has received research
support from Philips Healthcare and Bayer HealthCare. Dr. Borges-Neto is
a member of the speaker's bureau and advisory board for and has received
grant support from Astellas and is a member of the advisory board for
and has received grant support from GE Healthcare. Dr. Hochman has
received a consulting fee and modest honoraria from GlaxoSmithKline. All
other authors have reported that they have no relationships relevant to
the contents of this paper to disclose.
NR 65
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Z9 34
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
EI 1876-7591
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD JUN
PY 2014
VL 7
IS 6
BP 593
EP 604
DI 10.1016/j.jcmg.2013.10.021
PG 12
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA AJ0HP
UT WOS:000337331800008
PM 24925328
ER
PT J
AU Moissoglu, K
Kiessling, V
Wan, C
Hoffman, BD
Norambuena, A
Tamm, LK
Schwartz, MA
AF Moissoglu, Konstadinos
Kiessling, Volker
Wan, Chen
Hoffman, Brenton D.
Norambuena, Andres
Tamm, Lukas K.
Schwartz, Martin Alexander
TI Regulation of Rac1 translocation and activation by membrane domains and
their boundaries
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Rac; FRET; Lipid rafts; Supported bilayers; Domain boundaries
ID LIPID RAFTS; IN-VIVO; DISSOCIATION; PROTEINS; DYNAMICS; GTPASES; PLANAR;
RHOGDI; CELLS; FRET
AB The activation of Rac1 and related Rho GTPases involves dissociation from Rho GDP-dissociation inhibitor proteins and translocation to membranes, where they bind effectors. Previous studies have suggested that the binding of Rac1 to membranes requires, and colocalizes with, cholesterol-rich liquid-ordered (lo) membrane domains (lipid rafts). Here, we have developed a fluorescence resonance energy transfer ( FRET) assay that robustly detects Rac1 membrane targeting in living cells. Surprisingly, FRET with acceptor constructs that were targeted to either raft or non-raft areas indicated that Rac1 was present in both regions. Functional studies showed that Rac1 localization to non-raft regions decreased GTP loading as a result of inactivation by GTPase-activating proteins. In vitro, Rac1 translocation to supported lipid bilayers also required lo domains, yet Rac1 was concentrated in the liquiddisordered (ld) phase. Single-molecule analysis demonstrated that translocation occurred preferentially at lo-ld boundaries. These results, therefore, suggest that Rac1 translocates to the membrane at domain boundaries, then diffuses into raft and non-raft domains, which controls interactions. These findings resolve discrepancies in our understanding of Rac biology and identify novel mechanisms by which lipid rafts modulate Rho GTPase signaling.
C1 [Moissoglu, Konstadinos; Hoffman, Brenton D.; Norambuena, Andres; Schwartz, Martin Alexander] Univ Virginia, Robert M Berne Cardiovasc Res Ctr, Charlottesville, VA 22908 USA.
[Moissoglu, Konstadinos; Hoffman, Brenton D.; Norambuena, Andres; Schwartz, Martin Alexander] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
[Kiessling, Volker; Wan, Chen; Tamm, Lukas K.] Univ Virginia, Ctr Membrane Biol, Charlottesville, VA 22908 USA.
[Kiessling, Volker; Wan, Chen; Tamm, Lukas K.] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA.
[Schwartz, Martin Alexander] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA.
RP Moissoglu, K (reprint author), NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM konstadinos.moissoglu@nih.gov; martin.schwartz@yale.edu
FU National Institutes of Health [R01 GM47214, U54 GM64346, P01 GM51329,
R37 AI30577]
FX This work was supported by the National Institutes of Health [grant
numbers R01 GM47214, U54 GM64346 to M.A.S., P01 GM51329, R37 AI30577 to
L. K. T.]. Deposited in PMC for release after 12 months.
NR 27
TC 10
Z9 10
U1 1
U2 6
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD JUN 1
PY 2014
VL 127
IS 11
BP 2565
EP 2576
DI 10.1242/jcs.149088
PG 12
WC Cell Biology
SC Cell Biology
GA AI9AF
UT WOS:000337217400018
PM 24695858
ER
PT J
AU Davis, AS
Richter, A
Becker, S
Moyer, JE
Sandouk, A
Skinner, J
Taubenberger, JK
AF Davis, A. Sally
Richter, Anke
Becker, Steven
Moyer, Jenna E.
Sandouk, Aline
Skinner, Jeff
Taubenberger, Jeffery K.
TI Characterizing and Diminishing Autofluorescence in Formalin-fixed
Paraffin-embedded Human Respiratory Tissue
SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
LA English
DT Article
DE autofluorescence; formalin-fixation; paraffin-embedded tissue;
immunohistochemistry; immunofluorescence; human; respiratory; confocal
microscopy
ID BACKGROUND AUTOFLUORESCENCE; IMMUNOFLUORESCENCE; REDUCTION;
FLUORESCENCE; MICROSCOPY; COLLAGEN; CELLS
AB Tissue autofluorescence frequently hampers visualization of immunofluorescent markers in formalin-fixed paraffin-embedded respiratory tissues. We assessed nine treatments reported to have efficacy in reducing autofluorescence in other tissue types. The three most efficacious were Eriochrome black T, Sudan black B and sodium borohydride, as measured using white light laser confocal (2) (multi-lambda) analysis. We also assessed the impact of steam antigen retrieval and serum application on human tracheal tissue autofluorescence. Functionally fitting this (2) data to 2-dimensional Gaussian surfaces revealed that steam antigen retrieval and serum application contribute minimally to autofluorescence and that the three treatments are disparately efficacious. Together, these studies provide a set of guidelines for diminishing autofluorescence in formalin-fixed paraffin-embedded human respiratory tissue. Additionally, these characterization techniques are transferable to similar questions in other tissue types, as demonstrated on frozen human liver tissue and paraffin-embedded mouse lung tissue fixed in different fixatives.
C1 [Davis, A. Sally; Moyer, Jenna E.; Sandouk, Aline; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, NIH, Bethesda, MD 20892 USA.
[Becker, Steven] NIAID, Bioimaging Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
[Skinner, Jeff] NIAID, Immunogenet Lab, Div Intramural Res, Bethesda, MD 20892 USA.
[Richter, Anke] Naval Postgrad Sch, Def Resources Management Inst, Grad Sch Int Studies, Monterey, CA USA.
[Davis, A. Sally] N Carolina State Univ, Coll Vet Med, Dept Populat Hlth & Pathobiol, Raleigh, NC USA.
RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, NIH, 33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
EM taubenbergerj@niaid.nih.gov
OI Davis, Anne/0000-0001-5711-3936; Skinner, Jeff/0000-0001-5697-0442
FU NIH; NIAID
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This research
was supported by the intramural research funds of the NIH and the NIAID.
NR 20
TC 4
Z9 4
U1 4
U2 19
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0022-1554
EI 1551-5044
J9 J HISTOCHEM CYTOCHEM
JI J. Histochem. Cytochem.
PD JUN
PY 2014
VL 62
IS 6
BP 405
EP 423
DI 10.1369/0022155414531549
PG 19
WC Cell Biology
SC Cell Biology
GA AJ3WN
UT WOS:000337598700002
PM 24722432
ER
PT J
AU Rizvi, SM
Salam, N
Geng, J
Qi, Y
Bream, JH
Duggal, P
Hussain, SK
Martinson, J
Wolinsky, SM
Carrington, M
Raghavan, M
AF Rizvi, Syed Monem
Salam, Nasir
Geng, Jie
Qi, Ying
Bream, Jay H.
Duggal, Priya
Hussain, Shehnaz K.
Martinson, Jeremy
Wolinsky, Steven M.
Carrington, Mary
Raghavan, Malini
TI Distinct Assembly Profiles of HLA-B Molecules
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MHC CLASS-I; IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIGEN PRESENTATION;
MONOCLONAL-ANTIBODIES; PEPTIDE PRESENTATION; HLA-B44 SUPERTYPE;
HEAVY-CHAIN; TAPASIN; COMPLEX; HIV-1
AB MHC class I polymorphisms are known to influence outcomes in a number of infectious diseases, cancers, and inflammatory diseases. Human MHC class I H chains are encoded by the HLA-A, HLA-B, and HLA-C genes. These genes are highly polymorphic, with the HLA-B locus being the most variable. Each HLA class I protein binds to a distinct set of peptide Ags, which are presented to CD8(+) T cells. HLA-disease associations have been shown in some cases to link to the peptide-binding characteristics of individual HLA class I molecules. In this study, we show that polymorphisms at the HLA-B locus profoundly influence the assembly characteristics of HLA-B molecules and the stabilities of their peptide-deficient forms. In particular, dependence on the assembly factor tapasin is highly variable, with frequent occurrence of strongly tapasin-dependent or independent allotypes. Several polymorphic HLA-B residues located near the C-terminal end of the peptide are key determinants of tapasin-independent assembly. In vitro refolded forms of tapasin-independent allotypes assemble more readily with peptides compared to tapasin-dependent allotypes that belong to the same supertype, and, during refolding, reduced aggregation of tapasin-independent allotypes is observed. Paradoxically, in HIVinfected individuals, greater tapasin-independent HLA-B assembly confers more rapid progression to death, consistent with previous findings that some HLA-B allotypes shown to be tapasin independent are associated with rapid progression to multiple AIDS outcomes. Together, these findings demonstrate significant variations in the assembly of HLA-B molecules and indicate influences of HLA-B-folding patterns upon infectious disease outcomes.
C1 [Rizvi, Syed Monem; Salam, Nasir; Geng, Jie; Raghavan, Malini] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
[Qi, Ying; Carrington, Mary] Frederick Natl Lab Canc Res, Leidos Biomed Res, Frederick, MD 21702 USA.
[Qi, Ying; Carrington, Mary] MIT, Ragon Inst MGH, Cambridge, MA 02139 USA.
[Qi, Ying; Carrington, Mary] Harvard Univ, Cambridge, MA 02139 USA.
[Bream, Jay H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
[Duggal, Priya] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Hussain, Shehnaz K.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA.
[Hussain, Shehnaz K.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.
[Martinson, Jeremy] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA.
[Wolinsky, Steven M.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA.
RP Raghavan, M (reprint author), Univ Michigan, 5641 Med Sci Bldg 2,1150 West Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM malinir@umich.edu
RI Salam, Nasir/C-8049-2015;
OI Salam, Nasir/0000-0001-9133-1304; Martinson, Jeremy/0000-0003-4673-7238
FU National Institutes of Health [AI044115]; University of Michigan Medical
School Protein Folding Disease Initiative; Frederick National Laboratory
for Cancer Research [HHSN261200800001E]; National Institute of Allergy
and Infectious Diseases; National Cancer Institute
FX This work was supported by National Institutes of Health Grant AI044115
(to M. R.) and in part by the University of Michigan Medical School
Protein Folding Disease Initiative. This work utilized the DNA
Sequencing and Hybridoma Cores of the University of Michigan Medical
School. This work was also supported in part by Frederick National
Laboratory for Cancer Research Contract HHSN261200800001E and by the
Intramural Research Program of the National Institutes of Health,
Frederick National Laboratory, Center for Cancer Research. Some data in
this manuscript were collected by the Multicenter AIDS Cohort Study
(MACS) with centers (Principal Investigators) at: Johns Hopkins
University Bloomberg School of Public Health (Joseph Margolick),
U01-AI35042; Northwestern University (S. M. W.), U01-AI35039; University
of California, Los Angeles (Roger Detels), U01-AI35040; University of
Pittsburgh (Charles Rinaldo), U01-AI35041; the Center for Analysis and
Management of MACS and Johns Hopkins University Bloomberg School of
Public Health (Lisa Jacobson), UM1-AI35043. The MACS is funded primarily
by the National Institute of Allergy and Infectious Diseases, with
additional cofunding from the National Cancer Institute.
NR 58
TC 15
Z9 15
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2014
VL 192
IS 11
BP 4967
EP 4976
DI 10.4049/jimmunol.1301670
PG 10
WC Immunology
SC Immunology
GA AI8MT
UT WOS:000337171800007
PM 24790147
ER
PT J
AU Wu, ZL
Chen, XC
Liu, F
Chen, W
Wu, P
Wieschhaus, AJ
Chishti, AH
Roche, PA
Chen, WM
Lin, TJ
AF Wu, Zhengli
Chen, Xiaochun
Liu, Fang
Chen, Wei
Wu, Ping
Wieschhaus, Adam J.
Chishti, Athar H.
Roche, Paul A.
Chen, Wei-Min
Lin, Tong-Jun
TI Calpain-1 Contributes to IgE-Mediated Mast Cell Activation
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID KINASE-C-ALPHA; KAPPA-B-ALPHA; MU-CALPAIN; CALCIUM; DEGRADATION;
PLATELETS; SNAP-23; DEGRANULATION; NEURONS; PATHWAY
AB Mast cells play a central role in allergy through secretion of both preformed and newly synthesized mediators. Mast cell mediator secretion is controlled by a complex network of signaling events. Despite intensive studies, signaling pathways in the regulation of Mast cell mediator secretion remain incompletely defined. In this study, we examined the role of calpain in IgE-dependent mast cell activation. IgE-mediated activation of mouse bone marrow-derived mast cells enhanced calpain activity. Inhibition of calpain activity by a number of calpain inhibitors reduced IgE-mediated mast cell degranulation both in vitro and in vivo. Calpain inhibitors blocked IgE-mediated TNF and IL-6 production in vitro and reduced late- phase allergic response in vivo. Importantly, mouse calpain-1 null bone marrow- derived mast cells showed reduced IgE-mediated mast cell degranulation in vitro and in vivo, diminished cytokine and chemokine production in vitro, and impaired late- phase allergic response in vivo. Further studies revealed that calpain-1 deficiency led to specific attenuation of IkB-NF-kB pathway and IKK-SNAP23 pathway, whereas calcium flux, MAPK, Akt, and NFAT pathway proceed normally in IgE- activated calpain-1 null mast cells. Thus, calpain-1 is identified as a novel regulator in IgE- mediated mast cell activation and could serve as a potential therapeutic target for the management of allergic inflammation.
C1 [Wu, Zhengli; Liu, Fang; Wu, Ping; Lin, Tong-Jun] Dalhousie Univ, IWK Hlth Ctr, Dept Microbiol & Immunol, Halifax, NS B3K 6R8, Canada.
[Wu, Zhengli; Liu, Fang; Wu, Ping; Lin, Tong-Jun] Dalhousie Univ, IWK Hlth Ctr, Dept Pediat, Halifax, NS B3K 6R8, Canada.
[Chen, Xiaochun] Fujian Med Univ, Affiliated Union Hosp, Dept Neurol, Fuzhou 350001, Fujian, Peoples R China.
[Chen, Wei] Jilin Univ, Coll Vet Med, Changchun 130062, Jilin, Peoples R China.
[Wieschhaus, Adam J.; Chishti, Athar H.] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Dept Mol Physiol & Pharmacol, Boston, MA 02111 USA.
[Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Wei-Min] Fujian Prov Hosp, Dept Hematol, Fuzhou 350000, Fujian, Peoples R China.
RP Lin, TJ (reprint author), IWK Hlth Ctr, Dept Pediat, 5850 Univ Ave, Halifax, NS B3K 6R8, Canada.
EM chenweiming@medmail.com.cn; tong-jun.lin@dal.ca
FU Canadian Institutes of Health Research; Izaak Walton Killam Health
Center; National Institutes of Health Grant [NIH-HL089517]
FX This work was supported by grants from the Canadian Institutes of Health
Research and the Izaak Walton Killam Health Center (to T.-J.L.) and
National Institutes of Health Grant NIH-HL089517 (to A.H.C.). Z.W. is a
recipient of a postdoctoral fellowship from the Izaak Walton Killam
Health Center.
NR 41
TC 5
Z9 5
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2014
VL 192
IS 11
BP 5130
EP 5139
DI 10.4049/jimmunol.1301677
PG 10
WC Immunology
SC Immunology
GA AI8MT
UT WOS:000337171800024
PM 24760147
ER
PT J
AU Xu, LL
Li, G
Wang, J
Fan, YL
Wan, ZP
Zhang, SS
Shaheen, S
Li, J
Wang, L
Yue, C
Zhao, Y
Wang, F
Brzostowski, J
Chen, YH
Zheng, WJ
Liu, WL
AF Xu, Liling
Li, Gen
Wang, Jing
Fan, Yilin
Wan, Zhengpeng
Zhang, Shaosen
Shaheen, Samina
Li, Jing
Wang, Li
Yue, Cai
Zhao, Yan
Wang, Fei
Brzostowski, Joseph
Chen, Ying-Hua
Zheng, Wenjie
Liu, Wanli
TI Through an ITIM-Independent Mechanism the Fc gamma RIIB Blocks B Cell
Activation by Disrupting the Colocalized Microclustering of the B Cell
Receptor and CD19
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; FAMILY-BASED ASSOCIATION; ANTIGEN
RECEPTOR; LIPID RAFTS; CD19/CD21 COMPLEX; GENETIC SUSCEPTIBILITY;
SIGNAL-TRANSDUCTION; AUTOIMMUNE-DISEASE; IMMUNE SYNAPSE; POLYMORPHISM
AB B cell activation is regulated through the interplay of the BCR with the inhibitory coreceptor Fc gamma RIIB and the activating coreceptor CD19. Recent studies suggest that Ag-driven BCR microclusters are efficiently converted to a signaling active state on colocalization with CD19 microclusters. Using total internal reflection fluorescence microscopy-based, high-resolution, high-speed live-cell and molecule imaging approaches, we show that when co-ligated to the BCR, the Fc gamma RIIB can inhibit B cell activation by blocking the colocalization of BCR and CD19 microclusters within the B cell immunological synapse. Remarkably, this inhibitory function of FcgRIIB is dependent not on its well-characterized ITIM-containing cytoplasmic domain, but its transmembrane domain. Indeed, human primary B cells from systemic lupus erythematosus patients homozygous for gene encoding the loss-of-function transmembrane domain mutant Fc gamma RIIB-I232T fail to block the synaptic colocalization of the BCR with CD19, leading to dysregulated recruitment of downstream signaling molecule p-PI3K to membrane proximal signalosome. This inhibitory function of Fc gamma RIIB in impairing the spatial-temporal colocalization of BCR and CD19 microclusters in the B cell immunological synapse may help explain the hyper-reactive features of systemic lupus erythematosus patient B cells in reported studies. These observations may also provide new targets for therapies for systemic autoimmune disease.
C1 [Xu, Liling; Li, Gen; Wang, Jing; Fan, Yilin; Wan, Zhengpeng; Zhang, Shaosen; Shaheen, Samina; Chen, Ying-Hua; Liu, Wanli] Tsinghua Univ, Sch Life Sci, Minist Educ, Key Lab Prot Sci, Beijing 100084, Peoples R China.
[Xu, Liling; Li, Gen; Li, Jing; Wang, Li; Yue, Cai; Zhao, Yan; Zheng, Wenjie] Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Rheumatol & Clin Immunol, Beijing 100730, Peoples R China.
[Xu, Liling; Li, Gen; Li, Jing; Wang, Li; Yue, Cai; Zhao, Yan; Zheng, Wenjie] Chinese Acad Med Sci, Beijing 100730, Peoples R China.
[Li, Jing; Wang, Li; Yue, Cai; Zhao, Yan; Zheng, Wenjie] Minist Educ, Key Lab Rheumatol & Clin Immunol, Beijing 100730, Peoples R China.
[Wang, Fei] Chinese Acad Sci, Chengdu Inst Biol, Chengdu 610041, Peoples R China.
[Brzostowski, Joseph] NIAID, Immunogenet Lab, Imaging Facil, NIH, Rockville, MD 20852 USA.
[Liu, Wanli] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Collaborat Innovat Ctr Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China.
RP Liu, WL (reprint author), Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
EM chenyh@mail.tsinghua.edu.cn; wenjzheng@gmail.com;
liuwanli@biomed.tsinghua.edu.cn
FU Ministry of Science and Technology of China [2014CB542500,
2014AA020527]; National Science Foundation of China [81361120384,
31270913]; Beijing Natural Science Foundation [5132016]; Ph.D. Programs
Foundation of Ministry of Education of China [20130002110059,
20120002120007]; Tsinghua University Initiative Scientific Research
Program [20131089279]; Chinese Medical Association [12040670367]
FX This work was supported by the Ministry of Science and Technology of
China (Grants 2014CB542500 and 2014AA020527), the National Science
Foundation of China (Grants 81361120384 and 31270913), the Beijing
Natural Science Foundation (Grant 5132016), the Ph.D. Programs
Foundation of Ministry of Education of China (Grants 20130002110059 and
20120002120007), the Tsinghua University Initiative Scientific Research
Program (Grant 20131089279), and the Chinese Medical Association (Grant
12040670367).
NR 53
TC 6
Z9 9
U1 1
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2014
VL 192
IS 11
BP 5179
EP 5191
DI 10.4049/jimmunol.1400101
PG 13
WC Immunology
SC Immunology
GA AI8MT
UT WOS:000337171800029
PM 24790152
ER
PT J
AU Percopo, CM
Dyer, KD
Garcia-Crespo, KE
Gabryszewski, SJ
Shaffer, AL
Domachowske, JB
Rosenberg, HF
AF Percopo, Caroline M.
Dyer, Kimberly D.
Garcia-Crespo, Katia E.
Gabryszewski, Stanislaw J.
Shaffer, Arthur L., III
Domachowske, Joseph B.
Rosenberg, Helene F.
TI B Cells Are Not Essential for Lactobacillus-Mediated Protection against
Lethal Pneumovirus Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID INFLUENZA-VIRUS INFECTION; LYMPHOID-TISSUE IBALT; INNATE IMMUNITY; MICE;
PNEUMONIA; RESISTANCE; MACROPHAGES; ACTIVATION; PATHOLOGY; ANTIBODY
AB We have shown previously that priming of respiratory mucosa with live Lactobacillus species promotes robust and prolonged survival from an otherwise lethal infection with pneumonia virus of mice, a property known as heterologous immunity. Lactobacillus priming results in a moderate reduction in virus recovery and a dramatic reduction in virus-induced proinflammatory cytokine production; the precise mechanisms underlying these findings remain to be elucidated. Because B cells have been shown to promote heterologous immunity against respiratory virus pathogens under similar conditions, in this study we explore the role of B cells in Lactobacillus-mediated protection against acute pneumovirus infection. We found that Lactobacillus-primed mice feature elevated levels of airway Igs IgG, IgA, and IgM and lung tissues with dense, B cell (B220(+))-enriched peribronchial and perivascular infiltrates with germinal centers consistent with descriptions of BALT. No B cells were detected in lung tissue of Lactobacillus-primed B cell deficient mu MT mice or Jh mice, and Lactobacillus-primed mu MT mice had no characteristic infiltrates or airway Igs. Nonetheless, we observed diminished virus recovery and profound suppression of virus-induced proinflammatory cytokines CCL2, IFN-gamma and CXCL10 in both wild-type and Lactobacillus-primed mu MT mice. Furthermore, Lactobacillus plantarum-primed, B cell-deficient mu MTand Jh mice were fully protected from an otherwise lethal pneumonia virus of mice infection, as were their respective wild-types. We conclude that B cells are dispensable for Lactobacillus-mediated heterologous immunity and were not crucial for promoting survival in response to an otherwise lethal pneumovirus infection.
C1 [Percopo, Caroline M.; Dyer, Kimberly D.; Garcia-Crespo, Katia E.; Gabryszewski, Stanislaw J.; Rosenberg, Helene F.] NIAID, Inflammat Immunobiol Sect, NIH, Bethesda, MD 20892 USA.
[Shaffer, Arthur L., III] NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
[Domachowske, Joseph B.] SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA.
RP Rosenberg, HF (reprint author), NIAID, Bldg 10,Room 11C215,MSC 1883,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases Division of
Intramural Research [AI000943]
FX This work was supported by National Institute of Allergy and Infectious
Diseases Division of Intramural Research AI000943 (to H.F.R.).
NR 40
TC 7
Z9 7
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD JUN 1
PY 2014
VL 192
IS 11
BP 5265
EP 5272
DI 10.4049/jimmunol.1400087
PG 8
WC Immunology
SC Immunology
GA AI8MT
UT WOS:000337171800037
PM 24748495
ER
PT J
AU Ramirez, CM
Lin, CS
Abdelmohsen, K
Goedeke, L
Yoon, JH
Madrigal-Matute, J
Martin-Ventura, JL
Vo, DT
Uren, PJ
Penalva, LO
Gorospe, M
Fernandez-Hernando, C
AF Ramirez, Cristina M.
Lin, Chin Sheng
Abdelmohsen, Kotb
Goedeke, Leigh
Yoon, Je-Hyun
Madrigal-Matute, Julio
Martin-Ventura, Jose L.
Vo, Dat T.
Uren, Philip J.
Penalva, Luiz O.
Gorospe, Myriam
Fernandez-Hernando, Carlos
TI RNA binding protein HuR regulates the expression of ABCA1
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE ATP binding cassette transporter A1; human antigen R;
posttranscriptional regulation; lipid homeostasis; cholesterol efflux
ID HIGH-DENSITY-LIPOPROTEIN; CASSETTE TRANSPORTER A1; CHOLESTEROL EFFLUX;
POSTTRANSCRIPTIONAL REGULATION; OXIDATIVE STRESS; LIPID-METABOLISM;
MESSENGER-RNAS; TRANSLATION; MICRORNAS; DISEASE
AB ABCA1 is a major regulator of cellular cholesterol efflux and plasma HDL biogenesis. Even though the transcriptional activation of ABCA1 is well established, the posttranscriptional regulation of ABCA1 expression is poorly understood. Here, we investigate the potential contribution of the RNA binding protein (RBP) human antigen R (HuR) on the posttranscriptional regulation of ABCA1 expression. RNA immunoprecipitation assays demonstrate a direct interaction between HuR and ABCA1 mRNA. We found that HuR binds to the 3' untranslated region of ABCA1 and increases ABCA1 translation, while HuR silencing reduces ABCA1 expression and cholesterol efflux to ApoA1 in human hepatic (Huh-7) and monocytic (THP-1) cells. Interestingly, cellular cholesterol levels regulate the expression, intracellular localization, and interaction between HuR and ABCA1 mRNA. Finally, we found that HuR expression was significantly increased in macrophages from human atherosclerotic plaques, suggesting an important role for this RBP in controlling macrophage cholesterol metabolism in vivo. In summary, we have identified HuR as a novel posttranscriptional regulator of ABCA1 expression and cellular cholesterol homeostasis, thereby opening new avenues for increasing cholesterol efflux from atherosclerotic foam macrophages and raising circulating HDL cholesterol levels.
C1 [Ramirez, Cristina M.; Goedeke, Leigh; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Vasc Biol & Therapeut Program, Dept Comparat Med, New Haven, CT 06520 USA.
[Ramirez, Cristina M.; Lin, Chin Sheng; Goedeke, Leigh; Madrigal-Matute, Julio; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Med, New York, NY 10016 USA.
[Ramirez, Cristina M.; Lin, Chin Sheng; Goedeke, Leigh; Madrigal-Matute, Julio; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA.
[Lin, Chin Sheng] Triserv Gen Hosp, Natl Def Med Ctr, Div Cardiol, Dept Med, Taipei, Taiwan.
[Abdelmohsen, Kotb; Yoon, Je-Hyun; Gorospe, Myriam] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Martin-Ventura, Jose L.] Univ Autonoma Madrid, IIS Fundac Jimenez Diaz, Vasc Res Lab, Madrid 28040, Spain.
[Vo, Dat T.; Penalva, Luiz O.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Childrens Canc Res Inst, San Antonio, TX 78229 USA.
[Uren, Philip J.] Univ So Calif, Los Angeles, CA 90089 USA.
RP Fernandez-Hernando, C (reprint author), Yale Univ, Sch Med, Vasc Biol & Therapeut Program, Dept Comparat Med, 333 Cedar St, New Haven, CT 06520 USA.
EM carlos.fernandez@yale.edu
OI Ramirez, Cristina M/0000-0003-2589-0786
FU National Institutes of Health [R01HL107953, R01HL106063, 1F31AG043318];
American Heart Association [12POST9780016]; Tri-Service General Hospital
[TSGH-C103-027]; National Institute on Aging-Intramural Research
Program; National Institutes of Health
FX This work was supported by National Institutes of Health Grants
R01HL107953 and R01HL106063 (C.F-H.) and 1F31AG043318-01 (L. G.), and
American Heart Association Grant 12POST9780016 (C. M. R.). C. S. Lin was
supported by Tri-Service General Hospital (TSGH-C103-027). K.
Abdelmohsen, J-H. Yoon, and M. Gorospe were supported by the National
Institute on Aging-Intramural Research Program, the National Institutes
of Health.
NR 41
TC 3
Z9 3
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD JUN
PY 2014
VL 55
IS 6
BP 1066
EP 1076
DI 10.1194/jlr.M044925
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AI8BY
UT WOS:000337130900008
PM 24729624
ER
PT J
AU Kim, DS
Crosslin, DR
Auer, PL
Suzuki, SM
Marsillach, J
Burt, AA
Gordon, AS
Meschia, JF
Nalls, MA
Worrall, BB
Longstreth, WT
Gottesman, RF
Furlong, CE
Peters, U
Rich, SS
Nickerson, DA
Jarvik, GP
AF Kim, Daniel Seung
Crosslin, David R.
Auer, Paul L.
Suzuki, Stephanie M.
Marsillach, Judit
Burt, Amber A.
Gordon, Adam S.
Meschia, James F.
Nalls, Mike A.
Worrall, Bradford B.
Longstreth, W. T., Jr.
Gottesman, Rebecca F.
Furlong, Clement E.
Peters, Ulrike
Rich, Stephen S.
Nickerson, Deborah A.
Jarvik, Gail P.
CA NHLBI Exome Sequencing Project
TI Rare coding variation in paraoxonase-1 is associated with ischemic
stroke in the NHLBI Exome Sequencing Project
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE rare variation; genetics; atherosclerosis
ID MISSING HERITABILITY; VASCULAR-DISEASE; HEART-DISEASE; CHOLESTEROL;
POLYMORPHISMS; DIETARY
AB HDL-associated paraoxonase-1 (PON1) is an enzyme whose activity is associated with cerebrovascular disease. Common PON1 genetic variants have not been consistently associated with cerebrovascular disease. Rare coding variation that likely alters PON1 enzyme function may be more strongly associated with stroke. The National Heart, Lung, and Blood Institute Exome Sequencing Project sequenced the coding regions (exomes) of the genome for heart, lung, and blood-related phenotypes (including ischemic stroke). In this sample of 4,204 unrelated participants, 496 had verified, noncardioembolic ischemic stroke. After filtering, 28 nonsynonymous PON1 variants were identified. Analysis with the sequence kernel association test, adjusted for covariates, identified significant associations between PON1 variants and ischemic stroke (P = 3.01 x 10(-3)). Stratified analyses demonstrated a stronger association of PON1 variants with ischemic stroke in African ancestry (AA) participants (P = 5.03 x 10(-3)). Ethnic differences in the association between PON1 variants with stroke could be due to the effects of PON1(Val109Ile) (overall P = 7.88 x 10(-3); AA P = 6.52 x 10(- 4)), found at higher frequency in AA participants (1.16% vs. 0.02%) and whose protein is less stable than the common allele. In summary, rare genetic variation in PON1 was associated with ischemic stroke, with stronger associations identified in those of AA. Increased focus on PON1 enzyme function and its role in cerebrovascular disease is warranted.
C1 [Kim, Daniel Seung; Crosslin, David R.; Suzuki, Stephanie M.; Marsillach, Judit; Burt, Amber A.; Furlong, Clement E.; Jarvik, Gail P.] Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
[Kim, Daniel Seung; Crosslin, David R.; Marsillach, Judit; Gordon, Adam S.; Furlong, Clement E.; Nickerson, Deborah A.; Jarvik, Gail P.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA.
[Auer, Paul L.; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Auer, Paul L.] Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA.
[Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Nalls, Mike A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Worrall, Bradford B.; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA.
[Worrall, Bradford B.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Longstreth, W. T., Jr.; Peters, Ulrike] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Gottesman, Rebecca F.] Johns Hopkins Univ, Sch Med, Dept Neurol, Cerebrovasc Div, Baltimore, MD 21205 USA.
RP Jarvik, GP (reprint author), Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
EM pair@u.washington.edu
RI Jarvik, Gail/N-6476-2014; Marsillach, Judit/I-1329-2015
OI Jarvik, Gail/0000-0002-6710-8708; Marsillach, Judit/0000-0002-3061-6266
FU WA State Life Sciences Discovery Fund [265508]; National Heart, Lung,
and Blood Institute (NHLBI); LungGO Sequencing Project [HL-102923];
Women's Health Initiative Sequencing Project [HL-102924]; BroadGO
Sequencing Project [HL-102925]; SeattleGO Sequencing Project
[HL-102926]; HeartGO Sequencing Project [HL-103010]; National Institutes
of Health (NIH) [ES09883, T32ES007032]; Intramural Research Program of
the National Institute of Aging, NIH [Z01 AG-000954-06]; Benjamin and
Margaret Hall Endowed Fellowship in Genome Sciences; Markey Foundation
award; NIH [5T31HG000035-18, 1F31MH101905-01]
FX This work was supported in part by WA State Life Sciences Discovery Fund
(265508, to the Northwest Institute of Genetic Medicine). The National
Heart, Lung, and Blood Institute (NHLBI) funded the multicenter effort
with the following grants: the LungGO Sequencing Project (HL-102923),
the Women's Health Initiative Sequencing Project (HL-102924), the
BroadGO Sequencing Project (HL-102925), the SeattleGO Sequencing Project
(HL-102926), and the HeartGO Sequencing Project (HL-103010). This work
was also supported by National Institutes of Health (NIH) Grants ES09883
and T32ES007032 (S. M. S.); the Intramural Research Program of the
National Institute of Aging, NIH Project Z01 AG-000954-06 (M.A.N.); and
the Benjamin and Margaret Hall Endowed Fellowship in Genome Sciences, a
Markey Foundation award, and NIH Grants 5T31HG000035-18 and
1F31MH101905-01 (D. S. K.). Funding sources for specific cohorts are
presented in the supplementary NHLBI Exome Sequencing Project (ESP)
Banner.
NR 20
TC 11
Z9 12
U1 1
U2 6
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
EI 1539-7262
J9 J LIPID RES
JI J. Lipid Res.
PD JUN
PY 2014
VL 55
IS 6
BP 1173
EP 1178
DI 10.1194/jlr.P049247
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AI8BY
UT WOS:000337130900018
PM 24711634
ER
PT J
AU Friedman, DI
McDermott, MP
Kieburtz, K
Kupersmith, M
Stoutenburg, A
Keltner, JL
Feldon, SE
Schron, E
Corbett, JJ
Wall, M
AF Friedman, Deborah I.
McDermott, Michael P.
Kieburtz, Karl
Kupersmith, Mark
Stoutenburg, Ann
Keltner, John L.
Feldon, Steven E.
Schron, Eleanor
Corbett, James J.
Wall, Michael
CA NORDIC IIHTT Study Grp
TI The Idiopathic Intracranial Hypertension Treatment Trial: Design
Considerations and Methods
SO JOURNAL OF NEURO-OPHTHALMOLOGY
LA English
DT Article
ID RETINOL-BINDING-PROTEIN; QUALITY-OF-LIFE; PSEUDOTUMOR CEREBRI;
WEIGHT-LOSS; PHONE INTERVENTIONS; CEREBROSPINAL-FLUID; VITAMIN-A;
ACETAZOLAMIDE; PAPILLEDEMA; DEPRESSION
AB Background: The objectives of this study were to present the rationale for the main aspects of the study design and describe the trial methodology for the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT).
Methods: Eligible candidates with mild visual field loss (automated perimetric mean deviation [PMD] 22 to 27 dB) were randomized to receive either acetazolamide or matching placebo tablets. Randomized participants were offered participation in a supervised dietary program. The primary outcome variable, PMD, was measured at 6 months. Additionally, cerebrospinal fluid from subjects and serum from study participants and matched controls were collected for genetic analysis and vitamin A studies. An ancillary optical coherence substudy was added to investigate the changes of papilledema in the optic nerve head and retina that correlate with Frisen grading, visual field deficits, and low-contrast visual acuity.
Results: The randomized trial entered 165 participants from March 17, 2010, through November 27, 2012, from the United States and Canada. The primary outcome (month 6) visits were successfully completed by June 15, 2013. Blood specimens were obtained from 165 controls without IIH to investigate vitamin A metabolism and genetic markers of potential risk factors for IIH.
Conclusions: The IIHTT is the first randomized, double-masked placebo-controlled trial to study the effectiveness of medical treatment for patients with IIH. (C) 2014 by North American Neuro-Ophthalmology Society
C1 [Friedman, Deborah I.] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA.
[Friedman, Deborah I.] Univ Texas SW Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75390 USA.
[Feldon, Steven E.] Univ Rochester, Sch Med & Dent, Dept Ophthalmol, Rochester, NY USA.
[McDermott, Michael P.; Feldon, Steven E.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA.
[Feldon, Steven E.] Univ Rochester, Sch Med & Dent, Dept Neurosurg, Rochester, NY USA.
[Feldon, Steven E.] Univ Rochester, Sch Med & Dent, Dept Visual Sci, Rochester, NY USA.
[Kieburtz, Karl; Stoutenburg, Ann] Univ Rochester, Sch Med & Dent, Ctr Human Expt Therapeut, Rochester, NY USA.
[McDermott, Michael P.] Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Biol, Rochester, NY USA.
[Wall, Michael] Univ Iowa, Coll Med, Iowa City, IA USA.
[Wall, Michael] Iowa City Vet Affairs Hlth Care Syst, Iowa City, IA USA.
[Schron, Eleanor] NEI, Bethesda, MD 20892 USA.
[Keltner, John L.] Univ Calif Davis, Med Ctr, Dept Ophthalmol & Vis Sci, Sacramento, CA 95817 USA.
[Kupersmith, Mark] Mt Sinai Sch Med, Dept Neurol, New York, NY USA.
[Kupersmith, Mark] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
RP Friedman, DI (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd,MC 9036, Dallas, TX 75390 USA.
EM Deborah.Friedman@utsouthwestern.edu
OI Bruce, Beau/0000-0003-3003-2962
FU National Eye Institute [1U10EY017281-01A1, 1U10EY017387-01A1,
3U10EY017281-01A1S1, 3U10EY017281-01A1S2]
FX Supported by National Eye Institute (1U10EY017281-01A1,
1U10EY017387-01A1, 3U10EY017281-01A1S1, 3U10EY017281-01A1S2).
NR 54
TC 21
Z9 21
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1070-8022
EI 1536-5166
J9 J NEURO-OPHTHALMOL
JI J. Neuro-Ophthal.
PD JUN
PY 2014
VL 34
IS 2
BP 107
EP 117
DI 10.1097/WNO.0000000000000114
PG 11
WC Clinical Neurology; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA AI9IL
UT WOS:000337246200002
PM 24739993
ER
PT J
AU Deyo, RA
Dworkin, SF
Amtmann, D
Andersson, G
Borenstein, D
Carragee, E
Carrino, J
Chou, R
Cook, K
DeLitto, A
Goertz, C
Khalsa, P
Loeser, J
Mackey, S
Panagis, J
Rainville, J
Tosteson, T
Turk, D
Von Korff, M
Weinertt, DK
AF Deyo, Richard A.
Dworkin, Samuel F.
Amtmann, Dagmar
Andersson, Gunnar
Borenstein, David
Carragee, Eugene
Carrino, John
Chou, Roger
Cook, Karon
DeLitto, Anthony
Goertz, Christine
Khalsa, Partap
Loeser, John
Mackey, Sean
Panagis, James
Rainville, James
Tosteson, Tor
Turk, Dennis
Von Korff, Michael
Weinertt, Debra K.
TI Report of the NIH Task Force on Research Standards for Chronic Low Back
Pain
SO JOURNAL OF PAIN
LA English
DT Article
DE Low back pain; chronic low back pain; research standards; minimum
dataset; NIH Task Force
ID CLINICAL-PRACTICE GUIDELINE; DEFINING CHRONIC PAIN; INFORMATION-SYSTEM
PROMIS; FUNCTION ITEM BANK; QUALITY-OF-LIFE; PRIMARY-CARE; PROGNOSTIC
APPROACH; SCREENING TOOL; START BACK; OUTCOME MEASURES
AB Despite rapidly increasing intervention, functional disability due to chronic low back pain (cLBP) has increased in recent decades. We often cannot identify mechanisms to explain the major negative impact cLBP has on patients' lives. Such cLBP is often termed non-specific and may be due to multiple biologic and behavioral etiologies. Researchers use varied inclusion criteria, definitions, baseline assessments, and outcome measures, which impede comparisons and consensus. Therefore, NIH Pain Consortium charged a Research Task Force (RTF) to draft standards for research on cLBP. The resulting multidisciplinary panel recommended using 2 questions to define cLBP; cLBP by its impact (defined by pain intensity, pain interference, and physical function); use of a minimum dataset to describe research participants (drawing heavily on the PROMIS methodology); reporting "responder analyses" in addition to mean outcome scores; and suggestions for future research and dissemination. The Pain Consortium has approved the recommendations, which investigators should incorporate into NIH grant proposals. The RTF believes that these recommendations will advance the field, help to resolve controversies, and facilitate future research addressing the genomic, neurologic, and other mechanistic substrates of chronic low back pain. We expect that the RTF recommendations will become a dynamic document and undergo continual improvement.
Perspective: A task force was convened by the NIH Pain Consortium with the goal of developing research standards for chronic low back pain. The results included recommendations for definitions, a minimum dataset, reporting outcomes, and future research. Greater consistency in reporting should facilitate comparisons among studies and the development of phenotypes. (C) 2014 by the American Pain Society. Published by Elsevier Inc. All rights reserved
C1 [Deyo, Richard A.; Chou, Roger] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
[Dworkin, Samuel F.; Amtmann, Dagmar; Loeser, John; Turk, Dennis] Univ Washington, Seattle, WA 98195 USA.
[Andersson, Gunnar] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Borenstein, David] George Washington Univ, Washington, DC USA.
[Carragee, Eugene; Mackey, Sean] Stanford Univ, Stanford, CA 94305 USA.
[Carrino, John] Johns Hopkins Univ, Baltimore, MD USA.
[Cook, Karon] Northwestern Univ, Evanston, IL USA.
[DeLitto, Anthony; Weinertt, Debra K.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[DeLitto, Anthony; Weinertt, Debra K.] Univ Pittsburgh, Pittsburgh, PA USA.
[Goertz, Christine] Palmer Coll Chiropract, Davenport, IA USA.
[Khalsa, Partap] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA.
[Panagis, James] NIAMSD, Bethesda, MD 20892 USA.
[Rainville, James] New England Baptist Hosp, Roxbury Crossing, MA USA.
[Tosteson, Tor] Dartmouth Coll, Hanover, NH USA.
[Von Korff, Michael] Grp Hlth Res Inst, Seattle, WA USA.
RP Deyo, RA (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM deyor@ohsu.edu
FU National Center for Complementary and Alternative Medicine; National
Institute for Arthritis, Musculoskeletal, and Skin Diseases
FX This study was supported by the National Center for Complementary and
Alternative Medicine and the National Institute for Arthritis,
Musculoskeletal, and Skin Diseases.
NR 127
TC 29
Z9 29
U1 9
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 1526-5900
J9 J PAIN
JI J. Pain
PD JUN
PY 2014
VL 15
IS 6
BP 569
EP 585
DI 10.1016/j.jpain.2014.03.005
PG 17
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AJ0HM
UT WOS:000337331400001
PM 24787228
ER
PT J
AU Beck, JD
Youngblood, M
Atkinson, JC
Mauriello, S
Kaste, LM
Badner, VM
Beaver, S
Becerra, K
Singer, R
AF Beck, James D.
Youngblood, Marston, Jr.
Atkinson, Jane C.
Mauriello, Sally
Kaste, Linda M.
Badner, Victor M.
Beaver, Shirley
Becerra, Karen
Singer, Richard
TI The prevalence of caries and tooth loss among participants in the
Hispanic Community Health Study/Study of Latinos
SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION
LA English
DT Article
DE Hispanic; Latino; caries; tooth loss
ID DESIGN
AB Background. The Hispanic and Latino population is projected to increase from 16.7 percent to 30.0 percent by 2050. Previous U. S. national surveys had minimal representation of Hispanic and Latino participants other than Mexicans, despite evidence suggesting that Hispanic or Latino country of origin and degree of acculturation influence health outcomes in this population. In this article, the authors describe the prevalence and mean number of cavitated, decayed and filled surfaces, missing teeth and edentulism among Hispanics and Latinos of different national origins.
Methods. Investigators in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)-Pa multicenter epidemiologic study funded by the National Heart, Lung, and Blood Institute with funds transferred from six other institutes, including the National Institute of Dental and Craniofacial Research-Pconducted in-Pperson examinations and interviews with more than 16,000 participants aged 18 to 74 years in four U. S. cities between March 2008 and June 2011. The investigators identified missing, filled and decayed teeth according to a modified version of methods used in the National Health and Nutrition Examination Survey. The authors computed prevalence estimates (weighted percentages), weighted means and standard errors for measures.
Results. The prevalence of decayed surfaces ranged from 20.2 percent to 35.5 percent, depending on Hispanic or Latino background, whereas the prevalence of decayed and filled surfaces ranged from 82.7 percent to 87.0 percent, indicating substantial amounts of dental treatment. The prevalence of missing teeth ranged from 49.8 percent to 63.8 percent and differed according to Hispanic or Latino background. Significant differences in the mean number of decayed surfaces, decayed or filled surfaces and missing teeth according to Hispanic and Latino background existed within each of the age groups and between women and men.
Conclusions. Oral health status differs according to Hispanic or Latino background, even with adjustment for age, sex and other characteristics.
C1 [Beck, James D.; Mauriello, Sally] Univ N Carolina, Sch Dent, Dept Dent Ecol, Chapel Hill, NC 27599 USA.
[Youngblood, Marston, Jr.] Hispan Community Hlth Study Study Latinos, Chapel Hill, NC USA.
[Youngblood, Marston, Jr.] Univ N Carolina, Collaborat Studies Coordinating Ctr, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Atkinson, Jane C.] Natl Inst Dent & Craniofacial Res, Clin Res Ctr, Div Extramural Res, Bethesda, MD USA.
[Kaste, Linda M.] Univ Illinois, Dept Pediat Dent, Coll Dent, Chicago, IL 60680 USA.
[Badner, Victor M.] Yeshiva Univ, Albert Einstein Coll Med, Dept Dent, Bronx, NY USA.
[Badner, Victor M.] Yeshiva Univ, Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY USA.
[Badner, Victor M.] Yeshiva Univ, Albert Einstein Coll Med, Dept Dent, Jacobi Med Ctr, Bronx, NY USA.
[Beaver, Shirley] Stanford Brown Coll, Dent Hyg Program, Skokie, IL USA.
[Becerra, Karen] Gary & Mary West Hlth Inst, San Diego, CA USA.
[Singer, Richard] Nova SE Univ, Coll Dent Med, Dept Orthodont, Ft Lauderdale, FL 33314 USA.
RP Beck, JD (reprint author), Univ N Carolina, Sch Dent, Dept Dent Ecol, 1617 Koury Oral Hlth Sci Bldg,CB 7450, Chapel Hill, NC 27599 USA.
EM james_beck@unc.edu
FU National Heart, Lung, and Blood Institute (NHLBI) to the University of
North Carolina, Chapel Hill [N01-HC65233]; University of Miami
[N01-HC65234]; Albert Einstein College of Medicine, Bronx [N01-HC65235];
Northwestern University, Evanston, Ill. [N01-HC65236]; San Diego State
University [N01-HC65237]; NHLBI; National Center on Minority Health and
Health Disparities; National Institute on Deafness and Other
Communication Disorders; National Institute of Dental and Craniofacial
Research; National Institute of Diabetes and Digestive and Kidney
Diseases; National Institute of Neurological Disorders and Stroke;
National Institutes of Health Office of Dietary Supplements
FX The Hispanic/Latino Community Health Study/Study of Latinos was carried
out as a collaborative study supported by contracts from the National
Heart, Lung, and Blood Institute (NHLBI) to the University of North
Carolina, Chapel Hill (N01-HC65233); the University of Miami
(N01-HC65234); Albert Einstein College of Medicine, Bronx, N.Y.
(N01-HC65235); Northwestern University, Evanston, Ill. (N01-HC65236);
and San Diego State University (N01-HC65237). The following institutes,
centers and offices contribute to the HCHS/SOL through a transfer of
funds to the NHLBI: the National Center on Minority Health and Health
Disparities, the National Institute on Deafness and Other Communication
Disorders, the National Institute of Dental and Craniofacial Research,
the National Institute of Diabetes and Digestive and Kidney Diseases,
the National Institute of Neurological Disorders and Stroke, and the
National Institutes of Health Office of Dietary Supplements.
NR 20
TC 7
Z9 7
U1 1
U2 4
PU AMER DENTAL ASSOC
PI CHICAGO
PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA
SN 0002-8177
EI 1943-4723
J9 J AM DENT ASSOC
JI J. Am. Dent. Assoc.
PD JUN
PY 2014
VL 145
IS 6
BP 531
EP 540
PG 10
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA AI8MS
UT WOS:000337171600006
PM 24878707
ER
PT J
AU Haley, DF
Golin, C
El-Sadr, W
Hughes, JP
Wang, J
Isler, MR
Mannheimer, S
Kuo, I
Lucas, J
DiNenno, E
Justman, J
Frew, PM
Emel, L
Rompalo, A
Polk, S
Adimora, AA
Rodriquez, L
Soto-Torres, L
Hodder, S
AF Haley, Danielle F.
Golin, Carol
El-Sadr, Wafaa
Hughes, James P.
Wang, Jing
Isler, Malika Roman
Mannheimer, Sharon
Kuo, Irene
Lucas, Jonathan
DiNenno, Elizabeth
Justman, Jessica
Frew, Paula M.
Emel, Lynda
Rompalo, Anne
Polk, Sarah
Adimora, Adaora A.
Rodriquez, Lorenna
Soto-Torres, Lydia
Hodder, Sally
CA HIV Prevention Trials Network HPTN
TI Venue-Based Recruitment of Women at Elevated Risk for HIV: An HIV
Prevention Trials Network Study
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID SEXUALLY-TRANSMITTED INFECTIONS; BEHAVIORAL SURVEILLANCE SYSTEM; VACCINE
EFFICACY TRIALS; AFRICAN-AMERICAN WOMEN; UNITED-STATES; CLINICAL-TRIALS;
INCARCERATION RATES; HEALTH DISPARITIES; SEX PARTNERS; US
AB Background: The challenge of identifying and recruiting U. S. women at elevated risk for HIV acquisition impedes prevention studies and services. HIV Prevention Trials Network (HPTN) 064 was a U. S. multisite, longitudinal cohort study designed to estimate HIV incidence among women living in communities with prevalent HIV and poverty. Venue-based sampling (VBS) methodologies and participant and venue characteristics are described.
Methods: Eligible women were recruited from 10 U. S. communities with prevalent HIV and poverty using VBS. Participant eligibility criteria included age 18-44 years, residing in a designated census tract/zip code, and self-report of at least one high-risk personal and/or male sexual partner characteristic associated with HIV acquisition (e. g., incarceration history). Ethnography was conducted to finalize recruitment areas and venues.
Results: Eight thousand twenty-nine women were screened and 2,099 women were enrolled (88% black, median age 29 years) over 14 months. The majority of participants were recruited from outdoor venues (58%), retail spaces (18%), and social service organizations (13%). The proportion of women recruited per venue category varied by site. Most participants (73%) had both individual and partner characteristics that qualified them for the study; 14% were eligible based on partner risk only.
Conclusion: VBS is a feasible and effective approach to rapidly recruit a population of women at enhanced risk for HIV in the United States. Such a recruitment approach is needed in order to engage women most at risk and requires strong community engagement.
C1 [Haley, Danielle F.; Lucas, Jonathan] FHI 360, Durham, NC USA.
[Haley, Danielle F.; Frew, Paula M.] Emory Univ, Dept Behav Sci & Hlth Educ, Rollins Sch Publ Hlth, Atlanta, GA 30033 USA.
[Golin, Carol; Adimora, Adaora A.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Golin, Carol; Adimora, Adaora A.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[El-Sadr, Wafaa; Justman, Jessica] Columbia Univ, Mailman Sch Publ Hlth, Int Ctr AIDS Care & Treatment Programs, New York, NY USA.
[Hughes, James P.; Wang, Jing; Emel, Lynda] Fred Hutchinson Canc Res Ctr, Dept Biostat, Seattle, WA 98104 USA.
[Hughes, James P.] Univ Washington, Div Infect Dis, Seattle, WA 98195 USA.
[Isler, Malika Roman] Univ N Carolina, Sch Med, Dept Social Med, Chapel Hill, NC USA.
[Isler, Malika Roman] Univ N Carolina, North Carolina Translat & Clin Sci Inst, Chapel Hill, NC USA.
[Mannheimer, Sharon] Columbia Univ, Harlem Hosp Ctr, New York, NY USA.
[Mannheimer, Sharon] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Kuo, Irene] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA.
[DiNenno, Elizabeth] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Frew, Paula M.] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA 30033 USA.
[Rompalo, Anne; Polk, Sarah] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Rodriquez, Lorenna] Bronx Lebanon Hosp Ctr, New York, NY USA.
[Soto-Torres, Lydia] NIAID, NIH, Bethesda, MD 20892 USA.
[Hodder, Sally] Rutgers State Univ, New Jersey Med Sch, Newark, NJ 07102 USA.
RP Haley, DF (reprint author), Emory Univ, Dept Behav Sci & Hlth Educ, 1518 Clifton Rd Northeast, Atlanta, GA 30033 USA.
EM dfhaley@emory.edu
OI Frew, Paula/0000-0002-3078-9124
FU National Institute of Allergy and Infectious Diseases, National
Institute on Drug Abuse; National Institute of Mental Health [UM1
AI068619, U01-AI068613, UM1-AI068613]; Centers for Innovative Research
to Control AIDS, Mailman School of Public Health, Columbia University
[5U1Al069466]; University of North Carolina Clinical Trials Unit
[AI069423]; University of North Carolina Clinical Trials Research Center
of the Clinical and Translational Science Award [RR 025747]; University
of North Carolina Center for AIDS Research [AI050410]; Emory University
HIV/AIDS Clinical Trials Unit [5UO1AI069418]; Center for AIDS Research
[P30 AI050409]; Clinical and Translational Science Award [UL1 RR025008];
Terry Beirn Community Programs for Clinical Research on AIDS Clinical
Trials Unit [5 UM1 AI069503-07]; Johns Hopkins Adult AIDS Clinical Trial
Unit [AI069465]; Johns Hopkins Clinical and Translational Science Award
[UL1 RR 25005]; HPTN Scholars Program; National Institute of Allergy and
Infectious Disease; National Institute of Mental Health; Emory
University Laney Graduate School Robert W. Woodruff Pre-Doctoral
Fellowship; National Institute of Allergy and Infectious Diseases;
National Institutes of Health; Centers for Disease Control and
Prevention; HPTN
FX Funding for this study provided through grants from the National
Institute of Allergy and Infectious Diseases, National Institute on Drug
Abuse, and National Institute of Mental Health (UM1 AI068619,
U01-AI068613, and UM1-AI068613); Centers for Innovative Research to
Control AIDS, Mailman School of Public Health, Columbia University
(5U1Al069466); University of North Carolina Clinical Trials Unit
(AI069423); University of North Carolina Clinical Trials Research Center
of the Clinical and Translational Science Award (RR 025747); University
of North Carolina Center for AIDS Research (AI050410); Emory University
HIV/AIDS Clinical Trials Unit (5UO1AI069418), Center for AIDS Research
(P30 AI050409), and Clinical and Translational Science Award (UL1
RR025008); The Terry Beirn Community Programs for Clinical Research on
AIDS Clinical Trials Unit(5 UM1 AI069503-07); The Johns Hopkins Adult
AIDS Clinical Trial Unit (AI069465); The Johns Hopkins Clinical and
Translational Science Award (UL1 RR 25005); and the HPTN Scholars
Program funded by the National Institute of Allergy and Infectious
Disease and the National Institute of Mental Health. The primary
author's time has been supported in part by the Emory University Laney
Graduate School Robert W. Woodruff Pre-Doctoral Fellowship.; The views
expressed herein are those of the authors and do not necessarily
represent the views of the National Institute of Allergy and Infectious
Diseases, the National Institute of Mental Health, the National
Institutes of Health, the Centers for Disease Control and Prevention,
the HPTN, or its funders.
NR 58
TC 4
Z9 4
U1 1
U2 12
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
EI 1931-843X
J9 J WOMENS HEALTH
JI J. Womens Health
PD JUN
PY 2014
VL 23
IS 6
BP 541
EP 551
DI 10.1089/jwh.2013.4654
PG 11
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 AI9BT
UT WOS:000337222700011
PM 24742266
ER
PT J
AU Whitson, HE
Arnold, AM
Yee, LM
Mukamal, KJ
Kizer, JR
Djousse, L
Ix, JH
Siscovick, D
Tracy, RP
Thielke, SM
Hirsch, C
Newman, AB
Zieman, S
AF Whitson, Heather E.
Arnold, Alice M.
Yee, Laura M.
Mukamal, Kenneth J.
Kizer, Jorge R.
Djousse, Luc
Ix, Joachim H.
Siscovick, David
Tracy, Russell P.
Thielke, Stephen M.
Hirsch, Calvin
Newman, Anne B.
Zieman, Susan
TI Serum Carboxymethyl-Lysine, Disability, and Frailty in Older Persons:
The Cardiovascular Health Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Biomarkers; Disablement process; Epidemiology; Frailty; Metabolism
ID GLYCATION END-PRODUCTS; DISEASE MORTALITY; OXIDATIVE STRESS;
CROSS-LINKING; ADULTS; ENDPRODUCTS; WOMEN; COMPLICATIONS; PHENOTYPE;
FOODS
AB Background. Advanced glycation endproducts are biologically active compounds that accumulate in disordered metabolism and normal aging. Carboxymethyl-lysine (CML), a ubiquitous human advanced glycation endproduct, has been associated with age-related conditions and mortality. Our objective was to ascertain the relationship between CML and geriatric outcomes (disability and frailty) in a large cohort of older men and women.
Methods. In 1996-1997, serum CML was measured in 3,373 Cardiovascular Health Study participants (mean age 78.1 +/- 4.8 years). Disability, defined as difficulty in any of six activities of daily living, was assessed every 6-12 months for 14 years. Frailty was defined according to five standard criteria at the 1996-1997 visit. Cox proportional hazard models estimated the relationship between CML and incident disability (N = 2,643). Logistic regression models estimated the relationship between CML and prevalent frailty.
Results. Adjusting for multiple potential confounders, higher CML was associated with incident disability (hazard ratio per standard deviation [225 ng/mL] increase: 1.05, 95% CI 1.01-1.11). In men, odds of frailty increased with higher CML values (odds ratio = 1.30 per standard deviation, 95% CI 1.14-1.48), but the relationship was attenuated by adjustment for cognitive status, kidney function, and arthritis. CML was not associated with frailty in women.
Conclusions. Higher serum CML levels in late life are associated with incident disability and prevalent frailty. Further work is needed to understand CML's value as a risk stratifier, biomarker, or target for interventions that promote healthy aging.
C1 [Whitson, Heather E.] Duke Univ, Dept Med, Durham, NC USA.
[Whitson, Heather E.] GRECC, Durham VA Med Ctr, Durham, NC USA.
[Arnold, Alice M.; Yee, Laura M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Mukamal, Kenneth J.; Djousse, Luc] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Ix, Joachim H.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Ix, Joachim H.] Univ Calif San Diego, Dept Prevent & Family Med, San Diego, CA 92103 USA.
[Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA.
[Siscovick, David] Univ Washington, Dept Med, Seattle, WA USA.
[Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, VT USA.
[Thielke, Stephen M.] Puget Sound VA Med Ctr, Seattle, WA USA.
[Thielke, Stephen M.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA.
[Hirsch, Calvin] Univ Calif Davis, Dept Med, Davis, CA USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Zieman, Susan] NIA, NIH, Bethesda, MD 20892 USA.
RP Whitson, HE (reprint author), DUMC 3003, Durham, NC 27710 USA.
EM heather.whitson@duke.edu
RI Newman, Anne/C-6408-2013; Djousse, Luc/F-5033-2017
OI Newman, Anne/0000-0002-0106-1150; Djousse, Luc/0000-0002-9902-3047
FU National Heart, Lung, and Blood Institute [HL094555, HL080295]; National
Institute on Aging [AG-023629]; [HHSN268201200036C];
[N01-HHSN268200800007C]; [N01 HC-55222]; [N01-HC-85079];
[N01-HC-85080]; [N01-HC-85081]; [N01-HC-85082]; [N01-HC-85083];
[N01-HC-85086]; [K23 AG032867]; [5P30AG028716]
FX This research was supported by contracts HHSN268201200036C,
N01-HHSN268200800007C, N01 HC-55222, N01-HC-85079, N01-HC-85080,
N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85086, and grants
HL094555 and HL080295 from the National Heart, Lung, and Blood
Institute, with additional contribution from the National Institute of
Neurological Disorders and Stroke and by AG-023629 from the National
Institute on Aging. A full list of principal CHS investigators and
institutions can be found at http://www.chs-nhlbi.org. H.E.W. is
supported by K23 AG032867 and 5P30AG028716.
NR 33
TC 3
Z9 3
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUN
PY 2014
VL 69
IS 6
BP 710
EP 716
DI 10.1093/gerona/glt155
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AI8BI
UT WOS:000337128500011
PM 24127427
ER
PT J
AU Murphy, RA
Ip, EH
Zhang, Q
Boudreau, RM
Cawthon, PM
Newman, AB
Tylavsky, FA
Visser, M
Goodpaster, BH
Harris, TB
AF Murphy, Rachel A.
Ip, Edward H.
Zhang, Qiang
Boudreau, Robert M.
Cawthon, Peggy M.
Newman, Anne B.
Tylavsky, Frances A.
Visser, Marjolein
Goodpaster, Bret H.
Harris, Tamara B.
CA Hlth Aging Body Composition Study
TI Transition to Sarcopenia and Determinants of Transitions in Older
Adults: A Population-Based Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Muscle; Aging; Physical function; Sarcopenia; Epidemiology
ID DENSITY TESTING INTERVAL; VISCERAL ADIPOSE-TISSUE; SKELETAL-MUSCLE MASS;
BODY-COMPOSITION; PHYSICAL-DISABILITY; MOBILITY DISABILITY;
RACIAL-DIFFERENCES; RISK-FACTORS; HEALTH; WOMEN
AB Background. Diagnostic criteria for sarcopenia from appendicular lean mass (ALM), strength, and performance have been proposed, but little is known regarding the progression of sarcopenia. We examined the time course of sarcopenia and determinants of transitioning toward and away from sarcopenia.
Methods. ALM, gait speed, and grip strength were assessed seven times over 9 years in 2,928 initially well-functioning adults aged 70-79. Low ALM was defined as less than 7.95 kg/m(2) (men) or less than 6.24 kg/m(2) (women), low performance as gait speed less than 1.0 m/s, low strength as grip strength less than 30 kg (men) or less than 20 kg (women). Presarcopenia was defined as low ALM and sarcopenia as low ALM with low performance or low strength. Hidden Markov modeling was used to characterize states of ALM, strength, and performance and model transitions leading to sarcopenia and death. Determinants of transitioning toward and away from sarcopenia were examined with logistic regression.
Results. Initially, 54% of participants had normal ALM, strength, and performance; 21% had presarcopenia; 5% had sarcopenia; and 20% had intermediate characteristics. Of participants with normal ALM, strength, and performance, 1% transitioned to presarcopenia and none transitioned to sarcopenia. The greatest transition to sarcopenia (7%) was in presarcopenic individuals. Low-functioning and sarcopenia states were more likely to lead to death (12% and 13%). Higher body mass index (p < .001) and pain (p = .05) predicted transition toward sarcopenia, whereas moderate activity predicted transition from presarcopenia to more normal states (p = .02).
Conclusions. Pain, physical activity, and body mass index, potentially modifiable factors, are determinants of transitions. Promotion of health approaching old age is important as few individuals transition away from their initial state.
C1 [Murphy, Rachel A.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20814 USA.
[Ip, Edward H.; Zhang, Qiang] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
[Boudreau, Robert M.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15260 USA.
[Cawthon, Peggy M.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Tylavsky, Frances A.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Visser, Marjolein] Vrije Univ Amsterdam, Dept Hlth Sci, Amsterdam, Netherlands.
[Visser, Marjolein] EMGO Inst, Amsterdam, Netherlands.
[Visser, Marjolein] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands.
[Goodpaster, Bret H.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA.
RP Murphy, RA (reprint author), NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, 7201 Wisconsin Ave,3C-309, Bethesda, MD 20814 USA.
EM Rachel.murphy@nih.gov
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187
FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG028050]; National Institute of Nursing Research
[R01-NR-012459, R01-AG031827A]; Intramural Research Program of the
National Institutes of Health, National Institute on Aging; Banting
Postdoctoral Fellowship
FX This research was supported by National Institute on Aging (Contracts
N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106); National Institute on
Aging (grant R01-AG028050); National Institute of Nursing Research
(grants R01-NR-012459 and R01-AG031827A). This research was supported in
part by the Intramural Research Program of the National Institutes of
Health, National Institute on Aging. R.A.M. is supported by a Banting
Postdoctoral Fellowship.
NR 39
TC 12
Z9 12
U1 1
U2 11
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUN
PY 2014
VL 69
IS 6
BP 751
EP 758
DI 10.1093/gerona/glt131
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AI8BI
UT WOS:000337128500016
PM 24013673
ER
PT J
AU Burch, JB
Augustine, AD
Frieden, LA
Hadley, E
Howcroft, TK
Johnson, R
Khalsa, PS
Kohanski, RA
Li, XL
Macchiarini, F
Niederehe, G
Oh, YS
Pawlyk, AC
Rodriguez, H
Rowland, JH
Shen, GL
Sierra, F
Wise, BC
AF Burch, John B.
Augustine, Alison Deckhut
Frieden, Leslie A.
Hadley, Evan
Howcroft, T. Kevin
Johnson, Ron
Khalsa, Partap S.
Kohanski, Ronald A.
Li, Xiao Ling
Macchiarini, Francesca
Niederehe, George
Oh, Young S.
Pawlyk, Aaron C.
Rodriguez, Henry
Rowland, Julia H.
Shen, Grace L.
Sierra, Felipe
Wise, Bradley C.
TI Advances in Geroscience: Impact on Healthspan and Chronic Disease
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Chronic disease; Geroscience
AB Population aging is unprecedented, without parallel in human history, and the 21st century will witness even more rapid aging than did the century just past. Improvements in public health and medicine are having a profound effect on population demographics worldwide. By 2017, there will be more people over the age of 65 than under age 5, and by 2050, two billion of the estimated nine billion people on Earth will be older than 60 (http://unfpa.org/ageingreport/). Although we can reasonably expect to live longer today than past generations did, the age-related disease burden we will have to confront has not changed. With the proportion of older people among the global population being now higher than at any time in history and still expanding, maintaining health into old age (or healthspan) has become a new and urgent frontier for modern medicine. Geroscience is a cross-disciplinary field focused on understanding the relationships between the processes of aging and age-related chronic diseases. On October 30-31, 2013, the trans-National Institutes of Health GeroScience Interest Group hosted a Summit to promote collaborations between the aging and chronic disease research communities with the goal of developing innovative strategies to improve healthspan and reduce the burden of chronic disease.
C1 [Burch, John B.] NIH, Ctr Sci Review, Bethesda, MD 20892 USA.
[Augustine, Alison Deckhut] NIAID, Immunoregulat Sect, Basic Immunol Branch, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA.
[Frieden, Leslie A.] Natl Inst Dent & Craniofacial Res, Res Training & Career Dev Branch, Bethesda, MD USA.
[Hadley, Evan] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA.
[Howcroft, T. Kevin] NCI, NIH, Div Canc Biol, Bethesda, MD 20892 USA.
[Johnson, Ron] NCI, Canc Etiol Branch, DNA & Chromosome Aberrat Branch, Div Canc Biol, Bethesda, MD 20892 USA.
[Khalsa, Partap S.] Natl Ctr Complementary & Alternat Med, Div Extramural Res, Bethesda, MD USA.
[Kohanski, Ronald A.; Sierra, Felipe] NIA, Div Aging Biol, Bethesda, MD 20892 USA.
[Li, Xiao Ling] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
[Macchiarini, Francesca] NIAID, Program Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA.
[Niederehe, George] NIMH, Geriatr & Aging Proc Res Branch, Bethesda, MD 20892 USA.
[Oh, Young S.] NHLBI, Vasc Biol & Hypertens Branch, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Pawlyk, Aaron C.] NIDDK, Div Diabet Endocrinol & Metab Dis, Bethesda, MD 20892 USA.
[Rodriguez, Henry] NCI, Off Canc Clin Prote Res, Off Director, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Rowland, Julia H.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Shen, Grace L.] NEI, Retinal Dis Program, Div Extramural Res, NIH, Bethesda, MD 20892 USA.
[Wise, Bradley C.] NIA, Neurobiol Aging Branch, Div Neurosci, Bethesda, MD 20892 USA.
RP Kohanski, RA (reprint author), NIA, Div Aging Biol, Gateway Bldg,Suite 2C231,7201 Wisconsin Ave, Bethesda, MD 20892 USA.
EM kohanskir@mail.nih.gov
NR 0
TC 37
Z9 37
U1 0
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUN
PY 2014
VL 69
SU 1
BP S1
EP S3
DI 10.1093/gerona/glu041
PG 3
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA AI8BT
UT WOS:000337130200001
PM 24833579
ER
PT J
AU Kristinsson, SY
Anderson, WF
Landgren, O
AF Kristinsson, S. Y.
Anderson, W. F.
Landgren, O.
TI Improved long-term survival in multiple myeloma up to the age of 80
years
SO LEUKEMIA
LA English
DT Letter
ID DEXAMETHASONE; LENALIDOMIDE
C1 [Kristinsson, S. Y.] Karolinska Univ Hosp Solna, Dept Med, Div Hematol, Stockholm, Sweden.
[Kristinsson, S. Y.] Karolinska Inst, Stockholm, Sweden.
[Kristinsson, S. Y.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Kristinsson, S. Y.] Landspitali Natl Univ Hosp, Dept Hematol, Reykjavik, Iceland.
[Anderson, W. F.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Landgren, O.] NCI, Multiple Myeloma Sect, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Kristinsson, SY (reprint author), Karolinska Univ Hosp Solna, Dept Med, Div Hematol, Stockholm, Sweden.
EM sigyngvi@hi.is
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
NR 16
TC 30
Z9 33
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
EI 1476-5551
J9 LEUKEMIA
JI Leukemia
PD JUN
PY 2014
VL 28
IS 6
BP 1346
EP 1348
DI 10.1038/leu.2014.23
PG 4
WC Oncology; Hematology
SC Oncology; Hematology
GA AI9DV
UT WOS:000337230300021
PM 24418994
ER
PT J
AU Ebong, IA
Watson, KE
Goff, DC
Bluemke, DA
Srikanthan, P
Horwich, T
Bertoni, AG
AF Ebong, Imo A.
Watson, Karol E.
Goff, David C., Jr.
Bluemke, David A.
Srikanthan, Preethi
Horwich, Tamara
Bertoni, Alain G.
TI Age at menopause and incident heart failure: the Multi-Ethnic Study of
Atherosclerosis
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Menopause; Heart failure; Estrogen
ID METABOLIC RISK-FACTORS; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN;
MYOCARDIAL PERFORMANCE; HORMONE REPLACEMENT; MESA; OBESITY; ETHNICITY;
ASSOCIATION; POPULATIONS
AB Objective: This study aims to evaluate the associations of early menopause (menopause occurring before age 45 years) and age at menopause with incident heart failure (HF) in postmenopausal women. We also explored the associations of early menopause and age at menopause with left ventricular (LV) measures of structure and function in postmenopausal women.
Methods: We included 2,947 postmenopausal women, aged 45 to 84 years without known cardiovascular disease (2000-2002), from the Multi-Ethnic Study of Atherosclerosis. Cox proportional hazards models were used to examine the associations of early menopause and age at menopause with incident HF. In 2,123 postmenopausal women in whom cardiac magnetic resonance imaging was obtained at baseline, we explored the associations of early menopause and age at menopause with LV measures using multivariable linear regression.
Results: Across a median follow-up of 8.5 years, we observed 71 HF events. There were no significant interactions with ethnicity for incident HF (P-interaction > 0.05). In adjusted analysis, early menopause was associated with an increased risk of incident HF (hazard ratio, 1.66; 95% CI, 1.01-2.73), whereas every 1-year increase in age at menopause was associated with a decreased risk of incident HF (hazard ratio, 0.96; 95% CI, 0.94-0.99). We observed significant interactions between early menopause and ethnicity for LV mass-to-volume ratio (LVMVR; P-interaction = 0.02). In Chinese-American women, early menopause was associated with a higher LVMVR (+0.11; P = 0.0002), whereas every 1-year increase in age at menopause was associated with a lower LVMVR (-0.004; P = 0.04) at baseline.
Conclusions: Older age at menopause is independently associated with a decreased risk of incident HF. Concentric LV remodeling, indicated by a higher LVMVR, is present in Chinese-American women who experienced early menopause at baseline.
C1 [Ebong, Imo A.] Univ So Calif, Dept Med, Los Angeles, CA 90033 USA.
[Watson, Karol E.; Horwich, Tamara] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Los Angeles, CA 90095 USA.
[Goff, David C., Jr.] Colorado Sch Publ Hlth, Aurora, CO USA.
[Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Srikanthan, Preethi] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.
[Bertoni, Alain G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Med, Winston Salem, NC 27103 USA.
[Bertoni, Alain G.] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol, Winston Salem, NC 27103 USA.
RP Ebong, IA (reprint author), Univ So Calif, Dept Med, 2020 Zonal Ave, Los Angeles, CA 90033 USA.
EM ebong@usc.edu
OI Bluemke, David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169]
FX The Multi-Ethnic Study of Atherosclerosis was supported by contracts
N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and
Blood Institute.
NR 37
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1072-3714
EI 1530-0374
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD JUN
PY 2014
VL 21
IS 6
BP 585
EP 591
DI 10.1097/gme.0000000000000138
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AI8HR
UT WOS:000337153300010
PM 24423934
ER
PT J
AU Gierach, GL
Pfeiffer, RM
Patel, DA
Black, A
Schairer, C
Gill, A
Brinton, LA
Sherman, ME
AF Gierach, Gretchen L.
Pfeiffer, Ruth M.
Patel, Deesha A.
Black, Amanda
Schairer, Catherine
Gill, Abegail
Brinton, Louise A.
Sherman, Mark E.
TI Long-term overall and disease-specific mortality associated with benign
gynecologic surgery performed at different ages
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Bilateral oophorectomy; Cohort studies; Hysterectomy; Mortality
ID FRAMINGHAM RISK SCORE; BILATERAL OOPHORECTOMY; OVARIAN CONSERVATION;
HYSTERECTOMY; WOMEN; MENOPAUSE; HEALTH; SURVIVAL; THERAPY; COHORT
AB Objective: As bilateral salpingo-oophorectomy is frequently performed with hysterectomy for nonmalignant conditions, defining health outcomes associated with benign bilateral salpingo-oophorectomy performed at different ages is critical.
Methods: We assessed mortality risk associated with benign total abdominal hysterectomy or bilateral salpingo-oophorectomy among 52,846 Breast Cancer Detection Demonstration Project follow-up study participants. Surgery and risk factor data were ascertained via baseline interview (1979-1986) and three questionnaires (1987-1998). During follow-up through December 2005 (mean, 22.1 y), 13,734 deaths were identified. We estimated hazard ratios (HRs) and 95% CIs for overall and disease-specific mortality for total abdominal hysterectomy or bilateral salpingo-oophorectomy performed by age 35, 40, 45, 50, or 55 years, compared with not having surgery, using landmark analyses and multivariable Cox regression.
Results: Undergoing bilateral salpingo-oophorectomy by age 35 years was associated with increased mortality risk (HR35 (y), 1.20; 95% CI, 1.08-1.34), which decreased with age (HR40 (y), 1.12; 95% CI, 1.04-1.21; HR45 (y), 1.10; 95% CI, 1.03-1.17). Total abdominal hysterectomy alone performed by age 40 years was associated with increased mortality risk to a lesser extent (HR40 y, 1.08; 95% CI, 1.01-1.15). Analyses based on matched propensity scores related to having gynecologic surgery yielded similar results. Elevated mortality risks were largely attributable to noncancer causes.
Conclusions: Benign gynecologic surgeries among young women are associated with increased mortality risk, which attenuates with age.
C1 [Gierach, Gretchen L.; Patel, Deesha A.; Brinton, Louise A.; Sherman, Mark E.] NCI, Hormonal & Reprod Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.; Schairer, Catherine] NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA.
[Black, Amanda] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Gill, Abegail] Walter Reed Natl Mil Med Ctr, John P Murtha Canc Ctr, Bethesda, MD USA.
RP Gierach, GL (reprint author), Rm 7-E108,MSC 9774,9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM gierachg@mail.nih.gov
RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016
OI Brinton, Louise/0000-0003-3853-8562; Gierach,
Gretchen/0000-0002-0165-5522
FU National Cancer Institute, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health.
NR 23
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U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1072-3714
EI 1530-0374
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD JUN
PY 2014
VL 21
IS 6
BP 592
EP 601
DI 10.1097/gme.0000000000000118
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AI8HR
UT WOS:000337153300011
PM 24253486
ER
PT J
AU Glaser, RL
Dimitrakakis, C
AF Glaser, Rebecca L.
Dimitrakakis, Constantine
TI Rapid response of breast cancer to neoadjuvant intramammary
testosterone-anastrozole therapy: neoadjuvant hormone therapy in breast
cancer
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article
DE Testosterone; Anastrozole; Breast cancer; Intramammary; Neoadjuvant
ID ANDROGEN RECEPTOR; ESTROGEN; EXPRESSION; ENDOCRINE; TISSUE; WOMEN; MEN
AB Objective: Experimental and clinical data support the inhibitory effect of testosterone on breast tissue and breast cancer. However, testosterone is aromatized to estradiol, which exerts the opposite effect. The aim of this study was to determine the effect of testosterone, combined with the aromatase inhibitor anastrozole, on a hormone receptor positive, infiltrating ductal carcinoma in the neoadjuvant setting.
Methods: To determine clinical response, we obtained serial ultrasonic measurements and mammograms before and after therapy. Three combination implants-each containing 60 mg of testosterone and 4 mg of anastrozole-were placed anterior, superior, and inferior to a 2.4-cm tumor in the left breast. Three additional testosterone-anastrozole implants were again placed peritumorally 48 days later.
Results: By day 46, there was a sevenfold reduction in tumor volume, as measured on ultrasound. By week 13, we documented a 12-fold reduction in tumor volume, demonstrating a rapid logarithmic response to intramammary testosterone-anastrozole implant therapy, equating to a daily response rate of 2.78% and a tumor half-life of 23 days. Therapeutic systemic levels of testosterone were achieved without elevation of estradiol, further demonstrating the efficacy of anastrozole combined with testosterone.
Conclusions: This novel therapy, delivered in the neoadjuvant setting, has the potential to identify early responders and to evaluate the effectiveness of therapy in vivo. This may prove to be a new approach to both local and systemic therapies for breast cancer in subgroups of patients. In addition, it can be used to reduce tumor volume, allowing for less surgical intervention and better cosmetic oncoplastic results.
C1 [Glaser, Rebecca L.] Millennium Wellness Ctr, Dayton, OH USA.
[Glaser, Rebecca L.] Wright State Univ, Boonshoft Sch Med, Dept Surg, Dayton, OH 45435 USA.
[Dimitrakakis, Constantine] Univ Athens, Sch Med, Dept Ob Gyn 1, GR-11527 Athens, Greece.
[Dimitrakakis, Constantine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Glaser, RL (reprint author), 228 East Spring Valley Rd, Dayton, OH 45458 USA.
EM rglaser@woh.rr.com
NR 20
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U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
EI 1530-0374
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD JUN
PY 2014
VL 21
IS 6
BP 673
EP 678
DI 10.1097/gme.0000000000000096
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AI8HR
UT WOS:000337153300021
PM 24149917
ER
PT J
AU Miao, HX
Gomella, AA
Chedid, N
Chen, L
Wen, H
AF Miao, Houxun
Gomella, Andrew A.
Chedid, Nicholas
Chen, Lei
Wen, Han
TI Fabrication of 200 nm Period Hard X-ray Phase Gratings
SO NANO LETTERS
LA English
DT Article
DE X-ray grating far-field interferometer; X-ray phase contrast imaging;
nanoimprint lithography; cryogenic reactive ion etch; atomic layer
deposition; electroplating
ID DIFFRACTION GRATINGS; COMPACT SOURCE; INTERFEROMETER; DEPOSITION; GOLD
AB Far field X-ray grating interferometry achieves extraordinary phase sensitivity in imaging weakly absorbing samples, provided that the grating period is within the transverse coherence length of the X-ray source. Here we describe a cost-efficient process to fabricate large area, 100 nm half-pitch hard X-ray phase gratings with an aspect ratio of 32. The nanometric gratings are suitable for ordinary compact X-ray sources having low spatial coherence, as demonstrated by X-ray diffraction experiments.
C1 [Miao, Houxun; Gomella, Andrew A.; Chedid, Nicholas; Wen, Han] NHLBI, Imaging Phys Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Chen, Lei] NIST, Ctr Nanoscale Sci & Technol, Gaithersburg, MD 20899 USA.
RP Miao, HX (reprint author), NHLBI, Imaging Phys Lab, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM miaoh@mail.nih.gov; han.wen@nih.gov
RI Wen, Han/G-3081-2010
OI Wen, Han/0000-0001-6844-2997
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, U.S.
FX We sincerely thank Eric Bennett, Gary Melvin, and Dumitru Mazilu of the
National Heart, Lung, and Blood Institute of National Institutes of
Health for their assistance in mechanical engineering and the staff of
the Center for Nanoscale Science and Technology of National Institute of
Standards and Technology for assistance on the fabrication. This work
was supported by the Intramural Research Program of National Heart,
Lung, and Blood Institute, National Institutes of Health, U.S. Certain
commercial equipment, instruments, or materials (or suppliers) are
identified in this paper to foster understanding. Such identification
does not imply recommendation or endorsement by the National Institute
of Standards and Technology, nor does it imply that the materials or
equipment identified are necessarily the best available for the purpose.
NR 41
TC 4
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U1 2
U2 21
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1530-6984
EI 1530-6992
J9 NANO LETT
JI Nano Lett.
PD JUN
PY 2014
VL 14
IS 6
BP 3453
EP 3458
DI 10.1021/nl5009713
PG 6
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA AJ0JP
UT WOS:000337337100073
PM 24845537
ER
PT J
AU Brooks, PJ
Tagle, DA
Groft, S
AF Brooks, Philip J.
Tagle, Danilo A.
Groft, Steve
TI Expanding rare disease drug trials based on shared molecular etiology
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID FAMILIAL DYSAUTONOMIA; CYSTIC-FIBROSIS; NONSENSE MUTATIONS; STORAGE
DISORDERS; GENETIC-DISEASES; GAUCHER-DISEASE; SUPPRESSION; REPAIR;
CHAPERONES; MECHANISM
AB Current clinical trial approaches in rare disease test one drug on one indication defined by a clinical phenotype. For targeted drugs, grouping patients by molecular etiology would make much more sense.
C1 [Brooks, Philip J.; Groft, Steve] NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Tagle, Danilo A.] NIH, Off Special Initiat, Off Director, Natl Ctr Adv Translat Sci, Bethesda, MD USA.
RP Brooks, PJ (reprint author), NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
EM pjbrooks@mail.nih.gov
FU Intramural NIH HHS [Z99 TR999999]
NR 44
TC 3
Z9 3
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
EI 1546-1696
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD JUN
PY 2014
VL 32
IS 6
BP 515
EP 518
DI 10.1038/nbt.2924
PG 4
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA AI9EV
UT WOS:000337233800007
PM 24911489
ER
PT J
AU Milius, D
Dove, ES
Chalmers, D
Dyke, SOM
Kato, K
Nicolas, P
Ouellette, BFF
Ozenberger, B
Rodriguez, LL
Zeps, N
Joly, Y
AF Milius, Djims
Dove, Edward S.
Chalmers, Donald
Dyke, Stephanie O. M.
Kato, Kazuto
Nicolas, Pilar
Ouellette, B. F. Francis
Ozenberger, Brad
Rodriguez, Laura L.
Zeps, Nikolajs
Joly, Yann
TI The International Cancer Genome Consortium's evolving data-protection
policies
SO NATURE BIOTECHNOLOGY
LA English
DT Letter
ID PRIVACY; ANONYMIZATION; GENOTYPES; LIMITS; ERA
C1 [Milius, Djims; Dove, Edward S.; Joly, Yann] McGill Univ, Ctr Genom & Policy, Montreal, PQ, Canada.
[Chalmers, Donald] Univ Tasmania, Fac Law, Hobart, Tas 7001, Australia.
[Dyke, Stephanie O. M.] Wellcome Trust Sanger Inst, Cambridge, England.
[Kato, Kazuto] Osaka Univ, Grad Sch Med, Dept Biomed Eth & Publ Policy, Osaka, Japan.
[Nicolas, Pilar] Univ Basque Country, Univ Deusto, Interuniv Chair Law & Human Genome, E-48080 Bilbao, Spain.
[Ouellette, B. F. Francis] Ontario Inst Canc Res, Informat & Biocomp Program, Toronto, ON, Canada.
[Ouellette, B. F. Francis] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON, Canada.
[Ozenberger, Brad; Rodriguez, Laura L.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Zeps, Nikolajs] Univ Western Australia, Sch Pathol & Lab Med, Crawley, WA, Australia.
RP Milius, D (reprint author), McGill Univ, Ctr Genom & Policy, Montreal, PQ, Canada.
EM yann.joly@mail.mcgill.ca
RI Chalmers, Don/J-7658-2014
OI Chalmers, Don/0000-0002-7925-8818
NR 28
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Z9 6
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
EI 1546-1696
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD JUN
PY 2014
VL 32
IS 6
BP 519
EP 523
DI 10.1038/nbt.2926
PG 5
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA AI9EV
UT WOS:000337233800008
PM 24911490
ER
PT J
AU Johnson, LM
Turkbey, B
Figg, WD
Choyke, PL
AF Johnson, Linda M.
Turkbey, Baris
Figg, William D.
Choyke, Peter L.
TI Multiparametric MRI in prostate cancer management
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Review
ID CONTRAST-ENHANCED MRI; APPARENT DIFFUSION-COEFFICIENT; SEMINAL-VESICLE
INVASION; RADICAL PROSTATECTOMY; 3 T; PERIPHERAL ZONE; TUMOR-DETECTION;
ENDORECTAL MRI; EXTRACAPSULAR EXTENSION; POSTBIOPSY HEMORRHAGE
AB Prostate cancer is the second most common cancer in men worldwide. The clinical behaviour of prostate cancer ranges from low-grade indolent tumours that never develop into clinically significant disease to aggressive, invasive tumours that may progress rapidly to metastatic disease and death. Therefore, there is an urgent clinical need to detect high-grade cancers and to differentiate them from the indolent, slow-growing tumours. Conventional methods of cancer detection-such as levels of prostate-specific antigen (PSA) in serum, digital rectal examination, and random biopsies-are limited in their sensitivity, specificity, or both. The combination of conventional anatomical MRI and functional magnet resonance sequences -known as multiparametric MRI (mp- MRI)- is emerging as an accurate tool for identifying clinically relevant tumours owing to its ability to localize them. In this Review, we discuss the value of mp-MRI in localized and metastatic prostate cancer, highlighting its role in the detection, staging, and treatment planning of prostate cancer.
C1 [Johnson, Linda M.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
[Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
[Figg, William D.] NCI, Clin Pharmacol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, 10 Ctr Dr,MSC 1182,Bldg 10, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
RI Figg Sr, William/M-2411-2016
FU NIH
FX The authors would like to thank the NIH intramural funding programme for
financial support.
NR 103
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Z9 38
U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
EI 1759-4782
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD JUN
PY 2014
VL 11
IS 6
BP 346
EP 353
DI 10.1038/nrclinonc.2014.69
PG 8
WC Oncology
SC Oncology
GA AI8PR
UT WOS:000337183300009
PM 24840072
ER
PT J
AU Birmingham, K
Gradinaru, V
Anikeeva, P
Grill, WM
Pikov, V
McLaughlin, B
Pasricha, P
Weber, D
Ludwig, K
Famm, K
AF Birmingham, Karen
Gradinaru, Viviana
Anikeeva, Polina
Grill, Warren M.
Pikov, Victor
McLaughlin, Bryan
Pasricha, Pankaj
Weber, Douglas
Ludwig, Kip
Famm, Kristoffer
TI Bioelectronic medicines: a research roadmap
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Editorial Material
C1 [Birmingham, Karen; Famm, Kristoffer] GlaxoSmithKline, Bioelect R&D, Stevenage SG1 2NY, Herts, England.
[Gradinaru, Viviana] CALTECH, Pasadena, CA 91125 USA.
[Anikeeva, Polina] MIT, Cambridge, MA 02139 USA.
[Grill, Warren M.] Duke Univ, Durham, NC 27708 USA.
[Pikov, Victor] Huntington Med Res Inst, Pasadena, CA 91105 USA.
[McLaughlin, Bryan] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA.
[Pasricha, Pankaj] Johns Hopkins Univ, Sch Med, Johns Hopkins Ctr Neurogastroenterol, Baltimore, MD 21205 USA.
[Weber, Douglas] Def Adv Res Projects Agcy, Biol Technol Off, Arlington, VA 22203 USA.
[Ludwig, Kip] Natl Inst Neurol Disorders & Stroke, North Bethesda, MD 20852 USA.
RP Famm, K (reprint author), GlaxoSmithKline, Bioelect R&D, Stevenage SG1 2NY, Herts, England.
EM kristoffer.h.famm@gsk.com
OI Grill, Warren/0000-0001-5240-6588
NR 5
TC 32
Z9 33
U1 5
U2 54
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
EI 1474-1784
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD JUN
PY 2014
VL 13
IS 6
BP 399
EP 400
DI 10.1038/nrd4351
PG 2
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA AI8MA
UT WOS:000337169000001
PM 24875080
ER
PT J
AU Holmstrom, KM
Finkel, T
AF Holmstroem, Kira M.
Finkel, Toren
TI Cellular mechanisms and physiological consequences of redox-dependent
signalling
SO NATURE REVIEWS MOLECULAR CELL BIOLOGY
LA English
DT Review
ID PROTEIN-TYROSINE PHOSPHATASES; OXIDATIVE STRESS; HYDROGEN-PEROXIDE;
LIFE-SPAN; STEM-CELLS; REVERSIBLE INACTIVATION; SELF-RENEWAL;
CAENORHABDITIS-ELEGANS; SUPEROXIDE-PRODUCTION; METHIONINE OXIDATION
AB Reactive oxygen species (ROS), which were originally characterized in terms of their harmful effects on cells and invading microorganisms, are increasingly implicated in various cell fate decisions and signal transduction pathways. The mechanism involved in ROS-dependent signalling involves the reversible oxidation and reduction of specific amino acids, with crucial reactive Cys residues being the most frequent target. In this Review, we discuss the sources of ROS within cells and what is known regarding how intracellular oxidant levels are regulated. We further discuss the recent observations that reduction-oxidation (redox)-dependent regulation has a crucial role in an ever-widening range of biological activities-from immune function to stem cell self-renewal, and from tumorigenesis to ageing.
C1 [Holmstroem, Kira M.; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Finkel, T (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
OI Holmstrom, Kira/0000-0001-6434-7909
FU US National Institutes of Health (NIH) Intramural Funds; Leducq
Foundation
FX The authors are grateful to members of the Finkel laboratory for helpful
comments and to I. Rovira for help in preparing the manuscript. This
work was supported by US National Institutes of Health (NIH) Intramural
Funds and The Leducq Foundation.
NR 119
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U1 21
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0072
EI 1471-0080
J9 NAT REV MOL CELL BIO
JI Nat. Rev. Mol. Cell Biol.
PD JUN
PY 2014
VL 15
IS 6
BP 411
EP 421
DI 10.1038/nrm3801
PG 11
WC Cell Biology
SC Cell Biology
GA AI9IE
UT WOS:000337245500012
PM 24854789
ER
PT J
AU Daniels, RD
Kubale, TL
Yiin, JH
Dahm, MM
Hales, TR
Baris, D
Zahm, SH
Beaumont, JJ
Waters, KM
Pinkerton, LE
AF Daniels, Robert D.
Kubale, Travis L.
Yiin, James H.
Dahm, Matthew M.
Hales, Thomas R.
Baris, Dalsu
Zahm, Shelia H.
Beaumont, James J.
Waters, Kathleen M.
Pinkerton, Lynne E.
TI Mortality and cancer incidence in a pooled cohort of US firefighters
from San Francisco, Chicago and Philadelphia (1950-2009)
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID FLORIDA PROFESSIONAL FIREFIGHTERS; HEALTH INTERVIEW SURVEY; CENTRAL
UNITED-STATES; TABLE ANALYSIS SYSTEM; FIRE FIGHTERS; OCCUPATIONAL
EXPOSURES; INCIDENCE RATES; ALCOHOL-USE; TOBACCO USE; OBESITY
AB Objectives To examine mortality patterns and cancer incidence in a pooled cohort of 29 993 US career firefighters employed since 1950 and followed through 2009.
Methods Mortality and cancer incidence were evaluated by life table methods with the US population referent. Standardised mortality (SMR) and incidence (SIR) ratios were determined for 92 causes of death and 41 cancer incidence groupings. Analyses focused on 15 outcomes of a priori interest. Sensitivity analyses were conducted to examine the potential for significant bias.
Results Person-years at risk totalled 858 938 and 403 152 for mortality and incidence analyses, respectively. All-cause mortality was at expectation (SMR = 0.99, 95% CI 0.97 to 1.01, n = 12 028). There was excess cancer mortality (SMR = 1.14, 95% CI 1.10 to 1.18, n = 3285) and incidence (SIR = 1.09, 95% CI 1.06 to 1.12, n = 4461) comprised mainly of digestive (SMR = 1.26, 95% CI 1.18 to 1.34, n = 928; SIR = 1.17, 95% CI 1.10 to 1.25, n = 930) and respiratory (SMR= 1.10, 95% CI 1.04 to 1.17, n = 1096; SIR = 1.16, 95% CI 1.08 to 1.24, n = 813) cancers. Consistent with previous reports, modest elevations were observed in several solid cancers; however, evidence of excess lymphatic or haematopoietic cancers was lacking. This study is the first to report excess malignant mesothelioma (SMR= 2.00, 95% CI 1.03 to 3.49, n = 12; SIR = 2.29, 95% CI 1.60 to 3.19, n = 35) among US firefighters. Results appeared robust under differing assumptions and analytic techniques.
Conclusions Our results provide evidence of a relation between firefighting and cancer. The new finding of excess malignant mesothelioma is noteworthy, given that asbestos exposure is a known hazard of firefighting.
C1 [Daniels, Robert D.; Kubale, Travis L.; Yiin, James H.; Dahm, Matthew M.; Hales, Thomas R.; Waters, Kathleen M.; Pinkerton, Lynne E.] NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA.
[Baris, Dalsu; Zahm, Shelia H.] NCI, Div Canc Epidemiol & Genet, Gaithersburg, MD USA.
[Beaumont, James J.] UC Davis Dept Publ Hlth Sci, Sacramento, CA USA.
RP Daniels, RD (reprint author), NIOSH, Div Surveillance Hazard Evaluat & Field Studies, 4676 Columbia Pkwy,Mailstop R-13, Cincinnati, OH 45226 USA.
EM rtd2@cdc.gov
RI Zahm, Shelia/B-5025-2015
FU National Institute for Occupational Safety and Health (NIOSH) by
National Occupational Research Agenda (NORA); US Fire Administration
(USFA); National Institutes of Health (NIH), National Cancer Institute
(NCI)
FX Research funding was provided by the National Institute for Occupational
Safety and Health (NIOSH) by intramural award under the National
Occupational Research Agenda (NORA), and by the US Fire Administration
(USFA). This research was also supported, in part, by the intramural
research programme of the National Institutes of Health (NIH), National
Cancer Institute (NCI).
NR 45
TC 28
Z9 29
U1 2
U2 19
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
EI 1470-7926
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD JUN
PY 2014
VL 71
IS 6
BP 388
EP 397
DI 10.1136/oemed-2013-101662
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AI9MV
UT WOS:000337257600003
PM 24142974
ER
PT J
AU Huynh, N
Nicholson, BP
Agron, E
Clemons, TE
Bressler, SB
Rosenfeld, PJ
Chew, EY
AF Nancy Huynh
Nicholson, Benjamin P.
Agron, Elvira
Clemons, Traci E.
Bressler, Susan B.
Rosenfeld, Philip J.
Chew, Emily Y.
CA Age-Related Eye Dis Study 2 Res Gr
TI Visual Acuity after Cataract Surgery in Patients with Age-Related
Macular Degeneration
SO OPHTHALMOLOGY
LA English
DT Article
ID HIGH-DOSE SUPPLEMENTATION; BEAVER DAM EYE; CLINICAL-TRIAL;
BETA-CAROTENE; UNITED-STATES; VISION LOSS; VITAMIN-C; DISEASE;
RANIBIZUMAB; RISK
AB Objective: To evaluate visual acuity outcomes after cataract surgery in persons with varying degrees of severity of age-related macular degeneration (AMD).
Design: Cohort study.
Participants: A total of 1232 eyes of 793 participants who underwent cataract surgery during the Age-Related Eye Disease Study 2, a prospective, multicenter, randomized controlled trial of nutritional supplements for treatment of AMD.
Methods: Preoperative and postoperative characteristics of participants who underwent cataract extraction during the 5-year trial were analyzed. Both clinical data and standardized red-reflex lens and fundus photographs were obtained at baseline and annually. Photographs were graded by a centralized reading center for cortical and posterior subcapsular lens opacities and for AMD severity. Cataract surgery was documented at annual study visits or by history during the 6-month telephone calls. Analyses were conducted using multivariate repeated-measures regression.
Main Outcome Measures: Change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA.
Results: Adjusting for age at time of surgery, gender, interval between preoperative and postoperative visits, and type and severity of cataract, the mean changes in visual acuity were as follows: eyes with mild AMD (n = 30) gained 11.2 letters (95% confidence interval [CI], 6.9-15.5), eyes with moderate AMD (n = 346) gained 11.1 letters (95% CI, 9.1-13.2), eyes with severe AMD (n = 462) gained 8.7 letters (95% CI, 6.7-10.7), eyes with noncentral geographic atrophy (n = 70) gained 8.9 letters (95% CI, 5.8-12.1), and eyes with advanced AMD (central geographic atrophy, neovascular disease, or both; n = 324) gained 6.8 letters (95% CI, 4.9-8.8). The visual acuity gain across all AMD severity groups was statistically significant from preoperative values (P < 0.0001). Conclusions: Mean visual acuities improved significantly after cataract surgery across varying degrees of AMD severity. (C) 2014 by the American Academy of Ophthalmology.
C1 [Nancy Huynh; Nicholson, Benjamin P.; Agron, Elvira; Chew, Emily Y.] NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Clemons, Traci E.] EMMES Corp, Rockville, MD USA.
[Bressler, Susan B.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
RP Chew, EY (reprint author), NEI, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
FU Research to Prevent Blindness, Inc., New York, New York; National Eye
Institute, National Institutes of Health, Bethesda, Maryland
[HHS-N-260-2005-00007-C]; Administrative Data Base (ADB)
[N01-EY-5-0007]; EMMES Corporation; Jaeb Center; Allergan, Bausch Lomb;
Bayer Healthcare; Genentech, Lumenis, Inc.; Notal Vision Ltd; Novartis;
Regeneron; Thrombogenics; Sanofi-Aventis
FX The author(s) have made the following disclosure(s): Susan B. Bressler:
Consultante-GlaxoSmithKline; Financial support-EMMES Corporation, the
Jaeb Center, Allergan, Bausch & Lomb, Bayer Healthcare, Genentech,
Lumenis, Inc., Notal Vision Ltd, Novartis, Regeneron, Thrombogenics,
Sanofi-Aventis; Lecturere-Providers of continuing medical education
materials; these grants are negotiated and administered by the School of
Medicine, which receives the grants through the Office of Research
Administration ( individual investigators who participate in such
sponsored projects are not compensated directly by the sponsor but may
receive salary or other support from the institution to support their
effort on the projects). Philip J. Rosenfeld: Consultante-Oraya,
Novartis, Chengdu Kanghong Biotech, Acucela, Thrombogenics, Canon;
Financial support- Carl Zeiss Meditec, Alexion, Potentia,
GlaxoSmithKline; Lecturer-Carl Zeiss Meditec, Allergan, Topcon.;
Supported by Research to Prevent Blindness, Inc., New York, New York
(Physician-Scientist grant to S. B. B.); the National Eye Institute,
National Institutes of Health, Bethesda, Maryland (contract no.:
HHS-N-260-2005-00007-C; Administrative Data Base (ADB) contract no.:
N01-EY-5-0007). The sponsor and funding organization participated in the
design and conduct of the study; collection, management, analysis, and
interpretation of data; and the preparation, review, and approval of the
manuscript.
NR 28
TC 9
Z9 9
U1 1
U2 8
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 JUN
PY 2014
VL 121
IS 6
BP 1229
EP 1236
DI 10.1016/j.ophtha.2013.12.035
PG 8
WC Ophthalmology
SC Ophthalmology
GA AJ0KG
UT WOS:000337339100015
ER
PT J
AU Barnette, AR
Horbar, JD
Soll, RF
Pfister, RH
Nelson, KB
Kenny, MJ
Raju, TNK
Bingham, PM
Inder, TE
AF Barnette, Alan R.
Horbar, Jeffrey D.
Soll, Roger F.
Pfister, Robert H.
Nelson, Karin B.
Kenny, Michael J.
Raju, Tonse N. K.
Bingham, Peter M.
Inder, Terrie E.
TI Neuroimaging in the Evaluation of Neonatal Encephalopathy
SO PEDIATRICS
LA English
DT Article
DE neonatal encephalopathy; computed tomography; MRI; cranial ultrasound
ID HYPOXIC-ISCHEMIC ENCEPHALOPATHY; RADIATION-EXPOSURE; NEWBORN
ENCEPHALOPATHY; COMPUTED-TOMOGRAPHY; IONIZING-RADIATION; MATTER INJURY;
RISK-FACTORS; CANCER; CT; ULTRASONOGRAPHY
AB BACKGROUND AND OBJECTIVE: Computed tomography (CT) is still used for neuroimaging of infants with known or suspected neurologic disorders. Alternative neuroimaging options that do not expose the immature brain to radiation include MRI and cranial ultrasound. We aim to characterize and compare the use and findings of neuroimaging modalities, especially CT, in infants with neonatal encephalopathy.
METHODS: The Vermont Oxford Network Neonatal Encephalopathy Registry enrolled 4171 infants (>= 36 weeks' gestation or treated with therapeutic hypothermia) between 2006 and 2010 who were diagnosed with encephalopathy in the first 3 days of life. Demographic, perinatal, and medical conditions were recorded, along with treatments, comorbidities, and outcomes. The modality, timing, and results of neuroimaging were also collected.
RESULTS: CT scans were performed on 933 of 4107 (22.7%) infants, and 100 of 921 (10.9%) of those received multiple CT scans. Compared with MRI, CT provided less detailed evaluation of cerebral injury in areas of prognostic significance, but was more sensitive than cranial ultrasound for hemorrhage and deep brain structural abnormalities.
CONCLUSIONS: CT is commonly used for neuroimaging in newborn infants with neonatal encephalopathy despite concerns over potential harm from radiation exposure. The diagnostic performance of CT is inferior to MRI in identifying neonatal brain injury. Our data suggest that using cranial ultrasound for screening, followed by MRI would be more appropriate than CT at any stage to evaluate infants with neonatal encephalopathy.
C1 [Barnette, Alan R.] St Francis Med Ctr, Dept Pediat, Cape Girardeau, MO 63703 USA.
[Barnette, Alan R.; Inder, Terrie E.] Washington Univ, St Louis Childrens Hosp, Sch Med, Edward Mallinckrodt Dept Pediat, St Louis, MO 63110 USA.
[Inder, Terrie E.] Washington Univ, St Louis Childrens Hosp, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Inder, Terrie E.] Washington Univ, St Louis Childrens Hosp, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Horbar, Jeffrey D.; Soll, Roger F.; Pfister, Robert H.] Univ Vermont, Coll Med, Dept Pediat, Burlington, VT USA.
[Bingham, Peter M.] Univ Vermont, Coll Med, Dept Neurol, Burlington, VT USA.
[Kenny, Michael J.] Univ Vermont, Coll Med, Biostat Core, Burlington, VT USA.
[Soll, Roger F.] Vermont Oxford Network, Burlington, VT USA.
[Nelson, Karin B.] Childrens Hosp, Med Ctr, Dept Neurol, Washington, DC USA.
[Nelson, Karin B.] NINDS, NIH, Bethesda, MD 20892 USA.
[Raju, Tonse N. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Barnette, AR (reprint author), St Francis Med Ctr, Dept Pediat, 211 St Francis Dr, Cape Girardeau, MO 63703 USA.
EM abarnette@sfmc.net
FU Doris Duke Charitable Foundation
FX Dr Inder received support from the Doris Duke Charitable Foundation.
NR 36
TC 8
Z9 9
U1 0
U2 3
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD JUN
PY 2014
VL 133
IS 6
BP E1508
EP E1517
DI 10.1542/peds.2013-4247
PG 10
WC Pediatrics
SC Pediatrics
GA AI8MY
UT WOS:000337172600004
PM 24864165
ER
PT J
AU Husain, SR
Ohya, Y
Toguchida, J
Puri, RK
AF Husain, Syed R.
Ohya, Yoshikazu
Toguchida, Junya
Puri, Raj K.
TI Current Status of Multipotent Mesenchymal Stromal Cells
SO TISSUE ENGINEERING PART B-REVIEWS
LA English
DT Editorial Material
C1 [Husain, Syed R.; Puri, Raj K.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Ohya, Yoshikazu] Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci, Kashiwa, Chiba, Japan.
[Toguchida, Junya] Kyoto Univ, Inst Frontier Med Sci, Dept Tissue Regenerat, Kyoto, Japan.
[Toguchida, Junya] Kyoto Univ, Ctr iPS Cell Res & Applicat, Dept Cell Growth & Differentiat, Kyoto, Japan.
RP Husain, SR (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, HFM 735,NIH Bldg 29B,29 Lincoln Dr,MSC4555, Bethesda, MD 20892 USA.
EM syed.husain@fda.hhs.gov
NR 2
TC 2
Z9 2
U1 1
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3368
EI 1937-3376
J9 TISSUE ENG PART B-RE
JI Tissue Eng. Part B-Rev.
PD JUN
PY 2014
VL 20
IS 3
BP 189
EP 189
DI 10.1089/ten.teb.2014.0105
PG 1
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA AI9JU
UT WOS:000337249700001
PM 24568643
ER
PT J
AU Stroncek, DF
Sabatino, M
Ren, JQ
England, L
Kuznetsov, SA
Klein, HG
Robey, PG
AF Stroncek, David F.
Sabatino, Marianna
Ren, Jiaqiang
England, Lee
Kuznetsov, Sergei A.
Klein, Harvey G.
Robey, Pamela G.
TI Establishing a Bone Marrow Stromal Cell Transplant Program at the
National Institutes of Health Clinical Center
SO TISSUE ENGINEERING PART B-REVIEWS
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; VERSUS-HOST-DISEASE; IN-VIVO; SENESCENCE;
THERAPY; CULTURE; REPAIR; RECONSTRUCTION; DEFECTS
AB A repository of cryopreserved bone marrow stromal cell (BMSC) products prepared from marrow aspirates of healthy subjects has been created and is being used to treat patients with inflammatory bowel disease, cardiovascular disease, and acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. New methods of manufacturing BMSCs are being investigated including the use of an automated bioreactor for BMSC expansion and the replacement of fetal bovine serum with human platelet lysate as a media supplement. Efforts are also being made to identify markers that can be used to assess the potency of BMSCs.
C1 [Stroncek, David F.; Sabatino, Marianna; Ren, Jiaqiang; England, Lee; Klein, Harvey G.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kuznetsov, Sergei A.; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C711, Bethesda, MD 20892 USA.
EM dstroncek@cc.nih.gov
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
FU NCI; NIAID; NINDS; NIDCR; NIAMS; NIBIB; NHLBI
FX The authors thank the entire staff of the Cell Processing Section, DTM,
CC, NIH for their contributions to the BMSC TC. Funds for this program
were contributed to the BMSC TC by the intramural research programs of
the NCI, NIAID, NINDS, NINDS, NIDCR, NIAMS, NIBIB, and NHLBI.
NR 37
TC 9
Z9 9
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3368
EI 1937-3376
J9 TISSUE ENG PART B-RE
JI Tissue Eng. Part B-Rev.
PD JUN
PY 2014
VL 20
IS 3
BP 200
EP 205
DI 10.1089/ten.teb.2013.0529
PG 6
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA AI9JU
UT WOS:000337249700003
PM 24368014
ER
PT J
AU Battiwalla, M
Barrett, AJ
AF Battiwalla, Minoo
Barrett, A. John
TI Bone Marrow Mesenchymal Stromal Cells to Treat Complications Following
Allogeneic Stem Cell Transplantation
SO TISSUE ENGINEERING PART B-REVIEWS
LA English
DT Article
ID VERSUS-HOST-DISEASE; HEMATOLOGIC MALIGNANCY PATIENTS; IN-VITRO;
TISSUE-REPAIR; MOUSE MODEL; ENGRAFTMENT; MICE; COTRANSPLANTATION;
PROLIFERATION; SUPPRESSION
AB Allogeneic hematopoietic stem cell transplantation (HSCT) is a technologically complicated procedure that represents the only cure for many hematologic malignancies. However, HSCT is often complicated by life-threatening toxicities related to the chemo-radiation conditioning regimen, poor engraftment of donor HSCs, the hyperinflammatory syndrome of graft-versus-host disease (GVHD), infection risks from immunosuppression, and end-organ damage. Bone marrow stromal cells (MSCs), also known as "mesenchymal stromal cells,'' not only play a nurturing role in the hematopoietic microenvironment but also can differentiate into other cell types of mesenchymal origin. MSCs are poorly immunogenic, and they can modulate immunological responses through interactions with a wide range of innate and adaptive immune cells to reduce inflammation. They are easily expanded ex vivo and after infusion, home to sites of injury and inflammation to promote tissue repair. Despite promising early trial results in HSCT with significant responses that have translated into survival benefits, there have been significant barriers to successful commercialization as an off-the-shelf therapy. Current efforts with MSCs in the HSCT setting are geared toward determining the factors determining potency, understanding the precise mechanisms of action in human HSCT, knowing their kinetics and fate, optimizing dose and schedule, incorporating biomarkers as response surrogates, addressing concerns about safety, optimizing clinical trial design, and negotiating the uncharted regulatory landscape for licensable cellular therapy.
C1 [Battiwalla, Minoo; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
EM barrettjj@nhlbi.nih.gov
FU Intramural Research Program of the National Heart, Lung, and Blood
Institute
FX This work was supported in part by the Intramural Research Program of
the National Heart, Lung, and Blood Institute.
NR 56
TC 7
Z9 7
U1 0
U2 5
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3368
EI 1937-3376
J9 TISSUE ENG PART B-RE
JI Tissue Eng. Part B-Rev.
PD JUN
PY 2014
VL 20
IS 3
BP 211
EP 217
DI 10.1089/ten.teb.2013.0566
PG 7
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA AI9JU
UT WOS:000337249700005
PM 24410434
ER
PT J
AU Agarwal, I
Glazer, NL
Barasch, E
Biggs, ML
Djousse, L
Fitzpatrick, AL
Gottdiener, JS
Ix, JH
Kizer, JR
Rimm, EB
Siscovick, DS
Tracy, RP
Zieman, SJ
Mukamal, KJ
AF Agarwal, Isha
Glazer, Nicole L.
Barasch, Eddy
Biggs, Mary L.
Djousse, Luc
Fitzpatrick, Annette L.
Gottdiener, John S.
Ix, Joachim H.
Kizer, Jorge R.
Rimm, Eric B.
Siscovick, David S.
Tracy, Russell P.
Zieman, Susan J.
Mukamal, Kenneth J.
TI Fibrosis-Related Biomarkers and Risk of Total and Cause-Specific
Mortality The Cardiovascular Health Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE biomarkers; fibrosis; inflammation; mortality
ID GROWTH-FACTOR BETA-1; TGF-BETA; DIABETIC-NEPHROPATHY;
PULMONARY-FIBROSIS; CARDIAC FIBROSIS; DISEASE; SERUM; INFLAMMATION;
PIRFENIDONE; INHIBITION
AB Fibrosis has been implicated in diverse diseases of the liver, kidney, lungs, and heart, but its importance as a risk factor for mortality remains unconfirmed. We determined the prospective associations of 2 complementary biomarkers of fibrosis, transforming growth factor-beta (TGF-beta) and procollagen type III N-terminal propeptide (PIIINP), with total and cause-specific mortality risks among community-living older adults in the Cardiovascular Health Study (1996-2010). We measured circulating TGF-beta and PIIINP levels in plasma samples collected in 1996 and ascertained the number of deaths through 2010. Both TGF-beta and PIIINP were associated with elevated risks of total and pulmonary mortality after adjustment for sociodemographic, clinical, and biochemical risk factors. For total mortality, the hazard ratios per doubling of TGF-beta and PIIINP were 1.09 (95% confidence interval (CI): 1.01, 1.17; P = 0.02) and 1.14 (CI: 1.03, 1.27; P = 0.01), respectively. The corresponding hazard ratios for pulmonary mortality were 1.27 (CI: 1.01, 1.60; P = 0.04) for TGF-beta and 1.52 (CI: 1.11, 2.10; P = 0.01) for PIIINP. Associations of TGF-beta and PIIINP with total and pulmonary mortality were strongest among individuals with higher C-reactive protein concentrations (P for interaction < 0.05). Our findings provide some of the first large-scale prospective evidence that circulating biomarkers of fibrosis measured late in life are associated with death.
C1 [Agarwal, Isha; Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Glazer, Nicole L.] Boston Univ, Dept Med, Boston, MA 02215 USA.
[Barasch, Eddy] SUNY Stony Brook, St Francis Hosp, Dept Res & Educ, Roslyn, NY USA.
[Biggs, Mary L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Djousse, Luc] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Djousse, Luc] Boston Vet Affairs Healthcare Syst, Boston, MA USA.
[Fitzpatrick, Annette L.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Gottdiener, John S.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA.
[Ix, Joachim H.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Rimm, Eric B.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Tracy, Russell P.] Univ Vermont, Dept Biochem, Burlington, VT 05405 USA.
[Zieman, Susan J.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA.
[Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
RP Agarwal, I (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM Isha_Agarwal@hms.harvard.edu
RI Djousse, Luc/F-5033-2017
OI Djousse, Luc/0000-0002-9902-3047
FU National Heart, Lung, and Blood Institute [HL118775-01, HL 094555,
HL085083, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC 85083, N01HC85086]; National
Institute on Aging [AG023629]
FX This work was supported by grants HL118775-01, HL 094555, and HL085083
and contracts HHSN268201200036C, HHSN268200800007C, N01HC55222,
N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC 85083, and
N01HC85086 from the National Heart, Lung, and Blood Institute, with
additional contribution from the National Institute of Neurological
Disorders and Stroke. Additional support was provided by grant AG023629
from the National Institute on Aging.
NR 33
TC 9
Z9 9
U1 1
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2014
VL 179
IS 11
BP 1331
EP 1339
DI 10.1093/aje/kwu067
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AI6ZI
UT WOS:000337027400008
PM 24771724
ER
PT J
AU Litzelman, K
Witt, WP
Gangnon, RE
Nieto, FJ
Engelman, CD
Mailick, MR
Skinner, HG
AF Litzelman, Kristin
Witt, Whitney P.
Gangnon, Ronald E.
Nieto, F. Javier
Engelman, Corinne D.
Mailick, Marsha R.
Skinner, Halcyon G.
TI Association Between Informal Caregiving and Cellular Aging in the Survey
of the Health of Wisconsin: The Role of Caregiving Characteristics,
Stress, and Strain
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE caregivers; caregiver strain; population-based studies; stress;
psychological; Survey of the Health of Wisconsin
ID LEUKOCYTE TELOMERE LENGTH; CORONARY-HEART-DISEASE; AGE-RELATED DISEASE;
QUALITY-OF-LIFE; CARDIOVASCULAR HEALTH; PHYSICAL HEALTH; RISK-FACTOR;
DEVELOPMENTAL-DISABILITIES; LONGITUDINAL FINDINGS; PSYCHOLOGICAL STRESS
AB The pathophysiological consequences of caregiving have not been fully elucidated. We evaluated how caregiving, stress, and caregiver strain were associated with shorter relative telomere length (RTL), a marker of cellular aging. Caregivers (n = 240) and some noncaregivers (n = 98) in the 2008-2010 Survey of the Health of Wisconsin, comprising a representative sample of Wisconsin adults aged 21-74 years, reported their sociodemographic, health, and psychological characteristics. RTL was assayed from blood or saliva samples. Median T and S values were used to determine the telomere-to-single copy gene ratio (T/S) for each sample, and log(T/S) was used as the dependent variable in analyses. Multivariable generalized additive models showed that RTL did not differ between caregivers and noncaregivers (difference in log(T/S) = -0.03; P > 0.05), but moderate-to-high levels of stress versus low stress were associated with longer RTL (difference = 0.15; P = 0.04). Among caregivers, more hours per week of care, caring for a young person, and greater strain were associated with shorter RTL (P < 0.05). Caregivers with discordant levels of stress and strain (i.e., low perceived stress/high strain) compared with low stress/low strain had the shortest RTL (difference = -0.24; P = 0.02, P-interaction = 0.13), corresponding to approximately 10-15 additional years of aging. Caregivers with these characteristics may be at increased risk for accelerated aging. Future work is necessary to better elucidate these relationships and develop interventions to improve the long-term health and well-being of caregivers.
C1 [Litzelman, Kristin; Witt, Whitney P.; Gangnon, Ronald E.; Nieto, F. Javier; Engelman, Corinne D.; Skinner, Halcyon G.] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA.
[Gangnon, Ronald E.] Univ Wisconsin, Dept Biostat & Med Informat, Sch Med & Publ Hlth, Madison, WI USA.
[Mailick, Marsha R.] Univ Wisconsin, Sch Social Work, Madison, WI 53706 USA.
[Mailick, Marsha R.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA.
RP Litzelman, K (reprint author), NCI, 9609 Med Ctr Dr,MSC 9761,Room 3E620, Bethesda, MD 20892 USA.
EM kristin.litzelman@nih.gov
FU Wisconsin Partnership Program [233 PRJ56RV]; National Institutes of
Health [5UL 1RR025011, RO-1 CA132718]; National Heart, Lung, and Blood
Institute [1 RC2 HL101468]; National Institute on Aging [F31 AG 044073];
Center for Demography of Health and Aging at the University of
Wisconsin-Madison
FX Funding for SHOW was provided by the Wisconsin Partnership Program
(grant 233 PRJ56RV), the National Institutes of Health (Clinical and
Translational Science Award 5UL 1RR025011), and the National Heart,
Lung, and Blood Institute (grant 1 RC2 HL101468). Funding for this study
was provided by a training grant from the National Institute on Aging
(grant F31 AG 044073; Principal Investigator: Kristin Litzelman) and the
Center for Demography of Health and Aging at the University of
Wisconsin-Madison, which supported the caregiving component of the SHOW
interviews (Principal Investigator: Whitney P. Witt). The assays of
telomere length were supported by National Institutes of Health grant
RO-1 CA132718.
NR 117
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Z9 9
U1 3
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2014
VL 179
IS 11
BP 1340
EP 1352
DI 10.1093/aje/kwu066
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AI6ZI
UT WOS:000337027400009
PM 24780842
ER
PT J
AU Baker, D
Park, C
Sweeney, C
McCormack, L
Durkin, M
Brenner, R
Dabelea, D
Entwisle, B
AF Baker, Dean
Park, Christina
Sweeney, Carol
McCormack, Lacey
Durkin, Maureen
Brenner, Ruth
Dabelea, Dana
Entwisle, Barbara
TI Recruitment of Women in the National Children's Study Initial Vanguard
Study
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE birth cohort; children; epidemiology; National Children's Study;
population; recruitment; sampling
AB The initial Vanguard Study of the National Children's Study was conducted during 2009-2010 in 7 locations in the United States. A goal was to evaluate the feasibility and yield of a household-based sampling design to recruit pregnant women. A multistage area probability sampling design was used to identify study locations (generally, counties) that were subsequently divided into smaller geographical units, termed segments. Between 7 and 18 segments were selected in each location, and dwelling units within segments were listed. A household-based recruitment process was implemented, which included enumeration of households to identify age-eligible women, pregnancy screening to identify pregnant women eligible for immediate enrollment and nonpregnant women for telephone follow-up, and administration of informed consent to eligible women. After a recruitment period of 17-20 months, 67,181 (89%) households were enumerated, which identified 34,172 (88%) age-eligible women to whom the pregnancy screener was administered. Among those who completed the screener, 2,285 women became eligible for enrollment, of whom 1,399 (61%) enrolled. Although response rates were fairly high at initial contact and among pregnant women, the overall yield was lower than anticipated. In particular, telephone follow-up of nonpregnant women was not a practicable strategy for prospective recruitment of newly pregnant women.
C1 [Baker, Dean] Univ Calif Irvine, Ctr Occupat & Environm Hlth, Irvine, CA 92617 USA.
[Baker, Dean] Univ Calif Irvine, Sch Med, Dept Med, Irvine, CA 92617 USA.
[Park, Christina; Brenner, Ruth] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Childrens Study Program Off, Rockville, MD USA.
[Sweeney, Carol] Univ Utah, Sch Med, Dept Internal Med, Div Epidemiol, Salt Lake City, UT USA.
[McCormack, Lacey] S Dakota State Univ, Coll Educ & Human Sci, Dept Hlth & Nutr Sci, Brookings, SD 57007 USA.
[Durkin, Maureen] Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA.
[Durkin, Maureen] Univ Wisconsin, Dept Pediat, Madison, WI USA.
[Dabelea, Dana] Univ Colorado, Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA.
[Entwisle, Barbara] Univ N Carolina, Carolina Populat Ctr, Coll Arts & Sci, Chapel Hill, NC USA.
[Entwisle, Barbara] Univ N Carolina, Dept Sociol, Coll Arts & Sci, Chapel Hill, NC USA.
RP Baker, D (reprint author), Univ Calif Irvine, Ctr Occupat & Environm Hlth, Suite 100, Irvine, CA 92617 USA.
EM dbaker@uci.edu
RI Durkin, Maureen/B-7834-2015;
OI Sweeney, Carol/0000-0003-1113-7160
FU National Institutes of Health, Department of Health and Human Services
[N01-HD-53414, N01-HD-63416, N01-HD-53410, N01-HD-53415, N01-HD-53396,
N01-HD-53413, N01-HD-53411]
FX This work was supported by the National Institutes of Health, Department
of Health and Human Services, administered by the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (contracts
N01-HD-53414, N01-HD-63416, N01-HD-53410, N01-HD-53415, N01-HD-53396,
N01-HD-53413, and N01-HD-53411).
NR 17
TC 11
Z9 11
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2014
VL 179
IS 11
BP 1366
EP 1374
DI 10.1093/aje/kwu062
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AI6ZI
UT WOS:000337027400011
PM 24793429
ER
PT J
AU Blumberg, S
Enanoria, WTA
Lloyd-Smith, JO
Lietman, TM
Porco, TC
AF Blumberg, Seth
Enanoria, Wayne T. A.
Lloyd-Smith, James O.
Lietman, Thomas M.
Porco, Travis C.
TI Identifying Postelimination Trends for the Introduction and
Transmissibility of Measles in the United States
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE disease elimination; effective reproduction number; heterogeneity of
transmission; measles; preventable disease; transmissibility; United
States; vaccine coverage
ID VACCINATION COVERAGE; SIZE DISTRIBUTION; ELIMINATION; OUTBREAKS;
POLIOMYELITIS; IMMUNIZATION; POPULATION; VACCINES; DISEASES; CHILDREN
AB The continued elimination of measles requires accurate assessment of its epidemiology and a critical evaluation of how its incidence is changing with time. National surveillance of measles in the United States between 2001 and 2011 provides data on the number of measles introductions and the size of the resulting transmission chains. These data allow inference of the effective reproduction number, R-eff, and the probability of an outbreak occurring. Our estimate of 0.52 (95% confidence interval: 0.44, 0.60) for R-eff is smaller than prior results. Our findings are relatively insensitive to the possibility that as few as 75% of cases were detected. Although we confirm that measles remains eliminated, we identify an increasing trend in the number of measles cases with time. We show that this trend is likely attributable to an increase in the number of disease introductions rather than a change in the transmissibility of measles. However, we find that transmissibility may increase substantially if vaccine coverage drops by as little as 1%. Our general approach of characterizing the case burden of measles is applicable to the epidemiologic assessment of other weakly transmitting or vaccine-controlled pathogens that are either at risk of emerging or on the brink of elimination.
C1 [Blumberg, Seth; Enanoria, Wayne T. A.; Lietman, Thomas M.; Porco, Travis C.] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA.
[Blumberg, Seth; Lloyd-Smith, James O.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Enanoria, Wayne T. A.] Univ Calif Berkeley, Sch Publ Hlth, Ctr Infect Dis & Emergency Readiness, Berkeley, CA 94720 USA.
[Lloyd-Smith, James O.] Univ Calif Los Angeles, Ecol & Evolutionary Biol Dept, Los Angeles, CA USA.
[Lietman, Thomas M.] Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94143 USA.
[Lietman, Thomas M.; Porco, Travis C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Porco, TC (reprint author), Univ Calif San Francisco, Francis I Proctor Fdn, 513 Parnassus Ave, San Francisco, CA 94143 USA.
EM travis.porco@ucsf.edu
RI Lloyd-Smith, James/K-4080-2012
OI Lloyd-Smith, James/0000-0001-7941-502X
FU National Institute of Health Modeling Infectious Disease Agent Study
program [NIH NIGMS 1-U01-GM087728]; Research and Policy for Infectious
Disease Dynamics program of the Science and Technology Directorate,
Department of Homeland Security; National Institutes of Health, Fogarty
International Center; National Science Foundation [EF-0928690]; De Logi
Chair in Biological Sciences
FX This work was supported by the National Institute of Health Modeling
Infectious Disease Agent Study program (grant NIH NIGMS 1-U01-GM087728
to T. C. P., T. M. L., W. T. A. E., and S. B.); the Research and Policy
for Infectious Disease Dynamics program of the Science and Technology
Directorate, Department of Homeland Security (funding to S. B. and
J.O.L.-S.); the National Institutes of Health, Fogarty International
Center (funding to S. B. and J.O.L.-S.); the National Science Foundation
(grant EF-0928690 to J.O.L.-S.); and the De Logi Chair in Biological
Sciences (funding to J.O.L.-S.).
NR 26
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Z9 11
U1 2
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2014
VL 179
IS 11
BP 1375
EP 1382
DI 10.1093/aje/kwu068
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AI6ZI
UT WOS:000337027400012
PM 24786800
ER
PT J
AU Adams, KF
Harris, TB
Kipnis, V
AF Adams, Kenneth F.
Harris, Tamara B.
Kipnis, Victor
TI RE: "BODY MASS AND WEIGHT CHANGE IN ADULTS IN RELATION TO MORTALITY
RISK" Reply
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
C1 [Adams, Kenneth F.] Minnesota Dept Hlth, Minnesota Canc Surveillance Syst, St Paul, MN 55164 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Kipnis, Victor] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Adams, KF (reprint author), Minnesota Dept Hlth, Minnesota Canc Surveillance Syst, St Paul, MN 55164 USA.
EM kenneth.adams@state.mn.us
NR 3
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 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2014
VL 179
IS 11
BP 1403
EP 1404
DI 10.1093/aje/kwu100
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA AI6ZI
UT WOS:000337027400016
PM 24786798
ER
PT J
AU Ning, L
Kurihara, H
de Vega, S
Ichikawa-Tomikawa, N
Xu, Z
Nonaka, R
Kazuno, S
Yamada, Y
Miner, JH
Arikawa-Hirasawa, E
AF Ning, Liang
Kurihara, Hidetake
de Vega, Susana
Ichikawa-Tomikawa, Naoki
Xu, Zhuo
Nonaka, Risa
Kazuno, Saiko
Yamada, Yoshihiko
Miner, Jeffrey H.
Arikawa-Hirasawa, Eri
TI Laminin alpha 1 Regulates Age-Related Mesangial Cell Proliferation and
Mesangial Matrix Accumulation through the TGF-beta Pathway
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID GLOMERULAR-BASEMENT-MEMBRANE; GROWTH-FACTOR-BETA; DIABETIC-NEPHROPATHY;
EXTRACELLULAR-MATRIX; TRANSFORMING GROWTH-FACTOR-BETA-1; KIDNEY-DISEASE;
IN-VIVO; A-CHAIN; EXPRESSION; RECEPTOR
AB Laminin alpha 1 (LAMA1), a subunit of the Laminin-111 basement membrane component, has been implicated in various biological functions in vivo and in vitro. Although LAMA1 is present in kidney, its roles in the kidney are unknown because of early embryonic lethality. Herein, we used a viable conditional knockout mouse model with a deletion of Lama1 in the epiblast Lineage (Lama1(cko)) to study the role of LAMA1 in kidney development and function. Adult Lama1(cko) mice developed focal glomerulosclerosis and proteinuria with age. In addition, mesangial cell proliferation was increased, and the mesangial matrix, which normally contains Laminin-111, was greatly expanded. In vitro, mesangial cells from Lama1(cko) mice exhibited significantly increased proliferation compared with those from controls. This increased proliferation was inhibited by the addition of exogenous LAMA1-containing laminin-111, but not by Laminin-211 or Laminin-511, suggesting a specific role for LAMA1 in regulating mesangial cell behavior. Moreover, the absence of LAMA1 increased transforming growth factor (TGF)-beta 1 induced Smad2 phosphorylation, and inhibitors of TGF-beta 1 receptor I kinase blocked Smad2 phosphorylation in both control and Lama1(cko) mesangial cells, indicating that the increased Smad2 phosphorylation occurred in the absence of LAMA1 via the TGF-beta 1 receptor. These findings suggest that LAMA1 plays a critical role in kidney function and kidney aging by regulating the mesangial cell population and mesangial matrix deposition through TGF-beta/Smad signaling.
C1 [Ning, Liang; de Vega, Susana; Ichikawa-Tomikawa, Naoki; Xu, Zhuo; Nonaka, Risa; Arikawa-Hirasawa, Eri] Juntendo Univ, Grad Sch Med, Biomed Res Ctr, Res Inst Dis Old Age, Tokyo 1138421, Japan.
[Kurihara, Hidetake] Juntendo Univ, Grad Sch Med, Biomed Res Ctr, Dept Anat & Life Struct, Tokyo 1138421, Japan.
[Arikawa-Hirasawa, Eri] Juntendo Univ, Grad Sch Med, Biomed Res Ctr, Dept Neurol, Tokyo 1138421, Japan.
[Kazuno, Saiko] Juntendo Univ, Grad Sch Med, Biomed Res Ctr, Div Prote & Biomol Sci, Tokyo 1138421, Japan.
[Ichikawa-Tomikawa, Naoki] Fukushima Med Univ, Sch Med, Dept Basic Pathol, Fukushima, Japan.
[Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Miner, Jeffrey H.] Washington Univ, Sch Med, Dept Internal Med, Div Renal, St Louis, MO 63110 USA.
RP Arikawa-Hirasawa, E (reprint author), Juntendo Univ, Grad Sch Med, Res Inst Dis Old Age, Bunkyo Ku, 2-1-1 Hongo, Tokyo 1138421, Japan.
EM ehirasaw@juntendo.ac.jp
FU Ministry of Education, Culture, Sports, Science, and Technology (MEXT),
Japan [24790860]; NIH Intramural Program of the National Institute of
Dental and Craniofacial Research; NIH [R01DK078314]; MEXT Supported
Program for the Strategic Research Foundation at Private Universities;
[17082008]; [2230023]
FX Supported by a Ministry of Education, Culture, Sports, Science, and
Technology (MEXT), Japan, Grant-in-Aid for Young Scientists (B) 24790860
(L.N.) and grants 17082008 and 2230023 (E.A.-H.), NIH Intramural Program
of the National Institute of Dental and Craniofacial Research grant
(Y.Y.), NIH grant R01DK078314 (J.H.M.), and MEXT Supported Program for
the Strategic Research Foundation at Private Universities (2011 to
2015).
NR 52
TC 9
Z9 10
U1 0
U2 9
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 JUN
PY 2014
VL 184
IS 6
BP 1683
EP 1694
DI 10.1016/j.ajpath.2014.02.006
PG 12
WC Pathology
SC Pathology
GA AI5ZE
UT WOS:000336948700007
PM 24720953
ER
PT J
AU Wang, Y
Feng, DC
Wang, H
Xu, MJ
Park, O
Li, YM
Gao, B
AF Wang, Yan
Feng, Dechun
Wang, Hua
Xu, Ming-Jiang
Park, Ogyi
Li, Yongmei
Gao, Bin
TI STAT4 Knockout Mice Are More Susceptible to Concanavalin A-Induced
T-Cell Hepatitis
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MEDIATED LIVER-INJURY; ISCHEMIA/REPERFUSION
INJURY; SERINE PHOSPHORYLATION; IFN-GAMMA; IL-12; INFLAMMATION;
ACTIVATION; INTERLEUKIN-12; INVOLVEMENT
AB STAT4, which is activated mainly by IL-12, promotes inflammatory responses by inducing Th1 and Th2 cytokines. Recent genome-wide association studies indicate that STAT4 gene variants are associated with risk of various types of liver diseases, but how STAT4 contributes to liver disease pathogenesis remains obscure. In this study, STAT4 activation was detected in liver immune cells from patients with viral hepatitis and autoimmune hepatitis, as well as in a mouse model of concanavaLin A (Con A)-induced hepatitis. Such STAT4 activation was detected mainly in T cells, natural killer T cells, and macrophages and Kupffer cells, and was diminished in I112a/and 11/26/mice. As expected, disruption of the Stat4 gene reduced production of Th1 and Th2 cytokines, but surprisingly exacerbated Con A-induced liver injury. Similarly, disruption of IL12a or 11126 also augmented Con A-induced hepatocellular damage. Further studies showed that hepatic natural killer T (NKT) cells from Con A-treated Stat4(-/-) mice had higher levels of FasL expression and increased cytotoxicity against hepatocytes than those from Con A-treated WT mice. In vitro, blocking FasL attenuated Stat4(-/-) NKT cytotoxicity against hepatocytes. In conclusion, despite up-regulation of proinflammatory cytokines, STAT4 protects against acute T-cell hepatitis, which is mediated by direct or indirect down-regulation of FasL expression on NKT cells.
C1 [Wang, Yan; Feng, Dechun; Wang, Hua; Xu, Ming-Jiang; Park, Ogyi; Li, Yongmei; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
[Wang, Yan] Peking Univ, Hosp 1, Dept Infect Dis, Beijing 100871, Peoples R China.
RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
RI Feng, Dechun/Q-5962-2016
FU NIH-National Institute on Alcohol Abuse and Alcoholism; China
Scholarship Council; Wu Mengchao Medical Science Foundation; National
Natural Science Foundation of China [81300312]; NIH
[N01-DK-7-0004/HHSN267200700004C]
FX Supported by the intramural program of the NIH-National Institute on
Alcohol Abuse and Alcoholism (B.G.), the China Scholarship Council
(Y.W.), the Wu Mengchao Medical Science Foundation (Y.W.), and National
Natural Science Foundation of China grant 81300312 (Y.W.). The Liver
Tissue Cell Distribution System, University of Minnesota, Minneapolis,
MN, is supported by NIH contract N01-DK-7-0004/HHSN267200700004C.
NR 40
TC 6
Z9 7
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 JUN
PY 2014
VL 184
IS 6
BP 1785
EP 1794
DI 10.1016/j.ajpath.2014.02.023
PG 10
WC Pathology
SC Pathology
GA AI5ZE
UT WOS:000336948700016
PM 24731448
ER
PT J
AU Martin, DL
Marks, M
Galdos-Cardenas, G
Gilman, RH
Goodhew, B
Ferrufino, L
Halperin, A
Sanchez, G
Verastegui, M
Escalante, P
Naquira, C
Levy, MZ
Bern, C
AF Martin, Diana L.
Marks, Morgan
Galdos-Cardenas, Gerson
Gilman, Robert H.
Goodhew, Brook
Ferrufino, Lisbeth
Halperin, Anthony
Sanchez, Gerardo
Verastegui, Manuela
Escalante, Patricia
Naquira, Cesar
Levy, Michael Z.
Bern, Caryn
TI Regional Variation in the Correlation of Antibody and T-Cell Responses
to Trypanosoma cruzi
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID CHAGAS-DISEASE; GENETIC-VARIABILITY; IMMUNE-RESPONSES; INTERFERON-GAMMA;
INFECTION; BLOOD; ARGENTINA; TRANSMISSION; PATHOGENESIS; POPULATIONS
AB Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major cause of morbidity and mortality in Central and South America. Geographic variations in the sensitivity of serologic diagnostic assays to T. cruzi may reflect differences in T cruzi exposure. We measured parasite-specific T-cell responses among seropositive individuals in two populations from South America with widely varying antibody titers against T. cruzi. Antibody titers among seropositive individuals were significantly lower in Arequipa, Peru compared with Santa Cruz, Bolivia. Similarly, the proportion of seropositive individuals with positive T-cell responses was lower in Peru than Bolivia, resulting in overall lower frequencies of interferon-gamma (IFN gamma)-secreting cells from Peruvian samples. However, the magnitude of the IFN gamma response was similar among the IFN gamma responders in both locations. These data indicate that immunological discrepancies based on geographic region are reflected in T-cell responses as well as antibody responses.
C1 [Martin, Diana L.; Goodhew, Brook] Ctr Dis Control & Prevent, Atlanta, GA 30329 USA.
NIH, Bethesda, MD 20892 USA.
Johns Hopkins Univ, Baltimore, MD USA.
[Galdos-Cardenas, Gerson; Ferrufino, Lisbeth] Hosp Univ Japones, Santa Cruz, Bolivia.
[Galdos-Cardenas, Gerson; Ferrufino, Lisbeth] Asociac Benef PRISMA, Lima, Peru.
[Gilman, Robert H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Naquira, Cesar] Arequipa Minist Hlth, Arequipa, Peru.
[Levy, Michael Z.] Univ Penn, Philadelphia, PA 19104 USA.
[Sanchez, Gerardo; Verastegui, Manuela] Univ Peruana Cayetano Heredia, Lima, Peru.
RP Martin, DL (reprint author), Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, MS D-65,1600 Clifton Rd NE, Atlanta, GA 30329 USA.
EM hzx3@cdc.gov; mmarkster@gmail.com; gerson_galdos@yahoo.es;
gilmanabob@gmail.com; isd6@cdc.gov; lisbeth_ferrufino@yahoo.es;
gjsg2@hotmail.com; mveraste@jhsph.edu; patriciaeem2008@gmail.com;
cesar.naquira@gmail.com; rnzlevy@mail.med.upenn.edu;
Caryn.Bern2@ucsf.edu
FU National Institutes of Health Tropical Medical Research Center [P50
AI074285]; National Institutes of Health Fogarty Scholars Program [R24
TW007988]
FX This work was funded by National Institutes of Health Tropical Medical
Research Center Grant P50 AI074285 and National Institutes of Health
Fogarty Scholars Program Grant R24 TW007988.
NR 35
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Z9 1
U1 1
U2 2
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD JUN
PY 2014
VL 90
IS 6
BP 1074
EP 1081
DI 10.4269/ajtmh.13-0391
PG 8
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA AI4FD
UT WOS:000336820200016
PM 24710614
ER
PT J
AU Genkinger, JM
Wang, M
Li, R
Albanes, D
Anderson, KE
Bernstein, L
van den Brandt, PA
English, DR
Freudenheim, JL
Fuchs, CS
Gapstur, SM
Giles, GG
Goldbohm, RA
Hakansson, N
Horn-Ross, PL
Koushik, A
Marshall, JR
McCullough, ML
Miller, AB
Robien, K
Rohan, TE
Schairer, C
Silverman, DT
Stolzenberg-Solomon, RZ
Virtamo, J
Willett, WC
Wolk, A
Ziegler, RG
Smith-Warner, SA
AF Genkinger, J. M.
Wang, M.
Li, R.
Albanes, D.
Anderson, K. E.
Bernstein, L.
van den Brandt, P. A.
English, D. R.
Freudenheim, J. L.
Fuchs, C. S.
Gapstur, S. M.
Giles, G. G.
Goldbohm, R. A.
Hakansson, N.
Horn-Ross, P. L.
Koushik, A.
Marshall, J. R.
McCullough, M. L.
Miller, A. B.
Robien, K.
Rohan, T. E.
Schairer, C.
Silverman, D. T.
Stolzenberg-Solomon, R. Z.
Virtamo, J.
Willett, W. C.
Wolk, A.
Ziegler, R. G.
Smith-Warner, S. A.
TI Dairy products and pancreatic cancer risk: a pooled analysis of 14
cohort studies
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE pancreatic cancer; dairy products; calcium intake; pooled analysis
ID FOOD-FREQUENCY QUESTIONNAIRE; VITAMIN-D STATUS; DIETARY ASSESSMENT;
UNITED-STATES; REGRESSION-MODELS; MALE SMOKERS; CALIFORNIA TEACHERS;
25-HYDROXYVITAMIN D; NUTRITIONAL FACTORS; EXOCRINE PANCREAS
AB .Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing a parts per thousand yen500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes a parts per thousand yen1300 with < 500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.
C1 [Genkinger, J. M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Wang, M.; Li, R.; Willett, W. C.; Smith-Warner, S. A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Wang, M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Albanes, D.; Schairer, C.; Silverman, D. T.; Stolzenberg-Solomon, R. Z.; Ziegler, R. G.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Anderson, K. E.] Univ Minnesota, Sch Publ Hlth, Mason Canc Ctr, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Bernstein, L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA.
[Bernstein, L.] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[van den Brandt, P. A.] Maastricht Univ, Sch Oncol & Dev Biol GROW, Dept Epidemiol, Maastricht, Netherlands.
[English, D. R.; Giles, G. G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Canc Epidemiol Ctr,Canc Council Victoria, Melbourne, Vic, Australia.
[Freudenheim, J. L.; Marshall, J. R.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Fuchs, C. S.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA.
[Fuchs, C. S.; Willett, W. C.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Fuchs, C. S.; Willett, W. C.] Harvard Univ, Sch Med, Boston, MA USA.
[Gapstur, S. M.; McCullough, M. L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Goldbohm, R. A.] TNO Qual Life, Dept Prevent & Hlth, Leiden, Netherlands.
[Hakansson, N.; Wolk, A.] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
[Horn-Ross, P. L.] Canc Prevent Inst Calif, Fremont, CA USA.
[Koushik, A.] Univ Montreal, Dept Social & Prevent Med, Montreal, PQ, Canada.
[Miller, A. B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Robien, K.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC USA.
[Rohan, T. E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Virtamo, J.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Willett, W. C.; Smith-Warner, S. A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
RP Genkinger, JM (reprint author), Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St, New York, NY 10019 USA.
EM jg3081@columbia.edu
RI Albanes, Demetrius/B-9749-2015;
OI Robien, Kim/0000-0002-2120-2280; Giles, Graham/0000-0003-4946-9099;
English, Dallas/0000-0001-7828-8188
FU National Institutes of Health [CA55075, CA139578]
FX This work was supported by National Institutes of Health grants #CA55075
and #CA139578.
NR 87
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U1 3
U2 17
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 JUN
PY 2014
VL 25
IS 6
BP 1106
EP 1115
DI 10.1093/annonc/mdu019
PG 10
WC Oncology
SC Oncology
GA AI6ZO
UT WOS:000337028100005
PM 24631943
ER
PT J
AU Akilzhanova, A
Nurkina, Z
Momynaliev, K
Ramanculov, E
Zhumadilov, Z
Rakhypbekov, T
Hayashida, N
Nakashima, M
Takamura, N
AF Akilzhanova, Ainur
Nurkina, Zhannur
Momynaliev, Kuvat
Ramanculov, Erlan
Zhumadilov, Zhaxibai
Rakhypbekov, Tolebay
Hayashida, Naomi
Nakashima, Masahiro
Takamura, Noboru
TI Genetic Profile and Determinants of Homocysteine Levels in Kazakhstan
Patients with Breast Cancer (vol 33, pg 4049, 2013)
SO ANTICANCER RESEARCH
LA English
DT Correction
C1 [Akilzhanova, Ainur; Hayashida, Naomi; Takamura, Noboru] Nagasaki Univ, Grad Sch Biomed Sci, Dept Global Hlth Med & Welf, Nagasaki 852, Japan.
[Akilzhanova, Ainur; Nurkina, Zhannur; Zhumadilov, Zhaxibai] Nazarbayev Univ, Ctr Life Sci, Dept Genom & Personalised Med, Astana, Kazakhstan.
[Akilzhanova, Ainur; Momynaliev, Kuvat; Ramanculov, Erlan] Natl Biotechnol Ctr, Astana, Kazakhstan.
[Rakhypbekov, Tolebay] Semey State Med Univ, Ctr Oncol, Semey, Kazakhstan.
[Nakashima, Masahiro] Nagasaki Univ, Grad Sch Biomed Sci, Dept Tumor & Diagnost Pathol, Nagasaki 852, Japan.
RP Akilzhanova, A (reprint author), Nagasaki Univ, Grad Sch Biomed Sci, Dept Global Hlth Med & Welf, Nagasaki 852, Japan.
NR 1
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U1 1
U2 7
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
EI 1791-7530
J9 ANTICANCER RES
JI Anticancer Res.
PD JUN
PY 2014
VL 34
IS 6
BP 3231
EP 3231
PG 1
WC Oncology
SC Oncology
GA AI4ZM
UT WOS:000336875200071
ER
PT J
AU Kessler, DC
Taylor, JA
Dunson, DB
AF Kessler, David C.
Taylor, Jack A.
Dunson, David B.
TI Learning phenotype densities conditional on many interacting predictors
SO BIOINFORMATICS
LA English
DT Article
ID DIRICHLET PROCESS MIXTURES; VARIABLE SELECTION; EM ALGORITHM;
REGRESSION; MODELS; EXPERTS
AB Motivation: Estimating a phenotype distribution conditional on a set of discrete-valued predictors is a commonly encountered task. For example, interest may be in how the density of a quantitative trait varies with single nucleotide polymorphisms and patient characteristics. The subset of important predictors is not usually known in advance. This becomes more challenging with a high-dimensional predictor set when there is the possibility of interaction.
Results: We demonstrate a novel non-parametric Bayes method based on a tensor factorization of predictor-dependent weights for Gaussian kernels. The method uses multistage predictor selection for dimension reduction, providing succinct models for the phenotype distribution. The resulting conditional density morphs flexibly with the selected predictors. In a simulation study and an application to molecular epidemiology data, we demonstrate advantages over commonly used methods.
C1 [Kessler, David C.] SAS Inst Inc, Adv Analyt Div, Cary, NC 27513 USA.
[Taylor, Jack A.] NIEHS, Mol & Genet Epidemiol Sect, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Taylor, Jack A.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Dunson, David B.] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA.
RP Kessler, DC (reprint author), SAS Inst Inc, Adv Analyt Div, Cary, NC 27513 USA.
EM dave.kessler@gmail.com
OI taylor, jack/0000-0001-5303-6398
FU Intramural Research Program of the NIH; National Institute of
Environmental Health Sciences [Z01 ES049032, R01ES017240, R01ES017436];
National Institute of Environmental Health Sciences training
[T32ES007018]
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences, Z01
ES049032. David Kessler's work was partially supported by National
Institute of Environmental Health Sciences training grant T32ES007018.
David Dunson's work was supported by Award Numbers R01ES017240 and
R01ES017436 from the National Institute of Environmental Health
Sciences.
NR 33
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Z9 1
U1 2
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD JUN 1
PY 2014
VL 30
IS 11
BP 1562
EP 1568
DI 10.1093/bioinformatics/btu040
PG 7
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 AI7CU
UT WOS:000337040200010
PM 24501099
ER
PT J
AU Volkow, ND
Tomasi, D
Wang, GJ
Studentsova, Y
Margus, B
Crawford, TO
AF Volkow, Nora D.
Tomasi, Dardo
Wang, Gene-Jack
Studentsova, Yana
Margus, Brad
Crawford, Thomas O.
TI Brain glucose metabolism in adults with ataxia-telangiectasia and their
asymptomatic relatives
SO BRAIN
LA English
DT Article
DE cerebellum; globus pallidus; fusiform gyrus; hippocampus; ataxia
telangiectasia mutated; ATM
ID PARKINSONS-DISEASE; ABNORMALITIES; MOTOR; CONNECTIVITY; STIMULATION;
CEREBELLUM; PHENOTYPE; DYSTONIA; BEHAVIOR; ATROPHY
AB Ataxia-Telangiectasia (A-T) is a recessive multi-system disorder with prominent cerebellar degeneration. Volkow et al. use PET to reveal widespread changes in brain glucose metabolism in patients with A-T, in addition to the anticipated reduction in cerebellar metabolism. Hyperactivity in the globus pallidus is indicative of basal ganglia involvement in the disorder.Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and F-18-fluorodeoxyglucose to measure brain glucose metabolism (quantified as A mu mol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic rates including hyperactivity in globus pallidus indicative of basal ganglia involvement. Changes in basal ganglia metabolism offer potential insight into targeting strategies for therapeutic deep brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions.
C1 [Volkow, Nora D.; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana] NIAAA, Rockville, MD 20857 USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
[Margus, Brad] AT Childrens Project, Coconut Creek, FL 33073 USA.
[Crawford, Thomas O.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA.
RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
RI Tomasi, Dardo/J-2127-2015
FU National Institutes of Health's (NIH) Intramural Research Program
National Institute on Alcohol Abuse and Alcoholism (NIAAA) [Y1AA3009];
A-T Children's Project
FX Research supported by National Institutes of Health's (NIH) Intramural
Research Program National Institute on Alcohol Abuse and Alcoholism
(NIAAA) #Y1AA3009 and by the A-T Children's Project and carried out at
Brookhaven National Laboratory.
NR 42
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U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD JUN
PY 2014
VL 137
BP 1753
EP 1761
DI 10.1093/brain/awu092
PN 6
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA AI6ZU
UT WOS:000337028900022
PM 24747834
ER
PT J
AU Ellis, MW
Schlett, CD
Millar, EV
Wilkins, KJ
Crawford, KB
Morrison-Rodriguez, SM
Pacha, LA
Gorwitz, RJ
Lanier, JB
Tribble, DR
AF Ellis, Michael W.
Schlett, Carey D.
Millar, Eugene V.
Wilkins, Kenneth J.
Crawford, Katrina B.
Morrison-Rodriguez, Stephanie M.
Pacha, Laura A.
Gorwitz, Rachel J.
Lanier, Jeffrey B.
Tribble, David R.
TI Hygiene Strategies to Prevent Methicillin-Resistant Staphylococcus
aureus Skin and Soft Tissue Infections: A Cluster-Randomized Controlled
Trial Among High-Risk Military Trainees
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE Staphylococcus aureus; methicillin-resistant Staphylococcus aureus
(MRSA); skin and soft tissue infection; chlorhexidine; military
ID HOUSEHOLD CONTACTS; MARINE RECRUITS; UNITED-STATES; COLONIZATION;
EPIDEMIOLOGY; CELLULITIS; CHILDREN; PREVALENCE; CALIFORNIA; MUPIROCIN
AB Background. Effective measures are needed to prevent methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) in high-risk community settings. The study objective was to evaluate the effect of personal hygiene-based strategies on rates of overall SSTI and MRSA SSTI.
Methods. We conducted a prospective, field-based, cluster-randomized trial in US Army Infantry trainees from May 2010 through January 2012. There were 3 study groups with incrementally increased education and hygiene-based interventions: standard (S), enhanced standard (ES), and chlorhexidine (CHG). The primary endpoints were incidence of overall SSTI and MRSA SSTI.
Results. The study included 30 209 trainees constituting 540 platoons (168 S, 192 ES, and 180 CHG). A total of 1203 (4%) participants developed SSTI, 316 (26%) due to MRSA. The overall SSTI rate was 4.15 (95% confidence interval [CI], 3.77-4.58) per 100 person-cycles. SSTI rates by study group were 3.48 (95% CI, 2.87-4.22) for S, 4.18 (95% CI, 3.56-4.90) for ES, and 4.71 (95% CI, 4.03-5.50) for CHG. The MRSA SSTI rate per 100 person-cycles for all groups was 1.10 (95% CI,.91-1.32). MRSA SSTI rates by study group were 1.0 (95% CI,.70-1.42) for S, 1.29 (95% CI,.98-1.71) for ES, and 0.97 (95% CI,.70-1.36) for CHG.
Conclusions. Personal hygiene and education measures, including once-weekly use of chlorhexidine body wash, did not prevent overall SSTI or MRSA SSTI in a high-risk population of military trainees.
C1 [Ellis, Michael W.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA.
[Schlett, Carey D.; Millar, Eugene V.; Crawford, Katrina B.; Morrison-Rodriguez, Stephanie M.; Tribble, David R.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Infect Dis Clin Res Program, Bethesda, MD 20814 USA.
[Wilkins, Kenneth J.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Pacha, Laura A.] US Army Publ Hlth Command, Army Inst Publ Hlth, Aberdeen Proving Ground, MD USA.
[Gorwitz, Rachel J.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Lanier, Jeffrey B.] Martin Army Community Hosp, Ft Benning, GA USA.
RP Ellis, MW (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM michael.ellis@usuhs.edu
FU Infectious Disease Clinical Research Program, a DoD program through the
Uniformed Services University of the Health Sciences; National Institute
of Allergy and Infectious Diseases, National Institutes of Health
[Y1-AI-5072]; CDC, National Center for Emerging and Zoonotic Infectious
Diseases, Division of Healthcare Quality Promotion [09FED914272]; DoD
Global Emerging Infections Surveillance program [C0366-11-HS]
FX The work was supported by the Infectious Disease Clinical Research
Program, a DoD program executed through the Uniformed Services
University of the Health Sciences. 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
(Interagency Agreement Y1-AI-5072). Additional funding was provided by
CDC, National Center for Emerging and Zoonotic Infectious Diseases,
Division of Healthcare Quality Promotion (Interagency Agreement
(09FED914272 to M. W. E.), and the DoD Global Emerging Infections
Surveillance program (C0366-11-HS to M. W. E.).
NR 38
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U1 0
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUN 1
PY 2014
VL 58
IS 11
BP 1540
EP 1548
DI 10.1093/cid/ciu166
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AI7AL
UT WOS:000337031200009
PM 24633684
ER
PT J
AU Chambers, HF
Bartlett, JG
Bonomo, RA
Chiou, C
Cosgrove, SE
Cross, HR
Daum, RS
Downing, M
Evans, SR
Knisely, J
Kreiswirth, BN
Lautenbach, E
Mickley, BS
Patel, R
Pettigrew, MM
Rodvold, KA
Spellberg, B
Fowler, VG
AF Chambers, Henry F.
Bartlett, John G.
Bonomo, Robert A.
Chiou, Christine
Cosgrove, Sara E.
Cross, Heather R.
Daum, Robert S.
Downing, Michele
Evans, Scott R.
Knisely, Jane
Kreiswirth, Barry N.
Lautenbach, Ebbing
Mickley, Brenda S.
Patel, Robin
Pettigrew, Melinda M.
Rodvold, Keith A.
Spellberg, Brad
Fowler, Vance G., Jr.
TI Antibacterial Resistance Leadership Group: Open for Business
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
DE antibacterial resistance; ARLG; Leadership Group; clinical trials;
clinical research
AB Funded by the National Institute of Allergy and Infectious Diseases, the Antibacterial Resistance Leadership Group (ARLG) is tasked with developing a clinical research agenda and conducting clinical studies to address the growing public health threat of antibacterial resistance. The ARLG has identified 4 high-priority areas of research: infections caused by gram-negative bacteria, infections caused by gram-positive bacteria, antimicrobial stewardship and infection prevention, and diagnostics. The ARLG will be accepting proposals from the scientific community for clinical research that addresses 1 or more of these high-priority areas. These studies should have the potential to transform medical practice and be unlikely to occur without ARLG support. The purpose of this article is to make interested parties aware of clinical research opportunities made available by ARLG and to encourage submission of clinical research proposals that address the problem of antibacterial resistance.
C1 [Chambers, Henry F.; Downing, Michele] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Bartlett, John G.; Cosgrove, Sara E.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Bonomo, Robert A.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Louis Stokes Cleveland Dept Vet Affairs Med Ctr, Med Serv, Cleveland, OH 44106 USA.
[Chiou, Christine; Knisely, Jane] NIH, Div Microbiol & Infect Dis, Inst Allergy & Infect Dis, Bethesda, MD 20892 USA.
[Cross, Heather R.; Mickley, Brenda S.; Fowler, Vance G., Jr.] Duke Univ, Duke Clin Res Inst, Durham, NC USA.
[Daum, Robert S.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
[Evans, Scott R.] Harvard Univ, Dept Biostat, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Kreiswirth, Barry N.] Rutgers State Univ, New Jersey Med Sch, TB Ctr, Publ Hlth Res Inst, Newark, NJ USA.
[Lautenbach, Ebbing] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Patel, Robin] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Patel, Robin] Mayo Clin, Dept Med, Rochester, MN USA.
[Pettigrew, Melinda M.] Yale Univ, Sch Publ Hlth, Dept Epidemiol, New Haven, CT USA.
[Rodvold, Keith A.] Univ Illinois, Coll Pharm, Chicago, IL USA.
[Rodvold, Keith A.] Univ Illinois, Coll Med, Chicago, IL USA.
[Spellberg, Brad] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.
[Fowler, Vance G., Jr.] Duke Univ, Dept Med, Durham, NC USA.
RP Fowler, VG (reprint author), Duke Univ, Med Ctr, Dept Med, Div Infect Dis, Box 102359,Hanes Bldg,Rm 153, Durham, NC 27710 USA.
EM fowle003@mc.duke.edu
FU NIAID NIH HHS [UM1-AI104681, AI063517-07, AI072219-05, R01 AI063517, R01
AI072219, UM1 AI104681]
NR 0
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U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUN 1
PY 2014
VL 58
IS 11
BP 1571
EP 1576
DI 10.1093/cid/ciu132
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AI7AL
UT WOS:000337031200013
PM 24610430
ER
PT J
AU Echouffo-Tcheugui, JB
Prorok, PC
AF Echouffo-Tcheugui, Justin B.
Prorok, Philip C.
TI Considerations in the design of randomized trials to screen for type 2
diabetes
SO CLINICAL TRIALS
LA English
DT Article
ID RISK-ASSESSMENT TOOLS; ADDITION-CAMBRIDGE; TASK-FORCE; CANCER; PROSTATE;
LUNG; PEOPLE; DEATH; INDIVIDUALS; MORTALITY
AB Background Randomized controlled trials (RCTs) are the most robust and valid approach to evaluate screening for diseases. Many in the diabetes research community have advocated sole reliance on RCTs for designing diabetes screening policies. However, the challenges of conducting RCTs of screening for type 2 diabetes may have been underappreciated.
Purpose Discuss the key theoretical concepts and practical challenges of designing and conducting RCTs of diabetes screening.
Methods Narrative and critical review of the literature pertaining to the theory and practice of designing and conducting RCTs of diabetes screening.
Results We present the theoretical basis of a diabetes screening trial, using concepts developed mainly in studies of cancer screening and illustrations from the Cambridge component of the Anglo Danish Dutch Study of Intensive Treatment In peOple with screeN-detected diabetes in primary care (ADDITION-Cambridge), the only extant trial of diabetes screening. We examine design issues, including the appropriate trial question, choice of design, and duration of follow-up, and address aspects of trial implementation, including recruitment, randomization, endpoint determination, sample size requirements, and screening interval.
Limitations The limited number of trials of diabetes screening did not permit us to illustrate many of the practical difficulties one encounters when implementing theoretical concepts.
Conclusion When diabetes screening trials are planned, we suggest careful consideration to potential areas of practical difficulty, especially the need for particularly large sample sizes and extended follow-up, and the choice of appropriate outcomes and screening intervals.
C1 [Echouffo-Tcheugui, Justin B.] Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA 30322 USA.
[Prorok, Philip C.] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Echouffo-Tcheugui, JB (reprint author), Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA.
EM jechouf@emory.edu
NR 44
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U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
EI 1740-7753
J9 CLIN TRIALS
JI Clin. Trials
PD JUN
PY 2014
VL 11
IS 3
BP 284
EP 291
DI 10.1177/1740774513517062
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI3UX
UT WOS:000336791500002
PM 24459176
ER
PT J
AU Snyder, PJ
Ellenberg, SS
Cunningham, GR
Matsumoto, AM
Bhasin, S
Barrett-Connor, E
Gill, TM
Farrar, JT
Cella, D
Rosen, RC
Resnick, SM
Swerdloff, RS
Cauley, JA
Cifelli, D
Fluharty, L
Pahor, M
Ensrud, KE
Lewis, CE
Molitch, ME
Crandall, JP
Wang, C
Budoff, MJ
Wenger, NK
Mohler, ER
Bild, DE
Cook, NL
Keaveny, TM
Kopperdahl, DL
Lee, D
Schwartz, AV
Storer, TW
Ershler, WB
Roy, CN
Raffel, LJ
Romashkan, S
Hadley, E
AF Snyder, Peter J.
Ellenberg, Susan S.
Cunningham, Glenn R.
Matsumoto, Alvin M.
Bhasin, Shalender
Barrett-Connor, Elizabeth
Gill, Thomas M.
Farrar, John T.
Cella, David
Rosen, Raymond C.
Resnick, Susan M.
Swerdloff, Ronald S.
Cauley, Jane A.
Cifelli, Denise
Fluharty, Laura
Pahor, Marco
Ensrud, Kristine E.
Lewis, Cora E.
Molitch, Mark E.
Crandall, Jill P.
Wang, Christina
Budoff, Matthew J.
Wenger, Nanette K.
Mohler, Emile R., III
Bild, Diane E.
Cook, Nakela L.
Keaveny, Tony M.
Kopperdahl, David L.
Lee, David
Schwartz, Ann V.
Storer, Thomas W.
Ershler, William B.
Roy, Cindy N.
Raffel, Leslie J.
Romashkan, Sergei
Hadley, Evan
TI The Testosterone Trials: Seven coordinated trials of testosterone
treatment in elderly men
SO CLINICAL TRIALS
LA English
DT Article
ID LEAN BODY-MASS; BENIGN PROSTATIC HYPERPLASIA; LOW SERUM TESTOSTERONE;
BONE-MINERAL DENSITY; OLDER MEN; MUSCLE STRENGTH; TRANSDERMAL
TESTOSTERONE; EXOGENOUS TESTOSTERONE; PHYSICAL PERFORMANCE; SEXUAL
FUNCTION
AB Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results.
Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions.
Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials.
Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation.
Potential limitations Setting the serum testosterone concentration sufficiently low to ensure that most men would be unequivocally testosterone deficient, as well as many other entry criteria, resulted in screening approximately 30 men in person to randomize one participant.
Conclusion Designing The Testosterone Trials as a coordinated set of seven trials afforded many important scientific and logistical advantages but required an intensive recruitment and screening effort.
C1 [Snyder, Peter J.] Univ Penn, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Ellenberg, Susan S.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Cunningham, Glenn R.] Baylor Coll Med, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA.
[Cunningham, Glenn R.] St Lukes Med Ctr, Houston, TX USA.
[Matsumoto, Alvin M.] Univ Washington, Sch Med,Dept Vet Affairs Puget Sound Hlth Care Sy, Geriatr Res Educ & Clin Ctr,Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA.
[Bhasin, Shalender] Harvard Univ, Sch Med, Brigham & Womens Hosp, Res Program Mens Hlth Aging & Metab, Boston, MA USA.
[Barrett-Connor, Elizabeth] Univ Calif San Diego, Sch Med, Dept Family & Preventat Med, La Jolla, CA 92093 USA.
[Gill, Thomas M.] Yale Univ, Sch Med, Div Geriatr Med, New Haven, CT USA.
[Farrar, John T.; Cifelli, Denise; Fluharty, Laura] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Cella, David] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
[Rosen, Raymond C.] New England Res Inst, Watertown, MA 02172 USA.
[Resnick, Susan M.] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA.
[Swerdloff, Ronald S.; Wang, Christina] Harbor Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst, Div Endocrinol, Torrance, CA USA.
[Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Pahor, Marco] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA.
[Ensrud, Kristine E.] Univ Minnesota, Dept Med, Div Epidemiol & Community Hlth, Minneapolis VA Hlth Care Syst, Minneapolis, MN 55455 USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA.
[Molitch, Mark E.] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA.
[Crandall, Jill P.] Albert Einstein Coll Med, Div Endocrinol & Geriatr, Bronx, NY 10467 USA.
[Budoff, Matthew J.] Harbor Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst, Div Cardiol, Torrance, CA USA.
[Wenger, Nanette K.] Emory Univ, Sch Med, Div Cardiol, Emory Heart & Vasc Ctr, Atlanta, GA 30322 USA.
[Mohler, Emile R., III] Univ Penn, Perelman Sch Med, Div Cardiovasc Dis, Philadelphia, PA 19104 USA.
[Mohler, Emile R., III] Univ Penn, Perelman Sch Med, Sect Vasc Med, Philadelphia, PA 19104 USA.
[Bild, Diane E.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Cook, Nakela L.] NHLBI, Clin Applicat & Prevent Branch, Div Cardiovasc Sci, Ctr Cardiovasc Outcomes Res, Bethesda, MD 20892 USA.
[Keaveny, Tony M.] Univ Calif Berkeley, Dept Mech Engn, Berkeley, CA 94720 USA.
[Keaveny, Tony M.] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA.
[Keaveny, Tony M.; Kopperdahl, David L.; Lee, David] ON Diagnost, Berkeley, CA USA.
[Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Storer, Thomas W.] Boston Med Ctr, Sect Endocrinol Diabet & Nutr, Boston, MA USA.
[Ershler, William B.] Inst Adv Studies Aging, Div Hematol Oncol, Falls Church, VA USA.
[Roy, Cindy N.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA.
[Raffel, Leslie J.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Romashkan, Sergei; Hadley, Evan] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA.
RP Snyder, PJ (reprint author), Univ Penn, Smilow Ctr Translat Res, Div Endocrinol Diabet & Metab, Perelman Sch Med, 3400 Civic Ctr Blvd, Philadelphia, PA 19104 USA.
EM pjs@mail.med.upenn.edu
RI Cauley, Jane/N-4836-2015
OI Cauley, Jane/0000-0003-0752-4408
FU National Institute on Aging, National Institutes of Health [U01
AG030644, U01 AG034661, R01 AG37679]; National Heart, Lung and Blood
Institute; National Institute of Neurological Diseases and Stroke;
National Institute of Child Health and Human Development; National
Institute on Aging [R01 AG037679]; AbbVie; Department of Veterans
Affairs Puget Sound Health Care System; Midcareer Investigator Award in
Patient-Oriented Research from the National Institute on Aging
[K24-AG021507]; Academic Leadership Award from the National Institute on
Aging [K07AG043587]; Claude D. Pepper Older Americans Independence
Center [P30-AG021342]; Intramural Research Program, National Institute
on Aging, National Institutes of Health; National Institute for
Diabetes, Digestive and Kidney Diseases, National Institutes of Health
[DK079626]
FX The Testosterone Trials were supported by a grant from the National
Institute on Aging, National Institutes of Health (U01 AG030644),
supplemented by funds from the National Heart, Lung and Blood Institute,
National Institute of Neurological Diseases and Stroke, and National
Institute of Child Health and Human Development. The Bone Trial was
supported by a grant from the National Institute on Aging (R01
AG037679). The Anemia Trial was supported by a grant from the National
Institute on Aging, National Institutes of Health (U01 AG034661) to the
Partnership for Anemia Clinical and Translational Trials in the Elderly
consortium. AbbVie (formerly Solvay and Abbott Laboratories) generously
provided funding, AndroGel, and placebo gel. A. M. M. was supported by
the Department of Veterans Affairs Puget Sound Health Care System. T. M.
G. was the recipient of a Midcareer Investigator Award in
Patient-Oriented Research (K24-AG021507) and is the recipient of an
Academic Leadership Award (K07AG043587), both from the National
Institute on Aging. The Yale Field Center was partially supported by the
Claude D. Pepper Older Americans Independence Center (P30-AG021342). S.
M. R. was supported by the Intramural Research Program, National
Institute on Aging, National Institutes of Health. C. E. L. was
supported by the National Institute for Diabetes, Digestive and Kidney
Diseases, National Institutes of Health (DK079626) to the UAB Diabetes
Research and Training Center. J.A.C. was supported by the National
Institute on Aging, National Institutes of Health (R01 AG37679).
NR 46
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U1 1
U2 7
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
EI 1740-7753
J9 CLIN TRIALS
JI Clin. Trials
PD JUN
PY 2014
VL 11
IS 3
BP 362
EP 375
DI 10.1177/1740774514524032
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI3UX
UT WOS:000336791500011
PM 24686158
ER
PT J
AU Baker, SG
AF Baker, Stuart G.
TI Principal stratification: All-or-none versus partial compliance
SO CLINICAL TRIALS
LA English
DT Letter
ID RANDOMIZED-TRIAL; NONCOMPLIANCE; INTENTION; TREAT
C1 NCI, Bethesda, MD 20892 USA.
RP Baker, SG (reprint author), NCI, 9609 Med Ctr Dr 5E638,MSC 9789, Bethesda, MD 20892 USA.
EM sb16i@nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1740-7745
EI 1740-7753
J9 CLIN TRIALS
JI Clin. Trials
PD JUN
PY 2014
VL 11
IS 3
BP 380
EP 381
DI 10.1177/1740774514524650
PG 2
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI3UX
UT WOS:000336791500013
PM 24844842
ER
PT J
AU Craig, MT
McBain, CJ
AF Craig, Michael T.
McBain, Chris J.
TI The emerging role of GABAB receptors as regulators of network dynamics:
fast actions from a 'slow' receptor?
SO CURRENT OPINION IN NEUROBIOLOGY
LA English
DT Article
ID NEOCORTICAL GABAERGIC NEURONS; PERSISTENT CORTICAL ACTIVITY; DENDRITIC
CA2+ SPIKES; PYRAMIDAL NEURONS; NEUROGLIAFORM CELLS; LAYER 1; PREFRONTAL
CORTEX; CEREBRAL-CORTEX; DISTINCT ROLES; DENTATE GYRUS
AB Convention holds that ionotropic receptors mediate fast neurotransmission and that 'slow' G-protein coupled metabotropic receptors have a secondary, modulatory role in the control of neuronal networks. Here, we discuss recent evidence showing that activation of metabotropic GABA(B) receptors in cortical layer 1 can powerfully inhibit principal cell activity and that their activation can rapidly halt ongoing network activity. Inputs from both within and outwith the cortex converge upon layer 1 where they target various populations of interneurons, including neurogliaform cells. We argue that neurogliaform cells are the main effector of a powerful inhibitory circuit that, acting through GABAB receptors, can be differentially recruited by long-range connections to serve in roles as diverse as conscious perception and memory consolidation.
C1 [Craig, Michael T.; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA.
RP McBain, CJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD 20892 USA.
EM mcbainc@mail.nih.gov
RI Craig, Michael/E-7070-2011
OI Craig, Michael/0000-0001-8481-6709
FU Intramural NIH HHS [ZIA HD001205-21]
NR 59
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U1 1
U2 6
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-4388
EI 1873-6882
J9 CURR OPIN NEUROBIOL
JI Curr. Opin. Neurobiol.
PD JUN
PY 2014
VL 26
BP 15
EP 21
DI 10.1016/j.conb.2013.10.002
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA AI4IB
UT WOS:000336827800004
PM 24650499
ER
PT J
AU Prussin, C
AF Prussin, Calman
TI Eosinophilic Gastroenteritis and Related Eosinophilic Disorders
SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Eosinophilic gastroenteritis; Eosinophilic gastritis; Eosinophilia; Food
allergy; EGID
ID PROTEIN-LOSING ENTEROPATHY; FOOD ALLERGY; GASTROINTESTINAL-DISEASE;
ELEMENTAL DIET; ESOPHAGITIS; MONTELUKAST; BUDESONIDE; CHILDREN; PATIENT;
GLUCOCORTICOSTEROIDS
AB Eosinophilic gastroenteritis (EGE) represents one member within the spectrum of diseases collectively referred to as eosinophilic gastrointestinal disorders, which includes eosinophilic esophagitis (EoE), gastritis, enteritis, and colitis. EGE is less common than EoE and involves a different site of disease but otherwise shares many common features with EoE. The clinical manifestations of EGE are protean and can vary from nausea and vomiting to protein-losing enteropathy or even bowel obstruction requiring surgery. Although systemic corticosteroids are an effective treatment for EGE, their use results in substantial corticosteroid toxicity. Accordingly, there is a great need for improved therapies for these patients.
C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Prussin, C (reprint author), NIAID, Lab Allerg Dis, NIH, 10 Ctr Dr,MSC-1881, Bethesda, MD 20892 USA.
EM cprussin@niaid.nih.gov
OI Prussin, Calman/0000-0002-3917-3326
FU Intramural NIH HHS [ZIA AI000993-07]
NR 55
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U1 1
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8553
EI 1558-1942
J9 GASTROENTEROL CLIN N
JI Gastroenterol. Clin. North Am.
PD JUN
PY 2014
VL 43
IS 2
BP 317
EP +
DI 10.1016/j.gtc.2014.02.013
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AI6SJ
UT WOS:000337007000012
PM 24813518
ER
PT J
AU Toke, ER
Lorincz, O
Csiszovszki, Z
Somogyi, E
Felfoldi, G
Molnar, L
Szipocs, R
Kolonics, A
Malissen, B
Lori, F
Trocio, J
Bakare, N
Horkay, F
Romani, N
Tripp, CH
Stoitzner, P
Lisziewicz, J
AF Toke, E. R.
Lorincz, O.
Csiszovszki, Z.
Somogyi, E.
Felfoldi, G.
Molnar, L.
Szipocs, R.
Kolonics, A.
Malissen, B.
Lori, F.
Trocio, J.
Bakare, N.
Horkay, F.
Romani, N.
Tripp, C. H.
Stoitzner, P.
Lisziewicz, J.
TI Exploitation of Langerhans cells for in vivo DNA vaccine delivery into
the lymph nodes
SO GENE THERAPY
LA English
DT Article
ID SKIN DENDRITIC CELLS; LINEAR POLYETHYLENIMINE; CANCER VACCINES; ANTIGEN;
MOUSE; MACROPINOCYTOSIS; BIODISTRIBUTION; RECEPTOR; IMMUNOTHERAPY;
IMMUNIZATION
AB There is no clinically available cancer immunotherapy that exploits Langerhans cells (LCs), the epidermal precursors of dendritic cells (DCs) that are the natural agent of antigen delivery. We developed a DNA formulation with a polymer and obtained synthetic 'pathogen-like' nanopartieles that preferentially targeted LCs in epidermal cultures. These nanoparticles applied topically under a patch-elicited robust immune responses in human subjects. To demonstrate the mechanism of action of this novel vaccination strategy in live animals, we assembled a high-resolution two-photon laser scanning-microscope. Nanoparticles applied on the native skin poorly penetrated and poorly induced LC motility. The combination of nanopartitle administration and skin treatment was essential both for efficient loading the vaccine into the epidermis and for potent activation of the LCs to migrate into the lymph nodes. LCs in the epidermis picked up nanoparticles and accumulated them in the nuclear region demonstrating an effective nuclear DNA delivery in vivo. Tissue distribution studies revealed that the majority of the DNA was targeted to the lymph nodes. Preclinical toxicity Of the LC-targeting DNA vaccine was limited to mild and transient local erythema caused by the skin treatment. This novel, clinically proven LC targeting:DNA vaccine platform technology broadens the options On DC-targeting vaccines to generate therapeutic immunity against cancer.
C1 [Toke, E. R.; Lorincz, O.; Csiszovszki, Z.; Somogyi, E.; Felfoldi, G.; Molnar, L.; Lisziewicz, J.] Genet Immun Kft, H-1045 Budapest, Hungary.
[Szipocs, R.; Kolonics, A.] Wigner RCP HAS, H-1121 Budapest, Hungary.
[Szipocs, R.; Kolonics, A.] R&D Ultrafast Lasers Ltd, H-1539 Budapest, Hungary.
[Malissen, B.] Aix Marseille Univ, CNRS UMR7280, Ctr Immunol Marseille Luminy, INSERM U1104, Marseille, France.
[Lori, F.; Trocio, J.; Bakare, N.] Res Inst Genet & Human Therapy, Bethesda, MD USA.
[Horkay, F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD USA.
[Romani, N.; Tripp, C. H.; Stoitzner, P.] Med Univ Innsbruck, Dept Dermatol & Venerol, A-6020 Innsbruck, Austria.
RP Lisziewicz, J (reprint author), eMMUNITY Inc, 4400 East West Hwy, Bethesda, MD 20814 USA.
EM julianna.lisziewicz@emmunityinc.com
OI stoitzner, patrizia/0000-0002-8488-6704; Malissen,
Bernard/0000-0003-1340-9342
FU NIH [N01-AI-70043]; Hungarian National Office for Research and
Technology (FIBERSC2) [TECH-09-A2-2009-0134, DVCLIN01]; Intramural
Research Program of the NICHD; NIH; COMET Center ONCOTYROL (Cell Therapy
Unit); Austrian Federal Ministries for Transport, Innovation and
Technology, and Economics, Family and Youth (via the Austrian Research
Promotion Agency / FFG); Standortagentur Tirol
FX We thank Drs Michael A Ussery and Hao Zhang (Division of AIDS, NIAID)
for their support. The study was supported by NIH (N01-AI-70043) and
Hungarian National Office for Research and Technology (FIBERSC2,
contract no. TECH-09-A2-2009-0134 and DVCLIN01). FH acknowledges the
support of the Intramural Research Program of the NICHD, NIH. CHT was in
part supported by the COMET Center ONCOTYROL (Cell Therapy Unit), which
is funded by the Austrian Federal Ministries for Transport, Innovation
and Technology, and Economics, Family and Youth (via the Austrian
Research Promotion Agency / FFG) and the Standortagentur Tirol.
NR 44
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U1 0
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
EI 1476-5462
J9 GENE THER
JI Gene Ther.
PD JUN
PY 2014
VL 21
IS 6
BP 566
EP 574
DI 10.1038/gt.2014.29
PG 9
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Research & Experimental Medicine
GA AI5CU
UT WOS:000336883800004
PM 24694539
ER
PT J
AU Wojcik, GL
Thio, CL
Kao, WHL
Latanich, R
Goedert, JJ
Mehta, SH
Kirk, GD
Peter, MG
Cox, AL
Kims, AY
Chungs, RT
Thomas, DL
Duggal, P
AF Wojcik, G. L.
Thio, C. L.
Kao, W. H. L.
Latanich, R.
Goedert, J. J.
Mehta, S. H.
Kirk, G. D.
Peter, M. G.
Cox, A. L.
Kims, A. Y.
Chungs, R. T.
Thomas, D. L.
Duggal, P.
TI Admixture analysis of spontaneous hepatitis C virus clearance in
individuals of African descent
SO GENES AND IMMUNITY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; INFECTION; IL28B; INFERENCE;
ANCESTRY; HOST; MAP
AB Hepatitis C virus (HCV) infects an estimated 3% of the global population with the majority of individuals (75-85%) failing to clear the virus without treatment, leading to chronic liver disease. Individuals of African descent have lower rates of clearance compared with individuals of European descent and this is not fully explained by social and environmental factors. This suggests that differences in genetic background may contribute to this difference in clinical outcome following HCV infection. Using 473 individuals and 792 721 single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS), we estimated local African ancestry across the genome. Using admixture mapping and logistic regression, we identified two regions of interest associated with spontaneous clearance of HCV (15q24, 20p12). A genome-wide significant variant was identified on chromosome 15 at the imputed SNP, rs55817928 (P=6.18 x 10(-8)) between the genes SCAPER and RCN. Each additional copy of the African ancestral C allele is associated with 2.4 times the odds of spontaneous clearance. Conditional analysis using this SNP in the logistic regression model explained one-third of the local ancestry association. Additionally, signals of selection in this area suggest positive selection due to some ancestral pathogen or environmental pressure in African, but not in European populations.
C1 [Wojcik, G. L.; Kao, W. H. L.; Mehta, S. H.; Kirk, G. D.; Thomas, D. L.; Duggal, P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Thio, C. L.; Kao, W. H. L.; Latanich, R.; Cox, A. L.; Thomas, D. L.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Goedert, J. J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Peter, M. G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Kims, A. Y.; Chungs, R. T.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA.
RP Duggal, P (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E6539, Baltimore, MD 21205 USA.
EM pduggal@jhsph.edu
FU Office of AIDS Research through the Center for Inherited Diseases at
Johns Hopkins University; National Institute on Drug Abuse [R01DA013324,
DA033541, DA012568, DA04334]; National Institute of Allergy and
Infectious Diseases [U19AI088791, AI082630, UO1-AI-35004, UO1-AI-31834,
UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Frederick
National Laboratory for Cancer Research [HHSN261200800001E]; Intramural
Research Programs of the National Institutes of Health; Frederick
National Laboratory for Cancer Research; 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 Other Communication Disorders; National Center for Research
Resources (UCSF-CTSI Grant) [UL1 RR024131]; Intramural Research Program
of the NIH, Frederick National Lab, Center for Cancer Research
FX Primary data are available through the central NIH GWAS data repository
at the National Center for Biotechnology Information (NCBI), National
Library of Medicine
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).
This project was funded in whole or in part by the Office of AIDS
Research through the Center for Inherited Diseases at Johns Hopkins
University, the National Institute on Drug Abuse (R01DA013324, DA033541,
DA012568 and DA04334), the National Institute of Allergy and Infectious
Diseases (U19AI088791 and AI082630), and the Frederick National
Laboratory for Cancer Research (contract HHSN261200800001E). This
research was supported in part by the Intramural Research Programs of
the National Institutes of Health and the Frederick National Laboratory
for Cancer Research. The WINS is funded by the National Institute of
Allergy and Infectious Diseases (U01-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 co-funded by the National
Cancer Institute, the National Institute on Drug Abuse, and the National
Institute on Deafness and Other Communication Disorders. Funding is also
provided by the National Center for Research Resources (UCSF-CTSI Grant
Number UL1 RR024131). The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government. This
Research was supported in part by the Intramural Research Program of the
NIH, Frederick National Lab, Center for Cancer Research.
NR 29
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U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1466-4879
EI 1476-5470
J9 GENES IMMUN
JI Genes Immun.
PD JUN
PY 2014
VL 15
IS 4
BP 241
EP 246
DI 10.1038/gene.2014.11
PG 6
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA AI5CT
UT WOS:000336883700006
PM 24622687
ER
PT J
AU Wright, MF
Lewis, KL
Fisher, TC
Hooker, GW
Emanuel, TE
Biesecker, LG
Biesecker, BB
AF Wright, Martha F.
Lewis, Katie L.
Fisher, Tyler C.
Hooker, Gillian W.
Emanuel, Toby E.
Biesecker, Leslie G.
Biesecker, Barbara B.
TI Preferences for results delivery from exome sequencing/genome sequencing
SO GENETICS IN MEDICINE
LA English
DT Article
DE expectations; genome; preferences; results; sequencing
ID GENETIC RESEARCH; PARTICIPANTS; EXPECTATIONS; CLINSEQ; RETURN
AB Purpose: The aim of this study was to explore the implications of sequencing information and stated preferences for return of results among research participants.
Methods: Six focus groups were held with 39 ClinSeq participants. The groups included participants who had received results, those who had not, those affected with cardiovascular disease, and healthy adults. Audio recordings of the sessions were transcribed and coded and analyzed for themes.
Results: All participants expressed interest in receiving results that are medically actionable, nonactionable, carrier, and less so variants that cannot be interpreted. Most participants preferred to receive results in person, although several endorsed use of Internet-based resources that they could return to. Participants identified benefits for health management along with satisfying curiosity, Making scientific contributions, and partnering in research. Value was seen in gaining control over health risks. Concerns were distress and/or fear that may result, Some participants were opposed to or ambivalent about learning certain types of results, particularly those having to do with diseases that were incurable or that might have implications for. the health of their children.
Conclusion: There was relative enthusiasm about the value of learning sequencing information, yet it was tempered by concern about negative feeling responses and aversion to learning about incurable conditions.
C1 [Wright, Martha F.; Lewis, Katie L.; Biesecker, Leslie G.] NHGRI, Genet Dis & Res Branch, NIH, Bethesda, MD 20892 USA.
[Fisher, Tyler C.; Hooker, Gillian W.; Biesecker, Barbara B.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Emanuel, Toby E.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
RP Biesecker, BB (reprint author), NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
EM barbarab@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health
FX The authors thank the focus group moderators, Barbara Rosenthal and
Chanza Baytop, and the ClinSeq participants for their time and
contributions. This work was supported by the Intramural Research
Program of the National Human Genome Research Institute, National
Institutes of Health.
NR 17
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD JUN
PY 2014
VL 16
IS 6
BP 442
EP 447
DI 10.1038/gim.2013.170
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA AI6UF
UT WOS:000337011800004
PM 24310310
ER
PT J
AU Stewart, DR
Brems, H
Gomes, AG
Ruppert, SL
Callens, T
Williams, J
Claes, K
Bober, MB
Hachen, R
Kaban, LB
Li, H
Lin, A
McDonald, M
Melancon, S
Ortenberg, J
Radtke, HB
Samson, I
Saul, RA
Shen, J
Siqveland, E
Toler, TL
van Maarle, M
Wallace, M
Williams, M
Legius, E
Messiaen, L
AF Stewart, Douglas R.
Brems, Hilde
Gomes, Alicia G.
Ruppert, Sarah L.
Callens, Tom
Williams, Jennifer
Claes, Kathleen
Bober, Michael B.
Hachen, Rachel
Kaban, Leonard B.
Li, Hua
Lin, Angela
McDonald, Marie
Melancon, Serge
Ortenberg, June
Radtke, Heather B.
Samson, Ignace
Saul, Robert A.
Shen, Joseph
Siqveland, Elizabeth
Toler, Tomi L.
van Maarle, Merel
Wallace, Margaret
Williams, Misti
Legius, Eric
Messiaen, Ludwine
TI Jaffe-Campanacci syndrome, revisited: detailed clinical and molecular
analyses determine whether patients have neurofibromatosis type 1,
coincidental manifestations, or a distinct disorder
SO GENETICS IN MEDICINE
LA English
DT Article
DE cafe-au-lait macule; giant cell lesion; Jaffe-Campanacci syndrome;
neurofibromatosis type 1; nonossifying-fibroma
ID GIANT-CELL GRANULOMA; OF-THE-LITERATURE; NF1 GENE;
ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS; MUTATIONAL SPECTRUM; PHENOTYPE;
CHERUBISM; DELETIONS; TUMORS; IDENTIFICATION
AB Purpose: "Jaffe-Campanacci syndrome" describes the complex of multiple nonossifying fibromas of the long bones, mandibular giant cell lesions, and cafe-au-lait macules in individuals without neurofibromas. We sought to determine whether Jaffe-Campanacci syndrome is a distinct genetic entity or a variant of neurofibromatosis type 1.
Methods: We performed germline NF1, SPRED1, and GNAS1 (exon 8) mutation testing on patients with Jaffe-Cainpanacci syndrome of Jaffe-Campanacci syndrome-related features, We also performed somatic NF1 mutation testing on nonossifying fibromas and giant, cell lesions.
Results: Pathogenic germline NF1 mutations Were identified 13 of 14 patients with multiple cafe-au-lait macules and niultiple non-ossifying fibromas or giant cell lesions ("classicar Jaffe-Campanacci syndrome); all 13 also fulfilled the National Institues of Health diagnostic criteria for neurofibromatosis type 1. Somatic NFI mutations were detected in two giant cell lesions but not in two nonossifying fibromas. No SPRED1 or GNAS1 (exon 8) mutations were detected in the seven NF1-negative patients with Jaffe-Campanacci syndrome, nonossifying fibromas, or giant cell lesions.
Conclusion: In this study, the majority of patients with cafe-au-lait macules and nonossifying fibromas Or giant cell lesions harbored a pathogenic gerinline NF1 mutation,suggesting that many Jaffe-Campanacci syndrome cases may-actually have neurofibromatosis type 1. We provide the first proof of specific somatic second-hit mutations affecting NFI in two giant cell lesions from two unrelated patients, establishing these as neurofibromatosis type 1-associated tumors.
C1 [Stewart, Douglas R.] NCI, Clin Genet Branch, Div Canc Epidemiol, NIH, Rockville, MD 20850 USA.
[Brems, Hilde; Legius, Eric] Univ Louvain, Dept Human Genet, Louvain, Belgium.
[Brems, Hilde; Legius, Eric] Leuven Univ Hosp, Ctr Human Genet, Louvain, Belgium.
[Gomes, Alicia G.; Callens, Tom; Williams, Jennifer; Messiaen, Ludwine] Univ Alabama Birmingham, Dept Genet, Med Genom Lab, Birmingham, AL USA.
[Ruppert, Sarah L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Claes, Kathleen] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium.
[Bober, Michael B.] Alfred I DuPont Hosp Children, Dept Pediat, Div Med Genet, Wilmington, DE USA.
[Hachen, Rachel] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
[Li, Hua; Wallace, Margaret] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA.
[Lin, Angela] MassGen Hosp Children, Genet Unit, Boston, MA USA.
[McDonald, Marie] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.
[McDonald, Marie] Duke Univ, Med Ctr, Dept Med Genet, Durham, NC USA.
[Melancon, Serge; Ortenberg, June] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Med Genet, Montreal, PQ H3H 1P3, Canada.
[Melancon, Serge; Ortenberg, June] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Pediat, Montreal, PQ H3H 1P3, Canada.
[Radtke, Heather B.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA.
[Samson, Ignace] Univ Hosp Leuven, Dept Orthoped Surg, Louvain, Belgium.
[Saul, Robert A.] Greenwood Genet Ctr, Greenwood, SC 29646 USA.
[Shen, Joseph] Childrens Hosp Cent Calif, Madera, CA USA.
[Siqveland, Elizabeth] Childrens Hosp & Clin Minnesota, Dept Genet, Minneapolis, MN USA.
[Toler, Tomi L.] Massachusetts Gen Hosp, Div Med Genet, Boston, MA 02114 USA.
[van Maarle, Merel] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands.
[Williams, Misti] LewisGale Reg Hlth Syst, Dept Clin Genet, Salem, VA USA.
RP Stewart, DR (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol, NIH, Rockville, MD 20850 USA.
EM drstewart@mail.nih.gov; lmessiaen@uabmc.edu
OI Bober, Michael/0000-0002-6178-1264; Toler, Tomi/0000-0002-1637-8310
FU Medical Genomics Laboratory at the University of Alabama Birmingham;
Hayward Foundation (MRW laboratory); Division of Intramural Research of
the National Human Genome Research Institute (NHGRI); Division of Cancer
Epidemiology and Genetics of the National Cancer Institute's Intramural
Research Program; National Cancer Institute, National Institutes of
Health; Research Foundation Flanders (FWO) at the KULeuven; Clinical
Research Foundation of the University Hospitals Leuven; FWO-Vlaanderen
[G057806N]
FX This work was supported by internal funds from the Medical Genomics
Laboratory at the University of Alabama Birmingham, the Hayward
Foundation (MRW laboratory), the Division of Intramural Research of the
National Human Genome Research Institute (NHGRI), the Division of Cancer
Epidemiology and Genetics of the National Cancer Institute's Intramural
Research Program, and in part with federal funds from the National
Cancer Institute, National Institutes of Health. H.B. is a postdoctoral
researcher of the Research Foundation Flanders (FWO) at the KULeuven.
The authors thank Kathleen Freson (Molecular and Vascular Biology,
KULeuven) for GNAS1 mutation analysis. E.L. is supported by the Clinical
Research Foundation of the University Hospitals Leuven and by a grant
from the FWO-Vlaanderen (G057806N).
NR 43
TC 4
Z9 4
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD JUN
PY 2014
VL 16
IS 6
BP 448
EP 459
DI 10.1038/gim.2013.163
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA AI6UF
UT WOS:000337011800005
PM 24232412
ER
PT J
AU Dickinson, D
Straub, RE
Trampush, J
Gao, Y
Feng, NP
Xie, B
Shin, JH
Lim, HK
Ursini, G
Bigos, KL
Kolachana, B
Hashimoto, R
Takeda, M
Baum, GL
Rujescu, D
Callicott, JH
Hyde, TM
Berman, KF
Kleinman, JE
Weinberger, DR
AF Dickinson, Dwight
Straub, Richard E.
Trampush, Joeyw.
Gao, Yuan
Feng, Ningping
Xie, Bin
Shin, Joo Heon
Lim, Hun Ki
Ursini, Gianluca
Bigos, Kristin L.
Kolachana, Bhaskar
Hashimoto, Ryota
Takeda, Masatoshi
Baum, Graham L.
Rujescu, Dan
Callicott, Joseph H.
Hyde, Thomas M.
Berman, Karen F.
Kleinman, Joel E.
Weinberger, Daniel R.
TI Differential Effects of Common Variants in SCN2A on General Cognitive
Ability, Brain Physiology, and messenger RNA Expression in Schizophrenia
Cases and Control Individuals
SO JAMA PSYCHIATRY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CLINICAL ANTIPSYCHOTIC TRIALS; EFFECTIVENESS
CATIE PROJECT; HUMAN INTELLIGENCE; INTELLECTUAL DISABILITY;
FUNCTIONAL-CAPACITY; PREFRONTAL CORTEX; GENETIC-VARIATION; RISK;
CHILDHOOD
AB IMPORTANCE One approach to understanding the genetic complexity of schizophrenia is to study associated behavioral and biological phenotypes that may be more directly linked to genetic variation.
OBJECTIVE To identify single-nucleotide polymorphisms associated with general cognitive ability (g) in people with schizophrenia and control individuals.
DESIGN, SETTING, AND PARTICIPANTS Genomewide association study, followed by analyses in unaffected siblings and independent schizophrenia samples, functional magnetic resonance imaging studies of brain physiology in vivo, and RNA sequencing in postmortem brain samples. The discovery cohort and unaffected siblings were participants in the National Institute of Mental Health Clinical Brain Disorders Branch schizophrenia genetics studies. Additional schizophrenia cohorts were from psychiatric treatment settings in the United States, Japan, and Germany. The discovery cohort comprised 339 with schizophrenia and 363 community control participants. Follow-up analyses studied 147 unaffected siblings of the schizophrenia cases and independent schizophrenia samples including a total of an additional 668 participants. Imaging analyses included 87 schizophrenia cases and 397 control individuals. Brain tissue samples were available for 64 cases and 61 control individuals.
MAIN OUTCOMES AND MEASURES We studied genomewide association with g, by group, in the discovery cohort. We used selected genotypes to test specific associations in unaffected siblings and independent schizophrenia samples. Imaging analyses focused on activation in the prefrontal cortex during working memory. Brain tissue studies yielded messenger RNA expression levels for RefSeq transcripts.
RESULTS The schizophrenia discovery cohort showed genomewide-significant association of g with polymorphisms in sodium channel gene SCN2A, accounting for 10.4% of g variance (rs10174400, P = 9.27 x 10(-10)). Control individuals showed a trend for g/genotype association with reversed allelic directionality. The genotype-by-group interaction was also genomewide significant (P = 1.75 x 10(-9)). Siblings showed a genotype association with g parallel to the schizophrenia group and the same interaction pattern. Parallel, but weaker, associations with cognition were found in independent schizophrenia samples. Imaging analyses showed a similar pattern of genotype associations by group and genotype-by-group interaction. Sequencing of RNA in brain revealed reduced expression in 2 of 3 SCN2A alternative transcripts in the patient group, with genotype-by-group interaction, that again paralleled the cognition effects.
CONCLUSIONS AND RELEVANCE The findings implicate SCN2A and sodium channel biology in cognitive impairment in schizophrenia cases and unaffected relatives and may facilitate development of cognition-enhancing treatments.
C1 [Dickinson, Dwight; Trampush, Joeyw.; Feng, Ningping; Kolachana, Bhaskar; Baum, Graham L.; Callicott, Joseph H.; Hyde, Thomas M.; Berman, Karen F.; Kleinman, Joel E.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Straub, Richard E.; Gao, Yuan; Xie, Bin; Shin, Joo Heon; Lim, Hun Ki; Ursini, Gianluca; Bigos, Kristin L.; Hyde, Thomas M.; Kleinman, Joel E.; Weinberger, Daniel R.] Johns Hopkins Univ Med Campus, Lieber Inst Brain Dev, Baltimore, MD USA.
[Ursini, Gianluca] Univ Bari Aldo Moro, Dept Basic Med Sci Neurosci & Sense Organs, Psychiat Neurosci Grp, Bari, Italy.
[Hashimoto, Ryota; Takeda, Masatoshi] Osaka Univ, United Grad Sch Child Dev, Mol Res Ctr Childrens Mental Dev, Osaka, Japan.
[Hashimoto, Ryota; Takeda, Masatoshi] Osaka Univ, Grad Sch Med, Dept Psychiat, Osaka, Japan.
[Rujescu, Dan] Univ Munich, Dept Psychiat, D-80539 Munich, Germany.
[Rujescu, Dan] Univ Halle Wittenberg, Dept Psychiat, D-06108 Halle, Germany.
[Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Weinberger, Daniel R.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
RP Weinberger, DR (reprint author), Johns Hopkins Univ, Sch Med, Lieber Inst Brain Dev, 855 NWolfe St, Baltimore, MD 21205 USA.
EM drweinberger@libd.org
RI Hashimoto, Ryota/P-8572-2014
OI Hashimoto, Ryota/0000-0002-5941-4238
FU Division of Intramural Research Programs, National Institute of Mental
Health, National Institutes of Health, Bethesda, Maryland; Clinical
Brain Disorders Branch; Lieber Institute for Brain Development,
Baltimore, Maryland
FX This work was supported by the Division of Intramural Research Programs,
National Institute of Mental Health, National Institutes of Health,
Bethesda, Maryland, as direct funding of the Clinical Brain Disorders
Branch (Dr Weinberger, principal investigator) and the Lieber Institute
for Brain Development, Baltimore, Maryland.
NR 77
TC 8
Z9 9
U1 4
U2 9
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD JUN
PY 2014
VL 71
IS 6
BP 647
EP 656
DI 10.1001/jamapsychiatry.2014.157
PG 10
WC Psychiatry
SC Psychiatry
GA AI5NQ
UT WOS:000336915600009
PM 24718902
ER
PT J
AU Nurnberger, JI
Koller, DL
Jung, J
Edenberg, HJ
Foroud, T
Guella, I
Vawter, MP
Kelsoe, JR
AF Nurnberger, John I., Jr.
Koller, Daniel L.
Jung, Jeesun
Edenberg, Howard J.
Foroud, Tatiana
Guella, Ilaria
Vawter, Marquis P.
Kelsoe, John R.
CA Psychiat Genomics Consortium
TI Identification of Pathways for Bipolar Disorder A Meta-analysis
SO JAMA PSYCHIATRY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; 7 COMMON DISEASES; PSYCHIATRIC-DISORDERS;
CALCIUM; GENES; RISK; SCHIZOPHRENIA; CACNA1C; LITHIUM; SYSTEM
AB IMPORTANCE Genome-wide investigations provide systematic information regarding the neurobiology of psychiatric disorders.
OBJECTIVE To identify biological pathways that contribute to risk for bipolar disorder (BP) using genes with consistent evidence for association in multiple genome-wide association studies (GWAS).
DATA SOURCES Four independent data sets with individual genome-wide data available in July 2011 along with all data sets contributed to the Psychiatric Genomics Consortium Bipolar Group by May 2012. A prior meta-analysis was used as a source for brain gene expression data.
STUDY SELECTION The 4 published GWAS were included in the initial sample. All independent BP data sets providing genome-wide data in the Psychiatric Genomics Consortium were included as a replication sample.
DATA EXTRACTION AND SYNTHESIS We identified 966 genes that contained 2 or more variants associated with BP at P < .05 in 3 of 4 GWAS data sets (n = 12 127 [5253 cases, 6874 controls]). Simulations using 10 000 replicates of these data sets corrected for gene size and allowed the calculation of an empirical P value for each gene; empirically significant genes were entered into a pathway analysis. Each of these pathways was then tested in the replication sample (n = 8396 [3507 cases, 4889 controls]) using gene set enrichment analysis for single-nucleotide polymorphisms. The 226 genes were also compared with results from a meta-analysis of gene expression in the dorsolateral prefrontal cortex.
MAIN OUTCOMES AND MEASURES Empirically significant genes and biological pathways.
RESULTS Among 966 genes, 226 were empirically significant (P < .05). Seventeen pathways were overrepresented in analyses of the initial data set. Six of the 17 pathways were associated with BP in both the initial and replication samples: corticotropin-releasing hormone signaling, cardiac beta-adrenergic signaling, phospholipase C signaling, glutamate receptor signaling, endothelin 1 signaling, and cardiac hypertrophy signaling. Among the 226 genes, 9 differed in expression in the dorsolateral prefrontal cortex in patients with BP: CACNA1C, DTNA, FOXP1, GNG2, ITPR2, LSAMP, NPAS3, NCOA2, and NTRK3.
CONCLUSIONS AND RELEVANCE Pathways involved in the genetic predisposition to BP include hormonal regulation, calcium channels, second messenger systems, and glutamate signaling. Gene expression studies implicate neuronal development pathways as well. These results tend to reinforce specific hypotheses regarding BP neurobiology and may provide clues for new approaches to treatment and prevention.
C1 [Nurnberger, John I., Jr.; Koller, Daniel L.; Edenberg, Howard J.; Foroud, Tatiana] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Nurnberger, John I., Jr.; Foroud, Tatiana] Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA.
[Jung, Jeesun] NIAAA, Neurogenet Lab, Intramural Res Program, Bethesda, MD USA.
[Edenberg, Howard J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
[Guella, Ilaria; Vawter, Marquis P.] Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav, Funct Genom Lab, Irvine, CA 92717 USA.
[Kelsoe, John R.] Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA.
[Kelsoe, John R.] Vet Affairs San Diego Healthcare Syst, Special Treatment & Evaluat Program, Dept Psychiat, San Diego, CA USA.
RP Nurnberger, JI (reprint author), Indiana Univ Sch Med, Dept Psychiat, Inst Psychiat Res, 791 Union Dr, Indianapolis, IN 46202 USA.
EM jnurnber@iupui.edu
RI Zhang, Peng/N-2920-2014; Collier, David/D-1649-2011; Mattheisen,
Manuel/B-4949-2012; Breen, Gerome/A-5540-2010; Melle, Ingrid
/B-4858-2011; Ruderfer, Douglas/M-5795-2016; Lohoff, Falk/M-7951-2016;
BELLIVIER, FRANK/H-5197-2012; McQuillin, Andrew/C-1623-2008; Schumacher,
Johannes/F-4970-2015;
OI Zhang, Peng/0000-0003-1182-1392; Collier, David/0000-0003-4087-1559;
Mattheisen, Manuel/0000-0002-8442-493X; Breen,
Gerome/0000-0003-2053-1792; Melle, Ingrid /0000-0002-9783-548X;
Ruderfer, Douglas/0000-0002-2365-386X; McQuillin,
Andrew/0000-0003-1567-2240; Bergen, Sarah/0000-0002-5888-0034; Jamain,
Stephane/0000-0002-4321-4100; McMahon, Francis/0000-0002-9469-305X;
Schumacher, Johannes/0000-0001-9217-6457; Stefansson,
Hreinn/0000-0002-9331-6666; Backlund, Lena/0000-0001-9399-5024;
Nurnberger, John/0000-0002-7674-1767; lichtenstein,
paul/0000-0003-3037-5287; Nothen, Markus/0000-0002-8770-2464; Etain,
Bruno/0000-0002-5377-1488; Edenberg, Howard/0000-0003-0344-9690;
Thorgeirsson, Thorgeir/0000-0002-5149-7040; McIntosh,
Andrew/0000-0002-0198-4588
FU William Lion Penzner Foundation (Department of Psychiatry, University of
California, Irvine); National Institute of Mental Health [R01 MH085801,
1 R01 MH094483-01A1]; National Institutes of Health [MH078151, MH081804,
MH059567, MH59553, MH080372, 1U54RR025204]; Genetic Association
Information Network; National Institute of Mental Health Intramural
Research Program; Tzedakah Foundation; American Philosophical Society;
Stardust Foundation; National Library of Medicine; Stanley Medical
Research Institute; Merck Genome Research Institute; Wellcome Trust;
Pritzker Neuropsychiatric Disorders Research Fund LLC; GlaxoSmithKline;
Research Council of Norway [167153/V50, 163070/V50, 175345/V50];
South-East Norway Health Authority [123-2004]; European Union (European
Network of Bipolar Research Expert Centres)
FX This work was supported by the William Lion Penzner Foundation
(Department of Psychiatry, University of California, Irvine), grants R01
MH085801 (Dr Vawter) and 1 R01 MH094483-01A1 (Dr Kelsoe) from the
National Institute of Mental Health, grants MH078151, MH081804, MH059567
supplement, MH59553, MH080372, and 1U54RR025204 from the National
Institutes of Health, the Genetic Association Information Network,
National Institute of Mental Health Intramural Research Program,
Tzedakah Foundation, American Philosophical Society, Stardust
Foundation, National Library of Medicine, Stanley Medical Research
Institute, Merck Genome Research Institute, Wellcome Trust, Pritzker
Neuropsychiatric Disorders Research Fund LLC, GlaxoSmithKline, and
grants for individual studies (see
http://www.nature.com/ng/journal/v43/n10/extref/ng.943-S1.pdf for a full
list of acknowledgments). The Thematically Organized Psychosis Study was
supported by grants 167153/V50, 163070/V50, and 175345/V50 from the
Research Council of Norway, grant 123-2004 from the South-East Norway
Health Authority, and the European Union (European Network of Bipolar
Research Expert Centres). The French sample collection and genotyping
were supported by the Centre National de Genotypage, Agence National de
la Recherche (ANR NEURO2006, MANAGE_BPAD), Institut National de la Sante
et de la Recherche Medicale, Assistance Publique-Hopitaux de Paris, and
Fondation FondaMental.
NR 40
TC 56
Z9 57
U1 2
U2 28
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD JUN
PY 2014
VL 71
IS 6
BP 657
EP 664
DI 10.1001/jamapsychiatry.2014.176
PG 8
WC Psychiatry
SC Psychiatry
GA AI5NQ
UT WOS:000336915600010
PM 24718920
ER
PT J
AU Rizzo, G
Veronese, M
Tonietto, M
Zanotti-Fregonara, P
Turkheimer, FE
Bertoldo, A
AF Rizzo, Gaia
Veronese, Mattia
Tonietto, Matteo
Zanotti-Fregonara, Paolo
Turkheimer, Federico E.
Bertoldo, Alessandra
TI Kinetic modeling without accounting for the vascular component impairs
the quantification of [C-11]PBR28 brain PET data
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE [C-11]PBR28; kinetic modeling; microglia; neuroinflammation; PK11195;
TSPO
ID POSITRON-EMISSION-TOMOGRAPHY; PROTEIN 18 KDA; VIVO RADIOLIGAND BINDING;
TRANSLOCATOR PROTEIN; IN-VIVO; ALZHEIMERS-DISEASE; NEUROINFLAMMATION;
MICROGLIA; TSPO; DEPRESSION
AB The positron emission tomography radioligand [C-11]PBR28 targets translocator protein (18 kDa) (TSPO) and is a potential marker of neuroinflammation. [C-11]PBR28 binding is commonly quantified using a two-tissue compartment model and an arterial input function. Previous studies with [C-11]-(R)-PK11195 demonstrated a slow irreversible binding component to the TSPO proteins localized in the endothelium of brain vessels, such as venous sinuses and arteries. However, the impact of this component on the quantification of [C-11]PBR28 data has never been investigated. In this work we propose a novel kinetic model for [C-11]PBR28. This model hypothesizes the existence of an additional irreversible component from the blood to the endothelium. The model was tested on a data set of 19 healthy subjects. A simulation was also performed to quantify the error generated by the standard two-tissue compartmental model when the presence of the irreversible component is not taken into account. Our results show that when the vascular component is included in the model the estimates that include the vascular component (2TCM-1K) are more than three-fold smaller, have a higher time stability and are better correlated to brain mRNA TSPO expression than those that do not include the model (2TCM).
C1 [Rizzo, Gaia; Tonietto, Matteo; Bertoldo, Alessandra] Univ Padua, Dept Informat Engn, I-35131 Padua, Italy.
[Veronese, Mattia; Turkheimer, Federico E.] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London, England.
[Zanotti-Fregonara, Paolo] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Zanotti-Fregonara, Paolo] Univ Bordeaux, CNRS, INCIA, UMR 5287, Talence, France.
RP Bertoldo, A (reprint author), Univ Padua, Dept Informat Engn, Via G Gradenigo 6-B, I-35131 Padua, Italy.
EM bertoldo@dei.unipd.it
RI Rizzo, Gaia/A-8697-2013; Turkheimer, Federico/B-9485-2012; Veronese,
Mattia/A-6012-2013;
OI Rizzo, Gaia/0000-0001-7272-8576; Turkheimer,
Federico/0000-0002-3766-3815; Veronese, Mattia/0000-0003-3562-0683;
Tonietto, Matteo/0000-0001-9591-5710
FU Intramural Research Program, National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH); Programme Grant
'Quantitative methodologies for Positron Emission Tomography', UK
Medical Research Council (MRC) [G1100809/1]
FX This work was supported in part by the Intramural Research Program,
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH) and by Programme Grant 'Quantitative methodologies for
Positron Emission Tomography', UK Medical Research Council (MRC) No.
G1100809/1.
NR 32
TC 16
Z9 16
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD JUN
PY 2014
VL 34
IS 6
BP 1060
EP 1069
DI 10.1038/jcbfm.2014.55
PG 10
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA AI4JH
UT WOS:000336831000017
PM 24667911
ER
PT J
AU Murphy, E
Steenbergen, C
AF Murphy, Elizabeth
Steenbergen, Charles
TI Sex, drugs, and trial design: sex influences the heart and drug
responses
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID EXERCISE CAPACITY; CLINICAL STATUS; INHIBITION; SILDENAFIL; FAILURE;
HYPERTROPHY; EXPRESSION; PDE5
AB Preclinical studies indicate that the phosphodiesterase 5 (PDE5) inhibitor sildenafil is protective against hypertrophy-induced cardiac remodeling. Despite an initial clinical study demonstrating sildenafil-dependent amelioration of pathological remodeling, the cardioprotective effect of this drug was not significant in a large placebo-controlled clinical trail. In this issue, Sasaki and colleagues reveal that the efficacy of PDE5 inhibition in female mice requires estrogen. Induction of cardiac stress in male and intact female mice resulted in increased activation of protein kinase G (PKG) signaling, which was further enhanced by sildenafil. PKG activity was not enhanced in ovariectomized. (OVX) female mice as a result of cardiac stress, but administration of estrogen restored PKG activation and enhancement by sildenafil. These data highlight the importance of considering sex-specific differences and drug responses in clinical trial design.
C1 [Murphy, Elizabeth] NHLBI, NIH, Bethesda, MD 20892 USA.
[Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
RP Murphy, E (reprint author), NHLBI, Cardiac Physiol Sect, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM murphy1@mail.nih.gov
FU NHLBI NIH HHS [R01 HL039752, ZOI-HL-006059, Z01 HL002065, R01-HL-39752,
Z01-HL-002065]
NR 14
TC 2
Z9 2
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
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUN
PY 2014
VL 124
IS 6
BP 2375
EP 2377
DI 10.1172/JCI6262
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI4XC
UT WOS:000336868800015
PM 24837428
ER
PT J
AU Bhadra, R
Moretto, MM
Castillo, JC
Petrovas, C
Ferrando-Martinez, S
Shokal, U
Leal, M
Koup, RA
Eleftherianos, I
Khan, IA
AF Bhadra, Rajarshi
Moretto, Magali M.
Castillo, Julio C.
Petrovas, Constantinos
Ferrando-Martinez, Sara
Shokal, Upasana
Leal, Manuel
Koup, Richard A.
Eleftherianos, Ioannis
Khan, Imtiaz A.
TI Intrinsic TGF-beta signaling promotes age-dependent CD8(+) T cell
polyfunctionality attrition
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID AGING IMMUNE-SYSTEM; GROWTH-FACTOR-BETA; ENCEPHALITOZOON-CUNICULI;
HELMINTH COINFECTION; AIDS PATIENTS; IN-VIVO; EFFECTOR; INFECTION;
MEMORY; VIRUS
AB Advanced age is associated with immune system deficits that result in an increased susceptibility to infectious diseases; however, specific mediators of age-dependent immune dysfunction have not been fully elucidated. Here we demonstrated that aged mice exhibit poor effector CD8(+) T cell polyfunctionality, primarily due to CD8(+) T cell-extrinsic deficits, and that reduced CD8(+) T cell polyfunctionality correlates with increased susceptibility to pathogenic diseases. In aged animals challenged with the parasite Encephalitozoon cuniculi, effector CD8(+) T cell survival and polyfunctionality were suppressed by highly elevated TGF-beta 1. Furthermore, TGF-beta depletion reduced effector CD8(+) T cell apoptosis in both young and aged mice and enhanced effector CD8(+) T cell polyfunctionality in aged mice. Surprisingly, intrinsic blockade of TGF-beta signaling in CD8(+) T cells was sufficient to rescue polyfunctionality in aged animals. Together, these data demonstrate that low levels of TGF-beta 1 promote apoptosis of CD8(+) effector T cells and high TGF-beta 1 levels associated with age result in both CD8(+) T cell apoptosis and an altered transcriptional profile, which correlates with loss of polyfunctionality. Furthermore, elevated TGF-beta levels are observed in the elderly human population and in aged Drosophila, suggesting that TGF-beta represents an evolutionarily conserved negative regulator of the immune response in aging organisms.
C1 [Bhadra, Rajarshi; Moretto, Magali M.; Khan, Imtiaz A.] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA.
[Bhadra, Rajarshi] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA.
[Castillo, Julio C.; Shokal, Upasana; Eleftherianos, Ioannis] George Washington Univ, Dept Biol Sci, Insect Infect & Immun Lab, Washington, DC 20037 USA.
[Petrovas, Constantinos; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Ferrando-Martinez, Sara; Leal, Manuel] Univ Seville, Virgen Rocio Univ Hosp, Clin Unit Infect Dis Microbiol & Prevent Med, Inst Biomed Seville IBiS,Lab Immunovirol,CSIC, Seville, Spain.
[Ferrando-Martinez, Sara] Hosp Gen Univ Gregorio Maranon, Lab InmunoBiol Mol, Madrid, Spain.
[Ferrando-Martinez, Sara] Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain.
[Ferrando-Martinez, Sara] Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Madrid, Spain.
RP Khan, IA (reprint author), George Washington Univ, 2300 1 St NW,Ross Hall Room 623, Washington, DC 20037 USA.
EM imti56@gwu.edu
RI Leal, Manuel/C-8458-2015; IBIS, INMUNOVIROLOGI/O-9246-2015;
OI Castillo, Julio/0000-0002-6921-810X
FU NIH [AI-096978]; Fondo de Investigaciones Sanitarias [CD 10/00382];
Redes Tematicas de Investigacion en SIDA (ISCIII RETIC) [RD12/0017/0029,
RD12/0017/0037]; Proyecto de Excelencia [CTS-6313]; Consejeri de Salud
[PI-0278]
FX This work was supported by a NIH grant (AI-096978) to I.A. Khan as well
as by Fondo de Investigaciones Sanitarias (CD 10/00382), Redes Tematicas
de Investigacion en SIDA (ISCIII RETIC RD12/0017/0029 and
RD12/0017/0037), Proyecto de Excelencia (CTS-6313), and Consejeri de
Salud (PI-0278) to M. Leal and S. Ferrando-Martinez. We thank Louis M.
Weiss (Albert Einstein College of Medicine, New York, New York, USA) for
critically reading the manuscript.
NR 65
TC 8
Z9 8
U1 0
U2 2
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUN
PY 2014
VL 124
IS 6
BP 2441
EP 2455
DI 10.1172/JCI70522
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI4XC
UT WOS:000336868800020
PM 24762437
ER
PT J
AU Sui, YJ
Hogg, A
Wang, YC
Frey, B
Yu, HF
Xia, Z
Venzon, D
McKinnon, K
Smedley, J
Gathuka, M
Klinman, D
Keele, BF
Langermann, S
Liu, LD
Franchini, G
Berzofsky, JA
AF Sui, Yongjun
Hogg, Alison
Wang, Yichuan
Frey, Blake
Yu, Huifeng
Xia, Zheng
Venzon, David
McKinnon, Katherine
Smedley, Jeremy
Gathuka, Mercy
Klinman, Dennis
Keele, Brandon F.
Langermann, Sol
Liu, Linda
Franchini, Genoveffa
Berzofsky, Jay A.
TI Vaccine-induced myeloid cell population dampens protective immunity to
SIV
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID CD8(+) T-CELLS; BLOOD MONONUCLEAR-CELLS; SUPPRESSOR-CELLS;
ALPHA-GALACTOSYLCERAMIDE; MUCOSAL TRANSMISSION; SIVMAC251 INFECTION;
DISEASE PROGRESSION; HIV-1 INFECTION; RHESUS MACAQUES; TUMOR-IMMUNITY
AB Vaccines are largely evaluated for their ability to promote adaptive immunity, with little focus on the induction ofnegative immune regulators. Adjuvants facilitate and enhance vaccine-induced immune responses and have been explored for mediating protection against HIV Using a regimen of peptide e priming followed by a modified vaccinia Ankara (MVA) boost in a nonhuman primate model, we found that an SW vaccine incorporating molecular adjuvants mediated partial protection against rectal SIVmac251 challenges. Animals treated with vaccine and multiple adjuvants exhibited a reduced viral load (VL) compared with those treated with vaccine only. Surprisingly, animals treated with adjuvant alone had reduced VLs that were comparable to or better than those of the vaccine-treated group. VL reduction was greatest in animals with the MHC class I allele Mamu-A*01 that were treated with adjuvant only and was largely dependent on CD8(+) T cells. Early VLs correlated with Ki67(+)CCR5(+)CD4(+) T cell frequency, while set-point VL was associated with expansion of a myeloid cell population that was phenotypically similar to myeloid-derived suppressor cells (MDSCs) and that suppressed T cell responses in vitro. MDSC expansion occurred in animals receiving vaccine and was not observed in the adjuvant-only group. Collectively, these results indicate that vaccine-induced MDSCs inhibit protective cellular immunity and suggest that preventing MDSC induction may be critical for effective AIDS vaccination.
C1 [Sui, Yongjun; Hogg, Alison; Wang, Yichuan; Frey, Blake; Yu, Huifeng; Xia, Zheng; McKinnon, Katherine; Franchini, Genoveffa; Berzofsky, Jay A.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
[Smedley, Jeremy; Gathuka, Mercy] NCI, Lab Anim Sci Program, NIH, Bethesda, MD 20892 USA.
[Klinman, Dennis] NCI, Expt Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Keele, Brandon F.] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
[Langermann, Sol; Liu, Linda] Amplimmune Inc, Gaithersburg, MD USA.
RP Sui, YJ (reprint author), NCI, Vaccine Branch, NIH, 41 Medlars Dr, Bethesda, MD 20892 USA.
EM suiy@mail.nih.gov; berzofsj@mail.nih.gov
OI Smedley, Jeremy/0000-0003-3369-4662
FU NIH [HHSN261200800001E]; NCI; Center for Cancer Research
FX We thank E.M. Lee, R. Pal, and S. Omdorff from Advanced Bio-Science
Laboratories Inc. for the VL and CD4 assays; D. Watkins (University of
Miami) for MHC typing; N. Miller (NIAID) for providing pathogenic
SIVmac251 challenge stock; M.R. Anver (NCI) for pathology support; the
NIAID tetramer core facility for providing the tetramers; the NIH
Nonhuman Primate Reagent Resource for providing anti-CD3 and anti-CD28
antibodies; Lisa Smith for secretarial assistance; and Masaki Terabe
(NCI) and Tim Greten (NCI) for helpful discussion. This work was
supported by the Intramural Program of the NIH, NCI, Center for Cancer
Research and in part by federal funds from the NCI, NIH, under contract
HHSN261200800001E.
NR 56
TC 15
Z9 16
U1 0
U2 15
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUN
PY 2014
VL 124
IS 6
BP 2538
EP 2549
DI 10.1172/JCI73518
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI4XC
UT WOS:000336868800028
PM 24837435
ER
PT J
AU Yu, WP
Zheng, H
Lin, W
Tajima, A
Zhang, Y
Zhang, XY
Zhang, HW
Wu, JH
Han, DS
Rahman, NA
Korach, KS
Gao, GF
Inoue, I
Li, XD
AF Yu, Wanpeng
Zheng, Han
Lin, Wei
Tajima, Astushi
Zhang, Yong
Zhang, Xiaoyan
Zhang, Hongwen
Wu, Jihua
Han, Daishu
Rahman, Nafis A.
Korach, Kenneth S.
Gao, George Fu
Inoue, Ituro
Li, Xiangdong
TI Estrogen promotes Leydig cell engulfment by macrophages in male
infertility
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID TRANSGENIC MALE-MICE; APOPTOTIC CELLS; PHOSPHOLIPID SCRAMBLASE; TARGETED
DISRUPTION; INCREASED EXPOSURE; RECEPTOR-ALPHA; P450 AROMATASE; MOUSE
TESTIS; GENE; MEN
AB Male infertility accounts for almost half of infertility cases worldwide. A subset of infertile men exhibit reduced testosterone and enhanced levels of estradiol (E2), though it is unclear how increased E2 promotes deterioration of male fertility. Here, we utilized a transgenic mouse strain that overexpresses human CYP19, which encodes aromatase (AROM+ mice), and mice with knockout of Esr1, encoding estrogen receptor alpha (ER alpha KO mice), to analyze interactions between viable Leydig cells (LCs) and testicular macrophages that may lead to male infertility. In AROM+ males, enhanced E2 promoted LC hyperplasia and macrophage activation via ER alpha signaling. E2 stimulated LCs to produce growth arrest-specific 6 (GAS6), which mediates phagocytosis of apoptotic cells by bridging cells with surface exposed phosphatidylserine (PS) to macrophage receptors, including the tyrosine kinases TYRO3, AXL, and MER. Overproduction of E2 increased apoptosis-independent extrusion of PS on LCs, which in turn promoted engulfment by E2/ER alpha-activated macrophages that was mediated by AXL-GAS6-PS interaction. We further confirmed E2-dependant engulfment of LCs by real-time 3D imaging. Furthermore, evaluation of molecular markers in the testes of patients with nonobstructive azoospermia (NOA) revealed enhanced expression of CYP19, GAS6, and AXL, which suggests that the AROM+ mouse model reflects human infertility. Together, these results suggest that GAS6 has a potential as a clinical biomarker and therapeutic target for male infertility.
C1 [Yu, Wanpeng; Zheng, Han; Lin, Wei; Zhang, Yong; Li, Xiangdong] China Agr Univ, Coll Biol Sci, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China.
[Tajima, Astushi; Inoue, Ituro] Natl Inst Genet, Div Human Genet, Shizuoka, Japan.
[Zhang, Xiaoyan; Han, Daishu] Chinese Acad Med Sci, Peking Union Med Coll, Sch Basic Med, Dept Cell Biol,Inst Basic Med Sci, Beijing 100730, Peoples R China.
[Zhang, Hongwen; Wu, Jihua] 306th Hosp PLA, Dept Gen Surg, Beijing, Peoples R China.
[Rahman, Nafis A.] Univ Turku, Inst Biomed, Dept Physiol, Turku, Finland.
[Korach, Kenneth S.] NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Grp, NIH, Bethesda, MD USA.
[Gao, George Fu] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China.
RP Li, XD (reprint author), China Agr Univ, Coll Biol Sci, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China.
EM gaof@im.ac.cn; xiangdongli@cau.edu.cn
RI Tajima, Atsushi/C-1053-2008;
OI Tajima, Atsushi/0000-0001-6808-5491; Korach, Kenneth/0000-0002-7765-418X
FU Natural Science Foundation of China [NSFC31071316]; National Science and
Technology Major Project [2013ZX10004608]; Ministry of
Science/Technology [2009CB941701]; CAU Scientific Fund [2012171034]
FX This work was supported by grants from the Natural Science Foundation of
China (NSFC31071316), National Science and Technology Major Project
(2013ZX10004608), Ministry of Science/Technology (2009CB941701), and the
CAU Scientific Fund (no. 2012171034).
NR 56
TC 12
Z9 12
U1 1
U2 12
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUN
PY 2014
VL 124
IS 6
BP 2709
EP 2721
DI 10.1172/JCI59901
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI4XC
UT WOS:000336868800041
PM 24762434
ER
PT J
AU Zhang, YJ
Berka, V
Song, AR
Sun, KQ
Wang, W
Zhang, WR
Ning, C
Li, CH
Zhang, QB
Bogdanov, M
Alexander, DC
Milburn, MV
Ahmed, MH
Lin, H
Idowu, M
Zhang, J
Kato, GJ
Abdulmalik, OY
Zhang, WZ
Dowhan, W
Kellems, RE
Zhang, PM
Jin, JP
Safo, M
Tsai, AL
Juneja, HS
Xia, Y
AF Zhang, Yujin
Berka, Vladimir
Song, Anren
Sun, Kaiqi
Wang, Wei
Zhang, Weiru
Ning, Chen
Li, Chonghua
Zhang, Qibo
Bogdanov, Mikhail
Alexander, Danny C.
Milburn, Michael V.
Ahmed, Mostafa H.
Lin, Han
Idowu, Modupe
Zhang, Jun
Kato, Gregory J.
Abdulmalik, Osheiza Y.
Zhang, Wenzheng
Dowhan, William
Kellems, Rodney E.
Zhang, Pumin
Jin, Jianping
Safo, Martin
Tsai, Ah-Lim
Juneja, Harinder S.
Xia, Yang
TI Elevated sphingosine-1-phosphate promotes sickling and sickle cell
disease progression
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID 1ST MOLECULAR DISEASE; SPHINGOSINE 1-PHOSPHATE; IN-VITRO; ANGIOGENESIS;
MICE; PATHOPHYSIOLOGY; ERYTHROCYTES; HEMOGLOBIN; ANEMIA; BLOOD
AB Sphingosine-l-phosphate (SIP) is a bioactive lipid that regulates ulticellular functions through interactions with its receptors on cell surfaces. S1P is enriched and stored in erythrocytes however it is not clear whether alterations in SlP are involved in the prevalent and debilitating hemolytic disorder sickle cell disease (SCD). Here using metabolomic screening we found that SlP is highly elevated in the blood of mice and humans with SCD. In murine models of SCD we demonstrated that elevated erythrocyte sphingosine kinase 1 (SPHK1) underlies sickling and disease progression by increasing SIP levels in the blood. Additionally we observed elevated SPHK1 activity in erythrocytes and increased S1P in blood collected from patients with SCD and demonstrated a direct impact of elevated SPHK1-mediated production of SIP on sickling that was independent of SIP receptor activation in isolated erythrocytes. Together our findings provide insights into erythrocyte pathophysiology revealing that a SPHK1-mediated elevation of SlP contributes to sickling and promotes disease progression and highlight potential therapeutic opportunities for SCD.
C1 [Zhang, Yujin; Song, Anren; Sun, Kaiqi; Wang, Wei; Zhang, Weiru; Ning, Chen; Li, Chonghua; Bogdanov, Mikhail; Dowhan, William; Kellems, Rodney E.; Jin, Jianping; Xia, Yang] Univ Texas Hlth Sci Ctr Houston, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
[Berka, Vladimir; Idowu, Modupe; Zhang, Wenzheng; Tsai, Ah-Lim; Juneja, Harinder S.] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Houston, TX 77030 USA.
[Sun, Kaiqi; Kellems, Rodney E.; Jin, Jianping; Xia, Yang] Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA.
[Wang, Wei; Zhang, Weiru; Xia, Yang] Cent S Univ, Xiangya Hosp 1, Dept Neurol, Changsha, Hunan, Peoples R China.
[Ning, Chen] Cent S Univ, Xiangya Hosp 1, Dept Urol, Changsha, Hunan, Peoples R China.
[Zhang, Qibo; Alexander, Danny C.; Milburn, Michael V.] Metabolon Inc, Durham, NC USA.
[Ahmed, Mostafa H.; Safo, Martin] Virginia Commonwealth Univ, Sch Pharm, Dept Med Chem, Richmond, VA USA.
[Ahmed, Mostafa H.; Safo, Martin] Virginia Commonwealth Univ, Inst Struct Biol & Drug Discovery, Richmond, VA USA.
[Lin, Han; Zhang, Pumin] Baylor Coll Med, Dept Physiol, Houston, TX 77030 USA.
[Zhang, Jun] Baylor Coll Med, Dept Hematol Oncol, Houston, TX 77030 USA.
[Kato, Gregory J.] NHLBI, Sickle Cell Dis Div, NIH, Bethesda, MD 20892 USA.
[Abdulmalik, Osheiza Y.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
RP Xia, Y (reprint author), Univ Texas Med Sch Houston, Dept Biochem & Mol Biol, 6431 Fannin St, Houston, TX 77030 USA.
EM yang.xia@uth.tmc.edu
RI Kato, Gregory/I-7615-2014; Lin, Han/M-9269-2016
OI Kato, Gregory/0000-0003-4465-3217; Lin, Han/0000-0002-8569-7972
FU NIH [HL119549, DK077748, DK083559, P01HL114457, HL095820]; American
Heart Association [10GRNT3760081, 12IRG9150001]; China Scholarship
Council [2009637520]; NIH/NHLBI [HL103186]
FX This work was supported by NIH grants HL119549 (to Y. Xia), DK077748 (to
Y. Xia), DK083559 (to Y. Xia), P01HL114457 (Project 3 to Y. Xia), and
HL095820 (to A.-L. Tsai) as well as American Heart Association grants
10GRNT3760081 and 12IRG9150001 (to Y. Xia), China Scholarship Council
2009637520 (to Weiru Zhang), and NIH/NHLBI grant HL103186 (to O.Y.
Abdulmalik).
NR 35
TC 34
Z9 36
U1 0
U2 12
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD JUN
PY 2014
VL 124
IS 6
BP 2750
EP 2761
DI 10.1172/JC174604
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA AI4XC
UT WOS:000336868800044
PM 24837436
ER
PT J
AU Mulligan, C
Fitzgerald, GA
Wang, DN
Mindell, JA
AF Mulligan, Christopher
Fitzgerald, Gabriel A.
Wang, Da-Neng
Mindell, Joseph A.
TI Functional characterization of a Na+-dependent dicarboxylate transporter
from Vibrio cholerae
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID COUPLED CITRATE TRANSPORTER; NONSTEROIDAL ANTIINFLAMMATORY DRUGS;
GENOMIC ORGANIZATION; STAPHYLOCOCCUS-AUREUS; ASPARTATE TRANSPORTER;
ESCHERICHIA-COLI; SLC13 FAMILY; PYROCOCCUS-HORIKOSHII;
INSULIN-RESISTANCE; CRYSTAL-STRUCTURE
AB The SLC13 transporter family, whose members play key physiological roles in the regulation of fatty acid synthesis, adiposity, insulin resistance, and other processes, catalyzes the transport of Krebs cycle intermediates and sulfate across the plasma membrane of mammalian cells. SLC13 transporters are part of the divalent anion: Na+ symporter (DASS) family that includes several well-characterized bacterial members. Despite sharing significant sequence similarity, the functional characteristics of DASS family members differ with regard to their substrate and coupling ion dependence. The publication of a high resolution structure of dimer VcINDY, a bacterial DASS family member, provides crucial structural insight into this transporter family. However, marrying this structural insight to the current functional understanding of this family also demands a comprehensive analysis of the transporter's functional properties. To this end, we purified VcINDY, reconstituted it into liposomes, and determined its basic functional characteristics. Our data demonstrate that VcINDY is a high affinity, Na+-dependent transporter with a preference for C-4- and C-5-dicarboxylates. Transport of the model substrate, succinate, is highly pH dependent, consistent with VcINDY strongly preferring the substrate's dianionic form. VcINDY transport is electrogenic with succinate coupled to the transport of three or more Na+ ions. In contrast to succinate, citrate, bound in the VcINDY crystal structure (in an inward-facing conformation), seems to interact only weakly with the transporter in vitro. These transport properties together provide a functional framework for future experimental and computational examinations of the VcINDY transport mechanism.
C1 [Mulligan, Christopher; Fitzgerald, Gabriel A.; Mindell, Joseph A.] Natl Inst Neurol Disorders & Stroke, Membrane Transport Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Wang, Da-Neng] NYU, Sch Med, Skirball Inst Biomol Med, Helen L & Martin Kimmel Ctr Biol & Med, New York, NY 10016 USA.
[Wang, Da-Neng] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA.
RP Mindell, JA (reprint author), Natl Inst Neurol Disorders & Stroke, Membrane Transport Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
EM mindellj@ninds.nih.gov
OI Fitzgerald, Gabriel/0000-0002-8235-0148; Mindell,
Joseph/0000-0002-6952-8247
FU Intramural Research Program of the National Institutes of Health (NIH);
National Institute of Neurological Disorders and Stroke; NIH
[R01-DK099023, R01-DK073973, R01-GM093825, R01-DA019676, U54-GM095315]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Institute of Neurological
Disorders and Stroke, and NIH grants (R01-DK099023, R01-DK073973,
R01-GM093825, R01-DA019676, and U54-GM095315).
NR 58
TC 15
Z9 15
U1 0
U2 4
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
EI 1540-7748
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD JUN
PY 2014
VL 143
IS 6
BP 745
EP 759
DI 10.1085/jgp.201311141
PG 15
WC Physiology
SC Physiology
GA AI8KM
UT WOS:000337162500008
PM 24821967
ER
PT J
AU Tian, Y
Schwieters, CD
Opella, SJ
Marassi, FM
AF Tian, Ye
Schwieters, Charles D.
Opella, Stanley J.
Marassi, Francesca M.
TI A practical implicit solvent potential for NMR structure calculation
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Protein structure; Calculation; Implicit solvent; EEFx; XPLOR-NIH; NMR
ID MOLECULAR-STRUCTURE DETERMINATION; MAGNETIC-RESONANCE SPECTROSCOPY;
PROTEIN-FOLDING THERMODYNAMICS; EFFECTIVE ENERGY FUNCTION; N-TERMINAL
DOMAIN; STRUCTURE VALIDATION; STRUCTURE REFINEMENT; PHOSPHOTRANSFERASE
SYSTEM; 3-DIMENSIONAL STRUCTURES; CONFORMATIONAL DATABASE
AB The benefits of protein structure refinement in water are well documented. However, performing structure refinement with explicit atomic representation of the solvent molecules is computationally expensive and impractical for NMR-restrained structure calculations that start from completely extended polypeptide templates. Here we describe a new implicit solvation potential, EEFx (Effective Energy Function for XPLOR-NIH), for NMR-restrained structure calculations of proteins in XPLOR-NIH. The key components of EEFx are an energy term for solvation energy that works together with other nonbonded energy functions, and a dedicated force field for conformational and nonbonded protein interaction parameters. The initial results obtained with EEFx show that significant improvements in structural quality can be obtained. EEFx is computationally efficient and can be used both to fold and refine structures. Overall, EEFx improves the quality of protein conformation and nonbonded atomic interactions. Moreover, such benefits are accompanied by enhanced structural precision and enhanced structural accuracy, reflected in improved agreement with the cross-validated dipolar coupling data. Finally, implementation of EEFx calculations is straightforward and computationally efficient. Overall, EEFx provides a useful method for the practical calculation of experimental protein structures in a physically realistic environment. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Tian, Ye; Marassi, Francesca M.] Sanford Burnham Med Res Inst, La Jolla, CA 92037 USA.
[Tian, Ye; Opella, Stanley J.] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
[Schwieters, Charles D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Marassi, FM (reprint author), Sanford Burnham Med Res Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM fmarassi@sbmri.org
FU National Institutes of Health [R01 GM100265, P01 AI074805, R21 GM094727,
P41 EB002031]; NIH Intramural Research Program of The Center for
Information Technology
FX This research was supported by Grants from the National Institutes of
Health (R01 GM100265; P01 AI074805 and R21 GM094727). It utilized the
Resource for Molecular Imaging of Proteins at UCSD, supported by NIH
Grant P41 EB002031). CDS was supported by funds from the NIH Intramural
Research Program of The Center for Information Technology.
NR 75
TC 7
Z9 7
U1 1
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
EI 1096-0856
J9 J MAGN RESON
JI J. Magn. Reson.
PD JUN
PY 2014
VL 243
BP 54
EP 64
DI 10.1016/j.jmr.2014.03.011
PG 11
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA AI7ZK
UT WOS:000337121300008
PM 24747742
ER
PT J
AU Thorwarth, A
Schnittert-Hubener, S
Schrumpf, P
Muller, I
Jyrch, S
Dame, C
Biebermann, H
Kleinau, G
Katchanov, J
Schuelke, M
Ebert, G
Steininger, A
Bonnemann, C
Brockmann, K
Christen, HJ
Crock, P
deZegher, F
Griese, M
Hewitt, J
Ivarsson, S
Hubner, C
Kapelari, K
Plecko, B
Rating, D
Stoeva, I
Ropers, HH
Gruters, A
Ullmann, R
Krude, H
AF Thorwarth, Anne
Schnittert-Huebener, Sarah
Schrumpf, Pamela
Mueller, Ines
Jyrch, Sabine
Dame, Christof
Biebermann, Heike
Kleinau, Gunnar
Katchanov, Juri
Schuelke, Markus
Ebert, Grit
Steininger, Anne
Boennemann, Carsten
Brockmann, Knut
Christen, Hans-Juergen
Crock, Patricia
deZegher, Francis
Griese, Matthias
Hewitt, Jacqueline
Ivarsson, Sten
Huebner, Christoph
Kapelari, Klaus
Plecko, Barbara
Rating, Dietz
Stoeva, Iva
Ropers, Hans-Hilger
Grueters, Annette
Ullmann, Reinhard
Krude, Heiko
TI Comprehensive genotyping and clinical characterisation reveal 27 novel
NKX2-1 mutations and expand the phenotypic spectrum
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID BENIGN HEREDITARY CHOREA; TRANSCRIPTION FACTOR-I; PAPILLARY
THYROID-CARCINOMA; ENHANCER-BINDING PROTEIN; EMBRYONIC STEM-CELLS;
FUNCTIONAL-CHARACTERIZATION; CONGENITAL HYPOTHYROIDISM;
RESPIRATORY-FAILURE; GANGLIONIC EMINENCES; EPITHELIAL-CELLS
AB Background NKX2-1 encodes a transcription factor with large impact on the development of brain, lung and thyroid. Germline mutations of NKX2-1 can lead to dysfunction and malformations of these organs. Starting from the largest coherent collection of patients with a suspected phenotype to date, we systematically evaluated frequency, quality and spectrum of phenotypic consequences of NKX2-1 mutations.
Methods After identifying mutations by Sanger sequencing and array CGH, we comprehensively reanalysed the phenotype of affected patients and their relatives. We employed electrophoretic mobility shift assay (EMSA) to detect alterations of NKX2-1 DNA binding. Gene expression was monitored by means of in situ hybridisation and compared with the expression level of MBIP, a candidate gene presumably involved in the disorders and closely located in close genomic proximity to NKX2-1.
Results Within 101 index patients, we detected 17 point mutations and 10 deletions. Neurological symptoms were the most consistent finding (100%), followed by lung affection (78%) and thyroidal dysfunction (75%). Novel symptoms associated with NKX2-1 mutations comprise abnormal height, bouts of fever and cardiac septum defects. In contrast to previous reports, our data suggest that missense mutations in the homeodomain of NKX2-1 not necessarily modify its DNA binding capacity and that this specific type of mutations may be associated with mild pulmonary phenotypes such as asthma. Two deletions did not include NKX2-1, but MBIP, whose expression spatially and temporarily coincides with NKX2-1 in early murine development.
Conclusions The high incidence of NKX2-1 mutations strongly recommends the routine screen for mutations in patients with corresponding symptoms. However, this analysis should not be confined to the exonic sequence alone, but should take advantage of affordable NGS technology to expand the target to adjacent regulatory sequences and the NKX2-1 interactome in order to maximise the yield of this diagnostic effort.
C1 [Thorwarth, Anne; Schnittert-Huebener, Sarah; Schrumpf, Pamela; Jyrch, Sabine; Biebermann, Heike; Kleinau, Gunnar; Grueters, Annette; Krude, Heiko] Charite, Inst Expt Pediat Endocrinol, D-13353 Berlin, Germany.
[Thorwarth, Anne; Mueller, Ines; Ebert, Grit; Steininger, Anne; Ropers, Hans-Hilger; Ullmann, Reinhard] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
[Dame, Christof] Charite, Dept Neonatol, D-13353 Berlin, Germany.
[Katchanov, Juri] Charite, Dept Neurol, D-13353 Berlin, Germany.
[Schuelke, Markus] Charite, Dept Neuropediat, D-13353 Berlin, Germany.
[Boennemann, Carsten] NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, NIH, Bethesda, MD 20892 USA.
[Brockmann, Knut] Univ Gottingen, Interdisciplinary Pediat Ctr Children Dev Disabil, Univ Med Ctr, D-37073 Gottingen, Germany.
[Christen, Hans-Juergen] Childrens & Youth Hosp Auf der Bult, Dept Neuropediat, Hannover, Germany.
[Crock, Patricia] John Hunter Childrens Hosp, Div Pediat Endocrinol & Diabet, Newcastle, NSW, Australia.
[deZegher, Francis] Univ Louvain, Dept Woman & Child, Louvain, Belgium.
[Griese, Matthias] Univ Munich, Dr von Haunersches Kinderspital, Munich, Germany.
[Hewitt, Jacqueline] Royal Childrens Hosp, Div Endocrinol & Diabet, Melbourne, Vic, Australia.
[Ivarsson, Sten] Univ Hosp MAS, Dept Clin Sci Pediat Endocrinol, Malmo, Sweden.
[Kapelari, Klaus] Med Univ Innsbruck, Dept Pediat & Adolescent Med, A-6020 Innsbruck, Austria.
[Plecko, Barbara] Univ Childrens Hosp Zurich, Div Child Neurol, Zurich, Switzerland.
[Rating, Dietz] Univ Heidelberg Hosp, Dept Neuropediat, Heidelberg, Germany.
[Stoeva, Iva] Med Univ Sofia, Dept Paediat Endocrinol Screening & Funct Endocri, Sofia, Bulgaria.
RP Krude, H (reprint author), Charite, Inst Expt Pediat Endocrinol, Augustenburger Pl 1, D-13353 Berlin, Germany.
EM ullmann@molgen.mpg.de; ullmann@molgen.mpg.de
FU Intramural NIH HHS [Z99 NS999999, ZIA NS003129-02, ZIA NS003129-03, ZIA
NS003129-04]
NR 86
TC 11
Z9 13
U1 1
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
EI 1468-6244
J9 J MED GENET
JI J. Med. Genet.
PD JUN
PY 2014
VL 51
IS 6
BP 375
EP 387
DI 10.1136/jmedgenet-2013-102248
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA AI4NE
UT WOS:000336841300003
PM 24714694
ER
PT J
AU Bear, KA
Solomon, BD
Antonini, S
Arnhold, IJP
Franca, MM
Gerkes, EH
Grange, DK
Hadley, DW
Jaaskelainen, J
Paulo, SS
Rump, P
Stratakis, CA
Thompson, EM
Willis, M
Winder, TL
Jorge, AAL
Roessler, E
Muenke, M
AF Bear, Kelly A.
Solomon, Benjamin D.
Antonini, Sonir
Arnhold, Ivo J. P.
Franca, Marcela M.
Gerkes, Erica H.
Grange, Dorothy K.
Hadley, Donald W.
Jaaskelainen, Jarmo
Paulo, Sabrina S.
Rump, Patrick
Stratakis, Constantine A.
Thompson, Elizabeth M.
Willis, Mary
Winder, Thomas L.
Jorge, Alexander A. L.
Roessler, Erich
Muenke, Maximilian
TI Pathogenic mutations in GLI2 cause a specific phenotype that is distinct
from holoprosencephaly
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID SONIC-HEDGEHOG; SPECTRUM; HYPOPITUITARISM; INDIVIDUALS; FREQUENCY;
VARIANTS; DEFECTS; DISEASE; GENE; ZIC2
AB Background Mutations in GLI2 have been associated with holoprosencephaly (HPE), a neuroanatomic anomaly resulting from incomplete cleavage of the developing forebrain, and an HPE-like phenotype involving pituitary anomalies and polydactyly.
Objective To characterise the genotypic and phenotypic findings in individuals with GLI2 variants and clarify clinical findings in individuals with loss-of-function mutations.
Methods Through the National Institutes of Health and collaborating centres, similar to 400 individuals with HPE spectrum disorders, endocrine disorders or craniofacial anomalies were screened for GLI2 mutations. Results were combined with all published cases. We compared the clinical and molecular features of individuals with truncating mutations to individuals with variants of unknown significance (defined as not resulting in protein truncation, reported in normal controls and/or deemed unlikely to be pathogenic by functional prediction software).
Results 112 individuals with variants in GLI2 were identified, with 43 having truncating mutations. Individuals with truncating mutations were more likely to have both pituitary anomalies and polydactyly versus those with variants of unknown significance (p<0.0001 by Fisher's exact test); only 1 of 43 had frank HPE. These individuals were more likely to have recognised penetrance (polydactyly or pituitary anomalies or both) than those without truncating mutations (p=0.0036 by Fisher's exact test). A common facial phenotype was seen in individuals (with midface hypoplasia, cleft lip/palate and hypotelorism) with truncating mutations.
Conclusions Individuals with truncating mutations in GLI2 typically present with pituitary anomalies, polydactyly and subtle facial features rather than HPE. This will be helpful in screening populations for GLI2 mutations and for counselling affected patients.
C1 [Bear, Kelly A.; Solomon, Benjamin D.; Hadley, Donald W.; Roessler, Erich; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Bear, Kelly A.] Tripler Army Med Ctr, Dept Pediat, Honolulu, HI 96859 USA.
[Solomon, Benjamin D.] Inova Hlth Syst, Inova Translat Med Inst, Div Med Genom, Falls Church, VA USA.
[Solomon, Benjamin D.] Inova Hlth Syst, Inova Childrens Hosp, Dept Pediat, Falls Church, VA USA.
[Antonini, Sonir; Paulo, Sabrina S.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pediat, Sao Paulo, Brazil.
[Arnhold, Ivo J. P.; Franca, Marcela M.] Univ Sao Paulo, Unidade Endocrinol Desenvolvimento, Lab Hormonios & Genet Mol LIM 42, Hosp Clin,Fac Med,Disciplina Endocrinol, Sao Paulo, Brazil.
[Gerkes, Erica H.; Rump, Patrick] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[Grange, Dorothy K.] Washington Univ Schl Mdcn, St Louis, MO USA.
[Jaaskelainen, Jarmo] Univ Eastern Finland, Dept Pediat, Kuopio, Finland.
[Jaaskelainen, Jarmo] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Thompson, Elizabeth M.] Womens & Childrens Hosp, South Australian Clin Genet Serv, SA Pathol, Adelaide, SA, Australia.
[Thompson, Elizabeth M.] Univ Adelaide, Dept Paediat, Adelaide, SA, Australia.
[Willis, Mary] Naval Med Ctr, Dept Pediat, San Diego, CA USA.
[Winder, Thomas L.] Prevent Genet, Marshfield, WI USA.
[Jorge, Alexander A. L.] Univ Sao Paulo, Unidade Endocrinol Genet, LIM 25, Disciplina Endocrinol,Hosp Clin,Fac Med, Sao Paulo, Brazil.
RP Muenke, M (reprint author), NHGRI, Med Genet Branch, 35 Convent Dr,Bldg 35,Room 1B 203, Bethesda, MD 20892 USA.
EM mamuenke@mail.nih.gov
RI Jorge, Alexander/C-7697-2012; ARNHOLD, IVO/D-2672-2012; Antonini, Sonir
/J-5264-2015
OI Jorge, Alexander/0000-0003-2567-7360;
FU Division of Intramural Research, National Human Genome Research
Institute, National Institutes of Health, Department of Health and Human
Services, USA
FX This research was supported by the Division of Intramural Research,
National Human Genome Research Institute, National Institutes of Health,
Department of Health and Human Services, USA. Pertaining to KAB, the
views expressed in this publication are those of the author and do not
reflect the official policy or position of the Department of the Army,
Department of Defense, or the US Government. Pertaining to MW, the views
expressed in this article are those of the author and do not necessarily
reflect the official policy or position of the Department of the Navy,
Department of Defense or the United States Government. The authors would
like to express their gratitude to the patients and families involved.
NR 28
TC 11
Z9 11
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
EI 1468-6244
J9 J MED GENET
JI J. Med. Genet.
PD JUN
PY 2014
VL 51
IS 6
BP 413
EP 418
DI 10.1136/jmedgenet-2013-102249
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA AI4NE
UT WOS:000336841300008
PM 24744436
ER
PT J
AU Ben-David, U
Biran, A
Scaffidi, P
Herold-Mende, C
Boehringer, M
Meshorer, E
Benvenisty, N
AF Ben-David, Uri
Biran, Alva
Scaffidi, Paola
Herold-Mende, Christel
Boehringer, Markus
Meshorer, Eran
Benvenisty, Nissim
TI Elimination of undifferentiated cancer cells by pluripotent stem cell
inhibitors
SO JOURNAL OF MOLECULAR CELL BIOLOGY
LA English
DT Letter
ID THERAPY
C1 [Ben-David, Uri; Benvenisty, Nissim] Hebrew Univ Jerusalem, Silberman Inst Life Sci, Stem Cell Unit, IL-91904 Jerusalem, Israel.
[Ben-David, Uri; Biran, Alva; Meshorer, Eran; Benvenisty, Nissim] Hebrew Univ Jerusalem, Silberman Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel.
[Scaffidi, Paola] NCI, NIH, Bethesda, MD 20892 USA.
[Scaffidi, Paola] UCL, UCL Canc Inst, London WC1E 6BT, England.
[Scaffidi, Paola] Canc Res UK London Res Inst, London WC2A 3LY, England.
[Herold-Mende, Christel] Heidelberg Univ, Dept Neurosurg, Div Neurosurg Res, Heidelberg, Germany.
[Boehringer, Markus] F Hoffmann La Roche & Cie AG, CH-4070 Basel, Switzerland.
RP Meshorer, E (reprint author), Hebrew Univ Jerusalem, Silberman Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel.
EM meshorer@huji.ac.il; nissimb@cc.huji.ac.il
FU Intramural NIH HHS
NR 10
TC 4
Z9 4
U1 0
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1674-2788
EI 1759-4685
J9 J MOL CELL BIOL
JI J. Mol. Cell Biol.
PD JUN
PY 2014
VL 6
IS 3
SI SI
BP 267
EP 269
DI 10.1093/jmcb/mju012
PG 3
WC Cell Biology
SC Cell Biology
GA AI7JR
UT WOS:000337065700010
PM 24683201
ER
PT J
AU Chang, KE
Edwards, N
Mishra, B
Hallett, M
Ray-Chaudhury, A
AF Chang, Ki-Eun
Edwards, Nancy
Mishra, Bibhuti
Hallett, Mark
Ray-Chaudhury, Abhik
TI Adult-Onset Alexander Disease in a Paraplegic African-American Male with
a Rare D138N Mutation in the GFAP Gene
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 12-15, 2014
CL Portland, OR
SP Amer Assoc Neuropathologists Inc
C1 [Chang, Ki-Eun] Penn State Coll Med, NIH, Hershey, PA USA.
[Edwards, Nancy; Hallett, Mark] NINDS, NIH, Bethesda, MD 20892 USA.
[Mishra, Bibhuti] Inova Fairfax Hosp, Falls Church, VA 22042 USA.
[Ray-Chaudhury, Abhik] NIH, 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 0022-3069
EI 1554-6578
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2014
VL 73
IS 6
MA 59
BP 600
EP 601
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AI3AZ
UT WOS:000336732100069
ER
PT J
AU Curtis, M
Mardekian, S
Miettinen, M
Andrews, E
AF Curtis, Mark
Mardekian, Stacey
Miettinen, Markku
Andrews, Edward
TI Succinate Dehydrogenase (SDH) Deficiency in Non-familial Pituitary
Adenomas
SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
LA English
DT Meeting Abstract
CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc
CY JUN 12-15, 2014
CL Portland, OR
SP Amer Assoc Neuropathologists Inc
C1 [Curtis, Mark] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
[Mardekian, Stacey; Andrews, Edward] Thomas Jefferson Univ Hosp, Dept Pathol, Philadelphia, PA 19107 USA.
[Miettinen, Markku] NCI, Pathol Lab, 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 0022-3069
EI 1554-6578
J9 J NEUROPATH EXP NEUR
JI J. Neuropathol. Exp. Neurol.
PD JUN
PY 2014
VL 73
IS 6
MA 119
BP 616
EP 617
PG 2
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA AI3AZ
UT WOS:000336732100126
ER
PT J
AU Ho, JE
Larson, MG
Ghorbani, A
Cheng, S
Coglianese, EE
Vasan, RS
Wang, TJ
AF Ho, Jennifer E.
Larson, Martin G.
Ghorbani, Anahita
Cheng, Susan
Coglianese, Erin E.
Vasan, Ramachandran S.
Wang, Thomas J.
TI Long-term Cardiovascular Risks Associated With an Elevated Heart Rate:
The Framingham Heart Study
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE cardiovascular disease; epidemiology; heart failure; risk factor
ID PACEMAKER IMPLANTATION; MYOCARDIAL-INFARCTION; PHYSICAL-ACTIVITY;
PROGNOSTIC-FACTOR; PULSE-RATE; MORTALITY; FAILURE; DISEASE; MEN;
ATHEROSCLEROSIS
AB Background-Higher heart rate has been associated with an adverse prognosis, but most prior studies focused on individuals with known cardiovascular disease or examined a limited number of outcomes. We sought to examine the association of baseline heart rate with both fatal and nonfatal outcomes during 2 decades of follow-up.
Methods and Results-Our study included 4058 Framingham Heart Study participants (mean age 55 years, 56% women). Cox models were performed with multivariable adjustment for clinical risk factors and physical activity. A total of 708 participants developed incident cardiovascular disease (303 heart failure, 343 coronary heart disease, and 216 stroke events), 48 received a permanent pacemaker, and 1186 died. Baseline heart rate was associated with incident cardiovascular disease (hazard ratio [HR] 1.15 per 1 SD [11 bpm] increase in heart rate, 95% CI 1.07 to 1.24, P=0.0002), particularly heart failure (HR 1.32, 95% CI 1.18 to 1.48, P<0.0001). Higher heart rate was also associated with higher all-cause (HR 1.17, 95% CI 1.11 to 1.24, P<0.0001) and cardiovascular mortality (HR 1.18, 95% CI 1.04 to 1.33, P=0.01). Spline analyses did not suggest a lower threshold beyond which the benefit of a lower heart rate abated or increased. In contrast, individuals with a higher heart rate had a lower risk of requiring permanent pacemaker placement (HR 0.55, 95% CI 0.38 to 0.79, P=0.001).
Conclusions-Individuals with a higher heart rate are at elevated long-term risk for cardiovascular events, in particular, heart failure, and all-cause death. On the other hand, a higher heart rate is associated with a lower risk of future permanent pacemaker implantation.
C1 [Ho, Jennifer E.; Larson, Martin G.; Cheng, Susan; Vasan, Ramachandran S.; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Ho, Jennifer E.; Larson, Martin G.; Cheng, Susan; Vasan, Ramachandran S.; Wang, Thomas J.] Boston Univ, Sch Med, Framingham, MA USA.
[Ho, Jennifer E.] Boston Univ, Cardiovasc Med Sect, Sch Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA.
[Ghorbani, Anahita] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Cheng, Susan] Harvard Univ, Sch Med, Dept Med, Div Cardiol,Brigham & Womens Hosp, Boston, MA USA.
[Coglianese, Erin E.] Loyola Univ Hlth Syst, Chicago, IL USA.
[Wang, Thomas J.] Vanderbilt Univ, Dept Med, Div Cardiovasc Med, Nashville, TN USA.
RP Ho, JE (reprint author), Boston Univ, Med Ctr, 88 East Newton St,C-818, Boston, MA 02118 USA.
EM jenho@bu.edu
OI Ho, Jennifer/0000-0002-7987-4768; Ramachandran,
Vasan/0000-0001-7357-5970
FU National Heart, Lung, and Blood Institute [N01-HC-25195]; National
Institutes of Health [K23-HL116780]; Boston University School of
Medicine Department of Medicine; Ellison Foundation
FX This work was partially supported by the Framingham Heart Study of the
National Heart, Lung, and Blood Institute (contract N01-HC-25195). Dr Ho
is supported by National Institutes of Health grant K23-HL116780 and a
Boston University School of Medicine Department of Medicine Career
Investment Award. Dr Cheng is supported by an award from the Ellison
Foundation.
NR 37
TC 20
Z9 20
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUN
PY 2014
VL 3
IS 3
AR e000668
DI 10.1161/JAHA.113.000668
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AI4QB
UT WOS:000336848800008
PM 24811610
ER
PT J
AU McDermott, MM
Guralnik, JM
Criqui, MH
Ferrucci, L
Zhao, LH
Liu, K
Domanchuk, K
Spring, B
Tian, L
Kibbe, M
Liao, YH
Jones, DL
Rejeski, WJ
AF McDermott, Mary M.
Guralnik, Jack M.
Criqui, Michael H.
Ferrucci, Luigi
Zhao, Lihui
Liu, Kiang
Domanchuk, Kathryn
Spring, Bonnie
Tian, Lu
Kibbe, Melina
Liao, Yihua
Jones, Donald Lloyd
Rejeski, W. Jack
TI Home-Based Walking Exercise in Peripheral Artery Disease: 12-Month
Follow-up of the Goals Randomized Trial
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE behavior change; exercise; mobility; peripheral artery disease; physical
functioning
ID ANKLE BRACHIAL INDEX; INTERMITTENT CLAUDICATION; PHYSICAL-ACTIVITY;
FUNCTIONAL PERFORMANCE; DAILY-LIFE; LEG SYMPTOMS; OLDER-ADULTS;
REHABILITATION; INTERVENTION; METAANALYSIS
AB Background-We studied whether a 6-month group-mediated cognitive behavioral (GMCB) intervention for peripheral artery disease (PAD) participants, which promoted home-based walking exercise, improved 6-minute walk and other outcomes at 12-month follow-up, 6 months after completing the intervention, compared to a control group.
Methods and Results-We randomized PAD participants to a GMCB intervention or a control group. During phase I (months 1 to 6), the intervention used group support and self-regulatory skills during weekly on-site meetings to help participants adhere to home-based exercise. The control group received weekly on-site lectures on topics unrelated to exercise. Primary outcomes were measured at the end of phase I. During phase II (months 7 to 12), each group received telephone contact. Compared to controls, participants randomized to the intervention increased their 6-minute walk distance from baseline to 12-month follow-up, (from 355.4 to 381.9 m in the intervention versus 353.1 to 345.6 m in the control group; mean difference=+34.1 m; 95% confidence interval [CI]=+14.6, +53.5; P<0.001) and their Walking Impairment Questionnaire (WIQ) speed score (from 36.1 to 46.5 in the intervention group versus 34.9 to 36.5 in the control group; mean difference =+8.8; 95% CI=+1.6, +16.1; P=0.018). Change in the WIQ distance score was not different between the 2 groups at 12-month follow-up (P=0.139).
Conclusions-A weekly on-site GMCB intervention that promoted home-based walking exercise intervention for people with PAD demonstrated continued benefit at 12-month follow-up, 6 months after the GMCB intervention was completed.
C1 [McDermott, Mary M.; Domanchuk, Kathryn; Jones, Donald Lloyd] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[McDermott, Mary M.; Zhao, Lihui; Liu, Kiang; Spring, Bonnie; Liao, Yihua; Jones, Donald Lloyd] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Kibbe, Melina] Northwestern Univ, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA.
[Tian, Lu] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Kibbe, Melina] Jesse Brown Vet Affairs Med Ctr, Chicago, IL USA.
[Rejeski, W. Jack] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA.
RP McDermott, MM (reprint author), 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
FU National Heart, Lung and Blood Institute [R01-HL088589, R01-HL107510];
National Institutes on Aging, National Institutes of Health
FX Supported by R01-HL088589 and R01-HL107510 from the National Heart, Lung
and Blood Institute. Supported, in part, by the Intramural Research
Program, National Institutes on Aging, National Institutes of Health.
NR 37
TC 21
Z9 22
U1 7
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUN
PY 2014
VL 3
IS 3
AR e000711
DI 10.1161/JAHA.113.000711
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AI4QB
UT WOS:000336848800010
PM 24850615
ER
PT J
AU Mandell, DT
Kristoff, J
Gaufin, T
Gautam, R
Ma, DZ
Sandler, N
Haret-Richter, G
Xu, CL
Aamer, H
Dufour, J
Trichel, A
Douek, DC
Keele, BF
Apetrei, C
Pandrea, I
AF Mandell, Daniel T.
Kristoff, Jan
Gaufin, Thaidra
Gautam, Rajeev
Ma, Dongzhu
Sandler, Netanya
Haret-Richter, George
Xu, Cuiling
Aamer, Hadega
Dufour, Jason
Trichel, Anita
Douek, Daniel C.
Keele, Brandon F.
Apetrei, Cristian
Pandrea, Ivona
TI Pathogenic Features Associated with Increased Virulence upon Simian
Immunodeficiency Virus Cross-Species Transmission from Natural Hosts
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID AFRICAN-GREEN MONKEYS; CD4(+) T-CELLS; IN-VIVO REPLICATION; INFECTED
SOOTY MANGABEYS; PRIMARY HIV-1 INFECTION; ACUTE SIV INFECTION; PLASMA
VIRAL LOAD; RHESUS MACAQUES; GASTROINTESTINAL-TRACT; PIGTAIL MACAQUES
AB While simian immunodeficiency viruses (SIVs) are generally nonpathogenic in their natural hosts, dramatic increases in pathogenicity may occur upon cross-species transmission to new hosts. Deciphering the drivers of these increases in virulence is of major interest for understanding the emergence of new human immunodeficiency viruses (HIVs). We transmitted SIVsab from the sabaeus species of African green monkeys (AGMs) to pigtailed macaques (PTMs). High acute viral replication occurred in all SIVsab-infected PTMs, yet the outcome of chronic infection was highly variable, ranging from rapid progression to controlled infection, which was independent of the dynamics of acute viral replication, CD4(+) T cell depletion, or preinfection levels of microbial translocation. Infection of seven PTMs with plasma collected at necropsy from a rapid-progressor PTM was consistently highly pathogenic, with high acute and chronic viral replication, massive depletion of memory CD4(+) T cells, and disease progression in all PTMs. The plasma inoculum used for the serial passage did not contain adventitious bacterial or viral contaminants. Single-genome amplification showed that this inoculum was significantly more homogenous than the inoculum directly derived from AGMs, pointing to a strain selection in PTMs. In spite of similar peak plasma viral loads between the monkeys in the two passages, immune activation/inflammation levels dramatically increased in PTMs infected with the passaged virus. These results suggest that strain selection and a massive cytokine storm are major factors behind increased pathogenicity of SIV upon serial passage and adaptation of SIVs to new hosts following cross-species transmission.
C1 [Mandell, Daniel T.; Gaufin, Thaidra; Gautam, Rajeev; Apetrei, Cristian] TNPRC, Div Microbiol, Covington, LA USA.
[Dufour, Jason] TNPRC, Div Vet Med, Covington, LA USA.
[Pandrea, Ivona] TNPRC, Div Comparat Pathol, Covington, LA USA.
[Kristoff, Jan; Ma, Dongzhu; Haret-Richter, George; Xu, Cuiling; Aamer, Hadega; Apetrei, Cristian; Pandrea, Ivona] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15260 USA.
[Sandler, Netanya; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Trichel, Anita] Univ Pittsburgh, Sch Med, Div Lab Anim Resourcese, Pittsburgh, PA USA.
[Apetrei, Cristian] Univ Pittsburgh, Sch Med, Dept Microbiol & Mol Genet, Pittsburgh, PA USA.
[Pandrea, Ivona] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA.
[Keele, Brandon F.] Leidos Biomed Res Inc, Frederick Natl Lab, AIDS & Canc Virus Program, Frederick, MD USA.
RP Pandrea, I (reprint author), Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15260 USA.
EM apetreic@pitt.edu; pandrea@pitt.edu
RI Haret-Richter, George S/G-3563-2015;
OI Utay, Netanya/0000-0002-6407-8670
FU National Institute of Allergy and Infectious Diseases (NIAID) [RO1
AI064066, R01 AI065325, P20 RR020159]; National Center for Research
Resources (NCRR) [RO1 RR025781]; National Heart, Lung and Blood
Institute [RO1 HL117715]; National Cancer Institute [HHSN261200800001E]
FX This work was supported by funds from grants RO1 AI064066 (I. P.) and
R01 AI065325 and P20 RR020159 (C. A.) from the National Institute of
Allergy and Infectious Diseases (NIAID), RO1 RR025781 (C. A. and I. P.)
from the National Center for Research Resources (NCRR), RO1 HL117715 (I.
P.) from the National Heart, Lung and Blood Institute, and in part with
federal funds from the National Cancer Institute under contract
HHSN261200800001E (B.F.K.).
NR 76
TC 8
Z9 8
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2014
VL 88
IS 12
BP 6778
EP 6792
DI 10.1128/JVI.03785-13
PG 15
WC Virology
SC Virology
GA AI5HF
UT WOS:000336895600022
PM 24696477
ER
PT J
AU Chen, ZY
Baz, M
Lu, J
Paskel, M
Santos, C
Subbarao, K
Jin, H
Matsuoka, Y
AF Chen, Zhongying
Baz, Mariana
Lu, Janine
Paskel, Myeisha
Santos, Celia
Subbarao, Kanta
Jin, Hong
Matsuoka, Yumiko
TI Development of a High-Yield Live Attenuated H7N9 Influenza Virus Vaccine
That Provides Protection against Homologous and Heterologous H7
Wild-Type Viruses in Ferrets
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RECEPTOR-BINDING SPECIFICITY; A VIRUS; HEMAGGLUTININ PROTEIN;
BRITISH-COLUMBIA; HUMAN INFECTION; MICE; TRANSMISSION; CONJUNCTIVITIS;
CHALLENGE; REPLICATION
AB Live attenuated H7N9 influenza vaccine viruses that possess the hemagglutinin (HA) and neuraminidase (NA) gene segments from the newly emerged wild-type (wt) A/Anhui/1/2013 (H7N9) and six internal protein gene segments from the cold-adapted influenza virus A/Ann Arbor/6/60 (AA ca) were generated by reverse genetics. The reassortant virus containing the original wt A/Anhui/1/2013 HA and NA sequences replicated poorly in eggs. Multiple variants with amino acid substitutions in the HA head domain that improved viral growth were identified by viral passage in eggs and MDCK cells. The selected vaccine virus containing two amino acid changes (N133D/G198E) in the HA improved viral titer by more than 10-fold (reached a titer of 10(8.6) fluorescent focus units/ml) without affecting viral antigenicity. Introduction of these amino acid changes into an H7N9 PR8 reassortant virus also significantly improved viral titers and HA protein yield in eggs. The H7N9 ca vaccine virus was immunogenic in ferrets. A single dose of vaccine conferred complete protection of ferrets from homologous wt A/Anhui/1/2013 (H7N9) and nearly complete protection from heterologous wt A/Netherlands/219/2003 (H7N7) challenge infection. Therefore, this H7N9 live attenuated influenza vaccine (LAIV) candidate has been selected for vaccine manufacture and clinical evaluation to protect humans from wt H7N9 virus infection.
C1 [Chen, Zhongying; Lu, Janine; Jin, Hong] MedImmune LLC, Mountain View, CA 94043 USA.
[Baz, Mariana; Paskel, Myeisha; Santos, Celia; Subbarao, Kanta; Matsuoka, Yumiko] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Chen, ZY (reprint author), MedImmune LLC, Mountain View, CA 94043 USA.
EM chenz@medimmune.com
FU Biomedical Advanced Research and Development Authority of the U.S.
Department of Health and Human Services [HHSO100201200012I]; NIAID, NIH
FX This study was funded in part by federal funds from Biomedical Advanced
Research and Development Authority of the U.S. Department of Health and
Human Services under the contract number HHSO100201200012I and by the
Intramural Research Program of NIAID, NIH. The work is conducted under a
Cooperative Research and Development Agreement between MedImmune and
NIAID/NIH.
NR 51
TC 20
Z9 21
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2014
VL 88
IS 12
BP 7016
EP 7023
DI 10.1128/JVI.00100-14
PG 8
WC Virology
SC Virology
GA AI5HF
UT WOS:000336895600041
PM 24719414
ER
PT J
AU Saisawat, P
Kohl, S
Hilger, AC
Hwang, DY
Gee, HY
Dworschak, GC
Tasic, V
Pennimpede, T
Natarajan, S
Sperry, E
Matassa, DS
Stajic, N
Bogdanovic, R
de Blaauw, I
Marcelis, CLM
Wijers, CHW
Bartels, E
Schmiedeke, E
Schmidt, D
Marzheuser, S
Grasshoff-Derr, S
Holland-Cunz, S
Ludwig, M
Nothen, MM
Draaken, M
Brosens, E
Heij, H
Tibboel, D
Herrmann, BG
Solomon, BD
de Klein, A
van Rooij, IALM
Esposito, F
Reutter, HM
Hildebrandt, F
AF Saisawat, Pawaree
Kohl, Stefan
Hilger, Alina C.
Hwang, Daw-Yang
Gee, Heon Yung
Dworschak, Gabriel C.
Tasic, Velibor
Pennimpede, Tracie
Natarajan, Sivakumar
Sperry, Ethan
Matassa, Danilo S.
Stajic, Natasa
Bogdanovic, Radovan
de Blaauw, Ivo
Marcelis, Carlo L. M.
Wijers, Charlotte H. W.
Bartels, Enrika
Schmiedeke, Eberhard
Schmidt, Dominik
Maerzheuser, Stefanie
Grasshoff-Derr, Sabine
Holland-Cunz, Stefan
Ludwig, Michael
Noethen, Markus M.
Draaken, Markus
Brosens, Erwin
Heij, Hugo
Tibboel, Dick
Herrmann, Bernhard G.
Solomon, Benjamin D.
de Klein, Annelies
van Rooij, Iris A. L. M.
Esposito, Franca
Reutter, Heiko M.
Hildebrandt, Friedhelm
TI Whole-exome resequencing reveals recessive mutations in TRAP1 in
individuals with CAKUT and VACTERL association
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE genetics and development; genetic renal disease; renal agenesis; renal
development; ureteric bud; vesicoureteral reflux
ID KIDNEY; HETEROTAXY; DISORDERS
AB Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole-exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat-shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle's loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or VACTERL association with CAKUT.
C1 [Saisawat, Pawaree; Hilger, Alina C.; Natarajan, Sivakumar; Sperry, Ethan] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Kohl, Stefan; Hwang, Daw-Yang; Gee, Heon Yung; Dworschak, Gabriel C.; Hildebrandt, Friedhelm] Harvard Univ, Sch Med, Dept Med, Boston Childrens Hosp, Boston, MA USA.
[Hilger, Alina C.; Dworschak, Gabriel C.; Bartels, Enrika; Schmidt, Dominik; Noethen, Markus M.; Draaken, Markus; Reutter, Heiko M.] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Tasic, Velibor] Univ Childrens Hosp, Dept Pediat Nephrol, Skopje, Macedonia.
[Pennimpede, Tracie; Herrmann, Bernhard G.] Max Planck Inst Mol Genet, Dev Genet Dept, D-14195 Berlin, Germany.
[Matassa, Danilo S.; Esposito, Franca] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy.
[Stajic, Natasa; Bogdanovic, Radovan] Univ Belgrade, Fac Med, Belgrade, Serbia.
[Stajic, Natasa; Bogdanovic, Radovan] Inst Mother & Child Healthcare Serbia, Belgrade, Serbia.
[de Blaauw, Ivo] Radboud Univ Nijmegen, Med Ctr, Dept Pediat Surg, NL-6525 ED Nijmegen, Netherlands.
[Marcelis, Carlo L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Wijers, Charlotte H. W.; van Rooij, Iris A. L. M.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands.
[Schmiedeke, Eberhard] Hosp Bremen Mitte, Ctr Child & Adolescent Hlth, Dept Pediat Surg & Urol, Bremen, Germany.
[Maerzheuser, Stefanie] Charite, Campus Virchow Clin, Dept Pediat Surg, Berlin, Germany.
[Grasshoff-Derr, Sabine] Univ Hosp Wurzburg, Dept Pediat Surg, Wurzburg, Germany.
[Holland-Cunz, Stefan] Heidelberg Univ, Dept Pediat Surg, Heidelberg, Germany.
[Ludwig, Michael] Univ Bonn, Dept Clin Chem & Clin Pharmacol, Bonn, Germany.
[Noethen, Markus M.; Draaken, Markus] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany.
[Brosens, Erwin; Tibboel, Dick] Erasmus MC Sophia, Dept Pediat Surg, Rotterdam, Netherlands.
[Brosens, Erwin; de Klein, Annelies] Erasmus MC Sophia, Dept Clin Genet, Rotterdam, Netherlands.
[Heij, Hugo] Emma Childrens Hosp, Pediat Surg Ctr Amsterdam, Amsterdam, Netherlands.
[Heij, Hugo] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Solomon, Benjamin D.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Reutter, Heiko M.] Univ Bonn, Childrens Hosp, Dept Neonatol, Bonn, Germany.
[Hildebrandt, Friedhelm] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Reutter, HM (reprint author), Univ Klinikum Bonn, Biomed Zentrum, Inst Humangenet, Sigmund Freud Str 25, D-53727 Bonn, Germany.
EM reutter@uni-bonn.de; friedhelm.hildebrandt@childrens.harvard.edu
RI Blaauw, I./L-4203-2015; Marcelis, C.L.M./L-4504-2015; Rooij, van,
Iris/A-5705-2014; Matassa, Danilo Swann/K-1596-2016; Esposito,
Franca/K-2024-2016;
OI Rooij, van, Iris/0000-0002-9519-966X; Matassa, Danilo
Swann/0000-0002-4259-9221; Esposito, Franca/0000-0001-9340-6875;
Draaken, Markus/0000-0002-4546-0786; Nothen, Markus/0000-0002-8770-2464
FU National Institutes of Health [R01-DK045345, R01-DK088767]; March of
Dimes Foundation [6FY11-241]; Division of Intramural Research; National
Human Genome Research Institute (NHGRI); National Institutes of Health
and Human services; Bundesministerium fur Bildung und Forschung
[01GM08107]; BONFOR program of the University of Bonn [O-149.0099,
O-149.0096]; Sophia Scientific Research Foundation [SSWO S13/9];
associazione Italiana per la Ricerca sul Cancro (AIRC) [IG13128];
Italian Ministry of Health [GR-2010-2310057]
FX We thank the physicians and families for participating in this study,
the German self-help organization for people with anorectal
malformations (SoMA eV), and all participating physicians, nurses,
research assistants, laboratory analysts, and project members of AGORA
(Aetiologic research into Genetic and Occupational/Environmental Risk
Factors for Anomalies in Children) for their support in building this
biobank. FH is an Investigator of the Howard Hughes Medical Institute, a
Doris Duke Distinguished Clinical Scientist, and a Frederick GL Huetwell
Professor. ACH, GCD, Enrika Bartels, ES, DS, SG-D, SM, SH-C, MMN, ML,
HMR, and MD are members of the 'Network for the Systematic Investigation
of the Molecular Causes, Clinical Implications and Psychosocial Outcome
of Congenital Uro-Rectal Malformations' (CURE-Net). This research was
supported by grants from the National Institutes of Health (to FH;
R01-DK045345 and R01-DK088767), by the March of Dimes Foundation
(6FY11-241), by the Division of Intramural Research, by the National
Human Genome Research Institute (NHGRI), by the National Institutes of
Health and Human services, by the Bundesministerium fur Bildung und
Forschung (grant 01GM08107), by the BONFOR program of the University of
Bonn (to Enrika Bartels; grant O-149.0099, and to GCD; grant
O-149.0096), by Sophia Scientific Research Foundation (to Enrika
Bartels; grant SSWO S13/9), by the associazione Italiana per la Ricerca
sul Cancro (AIRC) (to FE; grant IG13128), and by the Italian Ministry of
Health (to FE; grant GR-2010-2310057).
NR 21
TC 29
Z9 29
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
EI 1523-1755
J9 KIDNEY INT
JI Kidney Int.
PD JUN
PY 2014
VL 85
IS 6
BP 1310
EP 1317
DI 10.1038/ki.2013.417
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA AI4FG
UT WOS:000336820500013
PM 24152966
ER
PT J
AU Klisovic, RB
Blum, W
Liu, ZF
Xie, ZL
Kefauver, C
Huynh, L
Zwiebel, JA
Devine, SM
Byrd, JC
Grever, MR
Chan, KK
Marcucci, G
AF Klisovic, Rebecca B.
Blum, William
Liu, Zhongfa
Xie, Zhiliang
Kefauver, Cheryl
Huynh, Lenguyen
Zwiebel, James A.
Devine, Steven M.
Byrd, John C.
Grever, Michael R.
Chan, Kenneth K.
Marcucci, Guido
TI Phase I study of GTI-2040, a ribonucleotide reductase antisense, with
high dose cytarabine in patients with relapsed/refractory acute myeloid
leukemia
SO LEUKEMIA & LYMPHOMA
LA English
DT Article
DE Acute myeloid leukemia; antisense therapy; phase I study; GTI-2040;
ribonucleotide reductase
ID ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; R2 COMPONENT;
FLUDARABINE; METABOLISM; CELLS; 5-FLUOROURACIL; COMBINATION; MECHANISMS;
RESISTANCE
AB We hypothesized that GTI-2040, a 20-mer oligonucleotide complementary to the R2 subunit mRNA of ribonucleotide reductase, combined with high dose cytarabine (HiDAC) would result in enhanced cytotoxicity by favoring Ara-CTP DNA incorporation. In a phase I dose escalation trial, adults (>= 60 years) with refractory or relapsed acute myeloid leukemia (AML) received daily HiDAC plus infusional GTI-2040. Using a novel assay, evidence of intracellular drug accumulation and target R2 down-regulation was observed. GTI-2040/HiDAC can be administered safely. However, with no complete remissions observed, alternative doses and schedules may need to be investigated to achieve clinical activity in older patients with AML.
C1 [Klisovic, Rebecca B.; Blum, William; Huynh, Lenguyen; Devine, Steven M.; Byrd, John C.; Grever, Michael R.; Marcucci, Guido] Ohio State Univ, Div Hematol, Dept Med, Columbus, OH 43210 USA.
[Liu, Zhongfa; Xie, Zhiliang; Chan, Kenneth K.] Ohio State Univ, Div Pharmaceut, Coll Pharm, Columbus, OH 43210 USA.
[Blum, William; Kefauver, Cheryl; Devine, Steven M.; Byrd, John C.; Grever, Michael R.; Chan, Kenneth K.; Marcucci, Guido] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Zwiebel, James A.] NCI, Bethesda, MD 20892 USA.
RP Marcucci, G (reprint author), Ohio State Univ, Div Hematol & Oncol, A437A Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA.
EM guido.marcucci@osumc.edu
FU [NCI U01 CA 076576-10]; [NCI R21 CA 105879]
FX This study was supported by NCI U01 CA 076576-10 and NCI R21 CA 105879.
NR 29
TC 2
Z9 2
U1 1
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1042-8194
EI 1029-2403
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD JUN
PY 2014
VL 55
IS 6
BP 1332
EP 1336
DI 10.3109/10428194.2013.838764
PG 5
WC Oncology; Hematology
SC Oncology; Hematology
GA AI3FV
UT WOS:000336747100019
PM 24015841
ER
PT J
AU Manasanch, EE
Braylan, R
Stetler-Stevenson, M
Yuan, C
Gounden, V
Korde, N
Tageja, N
Bhutani, M
Calvo, K
Maric, I
Roschewski, M
Staudt, LM
Landgren, O
AF Manasanch, Elisabet E.
Braylan, Raul
Stetler-Stevenson, Maryalice
Yuan, Constance
Gounden, Verena
Korde, Neha
Tageja, Nishant
Bhutani, Manisha
Calvo, Katherine
Maric, Irina
Roschewski, Mark
Staudt, Louis M.
Landgren, Ola
TI Lack of MYD88 L265P in non-immunoglobulin M lymphoplasmacytic lymphoma
SO LEUKEMIA & LYMPHOMA
LA English
DT Letter
ID SOMATIC MUTATION; WALDENSTROMS MACROGLOBULINEMIA; MONOCLONAL GAMMOPATHY;
MGUS
C1 [Manasanch, Elisabet E.; Korde, Neha; Tageja, Nishant; Bhutani, Manisha; Roschewski, Mark; Landgren, Ola] NCI, Multiple Myeloma Sect, Bethesda, MD 20892 USA.
[Staudt, Louis M.] NCI, Metab Branch, Bethesda, MD 20892 USA.
[Braylan, Raul; Calvo, Katherine; Maric, Irina] NIH, Hematol Sect, Dept Lab Med, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice; Yuan, Constance] NIH, Flow Cytometry Unit, Pathol Lab, Bethesda, MD 20892 USA.
[Gounden, Verena] NIH, Dept Pathol, Bethesda, MD 20892 USA.
RP Landgren, O (reprint author), NCI, Multiple Myeloma Sect, Metab Branch, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 10 Room 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
OI Calvo, Katherine/0000-0002-0771-4191
NR 6
TC 7
Z9 7
U1 1
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1042-8194
EI 1029-2403
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD JUN
PY 2014
VL 55
IS 6
BP 1402
EP 1403
DI 10.3109/10428194.2013.831091
PG 2
WC Oncology; Hematology
SC Oncology; Hematology
GA AI3FV
UT WOS:000336747100031
PM 23915224
ER
PT J
AU Peterson, MD
Al Snih, S
Stoddard, J
Mcclain, J
Lee, IM
AF Peterson, Mark D.
Al Snih, Soham
Stoddard, Jonathan
Mcclain, James
Lee, I-Min
TI Adiposity and Insufficient MVPA Predict Cardiometabolic Abnormalities in
Adults
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE EXERCISE; ACCELEROMETRY; ADIPOSITY; SITTING TIME; INSULIN RESISTANCE
ID PHYSICAL-ACTIVITY; SEDENTARY BEHAVIORS; INSULIN-RESISTANCE; SITTING
TIME; LIFE-STYLE; MORTALITY; OBESITY; DISEASE; ASSOCIATIONS; WEIGHT
AB Objectives: The purpose of this study is to compare the extent to which different combinations of objectively measured sedentary behavior (SB) and physical activity contribute to cardiometabolic health. Design and Methods: A population representative sample of 5268 individuals, ages 20-85 yr, was included from the combined 2003-2006 National Health and Nutrition Examination Survey datasets. Activity categories were created on the combined basis of objectively measured SB and moderate-to-vigorous physical activity (MVPA) tertiles. Cardiometabolic abnormalities included elevated blood pressure, levels of triglycerides, fasting plasma glucose, C-reactive protein, homeostasis model assessment of insulin resistance value, and low HDL cholesterol level. Body mass index and dual-energy x-ray absorptiometry-derived percent body fat and android adiposity were also compared across groups. Predictors for a metabolically abnormal phenotype (>= 3 cardiometabolic abnormalities or insulin resistance) were determined. Results: Adults with the least SB and greatest MVPA exhibited the healthiest cardiometabolic profiles, whereas adults with the greatest SB and lowest MVPA were older and had elevated risk. Time spent in SB was not a predictor of the metabolically abnormal phenotype when MVPA was accounted for. Adults with the highest MVPA across SB tertiles did not differ markedly in prevalence of obesity, adiposity, and/or serum cardiometabolic risk factors; however, less MVPA was associated with substantial elevations of obesity and cardiometabolic risk. Android adiposity (per kilogram) was independently associated with the metabolically abnormal phenotype in both men (odds ratio, 2.36 (95% CI, 1.76-3.17), P < 0.001) and women (odds ratio, 2.00 (95% CI, 1.63-2.45), P < 0.001). Among women, greater SB and less lifestyle moderate activity and MVPA were each independently associated with the metabolically abnormal phenotype, whereas only less MVPA was associated with it in men. Conclusions: MVPA is a strong predictor of cardiometabolic health among adults, independent of time spent in SB.
C1 [Peterson, Mark D.; Stoddard, Jonathan] Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA.
[Al Snih, Soham] Univ Texas Med Branch, Dept Internal Med, Div Geriatr, Div Rehabil Sci,Sch Hlth Profess, Galveston, TX 77555 USA.
[Mcclain, James] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Lee, I-Min] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA.
RP Peterson, MD (reprint author), Univ Michigan Hosp & Hlth Syst, Dept Phys Med & Rehabil, 325 E Eisenhower Pkwy,Suite 300, Ann Arbor, MI 48108 USA.
EM mdpeterz@med.umich.edu
FU U.S. National Institutes of Health [R24 HD065702-03, CA154647]; National
Institutes of Health [1KO1-HD074706]
FX This study was funded by the U.S. National Institutes of Health: R24
HD065702-03 (M. Peterson and S. Al Snih). Dr. Peterson is funded by the
National Institutes of Health (1KO1-HD074706). I-Min Lee was supported
in part by grant CA154647 from the U.S. National Institutes of Health.
NR 24
TC 4
Z9 4
U1 1
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
EI 1530-0315
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD JUN
PY 2014
VL 46
IS 6
BP 1133
EP 1139
DI 10.1249/MSS.0000000000000212
PG 7
WC Sport Sciences
SC Sport Sciences
GA AI6FF
UT WOS:000336966200009
PM 24389519
ER
PT J
AU Antignani, A
Sarnovsky, R
FitzGerald, DJ
AF Antignani, Antonella
Sarnovsky, Robert
FitzGerald, David J.
TI ABT-737 Promotes the Dislocation of ER Luminal Proteins to the Cytosol,
Including Pseudomonas Exotoxin
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID RECOMBINANT IMMUNOTOXIN; CANCER-CELLS; BCL-2 FAMILY; STRESS; RECEPTOR;
COMBINATION; APOPTOSIS; BAK; IMMUNOTHERAPY; CYTOTOXICITY
AB Impaired apoptosis is often a key element in tumor development. Therefore, drugs mimicking prosurvival antagonists offer promise as cancer therapeutics. When ABT-737, a BH3-only mimetic, was added to KB3-1 human cervical adenocarcinoma cells, we noted an induction of an endoplasmic reticulum (ER) stress response and the dislocation of ER luminal proteins, including chaperones, to the cell cytosol. Furthermore, when immunotoxin (antibody-toxin chimeric molecule) and ABT-737 combinations were added to cells, there was enhanced toxin-mediated inhibition of protein synthesis, consistent with enhanced translocation of toxin to the cytosol. A similar enhancement was not seen with thapsigargin, suggesting that ER stress alone was not responsible for enhanced translocation. Cytosol preparations from ABT-737-treated but not from thapsigargin-treated cells revealed the presence of greater amounts of processed 37-kDa toxin fragment compared with the addition of immunotoxin alone. As early as 4 hours after the addition of ABT-737 and immunotoxin, there was release of mitochondrial cytochrome c and activation of caspase-3/7 indicating that the combination caused apoptotic cell death. These results were reflected in decreased cellular ATP levels that were noted with combinations of ABT-737 and immunotoxin but not with either agent alone or with combinations of thapsigargin and immunotoxin. We conclude that ABT-737 increases ER permeability, promoting the dislocation of toxin from the ER to the cytosol resulting in early apoptotic cell death. These mechanistic insights suggest why this class of BH3-only mimetic synergizes in a particular way with Pseudomonas exotoxin-based immunotoxins. (C) 2014 AACR.
C1 [Antignani, Antonella; Sarnovsky, Robert; FitzGerald, David J.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP FitzGerald, DJ (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5124, Bethesda, MD 20892 USA.
EM fitzgerd@helix.nih.gov
FU Intramural Research Program of the NIH, Center for Cancer Research,
National Cancer Institute
FX This research was supported by the Intramural Research Program of the
NIH, Center for Cancer Research, National Cancer Institute.
NR 35
TC 4
Z9 4
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JUN
PY 2014
VL 13
IS 6
BP 1655
EP 1663
DI 10.1158/1535-7163.MCT-13-0998
PG 9
WC Oncology
SC Oncology
GA AI8LX
UT WOS:000337168600025
PM 24739394
ER
PT J
AU Camp, KM
Parisi, MA
Acosta, PB
Berry, GT
Bilder, DA
Blau, N
Bodamer, OA
Brosco, JP
Brown, CS
Burlina, AB
Burton, BK
Chang, CS
Coates, PM
Cunningham, AC
Dobrowolski, SF
Ferguson, JH
Franklin, TD
Frazier, DM
Grange, DK
Greene, CL
Groft, SC
Harding, CO
Howell, RR
Huntington, KL
Hyatt-Knorr, HD
Jevaji, IP
Levy, HL
Lichter-Konecki, U
Lindegren, ML
Lloyd-Puryear, MA
Matalon, K
MacDonald, A
McPheeters, ML
Mitchell, JJ
Mofidi, S
Moseley, KD
Mueller, CM
Mulberg, AE
Nerurkar, LS
Ogata, BN
Pariser, AR
Prasad, S
Pridjian, G
Rasmussen, SA
Reddy, UM
Rohr, FJ
Singh, RH
Sirrs, SM
Stremer, SE
Tagle, DA
Thompson, SM
Urv, TK
Utz, JR
van Spronsen, F
Vockley, J
Waisbren, SE
Weglicki, LS
White, DA
Whitley, CB
Wilfond, BS
Yannicelli, S
Young, JM
AF Camp, Kathryn M.
Parisi, Melissa A.
Acosta, Phyllis B.
Berry, Gerard. T.
Bilder, Deborah A.
Blau, Nenad
Bodamer, Olaf A.
Brosco, Jeffrey P.
Brown, Christine S.
Burlina, Alberto B.
Burton, Barbara K.
Chang, Christine S.
Coates, Paul M.
Cunningham, Amy C.
Dobrowolski, Steven F.
Ferguson, John H.
Franklin, Thomas D.
Frazier, Dianne M.
Grange, Dorothy K.
Greene, Carol L.
Groft, Stephen C.
Harding, Cary O.
Howell, R. Rodney
Huntington, Kathleen L.
Hyatt-Knorr, Henrietta D.
Jevaji, Indira P.
Levy, Harvey L.
Lichter-Konecki, Uta
Lindegren, Mary Lou
Lloyd-Puryear, Michele A.
Matalon, Kimberlee
MacDonald, Anita
McPheeters, Melissa L.
Mitchell, John J.
Mofidi, Shideh
Moseley, Kathryn D.
Mueller, Christine M.
Mulberg, Andrew E.
Nerurkar, Lata S.
Ogata, Beth N.
Pariser, Anne R.
Prasad, Suyash
Pridjian, Gabriella
Rasmussen, Sonja A.
Reddy, Uma M.
Rohr, Frances J.
Singh, Rani H.
Sirrs, Sandra M.
Stremer, Stephanie E.
Tagle, Danilo A.
Thompson, Susan M.
Urv, Tiina K.
Utz, Jeanine R.
van Spronsen, Francjan
Vockley, Jerry
Waisbren, Susan E.
Weglicki, Linda S.
White, Desiree A.
Whitley, Chester B.
Wilfond, Benjamin S.
Yannicelli, Steven
Young, Justin M.
TI Phenylketonuria Scientific Review Conference: State of the science and
future research needs
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Phenylketonuria; Sapropterin; Hyperphenylalaninemia; Maternal PIN; Large
neutral amino acids; Glycomacropeptide
ID PHENYLALANINE-HYDROXYLASE DEFICIENCY; NEUTRAL AMINO-ACIDS;
DIHYDROPTERIDINE REDUCTASE DEFICIENCY; CONTINUOUSLY TREATED
PHENYLKETONURIA; TETRAHYDROBIOPTERIN LOADING TEST; GENOTYPE-PHENOTYPE
CORRELATIONS; THERAPEUTIC LIVER REPOPULATION; MATERNAL BLOOD
PHENYLALANINE; ENZYME REPLACEMENT THERAPY; TANDEM MASS-SPECTROMETRY
AB New developments in the treatment and management of phenylketonuria (PKU) as well as advances in molecular testing have emerged since the National Institutes of Health 2000 PKU Consensus Statement was released. An NIH State-of-the-Science Conference was convened in 2012 to address new findings, particularly the use of the medication sapropterin to treat some individuals with PKU, and to develop a research agenda. Prior to the 2012 conference, five working groups of experts and public members met over a 1-year period. The working groups addressed the following: long-term outcomes and management across the lifespan; PKU and pregnancy; diet control and management; pharmacologic interventions; and molecular testing, new technologies, and epidemiologic considerations. In a parallel and independent activity, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality conducted a systematic review of adjuvant treatments for PKU; its conclusions were presented at the conference. The conference included the findings of the working groups, panel discussions from industry and international perspectives, and presentations on topics such as emerging treatments for PKU, transitioning to adult care, and the U.S. Food and Drug Administration regulatory perspective. Over 85 experts participated in the conference through information gathering and/or as presenters during the conference, and they reached several important conclusions. The most serious neurological impairments in PKU are preventable with current dietary treatment approaches. However, a variety of more subtle physical, cognitive, and behavioral consequences of even well-controlled PKU are now recognized. The best outcomes in maternal PKU occur when blood phenylalanine (Phe) concentrations are maintained between 120 and 360 Rtnol/L before and during pregnancy. The dietary management treatment goal for individuals with PKU is a blood Phe concentration between 120 and 360 [tmol/L. The use of genotype information in the newborn period may yield valuable insights about the severity of the condition for infants diagnosed before maximal Phe levels are achieved. While emerging and established genotype-phenotype correlations may transform our understanding of PKU, establishing correlations with intellectual outcomes is more challenging. Regarding the use of sapropterin in PKU, there are significant gaps in predicting response to treatment; at least half of those with PKU will have either minimal or no response. A coordinated approach to PKU treatment improves long-term outcomes for those with PKU and facilitates the conduct of research to improve diagnosis and treatment. New drugs that are safe, efficacious, and impact a larger proportion of individuals with PKU are needed. However, it is imperative that treatment guidelines and the decision processes for determining access to treatments be tied to a solid evidence base with rigorous standards for robust and consistent data collection. The process that preceded the PKU State-of-the-Science Conference, the conference itself, and the identification of a research agenda have facilitated the development of clinical practice guidelines by professional organizations and serve as a model for other inborn errors of metabolism.
C1 [Camp, Kathryn M.; Coates, Paul M.; Lloyd-Puryear, Michele A.] NIH, Off Dietary Supplements, Bethesda, MD 20982 USA.
[Parisi, Melissa A.; Reddy, Uma M.; Urv, Tiina K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Acosta, Phyllis B.; Singh, Rani H.] Emory Univ, Atlanta, GA 30033 USA.
[Berry, Gerard. T.; Levy, Harvey L.; Waisbren, Susan E.] Harvard Univ, Boston Childrens Hosp, Sch Med, Boston, MA 02115 USA.
[Bilder, Deborah A.] Univ Utah, Dept Psychiat, Salt Lake City, UT 84108 USA.
[Blau, Nenad] Univ Childrens Hosp, Heidelberg, Germany.
[Blau, Nenad] Univ Childrens Hosp, Zurich, Switzerland.
[Bodamer, Olaf A.; Howell, R. Rodney] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Brosco, Jeffrey P.] Univ Miami, Mailman Ctr Child Dev, Miami, FL 33101 USA.
[Brown, Christine S.; Franklin, Thomas D.] Natl PKU Alliance, Encinitas, CA USA.
[Burlina, Alberto B.] Univ Hosp, I-35128 Padua, Italy.
[Burton, Barbara K.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[Chang, Christine S.] Agcy Healthcare Res & Qual, Rockville, MD 20850 USA.
[Cunningham, Amy C.; Pridjian, Gabriella] Tulane Univ, Sch Med, Hayward Genet Ctr, New Orleans, LA 70112 USA.
[Dobrowolski, Steven F.; Vockley, Jerry] Univ Pittsburgh, Pittsburgh, PA 15224 USA.
[Ferguson, John H.; Groft, Stephen C.; Hyatt-Knorr, Henrietta D.; Nerurkar, Lata S.] NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20982 USA.
[Frazier, Dianne M.] Univ N Carolina, Chapel Hill, NC 27599 USA.
[Grange, Dorothy K.] Washington Univ, St Louis Childrens Hosp, Sch Med, St Louis, MO 63110 USA.
[Greene, Carol L.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Harding, Cary O.; Huntington, Kathleen L.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA.
[Jevaji, Indira P.] NIH, Off Res Womens Hlth, Bethesda, MD 20817 USA.
[Lichter-Konecki, Uta] George Washington Univ, Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Lindegren, Mary Lou] Vanderbilt Univ, Sch Med, Nashville, TN 37203 USA.
[Matalon, Kimberlee] Univ Houston, Houston, TX 77204 USA.
[MacDonald, Anita] Birmingham Childrens Hosp, Birmingham B4 6NH, W Midlands, England.
[McPheeters, Melissa L.] Inst Med & Publ Hlth, Vanderbilt Evidence Based Practice Ctr, Nashville, TN 37203 USA.
[Mitchell, John J.] McGill Univ, Ctr Hlth, Montreal, PQ H3H 1P3, Canada.
[Mofidi, Shideh] Maria Fareri Childrens Hosp, Westchester Med Ctr, Valhalla, NY 10595 USA.
[Moseley, Kathryn D.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Mueller, Christine M.] US FDA, Off Orphan Prod Dev, Silver Spring, MD 20993 USA.
[Mulberg, Andrew E.; Pariser, Anne R.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Ogata, Beth N.] Univ Washington, Seattle, WA 98195 USA.
[Prasad, Suyash] BioMarin Pharmaceut Inc, San Rafael, CA 94901 USA.
[Rasmussen, Sonja A.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
[Rohr, Frances J.] Boston Childrens Hosp, Boston, MA 02115 USA.
[Sirrs, Sandra M.] Univ British Columbia, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada.
[Burlina, Alberto B.] PKU & Allied Disorders Wisconsin, Madison, WI 53705 USA.
[Tagle, Danilo A.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Thompson, Susan M.] Childrens Hosp Westrnead, Sydney, NSW 2145, Australia.
[Utz, Jeanine R.; Whitley, Chester B.] Univ Minnesota, Minneapolis, MN 55455 USA.
[van Spronsen, Francjan] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, NL-9700 AB Groningen, Netherlands.
[Weglicki, Linda S.] NINR, NIH, Bethesda, MD 20892 USA.
[White, Desiree A.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA.
[Wilfond, Benjamin S.] Univ Washington, Seattle Childrens Res Inst, Sch Med, Seattle, WA 98101 USA.
[Yannicelli, Steven] Nutricia North Amer, Rockville, MD 20850 USA.
[Young, Justin M.] Young Face Facial Plast & Reconstruct Surg, Cumming, GA 30041 USA.
RP Camp, KM (reprint author), 6100 Execut Blvd, Rockville, MD 20892 USA.
EM campkm@od.nih.gov; parisima@mail.nih.gov; pja1933@gmail.com;
gerard.berry@childrens.harvard.edu; deborah.bilder@hsc.utah.edu;
nenad.blau@med.uni-heidelberg.de; obodamer@med.miami.edu;
jbrosco@med.miami.edu; christine.brown@npkua.org;
alberto.burlina@unipd.it; bburton@luriechildrens.org;
christine.chang@ahrq.hhs.gov; coatesp@od.nih.gov; acunnin@tulane.edu;
dobrowolskis@upmc.edu; jferg@helix.nih.gov; tom.franklin@npkua.org;
dianne_frazier@med.unc.edu; grange_d@kids.wustl.edu;
cgreene@peds.umaryland.edu; stephen.groft@nih.gov; hardingc@ohsu.edu;
rhowell@miami.edu; huntingt@ohsu.edu; henrietta.hyatt-knorr@nih.gov;
indira.jevaji@cms.hhs.gov; harvey.levy@childrens.harvard.edu;
ulichter@cnmc.org; marylou.lindegren@vanderbilt.edu;
lloydpuryearma@od.nih.gov; kmatalon@uh.edu; anita.macdonald@bch.nhs.uk;
melissa.mcpheeters@vanderbilt.edu; john.mitchell@muhc.mcgill.ca;
shideh_mofidi@nymc.edu; kmoseley@usc.edu; christine.mueller@nih.gov;
andrew.mulberg@fda.hhs.gov; lnerurkar@gmail.com; bogata@uw.edu;
anne.pariser@fda.hhs.gov; sprasad@bmrn.com; pridjian@tulane.edu;
skr9@cdc.gov; reddyu@mail.nih.gov; frances.rohr@childrens.harvard.edu;
rsingh@emory.edu; sandra.sirrs@vch.ca; sstremer@yahoo.com;
danilo.tagle@nih.gov; sue.thompson@health.nsw.gov.au;
urvtiin@mail.nih.gov; jutz1@fairview.org; f.j.van.spronsen@umcg.nl;
vockleyg@upmc.edu; susan.waisbren@childrens.harvard.edu;
weglickils@mail.nih.gov; dawhite@wustl.edu; whitley@umn.edu;
benjamin.wilfond@seattlechildrens.org; steven.yannicelli@nutricia.com;
jmichaelyoung@yahoo.com
OI Berry, Gerard/0000-0001-5299-3313; Vockley, Jerry/0000-0002-8180-6457
NR 336
TC 43
Z9 43
U1 6
U2 74
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JUN
PY 2014
VL 112
IS 2
BP 87
EP 122
DI 10.1016/j.ymgme.2014.02.013
PG 36
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA AI7KF
UT WOS:000337067900002
PM 24667081
ER
PT J
AU Smith, D
Artursson, P
Avdeef, A
Di, L
Ecker, GF
Faller, B
Houston, JB
Kansy, M
Kerns, EH
Kramer, SD
Lennernas, H
van de Waterbeemd, H
Sugano, K
Testa, B
AF Smith, Dennis
Artursson, Per
Avdeef, Alex
Di, Li
Ecker, Gerhard F.
Faller, Bernard
Houston, J. Brian
Kansy, Manfred
Kerns, Edward H.
Kramer, Stefanie D.
Lennernaes, Hans
van de Waterbeemd, Han
Sugano, Kiyohiko
Testa, Bernard
TI Passive Lipoidal Diffusion and Carrier-Mediated Cell Uptake Are Both
Important Mechanisms of Membrane Permeation in Drug Disposition
SO MOLECULAR PHARMACEUTICS
LA English
DT Review
DE permeation; passive lipoidal diffusion; "carrier-mediated only" concept
ID PENETRANT STRUCTURE RELATIONSHIPS; WEAKLY BASIC DRUGS; STRATUM-CORNEUM;
EPIDERMAL PERMEABILITY; PHARMACEUTICAL DRUGS; URINARY-EXCRETION;
LIPID-MEMBRANES; TRANSPORT; BRAIN; SKIN
AB Recently, it has been proposed that drug permeation is essentially carrier-mediated only and that passive lipoidal diffusion is negligible. This opposes the prevailing hypothesis of drug permeation through biological membranes, which integrates the contribution of multiple permeation mechanisms, including both carrier-mediated and passive lipoidal diffusion, depending on the compound's properties, membrane properties, and solution properties. The prevailing hypothesis of drug permeation continues to be successful for application and prediction in drug development. Proponents of the carrier-mediated only concept argue against passive lipoidal diffusion. However, the arguments are not supported by broad pharmaceutics literature. The carrier-mediated only concept lacks substantial supporting evidence and successful applications in drug development.
C1 [Artursson, Per; Lennernaes, Hans] Uppsala Univ, Biomed Ctr, Dept Pharm, S-75263 Uppsala, Sweden.
[Di, Li] Pfizer Inc, Pharmacokinet Dynam & Metab, Groton, CT 06340 USA.
[Ecker, Gerhard F.] Univ Vienna, Dept Med Chem, A-141090 Vienna, Austria.
[Faller, Bernard] Novartis Inst Biomed Res, WSJ 350 3 04, CH-4002 Basel, Switzerland.
[Houston, J. Brian] Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PT, Lancs, England.
[Kansy, Manfred] F Hoffmann La Roche, Nonclin Safety Dept, CH-4070 Basel, Switzerland.
[Kerns, Edward H.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
[Kramer, Stefanie D.] ETH, Inst Pharmaceut Sci, Zurich, Switzerland.
[Sugano, Kiyohiko] Sandwich Labs, Res Formulat, Sandwich CT13 9NJ, Kent, England.
[Testa, Bernard] Univ Lausanne Hosp, Dept Pharm, CH-1011 Lausanne, Switzerland.
RP Smith, D (reprint author), 4 Maltings, Walmer CT14 7AR, Kent, England.
EM professordennis@deltic50.freeserve.co.uk
OI Ecker, Gerhard/0000-0003-4209-6883; Kramer, Stefanie
D./0000-0002-0426-4340
NR 82
TC 22
Z9 22
U1 7
U2 43
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD JUN
PY 2014
VL 11
IS 6
BP 1727
EP 1738
DI 10.1021/mp400713v
PG 12
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA AI5XB
UT WOS:000336941900001
PM 24724562
ER
PT J
AU Zhang, B
Jia, WH
Matsuda, K
Kweon, SS
Matsuo, K
Xiang, YB
Shin, AS
Jee, SH
Kim, DH
Cai, QY
Long, JR
Shi, JJ
Wen, WQ
Yang, G
Zhang, YF
Li, C
Li, BS
Guo, Y
Ren, ZF
Ji, BT
Pan, ZZ
Takahashi, A
Shin, MH
Matsuda, F
Gao, YT
Oh, JH
Kim, S
Ahn, YO
Chan, AT
Chang-Claude, J
Slattery, ML
Gruber, SB
Schumacher, FR
Stenzel, SL
Casey, G
Kim, HR
Jeong, JY
Park, JW
Li, HL
Hosono, S
Cho, SH
Kubo, M
Shu, XO
Zeng, YX
Zheng, W
AF Zhang, Ben
Jia, Wei-Hua
Matsuda, Koichi
Kweon, Sun-Seog
Matsuo, Keitaro
Xiang, Yong-Bing
Shin, Aesun
Jee, Sun Ha
Kim, Dong-Hyun
Cai, Qiuyin
Long, Jirong
Shi, Jiajun
Wen, Wanqing
Yang, Gong
Zhang, Yanfeng
Li, Chun
Li, Bingshan
Guo, Yan
Ren, Zefang
Ji, Bu-Tian
Pan, Zhi-Zhong
Takahashi, Atsushi
Shin, Min-Ho
Matsuda, Fumihiko
Gao, Yu-Tang
Oh, Jae Hwan
Kim, Soriul
Ahn, Yoon-Ok
Chan, Andrew T.
Chang-Claude, Jenny
Slattery, Martha L.
Gruber, Stephen B.
Schumacher, Fredrick R.
Stenzel, Stephanie L.
Casey, Graham
Kim, Hyeong-Rok
Jeong, Jin-Young
Park, Ji Won
Li, Hong-Lan
Hosono, Satoyo
Cho, Sang-Hee
Kubo, Michiaki
Shu, Xiao-Ou
Zeng, Yi-Xin
Zheng, Wei
CA Genetics Epidemiology Colorectal C
Colorectal Transdisciplinary COREC
Colon Canc Family Registry
TI Large-scale genetic study in East Asians identifies six new loci
associated with colorectal cancer risk
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; LYMPHOTOXIN-BETA-RECEPTOR; SUSCEPTIBILITY LOCI;
BREAST-CANCER; COLON-CANCER; CELL-GROWTH; EXPRESSION; MUTATIONS;
VARIANTS; METAANALYSIS
AB Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk (P = 3.42 x 10(-8) to 9.22 x 10(-21)) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9), and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways.
C1 [Zhang, Ben; Cai, Qiuyin; Long, Jirong; Shi, Jiajun; Wen, Wanqing; Yang, Gong; Zhang, Yanfeng; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA.
[Jia, Wei-Hua; Pan, Zhi-Zhong; Zeng, Yi-Xin] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China.
[Matsuda, Koichi] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan.
[Kweon, Sun-Seog; Shin, Min-Ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Kwangju, South Korea.
[Kweon, Sun-Seog] Chonnam Natl Univ, Hwasun Hosp, Jeonnam Reg Canc Ctr, Hwasun, South Korea.
[Matsuo, Keitaro; Hosono, Satoyo] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 812, Japan.
[Xiang, Yong-Bing; Gao, Yu-Tang; Li, Hong-Lan] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Shin, Aesun] Natl Canc Ctr, Mol Epidemiol Branch, Goyang Si, South Korea.
[Shin, Aesun; Ahn, Yoon-Ok] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Jee, Sun Ha; Kim, Soriul] Yonsei Univ, Grad Sch Publ Hlth, Inst Hlth Promot, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea.
[Kim, Dong-Hyun; Jeong, Jin-Young] Hallym Univ, Coll Med, Dept Social & Prevent Med, Okcheon Dong, South Korea.
[Li, Chun] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA.
[Li, Bingshan] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA.
[Guo, Yan] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA.
[Ren, Zefang] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou 510275, Guangdong, Peoples R China.
[Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Takahashi, Atsushi; Kubo, Michiaki] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan.
[Matsuda, Fumihiko] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan.
[Oh, Jae Hwan; Park, Ji Won] Natl Canc Ctr, Ctr Colorectal Canc, Goyang Si, South Korea.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA.
[Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA.
[Gruber, Stephen B.; Schumacher, Fredrick R.; Stenzel, Stephanie L.; Casey, Graham] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Kim, Hyeong-Rok] Chonnam Natl Univ, Sch Med, Dept Surg, Kwangju, South Korea.
[Park, Ji Won] Seoul Natl Univ Hosp, Dept Surg, Seoul 110744, South Korea.
[Cho, Sang-Hee] Chonnam Natl Univ, Sch Med, Dept Hematooncol, Kwangju, South Korea.
RP Zheng, W (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA.
EM wei.zheng@vanderbilt.edu
RI Shin, Aesun/E-9145-2014; Gallinger, Steven/E-4575-2013; Hoffmeister,
Michael/B-5745-2012; KURY, Sebastien/G-5971-2015; Kubo,
Michiaki/N-7947-2015; zhang, yanfeng/E-6971-2016; Brenner,
Hermann/B-4627-2017;
OI Shin, Aesun/0000-0002-6426-1969; Hoffmeister,
Michael/0000-0002-8307-3197; KURY, Sebastien/0000-0001-5497-0465; zhang,
yanfeng/0000-0002-3859-3839; Brenner, Hermann/0000-0002-6129-1572;
Bezieau, stephane/0000-0003-0095-1319; Matsuda,
Koichi/0000-0001-7292-2686; Matsuo, Keitaro/0000-0003-1761-6314
FU US National Institutes of Health (NIH) [R37CA070867, R01CA082729,
R01CA124558, R01CA148667, R01CA122364]; Vanderbilt University School of
Medicine. Studies; Asia Colorectal Cancer Consortium include the
Shanghai Women's Health Study (US NIH) [R37CA070867]; Shanghai Men's
Health Study (US NIH) [R01CA082729]; Shanghai Breast and Endometrial
Cancer Studies (US NIH) [R01CA064277, R01CA092585]; Shanghai Colorectal
Cancer Study 3 (US NIH) [R37CA070867]; Guangzhou Colorectal Cancer Study
(National Key Scientific and Technological Project)
[2011ZX09307-001-04]; National Basic Research Program [2011CB504303];
Natural Science Foundation of China [81072383]; Japan BioBank Colorectal
Cancer Study (grant from the Ministry of Education, Culture, Sports,
Science and Technology of the Japanese government); Hwasun Cancer
Epidemiology Study Colon and Rectum Cancer (HCES-CRC); Korea Center for
Disease Control and Prevention; Aichi Colorectal Cancer Study [17015018,
221S0001]; Korea-NCC (National Cancer Center) Colorectal Cancer Study
(Basic Science Research Program through-the National Research Foundation
of Korea [2010-0010276]; National Cancer Center Korea [0910220];
Korea-Seoul Colorectal Cancer Study; KCPS-II Colorectal Cancer Study
(National R&D Program for Cancer Control) [1220180]; Seoul RD Program
[10526]; GECCO; CORECT; CCFR; NIH [R01CA048998]; DACHS (German Federal
Ministry of Education and Research) [BR 1704/6-1, BR 1704/6-3, BR
1704/6-4, CH 117/1-1, 01KH0404, 01ER0814]; HPFS (US NIH) [P01CA055075,
UM1CA167552, R01137178, P50CA127003]; NHS (US NIH) [R01137178,
P50CA127003, P01CA087969]; OFCCR (US NIH) [U01CA074783]; PMH (US NIH)
[R01CA076366]; PHS (US NIH) [R01CA042182]
FX The authors are solely responsible for the scientific content of this
paper. The sponsors of this study had no role in study design, data
collection, analysis or interpretation, writing of the report or the
decision for submission. We thank all study participants and research
staff of all parent studies for their contributions and commitment to
this project, R. Courtney for DNA preparation, J. He for data processing
and analyses, X. Gun for suggestions on bioinformatics analysis, and
M.J. Daly and B.J. Rammer for editing and preparing the manuscript. The
work at the Vanderbilt University School of Medicine was supported by US
National Institutes of Health (NIH) grants R37CA070867, R01CA082729,
R01CA124558, R01CA148667 and R01CA122364, as well as by Ingram
Professorship and Research Reward funds from the Vanderbilt University
School of Medicine. Studies (grant support) participating in the Asia
Colorectal Cancer Consortium include the Shanghai Women's Health Study
(US NIH, R37CA070867), the Shanghai Men's Health Study (US NIH,
R01CA082729), the Shanghai Breast and Endometrial Cancer Studies (US
NIH, R01CA064277 and R01CA092585; contributing only controls), Shanghai
Colorectal Cancer Study 3 (US NIH, R37CA070867 and Ingram Professorship
funds), the Guangzhou Colorectal Cancer Study (National Key Scientific
and Technological Project, 2011ZX09307-001-04; the National Basic
Research Program, 2011CB504303, contributing only controls; the Natural
Science Foundation of China, 81072383, contributing only controls), the
Japan BioBank Colorectal Cancer Study (grant from the Ministry of
Education, Culture, Sports, Science and Technology of the Japanese
government), the Hwasun Cancer Epidemiology Study Colon and Rectum
Cancer (HCES-CRC; grants from the Korea Center for Disease Control and
Prevention and the Jeonnam Regional Cancer Center), the Aichi Colorectal
Cancer Study (Grant-in-Aid for Cancer Research, grant for the Third Term
Comprehensive Control Research for Cancer and Grants-in-Aid for
Scientific Research from the Japanese Ministry of Education, Culture,
Sports, Science and Technology, 17015018 and 221S0001), the Korea-NCC
(National Cancer Center) Colorectal Cancer Study (Basic Science Research
Program through-the National Research Foundation of Korea, 2010-0010276;
National Cancer Center Korea, 0910220), the Korea-Seoul Colorectal
Cancer Study (none reported) and the KCPS-II Colorectal Cancer Study
(National R&D Program for Cancer Control, 1220180; Seoul R&D Program,
10526).; We also thank B. Buecher of ASTERISK; U. Handte-Daub, M. Celik,
R. Hettler-Jensen, U. Benscheid and U. Eilber of DACHS; and P. Soule, H.
Ranu, I. Devivo, D.J. Hunter, Q. Guo, L. Zhu and H. Zhang of HPFS, NHS
and PHS, as well as the following state cancer registries for their
help: Alabama, Arizona, Arkansas, California, Colorado, Connecticut,
Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky,
Louisiana, Maine, Maryland, Massachusetts, Michigan, Nebraska, New
Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio,
Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee,
Texas, Virginia, Washington and Wyoming. We thank C. Berg and P. Prorok
of PLCO; T. Riley of Information Management Services, Inc.; B. O'Brien
of Westat, Inc.; B. Kopp and W Shao of SAIC-Frederick; the WHI
investigators (see
https://www.whi.org/researchers/SitePages/Write%20a%20Paper. aspx) and
the GECCO Coordinating Center. Participating studies (grant support) in
the GECCO, CORECT and CCFR GWAS meta-analysis are GECCO (US NIH,
U01CA137088 and R01CA059045), DALS (US NIH, R01CA048998), DACHS (German
Federal Ministry of Education and Research, BR 1704/6-1, BR 1704/6-3, BR
1704/6-4, CH 117/1-1,01KH0404 and 01ER0814), HPFS (US NIH, P01CA055075,
UM1CA167552, R01137178 and P50CA127003), NHS (US NIH, R01137178,
P50CA127003 and P01CA087969), OFCCR (US NIH, U01CA074783), PMH (US NIH,
R01CA076366), PHS (US NIH, R01CA042182), VITAL (US NIH, K05CA154337),
WHI (US NIH, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C and
268200764316C) and PLCO (US NIH, Z01CP 010200, U0IHG004446 and U01HG
004438). CORECT is supported by the National Cancer Institute as part of
the GAME-ON consortium (US NIH, U19CA148107) with additional support
from National Cancer Institute grants (R01CA81488 and P30CA014089), the
National Human Genome Research Institute at the US NIH (T32HG000040) and
the National Institute of Environmental Health Sciences at the US NIH
(T32ES013678). CCFR is supported by the National Cancer Institute, US
NIH under RFA CA-95-011 and through cooperative agreements with members
of the Colon Cancer Family Registry and principal investigators of the
Australasian Colorectal Cancer Family Registry (US NIH, U01CA097735),
the Familial Colorectal Neoplasia Collaborative Group (US NIH,
U01CA074799) (University of Southern California), the Mayo Clinic
Cooperative Family Registry for Colon Cancer Studies (US NIH,
U01CA074800), the Ontario Registry for Studies of Familial Colorectal
Cancer (US NIH, U01CA074783), the Seattle Colorectal Cancer Family
Registry (US NIH, U01CA074794) and the University of Hawaii Colorectal
Cancer Family Registry (US NIH, U01CA074806). The GWAS work was
supported by a National Cancer Institute grant (US NIH, U01CA122839).
OFCCR was supported by a GL2 grant from the Ontario Research Fund,
Canadian Institutes of Health Research and a Cancer Risk Evaluation
(CaRE) Program grant from the Canadian Cancer Society Research
Institute. T.J. Hudson and B.W. Zanke are recipients of Senior
Investigator Awards from the Ontario Institute for Cancer Research,
through support from the Ontario Ministry of Economic Development and
Innovation. ASTERISK was funded by a Regional Hospital Clinical Research
Program (PHRC) and supported by the Regional Council of Pays de la
Loire, the Groupement des Entreprises Francaises dans la Lutte contre le
Cancer (GEFLUC), the Association Anne de Bretagne Genetique and the
Ligue Regionale Contre le Cancer (LRCC).; PLCO data sets were accessed
with approval through dbGaP (CGEMS prostate cancer scan,
phs000207.v1.p1; CGEMS pancreatic cancer scan, phs000206.v4.p3; and GWAS
of Lung Cancer and Smoking, phs000093.v2.p2, which was funded by Z01CP
010200, U01HG004446 and U01HG 004438 from the US NIH).
NR 63
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U2 26
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 2014
VL 46
IS 6
BP 533
EP 542
DI 10.1038/ng.2985
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA AI4XU
UT WOS:000336870700008
PM 24836286
ER
PT J
AU Kohsaka, S
Shukla, N
Ameur, N
Ito, T
Ng, CKY
Wang, L
Lim, D
Marchetti, A
Viale, A
Pirun, M
Socci, ND
Qin, LX
Sciot, R
Bridge, J
Singer, S
Meyers, P
Wexler, LH
Barr, FG
Dogan, S
Fletcher, JA
Reis, JS
Ladanyi, M
AF Kohsaka, Shinji
Shukla, Neerav
Ameur, Nabahet
Ito, Tatsuo
Ng, Charlotte K. Y.
Wang, Lu
Lim, Diana
Marchetti, Angela
Viale, Agnes
Pirun, Mono
Socci, Nicholas D.
Qin, Li-Xuan
Sciot, Raf
Bridge, Julia
Singer, Samuel
Meyers, Paul
Wexler, Leonard H.
Barr, Frederic G.
Dogan, Snjezana
Fletcher, Jonathan A.
Reis-Filho, Jorge S.
Ladanyi, Marc
TI A recurrent neomorphic mutation in MYOD1 defines a clinically aggressive
subset of embryonal rhabdomyosarcoma associated with PI3K-AKT pathway
mutations
SO NATURE GENETICS
LA English
DT Article
ID TUMOR ALVEOLAR RHABDOMYOSARCOMA; SPINDLE-CELL RHABDOMYOSARCOMA;
GENOME-WIDE IDENTIFICATION; CHILDRENS ONCOLOGY GROUP; TARGET GENES;
SIGNALING PATHWAYS; STEM-CELLS; NEUROBLASTOMA; FUSION; DIFFERENTIATION
AB Rhabdomyosarcoma, a cancer of skeletal muscle lineage, is the most common soft-tissue sarcoma in children(1). Major subtypes of rhabdomyosarcoma include alveolar (ARMS) and embryonal (ERMS) tumors(2,3). Whereas ARMS tumors typically contain translocations generating PAX3-FOXO1 or PAX7-FOXO1 fusions that block terminal myogenic differentiation(4-6), no functionally comparable genetic event has been found in ERMS tumors. Here we report the discovery, through whole-exome sequencing, of a recurrent somatic mutation encoding p.Leu122Arg in the myogenic transcription factor MYOD1 in a distinct subset of ERMS tumors with poor outcomes that also often contain mutations altering PI3K-AKT pathway components. Previous mutagenesis studies had shown that MYOD1 with a p.Leu122Arg substitution can block wild-type MYOD1 function and bind to MYC consensus sequences(7), suggesting a possible switch from differentiation to proliferation. Our functional data now confirm this prediction. Thus, MYOD1 p.Leu122Arg defines a subset of rhabdomyosarcomas eligible for high-risk protocols and the development of targeted therapeutics.
C1 [Kohsaka, Shinji; Ameur, Nabahet; Ito, Tatsuo; Ng, Charlotte K. Y.; Wang, Lu; Lim, Diana; Marchetti, Angela; Dogan, Snjezana; Reis-Filho, Jorge S.; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Kohsaka, Shinji; Ameur, Nabahet; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Shukla, Neerav; Meyers, Paul; Wexler, Leonard H.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA.
[Viale, Agnes] Mem Sloan Kettering Canc Ctr, Genom Core Lab, New York, NY 10021 USA.
[Pirun, Mono; Socci, Nicholas D.] Mem Sloan Kettering Canc Ctr, Bioinformat Core Facil, New York, NY 10021 USA.
[Qin, Li-Xuan] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Sciot, Raf] Univ Hosp Gasthuisberg, Dept Pathol, B-3000 Louvain, Belgium.
[Sciot, Raf] Univ Louvain, Louvain, Belgium.
[Bridge, Julia] Univ Nebraska Med Ctr, Dept Pathol, Omaha, NE USA.
[Singer, Samuel] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA.
[Barr, Frederic G.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Fletcher, Jonathan A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Ladanyi, M (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA.
EM laaanyim@mskcc.org
OI Meyers, Paul/0000-0001-6146-6101
FU NIH [P01 CA047179]; NCI [P50 CA140146]; National Center for Research
Resources (NCRR) Clinical Translational Science Center grant; Virginia
and Daniel K. Ludwig Trust for Cancer Research; Yasuda Medical
Foundation; HIROKO International Academic Exchange Foundation;
Intramural Research Program of the National Cancer Institute; Anbinder
Fund; Cancer Center Core [NCI P30 CA008748]
FX We thank H. Hosoi (Kyoto Prefectural University of Medicine) and S.
Tanaka and M. Tsuda (both at Hokkaido University) for providing cell
lines. We also thank T. Akagi and K. Sasai (both at KAN Research
Institute, Inc.) for providing the pcx4bleo plasmid. We are also
grateful to J. Zhao for technical assistance with microarray analysis,
to L. Borsu for assistance with Sequenom analyses and to E. de Stanchina
and R. Tieu for the xenograft studies. This work was supported by a
generous donation from M.B. Zuckerman (M.L.), by NIH P01 CA047179
(S.S.), by NCI P50 CA140146 (M.L., N.D.S. and S.S.), by a National
Center for Research Resources (NCRR) Clinical Translational Science
Center grant (M.P. and N.D.S.) and by the Virginia and Daniel K. Ludwig
Trust for Cancer Research (J.A.F.). S.K. was supported in part by the
Yasuda Medical Foundation and the HIROKO International Academic Exchange
Foundation. F.G.B. is supported by the Intramural Research Program of
the National Cancer Institute.; The Memorial Sloan Kettering Cancer
Center Sequenom facility was supported by the Anbinder Fund, and the
Genomics and Bioinformatics Cores are supported by Cancer Center Core
grant NCI P30 CA008748.
NR 27
TC 29
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U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 2014
VL 46
IS 6
BP 595
EP 600
DI 10.1038/ng.2969
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA AI4XU
UT WOS:000336870700016
PM 24793135
ER
PT J
AU Lane, AA
Chapuy, B
Lin, CY
Tivey, T
Li, HB
Townsend, EC
van Bodegom, D
Day, TA
Wu, SC
Liu, HY
Yoda, A
Alexe, G
Schinzel, AC
Sullivan, TJ
Malinge, S
Taylor, JE
Stegmaier, K
Jaffe, JD
Bustin, M
te Kronnie, G
Izraeli, S
Harris, MH
Stevenson, KE
Neuberg, D
Silverman, LB
Sallan, SE
Bradner, JE
Hahn, WC
Crispino, JD
Pellman, D
Weinstock, DM
AF Lane, Andrew A.
Chapuy, Bjoern
Lin, Charles Y.
Tivey, Trevor
Li, Hubo
Townsend, Elizabeth C.
van Bodegom, Diederik
Day, Tovah A.
Wu, Shuo-Chieh
Liu, Huiyun
Yoda, Akinori
Alexe, Gabriela
Schinzel, Anna C.
Sullivan, Timothy J.
Malinge, Sebastien
Taylor, Jordan E.
Stegmaier, Kimberly
Jaffe, Jacob D.
Bustin, Michael
te Kronnie, Geertruy
Izraeli, Shai
Harris, Marian H.
Stevenson, Kristen E.
Neuberg, Donna
Silverman, Lewis B.
Sallan, Stephen E.
Bradner, James E.
Hahn, William C.
Crispino, John D.
Pellman, David
Weinstock, David M.
TI Triplication of a 21q22 region contributes to B cell transformation
through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation
SO NATURE GENETICS
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EMBRYONIC STEM-CELLS; DOWN-SYNDROME;
EXPRESSION; CHROMATIN; CRLF2; GENE; TRISOMY-21; MUTATIONS; PROTEINS
AB Down syndrome confers a 20-fold increased risk of B cell acute lymphoblastic leukemia (B-ALL)1, and polysomy 21 is most frequent somatic aneuploidy among all B-ALLs(2). Yet the mechanistic links between chromosome 21 triplication and B-ALL remain undefined. Here we show that germline triplication of only 31 genes orthologous to human chromosome 21q22 confers mouse progenitor B cell self renewal in vitro, maturation defects in vivo and B-ALL with either the BCR-ABL fusion protein or CRLF2 with activated JAK2. Chromosome 21q22 triplication suppresses histone H3 Lys27 trimethylation (H3K27me3) in progenitor B cells and B-ALLs, and 'bivalent' genes with both H3K27me3 and H3K4me3 at their promoters in wild-type progenitor B cells are preferentially overexpressed in triplicated cells. Human B-ALLs with polysomy 21 are distinguished by their overexpression of genes marked with H3K27me3 in multiple cell types. Overexpression of HMGN1, a nucleosome remodeling protein encoded on chromosome 21q22 (refs. 3-5), suppresses H3K27me3 and promotes both B cell proliferation in vitro and B-ALL in vivo.
C1 [Lane, Andrew A.; Chapuy, Bjoern; Lin, Charles Y.; Tivey, Trevor; Townsend, Elizabeth C.; van Bodegom, Diederik; Day, Tovah A.; Wu, Shuo-Chieh; Liu, Huiyun; Yoda, Akinori; Schinzel, Anna C.; Bradner, James E.; Hahn, William C.; Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Li, Hubo; Alexe, Gabriela; Silverman, Lewis B.; Sallan, Stephen E.; Pellman, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Schinzel, Anna C.; Taylor, Jordan E.; Stegmaier, Kimberly; Jaffe, Jacob D.; Hahn, William C.; Weinstock, David M.] Broad Inst, Cambridge, MA USA.
[Sullivan, Timothy J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Microarray Core, Boston, MA 02115 USA.
[Malinge, Sebastien] Inst Gustave Roussy, INSERM, U985, F-94805 Villejuif, France.
[Bustin, Michael] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
[te Kronnie, Geertruy] Univ Padua, Dept Pediat, Padua, Italy.
[Izraeli, Shai] Chaim Sheba Med Ctr, Dept Pediat Hematooncol, Ramat Gan, Israel.
[Izraeli, Shai] Tel Aviv Univ, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
[Harris, Marian H.] Childrens Hosp Boston, Dept Pathol, Boston, MA USA.
[Stevenson, Kristen E.; Neuberg, Donna] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Crispino, John D.] Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA.
[Pellman, David] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Lane, AA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
EM andrew_lane@dfci.harvard.edu; dweinstock@partners.org
RI Bustin, Michael/G-6155-2015
OI Crispino, John/0000-0002-8182-8306;
FU Conquer Cancer Foundation; Lauri Strauss Leukemia Foundation; Leukemia
and Lymphoma Society; Alex Lemonade Stand Foundation; US Department of
Defense; Israel Science Foundation; US Israel Binational Foundation;
Stellato Fund; US National Institutes of Health/National Cancer
Institute [CA15198-01, CA172387-A01]
FX We thank N. Kopp and A. Schlauch for technical assistance, M. Busslinger
(Research Institute of Molecular Pathology, Vienna) for the
Pax5+/- mice and M. Oshimura (Tottori University) for A9
cells carrying human chromosome 21. This research was supported by the
Conquer Cancer Foundation (.A.A.L.), the Lauri Strauss Leukemia
Foundation (A.A.L.), the Leukemia and Lymphoma Society (A.A.L.), the
Alex Lemonade Stand Foundation (A.A.L., H. Li and D.P.), the US
Department of Defense (C.Y.L.), the Israel Science Foundation (S.I.),
the US Israel Binational Foundation (J.D.C. and S.I.), the Stellato Fund
(D.M.W.), US National Institutes of Health/National Cancer Institute R01
awards CA15198-01 and CA172387-A01 (D.M.W.) and a Translational Research
Award from the Leukemia and Lymphoma Society (J.D.C. and D.M.W.).
NR 31
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U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD JUN
PY 2014
VL 46
IS 6
BP 618
EP 623
DI 10.1038/ng.2949
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA AI4XU
UT WOS:000336870700020
PM 24747640
ER
PT J
AU Rockey, SJ
AF Rockey, Sally J.
TI Mentorship matters for the biomedical workforce
SO NATURE MEDICINE
LA English
DT Editorial Material
AB The mentorship of early-career scientists is necessary to their individual career success and the future of the biomedical research enterprise as a whole. Recently launched NIH programs and tools aim to facilitate this important type of training.
C1 NIH, Bethesda, MD 20892 USA.
RP Rockey, SJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 OD999999]
NR 0
TC 4
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U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD JUN
PY 2014
VL 20
IS 6
BP 575
EP 575
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA AI7LB
UT WOS:000337071000009
PM 24901558
ER
PT J
AU Cottini, F
Hideshima, T
Xu, CX
Sattler, M
Dori, M
Agnelli, L
ten Hacken, E
Bertilaccio, MT
Antonini, E
Neri, A
Ponzoni, M
Marcatti, M
Richardson, PG
Carrasco, R
Kimmelman, AC
Wong, KK
Caigaris-Cappio, F
Blandino, G
Kuehl, WM
Anderson, KC
Tonon, G
AF Cottini, Francesca
Hideshima, Teru
Xu, Chunxiao
Sattler, Martin
Dori, Martina
Agnelli, Luca
ten Hacken, Elisa
Bertilaccio, Maria Teresa
Antonini, Elena
Neri, Antonino
Ponzoni, Maurilio
Marcatti, Magda
Richardson, Paul G.
Carrasco, Ruben
Kimmelman, Alec C.
Wong, Kwok-Kin
Caigaris-Cappio, Federico
Blandino, Giovanni
Kuehl, W. Michael
Anderson, Kenneth C.
Tonon, Giovanni
TI Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis
in hematological cancers
SO NATURE MEDICINE
LA English
DT Article
ID YES-ASSOCIATED PROTEIN; ABL TYROSINE KINASE; C-ABL; MULTIPLE-MYELOMA;
TUMOR-SUPPRESSOR; P73; PATHWAY; PHOSPHORYLATION; TUMORIGENESIS;
ACTIVATION
AB Oncogene-induced DNA damage elicits genomic instability in epithelial cancer cells, but apoptosis is blocked through inactivation of the tumor suppressor p53. In hematological cancers, the relevance of ongoing DNA damage and the mechanisms by which apoptosis is suppressed are largely unknown. We found pervasive DNA damage in hematologic malignancies, including multiple myeloma, lymphoma and leukemia, which leads to activation of a p53-independent, proapoptotic network centered on nuclear relocalization of ABL1 kinase. Although nuclear ABL1 triggers cell death through its interaction with the Hippo pathway coactivator YAP1 in normal cells, we show that low YAP1 levels prevent nuclear ABL1-induced apoptosis in these hematologic malignancies. YAP1 is under the control of a serine-threonine kinase, STK4. Notably, genetic inactivation of STK4 restores YAP1 levels, triggering cell death in vitro and in vivo. Our data therefore identify a new synthetic-lethal strategy to selectively target cancer cells presenting with endogenous DNA damage and low YAP1 levels.
C1 [Cottini, Francesca; Hideshima, Teru; Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
[Cottini, Francesca; Dori, Martina; Antonini, Elena; Tonon, Giovanni] Ist Ricovero & Cura Carattere Sci IRCCS San Raffa, Div Mol Oncol, Funct Genom Canc Unit, Milan, Italy.
[Xu, Chunxiao; Sattler, Martin; Carrasco, Ruben; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Xu, Chunxiao; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Xu, Chunxiao; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Dana Farber Canc Inst, Boston, MA USA.
[Agnelli, Luca; Neri, Antonino] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Hematol Unit, Milan, Italy.
[ten Hacken, Elisa; Bertilaccio, Maria Teresa; Caigaris-Cappio, Federico] IRCCS San Raffaele Sci Inst, Div Mol Oncol, Lab Lymphoid Malignancies, Milan, Italy.
[Ponzoni, Maurilio] IRCCS San Raffaele Sci Inst, Myeloma Unit, Pathol Unit, Milan, Italy.
[Marcatti, Magda] IRCCS San Raffaele Sci Inst, Myeloma Unit, Dept Hematol Oncol, Hematol & Bone Marrow Transplantat Unit, Milan, Italy.
[Kimmelman, Alec C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02115 USA.
[Caigaris-Cappio, Federico; Tonon, Giovanni] Univ Vita Salute San Raffaele, Milan, Italy.
[Caigaris-Cappio, Federico; Tonon, Giovanni] IRCCS San Raffaele Sci Inst, MAGIC Microenvironm & Genes Canc Blood Interdiv R, Milan, Italy.
[Blandino, Giovanni] Italian Natl Canc Inst Regina Elena, Translat Oncogen Unit, Rome, Italy.
[Kuehl, W. Michael] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA.
EM kenneth_anderson@dfci.harvard.edu; tonon.giovanni@hsr.it
OI neri, antonino/0000-0001-9047-5912
FU Fondazione CARIPLO, a Marie Curie International Reintegration Grant;
Associazione Raliana per la Ricerca sul Cancro (AIRC); Special Program
Molecular Clinical Oncology [9965]; NIH [P50100707, PO-1 78378, RO-1
50947]
FX We thank M. Sudol (Mount Sinai School of Medicine) for the eGFP-YAP1
construct, W Hahn (Dana-Farber Cancer Institute) for pLKO.1 shRNA
lentiviral vectors and S. Rosen (Northwestern University) and R. Burger
(University of Kiel) for MM.1R and INA-6 MM cells. We also thank E. Di
Cairano and L. Spagnuolo for immunohistochemical stains, F. Ghini and
A.M. Gasparri for technical help, the Dana-Farber Cancer Institute Flow
cytometry facility, D. Kufe and F. Bernassola for insightful
suggestions, C. Brennan for the bioinformatics analysis and members of
the Anderson and Tonon lab for sharing reagents and critical reading of
the manuscript. W.M.K. is supported by the Intramural Research Program
of the US National Institutes of Health (NIH), National Cancer
Institute, Center for Cancer Research. This work was supported by
Fondazione CARIPLO, a Marie Curie International Reintegration Grant and
the Associazione Raliana per la Ricerca sul Cancro (AIRC; AIRC Special
Program Molecular Clinical Oncology, 5 per milk no. 9980 to A.N. and
Investigator Grants and Special Program Molecular Clinical Oncology, 5
per mile no. 9965 to G.T.) (G.T.). K.C.A. is an American Cancer Society
Clinical Research Professor and is supported by NIH grants NIH SPORE
P50100707, PO-1 78378 and RO-1 50947.
NR 38
TC 54
Z9 56
U1 4
U2 19
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD JUN
PY 2014
VL 20
IS 6
BP 599
EP 606
DI 10.1038/nm.3562
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA AI7LB
UT WOS:000337071000021
PM 24813251
ER
PT J
AU Wang, RX
Yu, CR
Dambuza, IM
Mahdi, RM
Dolinska, MB
Sergeev, YV
Wingfield, PT
Kim, SH
Egwuagu, CE
AF Wang, Ren-Xi
Yu, Cheng-Rong
Dambuza, Ivy M.
Mahdi, Rashid M.
Dolinska, Monika B.
Sergeev, Yuri V.
Wingfield, Paul T.
Kim, Sung-Hye
Egwuagu, Charles E.
TI Interleukin-35 induces regulatory B cells that suppress autoimmune
disease
SO NATURE MEDICINE
LA English
DT Article
ID T-CELLS; MICE; EXPRESSION; RESPONSES; CYTOKINE; UVEITIS; IL-35;
INFLAMMATION; CONTRIBUTES; POPULATION
AB Interleukin-10 (IL-10)-producing regulatory B (Bred cells suppress autoimmune disease, and increased numbers of B-reg cells prevent host defense to infection and promote tumor growth and metastasis by converting resting CD4(+) T cells to regulatory T (T-reg) cells. The mechanisms mediating the induction and development of B-reg cells remain unclear. Here we show that IL-35 induces B-reg cells and promotes their conversion to a B-reg subset that produces IL-35 as well as IL-10. Treatment of mice with IL-35 conferred protection from experimental autoimmune uveitis (EAU), and mice lacking IL-35 (p35 knockout (KO) mice) or defective in IL-35 signaling (IL-12R beta 2 KO mice) produced less B-reg cells endogenously or after treatment with IL-35 and developed severe uveitis. Adoptive transfer of B-reg cells induced by recombinant IL-35 suppressed EAU when transferred to mice with established disease, inhibiting pathogenic T helper type 17 (T(H)17) and T(H)1 cells while promoting T-reg cell expansion. In B cells, IL-35 activates STAT1 and STAT3 through the IL-35 receptor comprising the IL-12R beta 2 and IL-27R alpha subunits. As IL-35 also induced the conversion of human B cells into B-reg cells, these findings suggest that IL-35 may be used to induce autologous B-reg and IL-35(+) B-reg cells and treat autoimmune and inflammatory disease.
C1 [Wang, Ren-Xi; Yu, Cheng-Rong; Dambuza, Ivy M.; Mahdi, Rashid M.; Kim, Sung-Hye; Egwuagu, Charles E.] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Dolinska, Monika B.; Sergeev, Yuri V.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Wingfield, Paul T.] NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA.
RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM egwuaguc@nei.nih.gov
FU NEI; NIH
FX The Intramural Research Programs of the NEI and NIH provided funding for
this research. We thank H. Young (National Cancer Institute, NIH) and
R.R. Caspi and C.-C. Chan (NEI, NIH) for critical reading of the
manuscript. We also thank C.-C. Chan for expert analyses of Fundus
images and histology sections. In addition, we thank A. O'Hara and C.A.
Hunter (University of Pennsylvania) for providing IL-27R alpha KO B
cells and R. Villasmil (NEI/NIH FLOW Cytometry Core facility) for cell
sorting and FACS analysis.
NR 36
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD JUN
PY 2014
VL 20
IS 6
BP 633
EP 641
DI 10.1038/nm.3554
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA AI7LB
UT WOS:000337071000025
PM 24743305
ER
PT J
AU Cui, GH
Jun, SB
Jin, X
Luo, GX
Pham, MD
Lovinger, DM
Vogel, SS
Costa, RM
AF Cui, Guohong
Jun, Sang Beom
Jin, Xin
Luo, Guoxiang
Pham, Michael D.
Lovinger, David M.
Vogel, Steven S.
Costa, Rui M.
TI Deep brain optical measurements of cell type-specific neural activity in
behaving mice
SO NATURE PROTOCOLS
LA English
DT Article
ID IN-VIVO; ACTIVATION; PROTEIN; MICROSCOPY
AB Recent advances in genetically encoded fluorescent sensors enable the monitoring of cellular events from genetically defined groups of neurons in vivo. In this protocol, we describe how to use a time-correlated single-photon counting (TCSPC)-based fiber optics system to measure the intensity, emission spectra and lifetime of fluorescent biosensors expressed in deep brain structures in freely moving mice. When combined with Cre-dependent selective expression of genetically encoded Ca2+ indicators (GECIs), this system can be used to measure the average neural activity from a specific population of cells in mice performing complex behavioral tasks. As an example, we used viral expression of GCaMPs in striatal projection neurons (SPNs) and recorded the fluorescence changes associated with calcium spikes from mice performing a lever-pressing operant task. The whole procedure, consisting of virus injection, behavior training and optical recording, takes 3-4 weeks to complete. With minor adaptations, this protocol can also be applied to recording cellular events from other cell types in deep brain regions, such as dopaminergic neurons in the ventral tegmental area. The simultaneously recorded fluorescence signals and behavior events can be used to explore the relationship between the neural activity of specific brain circuits and behavior.
C1 [Cui, Guohong; Jin, Xin; Luo, Guoxiang; Pham, Michael D.; Lovinger, David M.; Costa, Rui M.] NIAAA, Sect Vivo Neural Funct, Lab Integrat Neurosci, NIH, Bethesda, MD USA.
[Jun, Sang Beom] Ewha Womans Univ, Dept Elect Engn, Seoul, South Korea.
[Jin, Xin] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA.
[Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD USA.
[Vogel, Steven S.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
[Costa, Rui M.] Inst Gulbenkian Ciencias, Champalimaud Neurosci Programme, Oeiras, Portugal.
[Costa, Rui M.] Champalimaud Ctr, Lisbon, Portugal.
RP Vogel, SS (reprint author), NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
EM stevevog@mail.nih.gov; ruicosta@fchampalimaud.org
OI Vogel, Steven/0000-0002-3005-2667; Costa, Rui/0000-0003-0495-8374
FU US government funding from the Division of Intramural Clinical and
Biological Research of the National Institute on Alcohol Abuse and
Alcoholism; European Research Council [STG 243393]; International Early
Career Scientist grant from the Howard Hughes Medical Institute;
National Research Foundation of Korea grant [2011-0029485,
2012-0004003]; Smart IT Convergence System Research Center grant from
the Korean government (MEST) [SIRC-2011-0031866]; Ellison Medical
Foundation grant [AG-NS-0944-12]
FX We thank V. Jayaraman, R.A. Kerr, D.S. Kim, L.L. Looger, and K. Svoboda
from the GENIE Project, Janelia Farm Research Campus, Howard Hughes
Medical Institute for allowing us to use GCaMP6s vectors. We thank L.L.
Looger, J. Akerboom and D.S. Kim from the GENIE Project, Janelia Farm
Research Campus, Howard Hughes Medical Institute for permission to use
GCaMP5G vectors; L.L. Looger and Janelia Farm Research Campus of the
Howard Hughes Medical Institute for permission to use GCaMP3 vectors;
C.R. Gerfen for gifts of multiple bacterial artificial chromosome
transgenic mouse lines; and K. Jalink for gifts of DNA constructs of
EPAC (exchange proteins directly activated by cAMP) sensors. This work
was supported by US government funding from the Division of Intramural
Clinical and Biological Research of the National Institute on Alcohol
Abuse and Alcoholism to D.M.L., S.S.V. and R.M.C., by the European
Research Council (STG 243393), and by an International Early Career
Scientist grant from the Howard Hughes Medical Institute to R.M.C.; by a
National Research Foundation of Korea grant (2011-0029485, 2012-0004003)
and a Smart IT Convergence System Research Center grant
(SIRC-2011-0031866) from the Korean government (MEST) to S.B.J.; and by
an Ellison Medical Foundation grant (AG-NS-0944-12) to X. J.
NR 20
TC 11
Z9 12
U1 1
U2 23
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 JUN
PY 2014
VL 9
IS 6
BP 1213
EP 1228
DI 10.1038/nprot.2014.080
PG 16
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA AI8FS
UT WOS:000337145800002
PM 24784819
ER
PT J
AU Choyke, PL
AF Choyke, Peter L.
TI Science to Practice: Percutaneous Biopsies in the NIR Future-Will
Fluorescence Guide the Way?
SO RADIOLOGY
LA English
DT Editorial Material
ID INDOCYANINE GREEN
AB Sheth et al present a fascinating glimpse into the future of imaging-guided biopsies. Increasingly, such biopsies are being performed by fusing two or more modalities, such as computed tomography (CT) and ultrasonography (US). To this list should be added optical fluorescence guidance, which will complement all the advances hitherto developed for conventional imaging guidance. Similar progress is being made in the fields of endoscopy and surgery, and it is becoming clearer that optical fluorescence may light the path for many medical procedures in the "NIR," or near-infrared, future.
C1 NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182 Bldg 10,Room B3B69F, Bethesda, MD 20892 USA.
EM pchoyke@nih.gov
NR 5
TC 1
Z9 1
U1 0
U2 3
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD JUN
PY 2014
VL 271
IS 3
BP 623
EP 624
DI 10.1148/radiol.14140344
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI5GW
UT WOS:000336894600001
PM 24848955
ER
PT J
AU Sheth, RA
Heidari, P
Esfahani, SA
Wood, BJ
Mahmood, U
AF Sheth, Rahul A.
Heidari, Pedram
Esfahani, Shadi A.
Wood, Bradford J.
Mahmood, Umar
TI Interventional Optical Molecular Imaging Guidance during Percutaneous
Biopsy
SO RADIOLOGY
LA English
DT Article
ID INDOCYANINE GREEN; FLUORESCENCE; ENDOSCOPY
AB Purpose: To investigate indocyanine green (ICG) as a molecular beacon for malignant lesions within the liver and evaluate the ability of a developed handheld imaging system to allow measurement of ICG fluorescence within focal hepatic lesions with high target-to-background ratios in a mouse model.
Materials and Methods: All animal experiments were approved by the institutional animal care committee. A handheld optical molecular imaging device was constructed to pass through the introducer needle of a standard percutaneous biopsy kit. An ex vivo phantom system was constructed to quantify tissue attenuation properties of ICG in liver parenchyma. Subsequently, intrahepatic colorectal cancer metastases were generated in nude mice, and epifluorescence imaging of ICG, as well as histologic analysis of the explanted livers, was performed at 3 weeks after implantation (n = 6). Epifluorescence imaging with the handheld imaging device was then performed on intrahepatic colorectal metastases after the administration of ICG (n = 15) at 3, 6, and 24 hours after injection. Target-to-background ratios were calculated for each time point. Subsequently, a core biopsy of intrahepatic colorectal metastases was performed by using a standard clinical 18-gauge biopsy needle.
Results: There was avid localization of ICG to the focal lesions at all time points. Similarly, fluorescence within the tumors was greater than that within normal liver, as detected with the handheld imaging system (mean target-to-background ratio +/- standard deviation, 3.9 +/- 0.2 at 24 hours). A core biopsy of tumor and normal adjacent liver by using a standard biopsy needle demonstrated a sharp margin of fluorescence intensity at the tumor-liver interface.
Conclusion: The custom-designed molecular imaging device, in combination with ICG, readily allowed differentiation between normal and malignant tissue in a murine model of intrahepatic colorectal metastasis. (C) RSNA, 2014
C1 [Sheth, Rahul A.; Heidari, Pedram; Esfahani, Shadi A.; Mahmood, Umar] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA.
[Wood, Bradford J.] Ctr Clin, Ctr Intervent Oncol Radiol & Imaging Sci, Bethesda, MD USA.
[Wood, Bradford J.] NCI, NIH, Bethesda, MD 20892 USA.
RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, 55 Fruit St,White 427, Boston, MA 02114 USA.
EM umah-mood@mgh.harvard.edu
FU National Institutes of Health [U01CA084301]
FX This research was supported by the National Institutes of Health (grant
U01CA084301).
NR 14
TC 10
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U1 0
U2 5
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD JUN
PY 2014
VL 271
IS 3
BP 770
EP 777
DI 10.1148/radiol.14131880
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AI5GW
UT WOS:000336894600018
PM 24520946
ER
PT J
AU Resnik, DB
AF Resnik, David B.
TI Data Fabrication and Falsification and Empiricist Philosophy of Science
SO SCIENCE AND ENGINEERING ETHICS
LA English
DT Article
DE Data fabrication and falsification; Empiricism; Realism;
Observation/theory distinction; Ethics; Scientific practice
ID RETRACTED ARTICLE. SEE; PG 335; REALISM
AB Scientists have rules pertaining to data fabrication and falsification that are enforced with significant punishments, such as loss of funding, termination of employment, or imprisonment. These rules pertain to data that describe observable and unobservable entities. In this commentary I argue that scientists would not adopt rules that impose harsh penalties on researchers for data fabrication or falsification unless they believed that an aim of scientific research is to develop true theories and hypotheses about entities that exist, including unobservable ones. This argument presents a challenge for constructive empiricists, such as van Fraassen. Constructive empiricists need to be able to explain why rules pertaining to data fabrication and falsification do not threaten their philosophy of science.
C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Resnik, DB (reprint author), NIEHS, NIH, 111 Alexander Dr,Mail Drop CU 03,Box 12233, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102646-05]
NR 25
TC 2
Z9 2
U1 3
U2 24
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1353-3452
EI 1471-5546
J9 SCI ENG ETHICS
JI Sci. Eng. Ethics
PD JUN
PY 2014
VL 20
IS 2
BP 423
EP 431
DI 10.1007/s11948-013-9466-z
PG 9
WC Ethics; Engineering, Multidisciplinary; History & Philosophy Of Science;
Multidisciplinary Sciences; Philosophy
SC Social Sciences - Other Topics; Engineering; History & Philosophy of
Science; Science & Technology - Other Topics; Philosophy
GA AI5KR
UT WOS:000336905900010
PM 23982326
ER
PT J
AU Grabowski, MK
Gray, RH
Serwadda, D
Kigozi, G
Gravitt, PE
Nalugoda, F
Reynolds, SJ
Wawer, MJ
Watya, S
Quinn, TC
Tobian, AAR
AF Grabowski, Mary K.
Gray, Ronald H.
Serwadda, David
Kigozi, Godfrey
Gravitt, Patti E.
Nalugoda, Fred
Reynolds, Steven J.
Wawer, Maria J.
Watya, Stephen
Quinn, Thomas C.
Tobian, Aaron A. R.
TI High-risk human papillomavirus viral load and persistence among
heterosexual HIV-negative and HIV-positive men
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Article
ID FLAT PENILE LESIONS; MALE CIRCUMCISION; NATURAL-HISTORY;
CERVICAL-CANCER; KENYAN MEN; INFECTION; CLEARANCE; WOMEN; ACQUISITION;
CONCORDANCE
AB SObjectives High-risk human papillomavirus (HR-HPV) viral load is associated with HR-HPV transmission and HR-HPV persistence in women. It is unknown whether HR-HPV viral load is associated with persistence in HIV-negative or HIV-positive men.
Methods HR-HPV viral load and persistence were evaluated among 703 HIV-negative and 233 HIV-positive heterosexual men who participated in a male circumcision trial in Rakai, Uganda. Penile swabs were tested at baseline and 6, 12 and 24 months for HR-HPV using the Roche HPV Linear Array, which provides a semiquantitative measure of HPV shedding by hybridisation band intensity (graded: 1-4). Prevalence risk ratios (PRR) were used to estimate the association between HR-HPV viral load and persistent detection of HR-HPV.
Results HR-HPV genotypes with high viral load (grade: 3-4) at baseline were more likely to persist than HR-HPV genotypes with low viral load (grade: 1-2) among HIV-negative men (month 6: adjPRR=1.83, 95% CI 1.32 to 2.52; month 12: adjPRR=2.01, 95% CI 1.42 to 3.11), and HIV-positive men (month 6: adjPRR=1.33, 95% CI 1.06 to 1.67; month 12: adjPRR=1.73, 95% CI 1.18 to 2.54). Long-term persistence of HR-HPV was more frequent among HIV-positive men compared with HIV-negative men (month 24: adjPRR=2.27, 95% CI 1.47 to 3.51). Persistence of newly detected HR-HPV at the 6-month and 12-month visits with high viral load were also more likely to persist to 24 months than HR-HPV with low viral load among HIV-negative men (adjPRR=1.67, 95% CI 0.88 to 3.16).
Conclusions HR-HPV genotypes with high viral load are more likely to persist among HIV-negative and HIV-positive men, though persistence was more common among HIV-positive men overall. The results may explain the association between high HR-HPV viral load and HR-HPV transmission.
C1 [Grabowski, Mary K.; Gray, Ronald H.; Gravitt, Patti E.; Reynolds, Steven J.; Wawer, Maria J.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA.
[Gray, Ronald H.; Serwadda, David; Kigozi, Godfrey; Nalugoda, Fred; Reynolds, Steven J.; Wawer, Maria J.; Quinn, Thomas C.; Tobian, Aaron A. R.] Rakai Hlth Sci Program, Entebbe, Uganda.
[Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Gravitt, Patti E.] Perdana Univ, Grad Sch Med, Serdang, Malaysia.
[Reynolds, Steven J.; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Reynolds, Steven J.; Quinn, Thomas C.] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21287 USA.
[Watya, Stephen] Makerere Univ, Dept Urol, Kampala, Uganda.
[Tobian, Aaron A. R.] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21287 USA.
RP Tobian, AAR (reprint author), Johns Hopkins Univ, Dept Pathol, Carnegie 437,600 N Wolfe St, Baltimore, MD 21287 USA.
EM atobian1@jhmi.edu
FU National Institutes of Health [UO1AI51171]; Bill and Melinda Gates
Foundation [22006.02]; National Institute of Allergy and Infectious
Diseases (NIAID), NIH [U01-AI-068613, 3U01-AI075115-03S1,
1K23AI093152-01A1, R01AI087409-01A1]; NIH [1K23AI093152-01A1]; Doris
Duke Charitable Foundation Clinician Scientist Development Award
[22006.02]
FX The trials were funded by the National Institutes of Health
(#UO1AI51171) and the Bill and Melinda Gates Foundation (#22006.02).
National Institute of Allergy and Infectious Diseases (NIAID), NIH
grants U01-AI-068613, 3U01-AI075115-03S1, 1K23AI093152-01A1,
R01AI087409-01A1 and the NIAID Intramural Program provided laboratory
support. A. A. R. T. was supported by the NIH 1K23AI093152-01A1 and
Doris Duke Charitable Foundation Clinician Scientist Development Award
(#22006.02). The Fogarty International Center (#5D43TW001508 and
#2D43TW000010-19-AITRP) contributed to training.
NR 29
TC 10
Z9 10
U1 0
U2 4
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
EI 1472-3263
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD JUN
PY 2014
VL 90
IS 4
BP 337
EP 343
DI 10.1136/sextrans-2013-051230
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA AI5HZ
UT WOS:000336897700019
PM 24482488
ER
PT J
AU Viswanathan, S
Keating, A
Deans, R
Hematti, P
Prockop, D
Stroncek, DF
Stacey, G
Weiss, DJ
Mason, C
Rao, MS
AF Viswanathan, Sowmya
Keating, Armand
Deans, Robert
Hematti, Peiman
Prockop, Darwin
Stroncek, David F.
Stacey, Glyn
Weiss, Dan J.
Mason, Christopher
Rao, Mahendra S.
TI Soliciting Strategies for Developing Cell-Based Reference Materials to
Advance Mesenchymal Stromal Cell Research and Clinical Translation
SO STEM CELLS AND DEVELOPMENT
LA English
DT Article
ID BONE-MARROW; STEM-CELLS; INTERNATIONAL-SOCIETY; DIFFERENTIATION;
FIBROBLASTS; PRECURSORS; STATEMENT; RESPONSES; FRACTION; GROWTH
AB The mesenchymal stromal cell (MSC) field continues to rapidly progress with a number of clinical trials initiated and completed, with some reported successes in multiple clinical indications, and a growing number of companies established. The field, nevertheless, faces several challenges. Persistent issues include the definition of a MSC and comparability between MSC preparations. This is because of inherent cell heterogeneity, the absence of markers that are unique to MSCs, and the difficulty in precisely defining them by developmental origin. Differences in the properties of MSCs also depend on the site of tissue harvest, phenotypic and genotypic characteristics of the donor and the isolation, and storage and expansion methods used. These differences may be sufficient to ensure that attributes of the final MSC product could differ in potentially significant ways. Since there are currently no gold standards, we propose using a reference material to establish methods of comparability among MSC preparations. We suggest four possible "ruler scenarios'' and a method for global distribution. We further suggest that critical to establishing a reference material is the need to define protocols for comparing cells. The main purpose of this article is to solicit input in establishing a consensus-based comparison. A comparative approach will be critical to all stages of translation to better clarify mechanisms of MSC actions, define an optimal cell manufacturing process, ensure best practice clinical investigations, extend the use of an MSC product for new indications, protect an MSC product from imitators, and develop uniform reimbursement policies. Importantly, a reference material may enable a consensus on a practical definition of MSCs.
C1 [Viswanathan, Sowmya; Keating, Armand] Univ Hlth Network, Cell Therapy Program, Toronto, ON, Canada.
[Deans, Robert] Athersys Inc, Regenerat Med, Cleveland, OH USA.
[Hematti, Peiman] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA.
[Prockop, Darwin] Scott & White Mem Hosp & Clin, Coll Med, Texas A&M Hlth Sci Ctr, Inst Regenerat Med, Temple, TX USA.
[Stroncek, David F.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Stacey, Glyn] NIBSC MHRA, UK Stem Cell Bank, Div Cell Biol & Imaging, S Mimms, Herts, England.
[Weiss, Dan J.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
[Mason, Christopher] UCL, Adv Ctr Biochem Engn, Dept Biochem Engn, London, England.
[Rao, Mahendra S.] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA.
RP Rao, MS (reprint author), NIH, Ctr Regenerat Med, 50 South Dr Suite 1140, Bethesda, MD 20892 USA.
EM mahendra.rao@nih.gov
FU CCRM; ISCT; Alliance for Regenerative Medicine (ARM); Cell Therapy
Catapult; NIH; UK Science & Innovation Network via the British Consulate
General in Canada; Office of Science and Technology of the Embassy of
France
FX The authors would like to acknowledge sponsorship support from CCRM,
ISCT, Alliance for Regenerative Medicine (ARM), Cell Therapy Catapult,
the NIH, UK Science & Innovation Network via the British Consulate
General in Canada, and the Office of Science and Technology of the
Embassy of France for a workshop in March 2013 titled "Building Towards
a Standard for MSC's: A UK-U.S.-Canada led Workshop,'' which led to the
formation of the MSC Reference Materials Working Group.
NR 31
TC 33
Z9 36
U1 1
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1547-3287
EI 1557-8534
J9 STEM CELLS DEV
JI Stem Cells Dev.
PD JUN 1
PY 2014
VL 23
IS 11
BP 1157
EP 1167
DI 10.1089/scd.2013.0591
PG 11
WC Cell & Tissue Engineering; Hematology; Medicine, Research &
Experimental; Transplantation
SC Cell Biology; Hematology; Research & Experimental Medicine;
Transplantation
GA AI6DJ
UT WOS:000336959800001
PM 24422625
ER
PT J
AU Frawley, R
DeVito, M
Walker, NJ
Birnbaum, L
White, K
Smith, M
Maynor, T
Recio, L
Germolec, D
AF Frawley, Rachel
DeVito, Michael
Walker, Nigel J.
Birnbaum, Linda
White, Kimber, Jr.
Smith, Matthew
Maynor, Timothy
Recio, Leslie
Germolec, Dori
TI Relative Potency for Altered Humoral Immunity Induced by Polybrominated
and Polychlorinated Dioxins/Furans in Female B6C3F1/N Mice
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE 2; 3; 7; 8-tetrachlorodibenzo-p-dioxin; chlorinated furans; brominated
dioxins; brominated furans; relative potency; IgM antibody forming cell;
toxic equivalency factor; TEF
ID DIBENZO-P-DIOXINS; TOXIC EQUIVALENCY FACTORS; BIPHENYL CONGENERS;
BROMINATED DIOXIN; BILIARY-EXCRETION; C57BL/6J MICE; TCDD-LIKE; RATS;
DISAPPEARANCE; SENSITIVITY
AB The use of brominated flame retardants and incineration of bromine-containing materials has lead to an increase in polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) in the environment. Measurable amounts of PBDD/Fs have been detected in soil, seafood, and human breast milk and serum. Studies indicate that the relative potencies of some PBDD/Fs based on enzyme induction are equivalent to those of some polychlorinated dibenzo-p-dioxins and dibenzofurans. To assess the humoral immunity relative potencies of PBDD/Fs and compare them to their chlorinated analogs, female B6C3F1/N mice received a single oral exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetrabromodibenzofuran (TBDF), 2,3,7,8-tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-pentabromodibenzofuran (1PeBDF), 1,2,3,7,8-pentachlorodibenzofuran (1PeCDF), 2,3,4,7,8-pentabromodibenzofuran (4PeBDF), 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF), 2,3-dibromo-7,8-dichlorodibenzo-p-dioxin (DBDCDD), or 2,3,7-tribromodibenzo-p-dioxin (TriBDD). Inhibition of the immunoglobulin M (IgM) antibody forming cell response was measured 4 days following immunization with sheep red blood cells. The data were fit to a Hill model to estimate the ED50 for inhibition. Expression of xenobiotic metabolizing enzyme (XME) and thyroxine transport protein (Ttr) genes in liver was measured by PCR to assess aryl hydrocarbon-mediated responses. TCDD, TBDF, TCDF, 1PeBDF, 4PeBDF, 4PeCDF, and DBDCDD suppressed the IgM antibody response and Ttr gene expression, and upregulated phase I XME genes. 1PeCDF suppressed the IgM antibody response but only upregulated phase I XME genes; TriBDD had no effect on antibody response. The rank order of potency (ED50) for these chemicals was TCDD > TBDF > 4PeBDF > TCDF/4PeCDF/1PeBDF > 1PeCDF. Whereas TCDD was the most potent compound tested, the brominated analogs were more potent than their chlorinated analogs, suggesting that these compounds should be considered in toxic equivalency factor evaluation and risk assessment.
C1 [Frawley, Rachel; DeVito, Michael; Walker, Nigel J.; Birnbaum, Linda; Germolec, Dori] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda] NCI, NIH, Res Triangle Pk, NC 27709 USA.
[White, Kimber, Jr.; Smith, Matthew] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23284 USA.
[Maynor, Timothy; Recio, Leslie] ILS Inc, Res Triangle Pk, NC 27709 USA.
RP Frawley, R (reprint author), NIEHS, NTP, Toxicol Branch, 111 TW Alexander Dr,POB 12233,MD K2-15, Res Triangle Pk, NC 27709 USA.
EM frawleyr@niehs.nih.gov
RI Walker, Nigel/D-6583-2012;
OI Walker, Nigel/0000-0002-9111-6855; Frawley, Rachel/0000-0001-8490-8240
FU National Institutes of Health, National Institute of Environmental
Health Sciences (NIEHS); National Cancer Institute; NIEHS Research and
Development Contracts [N01-ES-55538, NO1-ES-00005]
FX National Institutes of Health, National Institute of Environmental
Health Sciences (NIEHS) and National Cancer Institute; NIEHS Research
and Development Contracts (N01-ES-55538, NO1-ES-00005).
NR 38
TC 2
Z9 2
U1 2
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD JUN
PY 2014
VL 139
IS 2
BP 488
EP 500
DI 10.1093/toxsci/kfu041
PG 13
WC Toxicology
SC Toxicology
GA AI7MO
UT WOS:000337075900019
PM 24713691
ER
PT J
AU Troisi, R
Stephansson, O
Jacobsen, J
Tretli, S
Rensen, HTSO
Gissler, M
Kaaja, R
Ekbom, A
Hoover, RN
Grotmol, T
AF Troisi, Rebecca
Stephansson, Olof
Jacobsen, Jacob
Tretli, Steinar
Rensen, Henrik Toft S. O.
Gissler, Mika
Kaaja, Risto
Ekbom, Anders
Hoover, Robert N.
Grotmol, Tom
TI Perinatal characteristics and bone cancer risk in offspring - a
Scandinavian population-based study
SO ACTA ONCOLOGICA
LA English
DT Article
ID GESTATIONAL HYPERTENSION; EWINGS-SARCOMA; TUMORS; OSTEOSARCOMA;
PREECLAMPSIA; CHILDHOOD; REGISTRY; NORWAY; GROWTH; EPIDEMIOLOGY
AB Background. We investigated perinatal factors in relation to bone cancer subtypes, osteosarcoma (OS), Ewing Sarcoma (ES) and chondrosarcoma (CS).
Materials and methods. All cases in Norway (1970-2009), Sweden (1974-2009) and Denmark (1980-2010) < 43 years were included (n = 914); 10 controls per case were selected from birth registries (which provided information on pregnancies) matched on birth country, sex and birth year (n = 9140). Unconditional logistic regression models including sex and birth year were used to compute relative risk (RR) and 95% confidence intervals (CI).
Results. Higher maternal education was associated with a 40% increase in OS risk (95% CI 1-93%). The RR for OS was 3.22 (95% CI 1.37-7.59) comparing offspring of hypertensive mothers with those of mothers with a normotensive pregnancy, and Cesarean section was associated with a 29% risk reduction (95% CI 0-50%). When gestational age, birth weight and birth length were assessed simultaneously, there were no associations with any of the bone tumor subtypes.
Conclusion. These results provided little evidence of an important role of pregnancy factors in the etiology of bone cancers. Higher maternal education may be associated with factors, possibly early nutrition or other correlates of socioeconomic status, that increase OS risk in offspring. The elevated OS risk associated with gestational hypertension and reduced risk associated with Cesarean section warrant replication.
C1 [Troisi, Rebecca; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Stephansson, Olof; Ekbom, Anders] Karolinska Univ Hosp & Inst, Dept Med, Clin Epidemiol Unit & Ctr, Stockholm, Sweden.
[Stephansson, Olof] Karolinska Univ Hosp & Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
[Jacobsen, Jacob; Rensen, Henrik Toft S. O.] Aarhus Univ, Dept Clin Epidemiol, Aarhus N, Denmark.
[Tretli, Steinar; Grotmol, Tom] Canc Registry Norway, Inst Populat Based Canc Res, Oslo, Norway.
[Gissler, Mika] THL Natl Inst Hlth & Welf, Helsinki, Finland.
[Gissler, Mika] Nord Sch Publ Hlth, Gothenburg, Sweden.
[Kaaja, Risto] Turku Univ, Turku, Finland.
RP Troisi, R (reprint author), Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,MSC 9773,9609-7E584, Rockville, MD 20850 USA.
EM troisir@mail.nih.gov
FU U.S. National Cancer Institute
FX This research was funded by the U.S. National Cancer Institute.
NR 27
TC 1
Z9 1
U1 0
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0284-186X
EI 1651-226X
J9 ACTA ONCOL
JI Acta Oncol.
PD JUN
PY 2014
VL 53
IS 6
BP 830
EP 838
DI 10.3109/0284186X.2013.862594
PG 9
WC Oncology
SC Oncology
GA AH9ZO
UT WOS:000336505600015
PM 24313390
ER
PT J
AU Bao, W
Bowers, K
Tobias, DK
Olsen, SF
Chavarro, J
Vaag, A
Kiely, M
Zhang, CL
AF Bao, Wei
Bowers, Katherine
Tobias, Deirdre K.
Olsen, Sjurdur F.
Chavarro, Jorge
Vaag, Allan
Kiely, Michele
Zhang, Cuilin
TI Prepregnancy low-carbohydrate dietary pattern and risk of gestational
diabetes mellitus: a prospective cohort study
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID CORONARY-HEART-DISEASE; INSULIN-RESISTANCE; IRON INTAKE; PROTEIN; WOMEN;
FAT; QUESTIONNAIRE; SCORE; METABOLISM; REGRESSION
AB Background: Low-carbohydrate diets (LCDs) have been vastly popular for weight loss. The association between a low-carbohydrate dietary pattern and risk of gestational diabetes mellitus (GDM) remains unknown.
Objective: We aimed to prospectively examine the association of 3 prepregnancy low-carbohydrate dietary patterns with risk of GDM.
Design: We included 21,411 singleton pregnancies in the Nurses' Health Study II. Prepregnancy LCD scores were calculated from validated food-frequency questionnaires, including an overall LCD score on the basis of intakes of carbohydrate, total protein, and total fat; an animal LCD score on the basis of intakes of carbohydrate, animal protein, and animal fat; and a vegetable LCD score on the basis of intakes of carbohydrate, vegetable protein, and vegetable fat. A higher score reflected a higher intake of fat and protein and a lower intake of carbohydrate, and it indicated closer adherence to a low-carbohydrate dietary pattern. RRs and 95% CIs were estimated by using generalized estimating equations with log-binomial models.
Results: We documented 867 incident GDM pregnancies during 10 y follow-up. Multivariable-adjusted RRs (95% CIs) of GDM for comparisons of highest with lowest quartiles were 1.27 (1.06, 1.51) for the overall LCD score (P-trend = 0.03), 1.36 (1.13, 1.64) for the animal LCD score (P-trend = 0.003), and 0.84 (0.69, 1.03) for the vegetable LCD score (P-trend = 0.08). Associations between LCD scores and GDM risk were not significantly modified by age, parity, family history of diabetes, physical activity, or overweight status.
Conclusions: A prepregnancy low-carbohydrate dietary pattern with high protein and fat from animal-food sources is positively associated with GDM risk, whereas a prepregnancy low-carbohydrate dietary pattern with high protein and fat from vegetable food sources is not associated with the risk. Women of reproductive age who follow a low-carbohydrate dietary pattern may consider consuming vegetable rather than animal sources of protein and fat to minimize their risk of GDM.
C1 [Bao, Wei; Kiely, Michele; Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Bowers, Katherine] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA.
[Tobias, Deirdre K.; Chavarro, Jorge] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Tobias, Deirdre K.; Chavarro, Jorge] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Olsen, Sjurdur F.] Statens Serum Inst, Dept Epidemiol Res, Ctr Fetal Programming, DK-2300 Copenhagen, Denmark.
[Chavarro, Jorge] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Chavarro, Jorge] Harvard Univ, Sch Med, Boston, MA USA.
[Vaag, Allan] Rigshosp, Dept Endocrinol, DK-2100 Copenhagen, Denmark.
RP Zhang, CL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM zhangcu@mail.nih.gov
RI Bowers, Katherine/N-5226-2015;
OI Bao, Wei/0000-0002-7301-5786
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH
[IIHSN275201000020C]; NIH [DK58845, CA50385, P30 DK46200, UM1 CA176726]
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development, NIH
(contract IIHSN275201000020C). The Nurses' Health Study II was funded by
the NIH (research grants DK58845, CA50385, P30 DK46200, and UM1
CA176726).
NR 42
TC 17
Z9 18
U1 2
U2 13
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN
PY 2014
VL 99
IS 6
BP 1378
EP 1384
DI 10.3945/ajcn.113.082966
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AH9NW
UT WOS:000336470100010
PM 24717341
ER
PT J
AU Moy, KA
Mondul, AM
Zhang, H
Weinstein, SJ
Wheeler, W
Chung, CC
Mannisto, S
Yu, K
Chanock, SJ
Albanes, D
AF Moy, Kristin A.
Mondul, Alison M.
Zhang, Han
Weinstein, Stephanie J.
Wheeler, William
Chung, Charles C.
Mannisto, Satu
Yu, Kai
Chanock, Stephen J.
Albanes, Demetrius
TI Genome-wide association study protein of circulating vitamin D-binding
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID 25-HYDROXYVITAMIN D; PANCREATIC-CANCER; MOLECULAR-CLONING;
PROSTATE-CANCER; GC-GLOBULIN; SERUM; RISK; ALBUMIN; FAMILY; METABOLISM
AB Background: Vitamin D status may influence a spectrum of health outcomes, including osteoporosis, arthritis, cardiovascular disease, and cancer. Vitamin D-binding protein (DBP) is the primary carrier of vitamin D in the circulation and regulates the bioavailability of 25-hydroxyvitamin D. Epidemiologic studies have shown direct DBP-risk relations and modification by DBP of vitamin D-disease associations.
Objective: We aimed to characterize common genetic variants that influence the DBP biochemical phenotype.
Design: We conducted a genome-wide association study (GWAS) of 1380 men through linear regression of single-nucleotide polymorphisms (SNPs) in the Illumina HumanHap500/550/610 array on fasting serum DBP, assuming an additive genetic model, with adjustment for age at blood collection.
Results: We identified 2 independent SNPs located in the gene encoding DBP, GC, that were highly associated with serum DBP: rs7041 (P = 1.42 X 10(-246)) and rs705117 (P = 4.7 x 10(-91)). For both SNPs, mean serum DBP decreased with increasing copies of the minor allele: mean DBP concentrations (nmol/L) were 7335, 5149, and 3152 for 0, 1, and 2 copies of rs7041 (T), respectively, and 6339, 4280, and 2341, respectively, for rs705117 (G). DBP was also associated with rs12144344 (P = 5.9 x 10(-7)) in ST6GALNAC3.
Conclusions: In this GWAS analysis, to our knowledge the first to examine this biochemical phenotype, 2 variants in GC one exonic and one intronic were associated with serum DBP concentrations at the genome-wide level of significance. Understanding the genetic contributions to circulating DBP may provide greater insights into the vitamin D binding, transport, and other functions of DBP and the effect of vitamin D status on health outcomes. The AlphaTocopherol, Beta-Carotene Cancer Prevention clinical trial was registered at clinicaltrials.gov as NCT00342992.
C1 [Moy, Kristin A.; Mondul, Alison M.; Weinstein, Stephanie J.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Zhang, Han; Yu, Kai] NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA.
[Chung, Charles C.] NCI, Canc Genom Res Lab, NIH, Bethesda, MD 20892 USA.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Wheeler, William] Informat Management Serv Inc, Silver Spring, MD USA.
[Mannisto, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Moy, KA (reprint author), Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM moyka@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015; Zhang, Han/K-2118-2016
OI Zhang, Han/0000-0001-7977-9616
FU Intramural Research Program of the National Cancer Institute, NIH, US
Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004,
HEISN261201000006C, HHSN261200800001E]
FX Supported by the Intramural Research Program of the National Cancer
Institute, NIH US Public Health Service (grant nos. N01-CN-45165,
N01-RC-45035, N01-RC-37004, HEISN261201000006C, and HHSN261200800001E).
NR 39
TC 10
Z9 10
U1 0
U2 14
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN
PY 2014
VL 99
IS 6
BP 1424
EP 1431
DI 10.3945/ajcn.113.080309
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AH9NW
UT WOS:000336470100015
PM 24740207
ER
PT J
AU Siega-Riz, AM
Sotres-Alvarez, D
Ayala, GX
Ginsberg, M
Himes, JH
Liu, K
Loria, CM
Mossavar-Rahmani, Y
Rock, CL
Rodriguez, B
Gellman, MD
Van Horn, L
AF Siega-Riz, Anna Maria
Sotres-Alvarez, Daniela
Ayala, Guadalupe X.
Ginsberg, Mindy
Himes, John H.
Liu, Kiang
Loria, Catherine M.
Mossavar-Rahmani, Yasniin
Rock, Cheryl L.
Rodriguez, Brendaly
Gellman, Marc D.
Van Horn, Linda
TI Food-group and nutrient-density intakes by Hispanic and Latino
backgrounds in the Hispanic Community Health Study/Study of Latinos
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID UNITED-STATES; MEXICAN-AMERICANS; SOCIOECONOMIC-STATUS; RECOVERY
BIOMARKERS; RISK-FACTORS; US ADULTS; ACCULTURATION; CONSUMPTION; DESIGN;
DIET
AB Background: Hispanics are a heterogeneous group of individuals with a variation in dietary habits that is reflective of their cultural heritage and country of origin. It is important to identify differences in their dietary habits because it has been well established that nutrition contributes substantially to the burden of preventable diseases and early deaths in the -United States.
Objective: We estimated the distribution of usual intakes (of both food groups and nutrients) by Hispanic and Latino backgrounds by using National Cancer Institute methodology.
Design: The Hispanic Community Health Study/Study of Latinos is a population-based cohort study that recruited participants who were 18-74 y of age from 4 US cities in 2008-2011 (Miami, Bronx, Chicago, and San Diego). Participants who provided at least one 24-h dietary recall and completed a food propensity questionnaire (n = 13,285) were included in the analyses. Results were adjusted for age, sex, field center, weekend, sequencing, and typical amount of intake.
Results: Overall, Cubans (n = 2128) had higher intakes of total energy, macronutrients (including all subtypes of fat), and alcohol than those of other groups. Mexicans (n = 5371) had higher intakes of vitamin C, calcium, and fiber. Lowest intakes of total energy, macronutrients, folate, iron, and calcium were reported by Dominicans (n = 1217), whereas Puerto Ricans (n = 2176) had lowest intakes of vitamin C and fiber. Food-group servings reflected nutrient intakes, 'with Cubans having higher intakes of refined grains, vegetables, red meat, and fats and Dominicans having higher intakes of fruit and poultry, whereas Puerto Ricans had lowest intakes of fruit and vegetables. Central and South Americans (n = 1468 and 925, respectively) were characterized by being second in their reported intakes of fruit and poultry and the highest in fish intake in comparison with other groups.
Conclusion: Variations in diet noted in this study, with additional analysis, may help explain diet-related differences in health outcomes observed in Hispanics and Latinos. This trial was registered at clinicaltrials.gov as NCT02060344.
C1 [Siega-Riz, Anna Maria] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27514 USA.
[Siega-Riz, Anna Maria] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC 27514 USA.
[Sotres-Alvarez, Daniela] Univ N Carolina, Gillings Sch Global Publ Hlth, Collaborat Studies Coordinator Ctr, Chapel Hill, NC 27514 USA.
[Ayala, Guadalupe X.] San Diego State Univ, Grad Sch Publ Hlth, Div Hlth Promot & Behav Sci, San Diego, CA 92182 USA.
[Ginsberg, Mindy; Mossavar-Rahmani, Yasniin] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Himes, John H.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Liu, Kiang] Univ Illinois, Dept Prevent Med, Chicago, IL USA.
[Van Horn, Linda] Univ Illinois, Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA.
[Loria, Catherine M.] NHLBI, Epidemiol Branch, Bethesda, MD 20892 USA.
[Rock, Cheryl L.] Univ Calif San Diego, Moores Univ Calif, San Diego Canc Ctr, Dept Family & Prevent Med, San Diego, CA 92103 USA.
[Rodriguez, Brendaly; Gellman, Marc D.] Univ Miami, Behav Med Res Ctr, Dept Psychol, Miami, FL USA.
RP Siega-Riz, AM (reprint author), Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, 2105-A McGavran Greenberg Bldg,135 Dauer Dr, Chapel Hill, NC 27514 USA.
EM am_siegariz@unc.edu
RI DeMarcus, Forrest/O-9190-2016; Sotres-Alvarez, Daniela/O-9085-2016
OI Sotres-Alvarez, Daniela/0000-0002-3226-6140
FU National Heart, Lung, and Blood Institute (NBLBI) [N01-HC65233];
University of Miami [N01-HC65234]; Albert Einstein College of Medicine
[N01-HC65235]; Northwestern University [N01-HC65236]; San Diego State
University [N01-HC65237]; National Institute on Minority Health and
Health Disparities; National Institute on Deafness and Other
Communication Disorders; National Institute of Dental and Craniofacial
Research; National Institute of Diabetes and Digestive and Kidney
Diseases; National Institute of Neurological Disorders and Stroke; NIH
Institution-Office of Dietary Supplements
FX The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) was
supported by contracts from the 'National Heart, Lung, and Blood
Institute (NBLBI) to the University of North Carolina (N01-HC65233),
University of Miami (N01-HC65234), Albert Einstein College of Medicine
(N01-HC65235), Northwestern University (N01-HC65236), and San Diego
State University (N01-HC65237). The following institutes, centers, and
offices contribute to the HCHS/SOL through a transfer of funds to the
NITLBI: the National Institute on Minority Health and Health
Disparities, the National Institute on Deafness and Other Communication
Disorders, the National Institute of Dental and Craniofacial Research,
the National Institute of Diabetes and Digestive and Kidney Diseases,
the National Institute of Neurological Disorders and Stroke, and the NIH
Institution-Office of Dietary Supplements.
NR 37
TC 17
Z9 17
U1 5
U2 19
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN
PY 2014
VL 99
IS 6
BP 1487
EP 1498
DI 10.3945/ajcn.113.082685
PG 12
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AH9NW
UT WOS:000336470100022
PM 24760972
ER
PT J
AU Weaver, CM
Dwyer, J
Fulgoni, VL
King, JC
Leveille, GA
MacDonald, RS
Ordovas, J
Schnakenberg, D
AF Weaver, Connie M.
Dwyer, Johanna
Fulgoni, Victor L., III
King, Janet C.
Leveille, Gilbert A.
MacDonald, Ruth S.
Ordovas, Jose
Schnakenberg, David
TI Processed foods: contributions to nutrition(1,2)
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID NUTRIENT-RICH FOODS; DIETARY; RECOMMENDATIONS; TECHNOLOGY; REDUCTION;
AMERICANS; SCIENCE; DISEASE; QUALITY; HEALTH
AB Both fresh and processed foods make up vital parts of the food supply. Processed food contributes to both food security (ensuring that sufficient food is available) and nutrition security (ensuring that food quality meets human nutrient needs). This ASN scientific statement focuses on one aspect of processed foods: their nutritional impacts. Specifically, this scientific statement 1) provides an introduction to how processed foods contribute to the health of populations, 2) analyzes the contribution of processed foods to "nutrients to encourage" and "constituents to limit" in the American diet as recommended by the Dietary Guidelines for Americans, 3) identifies the responsibilities of various stakeholders in improving the American diet, and 4) reviews emerging technologies and the research needed for a better understanding of the role of processed foods in a healthy diet. Analyses of the NHANES 2003-2008 show that processed foods provide both nutrients to encourage and constituents to limit as specified in the 2010 Dietary Guidelines for Americans. Of the nutrients to encourage, processed foods contributed 55% of dietary fiber, 48% of calcium, 43% of potassium, 34% of vitamin D, 64% of iron,65% of folate, and 46% of vitamin B-12. Of the constituents to limit, processed foods contributed 57% of energy, 52% of saturated fat, 75% of added sugars, and 57% of sodium. Diets are more likely to meet food guidance recommendations if nutrient-dense foods, either processed or not, are selected. Nutrition and food science professionals, the food industry, and other stakeholders can help to improve the diets of Americans by providing a nutritious food supply that is safe, enjoyable, affordable, and sustainable by communicating effectively and accurately with each other and by working together to improve the overall knowledge of consumers.
C1 [Weaver, Connie M.] Purdue Univ, Coll Hlth & Human Sci, Dept Nutr Sci, W Lafayette, IN 47907 USA.
[Dwyer, Johanna] Tufts Univ, Sch Med, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA USA.
[Dwyer, Johanna] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
[Dwyer, Johanna; Ordovas, Jose] NIH, Off Dietary Supplements, Bethesda, MD USA.
[Fulgoni, Victor L., III] Nutr Impact LLC, Battle Creek, MI USA.
[King, Janet C.] Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA.
[King, Janet C.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
[Leveille, Gilbert A.] Leveillt Associates, Denville, NJ USA.
[MacDonald, Ruth S.] Iowa State Univ, Dept Food Sci & Human Nutr, Ames, IA USA.
RP Weaver, CM (reprint author), Purdue Univ, Coll Hlth & Human Sci, Dept Nutr Sci, W Lafayette, IN 47907 USA.
NR 79
TC 16
Z9 19
U1 3
U2 56
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUN
PY 2014
VL 99
IS 6
BP 1525
EP 1542
DI 10.3945/ajcn.114.089284
PG 18
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AH9NW
UT WOS:000336470100030
PM 24760975
ER
PT J
AU Scheinberg, P
Rios, O
Scheinberg, P
Weinstein, B
Wu, CO
Young, NS
AF Scheinberg, Phillip
Rios, Olga
Scheinberg, Priscila
Weinstein, Barbara
Wu, Colin O.
Young, Neal S.
TI Prolonged cyclosporine administration after antithymocyte globulin
delays but does not prevent relapse in severe aplastic anemia
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID FOLLOW-UP; ASSOCIATION; HORSE
AB In severe aplastic anemia, approximately one-third of responders to standard horse antithymocyte globulin (h-ATG) plus cyclosporine (CsA) will relapse. Anecdotal experience has suggested that a gradual CsA taper might avoid relapse, but this practice has not been rigorously assessed prospectively. In 2003, we adopted a strategy to taper CsA beyond 6 months, with the intention to reduce hematologic relapse compared with our extensive historical experience. In total, 102 patients received h-ATG/CsA for 6 months in two sequential clinical protocols: 67 patients (66%) responded and all had the CsA dose tapered per protocol over the subsequent 18 months (total of 2 years). The rate of relapse at 5 years was 33% (95% CI 27-44%), which did not differ from our large historical relapse experience (patients treated before 2003) of 30-40%, in protocols in which CsA was simply discontinued at 6 months. However, time to relapse was prolonged by about 1 year with the longer CsA course. The rates of clonal evolution and overall survival did not differ between the two cohorts. We infer from this large prospective study that CsA taper as implemented delayed but did not prevent relapse. The kinetics of relapse with long course CsA does suggest that a lower long-term dose might be adequate to maintain patients in remission. Am. J. Hematol. 89:571-574, 2014. (c) Published 2014.
C1 [Scheinberg, Phillip; Rios, Olga; Scheinberg, Priscila; Weinstein, Barbara; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Scheinberg, Phillip] Hosp Sao Jose, Ctr Oncol, Hematol Serv, Sao Paulo, Brazil.
[Wu, Colin O.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
RP Scheinberg, P (reprint author), Rua Martiniano de Carvalho 951, BR-01321001 Sao Paulo, Brazil.
EM scheinbp@gmail.com
OI Scheinberg, Phillip/0000-0002-9047-4538
FU Intramural NIH HHS [Z99 HL999999]
NR 18
TC 2
Z9 3
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUN
PY 2014
VL 89
IS 6
BP 571
EP 574
DI 10.1002/ajh.23692
PG 4
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600203
PM 24971433
ER
PT J
AU van Beers, EJ
Samsel, L
Mendelsohn, L
Saiyed, R
Fertrin, KY
Brantner, CA
Daniels, MP
Nichols, J
McCoy, JP
Kato, GJ
AF van Beers, Eduard J.
Samsel, Leigh
Mendelsohn, Laurel
Saiyed, Rehan
Fertrin, Kleber Y.
Brantner, Christine A.
Daniels, Mathew P.
Nichols, James
McCoy, J. Philip
Kato, Gregory J.
TI Imaging flow cytometry for automated detection of hypoxia-induced
erythrocyte shape change in sickle cell disease
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID RED-BLOOD-CELLS; INTRACELLULAR POLYMERIZATION; FETAL-HEMOGLOBIN;
OXYGEN-TENSION; MICROCIRCULATION; ANEMIA; DEFORMABILITY; PERCENTAGE;
DISORDERS; GRADIENTS
AB In preclinical and early phase pharmacologic trials in sickle cell disease, the percentage of sickled erythrocytes after deoxygenation, an ex vivo functional sickling assay, has been used as a measure of a patient's disease outcome. We developed a new sickle imaging flow cytometry assay (SIFCA) and investigated its application. To perform the SIFCA, peripheral blood was diluted, deoxygenated (2% oxygen) for 2 hr, fixed, and analyzed using imaging flow cytometry. We developed a software algorithm that correctly classified investigator tagged sickled and normal erythrocyte morphology with a sensitivity of 100% and a specificity of 99.1%. The percentage of sickled cells as measured by SIFCA correlated strongly with the percentage of sickle cell anemia blood in experimentally admixed samples (R=0.98, P0.001), negatively with fetal hemoglobin (HbF) levels (R=-0.558, P=0.027), negatively with pH (R=-0.688, P=0.026), negatively with pretreatment with the antisickling agent, Aes-103 (5-hydroxymethyl-2-furfural) (R=-0.766, P=0.002), and positively with the presence of long intracellular fibers as visualized by transmission electron microscopy (R=0.799, P=0.002). This study shows proof of principle that the automated, operator-independent SIFCA is associated with predictable physiologic and clinical parameters and is altered by the putative antisickling agent, Aes-103. SIFCA is a new method that may be useful in sickle cell drug development. Am. J. Hematol. 89:598-603, 2014. (c) 2014 Wiley Periodicals, Inc.
C1 [van Beers, Eduard J.; Samsel, Leigh; Mendelsohn, Laurel; Saiyed, Rehan; Fertrin, Kleber Y.; Brantner, Christine A.; Daniels, Mathew P.; Nichols, James; McCoy, J. Philip; Kato, Gregory J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NHLBI, Electron Microscopy Core Facil, NIH, Bethesda, MD 20892 USA.
NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA.
RP Kato, GJ (reprint author), Univ Pittsburgh, Div Hematol Oncol, Dept Med, 200 Lothrop St,BST E1240, Pittsburgh, PA 15261 USA.
EM katogj@upmc.edu
RI Kato, Gregory/I-7615-2014; Fertrin, Kleber/M-4175-2013;
OI Kato, Gregory/0000-0003-4465-3217; Fertrin, Kleber/0000-0003-2637-3297;
Brantner, Christine/0000-0001-8172-901X
FU Intramural NIH HHS [ZIA HL006013-05]; NHLBI NIH HHS [ZIA HL006013]
NR 31
TC 13
Z9 13
U1 3
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUN
PY 2014
VL 89
IS 6
BP 598
EP 603
DI 10.1002/ajh.23699
PG 6
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600208
PM 24585634
ER
PT J
AU Soucie, JM
Miller, CH
Kelly, FM
Aschman, D
DiMichele, D
Konkle, BA
Kulkarni, R
Monahan, PE
AF Soucie, J. Michael
Miller, Connie H.
Kelly, Fiona M.
Aschman, Diane
DiMichele, Donna
Konkle, Barbara A.
Kulkarni, Roshni
Monahan, Paul E.
CA CDC Inhibitor Surveillance Working
TI National surveillance for hemophilia inhibitors in the United States:
Summary report of an expert meeting
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID FACTOR-VIII INHIBITORS; NIJMEGEN MODIFICATION; BETHESDA ASSAY; IX
INHIBITORS; C INHIBITORS; POPULATION; DIAGNOSIS; KINGDOM
AB On March 12, 2012, the Centers for Disease Control and Prevention (CDC) held a meeting of its partners in hemophilia treatment, community-based organizations, industry, and government to review data and discuss implementation issues relevant to planned United States (U.S.) national inhibitor surveillance. Issues discussed included the current status of inhibitor surveillance in the United Kingdom (UK) and the US, the results of a US inhibitor surveillance feasibility study, proposed national surveillance schemes, laboratory testing and reporting issues and potential opportunities for future inhibitor-related research. It was concluded that implementation of a national program of inhibitor surveillance using standardized testing through an established public health registry along with patient and care provider education and targeted research provide the best opportunity to inform efforts to develop and evaluate effective prevention strategies.Am. J. Hematol. 89:621-625, 2014. (c) 2014 Wiley Periodicals, Inc.
C1 [Soucie, J. Michael; Miller, Connie H.; Kelly, Fiona M.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Div Blood Disorders, Atlanta, GA USA.
[Aschman, Diane] Amer Thrombosis & Hemostasis Network, Chicago, IL USA.
[DiMichele, Donna] NHLBI, NIH, Bethesda, MD 20892 USA.
[Konkle, Barbara A.] Puget Sound Blood Ctr, Seattle, WA 98104 USA.
[Kulkarni, Roshni] Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA.
[Monahan, Paul E.] Univ N Carolina, Dept Pediat, Div Hematol Oncol, Chapel Hill, NC USA.
RP Soucie, JM (reprint author), Div Blood Disorders, 1600 Clifton Rd,MS E64, Atlanta, GA 30333 USA.
EM msoucie@cdc.gov
OI Miller, Connie H/0000-0002-3989-7973
FU Intramural CDC HHS [CC999999]
NR 15
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUN
PY 2014
VL 89
IS 6
BP 621
EP 625
DI 10.1002/ajh.23704
PG 5
WC Hematology
SC Hematology
GA AI1NU
UT WOS:000336618600212
PM 24616187
ER
PT J
AU Sorlie, PD
Allison, MA
Aviles-Santa, ML
Cai, JW
Daviglus, ML
Howard, AG
Kaplan, R
LaVange, LM
Raij, L
Schneiderman, N
Wassertheil-Smoller, S
Talavera, GA
AF Sorlie, Paul D.
Allison, Matthew A.
Aviles-Santa, M. Larissa
Cai, Jianwen
Daviglus, Martha L.
Howard, Annie G.
Kaplan, Robert
LaVange, Lisa M.
Raij, Leopoldo
Schneiderman, Neil
Wassertheil-Smoller, Sylvia
Talavera, Gregory A.
TI Prevalence of Hypertension, Awareness, Treatment, and Control in the
Hispanic Community Health Study/Study of Latinos
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure; epidemiology; Hispanics; hypertension; Latinos;
medically uninsured; socioeconomic status
ID CARDIOVASCULAR-DISEASE; MEXICAN-AMERICANS; RISK-FACTORS; DESIGN
AB BACKGROUND The prevention and control of hypertension is an essential component for reducing the burden of cardiovascular diseases. Here we describe the prevalence of hypertension in diverse Hispanic/Latino background groups and describe the proportion who are aware of their diagnosis, receiving treatment, and having their hypertension under control.
METHODS The Hispanic Community Health Study/Study of Latinos is a longitudinal cohort study of 16,415 Hispanics/Latinos, aged 18-74 years from 4 US communities (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA). At baseline (2008-2011) the study collected extensive measurements and completed questionnaires related to research on cardiovascular diseases. Hypertension was defined as measured blood pressure >= 140/90 mm Hg or use of antihypertensive medication.
RESULTS The total age-adjusted prevalence of hypertension in this study was 25.5% as compared with 27.4% in non-Hispanic whites in the National Health and Nutrition Examination Survey. Prevalence of hypertension increased with increasing age groups and was highest in Cuban, Puerto Rican, and Dominican background groups. The percent with hypertension who were aware, being treated with medication, or had their hypertension controlled was lower compared with US non-Hispanic whites with hypertension and it was lowest in those without health insurance.
CONCLUSIONS These findings indicate a significant deficit in treatment and control of hypertension among Hispanics/Latinos residing in the United States, particularly those without health insurance. Given the relative ease of identification of hypertension and the availability of low-cost medications, enabling better access to diagnostic and treatment services should reduce the burden of hypertension in Hispanic populations.
C1 [Sorlie, Paul D.; Aviles-Santa, M. Larissa] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Allison, Matthew A.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Cai, Jianwen; Howard, Annie G.; LaVange, Lisa M.] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA.
[Daviglus, Martha L.] Univ Illinois, Inst Minor Hlth Res, Chicago, IL USA.
[Kaplan, Robert; Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Raij, Leopoldo] Univ Miami, Miller Sch Med, Renal Hypertens Sect, Miami Vet Affairs Med Ctr,Renal Hypertens Div, Miami, FL 33136 USA.
[Raij, Leopoldo] South Florida Vet Affairs Fdn Res & Educ, Miami, FL USA.
[Schneiderman, Neil] Univ Miami, Dept Psychol, Miami, FL USA.
[Talavera, Gregory A.] San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA.
RP Sorlie, PD (reprint author), NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM SorlieP@mail.nih.gov
OI Allison, Matthew/0000-0003-0777-8272
FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC65233];
University of Miami [N01-HC65234]; Albert Einstein College of Medicine
[N01-HC65235]; Northwestern University [N01-HC65236]; San Diego State
University [N01-HC65237]; National Institute on Minority Health and
Health Disparities; National Institute on Deafness and Other
Communication Disorders; National Institute of Dental and Craniofacial
Research; National Institute of Diabetes and Digestive and Kidney
Diseases; National Institute of Neurological Disorders and Stroke;
National Institutes of Health, Office of Dietary Supplements
FX The authors thank the staff and participants of for their important
contributions. The study website is http://www.cscc.unc.edu/hchs/. The
HCHS/SOL was carried out as a collaborative study supported by contracts
from the National Heart, Lung, and Blood Institute (NHLBI) to the
University of North Carolina (N01-HC65233), University of Miami
(N01-HC65234), Albert Einstein College of Medicine (N01-HC65235),
Northwestern University (N01-HC65236), and San Diego State University
(N01-HC65237). The following institutes/centers/offices contribute to
the HCHS/SOL through a transfer of funds to the NHLBI: National
Institute on Minority Health and Health Disparities, National Institute
on Deafness and Other Communication Disorders, National Institute of
Dental and Craniofacial Research, National Institute of Diabetes and
Digestive and Kidney Diseases, National Institute of Neurological
Disorders and Stroke, and National Institutes of Health, Office of
Dietary Supplements.
NR 15
TC 29
Z9 30
U1 2
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0895-7061
EI 1941-7225
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD JUN
PY 2014
VL 27
IS 6
BP 793
EP 800
DI 10.1093/ajh/hpu003
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AI0HO
UT WOS:000336527400005
PM 24627442
ER
PT J
AU Campbell, ANC
Nunes, EV
Matthews, AG
Stitzer, M
Miele, GM
Polsky, D
Turrigiano, E
Walters, S
McClure, EA
Kyle, TL
Wahle, A
Van Veldhuisen, P
Goldman, B
Babcock, D
Stabile, PQ
Winhusen, T
Ghitza, UE
AF Campbell, Aimee N. C.
Nunes, Edward V.
Matthews, Abigail G.
Stitzer, Maxine
Miele, Gloria M.
Polsky, Daniel
Turrigiano, Eva
Walters, Scott
McClure, Erin A.
Kyle, Tiffany L.
Wahle, Aimee
Van Veldhuisen, Paul
Goldman, Bruce
Babcock, Dean
Stabile, Patricia Quinn
Winhusen, Theresa
Ghitza, Udi E.
TI Internet-Delivered Treatment for Substance Abuse: A Multisite Randomized
Controlled Trial
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID COGNITIVE-BEHAVIORAL THERAPY; CLINICAL-TRIALS; DEPENDENT OUTPATIENTS;
ALCOHOL-CONSUMPTION; COCAINE DEPENDENCE; ADDICTION; INCENTIVES; NETWORK;
CARE; INTERVENTIONS
AB Objective: Computer-delivered interventions have the potential to improve access to quality addiction treatment care. The objective of this study was to evaluate the effectiveness of the Therapeutic Education System (TES), an Internet-delivered behavioral intervention that includes motivational incentives, as a clinician-extender in the treatment of substance use disorders.
Method: Adult men and women (N=507) entering 10 outpatient addiction treatment programs were randomly assigned to receive 12 weeks of either treatment as usual (N=252) or treatment as usual plus TES, with the intervention substituting for about 2 hours of standard care per week (N=255). TES consists of 62 computerized interactive modules covering skills for achieving and maintaining abstinence, plus prize-based motivational incentives contingent on abstinence and treatment adherence. Treatment as usual consisted of individual and group counseling at the participating programs. The primary outcome measures were abstinence from drugs and heavy drinking (measured by twice-weekly urine drug screens and self-report) and time to dropout from treatment.
Results: Compared with patients in the treatment-as-usual group, those in the TES group had a lower dropout rate (hazard ratio=0.72, 95% CI=0.57, 0.92) and a greater abstinence rate (odds ratio=1.62, 95% CI=1.12, 2.35). This effect was more pronounced among patients who had a positive urine drug or breath alcohol screen at study entry (N=228) (odds ratio=2.18, 95% CI=1.30, 3.68).
Conclusions: Internet-delivered interventions such as TES have the potential to expand access and improve addiction treatment outcomes. Additional research is needed to assess effectiveness in non-specialty clinical settings and to differentiate the effects of the community reinforcement approach and contingency management components of TES.
C1 [Campbell, Aimee N. C.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
Columbia Univ, Dept Psychiat, New York, NY USA.
St Lukes Roosevelt Hosp, Dept Psychiat & Behav Hlth, New York, NY USA.
EMMES Corp, Rockville, MD USA.
Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
Univ N Texas, Hlth Sci Ctr, Sch Publ Hlth, Ft Worth, TX USA.
Med Univ S Carolina, Clin Neurosci Div, Charleston, SC USA.
Ctr Drug Free Living, Orlando, FL USA.
Zucker Hillside Hosp, North Shore Long Isl Jewish Hlth Syst, Glen Oaks, NY USA.
Midtown Community Mental Hlth Ctr, Indianapolis, IN USA.
HARBEL Prevent & Recovery Ctr, Baltimore, MD USA.
Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA.
NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA.
RP Campbell, ANC (reprint author), New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
EM anc2002@columbia.edu
OI Winhusen, Theresa/0000-0002-3364-0739
FU National Drug Abuse Treatment Clinical Trials Network, National
Institute on Drug Abuse (NIDA) [U10 DA013035, U10 DA015831, U10
DA013034, U10 DA013720, U10 DA013732, U10 DA020024, U10 DA013714, U10
DA015815, K24 DA022412]
FX Supported by grants from the National Drug Abuse Treatment Clinical
Trials Network, National Institute on Drug Abuse (NIDA): U10 DA013035
(to Dr. Nunes and John Rotrosen), U10 DA015831 (to Kathleen M. Carroll
and Roger D. Weiss), U10 DA013034 (Dr. Stitzer and Robert P. Schwartz),
U10 DA013720 (to Jose Szapocznik and Lisa R. Metsch), U10 DA013732 (to
Eugene C. Somoza), U10 DA020024 (to Madhukar H. Trivedi), U10 DA013714.
(to Dennis M. Donovan and John Roll), U10 DA015815 (to James L Sorensen
and Dennis McCarty), and K24 DA022412 (to Dr. Nunes).
NR 38
TC 31
Z9 31
U1 5
U2 35
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUN
PY 2014
VL 171
IS 6
BP 683
EP 690
DI 10.1176/appi.ajp.2014.13081055
PG 8
WC Psychiatry
SC Psychiatry
GA AI1TU
UT WOS:000336638600016
PM 24700332
ER
PT J
AU Muftuoglu, Y
Sohl, CD
Mislak, AC
Mitsuya, H
Sarafianos, SG
Anderson, KS
AF Muftuoglu, Yagmur
Sohl, Christal D.
Mislak, Andrea C.
Mitsuya, Hiroaki
Sarafianos, Stefan G.
Anderson, Karen S.
TI Probing the molecular mechanism of action of the HIV-1 reverse
transcriptase inhibitor 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA)
using pre-steady-state kinetics
SO ANTIVIRAL RESEARCH
LA English
DT Article
DE HIV; Reverse transcriptase; Enzyme kinetics; EFdA; Polymerase
ID IMMUNODEFICIENCY-VIRUS TYPE-1; MITOCHONDRIAL-DNA POLYMERASE; HOST
TOXICITY; 4'-ETHYNYL-2-FLUORO-2'-DEOXYADENOSINE; GAMMA; DISCRIMINATION;
NUCLEOTIDE; ENTECAVIR; SUBSTRATE; FIDELITY
AB The novel antiretroviral 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a potent nucleoside HIV-1 reverse transcriptase (RT) inhibitor (NRTI). Unlike other FDA-approved NRTIs, EFdA contains a 3'-hydroxyl. Pre-steady-state kinetics showed RT preferred incorporating EFdA-TP over native dATP. Moreover, RT slowly inserted nucleotides past an EFdA-terminated primer, resulting in delayed chain termination with unaffected fidelity. This is distinct from KP1212, another 3'-hydroxyl-containing RT inhibitor considered to promote viral lethal mutagenesis. New mechanistic features of RI inhibition by EFdA are revealed. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Muftuoglu, Yagmur; Sohl, Christal D.; Mislak, Andrea C.; Anderson, Karen S.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA.
[Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Infect Dis, Kumamoto 8608556, Japan.
[Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Hematol, Kumamoto 8608556, Japan.
[Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
[Sarafianos, Stefan G.] Univ Missouri, Sch Med, CS Bond Life Sci Ctr, Columbia, MO 65211 USA.
[Sarafianos, Stefan G.] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65211 USA.
[Sarafianos, Stefan G.] Univ Missouri, Sch Med, Dept Biochem, Columbia, MO 65211 USA.
RP Anderson, KS (reprint author), Yale Univ, Sch Med, Dept Pharmacol, 333 Cedar St, New Haven, CT 06520 USA.
EM karen.anderson@yale.edu
OI Sarafianos, Stefan G/0000-0002-5840-154X
FU NIH [R01 GM049551, F32 GM099289, AI076119, AI099284, AI100890, GM103368]
FX This work was supported by NIH grants R01 GM049551 (to K.S.A.), F32
GM099289 (to C.D.S.), and AI076119, AI099284, AI100890, and GM103368 (to
S.G.S.). We would like to thank Ligong Wang for the purification of the
pol accessory subunit.
NR 24
TC 7
Z9 7
U1 1
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
EI 1872-9096
J9 ANTIVIR RES
JI Antiviral Res.
PD JUN
PY 2014
VL 106
BP 1
EP 4
DI 10.1016/j.antiviral.2014.03.001
PG 4
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA AI4IA
UT WOS:000336827700001
PM 24632447
ER
PT J
AU Meza, R
ten Haaf, K
Kong, CY
Erdogan, A
Black, WC
Tammemagi, MC
Choi, SE
Jeon, J
Han, SS
Munshi, V
van Rosmalen, J
Pinsky, P
McMahon, PM
de Koning, HJ
Eric, J
Hazelton, WD
Plevritis, SK
AF Meza, Rafael
ten Haaf, Kevin
Kong, Chung Yin
Erdogan, Ayca
Black, William C.
Tammemagi, Martin C.
Choi, Sung Eun
Jeon, Jihyoun
Han, Summer S.
Munshi, Vidit
van Rosmalen, Joost
Pinsky, Paul
McMahon, Pamela M.
de Koning, Harry J.
Feuer, Eric J.
Hazelton, William D.
Plevritis, Sylvia K.
TI Comparative Analysis of 5 Lung Cancer Natural History and Screening
Models That Reproduce Outcomes of the NLST and PLCO Trials
SO CANCER
LA English
DT Article
DE Cancer Intervention and Surveillance Modeling Network (CISNET);
comparative modeling analyses; low-dose CT screening; lung cancer
screening; cancer natural history models; smoking and lung cancer;
simulation model
ID MULTISTAGE CARCINOGENESIS; MICROSIMULATION MODELS; POTENTIAL BENEFITS;
COLORECTAL-CANCER; UNITED-STATES; MORTALITY; SMOKING; PROSTATE; HEALTH;
RISK
AB BACKGROUNDThe National Lung Screening Trial (NLST) demonstrated that low-dose computed tomography screening is an effective way of reducing lung cancer (LC) mortality. However, optimal screening strategies have not been determined to date and it is uncertain whether lighter smokers than those examined in the NLST may also benefit from screening. To address these questions, it is necessary to first develop LC natural history models that can reproduce NLST outcomes and simulate screening programs at the population level.
METHODSFive independent LC screening models were developed using common inputs and calibration targets derived from the NLST and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). Imputation of missing information regarding smoking, histology, and stage of disease for a small percentage of individuals and diagnosed LCs in both trials was performed. Models were calibrated to LC incidence, mortality, or both outcomes simultaneously.
RESULTSInitially, all models were calibrated to the NLST and validated against PLCO. Models were found to validate well against individuals in PLCO who would have been eligible for the NLST. However, all models required further calibration to PLCO to adequately capture LC outcomes in PLCO never-smokers and light smokers. Final versions of all models produced incidence and mortality outcomes in the presence and absence of screening that were consistent with both trials.
CONCLUSIONSThe authors developed 5 distinct LC screening simulation models based on the evidence in the NLST and PLCO. The results of their analyses demonstrated that the NLST and PLCO have produced consistent results. The resulting models can be important tools to generate additional evidence to determine the effectiveness of lung cancer screening strategies using low-dose computed tomography. Cancer 2014;120:1713-1724. (c) 2014 American Cancer Society.
C1 [Meza, Rafael] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[ten Haaf, Kevin; van Rosmalen, Joost; de Koning, Harry J.] Erasmus Univ, Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands.
[Kong, Chung Yin; Choi, Sung Eun; Munshi, Vidit; McMahon, Pamela M.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Kong, Chung Yin; Choi, Sung Eun; Munshi, Vidit; McMahon, Pamela M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Erdogan, Ayca; Han, Summer S.; Plevritis, Sylvia K.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA.
[Black, William C.] Dartmouth Coll, Dept Radiol, Geisel Sch Med Dartmouth, Hanover, NH 03755 USA.
[Tammemagi, Martin C.] Brock Univ, Dept Community Hlth Sci, St Catharines, ON L2S 3A1, Canada.
[Jeon, Jihyoun; Hazelton, William D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Biostat & Biomath, Seattle, WA 98104 USA.
[van Rosmalen, Joost] Erasmus Univ, Med Ctr, Dept Biostat, Rotterdam, Netherlands.
[Pinsky, Paul] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Meza, R (reprint author), Univ Michigan, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
EM rmeza@umich.edu
OI van Rosmalen, Joost/0000-0002-9187-244X
FU Agency for Healthcare Research and Quality (AHRQ) [U01-CA152956]
FX This report is based on research conducted by the National Cancer
Institutes (NCI)'s Cancer Intervention and Surveillance Modeling Network
(CISNET) through support from an interagency agreement with the Agency
for Healthcare Research and Quality (AHRQ) (administrative supplement to
NCI grant U01-CA152956).
NR 31
TC 17
Z9 17
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUN 1
PY 2014
VL 120
IS 11
BP 1713
EP 1724
DI 10.1002/cncr.28623
PG 12
WC Oncology
SC Oncology
GA AI1OE
UT WOS:000336619700021
PM 24577803
ER
PT J
AU Reid, JM
Buhrow, SA
Gilbert, JA
Jia, L
Shoji, M
Snyder, JP
Ames, MM
AF Reid, Joel M.
Buhrow, Sarah A.
Gilbert, Judith A.
Jia, Lee
Shoji, Mamoru
Snyder, James P.
Ames, Matthew M.
TI Mouse pharmacokinetics and metabolism of the curcumin analog,
4-piperidinone,3,5-bis[(2-fluorophenyl)methylene]-acetate(3E,5E) (EF-24;
NSC 716993)
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE EF-24; Curcumin; LC/MS/MS; Pharmacokinetics; Mouse
ID CHEMOPREVENTIVE AGENT CURCUMIN; CANCER-CELLS; IN-VIVO; EF24; ANTICANCER;
ANGIOGENESIS; APOPTOSIS; PATHWAY; ENZYME; TISSUE
AB Curcumin, a keto-enol constituent of turmeric, has in vitro and in vivo antitumor activity. However, in vivo potency is low due to poor oral absorption. The mono-carbonyl analog, 3,5-bis[(2-fluorophenyl)methylene]-4-piperidinone acetate (EF-24, NSC 716993), exhibited broad-spectrum activity in the NCI anticancer cell line screen and potent antiangiogenesis activity in a HUVEC cell migration assay. The purpose of this study was to characterize the preclinical pharmacology of EF-24 in mice.
EF-24 plasma stability, protein binding, pharmacokinetics, and metabolism were characterized utilizing an LC/MS/MS assay.
An LC/MS/MS assay incorporated protein precipitation with methanol, reverse-phase HPLC separation under gradient elution using an aqueous methanol mobile phase containing 0.1 % formic acid, and positive electrospray ionization detection of the m/z 312 > 149 transition for EF-24. The assay was linear over the range 7.8-1,000 nM. Plasma protein binding was > 98 % with preferential binding to albumin. EF-24 plasma disposition in mice after i.v. administration of a 10 mg/kg dose was best fit to a 3-compartment open model. The terminal elimination half-life and plasma clearance values were 73.6 min and 0.482 L/min/kg, respectively. EF-24 bioavailability was 60 and 35 % after oral and i.p. administration, respectively. NADPH-dependent metabolism of EF-24 loss in liver microsomal preparations yielded several metabolites consistent with EF-24 hydroxylation and reduction.
C1 [Reid, Joel M.; Buhrow, Sarah A.; Gilbert, Judith A.; Ames, Matthew M.] Mayo Clin, Div Oncol Res, Dept Oncol, Rochester, MN 55905 USA.
[Jia, Lee] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, DCTD, Rockville, MD 20852 USA.
[Shoji, Mamoru] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA.
[Snyder, James P.] Emory Univ, Dept Chem, Atlanta, GA 30322 USA.
[Snyder, James P.] Emory Univ, Mory Inst Drug Dev, Atlanta, GA 30322 USA.
RP Reid, JM (reprint author), Mayo Clin, Div Oncol Res, Dept Oncol, 200 First St SW, Rochester, MN 55905 USA.
EM reid@mayo.edu
FU National Cancer Institute [N01-CM-07105, 5 R21 CA139035-2]; US
Department of Defense, Division of US Army [DAMD17-00-1-0241, BC074220]
FX MS and JPS are grateful to Dennis Liotta (Emory University) for generous
support of preparation of the curcumin analogs. This study was supported
by National Cancer Institute Contract N01-CM-07105, US Department of
Defense, Division of US Army DAMD17-00-1-0241 (MS and JPS), BC074220 (MS
and JPS) and National Cancer Institute 5 R21 CA139035-2 (MS and JPS).
NR 28
TC 5
Z9 5
U1 2
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
EI 1432-0843
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD JUN
PY 2014
VL 73
IS 6
BP 1137
EP 1146
DI 10.1007/s00280-014-2447-3
PG 10
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA AH8NV
UT WOS:000336395700005
PM 24760417
ER
PT J
AU Avidan, G
Tanzer, M
Hadj-Bouziane, F
Liu, N
Ungerleider, LG
Behrmann, M
AF Avidan, Galia
Tanzer, Michal
Hadj-Bouziane, Fadila
Liu, Ning
Ungerleider, Leslie G.
Behrmann, Marlene
TI Selective Dissociation Between Core and Extended Regions of the Face
Processing Network in Congenital Prosopagnosia
SO CEREBRAL CORTEX
LA English
DT Article
DE face processing; functional connectivity; neurodevelopmental disorders;
prosopagnosia; ventral visual cortex
ID DEVELOPMENTAL PROSOPAGNOSIA; TEMPORAL CORTEX; FUSIFORM GYRUS; FUNCTIONAL
CONNECTIVITY; DETAILED EXPLORATION; CORTICAL NETWORK; VISUAL-CORTEX;
PERCEPTION; RECOGNITION; SYSTEM
AB There is growing consensus that accurate and efficient face recognition is mediated by a neural circuit composed of a posterior "core" and an anterior "extended" set of regions. Here, we characterize the distributed face network in human individuals with congenital prosopagnosia (CP)-a lifelong impairment in face processing-relative to that of matched controls. Using functional magnetic resonance imaging, we first uncover largely normal activation patterns in the posterior core face patches in CP. We also document normal activity of the amygdala (emotion processing) as well as normal or even enhanced functional connectivity between the amygdala and the core regions. Critically, in the same individuals, activation of the anterior temporal cortex (identity processing) is reduced and connectivity between this region and the posterior core regions is disrupted. The dissociation between the neural profiles of the anterior temporal lobe and amygdala was evident both during a task-related face scan and during a resting state scan, in the absence of visual stimulation. Taken together, these findings elucidate selective disruptions in neural circuitry in CP and offer an explanation for the known differential difficulty in identity versus emotional expression recognition in many individuals with CP.
C1 [Avidan, Galia; Tanzer, Michal] Ben Gurion Univ Negev, Dept Psychol, IL-84105 Beer Sheva, Israel.
[Hadj-Bouziane, Fadila] Lyon Neurosci Res Ctr, CNRS, INSERM, U1028,UMR5292,ImpAct Team, Bron, France.
[Liu, Ning; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Behrmann, Marlene] Carnegie Mellon Univ, Dept Psychol, Pittsburgh, PA 15213 USA.
RP Avidan, G (reprint author), Ben Gurion Univ Negev, Dept Psychol, POB 653, IL-84105 Beer Sheva, Israel.
EM galiaa@bgu.ac.il
RI Avidan, Galia/B-9347-2011;
OI Avidan, Galia/0000-0003-2293-3859; Behrmann, Marlene/0000-0002-3814-1015
FU Israeli Science Foundation (ISF) [384/10]; National Institutes of Mental
Health [MH54246]; National Science Foundation [NSF BCS0923763, NSF
SBE-0542013]; NIMH Intramural Research program
FX This research was supported by a grant from the Israeli Science
Foundation (ISF, 384/10) to G. A., and from grants from the National
Institutes of Mental Health (MH54246), and the National Science
Foundation (NSF BCS0923763; NSF SBE-0542013 to the Temporal Dynamics of
Learning Center, an NSF Science of Learning Center) to M. B. F.H.-B.,
N.L., and L. G. U. were supported by the NIMH Intramural Research
program.
NR 57
TC 54
Z9 54
U1 2
U2 23
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD JUN
PY 2014
VL 24
IS 6
BP 1565
EP 1578
DI 10.1093/cercor/bht007
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA AI0IG
UT WOS:000336529700014
PM 23377287
ER
PT J
AU Castro, FA
Liu, XD
Forsti, A
Ji, JG
Sundquist, J
Sundquist, K
Koshiol, J
Hemminki, K
AF Castro, Felipe A.
Liu, Xiangdong
Forsti, Asta
Ji, Jianguang
Sundquist, Jan
Sundquist, Kristina
Koshiol, Jill
Hemminki, Kari
TI Increased Risk of Hepatobiliary Cancers After Hospitalization for
Autoimmune Disease
SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Article
DE Risk Factor; Cohort; Survival; Hepatocellular Carcinoma
ID PRIMARY BILIARY-CIRRHOSIS; POPULATION-BASED COHORT; PRIMARY SCLEROSING
CHOLANGITIS; INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; TRACT
CANCER; HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; PERNICIOUS-ANEMIA;
CELIAC-DISEASE
AB BACKGROUND & AIMS: Some autoimmune diseases are associated with increased risk of liver cancer. However, there has been no comprehensive evaluation of autoimmune diseases among patients who develop different subtypes of hepatobiliary cancer. We examined the association between autoimmune diseases and cancers of the liver and biliary tract in the Swedish population.
METHODS: We analyzed data from national datasets at the Center for Primary Health Care Research (Lund University, Sweden). Data on patients with autoimmune disorders were retrieved from the Swedish Hospital Discharge Register, from 1964 through 2008; 33 diseases were evaluated. Hepatobiliary cancer cases were retrieved from the Swedish Cancer Registry. We calculated standardized incidence ratios (SIRs) and hazard ratios for incident cancers and deaths from hepatobiliary cancers.
RESULTS: Among 402,462 patients with autoimmune disorders, 582 were diagnosed with primary liver cancer, 330 with gallbladder cancer, 115 with extrahepatic bile duct cancer, and 43 with ampulla of Vater cancers. We identified 14 autoimmune conditions that were significantly associated with increased risk of primary liver cancer (overall SIR [any autoimmune disease], 2.1; 95% confidence interval [CI], 2.0-2.3), 5 conditions associated with gallbladder cancer (overall SIR, 1.3; 95% CI, 1.1-1.4), and 3 associated with extrahepatic bile duct cancer (overall SIR, 1.6; 95% CI, 1.3-1.9). The autoimmune disorders with the strongest association with primary liver cancer were primary biliary cirrhosis (SIR, 39.5; 95% CI, 28.2-53.8) and autoimmune hepatitis (SIR, 29.0; 95% CI, 9.1-68.2); ulcerative colitis was strongly associated with extrahepatic bile duct cancer (SIR, 5.6; 95% CI, 3.6-8.4). Celiac disease, Crohn's disease, systemic sclerosis, and ulcerative colitis were associated with at least 2 types of cancer. Increased hazard ratios were observed only for patients with biliary tract cancer who had been hospitalized for autoimmune conditions.
CONCLUSIONS: In a study of the Swedish population, we identified an increased risk of hepatobiliary cancers among individuals diagnosed with autoimmune disease. Associations among different cancer types indicate that shared immunomodulatory mechanisms determine susceptibility to hepatobiliary cancer.
C1 [Castro, Felipe A.; Koshiol, Jill] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Liu, Xiangdong; Forsti, Asta; Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina; Hemminki, Kari] Lund Univ, Ctr Primary Hlth Care Res, Malmo, Sweden.
[Forsti, Asta; Hemminki, Kari] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany.
[Sundquist, Jan; Sundquist, Kristina] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Stanford, CA 94305 USA.
RP Castro, FA (reprint author), NCI Shady Grove, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr 6-E230, Rockville, MD 20850 USA.
EM felipe.castro@nih.gov
RI Ji, Jianguang/E-9579-2011
OI Ji, Jianguang/0000-0003-0324-9496
FU Deutsche Krebshilfe, ALF project grant, Lund, Sweden; Swedish Council
for Working Life and Social Research; National Institute of Health;
National Cancer Institute, Division of Cancer Epidemiology and Genetics,
USA
FX This work was supported by Deutsche Krebshilfe, ALF project grant, Lund,
Sweden and the Swedish Council for Working Life and Social Research. The
study was also supported by the Intramural Research Program of the
National Institute of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics, USA.
NR 45
TC 8
Z9 8
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1542-3565
EI 1542-7714
J9 CLIN GASTROENTEROL H
JI Clin. Gastroenterol. Hepatol.
PD JUN
PY 2014
VL 12
IS 6
BP 1038
EP +
DI 10.1016/j.cgh.2013.11.007
PG 15
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH9ZI
UT WOS:000336504700026
PM 24246767
ER
PT J
AU Turnbull, AE
Krall, JR
Ruhl, AP
Curtis, JR
Halpern, SD
Lau, BM
Needham, DM
AF Turnbull, Alison E.
Krall, Jenna R.
Ruhl, A. Parker
Curtis, J. Randall
Halpern, Scott D.
Lau, Bryan M.
Needham, Dale M.
TI A Scenario-Based, Randomized Trial of Patient Values and Functional
Prognosis on Intensivist Intent to Discuss Withdrawing Life Support
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE decision making; intensive care; life support care; prognosis;
resuscitation orders; withholding treatment
ID MORTALITY PROBABILITY-MODELS; IMPROVING PALLIATIVE CARE; MECHANICAL
VENTILATION; CHAINED EQUATIONS; FOCUSING ILLUSION; UNIT; PHYSICIANS;
ASSOCIATION; IMPUTATION; COMFORT
AB Objectives: To evaluate the effect of 1) patient values as expressed by family members and 2) a requirement to document patients' functional prognosis on intensivists' intention to discuss withdrawal of life support in a hypothetical family meeting.
Design: A three-armed, randomized trial.
Setting: One hundred seventy-nine U.S. hospitals with training programs in critical care accredited by the Accreditation Council for Graduate Medical Education.
Subjects: Six hundred thirty intensivists recruited via e-mail invitation from a database of 1,850 eligible academic intensivists.
Interventions: Each intensivist was randomized to review 10, online, clinical scenarios with a range of illness severities involving a hypothetical patient (Mrs. X). In control-group scenarios, the patient did not want continued life support without a reasonable chance of independent living. In the first experimental arm, the patient wanted life support regardless of functional outcome. In the second experimental arm, patient values were identical to the control group, but intensivists were required to record the patient's estimated 3-month functional prognosis.
Measurements and Main Results: Response to the question: Would you bring up the possibility of withdrawing life support with Mrs. X's family? answered using a five-point Likert scale. There was no effect of patient values on whether intensivists intended to discuss withdrawal of life support (p = 0.81), but intensivists randomized to record functional prognosis were 49% more likely (95% CI, 20-85%) to discuss withdrawal.
Conclusions: In this national, scenario-based, randomized trial, patient values had no effect on intensivists' decisions to discuss withdrawal of life support with family. However, requiring intensivists to record patients' estimated 3-month functional outcome substantially increased their intention to discuss withdrawal.
C1 [Turnbull, Alison E.; Lau, Bryan M.] Johns Hopkins Univ Bloomberg, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA.
[Turnbull, Alison E.; Ruhl, A. Parker; Needham, Dale M.] Johns Hopkins Med, Outcomes Crit Illness & Surg OACIS Grp, Baltimore, MD USA.
[Turnbull, Alison E.; Ruhl, A. Parker; Needham, Dale M.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA.
[Krall, Jenna R.] Johns Hopkins Univ Bloomberg, Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Ruhl, A. Parker] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Curtis, J. Randall] Univ Washington, Sch Med, Div Pulm & Crit Care Med, Seattle, WA USA.
[Curtis, J. Randall] Univ Washington, Sch Med, Palliat Care Ctr Excellence, Seattle, WA USA.
[Halpern, Scott D.] Univ Penn, Perelman Sch Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA.
[Halpern, Scott D.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Halpern, Scott D.] Univ Penn, Perelman Sch Med, Fostering Improvement End Of Life Decis Sci FIELD, Philadelphia, PA 19104 USA.
[Needham, Dale M.] Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD USA.
RP Turnbull, AE (reprint author), Johns Hopkins Univ Bloomberg, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA.
EM turnbull@jhmi.edu
FU National Institutes of Health (NIH); National Institute on Aging
[T32-AG000247]; Johns Hopkins University Sommer Scholars Program; NIH
[T32-AG000247]
FX Dr. Turnbull received support for article research from the National
Institutes of Health (NIH) (supported by a postdoctoral training grant
from the National Institute on Aging, T32-AG000247). Dr. Turnbull is
supported by the Johns Hopkins University Sommer Scholars Program. Dr.
Krall received grant support from the National Institute on Aging
(T32-AG000247) and received support for article research from the NIH
(T32-AG000247). The remaining authors have disclosed that they do not
have any potential conflicts of interest.
NR 37
TC 15
Z9 15
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD JUN
PY 2014
VL 42
IS 6
BP 1455
EP 1462
DI 10.1097/CCM.0000000000000227
PG 8
WC Critical Care Medicine
SC General & Internal Medicine
GA AH6UM
UT WOS:000336266900031
PM 24584065
ER
PT J
AU Dimas, AS
Lagou, V
Barker, A
Knowles, JW
Magi, R
Hivert, MF
Benazzo, A
Rybin, D
Jackson, AU
Stringham, HM
Song, C
Fischer-Rosinsky, A
Boesgaard, TW
Grarup, N
Abbasi, FA
Assimes, TL
Hao, K
Yang, X
Lecoeur, C
Barroso, I
Bonnycastle, LL
Bottcher, Y
Bumpstead, S
Chines, PS
Erdos, MR
Graessler, J
Kovacs, P
Morken, MA
Narisu, N
Payne, F
Stancakova, A
Swift, AJ
Tonjes, A
Bornstein, SR
Cauchi, S
Froguel, P
Meyre, D
Schwarz, PEH
Haring, HU
Smith, U
Boehnke, M
Bergman, RN
Collins, FS
Mohlke, KL
Tuomilehto, J
Quertemous, T
Lind, L
Hansen, T
Pedersen, O
Walker, M
Pfeiffer, AFH
Spranger, J
Stumvoll, M
Meigs, JB
Wareham, NJ
Kuusisto, J
Laakso, M
Langenberg, C
Dupuis, J
Watanabe, RM
Florez, JC
Ingelsson, E
McCarthy, MI
Prokopenko, I
AF Dimas, Antigone S.
Lagou, Vasiliki
Barker, Adam
Knowles, Joshua W.
Maegi, Reedik
Hivert, Marie-France
Benazzo, Andrea
Rybin, Denis
Jackson, Anne U.
Stringham, Heather M.
Song, Ci
Fischer-Rosinsky, Antje
Boesgaard, Trine Wellov
Grarup, Niels
Abbasi, Fahim A.
Assimes, Themistocles L.
Hao, Ke
Yang, Xia
Lecoeur, Cecile
Barroso, Ines
Bonnycastle, Lori L.
Boettcher, Yvonne
Bumpstead, Suzannah
Chines, Peter S.
Erdos, Michael R.
Graessler, Jurgen
Kovacs, Peter
Morken, Mario A.
Narisu, Narisu
Payne, Felicity
Stancakova, Alena
Swift, Amy J.
Toenjes, Anke
Bornstein, Stefan R.
Cauchi, Stephane
Froguel, Philippe
Meyre, David
Schwarz, Peter E. H.
Haering, Hans-Ulrich
Smith, Ulf
Boehnke, Michael
Bergman, Richard N.
Collins, Francis S.
Mohlke, Karen L.
Tuomilehto, Jaakko
Quertemous, Thomas
Lind, Lars
Hansen, Torben
Pedersen, Oluf
Walker, Mark
Pfeiffer, Andreas F. H.
Spranger, Joachim
Stumvoll, Michael
Meigs, James B.
Wareham, Nicholas J.
Kuusisto, Johanna
Laakso, Markku
Langenberg, Claudia
Dupuis, Josee
Watanabe, Richard M.
Florez, Jose C.
Ingelsson, Erik
McCarthy, Mark I.
Prokopenko, Inga
CA MAGIC Investigators
TI Impact of Type 2 Diabetes Susceptibility Variants on Quantitative
Glycemic Traits Reveals Mechanistic Heterogeneity
SO DIABETES
LA English
DT Article
ID BETA-CELL FUNCTION; SCALE ASSOCIATION ANALYSIS; BODY-MASS INDEX; INSULIN
SENSITIVITY; PROINSULIN LEVELS; COMMON VARIANT; TCF7L2 GENE; GLUCOSE;
GENOME; LOCI
AB Patients with established type 2 diabetes display both beta-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF712, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition.
C1 [Dimas, Antigone S.; Lagou, Vasiliki; Maegi, Reedik; Ingelsson, Erik; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Dimas, Antigone S.] Biomed Sci Res Ctr, Athens, Greece.
[Lagou, Vasiliki; Maegi, Reedik; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Barker, Adam; Wareham, Nicholas J.; Langenberg, Claudia] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England.
[Knowles, Joshua W.; Abbasi, Fahim A.; Assimes, Themistocles L.; Quertemous, Thomas] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Knowles, Joshua W.; Abbasi, Fahim A.; Assimes, Themistocles L.; Quertemous, Thomas] Stanford Univ, Sch Med, Cardiovasc Inst, Stanford, CA 94305 USA.
[Maegi, Reedik] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada.
[Hivert, Marie-France; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Benazzo, Andrea] Univ Ferrara, Dept Biol & Evolut, I-44100 Ferrara, Italy.
[Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA.
[Jackson, Anne U.; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Jackson, Anne U.; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Song, Ci; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden.
[Song, Ci] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Fischer-Rosinsky, Antje; Pfeiffer, Andreas F. H.; Spranger, Joachim] Charite, Dept Endocrinol & Metab, D-13353 Berlin, Germany.
[Boesgaard, Trine Wellov] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
[Grarup, Niels; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
[Hao, Ke] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY USA.
[Yang, Xia] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA USA.
[Lecoeur, Cecile; Cauchi, Stephane; Froguel, Philippe; Meyre, David] Univ Lille 2, Inst Pasteur, Inst Biol, CNRS,UMR8199, Lille, France.
[Barroso, Ines; Bumpstead, Suzannah; Payne, Felicity] Wellcome Trust Sanger Inst, Hinxton, England.
[Barroso, Ines] Univ Cambridge, Metab Res Labs, Cambridge, England.
[Barroso, Ines] Addenbrookes Hosp, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Inst Metab Sci, Cambridge, England.
[Bonnycastle, Lori L.; Chines, Peter S.; Erdos, Michael R.; Morken, Mario A.; Narisu, Narisu; Swift, Amy J.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA.
[Boettcher, Yvonne; Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Med Ctr, IFB AdiposityDis, D-04109 Leipzig, Germany.
[Graessler, Jurgen; Bornstein, Stefan R.; Schwarz, Peter E. H.] Univ Dresden, Div Prevent & Care Diabet, Dept Med 3, Dresden, Germany.
[Kovacs, Peter] Interdisciplinary Ctr Clin Res Leipzig, Leipzig, Germany.
[Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, D-04109 Leipzig, Germany.
[Froguel, Philippe; Prokopenko, Inga] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, London, England.
[Meyre, David] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada.
[Haering, Hans-Ulrich] Univ Tubingen, Dept Internal Med, Div Endocrinol Diabetol Vasc Med Nephrol & Clin C, Tubingen, Germany.
[Smith, Ulf] Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Lundberg Lab Diabet Res,Ctr Excellence Metab & Ca, Gothenburg, Sweden.
[Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
[Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.
[Tuomilehto, Jaakko] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia.
[Lind, Lars] Uppsala Univ, Akad Sjukhuset, Dept Med Sci, Uppsala, Sweden.
[Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
[Pedersen, Oluf] Hagedorn Res Inst, Copenhagen, Denmark.
[Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Inst Biomed Sci, Copenhagen, Denmark.
[Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark.
[Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Pfeiffer, Andreas F. H.] German Inst Human Nutr, Dept Clin Nutr, Nuthetal, Germany.
[Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[McCarthy, Mark I.] Churchill Hosp, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford OX3 7LJ, England.
RP Prokopenko, I (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
EM rwatanab@usc.edu; jcflorez@partners.org; erik.ingelsson@medsci.uu.se;
mark.mccarthy@drl.ox.ac.uk; i.prokopenko@imperial.ac.uk
RI Grarup, Niels/K-2807-2015; Prokopenko, Inga/H-3241-2014; Schwarz,
Peter/B-5127-2013;
OI Grarup, Niels/0000-0001-5526-1070; Prokopenko, Inga/0000-0003-1624-7457;
Schwarz, Peter/0000-0001-6317-7880; Magi, Reedik/0000-0002-2964-6011;
Song, Ci/0000-0002-0947-9068; Rybin, Denis/0000-0002-3657-4829; Assimes,
Themistocles/0000-0003-2349-0009; Payne, Felicity/0000-0003-4228-581X
FU European Community [HEALTH-F4-2007-201413, LSHM-CT-2004-512013];
Wellcome Trust [WT098051, 098381]; Cambridge Biomedical Research Centre
of the U.K. National Institute for Health Research; Medical Research
Council Centre for Obesity and Related Metabolic Diseases; National
Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]; Affymetrix Inc. [N02-HL-6-4278]; Robert Dawson Evans
Endowment of the Department of Medicine at Boston University School of
Medicine; Boston Medical Center; National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) [R01 DK-078616]; NIDDK [K24
DK-080140]; Doris Duke Charitable Foundation Clinical Scientist
Development Award; NIH [DK-069922, U54 DA021519, DK-062370, DK-072193,
RR01066]; National Human Genome Research Institute [1 Z01 HG000024];
Agence Nationale de la Recherche; Conseil Regional Nord-Pas de
Calais/Fonds europeen de developpement economique et regional; Academy
of Finland [124243]; Clinical Research Group [KFO218/1]; Deutsche
Forschungsgemeinschaft (DFG) [SP716/2-1]; German Bundesministerium fur
Bildung und Forschung (BMBF); Mallinckrodt General Clinical Research
Program, National Center for Research Resources; Swedish Research
Council; Swedish Heart-Lung Foundation; Swedish Foundation for Strategic
Research; Royal Swedish Academy of Science; Lundbeck Foundation Centre
of Applied Medical Genomics for Personalized Disease Prediction,
Prevention; Care; Danish Diabetes Association; Danish Research Council;
European Union [QLG1-CT-2001-01252]; AstraZeneca; German Research
Council [SF8-1052]; German Diabetes Association; Diabetes Hi Ifs;
Forschungsfonds Deutschland; Boehringer Ingelheim Foundation; BMBF [FKZ:
01E01001]; European Commission under the Marie Curie Intra-European
Fellowship; European Foundation; National Center for Research Resources,
NIH [2 M01 RR000070]; U.S. Public Health Service; American Heart
Association Fellow [10FTF3360005]
FX The major funding for this meta-analysis was provided through the
Seventh Framework Programme of the European Community (FP7/2007-2013),
the ENGAGE project, and grant agreement HEALTH-F4-2007-201413. As part
of the Ely Study, I.B. was supported by Wellcome Trust grant WT098051,
the Cambridge Biomedical Research Centre of the U.K. National Institute
for Health Research, and the Medical Research Council Centre for Obesity
and Related Metabolic Diseases. The EUGENE2 Study was supported by grant
LSHM-CT-2004-512013 from the European Community FP6 EUGENE2. The
Framingham Heart Study was conducted in part using data and resources
from the Framingham Heart Study of the National Heart, Lung, and Blood
Institute of the National Institutes of Health (NIH) and Boston
University School of Medicine. The analyses reflect intellectual input
and resource development from the Framingham Heart Study investigators
participating in the SNP Health Association Resource project. This work
was partially supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (contract no. N01-HC-25195) and its
contract with Affymetrix Inc. for genotyping services (contract no.
N02-HL-6-4278). A portion of this research utilized the Linux Cluster
for Genetic Analysis (LinGA-II), which is funded by the Robert Dawson
Evans Endowment of the Department of Medicine at Boston University
School of Medicine and Boston Medical Center. The Framingham Heart Study
was also supported by National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) grant R01 DK-078616 to J.B.M., J.D., and J.C.F.;
NIDDK grant K24 DK-080140 to J.B.M.; and a Doris Duke Charitable
Foundation Clinical Scientist Development Award to J.C.F. Support for
the Finland-United States Investigation of NIDDM Genetics was provided
by NIH grants DK-069922 (to R.M.W.), U54 DA021519 (to R.M.W.), DK-062370
(to M.B.), and DK-072193 (to K.L.M.). Additional support comes from the
National Human Genome Research Institute intramural project number 1 Z01
HG000024 (to F.S.C.). The Metabolisches Syndrom Berlin Potsdam
(MESYBEPO) Study was supported by grants from Agence Nationale de la
Recherche and Conseil Regional Nord-Pas de Calais/Fonds europeen de
developpement economique et regional. Support for the Metabolic Syndrome
in Men Study was provided by grant 124243 from the Academy of Finland.
In the MESYBEPO Study, J.S. was supported by Clinical Research Group
grant KFO218/1, Heisenberg Professorship SP716/2-1 of the Deutsche
Forschungsgemeinschaft (DFG), and a research group on molecular
nutrition of the German Bundesministerium fur Bildung und Forschung
(BMBF). The Partners/Roche Cohort was supported by the Mallinckrodt
General Clinical Research Program, National Center for Research
Resources, and NIH grant RR01066. In the Prospective Investigation of
the Vasculature in Uppsala Seniors and the Uppsala Longitudinal Study of
Adult Men, the SNP Technology Platform is supported by Uppsala
University, Uppsala University Hospital, and the Swedish Research
Council for Infrastructures. El. was supported by grants from the
Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish
Foundation for Strategic Research, and the Royal Swedish Academy of
Science. The QTL families and UNG92 Study is supported by the Lundbeck
Foundation Centre of Applied Medical Genomics for Personalized Disease
Prediction, Prevention, and Care, The Danish Diabetes Association, and
The Danish Research Council.; The Relationship between Insulin
Sensitivity and Cardiovascular Disease Study is supported by European
Union grant QLG1-CT-2001-01252 and AstraZeneca. The Sorbs Study was
supported by grants from the German Research Council (SF8-1052 "Obesity
mechanisms") and the German Diabetes Association and the Diabetes Hi Ifs
und Forschungsfonds Deutschland. P.K. is funded by the Boehringer
Ingelheim Foundation. The Integrated Research and Treatment Center
Adiposity Diseases is supported by BMBF grant FKZ: 01E01001. I.P. and
V.L. were partially funded through the Seventh Framework Programme of
the European Community (grant FP7/2007-2013) and the ENGAGE project
grant agreement HEALTH-F4-2007-201413. R.M. is funded by the European
Commission under the Marie Curie Intra-European Fellowship and a
European Foundation for the Study of Diabetes New Horizons grant. M.I.M.
is supported by Wellcome Trust grant 098381. Sample collection for the
Stanford IST Cohort was carried out in part in the Clinical and
Translational Research Unit, Stanford University, with funds provided by
the National Center for Research Resources, NIH grant 2 M01 RR000070,
and the U.S. Public Health Service. J.W.K. is supported by American
Heart Association Fellow to Faculty Transition award 10FTF3360005.
NR 44
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U2 32
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD JUN
PY 2014
VL 63
IS 6
BP 2158
EP 2171
DI 10.2337/db13-0949
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AI1VS
UT WOS:000336643900039
PM 24296717
ER
PT J
AU Vassy, JL
Hivert, MF
Porneala, B
Dauriz, M
Florez, JC
Dupuis, J
Siscovick, DS
Fornage, M
Rasmussen-Torvik, LJ
Bouchard, C
Meigs, JB
AF Vassy, Jason L.
Hivert, Marie-France
Porneala, Bianca
Dauriz, Marco
Florez, Jose C.
Dupuis, Josee
Siscovick, David S.
Fornage, Myriam
Rasmussen-Torvik, Laura J.
Bouchard, Claude
Meigs, James B.
TI Polygenic Type 2 Diabetes Prediction at the Limit of Common Variant
Detection
SO DIABETES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISMS;
DENSITY-LIPOPROTEIN-CHOLESTEROL; LIFE-STYLE INTERVENTION; RISK-FACTORS;
AFRICAN-AMERICANS; GLUCOSE-TOLERANCE; RECLASSIFICATION; POPULATION;
MELLITUS
AB Genome-wide association studies (GWAS) may have reached their limit of detecting common type 2 diabetes (T2D)-associated genetic variation. We evaluated the performance of current polygenic T2D prediction. Using data from the Framingham Offspring (FOS) and the Coronary Artery Risk Development in Young Adults (CARDIA) studies, we tested three hypotheses: 1) a 62-locus genotype risk score (GRS(t)) improves T2D prediction compared with previous less inclusive GRS(t); 2) separate GRS for beta-cell (GRS(beta)) and insulin resistance (GRS(IR)) independently predict T2D; and 3) the relationships between T2D and GRS(t), GRS(beta), or GRS(IR) do not differ between blacks and whites. Among 1,650 young white adults in CARDIA, 820 young black adults in CARDIA, and 3,471 white middle-aged adults in FOS, cumulative T2D incidence was 5.9%, 14.4%, and 12.9%, respectively, over 25 years. The 62-locus GRS(t) was significantly associated with incident T2D in all three groups. In FOS but not CARDIA, the 62-locus GRSt improved the model C statistic (0.698 and 0.726 for models without and with GRS(t), respectively; P < 0.001) but did not materially improve risk reclassification in either study. Results were similar among blacks compared with whites. The GRS(beta) but not GRS(IR) predicted incident T2D among FOS and CARDIA whites. At the end of the era of common variant discovery for T2D, polygenic scores can predict T2D in whites and blacks but do not outperform clinical models. Further optimization of polygenic prediction may require novel analytic methods, including less common as well as functional variants.
C1 [Vassy, Jason L.; Hivert, Marie-France; Dauriz, Marco; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA.
[Vassy, Jason L.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA USA.
[Vassy, Jason L.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA.
[Hivert, Marie-France] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA.
[Hivert, Marie-France] Univ Sherbrooke, Dept Med, Div Endocrinol, Sherbrooke, PQ J1K 2R1, Canada.
[Porneala, Bianca; Dauriz, Marco; Meigs, James B.] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA.
[Dauriz, Marco] Univ Verona Med Sch & Hosp Trust Verona, Div Endocrinol & Metab Dis, Dept Med, Verona, Italy.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Dupuis, Josee] Boston Univ Sch Publ Hlth, Depat Biostat, Boston, MA USA.
[Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Rasmussen-Torvik, Laura J.] Northwestern Univ Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA.
[Bouchard, Claude] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA USA.
RP Meigs, JB (reprint author), Harvard Univ, Sch Med, Boston, MA USA.
EM jmeigs@partners.org
RI Bouchard, Claude/A-7637-2009; Dauriz, Marco/S-5843-2016
OI Dauriz, Marco/0000-0002-5542-5941
FU National Institutes of Health [R01-DK-078616, K24-DK-080140,
U01-HG-006500, L30-DK089597]; National Heart, Lung, and Blood Institute
(NHLBI); University of Alabama at Birmingham [HHSN268201300025C,
HHSN268201300026C]; Northwestern University [HHSN268201300027C];
University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research
Institute [HHSN268201300029C]; Johns Hopkins University School of
Medicine [HHSN268200900041C]; Intramural Research Program of the
National Institute on Aging; NHLBI [N01-HC-25195]; Affymetrix, Inc.
[N02-HL-6-4278]
FX This work was supported by National Institutes of Health grants
(R01-DK-078616 and K24-DK-080140 to J.B.M. and U01-HG-006500 and
L30-DK089597 to J.L.V.). The CARDIA Study is conducted and supported by
the National Heart, Lung, and Blood Institute (NHLBI) in collaboration
with the University of Alabama at Birmingham (HHSN268201300025C and
HHSN268201300026C), Northwestern University (HHSN268201300027C),
University of Minnesota (HHSN268201300028C), Kaiser Foundation Research
Institute (HHSN268201300029C), and Johns Hopkins University School of
Medicine (HHSN268200900041C). CARDIA is also partially supported by the
Intramural Research Program of the National Institute on Aging. This
manuscript was reviewed by CARDIA personnel for scientific content. The
Framingham Heart Study was supported by the NHLBI (contract number
N01-HC-25195) and its contract with Affymetrix, Inc., for genotyping
services (contract number N02-HL-6-4278). A portion of this research was
conducted using the Linux Clusters for Genetic Analysis (LinGA)
computing resources at the Boston University Medical Campus.
NR 44
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U1 0
U2 18
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
EI 1939-327X
J9 DIABETES
JI Diabetes
PD JUN
PY 2014
VL 63
IS 6
BP 2172
EP 2182
DI 10.2337/db13-1663
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AI1VS
UT WOS:000336643900040
PM 24520119
ER
PT J
AU Kuo, I
Golin, CE
Wang, J
Haley, DF
Hughes, J
Mannheimer, S
Justman, J
Rompalo, A
Frew, PM
Adimora, AA
Soto-Torres, L
Hodder, S
AF Kuo, Irene
Golin, Carol E.
Wang, Jing
Haley, Danielle F.
Hughes, James
Mannheimer, Sharon
Justman, Jessica
Rompalo, Anne
Frew, Paula M.
Adimora, Adaora A.
Soto-Torres, Lydia
Hodder, Sally
CA HPTN 064 Study Team
TI Substance use patterns and factors associated with changes over time in
a cohort of heterosexual women at risk for HIV acquisition in the United
States
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Women; Substance use; Opiate use; Cocaine use; Binge drinking; HIV
ID NATIONAL EPIDEMIOLOGIC SURVEY; INJECTION-DRUG USERS; AFRICAN-AMERICAN;
CRACK COCAINE; YOUNG-ADULTS; CONCURRENT PARTNERSHIPS; SEXUAL
PARTNERSHIPS; INTERAGENCY HIV; USE BEHAVIORS; CONDOM USE
AB Background: Substance use is associated with HIV sexual risk behaviors, yet few studies have examined substance use patterns longitudinally. We evaluated the types and frequency of substances used over a six-month period among U.S. women at risk for HIV acquisition.
Methods: Women reporting unprotected sex with a man in the previous six months and at least one other personal or partner HIV risk characteristic enrolled in a multisite cohort study and completed interviews about substance use at study visits. Prevalence and frequency of substance use at the baseline and six-month visits were compared and correlates of decreased substance use at the six-month visit were assessed.
Results: Of 2099 women enrolled, 1882 had substance use data at baseline and six-months. Of these, 76.1% reported using at least one drug or binge drinking in the previous six months; 37.5% were frequent and 38.6% non-frequent substance users. Binge drinking was most frequently reported (63.3%), followed by cocaine (25.0%) and opioids (16.5%). Fifty-five percent of opiate users and 30% of cocaine users reported daily/almost daily use. At the six-month visit, 40.5% reported a decrease in frequency of use. Adjusting for income and type of drug used, poly-substance users were less likely to decrease frequency of use compared to those who only used one substance.
Conclusion: A substantial decrease in frequency of substance use over time was observed in this cohort. Poly-substance users were less likely to reduce frequency of use over time, suggesting that specific substance use interventions targeting these users are warranted. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Kuo, Irene] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC 20052 USA.
[Golin, Carol E.; Adimora, Adaora A.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Golin, Carol E.; Adimora, Adaora A.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Wang, Jing; Hughes, James] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Haley, Danielle F.] FHI 360, Durham, NC USA.
[Haley, Danielle F.; Frew, Paula M.] Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA USA.
[Hughes, James] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Mannheimer, Sharon] Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, New York, NY 10032 USA.
[Mannheimer, Sharon; Justman, Jessica] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Rompalo, Anne] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Frew, Paula M.] Emory Univ, Dept Med, Div Infect Dis, Atlanta, GA 30322 USA.
[Soto-Torres, Lydia] NIAID, NIH, Bethesda, MD 20892 USA.
[Hodder, Sally] Rutgers, New Jersey Med Sch, Newark, NJ USA.
RP Kuo, I (reprint author), George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, 950 New Hampshire Ave NW,5th Floor, Washington, DC 20052 USA.
EM ikuo@gwu.edu
OI Frew, Paula/0000-0002-3078-9124
FU National Institute of Allergy and Infectious Diseases; National
Institute on Drug Abuse; National Institute of Mental Health [UM1
AI068619, U01-AI068613, UM1-AI068613]; Centers for Innovative Research
to Control AIDS, Mailman School of Public Health, Columbia University
[5U1AI069466]; University of North Carolina Clinical Trials Unit
[AI069423]; University of North Carolina Clinical Trials Research Center
of the Clinical and Translational Science Award [RR 025747]; University
of North Carolina Center for AIDS Research [AI050410]; Emory University
HIV/AIDS Clinical Trials Unit [5UO1AI069418]; Center for AIDS Research
[P30 AI050409]; Clinical and Translational Science Award [UL1 RR025008];
Terry Beirn Community Programs for Clinical Research on AIDS Clinical
Trials Unit [5UM1 AI069503-07]; Johns Hopkins Adult AIDS Clinical Trial
Unit [AI069465]; Johns Hopkins Clinical and Translational Science Award
[UL1 RR 25005]
FX Nothing declared. Grant support provided by the National Institute of
Allergy and Infectious Diseases, National Institute on Drug Abuse, and
National Institute of Mental Health (cooperative agreement no. UM1
AI068619, U01-AI068613, and UM1-AI068613); Centers for Innovative
Research to Control AIDS, Mailman School of Public Health, Columbia
University (5U1AI069466); University of North Carolina Clinical Trials
Unit (AI069423); University of North Carolina Clinical Trials Research
Center of the Clinical and Translational Science Award (RR 025747);
University of North Carolina Center for AIDS Research (AI050410); Emory
University HIV/AIDS Clinical Trials Unit (5UO1AI069418), Center for AIDS
Research (P30 AI050409), and Clinical and Translational Science Award
(UL1 RR025008); The Terry Beirn Community Programs for Clinical Research
on AIDS Clinical Trials Unit (5UM1 AI069503-07) and; The Johns Hopkins
Adult AIDS Clinical Trial Unit (AI069465) and The Johns Hopkins Clinical
and Translational Science Award (UL1 RR 25005). The views expressed
herein are solely the responsibility of the authors and do not
necessarily represent the official views of the National Institute of
Allergy and Infectious Diseases, the National Institute of Mental
Health, the National Institutes of Health, the HPTN, or its funders.
NR 53
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U2 12
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD JUN 1
PY 2014
VL 139
BP 93
EP 99
DI 10.1016/j.drugalcdep.2014.03.007
PG 7
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA AI2SI
UT WOS:000336708000013
PM 24698079
ER
PT J
AU Keyes, KM
Shmulewitz, D
Greenstein, E
McLaughlin, KA
Wall, M
Aharonovich, E
Weizman, A
Frisch, A
Spivak, B
Grant, BF
Hasin, D
AF Keyes, Katherine M.
Shmulewitz, Dvora
Greenstein, Eliana
McLaughlin, Katie A.
Wall, Melanie
Aharonovich, Efrat
Weizman, Abraham
Frisch, Amos
Spivak, Baruch
Grant, Bridget F.
Hasin, Deborah
TI Exposure to the Lebanon War of 2006 and effects on alcohol use
disorders: The moderating role of childhood maltreatment (vol 134, pg
296, 2014)
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Correction
C1 [Keyes, Katherine M.; Hasin, Deborah] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Shmulewitz, Dvora; Greenstein, Eliana; Aharonovich, Efrat; Hasin, Deborah] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Shmulewitz, Dvora; Greenstein, Eliana; Aharonovich, Efrat; Hasin, Deborah] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[McLaughlin, Katie A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Gen Pediat, Boston, MA 02115 USA.
[Wall, Melanie] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA.
[Weizman, Abraham; Frisch, Amos; Spivak, Baruch] Tel Aviv Univ, Sackler Fac Med, Felsenstein Med Res Ctr, IL-69978 Tel Aviv, Israel.
[Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD USA.
RP Keyes, KM (reprint author), Columbia Univ, Dept Epidemiol, 722 West 168th St,Suite 503, New York, NY 10032 USA.
EM kmk2104@columbia.edu
NR 1
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD JUN 1
PY 2014
VL 139
BP 182
EP 182
DI 10.1016/j.drugalcdep.2014.03.019
PG 1
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA AI2SI
UT WOS:000336708000027
ER
PT J
AU Lowe, JR
Duncan, AF
Bann, CM
Fuller, J
Hintz, SR
Das, A
Higgins, RD
Watterberg, KL
AF Lowe, Jean R.
Duncan, Andrea Freeman
Bann, Carla M.
Fuller, Janell
Hintz, Susan R.
Das, Abhik
Higgins, Rosemary D.
Watterberg, Kristi L.
CA Eunice Kennedy Shriver Natl Inst C
TI Early working memory as a racially and ethnically neutral measure of
outcome in extremely preterm children at 18-22 months (vol 89, pg 1055,
2013)
SO EARLY HUMAN DEVELOPMENT
LA English
DT Correction
C1 [Lowe, Jean R.; Duncan, Andrea Freeman; Fuller, Janell; Watterberg, Kristi L.] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
[Bann, Carla M.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
[Hintz, Susan R.] Stanford Univ, Palo Alto, CA 94304 USA.
[Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Lowe, JR (reprint author), Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
EM jrlowe@unm.edu
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-3782
EI 1872-6232
J9 EARLY HUM DEV
JI Early Hum. Dev.
PD JUN
PY 2014
VL 90
IS 6
BP 319
EP 319
DI 10.1016/j.earlhumdev.2014.03.004
PG 1
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA AI2UW
UT WOS:000336714600009
ER
PT J
AU Parra, GI
Green, KY
AF Parra, Gabriel I.
Green, Kim Y.
TI Sequential Gastroenteritis Episodes Caused by 2 Norovirus Genotypes
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
AB We investigated sequential episodes of acute norovirus gastroenteritis in a young child within an 11-month period. The infections were caused by 2 distinct genotypes (GII.4 and GII.6). Failure to achieve cross-protective immunity was linked to absence of an enduring and cross-reactive mucosal immune response, a critical consideration for vaccine design.
C1 [Parra, Gabriel I.; Green, Kim Y.] NIH, Bethesda, MD 20892 USA.
RP Parra, GI (reprint author), NIAID, Infect Dis Lab, Caliciviruses Sect, NIH, Room 6318,Bldg 50,50 South Dr, Bethesda, MD 20892 USA.
EM parrag@niaid.nih.gov; kgreen@niaid.nih.gov
OI Parra, Gabriel/0000-0002-1102-4740
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This research was funded by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 15
TC 12
Z9 12
U1 0
U2 11
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
EI 1080-6059
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD JUN
PY 2014
VL 20
IS 6
BP 1016
EP 1018
DI 10.3201/eid2006.131627
PG 3
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AI0SZ
UT WOS:000336561600014
PM 24857806
ER
PT J
AU Abrams, JA
Appelman, HD
Beer, DG
Berry, LD
Chak, A
Falk, GW
Fitzgerald, RC
Ginsberg, GG
Grady, WM
Joshi, BP
Lynch, JP
Markowitz, S
Richmond, ES
Rustgi, AK
Seibel, EJ
Shaheen, NJ
Shyr, Y
Umar, A
Wang, KK
Wang, TC
Wang, TD
Yassin, R
AF Abrams, Julian A.
Appelman, Henry D.
Beer, David G.
Berry, Lynne D.
Chak, Amitabh
Falk, Gary W.
Fitzgerald, Rebecca C.
Ginsberg, Gregory G.
Grady, William M.
Joshi, Bishnu P.
Lynch, John P.
Markowitz, Sanford
Richmond, Ellen S.
Rustgi, Anil K.
Seibel, Eric J.
Shaheen, Nicholas J.
Shyr, Yu
Umar, Asad
Wang, Kenneth K.
Wang, Timothy C.
Wang, Thomas D.
Yassin, Rihab
TI Barrett's Esophagus Translational Research Network (BETRNet): The
Pivotal Role of Multi-institutional Collaboration in Esophageal
Adenocarcinoma Research
SO GASTROENTEROLOGY
LA English
DT Editorial Material
C1 [Abrams, Julian A.; Wang, Timothy C.] Columbia Univ, Med Ctr, Div Digest & Liver Dis, New York, NY 10027 USA.
[Appelman, Henry D.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Beer, David G.] Univ Michigan, Thorac Surg Sect, Ann Arbor, MI 48109 USA.
[Berry, Lynne D.] Vanderbilt Univ, Sch Med, Ctr Quantitat Sci, Nashville, TN 37212 USA.
[Chak, Amitabh] Case Western Reserve Univ, Div Gastroenterol, Cleveland, OH 44106 USA.
[Falk, Gary W.; Ginsberg, Gregory G.; Lynch, John P.; Rustgi, Anil K.] Univ Penn, Div Gastroenterol, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Fitzgerald, Rebecca C.] Hutchison MRC Res Ctr, MRC Canc Unit, Cambridge, England.
[Grady, William M.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Sch Med, Seattle, WA 98195 USA.
[Grady, William M.] Univ Washington, Sch Med, Div Gastroenterol, Seattle, WA 98195 USA.
[Joshi, Bishnu P.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Markowitz, Sanford] Case Western Reserve Univ, Div Hematol Oncol, Cleveland, OH 44106 USA.
[Markowitz, Sanford] Univ Hosp Cleveland, Cleveland, OH 44106 USA.
[Richmond, Ellen S.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Seibel, Eric J.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA.
[Shaheen, Nicholas J.] Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA.
[Shyr, Yu] Vanderbilt Univ, Sch Med, Ctr Quantitat Sci, Nashville, TN 37212 USA.
[Umar, Asad] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Wang, Kenneth K.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Wang, Thomas D.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Yassin, Rihab] NCI, Div Canc Biol, Bethesda, MD 20892 USA.
RP Abrams, JA (reprint author), Columbia Univ, Med Ctr, Div Digest & Liver Dis, New York, NY 10027 USA.
OI Falk, Gary/0000-0002-7143-1436
FU Department of Health [NIHR-RP-02-12-011]; Medical Research Council
[MC_UU_12022/2, MC_U105365007]; NCATS NIH HHS [U18 TR000536]; NCI NIH
HHS [U54 CA163004, U01 CA152756, U54 CA163060, U01CA182940, P50
CA095103, U54 CA163059, U01CA152756, U01 CA182940, U01 CA163056]; NIH
HHS [K26 OD012097]
NR 5
TC 2
Z9 2
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 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2014
VL 146
IS 7
BP 1586
EP 1590
DI 10.1053/j.gastro.2014.04.014
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH9YD
UT WOS:000336500900007
PM 24768332
ER
PT J
AU Erlinger, S
Arias, IM
Dhumeaux, D
AF Erlinger, Serge
Arias, Irwin M.
Dhumeaux, Daniel
TI Inherited Disorders of Bilirubin Transport and Conjugation: New Insights
Into Molecular Mechanisms and Consequences
SO GASTROENTEROLOGY
LA English
DT Article
DE Crigler-Najjar Syndrome; Hepatic Storage Disease; Glucuronosyl
Transferase; Bile Secretion; Kernicterus
ID CRIGLER-NAJJAR-SYNDROME; DUBIN-JOHNSON-SYNDROME; ORGANIC-ANION
TRANSPORT; SYNDROME TYPE-I; GLUCURONOSYLTRANSFERASE 1A1 UGT1A1;
ORTHOTOPIC LIVER-TRANSPLANTATION; RESISTANCE-ASSOCIATED PROTEIN-2;
CANALICULAR MEMBRANE-VESICLES; SPORADIC COLORECTAL-CANCER; MUTANT TR
RATS
AB Inherited disorders of bilirubin metabolism might reduce bilirubin uptake by hepatocytes, bilirubin conjugation, or secretion of bilirubin into bile. Reductions in uptake could increase levels of unconjugated or conjugated bilirubin (Rotor syndrome). Defects in bilirubin conjugation could increase levels of unconjugated bilirubin; the effects can be benign and frequent (Gilbert syndrome) or rare but severe, increasing the risk of bilirubin encephalopathy (Crigler-Najjar syndrome). Impairment of bilirubin secretion leads to accumulation of conjugated bilirubin (Dubin-Johnson syndrome). We review the genetic causes and pathophysiology of disorders of bilirubin transport and conjugation as well as clinical and therapeutic aspects. We also discuss the possible mechanisms by which hyperbilirubinemia protects against cardiovascular disease and the metabolic syndrome and the effects of specific genetic variants on drug metabolism and cancer development.
C1 [Erlinger, Serge] Univ Paris 07, Paris, France.
[Arias, Irwin M.] NIH, Bethesda, MD 20892 USA.
[Dhumeaux, Daniel] Univ Paris Est, Hop Henri Mondor, Creteil, France.
RP Erlinger, S (reprint author), 1422 Route Mauvares, F-13840 Rognes, France.
EM serge.erlinger@gmail.com
NR 135
TC 22
Z9 23
U1 5
U2 25
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2014
VL 146
IS 7
BP 1625
EP 1638
DI 10.1053/j.gastro.2014.03.047
PG 14
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH9YD
UT WOS:000336500900018
PM 24704527
ER
PT J
AU Keenan, BP
Saenger, Y
Kafrouni, MI
Leubner, A
Lauer, P
Maitra, A
Rucki, AA
Gunderson, AJ
Coussens, LM
Brockstedt, DG
Dubensky, TW
Hassan, R
Armstrong, TD
Jaffee, EM
AF Keenan, Bridget P.
Saenger, Yvonne
Kafrouni, Michel I.
Leubner, Ashley
Lauer, Peter
Maitra, Anirban
Rucki, Agnieszka A.
Gunderson, Andrew J.
Coussens, Lisa M.
Brockstedt, Dirk G.
Dubensky, Thomas W., Jr.
Hassan, Raffit
Armstrong, Todd D.
Jaffee, Elizabeth M.
TI A Listeria Vaccine and Depletion of T-Regulatory Cells Activate Immunity
Against Early Stage Pancreatic Intraepithelial Neoplasms and Prolong
Survival of Mice
SO GASTROENTEROLOGY
LA English
DT Article
DE Pancreatic Cancer; Listeria Vaccine; Tumor Microenvironment; Immunity
ID DUCTAL ADENOCARCINOMA; ONCOGENIC KRAS; ADOPTIVE TRANSFER;
SUPPRESSOR-CELLS; MOUSE MODEL; TC17 CELLS; CANCER; IMMUNOTHERAPY;
MONOCYTOGENES; TUMORS
AB BACKGROUND & AIMS: Premalignant lesions and early stage tumors contain immunosuppressive microenvironments that create barriers for cancer vaccines. Kras(G12D/+);Trp53(R172H/+); Pdx-1-Cre (KPC) mice, which express an activated form of Kras in pancreatic tissues, develop pancreatic intraepithelial neoplasms (PanIN) that progress to pancreatic ductal adenocarcinoma (PDA). We used these mice to study immune suppression in PDA. METHODS: We immunized KPC and Kras(G12D/+); Pdx-1-Cre mice with attenuated intracellular Listeria monocytogenes (which induces CD4(+) and CD8(+) T-cell immunity) engineered to express Kras(G12D) (LM-Kras). The vaccine was given alone or in sequence with an anti-CD25 antibody (PC61) and cyclophosphamide to deplete T-regulatory (Treg) cells. Survival times were measured; pancreatic and spleen tissues were collected and analyzed by histologic, flow cytometry, and immunohistochemical analyses. RESULTS: Interferon gamma-mediated, CD8(+) T-cell responses were observed in KPC and Kras(G12D/+); Pdx-1-Cre mice given LM-Kras, but not in unvaccinated mice. Administration of LM-Kras to KPC mice 4-6 weeks old (with early stage PanINs), depleted of Treg cells, significantly prolonged survival and reduced PanIN progression (median survival, 265 days), compared with unvaccinated mice (median survival, 150 days; P = .002), mice given only LM-Kras (median survival, 150 days; P = .050), and unvaccinated mice depleted of Treg cells (median survival, 170 days; P = .048). In 8- to 12-week-old mice (with late-stage PanINs), LM-Kras, alone or in combination with Treg cell depletion, did not increase survival time or slow PanIN progression. The combination of LM-Kras and Treg cell depletion reduced numbers of Foxp3(+)CD4(+) T cells in pancreatic lymph nodes, increased numbers of CD4(+) T cells that secrete interleukin 17 and interferon gamma, and caused CD11b(+)Gr1(+) cells in the pancreas to acquire an immunostimulatory phenotype. CONCLUSIONS: Immunization of KPC mice with Listeria monocytogenes engineered to express Kras(G12D), along with depletion of Treg cells, reduces progression of early stage, but not late-stage, PanINs. This approach increases infiltration of the lesion with inflammatory cells. It might be possible to design immunotherapies against premalignant pancreatic lesions to slow or prevent progression to PDA.
C1 [Keenan, Bridget P.; Kafrouni, Michel I.; Leubner, Ashley; Rucki, Agnieszka A.; Armstrong, Todd D.; Jaffee, Elizabeth M.] Johns Hopkins, Sidney Kimmel Canc Ctr, Baltimore, MD 21231 USA.
[Keenan, Bridget P.; Kafrouni, Michel I.; Leubner, Ashley; Rucki, Agnieszka A.; Armstrong, Todd D.; Jaffee, Elizabeth M.] Johns Hopkins, Skip Viragh Ctr Clin Pancreat Canc Res, Baltimore, MD 21231 USA.
[Keenan, Bridget P.; Kafrouni, Michel I.; Leubner, Ashley; Rucki, Agnieszka A.; Armstrong, Todd D.; Jaffee, Elizabeth M.] Johns Hopkins, Sol Goldman Pancreat Canc Ctr, Baltimore, MD 21231 USA.
[Keenan, Bridget P.] Johns Hopkins Univ, Sch Med, Grad Program Immunol, Baltimore, MD USA.
[Saenger, Yvonne] Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Oncol, New York, NY USA.
[Saenger, Yvonne] Mt Sinai Sch Med, Dept Dermatol, New York, NY USA.
[Lauer, Peter; Brockstedt, Dirk G.; Dubensky, Thomas W., Jr.] Aduro BioTech Inc, Berkeley, CA USA.
[Maitra, Anirban] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Maitra, Anirban] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA.
[Gunderson, Andrew J.; Coussens, Lisa M.] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Cell & Dev Biol, Portland, OR 97201 USA.
[Hassan, Raffit] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Jaffee, EM (reprint author), Johns Hopkins, Sidney Kimmel Canc Ctr, 1650 Orleans St, Baltimore, MD 21231 USA.
EM ejaffee@jhmi.edu
FU National Cancer Institute, National Institutes of Health [P50CA062924,
R01CA122081, U19CA113341]; National Institutes of Health, National
Cancer Institute, Center for Cancer Research
FX Supported by grants from the National Cancer Institute, National
Institutes of Health (P50CA062924, R01CA122081, and U19CA113341 to
E.M.J.), and supported in part by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 48
TC 25
Z9 26
U1 0
U2 15
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2014
VL 146
IS 7
BP 1784
EP +
DI 10.1053/j.gastro.2014.02.055
PG 17
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH9YD
UT WOS:000336500900032
PM 24607504
ER
PT J
AU Koerner, JF
Coleman, CN
Murrain-Hill, P
FitzGerald, DJ
Sullivan, JM
AF Koerner, John F.
Coleman, C. Norman
Murrain-Hill, Paula
FitzGerald, Denis J.
Sullivan, Julie M.
TI THE MEDICAL DECISION MODEL AND DECISION MAKER TOOLS FOR MANAGEMENT OF
RADIOLOGICAL AND NUCLEAR INCIDENTS
SO HEALTH PHYSICS
LA English
DT Article; Proceedings Paper
CT Conrad-Global Conference on Radiation Topics-Preparedness, Response,
Protection and Research
CY MAY 13-16, 2013
CL Munich, GERMANY
DE accidents; nuclear; accidents; power reactor; emergencies; radiological;
risk communication
AB Effective decision making during a rapidly evolving emergency such as a radiological or nuclear incident requires timely interim decisions and communications from onsite decision makers while further data processing, consultation, and review are ongoing by reachback experts. The authors have recently proposed a medical decision model for use during a radiological or nuclear disaster, which is similar in concept to that used in medical care, especially when delay in action can have disastrous effects. For decision makers to function most effectively during a complex response, they require access to onsite subject matter experts who can provide information, recommendations, and participate in public communication efforts. However, in the time before this expertise is available or during the planning phase, just-in-time tools are essential that provide critical overview of the subject matter written specifically for the decision makers. Recognizing the complexity of the science, risk assessment, and multitude of potential response assets that will be required after a nuclear incident, the Office of the Assistant Secretary for Preparedness and Response, in collaboration with other government and non-government experts, has prepared a practical guide for decision makers. This paper illustrates how the medical decision model process could facilitate onsite decision making that includes using the deliberative reachback process from science and policy experts and describes the tools now available to facilitate timely and effective incident management.
C1 [Koerner, John F.; Coleman, C. Norman; Murrain-Hill, Paula; FitzGerald, Denis J.; Sullivan, Julie M.] US Dept HHS, Off Assistant Secretary Preparedness & Response, Off Emergency Management, Washington, DC 20201 USA.
[Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Sullivan, Julie M.] AAAS Sci & Technol Policy, Washington, DC USA.
RP Koerner, JF (reprint author), US Dept HHS, Off Assistant Secretary Preparedness & Response, Off Emergency Management, Washington, DC 20201 USA.
EM john.koerner@hhs.gov
NR 7
TC 5
Z9 5
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD JUN
PY 2014
VL 106
IS 6
BP 645
EP 651
DI 10.1097/HP.0000000000000053
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA AH9YG
UT WOS:000336501300004
PM 24776895
ER
PT J
AU Macri, V
Mahida, SN
Zhang, ML
Sinner, MF
Dolmatova, EV
Tucker, NR
McLellan, M
Shea, MA
Milan, DJ
Lunetta, KL
Benjamin, EJ
Ellinor, PT
AF Macri, Vincenzo
Mahida, Saagar N.
Zhang, Michael L.
Sinner, Moritz F.
Dolmatova, Elena V.
Tucker, Nathan R.
McLellan, Micheal
Shea, Marisa A.
Milan, David J.
Lunetta, Kathryn L.
Benjamin, Emelia J.
Ellinor, Patrick T.
TI A novel trafficking-defective HCN4 mutation is associated with
early-onset atrial fibrillation
SO HEART RHYTHM
LA English
DT Article
DE HCN4; Mutation; Atrial fibrillation; Electrophysiology
ID FUNCTIONAL EXPRESSION; SINUS BRADYCARDIA; PACEMAKER CHANNEL; DOMAIN;
HAPLOINSUFFICIENCY; DYSFUNCTION; TERMINUS; GENES
AB BACKGROUND Atrial fibrillation (AF) is the most common arrhythmia, and a recent genome-wide association study identified the hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) as a novel AF susceptibility locus. HCN4 encodes for the cardiac pacemaker channel, and HCN4 mutations are associated with familial sinus bradycardia and AF.
OBJECTIVE The purpose of this study was to determine whether novel variants in the coding region of HCN4 contribute to the susceptibility for AF.
METHODS We sequenced the coding region of HCN4 for novel variants from 527 cases with early-onset AF from the Massachusetts General Hospital AF Study and 443 referents from the Framingham Heart Study. We used site-directed mutagenesis, cellular electrophysiology, immunocytochemistry, and confocal microscopy to functionally characterize novel variants.
RESULTS We found the frequency of novel coding HCN4 variants was 2-fold greater for individuals with AF (7 variants) compared to the referents (3 variants). We determined that of the 7 novel HCN4 variants in our AF cases, 1 (p.Pro257Ser, located in the amino-terminus adjacent to the first transmembrane spanning domain) did not traffic to cell membrane, whereas the remaining 6 were not functionally different from wild type. In addition, the 3 novel variants in our referents did not alter function compared to wild-type. Coexpression studies showed that the p.Pro257Ser mutant channel failed to colocalize with the wild-type HCN4 channel on the cell membrane.
CONCLUSION Our findings are consistent with HCN4 haploinsufficiency as the likely mechanism for early-onset AF in the p. Pro257Ser carrier.
C1 [Macri, Vincenzo; Mahida, Saagar N.; Zhang, Michael L.; Sinner, Moritz F.; Dolmatova, Elena V.; Tucker, Nathan R.; McLellan, Micheal; Milan, David J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
[Macri, Vincenzo; Mahida, Saagar N.; Dolmatova, Elena V.; Tucker, Nathan R.; Milan, David J.; Ellinor, Patrick T.] Harvard Univ, Sch Med, Boston, MA USA.
[Sinner, Moritz F.] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany.
[Sinner, Moritz F.; Lunetta, Kathryn L.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Sinner, Moritz F.; Lunetta, Kathryn L.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Shea, Marisa A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
RP Ellinor, PT (reprint author), Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA.
EM ellinor@mgh.harvard.edu
OI Benjamin, Emelia/0000-0003-4076-2336
FU National Institutes of Health [1RO1HL104156, 1K2411L105780,
1RO1HL092577]; Established Investigator Award from the American Heart
Association [13EIA14220013]; National Heart, Lung, and Blood Institute
[T32HL007208]; Heart Rhythm Society (The Max Schaldach Fellowship in
Cardiac Pacing and Electrophysiology)
FX Drs. Macri and Mahida contributed equally to this manuscript. The
current work was funded by National Institutes of Health Grants
1RO1HL104156 and 1K2411L105780 to Dr. Elinor and Grant 1RO1HL092577 to
Drs. Benjamin and Elinor. Dr. Ellinor is supported by an Established
Investigator Award from the American Heart Association (13EIA14220013).
Dr. Tucker was supported by award number T32HL007208 from the National
Heart, Lung, and Blood Institute. Dr. Macri is supported by the Heart
Rhythm Society (The Max Schaldach Fellowship in Cardiac Pacing and
Electrophysiology).
NR 25
TC 9
Z9 9
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
EI 1556-3871
J9 HEART RHYTHM
JI Heart Rhythm
PD JUN
PY 2014
VL 11
IS 6
BP 1055
EP 1062
DI 10.1016/j.hrthm.2014.03.002
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA AH8NU
UT WOS:000336395600021
PM 24607718
ER
PT J
AU Yudkin, D
Hayward, BE
Aladjem, MI
Kumari, D
Usdin, K
AF Yudkin, Dmitry
Hayward, Bruce E.
Aladjem, Mirit I.
Kumari, Daman
Usdin, Karen
TI Chromosome fragility and the abnormal replication of the FMR1 locus in
fragile X syndrome
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID DNA-REPLICATION; CGG-REPEAT; TRINUCLEOTIDE REPEATS; DELAYED REPLICATION;
MENTAL-RETARDATION; POLYMERASE-DELTA; CALF THYMUS; SITE; GENE; EXPANSION
AB Fragile X Syndrome (FXS) is a learning disability seen in individuals who have > 200 CGGaEuro cent CCG repeats in the 5' untranslated region of the X-linked FMR1 gene. Such alleles are associated with a fragile site, FRAXA, a gap or constriction in the chromosome that is coincident with the repeat and is induced by folate stress or thymidylate synthase inhibitors like fluorodeoxyuridine (FdU). The molecular basis of the chromosome fragility is unknown. Previous work has suggested that the stable intrastrand structures formed by the repeat may be responsible, perhaps via their ability to block DNA synthesis. We have examined the replication dynamics of normal and FXS cells with and without FdU. We show here that an intrinsic problem with DNA replication exists in the FMR1 gene of individuals with FXS even in the absence of FdU. Our data suggest a model for chromosome fragility in FXS in which the repeat impairs replication from an origin of replication (ORI) immediately adjacent to the repeat. The fact that the replication problem occurs even in the absence of FdU suggests that this phenomenon may have in vivo consequences, including perhaps accounting for the loss of the X chromosome containing the fragile site that causes Turner syndrome (45, X0) in female carriers of such alleles. Our data on FRAXA may also be germane for the other FdU-inducible fragile sites in humans, that we show here share many common features with FRAXA.
C1 [Yudkin, Dmitry; Hayward, Bruce E.; Kumari, Daman; Usdin, Karen] NIDDK, Sect Gene Struct & Dis, Lab Cell & Mol Biol, Bethesda, MD 20892 USA.
[Aladjem, Mirit I.] NCI, DNA Replicat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Yudkin, Dmitry] Inst Mol & Cellular Biol SB RAS, Dept Genom Divers & Evolut, Novosibirsk 630090, Russia.
RP Usdin, K (reprint author), NIH, Bldg 8,Room 2A19,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA.
EM ku@helix.nih.gov
RI Yudkin, Dmitry/N-6135-2015; Aladjem, Mirit/G-2169-2010
OI Yudkin, Dmitry/0000-0002-8940-9173; Aladjem, Mirit/0000-0002-1875-3110
FU National Institute of Diabetes, Digestive and Kidney Diseases, National
Institutes of Health; Center for Cancer Research, National Cancer
Institute, National Institutes of Health; Russian Foundation for Basic
Research
FX This work was supported by a grant from the intramural program of the
National Institute of Diabetes, Digestive and Kidney Diseases, National
Institutes of Health to K U.; from the Center for Cancer Research,
National Cancer Institute, National Institutes of Health to M.A. and
from the Russian Foundation for Basic Research to D.Y.
NR 57
TC 14
Z9 14
U1 1
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUN 1
PY 2014
VL 23
IS 11
BP 2940
EP 2952
DI 10.1093/hmg/ddu006
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AH9ST
UT WOS:000336483200012
PM 24419320
ER
PT J
AU Moayyeri, A
Hsu, YH
Karasik, D
Estrada, K
Xiao, SM
Nielson, C
Srikanth, P
Giroux, S
Wilson, SG
Zheng, HF
Smith, AV
Pye, SR
Leo, PJ
Teumer, A
Hwang, JY
Ohlsson, C
McGuigan, F
Minster, RL
Hayward, C
Olmos, JM
Lyytikainen, LP
Lewis, JR
Swart, KMA
Masi, L
Oldmeadow, C
Holliday, EG
Cheng, SL
van Schoor, NM
Harvey, NC
Kruk, M
Fabiola Del Greco, M
Igl, W
Trummer, O
Grigoriou, E
Luben, R
Liu, CT
Zhou, YH
Oei, L
Medina-Gomez, C
Zmuda, J
Tranah, G
Brown, SJ
Williams, FM
Soranzo, N
Jakobsdottir, J
Siggeirsdottir, K
Holliday, KL
Hannemann, A
Go, MJ
Garcia, M
Polasek, O
Laaksonen, M
Zhu, K
Enneman, AW
McEvoy, M
Peel, R
Sham, PC
Jaworski, M
Johansson, A
Hicks, AA
Pludowski, P
Scott, R
Dhonukshe-Rutten, RAM
van der Velde, N
Kahonen, M
Viikari, JS
Sievanen, H
Raitakari, OT
Gonzalez-Macias, J
Hernandez, JL
Mellstroom, D
Ljunggren, O
Cho, YS
Volker, U
Nauck, M
Homuth, G
Volzke, H
Haring, R
Brown, MA
McCloskey, E
Nicholson, GC
Eastell, R
Eisman, JA
Jones, G
Reid, IR
Dennison, EM
Wark, J
Boonen, S
Vanderschueren, D
Wu, FCW
Aspelund, T
Richards, JB
Bauer, D
Hofman, A
Khaw, KT
Dedoussis, G
Obermayer-Pietsch, B
Gyllensten, U
Pramstaller, PP
Lorenc, RS
Cooper, C
Kung, AWC
Lips, P
Alen, M
Attia, J
Brandi, ML
de Groot, LCPGM
Lehtimaki, T
Riancho, JA
Campbell, H
Liu, YM
Harris, TB
Akesson, K
Karlsson, M
Lee, JY
Wallaschofski, H
Duncan, EL
O'Neill, TW
Gudnason, V
Spector, TD
Rousseau, F
Orwoll, E
Cummings, SR
Wareham, NJ
Rivadeneira, F
Uitterlinden, AG
Prince, RL
Kiel, DP
Reeve, J
Kaptoge, SK
AF Moayyeri, Alireza
Hsu, Yi-Hsiang
Karasik, David
Estrada, Karol
Xiao, Su-Mei
Nielson, Carrie
Srikanth, Priya
Giroux, Sylvie
Wilson, Scott G.
Zheng, Hou-Feng
Smith, Albert V.
Pye, Stephen R.
Leo, Paul J.
Teumer, Alexander
Hwang, Joo-Yeon
Ohlsson, Claes
McGuigan, Fiona
Minster, Ryan L.
Hayward, Caroline
Olmos, Jose M.
Lyytikaeinen, Leo-Pekka
Lewis, Joshua R.
Swart, Karin M. A.
Masi, Laura
Oldmeadow, Chris
Holliday, Elizabeth G.
Cheng, Sulin
van Schoor, Natasja M.
Harvey, Nicholas C.
Kruk, Marcin
Fabiola Del Greco, M.
Igl, Wilmar
Trummer, Olivia
Grigoriou, Efi
Luben, Robert
Liu, Ching-Ti
Zhou, Yanhua
Oei, Ling
Medina-Gomez, Carolina
Zmuda, Joseph
Tranah, Greg
Brown, Suzanne J.
Williams, Frances M.
Soranzo, Nicole
Jakobsdottir, Johanna
Siggeirsdottir, Kristin
Holliday, Kate L.
Hannemann, Anke
Go, Min Jin
Garcia, Melissa
Polasek, Ozren
Laaksonen, Marika
Zhu, Kun
Enneman, Anke W.
McEvoy, Mark
Peel, Roseanne
Sham, Pak Chung
Jaworski, Maciej
Johansson, Asa
Hicks, Andrew A.
Pludowski, Pawel
Scott, Rodney
Dhonukshe-Rutten, Rosalie A. M.
van der Velde, Nathalie
Kaehoenen, Mika
Viikari, Jorma S.
Sievaenen, Harri
Raitakari, Olli T.
Gonzalez-Macias, Jesus
Hernandez, Jose L.
Mellstroem, Dan
Ljunggren, Oesten
Cho, Yoon Shin
Voelker, Uwe
Nauck, Matthias
Homuth, Georg
Voelzke, Henry
Haring, Robin
Brown, Matthew A.
McCloskey, Eugene
Nicholson, Geoffrey C.
Eastell, Richard
Eisman, John A.
Jones, Graeme
Reid, Ian R.
Dennison, Elaine M.
Wark, John
Boonen, Steven
Vanderschueren, Dirk
Wu, Frederick C. W.
Aspelund, Thor
Richards, J. Brent
Bauer, Doug
Hofman, Albert
Khaw, Kay-Tee
Dedoussis, George
Obermayer-Pietsch, Barbara
Gyllensten, Ulf
Pramstaller, Peter P.
Lorenc, Roman S.
Cooper, Cyrus
Kung, Annie Wai Chee
Lips, Paul
Alen, Markku
Attia, John
Luisa Brandi, Maria
de Groot, Lisette C. P. G. M.
Lehtimaeki, Terho
Riancho, Jose A.
Campbell, Harry
Liu, Yongmei
Harris, Tamara B.
Akesson, Kristina
Karlsson, Magnus
Lee, Jong-Young
Wallaschofski, Henri
Duncan, Emma L.
O'Neill, Terence W.
Gudnason, Vilmundur
Spector, Timothy D.
Rousseau, Francois
Orwoll, Eric
Cummings, Steven R.
Wareham, Nick J.
Rivadeneira, Fernando
Uitterlinden, Andre G.
Prince, Richard L.
Kiel, Douglas P.
Reeve, Jonathan
Kaptoge, Stephen K.
TI Genetic determinants of heel bone properties: genome-wide association
meta-analysis and replication in the GEFOS/GENOMOS consortium
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID X-RAY ABSORPTIOMETRY; QUANTITATIVE ULTRASOUND; MINERAL DENSITY;
OSTEOPOROSIS; FRACTURE; RISK; DENSITOMETRY; PHENOTYPES; CALCANEUS; WOMEN
AB Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
C1 [Moayyeri, Alireza; Luben, Robert; Khaw, Kay-Tee; Reeve, Jonathan; Kaptoge, Stephen K.] Univ Cambridge, Dept Publ Hlth Primary Care, Cambridge CB1 8RN, England.
[Moayyeri, Alireza; Wilson, Scott G.; Williams, Frances M.; Richards, J. Brent; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA.
[Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA.
[Estrada, Karol; Oei, Ling; Medina-Gomez, Carolina; Enneman, Anke W.; van der Velde, Nathalie; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Estrada, Karol; Oei, Ling; Medina-Gomez, Carolina; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Estrada, Karol] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit,Dept Med, Boston, MA USA.
[Estrada, Karol] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Estrada, Karol; Oei, Ling; Medina-Gomez, Carolina; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Netherlands Consortium Healthy Aging NCHA, Netherlands Genom Initiat NGI, Leiden, Netherlands.
[Xiao, Su-Mei; Kung, Annie Wai Chee] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Xiao, Su-Mei; Kung, Annie Wai Chee] Univ Hong Kong, Res Ctr Heart Brain Hormone & Healthy Aging, Hong Kong, Hong Kong, Peoples R China.
[Sham, Pak Chung] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China.
[Sham, Pak Chung] Univ Hong Kong, Ctr Reprod Dev & Growth, Hong Kong, Hong Kong, Peoples R China.
[Nielson, Carrie; Srikanth, Priya] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA.
[Orwoll, Eric] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA.
[Giroux, Sylvie; Rousseau, Francois] HSFA, Ctr Rech CHU Quebec, Quebec City, PQ, Canada.
[Wilson, Scott G.; Lewis, Joshua R.; Zhu, Kun; Prince, Richard L.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Wilson, Scott G.; Lewis, Joshua R.; Brown, Suzanne J.; Zhu, Kun; Prince, Richard L.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Perth, WA 6000, Australia.
[Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Med, Montreal, PQ, Canada.
[Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Human Genet, Montreal, PQ, Canada.
[Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Epidemiol, Montreal, PQ, Canada.
[Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Biostat, Montreal, PQ, Canada.
[Smith, Albert V.; Jakobsdottir, Johanna; Siggeirsdottir, Kristin; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Siggeirsdottir, Kristin; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Pye, Stephen R.; Holliday, Kate L.; O'Neill, Terence W.] Univ Manchester, Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Epidemiol Unit, Manchester M13 9WL, Lancs, England.
[Wu, Frederick C. W.] Univ Manchester, Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Androl Res Unit,Dev & Regenerat Biomed Res Grp, Manchester M13 9WL, Lancs, England.
[Leo, Paul J.; Brown, Matthew A.; Duncan, Emma L.] Univ Queensland, Diamantina Inst, Human Genet Grp, Brisbane, Qld, Australia.
[Teumer, Alexander; Voelker, Uwe; Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany.
[Hannemann, Anke; Nauck, Matthias; Haring, Robin; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Clin Chem, Greifswald, Germany.
[Hannemann, Anke; Nauck, Matthias; Haring, Robin; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Lab Med, Greifswald, Germany.
[Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Hwang, Joo-Yeon; Go, Min Jin; Lee, Jong-Young] NIH, Ctr Genome Sci, Chungcheongbuk, South Korea.
[Ohlsson, Claes; Mellstroem, Dan] Univ Gothenburg, Ctr Bone & Arthrit Res, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
[McGuigan, Fiona; Akesson, Kristina; Karlsson, Magnus] Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci, Malmo, Sweden.
[Karlsson, Magnus] Lund Univ, Dept Orthopaed, Malmo, Sweden.
[Minster, Ryan L.] Univ Pittsburgh, Dept Human Genet, Pitsburgh, PA USA.
[Zmuda, Joseph] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pitsburgh, PA USA.
[Hayward, Caroline] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Olmos, Jose M.; Gonzalez-Macias, Jesus; Hernandez, Jose L.; Riancho, Jose A.] Univ Cantabria, Dept Med, E-39005 Santander, Spain.
[Olmos, Jose M.; Gonzalez-Macias, Jesus; Hernandez, Jose L.; Riancho, Jose A.] Hosp Univ Marques Valdecilla, Dept Internal Med, Santander, Spain.
[Olmos, Jose M.; Gonzalez-Macias, Jesus; Hernandez, Jose L.; Riancho, Jose A.] Inst Formac & Invest Marques Valdecilla IFIMAV, Santander, Spain.
[Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland.
[Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Univ Tampere, Dept Clin Chem, Sch Med, FIN-33101 Tampere, Finland.
[Kaehoenen, Mika] Univ Tampere, Dept Clin Physiol, Sch Med, FIN-33101 Tampere, Finland.
[Swart, Karin M. A.; van Schoor, Natasja M.] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Lips, Paul] Vrije Univ Amsterdam, Med Ctr, Dept Endocrinol, Amsterdam, Netherlands.
[Lips, Paul] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Masi, Laura] Univ Florence, Metab Bone Dis Unit AOUC, Florence, Italy.
[Luisa Brandi, Maria] Univ Florence, Dept Surg & Translat Med, Florence, Italy.
[Oldmeadow, Chris; Holliday, Elizabeth G.; McEvoy, Mark; Peel, Roseanne; Scott, Rodney; Attia, John] Univ Newcastle, John Hunter Hosp, Newcastle, NSW 2300, Australia.
[Oldmeadow, Chris; Holliday, Elizabeth G.; McEvoy, Mark; Peel, Roseanne; Scott, Rodney; Attia, John] Hunter Med Res Inst, Newcastle, NSW, Australia.
[Cheng, Sulin] Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla, Finland.
[Harvey, Nicholas C.; Dennison, Elaine M.; Cooper, Cyrus] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England.
[Kruk, Marcin; Jaworski, Maciej; Pludowski, Pawel; Lorenc, Roman S.] Childrens Mem Hlth Inst, Dept Biochem Radioimmunol & Expt Med, Warsaw, Poland.
[Fabiola Del Greco, M.; Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.
[Fabiola Del Greco, M.; Hicks, Andrew A.; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, Lubeck, Germany.
[Igl, Wilmar; Johansson, Asa; Gyllensten, Ulf] SciLifeLab, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Ljunggren, Oesten] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Trummer, Olivia; Obermayer-Pietsch, Barbara] Med Univ Graz, Div Endocrinol & Metab, Dept Internal Med, Graz, Austria.
[Grigoriou, Efi; Dedoussis, George] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece.
[Liu, Ching-Ti; Zhou, Yanhua] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Tranah, Greg; Bauer, Doug; Cummings, Steven R.] Univ Calif San Francisco, San Francisco Coordinating Ctr, Calif Pacif Med Ctr Res Inst, San Francisco, CA 94143 USA.
[Tranah, Greg; Bauer, Doug; Cummings, Steven R.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Soranzo, Nicole] Wellcome Trust Res Labs, Sanger Inst, Cambridge, England.
[Garcia, Melissa; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Polasek, Ozren] Univ Split, Sch Med, Dept Publ Hlth, Split, Croatia.
[Laaksonen, Marika] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland.
[Dhonukshe-Rutten, Rosalie A. M.; de Groot, Lisette C. P. G. M.] Wageningen Univ, Dept Human Nutr, NL-6700 AP Wageningen, Netherlands.
[van der Velde, Nathalie] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, Sect Geriatr, NL-1105 AZ Amsterdam, Netherlands.
[Kaehoenen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
[Viikari, Jorma S.] Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland.
[Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland.
[Viikari, Jorma S.] Univ Turku, Dept Med, Turku, Finland.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Sievaenen, Harri] UKK Inst Hlth Promot Res, Tampere, Finland.
[Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon, South Korea.
[McCloskey, Eugene] Univ Sheffield, Natl Inst Hlth & Res NIHR, Musculoskeletal Biomed Res Unit, Sheffield, S Yorkshire, England.
[McCloskey, Eugene; Eastell, Richard] Univ Sheffield, Acad Unit Bone Metab, Metab Bone Ctr, Sheffield, S Yorkshire, England.
[Nicholson, Geoffrey C.] Univ Queensland, Rural Clin Sch, Toowoomba, Qld, Australia.
[Eisman, John A.] Garvan Inst Med Res, Clin Translat & Adv Educ & Osteoporosis & Bone Bi, Sydney, NSW, Australia.
[Eisman, John A.] Univ New S Wales, Dept ofMedicine, Kensington, NSW 2033, Australia.
[Eisman, John A.] Univ Notre Dame, Sch Med Sydney, Sydney, NSW, Australia.
[Eisman, John A.] St Vincents Hosp, Dept Endocrinol, Sydney, NSW 2010, Australia.
[Jones, Graeme] Univ Tasmania, Menzies Res Inst, Hobart, Tas, Australia.
[Reid, Ian R.] Univ Auckland, Auckland 1, New Zealand.
[Wark, John] Royal Melbourne Hosp, Dept Clin Sci, Melbourne, Vic, Australia.
[Boonen, Steven] Katholieke Univ Leuven, Div Geriatr Med, Leuven, Belgium.
[Boonen, Steven] Katholieke Univ Leuven, Ctr Metab Bone Dis, Leuven, Belgium.
[Vanderschueren, Dirk] Katholieke Univ Leuven, Dept Androl & Endocrinol, Leuven, Belgium.
[Cooper, Cyrus; Reeve, Jonathan] Univ Oxford, NIHR Musculoskeletal Biomed Res Unit, Inst Musculoskeletal Sci, Oxford, England.
[Alen, Markku] Oulu Univ Hosp, Dept Rehabil Med, Oulu, Finland.
[Alen, Markku] Inst Hlth Sci, Oulu, Finland.
[Campbell, Harry] Ctr Populat Hlth Sci, Sch Med, Edinburgh, Midlothian, Scotland.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC USA.
[Duncan, Emma L.] Royal Brisbane & Womens Hosp, Dept Endocrinol, Brisbane, Qld, Australia.
[Rousseau, Francois] Univ Laval, Dept Mol Biol Med Biochem & Pathol, Quebec City, PQ, Canada.
[Rousseau, Francois] Univ Laval, APOGEE Net, CanGeneTest Network Genet Hlth Serv & Policy, Quebec City, PQ, Canada.
[Wareham, Nick J.] Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
[Reeve, Jonathan; Kaptoge, Stephen K.] Strangeways Res Lab, Cambridge CB1 4RN, England.
RP Kaptoge, SK (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge CB1 8RN, England.
EM stephen@srl.cam.ac.uk
RI Lyytikainen, Leo-Pekka/C-8544-2016; Oei, Ling/E-8163-2013; Smith,
Albert/K-5150-2015; Pye, Stephen/D-9236-2011; Hayward,
Caroline/M-8818-2016; Hicks, Andrew/E-9518-2017; Polasek,
Ozren/B-6002-2011; Rivadeneira, Fernando/O-5385-2015; Duncan,
Emma/L-1224-2013; Aspelund, Thor/C-5983-2008; Pramstaller,
Peter/C-2357-2008; Nicholson, Geoffrey/F-1901-2010; Leo,
Paul/B-3470-2011; Lewis, Joshua/D-5077-2013; Moayyeri,
Alireza/N-3332-2014; Reeve, Jonathan/C-7551-2012; Gudnason,
Vilmundur/K-6885-2015
OI Johansson, Asa/0000-0002-2915-4498; Brown, Matthew
A/0000-0003-0538-8211; de Groot, Lisette /0000-0003-2778-2789; Luben,
Robert/0000-0002-5088-6343; Soranzo, Nicole/0000-0003-1095-3852;
Karasik, David/0000-0002-8826-0530; Medina-Gomez,
Carolina/0000-0001-7999-5538; Lyytikainen,
Leo-Pekka/0000-0002-7200-5455; Oei, Ling/0000-0003-3523-458X; Smith,
Albert/0000-0003-1942-5845; Pye, Stephen/0000-0002-7263-2897; Hayward,
Caroline/0000-0002-9405-9550; Hicks, Andrew/0000-0001-6320-0411; van der
Velde, Nathalie/0000-0002-6477-6209; Kiel, Douglas/0000-0001-8474-0310;
Williams, Frances/0000-0002-2998-2744; Polasek,
Ozren/0000-0002-5765-1862; Rivadeneira, Fernando/0000-0001-9435-9441;
Duncan, Emma/0000-0002-8143-4403; Aspelund, Thor/0000-0002-7998-5433;
Nicholson, Geoffrey/0000-0002-0152-1153; Leo, Paul/0000-0001-8325-4134;
Lewis, Joshua/0000-0003-1003-8443; Moayyeri,
Alireza/0000-0002-9143-2161; Reeve, Jonathan/0000-0002-4364-2682;
Gudnason, Vilmundur/0000-0001-5696-0084
FU European Commission [HEALTH-F2-2008-201865-GEFOS]
FX This research and the Genetic Factors for Osteoporosis (GEFOS)
consortium have been funded by the European Commission
(HEALTH-F2-2008-201865-GEFOS). Several other sources of funding and
people have supported work in the contributing cohorts as acknowledged
in Supplementary Material, Table S2.
NR 43
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U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUN 1
PY 2014
VL 23
IS 11
BP 3054
EP 3068
DI 10.1093/hmg/ddt675
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA AH9ST
UT WOS:000336483200021
PM 24430505
ER
PT J
AU Nguyen, TA
Menendez, D
Resnick, MA
Anderson, CW
AF Nguyen, Thuy-Ai
Menendez, Daniel
Resnick, Michael A.
Anderson, Carl W.
TI Mutant TP53 Posttranslational Modifications: Challenges and
Opportunities
SO HUMAN MUTATION
LA English
DT Review
DE TP53; p53; phosphorylation; acetylation; methylation; ubiquitylation;
transcription
ID DNA-DAMAGE RESPONSE; TUMOR-SUPPRESSOR PROTEIN; WILD-TYPE P53;
PROSTATE-CANCER CELLS; PROLYL ISOMERASE PIN1; LI-FRAUMENI-SYNDROME;
POLO-LIKE KINASES; FUNCTIONS IN-VIVO; TETRAMERIZATION DOMAIN;
IONIZING-RADIATION
AB The wild-type (WT) human p53 (TP53) tumor suppressor can be posttranslationally modified at over 60 of its 393 residues. These modifications contribute to changes in TP53 stability and in its activity as a transcription factor in response to a wide variety of intrinsic and extrinsic stresses in part through regulation of protein-protein and protein-DNA interactions. The TP53 gene frequently is mutated in cancers, and in contrast to most other tumor suppressors, the mutations are mostly missense often resulting in the accumulation of mutant (MUT) protein, which may have novel or altered functions. Most MUT TP53s can be posttranslationally modified at the same residues as in WT TP53. Strikingly, however, codons for modified residues are rarely mutated in human tumors, suggesting that TP53 modifications are not essential for tumor suppression activity. Nevertheless, these modifications might alter MUT TP53 activity and contribute to a gain-of-function leading to increased metastasis and tumor progression. Furthermore, many of the signal transduction pathways that result in TP53 modifications are altered or disrupted in cancers. Understanding the signaling pathways that result in TP53 modification and the functions of these modifications in both WT TP53 and its many MUT forms may contribute to more effective cancer therapies.
C1 [Nguyen, Thuy-Ai; Menendez, Daniel; Resnick, Michael A.; Anderson, Carl W.] NIEHS, Mol Genet Lab, Chromosome Stabil Sect, Res Triangle Pk, NC 27709 USA.
[Anderson, Carl W.] Brookhaven Natl Lab, Dept Biosci, Upton, NY 11973 USA.
RP Anderson, CW (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
EM cwa@bnl.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences
FX We thank K. Bebenek for assistance with structural representations of
PTM residues, and D. W. Meek (University of Dundee) and K. Sakaguchi
(Hokkaido University) for comments and suggestions. This research was
supported in part by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences.
NR 179
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U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
EI 1098-1004
J9 HUM MUTAT
JI Hum. Mutat.
PD JUN
PY 2014
VL 35
IS 6
SI SI
BP 738
EP 755
DI 10.1002/humu.22506
PG 18
WC Genetics & Heredity
SC Genetics & Heredity
GA AI1NX
UT WOS:000336618900010
PM 24395704
ER
PT J
AU Ouimet, MC
Brown, TG
Guo, F
Klauer, SG
Simons-Morton, BG
Fang, YJ
Lee, SE
Gianoulakis, C
Dingus, TA
AF Ouimet, Marie Claude
Brown, Thomas G.
Guo, Feng
Klauer, Sheila G.
Simons-Morton, Bruce G.
Fang, Youjia
Lee, Suzanne E.
Gianoulakis, Christina
Dingus, Thomas A.
TI Higher Crash and Near-Crash Rates in Teenaged Drivers With Lower
Cortisol Response An 18-Month Longitudinal, Naturalistic Study
SO JAMA PEDIATRICS
LA English
DT Article
ID DELINQUENT MALE-ADOLESCENTS; PITUITARY-ADRENAL AXIS; LOW SALIVARY
CORTISOL; VIOLENT OFFENDERS; RISK-TAKING; EXTERNALIZING BEHAVIOR; NOVICE
DRIVERS; EARLY RELAPSE; AGGRESSION; BOYS
AB IMPORTANCE Road traffic crashes are one of the leading causes of injury and death among teenagers worldwide. Better understanding of the individual pathways to driving risk may lead to better-targeted intervention in this vulnerable group.
OBJECTIVE To examine the relationship between cortisol, a neurobiological marker of stress regulation linked to risky behavior, and driving risk.
DESIGN, SETTING, AND PARTICIPANTS The Naturalistic Teenage Driving Study was designed to continuously monitor the driving behavior of teenagers by instrumenting vehicles with kinematic sensors, cameras, and a global positioning system. During 2006-2008, a community sample of 42 newly licensed 16-year-old volunteer participants in the United States was recruited and driving behavior monitored. It was hypothesized in teenagers that higher cortisol response to stress is associated with (1) lower crash and near-crash (CNC) rates during their first 18 months of licensure and (2) faster reduction in CNC rates over time.
MAIN OUTCOMES AND MEASURES Participants' cortisol response during a stress-inducing task was assessed at baseline, followed by measurement of their involvement in CNCs and driving exposure during their first 18 months of licensure. Mixed-effect Poisson longitudinal regression models were used to examine the association between baseline cortisol response and CNC rates during the follow-up period.
RESULTS Participants with a higher baseline cortisol response had lower CNC rates during the follow-up period (exponential of the regression coefficient, 0.93; 95% CI, 0.88-0.98) and faster decrease in CNC rates over time (exponential of the regression coefficient, 0.98; 95%, CI, 0.96-0.99).
CONCLUSIONS AND RELEVANCE Cortisol is a neurobiological marker associated with teenaged-driving risk. As in other problem-behavior fields, identification of an objective marker of teenaged-driving risk promises the development of more personalized intervention approaches.
C1 [Ouimet, Marie Claude] Univ Sherbrooke, Fac Med & Hlth Sci, Longueuil, PQ J4K 0A8, Canada.
[Ouimet, Marie Claude; Simons-Morton, Bruce G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Brown, Thomas G.; Gianoulakis, Christina] McGill Univ, Res Ctr, Douglas Hosp, Montreal, PQ, Canada.
[Guo, Feng; Klauer, Sheila G.; Lee, Suzanne E.; Dingus, Thomas A.] Virginia Tech, Transportat Inst, Blacksburg, VA USA.
[Guo, Feng; Fang, Youjia] Virginia Tech, Dept Stat, Blacksburg, VA USA.
RP Ouimet, MC (reprint author), Univ Sherbrooke, Fac Med & Hlth Sci, 150 Charles Le Moyne Pl,Ste 200, Longueuil, PQ J4K 0A8, Canada.
EM marie.claude.ouimet@usherbrooke.ca
OI Simons-Morton, Bruce/0000-0003-1099-6617
FU National Institutes of Health [N01-HD-5-3405]; National Highway Traffic
Safety Administration; Quebec Health Research Fund (Fonds de recherche
du Quebec-Sante)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (grant N01-HD-5-3405) and by the National
Highway Traffic Safety Administration. Cortisol sampling kits and
analyses were provided by the Douglas Hospital Research Centre. Dr
Ouimet was supported through a career grant from the Quebec Health
Research Fund (Fonds de recherche du Quebec-Sante).
NR 50
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U1 1
U2 12
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD JUN
PY 2014
VL 168
IS 6
BP 517
EP 522
DI 10.1001/jamapediatrics.2013.5387
PG 6
WC Pediatrics
SC Pediatrics
GA AI4MZ
UT WOS:000336840800009
PM 24710522
ER
PT J
AU Bousquet, J
Gern, JE
Martinez, FD
Anto, JM
Johnson, CC
Holt, PG
Lemanske, RF
Le Souef, PN
Tepper, RS
von Mutius, ERM
Arshad, SH
Bacharier, LB
Becker, A
Belanger, K
Bergstrom, A
Bernstein, DI
Cabana, MD
Carroll, KN
Castro, M
Cooper, PJ
Gillman, MW
Gold, DR
Henderson, J
Heinrich, J
Hong, SJ
Jackson, DJ
Keil, T
Kozyrskyj, AL
Carlsen, KCL
Miller, RL
Momas, I
Morgan, WJ
Noel, P
Ownby, DR
Pinart, M
Ryan, PH
Schwaninger, JM
Sears, MR
Simpson, A
Smit, HA
Stern, DA
Subbarao, P
Valenta, R
Wang, XB
Weiss, ST
Wood, R
Wright, AL
Wright, RJ
Togias, A
Gergen, PJ
AF Bousquet, Jean
Gern, James E.
Martinez, Fernando D.
Anto, Josep M.
Johnson, Christine C.
Holt, Patrick G.
Lemanske, Robert F., Jr.
Le Souef, Peter N.
Tepper, Robert S.
von Mutius, Erika R. M.
Arshad, S. Hasan
Bacharier, Leonard B.
Becker, Allan
Belanger, Kathleen
Bergstrom, Anna
Bernstein, David I.
Cabana, Michael D.
Carroll, Kecia N.
Castro, Mario
Cooper, Philip J.
Gillman, Matthew W.
Gold, Diane R.
Henderson, John
Heinrich, Joachim
Hong, Soo-Jong
Jackson, Daniel J.
Keil, Thomas
Kozyrskyj, Anita L.
Carlsen, Karin C. Lodrup
Miller, Rachel L.
Momas, Isabelle
Morgan, Wayne J.
Noel, Patricia
Ownby, Dennis R.
Pinart, Mariona
Ryan, Patrick H.
Schwaninger, Julie M.
Sears, Malcolm R.
Simpson, Angela
Smit, Henriette A.
Stern, Debra A.
Subbarao, Padmaja
Valenta, Rudolf
Wang, Xiaobin
Weiss, Scott T.
Wood, Robert
Wright, Anne L.
Wright, Rosalind J.
Togias, Alkis
Gergen, Peter J.
TI Birth cohorts in asthma and allergic diseases: Report of a
NIAID/NHLBI/MeDALL joint workshop
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Allergy; asthma; birth cohorts; National Heart, Lung, and Blood
Institute (NHLBI); National Institute of Allergy and Infectious Disease
(NIAID); Mechanisms of the Development of Allergy (MeDALL)
ID EXHALED NITRIC-OXIDE; WHEEZING RHINOVIRUS ILLNESSES; 1ST 6 YEARS;
LUNG-FUNCTION; YOUNG-CHILDREN; EARLY-LIFE; AIRWAY RESPONSIVENESS;
PRESCHOOL-CHILDREN; CHILDHOOD ASTHMA; ATOPIC DISEASES
AB Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts.
C1 [Bousquet, Jean] Univ Hosp, Montpellier, France.
[Bousquet, Jean] INSERM, U1018, Villejuif, France.
[Gern, James E.; Lemanske, Robert F., Jr.; Jackson, Daniel J.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Martinez, Fernando D.; Stern, Debra A.] Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA.
[Anto, Josep M.; Pinart, Mariona] CREAL, Barcelona, Spain.
[Anto, Josep M.; Pinart, Mariona] IMIM Hosp del Mar Res Inst, Barcelona, Spain.
[Anto, Josep M.; Pinart, Mariona] CIBERESP, Barcelona, Spain.
[Anto, Josep M.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.
[Johnson, Christine C.] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA.
[Holt, Patrick G.] Univ Western Australia, Telethon Inst Child Hlth Res, Brisbane, Qld, Australia.
[Holt, Patrick G.] Univ Queensland, Queensland Childrens Med Res Inst, Brisbane, Qld, Australia.
[Le Souef, Peter N.] Univ Western Australia, Princess Margaret Hosp Children, Sch Paediat & Child Hlth, Perth, WA 6009, Australia.
[Tepper, Robert S.] Indiana Univ Sch Med, James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA.
[von Mutius, Erika R. M.] Univ Munich, Dr von Hauner Childrens Hosp, D-81377 Munich, Germany.
[Arshad, S. Hasan] Univ Southampton, Fac Med, Isle Of Wight, England.
[Arshad, S. Hasan] David Hide Asthma & Allergy Res Ctr, Isle Of Wight, England.
[Bacharier, Leonard B.] Washington Univ, St Louis, MO 63130 USA.
[Bacharier, Leonard B.] St Louis Childrens Hosp, St Louis, MO USA.
[Becker, Allan] Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB R3T 2N2, Canada.
[Belanger, Kathleen] Yale Univ, Sch Publ Hlth, Sch Med, Ctr Perinatal Pediat & Environm Epidemiol, New Haven, CT USA.
[Bergstrom, Anna] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Bernstein, David I.] Univ Cincinnati, Coll Med, Div Immunol Allergy & Rheumatol, Cincinnati, OH 45221 USA.
[Cabana, Michael D.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Cabana, Michael D.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Carroll, Kecia N.] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA.
[Castro, Mario] Washington Univ, Sch Med, Div Pulm & Crit Care Med, St Louis, MO 63130 USA.
[Cooper, Philip J.] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England.
[Cooper, Philip J.] Pontificia Univ Catolica Ecuador, Escuela Biol, Quito, Ecuador.
[Gillman, Matthew W.] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA.
[Gold, Diane R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA.
[Gold, Diane R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Henderson, John] Univ Bristol, Sch Social & Community Med, Bristol BS8 1TH, Avon, England.
[Heinrich, Joachim] German Ctr Environm Hlth, Helmholtz Zentrum, Inst Epidemiol 1, Munich, Germany.
[Hong, Soo-Jong] Univ Ulsan, Coll Med, Asan Med Ctr,Dept Pediat, Res Ctr Standardizat Allerg Dis,Childhood Asthma, Seoul, South Korea.
[Keil, Thomas] Charite, Inst Social Med Epidemiol & Hlth Econ, D-13353 Berlin, Germany.
[Keil, Thomas] Univ Wurzburg, Inst Clin Epidemiol & Biometry, Wurzburg, Germany.
[Kozyrskyj, Anita L.] Univ Alberta, Dept Pediat, Fac Med & Dent, Edmonton, AB, Canada.
[Carlsen, Karin C. Lodrup] Oslo Univ Hosp, Oslo, Norway.
[Carlsen, Karin C. Lodrup] Univ Oslo, N-0316 Oslo, Norway.
[Miller, Rachel L.] Columbia Univ, Dept Med, Div Pulm Allergy & Critcare Med, New York, NY USA.
[Momas, Isabelle] Paris Descartes Univ, Dept Publ Hlth & Biostat, Paris, France.
[Momas, Isabelle] Paris Municipal Dept Social Act Childhood & Hlth, Paris, France.
[Miller, Rachel L.] Univ Arizona, Dept Pediat, Tucson, AZ 85721 USA.
[Noel, Patricia] NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA.
[Ownby, Dennis R.] Georgia Regents Univ, Augusta, GA USA.
[Ryan, Patrick H.] Cincinnati Childrens Hosp Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH 45229 USA.
[Schwaninger, Julie M.; Togias, Alkis; Gergen, Peter J.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA.
[Sears, Malcolm R.] McMaster Univ, AstraZeneca Chair Resp Epidemiol, Dept Med, Hamilton, ON L8S 4L8, Canada.
[Simpson, Angela] Univ Manchester, Manchester Acad Hlth Sci Ctr, Ctr Resp & Allergy, Inst Inflammat & Repair, Manchester M13 9PL, Lancs, England.
[Simpson, Angela] Univ Hosp South Manchester, Manchester, Lancs, England.
[Smit, Henriette A.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Subbarao, Padmaja] Univ Toronto, Dept Pediat, Toronto, ON M5S 1A1, Canada.
[Valenta, Rudolf] Med Univ Vienna, Ctr Pathophysiol Infectiol & Immunol, Dept Pathophysiol & Allergy Res, Div Immunopathol, Vienna, Austria.
[Wang, Xiaobin] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Weiss, Scott T.] Harvard Univ, Sch Med, Dept Med, Channing Div Network Med, Boston, MA USA.
[Wood, Robert] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA.
[Wright, Anne L.] Univ Arizona, Coll Med, Arizona Resp Ctr, Tucson, AZ USA.
[Wright, Anne L.] Univ Arizona, Coll Med, Dept Pediat, Tucson, AZ USA.
[Wright, Rosalind J.] Icahn Sch Med, Dept Pediat, Mt Sinai, NY USA.
[Wright, Rosalind J.] Icahn Sch Med, Mindich Child Hlth & Dev Inst, Mt Sinai, NY USA.
RP Bousquet, J (reprint author), Ctr Hosp Montpellier, F-34295 Montpellier 05, France.
EM jean.bousquet@inserm.fr
RI Ryan, Patrick /L-7062-2015; Pinart, Mariona/L-1931-2015; Anto,
J/H-2676-2014; Holt, Patrick/H-1548-2011;
OI Pinart, Mariona/0000-0002-8223-1325; Anto, J/0000-0002-4736-8529; Holt,
Patrick/0000-0003-1193-0935; Simpson, Angela/0000-0003-2733-6666; von
Mutius, Erika/0000-0002-8893-4515
FU MeDALL (Mechanisms of the Development of Allergy, EU) [261357]; Division
of Allergy, Immunology, and Transplantation, National Institute of
Allergy and Infectious Diseases; Division of Lung Diseases, National
Heart, Lung, and Blood Institute
FX Supported by MeDALL (Mechanisms of the Development of Allergy, EU FP7
Grant agreement no. 261357). The workshop was supported in part by funds
from the Division of Allergy, Immunology, and Transplantation, National
Institute of Allergy and Infectious Diseases, and the Division of Lung
Diseases, National Heart, Lung, and Blood Institute.
NR 94
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U1 0
U2 15
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 JUN
PY 2014
VL 133
IS 6
BP 1535
EP 1546
DI 10.1016/j.jaci.2014.01.018
PG 12
WC Allergy; Immunology
SC Allergy; Immunology
GA AI2FI
UT WOS:000336672500004
PM 24636091
ER
PT J
AU Moore, WC
Hastie, AT
Li, XN
Li, HS
Busse, WW
Jarjour, NN
Wenzel, SE
Peters, SP
Meyers, DA
Bleecker, ER
AF Moore, Wendy C.
Hastie, Annette T.
Li, Xingnan
Li, Huashi
Busse, William W.
Jarjour, Nizar N.
Wenzel, Sally E.
Peters, Stephen P.
Meyers, Deborah A.
Bleecker, Eugene R.
CA Natl Heart Lung Blood Inst Severe
TI Sputum neutrophil counts are associated with more severe asthma
phenotypes using cluster analysis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Severe Asthma Research Program; severe asthma; sputum; eosinophils;
neutrophils; phenotype; cluster analysis
ID RANDOMIZED CONTROLLED-TRIAL; AIRWAY INFLAMMATION; REFRACTORY ASTHMA;
EOSINOPHIL COUNTS; RESEARCH-PROGRAM; DOUBLE-BLIND; CORTICOSTEROIDS;
CLARITHROMYCIN; EXACERBATIONS; PREVENTION
AB Background: Clinical cluster analysis from the Severe Asthma Research Program (SARP) identified 5 asthma subphenotypes that represent the severity spectrum of early-onset allergic asthma, late-onset severe asthma, and severe asthma with chronic obstructive pulmonary disease characteristics. Analysis of induced sputum from a subset of SARP subjects showed 4 sputum inflammatory cellular patterns. Subjects with concurrent increases in eosinophil (>= 2%) and neutrophil (>= 40%) percentages had characteristics of very severe asthma.
Objective: To better understand interactions between inflammation and clinical subphenotypes, we integrated inflammatory cellular measures and clinical variables in a new cluster analysis.
Methods: Participants in SARP who underwent sputum induction at 3 clinical sites were included in this analysis (n = 423). Fifteen variables, including clinical characteristics and blood and sputum inflammatory cell assessments, were selected using factor analysis for unsupervised cluster analysis.
Results: Four phenotypic clusters were identified. Cluster A (n = 132) and B (n = 127) subjects had mild-to-moderate early-onset allergic asthma with paucigranulocytic or eosinophilic sputum inflammatory cell patterns. In contrast, these inflammatory patterns were present in only 7% of cluster C (n = 117) and D (n = 47) subjects who had moderate-to-severe asthma with frequent health care use despite treatment with high doses of inhaled or oral corticosteroids and, in cluster D, reduced lung function. The majority of these subjects (>83%) had sputum neutrophilia either alone or with concurrent sputum eosinophilia. Baseline lung function and sputum neutrophil percentages were the most important variables determining cluster assignment.
Conclusion: This multivariate approach identified 4 asthma subphenotypes representing the severity spectrum from mild-to-moderate allergic asthma with minimal or eosinophil-predominant sputum inflammation to moderate-to-severe asthma with neutrophil-predominant or mixed granulocytic inflammation.
C1 [Moore, Wendy C.; Hastie, Annette T.; Li, Xingnan; Li, Huashi; Peters, Stephen P.; Meyers, Deborah A.; Bleecker, Eugene R.] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA.
[Moore, Wendy C.; Hastie, Annette T.; Li, Xingnan; Li, Huashi; Peters, Stephen P.; Meyers, Deborah A.; Bleecker, Eugene R.] Sect Pulm Crit Care Allergy & Immunol Dis, Winston Salem, NC USA.
[Busse, William W.; Jarjour, Nizar N.] Univ Wisconsin, Sch Med & Publ Hlth, Allergy Pulm & Crit Care Div, Madison, WI 53706 USA.
[Wenzel, Sally E.] Univ Pittsburgh, Sch Med Pulm Allergy & Crit Care Med, Bethesda, MD USA.
[Natl Heart Lung Blood Inst Severe] NHLBI, Severe Asthma Res Program, Bethesda, MD 20892 USA.
RP Moore, WC (reprint author), Wake Forest Sch Med, Dept Med, Ctr Genom & Personalized Med Res, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM wmoore@wakehealth.edu
FU National Heart, Lung, and Blood Institute (NHLBI); [HL69116];
[HL69167]; [HL69174]; [UL1RR025011]
FX The Severe Asthma Research Program (SARP) is a multicenter asthma
research group funded by the National Heart, Lung, and Blood Institute
(NHLBI) and consisting of the following universities (principal
investigators): Brigham & Women's Hospital-Elliot Israel; Cleveland
Clinic-Serpil C. Erzurum; Emory University-Anne M. Fitzpatrick; Imperial
College School of Medicine-Kian F. Chung; University of Pittsburgh-Sally
E. Wenzel; University of Texas-Medical Branch-William J. Calhoun;
University of Virginia-Benjamin Gaston, W. Gerald Teague; University of
Wisconsin-William W. Busse; Wake Forest University-Eugene R. Bleecker;
Washington University in St Louis-Mario Castro; Data Coordinating
Center-Douglas Curran-Everett; NHLBI-Patricia Noel, Robert Smith.;
Supported by grants HL69116, HL69167, HL69174, and UL1RR025011.
NR 33
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U1 0
U2 9
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 JUN
PY 2014
VL 133
IS 6
BP 1557
EP +
DI 10.1016/j.jaci.2013.10.011
PG 12
WC Allergy; Immunology
SC Allergy; Immunology
GA AI2FI
UT WOS:000336672500006
PM 24332216
ER
PT J
AU Jing, H
Zhang, Q
Zhang, Y
Hill, BJ
Dove, CG
Gelfand, EW
Atkinson, TP
Uzel, G
Matthews, HF
Mustillo, PJ
Lewis, DB
Kavadas, FD
Hanson, IC
Kumar, AR
Geha, RS
Douek, DC
Holland, SM
Freeman, AF
Su, HC
AF Jing, Huie
Zhang, Qian
Zhang, Yu
Hill, Brenna J.
Dove, Christopher G.
Gelfand, Erwin W.
Atkinson, T. Prescott
Uzel, Gulbu
Matthews, Helen F.
Mustillo, Peter J.
Lewis, David B.
Kavadas, Fotini D.
Hanson, I. Celine
Kumar, Ashish R.
Geha, Raif S.
Douek, Daniel C.
Holland, Steven M.
Freeman, Alexandra F.
Su, Helen C.
TI Somatic reversion in dedicator of cytokinesis 8 immunodeficiency
modulates disease phenotype
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Dedicator of cytokinesis 8; reversion; somatic repair; recombination;
gene conversion; intragenic single crossover; T cell; natural killer
cell; allergy; immunodeficiency
ID HYPER-IGE SYNDROME; STEM-CELL TRANSPLANTATION; DOCK8 DEFICIENCY;
MUTATIONS; KINETICS; SURVIVAL; MEMORY; RECOMBINATION; MOSAICISM; HUMANS
AB Background: Autosomal recessive loss-of-function mutations in dedicator of cytokinesis 8 (DOCK8) cause a combined immunodeficiency characterized by atopy, recurrent infections, and cancer susceptibility. A genotype-phenotype explanation for the variable disease expression is lacking.
Objective: We investigated whether reversions contributed to the variable disease expression.
Methods: Patients followed at the National Institutes of Health's Clinical Center were studied. We performed detailed genetic analyses and intracellular flow cytometry to detect DOCK8 protein expression within lymphocyte subsets.
Results: We identified 17 of 34 DOCK8-deficient patients who had germline mutations with variable degrees of reversion caused by somatic repair. Somatic repair of the DOCK8 mutations resulted from second-site mutation, original-site mutation, gene conversion, and intragenic crossover. Higher degrees of reversion were associated with recombination-mediated repair. DOCK8 expression was restored primarily within antigen-experienced T cells or natural killer cells but less so in naive T or B cells. Several patients exhibited multiple different repair events. Patients who had reversions were older and had less severe allergic disease, although infection susceptibility persisted. No patients were cured without hematopoietic cell transplantation.
Conclusions: In patients with DOCK8 deficiency, only certain combinations of germline mutations supported secondary somatic repair. Those patients had an ameliorated disease course with longer survival but still had fatal complications or required hematopoietic cell transplantation. These observations support the concept that some DOCK8-immunodeficient patients have mutable mosaic genomes that can modulate disease phenotype over time.
C1 [Jing, Huie; Zhang, Qian; Zhang, Yu; Dove, Christopher G.; Su, Helen C.] NIAID, Lab Host Def, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Uzel, Gulbu; Holland, Steven M.; Freeman, Alexandra F.] NIAID, Lab Clin Infect Dis, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Hill, Brenna J.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Gelfand, Erwin W.] Natl Jewish Hlth, Div Cell Biol, Dept Pediat, Div Allergy & Immunol, Denver, CO USA.
[Atkinson, T. Prescott] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Mustillo, Peter J.] Nationwide Childrens Hosp, Div Infect Dis & Immunol, Columbus, OH USA.
[Lewis, David B.] Stanford Univ, Div Immunol Allergy & Rheumatol, Dept Pediat, Stanford, CA 94305 USA.
[Kavadas, Fotini D.] Alberta Childrens Prov Gen Hosp, Dept Pediat, Sect Clin Immunol & Allergy, Calgary, AB, Canada.
[Kavadas, Fotini D.] Univ Calgary, Calgary, AB T2N 1N4, Canada.
[Hanson, I. Celine] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Sect Allergy & Immunol, Houston, TX 77030 USA.
[Kumar, Ashish R.] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immune Deficiency, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA.
[Kumar, Ashish R.] Univ Cincinnati, Cincinnati, OH 45221 USA.
[Geha, Raif S.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
[Geha, Raif S.] Childrens Hosp, Dept Pediat, Boston, MA 02115 USA.
[Geha, Raif S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Su, HC (reprint author), NIAID, Lab Host Def, Div Intramural Res, NIH, Bldg 10CRC,Rm 5W3940,10CRC Ctr Dr,MSC 1456, Bethesda, MD 20892 USA.
EM hsu@niaid.nih.gov
RI Su, Helen/H-9541-2015;
OI Su, Helen/0000-0002-5582-9110; Zhang, Qian/0000-0002-9040-3289
FU Intramural Research Program; Vaccine Research Center of the National
Institutes of Health, National Institute of Allergy and Infectious
Diseases
FX Supported by the Intramural Research Program and the Vaccine Research
Center of the National Institutes of Health, National Institute of
Allergy and Infectious Diseases.
NR 28
TC 25
Z9 25
U1 0
U2 5
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 JUN
PY 2014
VL 133
IS 6
BP 1667
EP 1675
DI 10.1016/j.jaci.2014.03.025
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA AI2FI
UT WOS:000336672500020
PM 24797421
ER
PT J
AU Buckner, CM
Moir, S
Kardava, L
Ho, J
Santich, BH
Kim, LJY
Funk, EK
Nelson, AK
Winckler, B
Chairez, CL
Theobald-Whiting, NL
Anaya-O'Brien, S
Alimchandani, M
Quezado, MM
Yao, MD
Kovacs, JA
Chun, TW
Fauci, AS
Malech, HL
De Ravin, SS
AF Buckner, Clarisa M.
Moir, Susan
Kardava, Lela
Ho, Jason
Santich, Brian H.
Kim, Leo Jin Young
Funk, Emily K.
Nelson, Amy K.
Winckler, Britanny
Chairez, Cheryl L.
Theobald-Whiting, Narda L.
Anaya-O'Brien, Sandra
Alimchandani, Meghna
Quezado, Martha M.
Yao, Michael D.
Kovacs, Joseph A.
Chun, Tae-Wook
Fauci, Anthony S.
Malech, Harry L.
De Ravin, Suk See
TI CXCR4/IgG-expressing plasma cells are associated with human
gastrointestinal tissue inflammation
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Plasma cells; primary and infectious immunodeficiencies;
gastrointestinal inflammation; inflammatory bowel disease; homing
receptors
ID ULCERATIVE-COLITIS; IMMUNOGLOBULIN-A; ANTIRETROVIRAL THERAPY;
MONOCLONAL-ANTIBODIES; IMMUNE ACTIVATION; HIV-1 INFECTION; SECRETING
CELLS; CROHNS-DISEASE; MUCOSAL; EXPRESSION
AB Background: We previously reported abnormalities in circulating B cells in patients with chronic granulomatous disease (CGD) and those with HIV infection. Gastrointestinal complications are common to both diseases and likely involve perturbation of immune cells, including plasma cells (PCs). IgA is the most abundant immunoglobulin in the human body, with roles in protection and maintenance of intestinal homeostasis. IgA is produced primarily by PCs residing in mucosal tissues that are also thought to circulate in the blood.
Objective: We sought to characterize and compare PCs in patients with infectious (HIV) and noninfectious (CGD and Crohn disease) diseases that have been associated with intestinal inflammation.
Methods: Phenotypic and transcriptional analyses were performed on cells isolated from the blood and colon.
Results: IgA-secreting CCR10-expressing PCs predominated in the guts of healthy subjects, whereas in patients with HIV, CGD, and Crohn disease, there was a significant increase in the proportion of IgG-secreting PCs. Where intestinal inflammation was present, IgG-secreting PCs expressed reduced levels of CCR10 and increased levels of CXCR4. The intensity of CXCR4 expression correlated with the frequency of IgG-expressing PCs and the frequency of CXCR4(+)/IgG(+) PCs was associated with the severity of intestinal inflammatory disease yet distinct from PCs and plasmablasts circulating in the blood.
Conclusions: These findings suggest that regardless of the underlying disease, the presence of CXCR4(+)/IgG(+) PCs in the gut is a strong yet localized indicator of intestinal inflammation. Furthermore, our findings suggest that CXCR4(+)/IgG(+) PCs might play a role in immune cell homeostasis during inflammatory processes of the gut.
C1 [Buckner, Clarisa M.; Moir, Susan; Kardava, Lela; Ho, Jason; Santich, Brian H.; Kim, Leo Jin Young; Funk, Emily K.; Nelson, Amy K.; Chairez, Cheryl L.; Chun, Tae-Wook; Fauci, Anthony S.] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA.
[Winckler, Britanny; Theobald-Whiting, Narda L.; Anaya-O'Brien, Sandra; Yao, Michael D.; Malech, Harry L.; De Ravin, Suk See] NIAID, Host Def Lab, Bethesda, MD 20892 USA.
[Alimchandani, Meghna; Quezado, Martha M.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Kovacs, Joseph A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr,6A02, Bethesda, MD 20892 USA.
EM smoir@niaid.nih.gov; sderavin@niaid.nih.gov
OI Malech, Harry/0000-0001-5874-5775
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX Supported by the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases, National Institutes of Health.
NR 33
TC 3
Z9 3
U1 0
U2 1
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 JUN
PY 2014
VL 133
IS 6
BP 1676
EP +
DI 10.1016/j.jaci.2013.10.050
PG 15
WC Allergy; Immunology
SC Allergy; Immunology
GA AI2FI
UT WOS:000336672500021
PM 24373354
ER
PT J
AU Szefler, SJ
Chmiel, JF
Fitzpatrick, AM
Giacoia, G
Green, TP
Jackson, DJ
Nielsen, HC
Phipatanakul, W
Raissy, HH
AF Szefler, Stanley J.
Chmiel, James F.
Fitzpatrick, Anne M.
Giacoia, George
Green, Thomas P.
Jackson, Daniel J.
Nielsen, Heber C.
Phipatanakul, Wanda
Raissy, Hengameh H.
TI Test for Respiratory and Asthma Control in Kids (TRACK): A validated
control tool for preschool-aged children Reply
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID QUESTIONNAIRE
C1 [Szefler, Stanley J.] Natl Jewish Hlth, Dept Pediat & Pharmacol, Denver, CO 80206 USA.
[Szefler, Stanley J.] Univ Colorado Sch Med, Denver, CO USA.
[Chmiel, James F.] Univ Hosp Rainbow Babies & Childrens Hosp, Cleveland, OH USA.
[Chmiel, James F.] Case Western Reserve Univ Sch Med, Cleveland, OH USA.
[Fitzpatrick, Anne M.] Emory Univ Dept Pediat, Atlanta, GA USA.
[Fitzpatrick, Anne M.] Childrens Healthcare Atlanta Ctr Dev Lung Biol, Atlanta, GA USA.
[Giacoia, George] Natl Inst Child Hlth & Dev, Bethesda, MD USA.
[Green, Thomas P.] Northwestern Univ Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL USA.
[Jackson, Daniel J.] Univ Wisconsin Sch Med & Publ Hlth, Dept Pediat, Madison, WI USA.
[Nielsen, Heber C.] Tufts Univ Sch Med, Tufts Med Ctr, Floating Hosp Children, Boston, MA USA.
[Phipatanakul, Wanda] Boston Childrens Hosp, Boston, MA USA.
[Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA.
[Raissy, Hengameh H.] Univ New Mexico Sch Med, Dept Pediat, Albuquerque, NM USA.
RP Szefler, SJ (reprint author), Natl Jewish Hlth, Dept Pediat & Pharmacol, Denver, CO 80206 USA.
EM Stanley.szefler@childrenscolorado.or
FU NCATS NIH HHS [UL1 TR000041]
NR 7
TC 0
Z9 0
U1 0
U2 3
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 JUN
PY 2014
VL 133
IS 6
BP 1776
EP 1777
DI 10.1016/j.jaci.2014.03.013
PG 3
WC Allergy; Immunology
SC Allergy; Immunology
GA AI2FI
UT WOS:000336672500040
PM 24786239
ER
PT J
AU Kirklin, JK
Naftel, DC
Pagani, FD
Kormos, RL
Stevenson, LW
Blume, ED
Miller, MA
Baldwin, JT
Young, JB
AF Kirklin, James K.
Naftel, David C.
Pagani, Francis D.
Kormos, Robert L.
Stevenson, Lynne W.
Blume, Elizabeth D.
Miller, Marissa A.
Baldwin, J. Timothy
Young, James B.
TI Sixth INTERMACS annual report: A 10,000-patient database
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Article
DE mechanical support; ventricular assist device; INTERMACS; advanced heart
failure; destination therapy
ID CIRCULATORY SUPPORT; DESTINATION THERAPY
AB The sixth annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 8 years of patient enrollment. The analysis is based on data from >10,000 patients and updates demographics, survival, adverse events and risk factors. Among patients with continuous-flow pumps, actuarial survival continues to be 80% at 1 year and 70% at 2 years. The report features a comparison of two eras of continuous-flow durable devices in the USA in terms of device strategy, patient profiles, adverse event burden, survival and quality of life. (C) 2014 International Society for Heart and Lung Transplantation. All rights reserved.
C1 [Kirklin, James K.; Naftel, David C.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
[Pagani, Francis D.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
[Kormos, Robert L.] Univ Pittsburgh, Presbyterian Univ Hosp, Med Ctr, Dept Surg, Pittsburgh, PA USA.
[Stevenson, Lynne W.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Blume, Elizabeth D.] Boston Childrens Hosp, Dept Pediat, Boston, MA USA.
[Miller, Marissa A.; Baldwin, J. Timothy] Natl Heart Lung & Blood Inst, Div Cardiovasc Dis, Adv Technol & Surg Branch, Bethesda, MD USA.
[Young, James B.] Cleveland Clin, Fdn Lerner Coll Med, Dept Med, Cleveland, OH 44106 USA.
RP Kirklin, JK (reprint author), Univ Alabama Birmingham, Dept Surg, Div Cardiovasc Surg, 760 Tinsley Harrison Towers, Birmingham, AL 35294 USA.
EM jkirklin@uab.edu
FU NHLBI [HHSN2682011000250]
FX This analysis and the INTERMACS device database are funded by a contract
grant from the NHLBI (HHSN2682011000250).
NR 7
TC 359
Z9 362
U1 2
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD JUN
PY 2014
VL 33
IS 6
BP 555
EP 564
DI 10.1016/j.healun.2014.04.010
PG 10
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA AI1TG
UT WOS:000336637100001
PM 24856259
ER
PT J
AU Dang, HT
Budhu, A
Wang, XW
AF Dang, Hien T.
Budhu, Anuradha
Wang, Xin W.
TI The origin of cancer stem cells
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Hepatocellular carcinoma; Cancer stem cells; Hepatocarcinogenesis; IL-6;
HCC progenitor cells; Foci altered hepatocytes
ID HEPATOCELLULAR-CARCINOMA; LIVER-CANCER; MICROENVIRONMENT
AB Hepatocellular carcinoma (HCC) is a slowly developing malignancy postulated to evolve from premalignant lesions in chronically damaged livers. However, it was never established that premalignant lesions actually contain tumor progenitors that give rise to cancer. Here, we describe the isolation and characterization of HCC progenitor cells (HcPCs) from different mouse HCC models. Unlike fully malignant HCC, HcPCs give rise to cancer only when introduced into a liver undergoing chronic damage and compensatory proliferation. Although HcPCs exhibit a similar transcriptomic profile to bipotential hepatobiliary progenitors, the latter do not give rise to tumors. Cells resembling HcPCs reside within dysplastic lesions that appear several months before HCC nodules. Unlike early hepatocarcinogenesis, which depends on paracrine IL-6 production by inflammatory cells, due to upregulation of LIN28 expression, HcPCs had acquired autocrine IL-6 signaling that stimulates their in vivo growth and malignant progression. This may be a general mechanism that drives other IL-6-producing malignancies. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Dang, Hien T.; Budhu, Anuradha; Wang, Xin W.] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Wang, XW (reprint author), NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM xw3u@nih.gov
RI Wang, Xin/B-6162-2009
NR 9
TC 3
Z9 3
U1 2
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD JUN
PY 2014
VL 60
IS 6
BP 1304
EP 1305
DI 10.1016/j.cell.2013.09.031
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH9BO
UT WOS:000336434300026
PM 24631602
ER
PT J
AU Han, H
Noureddin, M
Witthaus, M
Park, YJ
Hoofnagle, JH
Liang, TJ
Rotman, Y
AF Han, Hwalih
Noureddin, Mazen
Witthaus, Michael
Park, Yoon J.
Hoofnagle, Jay H.
Liang, T. Jake
Rotman, Yaron
TI Temperature rise after peginterferon alfa-2a injection in patients with
chronic hepatitis C is associated with virological response and is
modulated by IL28B genotype (vol 59, pg 957, 2013)
SO JOURNAL OF HEPATOLOGY
LA English
DT Correction
C1 [Han, Hwalih; Noureddin, Mazen; Witthaus, Michael; Park, Yoon J.; Hoofnagle, Jay H.; Liang, T. Jake; Rotman, Yaron] Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, NIH, Bethesda, MD USA.
RP Rotman, Y (reprint author), NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9C434,MSC 1800, Bethesda, MD 20892 USA.
EM rotmany@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD JUN
PY 2014
VL 60
IS 6
BP 1334
EP 1335
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AH9BO
UT WOS:000336434300037
PM 25467605
ER
PT J
AU Graham, BS
AF Graham, Barney S.
TI Protecting the Family to Protect the Child: Vaccination Strategy Guided
by RSV Transmission Dynamics
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID RESPIRATORY SYNCYTIAL VIRUS; INFECTIONS; MORTALITY; DISEASE; INFANTS
C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,MSC 3017,Bldg 40,Rm 2502, Bethesda, MD 20892 USA.
EM bgraham@nih.gov
FU Intramural NIH HHS
NR 11
TC 11
Z9 11
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 1
PY 2014
VL 209
IS 11
BP 1679
EP 1681
DI 10.1093/infdis/jiu075
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AH9TP
UT WOS:000336485900001
PM 24523511
ER
PT J
AU Meissner, EG
Bon, D
Prokunina-Olsson, L
Tang, W
Masur, H
O'Brien, TR
Herrmann, E
Kottilil, S
Osinusi, A
AF Meissner, Eric G.
Bon, Dimitra
Prokunina-Olsson, Ludmila
Tang, Wei
Masur, Henry
O'Brien, Thomas R.
Herrmann, Eva
Kottilil, Shyamasundaran
Osinusi, Anuoluwapo
TI IFNL4-Delta G Genotype Is Associated With Slower Viral Clearance in
Hepatitis C, Genotype-1 Patients Treated With Sofosbuvir and Ribavirin
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE viral kinetics; pharmacokinetics; IL28B; IFNL4; haplotype; SVR;
hepatitis C virus; DAA therapy; relapse
ID INFECTION; HCV; VIRUS; KINETICS; THERAPY
AB Response to pegylated interferon-alpha and ribavirin (IFN-alpha/RBV) treatment for chronic hepatitis C virus (HCV) infection is influenced by host genetic factors, but their role for IFN-alpha-free, direct-acting antiviral (DAA) regimens is unclear. An exonic deletion allele (IFNL4-Delta G) bolsters the established association with IFN-alpha/RBV therapy treatment outcome of another IFNL4 variant, rs12979860, which is located upstream of IFNL3 (IL28B). We report that in patients treated with the DAA sofosbuvir along with RBV, IFNL4-Delta G is associated with slower early viral decay, due to slower loss of free virus (P = .039) and decreased drug efficacy (P = .048), suggesting functional relevance of IFN-lambda 4 in IFN-alpha-free DAA therapies.
C1 [Meissner, Eric G.; Kottilil, Shyamasundaran; Osinusi, Anuoluwapo] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Bon, Dimitra; Herrmann, Eva] Goethe Univ Frankfurt, Inst Biostat & Math Modeling, Frankfurt, Germany.
[Prokunina-Olsson, Ludmila; Tang, Wei] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Masur, Henry] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Osinusi, Anuoluwapo] Sci Applicat Int Corp Frederick Inc, Clin Monitoring Res Program, Clin Res Directorate, Frederick, MD USA.
[Osinusi, Anuoluwapo] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA.
RP Meissner, EG (reprint author), 10 Ctr Dr,Bldg 10 Room 11N204, Bethesda, MD 20892 USA.
EM eric.meissner@nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; National Institutes of Health Clinical Center;
Division of Cancer Epidemiology and Genetics of the National Cancer
Institute; National Institute of Allergy and Infectious Diseases; German
Research Foundation (DFG) by the clinical research unit [KFO 129]
FX This work was supported in part, with federal funds from the National
Cancer Institute, National Institutes of Health, under contract
HHSN261200800001E, the National Institutes of Health Clinical Center,
and the Division of Cancer Epidemiology and Genetics of the National
Cancer Institute. This research was supported, in part, by the
intramural program of the National Institute of Allergy and Infectious
Diseases. The study was also supported, in part, by the German Research
Foundation (DFG) by the clinical research unit KFO 129.
NR 15
TC 41
Z9 41
U1 0
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 1
PY 2014
VL 209
IS 11
BP 1700
EP 1704
DI 10.1093/infdis/jit827
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AH9TP
UT WOS:000336485900005
PM 24367041
ER
PT J
AU Preston, MD
Assefa, SA
Ocholla, H
Sutherland, CJ
Borrmann, S
Nzila, A
Michon, P
Hien, TT
Bousema, T
Drakeley, CJ
Zongo, I
Ouedraogo, JB
Djimde, AA
Doumbo, OK
Nosten, F
Fairhurst, RM
Conway, DJ
Roper, C
Clark, TG
AF Preston, Mark D.
Assefa, Samuel A.
Ocholla, Harold
Sutherland, Colin J.
Borrmann, Steffen
Nzila, Alexis
Michon, Pascal
Tran Tinh Hien
Bousema, Teun
Drakeley, Christopher J.
Zongo, Issaka
Ouedraogo, Jean-Bosco
Djimde, Abdoulaye A.
Doumbo, Ogobara K.
Nosten, Francois
Fairhurst, Rick M.
Conway, David J.
Roper, Cally
Clark, Taane G.
TI PlasmoView: A Web-based Resource to Visualise Global Plasmodium
falciparum Genomic Variation
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Plasmodium falciparum; malaria; genomics; drug resistance; vaccine
targets; visualization
ID CHLOROQUINE RESISTANCE; ARTEMISININ RESISTANCE; MITOCHONDRIAL-DNA;
GENETIC DIVERSITY; WESTERN CAMBODIA; MALARIA; MUTATIONS; ORIGIN;
POPULATIONS; VARIANTS
AB Malaria is a global public health challenge, with drug resistance a major barrier to disease control and elimination. To meet the urgent need for better treatments and vaccines, a deeper knowledge of Plasmodium biology and malaria epidemiology is required. An improved understanding of the genomic variation of malaria parasites, especially the most virulent Plasmodium falciparum (Pf) species, has the potential to yield new insights in these areas. High-throughput sequencing and genotyping is generating large amounts of genomic data across multiple parasite populations. The resulting ability to identify informative variants, particularly single-nucleotide polymorphisms (SNPs), will lead to the discovery of intra- and inter-population differences and thus enable the development of genetic barcodes for diagnostic assays and clinical studies. Knowledge of genetic variability underlying drug resistance and other differential phenotypes will also facilitate the identification of novel mutations and contribute to surveillance and stratified medicine applications. The PlasmoView interactive web-browsing tool enables the research community to visualise genomic variation and annotation (eg, biological function) in a geographic setting. The first release contains over 600 000 high-quality SNPs in 631 Pf isolates from laboratory strains and four malaria-endemic regions (West Africa, East Africa, Southeast Asia and Oceania).
C1 [Preston, Mark D.; Assefa, Samuel A.; Sutherland, Colin J.; Bousema, Teun; Drakeley, Christopher J.; Conway, David J.; Roper, Cally; Clark, Taane G.] LSHTM, Dept Pathogen Mol Biol, London WC1E 7HT, England.
[Ocholla, Harold] Malawi Liverpool Wellcome Trust Clin Res Programm, Blantyre 3, Malawi.
[Ocholla, Harold] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England.
[Borrmann, Steffen; Nzila, Alexis] KEMRI Wellcome Trust Res Programme, Kilifi, Kenya.
[Borrmann, Steffen] Heidelberg Univ, Sch Med, Dept Infect Dis, D-69120 Heidelberg, Germany.
[Nzila, Alexis] King Fahd Univ Petr & Minerals, Dhahran 31262, Saudi Arabia.
[Michon, Pascal] Papua New Guinea Inst Med Res, Madang, Papua N Guinea.
[Tran Tinh Hien] Hosp Trop Dis, Oxford Univ Clin Res Unit, Wellcome Trust Major Overseas Program, Ho Chi Minh City, Vietnam.
[Zongo, Issaka; Ouedraogo, Jean-Bosco] Inst Rech Sci St, Bobo Dioulasso 01, Burkina Faso.
[Djimde, Abdoulaye A.; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali.
[Djimde, Abdoulaye A.] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England.
[Nosten, Francois] Mahidol Oxford Trop Med Res Unit, Bangkok 10400, Thailand.
[Nosten, Francois] Univ Oxford, Ctr Trop Med, Oxford OX3 7LJ, England.
[Nosten, Francois] Shoklo Malaria Res Unit, Mae Sot Tak 63110, Thailand.
[Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Preston, MD (reprint author), LSHTM, Dept Pathogen Mol Biol, Keppel St, London WC1E 7HT, England.
EM mark.preston@lshtm.ac.uk
RI Roper, Cally/K-2989-2013; Bousema, Teun/N-3574-2014; Preston,
Mark/P-1429-2015;
OI Roper, Cally/0000-0002-6545-309X; Preston, Mark/0000-0002-6506-3104;
Borrmann, Steffen/0000-0001-9189-4393; Conway,
David/0000-0002-8711-3037; Nosten, Francois/0000-0002-7951-0745
FU Medical Research Council, UK [MR/J005398/1]; Malaria Capacity
Development Consortium (HO Wellcome Trust) [WT084289MA]; National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, USA
FX This work was supported by the Medical Research Council, UK (MDP and TGC
MR/J005398/1) the Malaria Capacity Development Consortium (HO Wellcome
Trust Grant WT084289MA) and the Intramural Research Program, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, USA (RMF).
NR 34
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U1 0
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 1
PY 2014
VL 209
IS 11
BP 1808
EP 1815
DI 10.1093/infdis/jit812
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA AH9TP
UT WOS:000336485900018
PM 24338354
ER
PT J
AU Reedy, J
Krebs-Smith, SM
Miller, PE
Liese, AD
Kahle, LL
Park, Y
Subar, AF
AF Reedy, Jill
Krebs-Smith, Susan M.
Miller, Paige E.
Liese, Angela D.
Kahle, Lisa L.
Park, Yikyung
Subar, Amy F.
TI Higher Diet Quality Is Associated with Decreased Risk of All-Cause,
Cardiovascular Disease, and Cancer Mortality among Older Adults
SO JOURNAL OF NUTRITION
LA English
DT Article
ID MAJOR CHRONIC DISEASE; HEALTHY EATING INDEX; FOOD-FREQUENCY
QUESTIONNAIRE; GUIDELINES-FOR-AMERICANS; RETIRED-PERSONS DIET;
LIFE-STYLE FACTORS; MEDITERRANEAN DIET; 10-YEAR MORTALITY;
NATIONAL-INSTITUTES; ALCOHOL-CONSUMPTION
AB Increased attention in dietary research and guidance has been focused on dietary patterns, rather than on single nutrients or food groups, because dietary components are consumed in combination and correlated with one another. However, the collective body of research on the topic has been hampered by the lack of consistency in methods used. We examined the relationships between 4 indices the Healthy Eating Index-2010 (HEI-2010), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED), and Dietary Approaches to Stop Hypertension (DASH) and all-cause, cardiovascular disease (CVD), and cancer mortality in the NIH-AARP Diet and Health Study (n = 492,823). Data from a 124-item food-frequency questionnaire were used to calculate scores; adjusted HRs and 95% CIs were estimated. We documented 86,419 deaths, including 23,502 CVD- and 29,415 cancer-specific deaths, during 15 y of follow-up. Higher index scores were associated with a 12-28% decreased risk of all-cause, CVD, and cancer mortality. Specifically, comparing the highest with the lowest quintile scores, adjusted HRs for all-cause mortality for men were as follows: HEI-2010 HR: 0.78(95% Cl: 0.76, 0.80), AHEI-2010 HR: 0.76(95% Cl: 0.74, 0.78), aMED HR: 0 77 (95% Cl: 0.75, 0.79), and DASH HR: 0.83 (95% Cl: 0.80, 0.85); for women, these were HEI-2010 HR: 0.77 (95% Cl: 0.74, 0.80), AHEI-2010 HR: 0.76 (95% CI: 0.74, 0.79), aMED HR: 0.76 (95% Cl: 0.73, 0.79), and DASH HR: 0.78 (95% Cl: 0.75, 0.81). Similarly, high adherence on each index was protective for CVD and cancer mortality examined separately. These findings indicate that multiple scores reflect core tenets of a healthy diet that may lower the risk of mortality outcomes, including federal guidance as operationalized in the HEI-2010, Harvard's Healthy Eating Plate as captured in the AHEI-2010, a Mediterranean diet as adapted in an Americanized aMED, and the DASH Eating Plan as included in the DASH score.
C1 [Reedy, Jill; Krebs-Smith, Susan M.; Subar, Amy F.] NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Park, Yikyung] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Miller, Paige E.] Exponent, Chicago, IL USA.
[Liese, Angela D.] Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
[Kahle, Lisa L.] Informat Management Serv Inc, Calverton, MD USA.
RP Reedy, J (reprint author), NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM reedyj@mail.nih.gov
OI Park, Yikyung/0000-0002-6281-489X
NR 46
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U1 2
U2 35
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD JUN
PY 2014
VL 144
IS 6
BP 881
EP 889
DI 10.3945/jn.113.189407
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AH9LZ
UT WOS:000336465200014
PM 24572039
ER
PT J
AU Beydoun, MA
Gamaldo, AA
Beydoun, HA
Tanaka, T
Tucker, KL
Talegawkar, SA
Ferrucci, L
Zonderman, AB
AF Beydoun, May A.
Gamaldo, Alyssa A.
Beydoun, Hind A.
Tanaka, Toshiko
Tucker, Katherine L.
Talegawkar, Sameera A.
Ferrucci, Luigi
Zonderman, Alan B.
TI Caffeine and Alcohol Intakes and Overall Nutrient Adequacy Are
Associated with Longitudinal Cognitive Performance among US Adults
SO JOURNAL OF NUTRITION
LA English
DT Article
ID OLDER CHINESE ADULTS; MEDITERRANEAN DIET; RISK-FACTORS; MIDDLE-AGE;
EPIDEMIOLOGIC EVIDENCE; COFFEE CONSUMPTION; JAPANESE-AMERICANS;
CIGARETTE-SMOKING; ALZHEIMER-DISEASE; COMMUNITY SAMPLE
AB Among modifiable lifestyle factor's, diet may affect cognitive health. Cross-sectional and longitudinal associations may exist between dietary exposures [e.g., caffeine (mg/d), alcohol (g/d), and nutrient adequacy] and cognitive performance and change over time. This was a prospective cohort study, the Baltimore Longitudinal Study of Aging (n = 628-1305 persons depending on the cognitive outcome; similar to 2 visits/person). Outcomes included 10 cognitive scores, spanning various domains of cognition. Caffeine and alcohol intakes and a nutrient adequacy score (NAS) were estimated from 7-d food diaries. Among key findings, caffeine intake was associated with better baseline global cognition among participants with a baseline age (Age(base)) of y. A higher NAS was associated with better baseline global cognition performance (overall, women, Age(base) <70 y), better baseline verbal memory (immediate and delayed recall, Age(base) >= 70 y), and slower rate of decline or faster improvement in the attention domain (women). For an Age(base) of <70 y, alcohol consumption was associated with slower improvement on letter fluency and global cognition over time. Conversely, for an Age(base) of >= 70y and among women, alcohol intake was related to better baseline attention and working memory. In sum, patterns of diet and cognition associations indicate stratum-specific associations by sex and baseline age. The general observed trend was that of putative beneficial effects of caffeine intake and nutrient adequacy on domains of global cognition, verbal memory, and attention, and mixed effects of alcohol on domains of letter fluency, attention, and working memory. Further longitudinal studies conducted on larger samples of adults are needed to determine whether dietary factors individually or in combination are modifiers of cognitive trajectories among adults.
C1 [Beydoun, May A.; Gamaldo, Alyssa A.; Tanaka, Toshiko; Ferrucci, Luigi; Zonderman, Alan B.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Gamaldo, Alyssa A.] Univ S Florida, Sch Aging Studies, Tampa, FL USA.
[Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
[Tucker, Katherine L.] Univ Massachusetts, Lowell, MA USA.
[Talegawkar, Sameera A.] Johns Hopkins Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, Baltimore, MD USA.
RP Beydoun, MA (reprint author), NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM baydounm@mail.nih.gov
OI Tucker, Katherine/0000-0001-7640-662X; Zonderman, Alan
B/0000-0002-6523-4778
FU National Institute on Aging, Intramural Research Program (NIA/NIH/IRP)
FX Supported entirely by the National Institute on Aging, Intramural
Research Program (NIA/NIH/IRP).
NR 94
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U1 3
U2 21
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD JUN
PY 2014
VL 144
IS 6
BP 890
EP 901
DI 10.3945/jn.113.189027
PG 12
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AH9LZ
UT WOS:000336465200015
PM 24744319
ER
PT J
AU Richard, SA
Black, RE
Gilman, RH
Guerrant, RL
Kang, G
Lanata, CF
Molbak, K
Rasmussen, ZA
Sack, RB
Valentiner-Branth, P
Checkley, W
AF Richard, Stephanie A.
Black, Robert E.
Gilman, Robert H.
Guerrant, Richard L.
Kang, Gagandeep
Lanata, Claudio F.
Molbak, Kare
Rasmussen, Zeba A.
Sack, R. Bradley
Valentiner-Branth, Palle
Checkley, William
CA Childhood Malnutr Infection
TI Catch-Up Growth Occurs after Diarrhea in Early Childhood
SO JOURNAL OF NUTRITION
LA English
DT Article
ID RURAL BANGLADESH; LINEAR GROWTH; PERUVIAN CHILDREN; GUINEA-BISSAU;
RISK-FACTORS; MALNUTRITION; DISEASE; MORBIDITY; COMMUNITY; INFANTS
AB Diarrhea and linear growth faltering continue to burden low-income countries and are among the most important contributors to poor health during early childhood. Diarrhea is thought to adversely affect linear growth, but catch-up growth can occur if no additional insults are experienced. We sought to characterize catch-up growth in relation to diarrhea burden in a multisite dataset of 1007 children. Using longitudinal anthropometry and diarrheal surveillance data from 7 cohort studies in 4 countries, we examined the relation between diarrhea prevalence and growth in 3- to 6-mo periods using linear mixed-effect models. Growth during each period was calculated as a function of age using linear splines. We incorporated the longitudinal prevalence of diarrhea in both current and previous periods into the model. Diarrhea during the current period was associated with slower linear and ponderal growth. Faster (catch-up) growth in length was observed in children with no diarrhea in age groups immediately after an age group in which diarrhea was experienced [age group >6-12 mo: 0.03 mm/mo for each percentage diarrhea prevalence in the previous period (95% Cl: 0.007, 0.06) relative to 11.3 mm/mo mean growth rate; age group >12-18 mo: 0.04 mm/mo (95% Cl: 0.02, 0.06) relative to 8.9 mm/mo mean growth rate; age group >18-24 mo: 0.04 mm/mo (95% Cl: 0.003, 0.09) relative to 7.9 mm/mo mean growth rate]. The associations were stronger in boys than in girls when separate models were run. Similar results were observed when weight was the outcome variable. When diarrheal episodes are followed by diarrhea-free periods in the first 2 y of life, catch-up growth is observed that may allow children to regain their original trajectories. The finding of a greater effect of diarrhea on linear growth in boys than in girls was unexpected and requires additional study. Diarrhea burdens are high throughout the first 2 y of life in these study sites, therefore reducing the likelihood of catch-up growth. Extending diarrhea-free periods may increase the likelihood of catch-up growth and decrease the prevalence of stunting.
C1 [Richard, Stephanie A.; Black, Robert E.; Gilman, Robert H.; Checkley, William] Johns Hopkins Univ, Program Global Dis Epidemiol & Control, Dept Int Hlth, Bloomberg Sch Publ Heath, Baltimore, MD 21218 USA.
[Richard, Stephanie A.; Rasmussen, Zeba A.; Sack, R. Bradley] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Guerrant, Richard L.] Univ Virginia, Sch Med, Ctr Global Hlth, Charlottesville, VA 22908 USA.
[Kang, Gagandeep] Christian Med Coll & Hosp, Dept Gastrointestinal Sci, Vellore, Tamil Nadu, India.
[Lanata, Claudio F.] Inst Invest Nutr, Lima, Peru.
[Molbak, Kare; Valentiner-Branth, Palle] Statens Serum Inst, Div Epidemiol, DK-2300 Copenhagen, Denmark.
RP Checkley, W (reprint author), Johns Hopkins Univ, Program Global Dis Epidemiol & Control, Dept Int Hlth, Bloomberg Sch Publ Heath, Baltimore, MD 21218 USA.
EM wcheckl1@jhmi.edu
OI Moore, Sean/0000-0003-1150-6632; Kang, Gagandeep/0000-0002-3656-564X;
Fischer, Thea Kolsen/0000-0003-4812-980X
FU Bill and Melinda Gates Foundation; Consequences for Child Health and
Development (MAL-ED); National Heart, Lung, and Blood Institute/NIH
[R00HL096955]
FX S.A.R. and W.C. were supported in part by the Bill and Melinda Gates
Foundation project The Etiology, Risk Factors and Interactions of
Enteric Infections and Malnutrition and the Consequences for Child
Health and Development (MAL-ED). S.A.R. was a Sommer Scholar in the
Department of International Health while conducting this work. W.C was
supported by Pathway to Independence Award R00HL096955 from the National
Heart, Lung, and Blood Institute/NIH.
NR 44
TC 11
Z9 11
U1 1
U2 13
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD JUN
PY 2014
VL 144
IS 6
BP 965
EP 971
DI 10.3945/jn.113.187161
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA AH9LZ
UT WOS:000336465200025
PM 24699805
ER
PT J
AU Shurin, SB
Castle, VP
AF Shurin, Susan B.
Castle, Valerie P.
TI United States Biomedical Research Impacting Child Health and the Growth
of the National Institutes of Health Funding to Pediatric Departments
and Children's Hospitals
SO JOURNAL OF PEDIATRICS
LA English
DT Editorial Material
C1 [Shurin, Susan B.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Castle, Valerie P.] Univ Michigan Hlth Syst, Mott Childrens Hosp, Dept Pediat, Ann Arbor, MI USA.
RP Shurin, SB (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 2
TC 1
Z9 1
U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD JUN
PY 2014
VL 164
IS 6
BP 1248
EP +
DI 10.1016/j.jpeds.2014.03.026
PG 3
WC Pediatrics
SC Pediatrics
GA AH9YX
UT WOS:000336503200001
PM 24855924
ER
PT J
AU Wren, TAL
Kalkwarf, HJ
Zemel, BS
Lappe, JM
Oberfield, S
Shepherd, JA
Winer, KK
Gilsanz, V
AF Wren, Tishya A. L.
Kalkwarf, Heidi J.
Zemel, Babette S.
Lappe, Joan M.
Oberfield, Sharon
Shepherd, John A.
Winer, Karen K.
Gilsanz, Vicente
CA Bone Mineral Density Childhood
TI Longitudinal Tracking of Dual-Energy X-ray Absorptiometry Bone Measures
Over 6 Years in Children and Adolescents: Persistence of Low Bone Mass
to Maturity
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID MINERAL DENSITY; CHILDHOOD; PUBERTY; GROWTH; BLACK; AGE; ACCUMULATION;
OSTEOPOROSIS; MATURATION; DAUGHTERS
AB Objectives Early assessment of bone mass may be useful for predicting future osteoporosis risk if bone measures "track" during growth. This prospective longitudinal multicenter study examined tracking of bone measures in children and adolescents over 6 years to sexual and skeletal maturity.
Study design A total of 240 healthy male and 293 healthy female patients, ages 6-17 years, underwent yearly evaluations of height, weight, body mass index, skeletal age, Tanner stage, and dual-energy x-ray absorptiometry (DXA) bone measurements of the whole body, spine, hip, and forearm for 6 years. All subjects were sexually and skeletally mature at final follow-up. Correlation was performed between baseline and 6-year follow-up measures, and change in DXA Z-scores was examined for subjects who had baseline Z < -1.5.
Results DXA Z-scores (r = 0.66-0.87) had similar tracking to anthropometric measures (r = 0.64-0.74). Tracking was stronger for bone mineral density compared with bone mineral content and for girls compared with boys. Tracking was weakest during mid-to late puberty but improved when Z-scores were adjusted for height. Almost all subjects with baseline Z < -1.5 had final Z-scores below average, with the majority remaining less than -1.0.
Conclusions Bone status during childhood is a strong predictor of bone status in young adulthood, when peak bone mass is achieved. This suggests that bone mass measurements in children and adolescents may be useful for early identification of individuals at risk for osteoporosis later in life.
C1 [Wren, Tishya A. L.; Gilsanz, Vicente] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Kalkwarf, Heidi J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Zemel, Babette S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Lappe, Joan M.] Creighton Univ, Omaha, NE 68178 USA.
[Oberfield, Sharon] Columbia Univ, New York, NY USA.
[Shepherd, John A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Winer, Karen K.] NICHHD, Bethesda, MD 20892 USA.
RP Wren, TAL (reprint author), Childrens Hosp Los Angeles, 4650 Sunset Blvd,MS 69, Los Angeles, CA 90027 USA.
EM twren@chla.usc.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [NO1-HD-1-3228, NO1-HD-1-3329, NO1-HD-1-3330, NO1-HD-1-3331,
NO1-HD-1-3332, NO1-HD-1-3333]; National Center for Research Resources
[UL1 RR026314, UL1RR024134]
FX Supported by Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NO1-HD-1-3228, NO1-HD-1-3329, NO1-HD-1-3330,
NO1-HD-1-3331, NO1-HD-1-3332, and NO1-HD-1-3333) and the National Center
for Research Resources (UL1 RR026314 and UL1RR024134). The authors
declare no conflicts of interest.
NR 29
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Z9 20
U1 0
U2 7
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD JUN
PY 2014
VL 164
IS 6
BP 1280
EP +
DI 10.1016/j.jpeds.2013.12.040
PG 8
WC Pediatrics
SC Pediatrics
GA AH9YX
UT WOS:000336503200011
PM 24485819
ER
PT J
AU DeMauro, SB
D'Agostino, JA
Bann, C
Bernbaum, J
Gerdes, M
Bell, EF
Carlo, WA
D'Angio, CT
Das, A
Higgins, R
Hintz, SR
Laptook, AR
Natarajan, G
Nelin, L
Poindexter, BB
Sanchez, PJ
Shankaran, S
Stoll, BJ
Truog, W
Van Meurs, KP
Vohr, B
Walsh, MC
Kirpalani, H
AF DeMauro, Sara B.
D'Agostino, Jo Ann
Bann, Carla
Bernbaum, Judy
Gerdes, Marsha
Bell, Edward F.
Carlo, Waldemar A.
D'Angio, Carl T.
Das, Abhik
Higgins, Rosemary
Hintz, Susan R.
Laptook, Abbot R.
Natarajan, Girija
Nelin, Leif
Poindexter, Brenda B.
Sanchez, Pablo J.
Shankaran, Seetha
Stoll, Barbara J.
Truog, William
Van Meurs, Krisa P.
Vohr, Betty
Walsh, Michele C.
Kirpalani, Haresh
CA Eunice Kennedy Shriver Natl Inst
TI Developmental Outcomes of Very Preterm Infants with Tracheostomies
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID LOW-BIRTH-WEIGHT; BRONCHOPULMONARY DYSPLASIA; NEURODEVELOPMENTAL
OUTCOMES; PEDIATRIC TRACHEOSTOMIES; PHYSIOLOGICAL DEFINITION; MECHANICAL
VENTILATION; EMOTIONAL ASSESSMENT; CAFFEINE THERAPY; CURRENT TRENDS;
CHILDREN
AB Objectives To evaluate the neurodevelopmental outcomes of very preterm (<30 weeks) infants who underwent tracheostomy.
Study design Retrospective cohort study from 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network over 10 years (2001-2011). Infants who survived to at least 36 weeks (N = 8683), including 304 infants with tracheostomies, were studied. Primary outcome was death or neurodevelopmental impairment (NDI; a composite of >= 1 of developmental delay, neurologic impairment, profound hearing loss, severe visual impairment) at a corrected age of 18-22 months. Outcomes were compared using multiple logistic regression. We assessed the impact of timing by comparing outcomes of infants who underwent tracheostomy before and after 120 days of life.
Results Tracheostomies were associated with all neonatal morbidities examined and with most adverse neurodevelopmental outcomes. Death or NDI occurred in 83% of infants with tracheostomies and 40% of those without (OR adjusted for center 7.0, 95% CI 5.2-9.5). After adjustment for potential confounders, odds of death or NDI remained higher (OR 3.3, 95% CI 2.4-4.6), but odds of death alone were lower (OR 0.4, 95% CI 0.3-0.7) among infants with tracheostomies. Death or NDI was lower in infants who received their tracheostomies before, rather than after, 120 days of life (aOR 0.5, 95% CI 0.3-0.9).
Conclusions Tracheostomy in preterm infants is associated with adverse developmental outcomes and cannot mitigate the significant risk associated with many complications of prematurity. These data may inform counseling about tracheostomy in this vulnerable population.
C1 [DeMauro, Sara B.; D'Agostino, Jo Ann; Bernbaum, Judy; Gerdes, Marsha; Kirpalani, Haresh] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[DeMauro, Sara B.; Bernbaum, Judy; Gerdes, Marsha; Kirpalani, Haresh] Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA.
[Bann, Carla; D'Angio, Carl T.] Res Triangle Inst, Res Triangle Pk, NC 27709 USA.
[Bell, Edward F.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Das, Abhik] Univ Rochester, Dept Pediat, Rochester, NY USA.
[Higgins, Rosemary] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Neonatal Res Network, Rockville, MD USA.
[Hintz, Susan R.; Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Laptook, Abbot R.; Vohr, Betty] Brown Univ, Dept Pediat, Providence, RI 02912 USA.
[Natarajan, Girija; Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
[Nelin, Leif] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA.
[Nelin, Leif] Nationwide Childrens Hosp, Columbus, OH USA.
[Poindexter, Brenda B.] Indiana Univ, Dept Pediat, Indianapolis, IN 46204 USA.
[Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Stoll, Barbara J.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Truog, William] Childrens Mercy Hosp, Dept Pediat, Kansas City, MO 64108 USA.
[Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
RP DeMauro, SB (reprint author), Childrens Hosp Philadelphia, 34th St & Civ Ctr Blvd,2nd Floor Main, Philadelphia, PA 19104 USA.
EM DeMauro@email.chop.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD) for the Neonatal Research
Network; Generic Database Study; Candidiasis Study; Cord Clamping Study;
Delivery Room CPAP Study; Early Blood Pressure pilot study; PCV-7 Study;
Phototherapy Trial; Preemie aEEG pilot study; Preemie iNO Trial; SUPPORT
trial
FX Supported by grants from the National Institutes of Health and the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) for the Neonatal Research Network, including for the
Generic Database Study, Candidiasis Study, Cord Clamping Study, Delivery
Room CPAP Study, Early Blood Pressure pilot study, PCV-7 Study,
Phototherapy Trial, Preemie aEEG pilot study, Preemie iNO Trial, and
SUPPORT trial. Data collected at participating sites of the NICHD
Neonatal Research Network were transmitted to RTI International, the
data coordinating center for the network, which stored, managed, and
analyzed the data for this study. The authors declare no conflicts of
interest.
NR 47
TC 15
Z9 15
U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD JUN
PY 2014
VL 164
IS 6
BP 1303
EP +
DI 10.1016/j.jpeds.2013.12.014
PG 10
WC Pediatrics
SC Pediatrics
GA AH9YX
UT WOS:000336503200016
PM 24472229
ER
PT J
AU Diaz, SD
Smith, LM
LaGasse, LL
Derauf, C
Newman, E
Shah, R
Arria, A
Huestis, MA
Della Grotta, S
Dansereau, LM
Neal, C
Lester, BM
AF Diaz, Sabrina D.
Smith, Lynne M.
LaGasse, Linda L.
Derauf, Chris
Newman, Elana
Shah, Rizwan
Arria, Amelia
Huestis, Marilyn A.
Della Grotta, Sheri
Dansereau, Lynne M.
Neal, Charles
Lester, Barry M.
TI Effects of Prenatal Methamphetamine Exposure on Behavioral and Cognitive
Findings at 7.5 Years of Age
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID MATERNAL LIFE-STYLE; PHYSICALLY ABUSED-CHILDREN; INFANT DEVELOPMENT;
PSYCHOSOCIAL CHARACTERISTICS; INTRAUTERINE GROWTH; COCAINE EXPOSURE;
PREGNANCY; OUTCOMES; ENVIRONMENT; AMPHETAMINE
AB Objective To examine child behavioral and cognitive outcomes after prenatal exposure to methamphetamine.
Study design We enrolled 412 mother-infant pairs (204 methamphetamine-exposed and 208 unexposed matched comparisons) in the Infant Development, Environment, and Lifestyle study. The 151 children exposed to methamphetamine and 147 comparisons who attended the 7.5-year visit were included. Exposure was determined by maternal self-report and/or positive meconium toxicology. Maternal interviews assessed behavioral and cognitive outcomes using the Conners' Parent Rating Scale-Revised: Short Form.
Results After adjusting for covariates, children exposed to methamphetamine had significantly higher cognitive problems subscale scores than comparisons and were 2.8 times more likely to have cognitive problems scores that were above average on the Conners' Parent Rating Scale-Revised: Short Form. No association between prenatal methamphetamine exposure and behavioral problems, measured by the oppositional, hyperactivity, and attention-deficit/hyperactivity disorder index subscales, were found.
Conclusions Prenatal methamphetamine exposure was associated with increased cognitive problems, which may affect academic achievement and lead to increased negative behavioral outcomes.
C1 [Diaz, Sabrina D.; Smith, Lynne M.] Univ Calif Los Angeles, Harbor UCLA Med Ctr, LA Inst Biomed, Los Angeles, CA USA.
[Diaz, Sabrina D.; Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[LaGasse, Linda L.; Della Grotta, Sheri; Dansereau, Lynne M.; Lester, Barry M.] Brown Univ, Women & Infants Hosp, Brown Ctr Study Children Risk, Warren Alpert Med Sch, Providence, RI USA.
[Derauf, Chris] Mayo Clin, Rochester, MN USA.
[Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA.
[Shah, Rizwan] Blank Hosp Reg Child Protect Ctr Iowa Hlth, Des Moines, IA USA.
[Arria, Amelia] Univ Maryland, Sch Publ Hlth, Ctr Young Adult Hlth & Dev, College Pk, MD 20742 USA.
[Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Neal, Charles] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
RP Smith, LM (reprint author), Harbor UCLA Med Ctr, 1124 W Carson St,RB-1, Torrance, CA 90502 USA.
EM smith@labiomed.org
OI Arria, Amelia/0000-0002-6360-9265
FU National Institute on Drug Abuse [R01DA014918]; National Center on
Research Resources [UL1TR000124, U54RR026136]
FX Supported by the National Institute on Drug Abuse (R01DA014918) and the
National Center on Research Resources (UL1TR000124 and U54RR026136). The
authors declare no conflicts of interest.
NR 38
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PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD JUN
PY 2014
VL 164
IS 6
BP 1333
EP 1338
DI 10.1016/j.jpeds.2014.01.053
PG 6
WC Pediatrics
SC Pediatrics
GA AH9YX
UT WOS:000336503200022
PM 24630350
ER
PT J
AU James, A
Hoang, U
Seagroatt, V
Clacey, J
Goldacre, M
Leibenluft, E
AF James, Anthony
Hoang, Uy
Seagroatt, Valerie
Clacey, Joe
Goldacre, Michael
Leibenluft, Ellen
TI A Comparison of American and English Hospital Discharge Rates for
Pediatric Bipolar Disorder, 2000 to 2010
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE pediatric; bipolar disorder; hospital discharge rates
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SEVERE MOOD DYSREGULATION;
FOLLOW-UP; NATIONAL TRENDS; I DISORDER; CHILDREN; MANIA; ADOLESCENTS;
YOUTH; PREVALENCE
AB Objective: Controversy exists over the diagnosis and prevalence of pediatric bipolar disorder (PBD). Although several small surveys suggest that the rate of the PBD diagnosis in clinical settings is higher in the United States than in other countries, no comprehensive cross-national comparisons of clinical practice have been performed. Here, we used longitudinal national datasets from 2000 to 2010 to compare US and English hospital discharge rates for PBD in patients aged 1 to 19 years. Method: We used the English National Health Service (NHS) Hospital Episode Statistics (RES) dataset and the United States National Hospital Discharge Survey (NHDS) to compare US and English discharge rates for PBD (bipolar I disorder [BP-I], bipolar II disorder [BP-II], bipolar disorder not otherwise specified [BP-NOS], and cyclothymia). We also conducted cross-national comparisons for all other psychiatric diagnoses in youth and for adults with bipolar disorder (BD). Results: There was a 72.1-fold difference in discharge rates for PBD in youth between the United States and England (United States, 100.9 per 100,000 population, 95% confidence interval = 98.1-103.8, versus England, 1.4 per 100,000 population, 95% CI = 1.4-1.5). After controlling for cross-national differences in length of stay, discharge rates for PBD remained 12.5 times higher in the United States than in England. For all other child psychiatric diagnoses, the discharge rate was 3.9-fold higher, and for adults with BD 7.2-fold higher, in the United States than in England. Conclusion: The disparity between US and English discharge rates for PBD is markedly greater than the disparity for child psychiatric discharge rates overall and for adult rates of BD. This suggests that the difference in discharge rates for PBD may be due to differing diagnostic practices for PBD in the United States versus in England.
C1 [James, Anthony] Univ Oxford, Oxford OX3 7JX, England.
[James, Anthony; Clacey, Joe] Warneford Hosp, Oxford OX3 7JX, England.
[Hoang, Uy; Seagroatt, Valerie; Goldacre, Michael] Univ Oxford, Nuffield Dept Populat Hlth, Oxford OX3 7JX, England.
[Leibenluft, Ellen] NIMH, Bethesda, MD 20892 USA.
RP James, A (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England.
EM anthony.james@psych.ox.ac.uk
FU English National Institute for Health Research
FX The English National Institute for Health Research funds the Unit of
Health Care Epidemiology to undertake research using the English
national dataset.
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U1 2
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD JUN
PY 2014
VL 53
IS 6
BP 614
EP 624
DI 10.1016/j.jaac.2014.02.008
PG 11
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA AI0SO
UT WOS:000336560400005
PM 24839880
ER
PT J
AU Pan, PM
Salum, GA
Gadelha, A
Moriyama, T
Cogo-Moreira, H
Graeff-Martins, AS
Rosario, MC
Polanczyk, GV
Brietzke, E
Rohde, LA
Stringaris, A
Goodman, R
Leibenluft, E
Bressan, RA
AF Pan, Pedro Mario
Salum, Giovanni Abrahao
Gadelha, Ary
Moriyama, Tais
Cogo-Moreira, Hugo
Graeff-Martins, Ana Soledade
Rosario, Maria Conceicao
Polanczyk, Guilherme Vanoni
Brietzke, Elisa
Rohde, Luis Augusto
Stringaris, Argyris
Goodman, Robert
Leibenluft, Ellen
Bressan, Rodrigo Affonseca
TI Manic Symptoms in Youth: Dimensions, Latent Classes, and Associations
With Parental Psychopathology
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE mania; bipolar; latent; family history; factor analysis
ID DIFFICULTIES QUESTIONNAIRE SDQ; BIPOLAR SPECTRUM DISORDERS;
PSYCHIATRIC-DISORDERS; COMMUNITY SAMPLE; ADOLESCENTS; CHILDREN;
STRENGTHS; VALIDATION; PHENOMENOLOGY; METAANALYSIS
AB Objective: The purpose of the study was to define the latent structure of parent-reported manic symptoms and their association with functional impairment and familial risk in a community sample of Brazilian children. Method: We screened for manic symptoms in a community sample of 2,512 children 6 to 12 years of age. Parents of children with "episodes of going abnormally high" completed a detailed mania section (n = 479; 19.1%). Confirmatory factor analysis (CFA) tested a solution with "Under-Control (UC)" and "Exuberant (EX)" dimensions, investigating the severity (threshold) and factor loading of each symptom. We also used latent class analysis (LCA) to evaluate the latent categorical structure of manic symptoms. Associations of these latent constructs with psychiatric comorbidity, psychosocial impairment, and family history of psychopathology were tested. Results: The 2-dimensional model fit the data well. Only the UC dimension was associated with psychiatric morbidity, psychosocial impairment, and a family history of mania, depression, or suicide attempts. Both UC and EX items discriminated subjects with "episodes of going abnormally high," but EX items lay at the mild end of the severity spectrum, whereas UC items lay at the severe end. The LCA yielded a small group of children with high levels of manic symptoms and a distinct profile of psychiatric comorbidity and impairment ("high-symptom group"). Conclusion: In a large, community-based sample, we found a 2-dimensional latent structure for parent-reported manic symptoms in youth, and demonstrated familial associations between the UC dimension and affective disorders. Both UC and EX items are clinically useful, but their contributions vary with symptom severity.
C1 [Pan, Pedro Mario; Gadelha, Ary; Moriyama, Tais; Cogo-Moreira, Hugo; Rosario, Maria Conceicao; Brietzke, Elisa; Bressan, Rodrigo Affonseca] Univ Fed Sao Paulo, Sao Paulo, Brazil.
[Salum, Giovanni Abrahao; Rohde, Luis Augusto] Univ Fed Rio Grande do Sul, BR-90046900 Porto Alegre, RS, Brazil.
[Graeff-Martins, Ana Soledade; Polanczyk, Guilherme Vanoni] Univ Sao Paulo, BR-05508 Sao Paulo, Brazil.
[Stringaris, Argyris; Goodman, Robert] Kings Coll London, London WC2R 2LS, England.
[Leibenluft, Ellen] NIMH, Bethesda, MD USA.
RP Pan, PM (reprint author), LINC Edificio Pesquisas 2,Rua Pedro Toledo,669, BR-04039032 Sao Paulo, Brazil.
EM pedro.pan@unifesp.br
RI Rohde, Luis Augusto/A-6426-2008; Bressan, Rodrigo/E-9178-2010;
Graeff-Martins, Ana Soledade/K-1974-2012; Salum, Giovanni/A-7849-2010;
Polanczyk, Guilherme/C-2345-2012; Cogo-Moreira, Hugo/E-4602-2011; Pan,
Pedro/I-5167-2013;
OI Rohde, Luis Augusto/0000-0002-4552-4188; Bressan,
Rodrigo/0000-0002-0868-4449; Salum, Giovanni/0000-0002-7537-7289;
Polanczyk, Guilherme/0000-0003-2311-3289; Cogo-Moreira,
Hugo/0000-0001-9411-9237; Pan, Pedro/0000-0002-1943-6520; Gadelha,
Ary/0000-0002-0993-8017
FU National Council for Scientific and Technological Development (CNPq);
Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); Sao
Paulo Research Foundation (FAPESP)
FX This work was supported by the following Brazilian government agencies:
The National Council for Scientific and Technological Development
(CNPq); the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior
(CAPES), and the Sao Paulo Research Foundation (FAPESP).
NR 41
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PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD JUN
PY 2014
VL 53
IS 6
BP 625
EP 634
DI 10.1016/j.jaac.2014.03.003
PG 10
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA AI0SO
UT WOS:000336560400006
PM 24839881
ER
PT J
AU Wang, YJ
Abu-Asab, MS
Yu, CR
Tang, ZS
Shen, DF
Tuo, JS
Li, XR
Chan, CC
AF Wang, Yujuan
Abu-Asab, Manes S.
Yu, Cheng-Rong
Tang, Zhongshu
Shen, Defen
Tuo, Jingsheng
Li, Xuri
Chan, Chi-Chao
TI Platelet-derived growth factor (PDGF)-C inhibits neuroretinal apoptosis
in a mu rifle model of focal retinal degeneration
SO LABORATORY INVESTIGATION
LA English
DT Article
DE age-related macular degeneration; apoptosis; neuroprotection;
platelet-derived growth factor-C; retina
ID TISSUE-PLASMINOGEN ACTIVATOR; ANTI-VEGF TREATMENT; MACULAR DEGENERATION;
PDGF-C; PHOTORECEPTOR DEGENERATION; PIGMENT EPITHELIUM; ALPHA-RECEPTOR;
BLOOD-VESSELS; BETA-RECEPTOR; HUMAN RPE
AB Platelet-derived growth factor (PDGF)-C is a member of the PDGF family and is critical for neuronal survival in the central nervous system. We studied the possible survival and antiapoptotic effects of PDGF-C on focal retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) on C57BL/6N [Crb1(rd8)] (DKO rd8) background mice, a model for progressive and focal retinal degeneration. We found no difference in transcript and protein expression of PDGF-C in the retina between DKO rd8 mice and wild type (WT, C57BL/6N). Recombinant PDGF-CC protein (500 ng/eye) was injected intravitreally into the right eye of DKO rd8 mice with phosphate-buffered saline as controls into the left eye. The retinal effects of PDGF-C were assessed by fundoscopy, ocular histopathology, A2E levels, apoptotic molecule analysis, and direct flat mount retinal vascular labeling. We found that the PDGF-CC-treated eyes showed slower progression or attenuation of the focal retinal lesions, lesser photoreceptor and retinal pigment epithelial degeneration resulting in better-preserved photoreceptor structure. Lower expression of apoptotic molecules was detected in the PDGF-CC-treated eyes than in controls. In addition, no retinal neovascularization was observed after PDGF-CC treatment. Our results demonstrate that PDGF-C potently ameliorates photoreceptor degeneration via the suppression of apoptotic pathways without inducing retinal angiogenesis. The protective effects of PDGF-C suggest a novel alternative approach for potential age-related retinal degeneration treatment.
C1 [Wang, Yujuan; Shen, Defen; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Wang, Yujuan; Tang, Zhongshu; Li, Xuri] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510275, Guangdong, Peoples R China.
[Abu-Asab, Manes S.; Chan, Chi-Chao] NEI, Histopathol Core, NIH, Bethesda, MD 20892 USA.
[Yu, Cheng-Rong] NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Chan, CC (reprint author), NEI, Immunopathol Sect, NIH, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
RI wang, yujuan/C-8428-2016
FU National Eye Institute Intramural Research Program
FX The National Eye Institute Intramural Research Program supported the
study.
NR 61
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U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD JUN
PY 2014
VL 94
IS 6
BP 674
EP 682
DI 10.1038/labinvest.2014.60
PG 9
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA AI0TI
UT WOS:000336562500008
PM 24709779
ER
PT J
AU Li, GW
Zhang, P
Wang, JP
An, YL
Gong, QH
Gregg, EW
Yang, WY
Zhang, B
Shuai, Y
Hong, J
Engelgau, MM
Li, H
Roglic, G
Hu, Y
Bennett, PH
AF Li, Guangwei
Zhang, Ping
Wang, Jinping
An, Yali
Gong, Qiuhong
Gregg, Edward W.
Yang, Wenying
Zhang, Bo
Shuai, Ying
Hong, Jing
Engelgau, Michael M.
Li, Hui
Roglic, Gojka
Hu, Yinghua
Bennett, Peter H.
TI Cardiovascular mortality, all-cause mortality, and diabetes incidence
after lifestyle intervention for people with impaired glucose tolerance
in the Da Qing Diabetes Prevention Study: a 23-year follow-up study
SO LANCET DIABETES & ENDOCRINOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIALS; FASTING GLUCOSE; ADULT DEATHS; METFORMIN;
MELLITUS; PROGRAM; IMPACT; CHINA; RISK; METAANALYSIS
AB Background Lifestyle interventions among people with impaired glucose tolerance reduce the incidence of diabetes, but their effect on all-cause and cardiovascular disease mortality is unclear. We assessed the long-term effect of lifestyle intervention on long-term outcomes among adults with impaired glucose tolerance who participated in the Da Qing Diabetes Prevention Study.
Methods The study was a cluster randomised trial in which 33 clinics in Da Qing, China-serving 577 adults with impaired glucose tolerance-were randomised (1: 1: 1: 1) to a control group or lifestyle intervention groups (diet or exercise or both). Patients were enrolled in 1986 and the intervention phase lasted for 6 years. In 2009, we followed up participants to assess the primary outcomes of cardiovascular mortality, all-cause mortality, and incidence of diabetes in the intention-to-treat population.
Findings Of the 577 patients, 439 were assigned to the intervention group and 138 were assigned to the control group (one refused baseline examination). 542 (94%) of 576 participants had complete data for mortality and 568 (99%) contributed data to the analysis. 174 participants died during the 23 years of follow-up (121 in the intervention group vs 53 in the control group). Cumulative incidence of cardiovascular disease mortality was 11.9% (95% CI 8.8-15.0) in the intervention group versus 19.6% (12.9-26.3) in the control group (hazard ratio [HR] 0.59, 95% CI 0.36-0 96; p=0.033). All-cause mortality was 28.1% (95% CI 23.9-32 4) versus 38.4% (30.3-46.5; HR 0 71, 95% CI 0.51-0.99; p=0.049). Incidence of diabetes was 72.6% (68.4-76.8) versus 89.9% (84.9-94.9; HR 0.55, 95% CI 0.40-0.76; p=0.001).
Interpretation A 6-year lifestyle intervention programme for Chinese people with impaired glucose tolerance can reduce incidence of cardiovascular and all-cause mortality and diabetes. These findings emphasise the long-term clinical benefits of lifestyle intervention for patients with impaired glucose tolerance and provide further justification for adoption of lifestyle interventions as public health measures to control the consequences of diabetes.
C1 [Li, Guangwei; Yang, Wenying; Zhang, Bo; Shuai, Ying; Hong, Jing] China Japan Friendship Hosp, Dept Endocrinol, Beijing, Peoples R China.
[Li, Guangwei; An, Yali; Gong, Qiuhong] Natl Ctr Cardiol, Ctr Endocrinol & Cardiovasc Dis, Beijing, Peoples R China.
[Li, Guangwei; An, Yali; Gong, Qiuhong] Fuwai Hosp, Beijing, Peoples R China.
[Zhang, Ping; Gregg, Edward W.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA 30341 USA.
[Engelgau, Michael M.] Ctr Dis Control & Prevent, Ctr Global Hlth, Atlanta, GA 30341 USA.
[Wang, Jinping; Li, Hui; Hu, Yinghua] Da Qing First Hosp, Dept Cardiol, Da Qing, Peoples R China.
[Roglic, Gojka] WHO, Dept Management Noncommunicable Dis, CH-1211 Geneva, Switzerland.
[Bennett, Peter H.] NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA.
RP Li, GW (reprint author), Dept Endocrinol, 167 Beilishi Rd, Beijing 100037, Peoples R China.
EM guangwei_li@medmail.com.cn; pzhang@cdc.gov
FU CDC/WHO [U58/CCU424123-01-02]; China-Japan Friendship Hospital
FX Supported by CDC/WHO Cooperative Agreement No. U58/CCU424123-01-02 and
the China-Japan Friendship Hospital. We thank the participants in the
original Da Qing Diabetes Prevention Study and their proxies who
contributed to the follow-up study. We also thank Lingzhi Kong, China
Ministry of Health, the leadership at the China-Japan Friendship
Hospital, Da Qing First Hospital, the Da Qing City Health Bureau, and
the Beijing and West Pacific Regional Office of WHO for their general
support. We thank Xilin Yang (Tianjin Medical University), Yang Yang
(National Center of Cardiology and Fuwai Hospital, China), and Ted
Thompson (Centers for Disease Control and Prevention, USA) for
statistical advice. Our special thanks go to the late Prof Xiaoren Pan
as this study would not have been possible without his leadership in the
design and implementation of the original Da Qing Diabetes Prevention
Study. The contents of this report are solely the responsibility of the
authors and do not necessarily represent the official positions of the
Centers for Disease Control and Prevention, the National Institute of
Diabetes and Digestive and Kidney Diseases, or WHO.
NR 33
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U2 41
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2213-8587
J9 LANCET DIABETES ENDO
JI Lancet Diabetes Endocrinol.
PD JUN
PY 2014
VL 2
IS 6
BP 474
EP 480
DI 10.1016/S2213-8587(14)70057-9
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AI2YE
UT WOS:000336724300024
PM 24731674
ER
PT J
AU Amaratunga, C
Witkowski, B
Khim, N
Menard, D
Fairhurst, RM
AF Amaratunga, Chanaki
Witkowski, Benoit
Khim, Nimol
Menard, Didier
Fairhurst, Rick M.
TI Artemisinin resistance in Plasmodium falciparum
SO LANCET INFECTIOUS DISEASES
LA English
DT Letter
ID MALARIA
C1 [Amaratunga, Chanaki; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Witkowski, Benoit; Khim, Nimol; Menard, Didier] Inst Pasteur Cambodge, Malaria Mol Epidemiol Unit, Phnom Penh, Cambodia.
RP Amaratunga, C (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM rfairhurst@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI001000-01]
NR 3
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U1 1
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUN
PY 2014
VL 14
IS 6
BP 449
EP 450
DI 10.1016/S1473-3099(14)70777-7
PG 2
WC Infectious Diseases
SC Infectious Diseases
GA AH8UW
UT WOS:000336414700010
PM 24849722
ER
PT J
AU Herrick, JA
Lederman, RJ
Sullivan, B
Powers, JH
Palmore, TN
AF Herrick, Jesica A.
Lederman, Robert J.
Sullivan, Brigit
Powers, John H.
Palmore, Tara N.
TI Brucella arteritis: clinical manifestations, treatment, and prognosis
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID ABDOMINAL AORTIC-ANEURYSM; MYCOTIC-ANEURYSM; SURGICAL-TREATMENT; ROOT
ABSCESS; ENDOCARDITIS; DOXYCYCLINE; MELITENSIS; INFECTION;
PSEUDOANEURYSM; METAANALYSIS
AB Brucellosis is the most common bacterial zoonosis, and causes a considerable burden of disease in endemic countries. Cardiovascular involvement is the main cause of mortality due to infection with Brucella spp, and most commonly manifests as endocarditis, peripheral and cerebrovascular aneurysms, or arterial and venous thromboses. We report a case of brucellosis presenting as bacteraemia and aortic endarteritis 18 years after the last known exposure to risk factors for brucella infection. The patient was treated with doxycycline, rifampicin, and gentamicin, and underwent surgical repair of a penetrating aortic ulcer, with a good clinical recovery. We review the signs and symptoms, diagnostic approach, prognosis, and treatment of brucella arteritis. We draw attention to the absence of consensus about the optimum therapy for vascular brucellosis, and the urgent need for additional studies and renewed scientific interest in this major pathogen.
C1 [Herrick, Jesica A.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Palmore, Tara N.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Powers, John H.] NIAID, Sci Applicat Int Corp Support Collaborat Clin Res, Bethesda, MD 20892 USA.
[Lederman, Robert J.] NHLBI, Cardiovasc & Pulm Branch, Bethesda, MD 20892 USA.
[Sullivan, Brigit] NIH, Off Res Serv, Bethesda, MD 20892 USA.
[Powers, John H.] George Washington Univ, Sch Med, Washington, DC USA.
RP Herrick, JA (reprint author), Univ Illinois, Dept Med, Sect Infect Dis Immunol & Int Med, 808 South Wood St MC 735, Chicago, IL 60612 USA.
EM christe5@uic.edu
OI lederman, robert/0000-0003-1202-6673
FU federal funds from the National Institute of Allergy and Infectious
Diseases, National Institutes of Health [HHSN261200800001E]; National
Cancer Institute, National Institutes of Health; Collaborative Clinical
Research Branch, Clinical Research Directorate/CMRP; SAIC-Frederick
FX We thank the Fellows Editorial Board of the NIH for their valuable
assistance with editing of this Grand Round. JP is supported by the
Collaborative Clinical Research Branch, Clinical Research
Directorate/CMRP, SAIC-Frederick. This project was supported by federal
funds from the National Institute of Allergy and Infectious Diseases,
National Institutes of Health, and from the National Cancer Institute,
National Institutes of Health, under contract number HHSN261200800001E.
The content of this publication does not necessarily represent the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organisations imply
endorsement by the US Government.
NR 64
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUN
PY 2014
VL 14
IS 6
BP 520
EP 526
DI 10.1016/S1473-3099(13)70270-6
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA AH8UW
UT WOS:000336414700023
PM 24480149
ER
PT J
AU Boada, M
Antunez, C
Ramirez-Lorca, R
DeStefano, AL
Gonzalez-Perez, A
Gayan, J
Lopez-Arrieta, J
Ikram, MA
Hernandez, I
Marin, J
Galan, JJ
Bis, JC
Mauleon, A
Rosende-Roca, M
Moreno-Rey, C
Gudnasson, V
Moron, FJ
Velasco, J
Carrasco, JM
Alegret, M
Espinosa, A
Vinyes, G
Lafuente, A
Vargas, L
Fitzpatrick, AL
Launer, LJ
Saez, ME
Vazquez, E
Becker, JT
Lopez, OL
Serrano-Rios, M
Tarraga, L
van Duijn, CM
Real, LM
Seshadri, S
Ruiz, A
AF Boada, M.
Antunez, C.
Ramirez-Lorca, R.
DeStefano, A. L.
Gonzalez-Perez, A.
Gayan, J.
Lopez-Arrieta, J.
Ikram, M. A.
Hernandez, I.
Marin, J.
Galan, J. J.
Bis, J. C.
Mauleon, A.
Rosende-Roca, M.
Moreno-Rey, C.
Gudnasson, V.
Moron, F. J.
Velasco, J.
Carrasco, J. M.
Alegret, M.
Espinosa, A.
Vinyes, G.
Lafuente, A.
Vargas, L.
Fitzpatrick, A. L.
Launer, L. J.
Saez, M. E.
Vazquez, E.
Becker, J. T.
Lopez, O. L.
Serrano-Rios, M.
Tarraga, L.
van Duijn, C. M.
Real, L. M.
Seshadri, S.
Ruiz, A.
CA Alzheimer's Dis Neuroimaging Initi
TI ATP5H/KCTD2 locus is associated with Alzheimer's disease risk
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE Alzheimer's disease; genomics; GWAS; molecular epidemiology; SNP
ID GENOME-WIDE ASSOCIATION; LATE-ONSET ALZHEIMERS; IDENTIFIES VARIANTS;
COMMON VARIANTS; GENE; VISUALIZATION; POPULATION; EXPRESSION; CARRIERS;
MODIFY
AB To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheimer's disease (AD) cases; 12 040 controls) were selected, and in Stage II these were examined in an in silico analysis within the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium GWAS (1367 cases and 12904 controls). Six novel signals reaching P<5 x 10(-6) were genotyped in an independent Stage III sample (the Fundacio ACE data set) of 2200 sporadic AD patients and 2301 controls. We identified a novel association with AD in the adenosine triphosphate (ATP) synthase, H + transporting, mitochondrial F0 (ATP5H)/Potassium channel tetramerization domain-containing protein 2 (KCTD2) locus, which reached genome-wide significance in the combined discovery and genotyping sample (rs11870474, odds ratio (OR)= 1.58, P= 2.6 X 10(-7) in discovery and OR 1.43, P= 0.004 in Fundacio ACE data set; combined OR= 1.53, P= 4.7 X 10(-9)). This ATP5H/KCTD2 locus has an important function in mitochondrial energy production and neuronal hyperpolarization during cellular stress conditions, such as hypoxia or glucose deprivation.
C1 [Boada, M.; Hernandez, I.; Mauleon, A.; Rosende-Roca, M.; Alegret, M.; Espinosa, A.; Vinyes, G.; Lafuente, A.; Vargas, L.; Tarraga, L.; Ruiz, A.] Fdn ACE, Memory Clin, Inst Catala Neurociencies Aplicades, Barcelona 08029, Spain.
[Boada, M.] Univ Autonoma Barcelona VHIR UAB, Hosp Univ Vall dHebron Inst Recerca, E-08193 Barcelona, Spain.
[Antunez, C.; Marin, J.] Univ Hosp Virgen de la Arrixaca, Dementia Unit, Murcia, Spain.
[Ramirez-Lorca, R.; Gonzalez-Perez, A.; Gayan, J.; Galan, J. J.; Moreno-Rey, C.; Moron, F. J.; Velasco, J.; Carrasco, J. M.; Saez, M. E.; Vazquez, E.; Real, L. M.; Ruiz, A.] Neocodex, Dept Struct Genom, Seville, Spain.
[DeStefano, A. L.; Seshadri, S.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[DeStefano, A. L.; Seshadri, S.] Boston Univ, Sch Med, Dept Biostat, Boston, MA USA.
[Lopez-Arrieta, J.] Univ Hosp La Paz Cantoblanco, Memory Unit, Madrid, Spain.
[Ikram, M. A.; van Duijn, C. M.] Erasmus MC Univ Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Ikram, M. A.; van Duijn, C. M.] Netherlands Consortium Hlth Aging, Leiden, Netherlands.
[Bis, J. C.; Fitzpatrick, A. L.] Univ Washington, Dept Med, Seattle, WA USA.
[Gudnasson, V.] Kopavogur Univ Iceland, Icelandic Heart Assoc, Kopavogur, Iceland.
[Launer, L. J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Washington, DC USA.
[Becker, J. T.; Lopez, O. L.] Univ Pittsburgh, Sch Med, Alzheimers Dis Res Ctr, Dept Neurol, Pittsburgh, PA USA.
[Becker, J. T.] Univ Pittsburgh, Sch Med, Alzheimers Dis Res Ctr, Dept Psychiat, Pittsburgh, PA USA.
[Becker, J. T.] Univ Pittsburgh, Sch Med, Alzheimers Dis Res Ctr, Dept Psychol, Pittsburgh, PA USA.
[Serrano-Rios, M.] Hosp Clin San Carlos, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid, Spain.
[Seshadri, S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Ruiz, A (reprint author), Fdn ACE, CSO Cap Recerca, Inst Catala Neurociencies Aplicades, Marques Sentmenat 57, Barcelona 08029, Spain.
EM aruiz@fundacioace.com
RI Reposo, Ramirez-Lorca/D-7907-2014; Real, Luis M/K-9646-2014;
Gonzalez-Perez, Antonio/A-5247-2010; IBIS, INFECCIOSAS HU/C-1271-2016;
IBIS, TERAPIA CELULA/P-3297-2015;
OI Real, Luis M/0000-0003-4932-7429; Gonzalez-Perez,
Antonio/0000-0001-9771-5982; Ikram, Mohammad Arfan/0000-0003-0372-8585
FU Fundacion Alzheimur (Murcia); Ministerio de Educacion y Ciencia
[PCT-010000-2007-18, DEX-580000-2008-4]; Corporacion Tecnologica de
Andalucia [08/211]; Agencia IDEA [841318]; Diabetes Research Laboratory,
Biomedical Research Foundation; CIBER de Diabetes y Enfermedades
Metabolicas Asociadas; Alzheimer's Disease Neuroimaging Initiative
(ADNI); National Institutes of Health Grant [U01 AG024904]; National
Institute on Aging, the National Institute of Biomedical Imaging and
Bioengineering; Abbott; Janssen Alzheimer Immunotherapy Research
Development; Johnson & Johnson Pharmaceutical Research & Development
LLC; Medpace, Inc.; Merck Co., Inc.; Meso Scale Diagnostics, LLC;
Novartis Pharmaceuticals Corporation; Pfizer Inc; NIH [P30 AG010129, K01
AG030514]; Dana Foundation; Fundacio ACE collaborates with CIBERNED;
Alzheimer's Association; Alzheimer's Drug Discovery Foundation
FX We thank the patients and controls who participated in this project.
This work has been partially funded by the Fundacion Alzheimur (Murcia),
the Ministerio de Educacion y Ciencia (PCT-010000-2007-18),
(DEX-580000-2008-4; Gobierno de Espana), Corporacion Tecnologica de
Andalucia (08/211) and Agencia IDEA (841318) (Consejeria de Innovacion,
Junta de Andalucia). The Diabetes Research Laboratory, Biomedical
Research Foundation. University Hospital Clinico San Carlos has been
supported by CIBER de Diabetes y Enfermedades Metabolicas Asociadas
(CIBERDEM); CIBERDEM is an ISCIII Project. We are indebted to Trinitat
Port-Carbo ' and her family who are supporting Fundacio ' ACE research
programs. We also are indebted to TGEN investigators who provided a free
access to genotype data to other researchers via Coriell
Biorepositories. The genotypic and associated phenotypic data used in
the study, 'Multi-Site Collaborative Study for Genotype-Phenotype
Associations in Alzheimer's Disease (GenADA)' were provided by the
GlaxoSmithKline, R& D Limited. The data sets used for analyses described
in this manuscript were obtained from dbGaP through dbGaP accession
number phs000219. v1. p1. Funding support for the ` Genetic Consortium
for Late Onset Alzheimer's Disease' was provided through the Division of
Neuroscience, NIA. The Genetic Consortium for Late Onset Alzheimer's
Disease includes a genome-wide association study funded as part of the
Division of Neuroscience, NIA. Assistance with phenotype harmonization
and genotype cleaning, as well as with general study coordination, was
provided by Genetic Consortium for Late Onset Alzheimer's Disease. The
data sets used for analyses described in this manuscript were obtained
from dbGaP through dbGaP accession number phs000168. v1. p1. Data
collection and sharing for this project was funded by the Alzheimer's
Disease Neuroimaging Initiative (ADNI) (National Institutes of Health
Grant U01 AG024904). ADNI is funded by the National Institute on Aging,
the National Institute of Biomedical Imaging and Bioengineering and
through generous contributions from the following: Abbott; Alzheimer's
Association; Alzheimer's Drug Discovery Foundation; Amorfix Life
Sciences Ltd.; AstraZeneca; Bayer HealthCare; BioClinica, Inc.; Biogen
Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan
Pharmaceuticals Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd
and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics,
N. V.; Janssen Alzheimer Immunotherapy Research & Development, LLC;
Johnson & Johnson Pharmaceutical Research & Development LLC; Medpace,
Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; Novartis
Pharmaceuticals Corporation; Pfizer Inc.; Servier; Synarc Inc.; and
Takeda Pharmaceutical Company. The Canadian Institutes of Health
Research is providing funds to support ADNI clinical sites in Canada.
Private sector contributions are facilitated by the Foundation for the
National Institutes of Health (www.fnih.org). The grantee organization
is the Northern California Institute for Research and Education, and the
study is coordinated by the Alzheimer's Disease Cooperative Study at the
University of California, San Diego, CA, USA. ADNI data are disseminated
by the Laboratory for Neuro Imaging at the University of California, Los
Angeles, CA, USA. This research was also supported by NIH Grants P30
AG010129, K01 AG030514 and the Dana Foundation. Fundacio ACE
collaborates with CIBERNED.; The following have contributed to the
papers as collaborators: Alejandro Romo, Irene Blanca, Susana Ruiz, Mar
Buendia, Fuensanta Noguera-Perea, Emma Rodriguez-Noriega, Evaristo
Fernandez-Aranda, Agustina Legaz-Garcia, Laura Vivancos-Moreau, America
Morera, Marina Guitart, Susana Lara, Martirio Antequera-Torres,
Salvadora Manzanares, Sandra Castano, Blanca Garcia, Begona
Martinez-Herrada, Sergi Valero.
NR 43
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U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD JUN
PY 2014
VL 19
IS 6
BP 682
EP 687
DI 10.1038/mp.2013.86
PG 6
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA AI2BZ
UT WOS:000336663100010
PM 23857120
ER
PT J
AU Kasza, KA
Bansal-Travers, M
O'Connor, RJ
Compton, WM
Kettermann, A
Borek, N
Fong, GT
Cummings, KM
Hyland, AJ
AF Kasza, Karin A.
Bansal-Travers, Maansi
O'Connor, Richard J.
Compton, Wilson M.
Kettermann, Anna
Borek, Nicolette
Fong, Geoffrey T.
Cummings, K. Michael
Hyland, Andrew J.
TI Cigarette Smokers' Use of Unconventional Tobacco Products and
Associations With Quitting Activity: Findings From the ITC-4 U.S. Cohort
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID 4 COUNTRY SURVEY; SMOKELESS TOBACCO; SMOKING-CESSATION; ELECTRONIC
CIGARETTES; DELIVERY-SYSTEMS; POLYTOBACCO USE; PATTERNS; SNUS;
INITIATION; REDUCTION
AB The purpose of this study was to evaluate the prevalence and correlates of use of nicotine-containing tobacco products such as cigars, pipe tobacco, and cigarettes that promise less exposure to toxins; e-cigarettes; and smokeless tobacco products among a cohort of conventional cigarette smokers followed over the past decade. We also evaluated associations between use of such products and cigarette quitting.
Participants were 6,110 adult smokers in the United States, who were interviewed as part of the International Tobacco Control Four Country Survey between 2002 and 2011. Respondents reported their concurrent use of other smoked tobacco products (including cigars, pipe tobacco, and cigarillos), smokeless tobacco products (including chewing tobacco, snus, and snuff), unconventional cigarettes (including Omni, Accord, and Eclipse), and electronic cigarettes. Prevalence and correlates of use and associations between use and cigarette quitting were assessed using regression analyses via generalized estimating equations.
Most cigarette smokers did not use unconventional tobacco products, although use of any of these products started to rise at the end of the study period (2011). For each type of tobacco product evaluated, use was most prevalent among those aged 18-24 years. Smokers who did use unconventional tobacco products did not experience a clear cessation advantage.
During the past decade, relatively few cigarette smokers reported also using other tobacco products. Those that did use such products were no more likely to stop using conventional cigarettes compared with those who did not use such products.
C1 [Kasza, Karin A.] Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Buffalo, NY 14263 USA.
[Bansal-Travers, Maansi; O'Connor, Richard J.; Hyland, Andrew J.] Roswell Pk Canc Inst, Dept Hlth Behav, Buffalo, NY 14263 USA.
[Compton, Wilson M.] NIDA, NIH, Bethesda, MD 20892 USA.
[Kettermann, Anna; Borek, Nicolette] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA.
[Fong, Geoffrey T.] Univ Waterloo, Dept Psychol, Waterloo, CA USA.
[Fong, Geoffrey T.] Ontario Inst Canc Res, Toronto, ON, Canada.
[Cummings, K. Michael] Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA.
RP Kasza, KA (reprint author), Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Buffalo, NY 14263 USA.
EM karin.kasza@roswellpark.org
RI Fong, Geoffrey/H-2810-2014; O'Connor, Richard/A-6961-2009
OI Fong, Geoffrey/0000-0001-9098-6472;
FU Federal funds from the National Institute on Drug Abuse; National
Institutes of Health; U.S. Food and Drug Administration, Department of
Health and Human Services [HHSN271201100027C]; U.S. National Cancer
Institute [P50 CA111326, P01 CA138389, R01 CA100362, R01 CA125116];
Canadian Institutes of Health Research [57897, 79551, 115016]; National
Health and Medical Research Council of Australia [265903, 450110,
1005922]; Cancer Research UK [C312/A3726, C312/A6465, C312/A11039];
Robert Wood Johnson Foundation [045734]; Canadian Tobacco Control
Research Initiative [014578]; Ontario Institute for Cancer Research;
Canadian Cancer Society Research Institute
FX This study was supported by Federal funds from the National Institute on
Drug Abuse, National Institutes of Health, and the U.S. Food and Drug
Administration, Department of Health and Human Services, under Contract
No. HHSN271201100027C. The ITC Four Country Survey has been funded by
the U.S. National Cancer Institute (P50 CA111326, P01 CA138389, R01
CA100362, R01 CA125116), Canadian Institutes of Health Research (57897,
79551, and 115016), National Health and Medical Research Council of
Australia (265903, 450110, and 1005922), Cancer Research UK (C312/A3726,
C312/A6465, and C312/A11039), Robert Wood Johnson Foundation (045734),
and Canadian Tobacco Control Research Initiative (014578). Geoffrey T.
Fong is supported by a Senior Investigator Award from the Ontario
Institute for Cancer Research and a Prevention Scientist Award from the
Canadian Cancer Society Research Institute. The roles of Wilson Compton,
Nicolette Borek, and Anna Kettermann on this article are solely as
collaborators on HHSN271201100027C, with no involvement in any other
cited projects.
NR 46
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U1 2
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
EI 1469-994X
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD JUN
PY 2014
VL 16
IS 6
BP 672
EP 681
DI 10.1093/ntr/ntt212
PG 10
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA AH9UX
UT WOS:000336491000006
PM 24376276
ER
PT J
AU Sutin, AR
English, D
Evans, MK
Zonderman, AB
AF Sutin, Angelina R.
English, Devin
Evans, Michele K.
Zonderman, Alan B.
TI Perceived Sex Discrimination Amplifies the Effect of Antagonism on
Cigarette Smoking
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID RACIAL-DISCRIMINATION; NICOTINE WITHDRAWAL; PERSONALITY-TRAITS; 5-FACTOR
MODEL; MENTAL-HEALTH; UNITED-STATES; LIFE; DEPRESSION; PREDICTION;
HOSTILITY
AB Compared to men, the decline in smoking during the past few decades has been slower for women, and smoking-related morbidity and mortality has increased substantially. Identifying sex-specific risk factors will inform more targeted intervention/prevention efforts. The purpose of this research is to examine the interactive effect of psychological (trait antagonism) and social (perceived sex discrimination) factors on current cigarette smoking and whether these effects differ by sex.
Participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study (HANDLS; N = 454) and participants in the Health and Retirement Study (HRS; N = 8,155) completed measures of antagonism, perceived sex discrimination, and reported whether they smoked currently. Logistic regressions were used to predict smoking from antagonism, discrimination, and their interaction.
Antagonism was associated with an increased risk of smoking. For women, there was an interaction between antagonism and discrimination: among women who perceived sex discrimination, every standard deviation increase in antagonism was associated with a 2.5 increased risk of current smoking in HANDLS (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.46-4.39) and an almost 1.5 increased risk in HRS (OR = 1.43, 95% CI = 1.18-1.73). This interaction was not significant for men in either sample.
In 2 independent samples, perceived sex discrimination amplified the effect of antagonism on cigarette smoking for women but not men. A hostile disposition and a perceived hostile social environment have a synergistic effect on current cigarette smoking for women.
C1 [Sutin, Angelina R.] Florida State Univ, Coll Med, Dept Behav Sci & Social Med, Tallahassee, FL 32306 USA.
[English, Devin] George Washington Univ, Dept Psychol, Washington, DC 20052 USA.
[Evans, Michele K.; Zonderman, Alan B.] NIA, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA.
RP Sutin, AR (reprint author), Florida State Univ, Coll Med, Dept Behav Sci & Social Med, 1115 W Call St, Tallahassee, FL 32306 USA.
EM angelina.sutin@med.fsu.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health; National Institute on Aging [NIA U01AG009740]
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health. The
Health and Retirement Study is sponsored by the National Institute on
Aging (NIA U01AG009740) and is conducted by the University of Michigan.
NR 48
TC 0
Z9 0
U1 2
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
EI 1469-994X
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD JUN
PY 2014
VL 16
IS 6
BP 794
EP 799
DI 10.1093/ntr/ntt222
PG 6
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA AH9UX
UT WOS:000336491000020
PM 24477195
ER
PT J
AU Persoskie, A
Mao, QN
Chou, WYS
Hesse, BW
Zhao, XQ
Yu, GM
Li, YH
Xu, ZH
Song, MJ
Nie, XQ
Kim, P
Kreps, GL
AF Persoskie, Alexander
Mao, Qunan
Chou, Wen-Ying Sylvia
Hesse, Bradford W.
Zhao, Xiaoquan
Yu, Guoming
Li, Yinghua
Xu, Zihao
Song, Meijie
Nie, Xueqiong
Kim, Paula
Kreps, Gary L.
TI Absolute and Comparative Cancer Risk Perceptions Among Smokers in Two
Cities in China
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID UNREALISTIC OPTIMISM; SMOKING-CESSATION; CIGARETTE SMOKERS; HEALTH;
MORTALITY; IMPLEMENTATION; PREVALENCE; BELIEFS; DISEASE; BIAS
AB Introduction: Knowledge about health effects of smoking motivates quit attempts and sustained abstinence among smokers and also predicts greater acceptance of tobacco control efforts such as cigarette taxes and public smoking bans. We examined whether smokers in China, the world's largest consumer of cigarettes, recognized their heightened personal risk of cancer relative to nonsmokers.
Methods: A sample of Chinese people (N = 2,517; 555 current smokers) from 2 cities (Beijing and Hefei) estimated their personal risk of developing cancer, both in absolute terms (overall likelihood) and in comparative terms (relative to similarly aged people).
Results: Controlling for demographics, smokers judged themselves to be at significantly lower risk of cancer than did nonsmokers on the comparative measure. No significant difference emerged between smokers and nonsmokers in absolute estimates.
Conclusions: Smokers in China did not recognize their heightened personal risk of cancer, possibly reflecting ineffective warning labels on cigarette packs, a positive affective climate associated with smoking in China, and beliefs that downplay personal vulnerability among smokers (e. g., I don't smoke enough to increase my cancer risk; I smoke high-quality cigarettes that won't cause cancer).
C1 [Persoskie, Alexander; Chou, Wen-Ying Sylvia; Hesse, Bradford W.] NCI, Behav Res Program, Bethesda, MD 20892 USA.
[Mao, Qunan; Li, Yinghua; Nie, Xueqiong] Minist Hlth, Chinese Ctr Hlth Educ, Beijing, Peoples R China.
[Zhao, Xiaoquan; Kim, Paula; Kreps, Gary L.] George Mason Univ, Dept Commun, Fairfax, VA 22030 USA.
[Yu, Guoming; Xu, Zihao; Song, Meijie] Renmin Univ, Sch Journalism & Commun, Beijing, Peoples R China.
RP Persoskie, A (reprint author), NCI, Behav Res Program, 9609 Med Ctr Dr,Room 3E204, Bethesda, MD 20892 USA.
EM persoskieai@mail.nih.gov
OI Hesse, Bradford/0000-0003-1142-1161
FU Chinese Center for Health Education, Ministry of Health, China
FX This work was funded by the Chinese Center for Health Education,
Ministry of Health, China.
NR 41
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U1 1
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
EI 1469-994X
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD JUN
PY 2014
VL 16
IS 6
BP 899
EP 903
DI 10.1093/ntr/ntu028
PG 5
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA AH9UX
UT WOS:000336491000037
PM 24668289
ER
PT J
AU White, A
AF White, Amina
TI Responding to Prenatal Disclosure of Past Sexual Abuse
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; MATERNITY CARE; PREVALENCE; HISTORY;
TRAUMA
AB The American College of Obstetricians and Gynecologists recommends that physicians elicit a sexual abuse and rape trauma history for every patient, yet, in practice, physicians still may struggle to understand how best to obtain this history and what clinical obligations arise when a physician inquires and a woman discloses a remote history of childhood or adult sexual trauma during the course of her prenatal care. This commentary offers a practical strategy for responding to sexual trauma disclosure by developing a tailored obstetric care plan for avoiding retraumatization in labor. In this way, obstetricians may avoid causing harm and begin to meet the unique obstetric and psychological needs of sexual trauma survivors during pregnancy and delivery.
C1 NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
RP White, A (reprint author), NIH, Ctr Clin, Dept Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM amina.white@nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 11
TC 0
Z9 0
U1 0
U2 4
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 JUN
PY 2014
VL 123
IS 6
SI SI
BP 1344
EP 1347
DI 10.1097/AOG.0000000000000266
PG 4
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AI4BF
UT WOS:000336809600028
PM 24807334
ER
PT J
AU Pang, ALY
Title, AC
Rennert, OM
AF Pang, Alan Lap-Yin
Title, Alexandra C.
Rennert, Owen M.
TI Modulation of microRNA expression in human lung cancer cells by the G9a
histone methyltransferase inhibitor BIX01294
SO ONCOLOGY LETTERS
LA English
DT Article
DE G9a methyltransferase; microRNA; lung cancer; H1299; BIX01294
ID TUMOR-SUPPRESSOR; DNA METHYLATION; DOWN-REGULATION; EPIGENETIC
REGULATION; INDUCE APOPTOSIS; GENE; INVASION; TARGETS; AMPLIFICATION;
CARCINOMA
AB MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of their target genes at the post-transcriptional level. In cancer cells, miRNAs, depending on the biological functions of their target genes, may have a tumor-promoting or -suppressing effect. Treatment of cancer cells with inhibitors of DNA methylation and/or histone deacetylation modulates the expression level of miRNAs, which provides evidence for epigenetic regulation of miRNA expression. The consequences of inhibition of histone methyltransferase on miRNA expression, however, have not been thoroughly investigated. The present study examined the expression pattern of miRNAs in the non-small cell lung cancer cell line, H1299 with or without treatment of BIX01294, a potent chemical inhibitor of G9a methyltransferase that catalyzes the mono-and di-methylation of the lysine 9 residue of histone H3. By coupling microarray analysis with quantitative real-time polymerase chain reaction analysis, two miRNAs were identified that showed consistent downregulation following BIX01294 treatment. The results indicate that histone H3 methylation regulates miRNA expression in lung cancer cells, which may provide additional insight for future chemical treatment of lung cancer.
C1 [Pang, Alan Lap-Yin; Title, Alexandra C.; Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Genom, NIH, Bethesda, MD 20892 USA.
RP Pang, ALY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin & Dev Genom, NIH, 49 Convent Dr,Room 2C08,MSC 4429, Bethesda, MD 20892 USA.
EM alypang@yahoo.com
FU Intramural Research Program of Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Institutes of Health,
USA
FX The authors are supported by the Intramural Research Program of Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, USA.
NR 47
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Z9 1
U1 1
U2 10
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1792-1074
EI 1792-1082
J9 ONCOL LETT
JI Oncol. Lett.
PD JUN
PY 2014
VL 7
IS 6
BP 1819
EP 1825
DI 10.3892/ol.2014.2034
PG 7
WC Oncology
SC Oncology
GA AI0QY
UT WOS:000336555200013
ER
PT J
AU Wright, SE
Rewers-Felicins, KA
Quinlin, I
Chowdhury, NI
Ahmed, J
Eldridge, PW
Srivastava, SK
Pastan, I
AF Wright, Stephen E.
Rewers-Felicins, Kathleen A.
Quinlin, Imelda
Chowdhury, Nazrul I.
Ahmed, Jewel
Eldridge, Paul W.
Srivastava, Sanjay K.
Pastan, Ira
TI TGF alpha-PE38 enhances cytotoxic T-lymphocyte killing of breast cancer
cells
SO ONCOLOGY LETTERS
LA English
DT Article
DE TGF alpha-PE38; cytotoxic T lymphocyte; cancer; breast; mucin-1
ID BLOOD MONONUCLEAR-CELLS; EPIDERMAL-GROWTH-FACTOR; PSEUDOMONAS EXOTOXIN;
FACTOR-ALPHA; TUMOR-CELLS; VIABILITY; ASSAY; ADENOCARCINOMAS; XTT
AB The aim of the present study was to determine whether the combination of two modalities of immunotherapy, targeting two different tumor antigens, may be feasible and non-toxic, yet enhance the killing of a human breast cancer cell line. The first modality was tumor growth factor alpha-Pseudomonas exotoxin 38 (TGF alpha-PE38), which specifically targets and kills tumor cells that express the epidermal growth factor receptor. The second modality was mucin-1 (MUC1)-specific cytotoxic T lymphocytes (CTLs), generated by MUC1 stimulation of peripheral blood mononuclear cells, to target the human breast cancer cell line, MCF7. TGF alpha-PE38 exhibited specific lysis of the MCF7 cells in a concentration- and time-dependent manner. TGF alpha-PE38 did not kill the normal hematopoietic stem cells or CTLs. Furthermore, TGF alpha-PE38 was not inhibitory for the growth or differentiation of the normal human hematopoietic stem cells into erythroid and myeloid colonies. In addition, TGF alpha-PE38 did not inhibit the killing function of CTLs, either when preincubated or co-incubated with CTLs. Finally, therapeutic enhancement was observed, in that TGF alpha-PE38 and CTLs were additive in the specific lysis of the MCF7 cells. These two modalities of immunotherapy may be beneficial for humans with breast cancer with or without other therapies, including autologous hematopoietic stem cell transplantation, specifically for purging cancer cells from hematopoietic stem cells prior to transplantation.
C1 [Wright, Stephen E.; Rewers-Felicins, Kathleen A.; Quinlin, Imelda; Chowdhury, Nazrul I.; Ahmed, Jewel] Texas Tech Univ, Hlth Sci Ctr, Womens Hlth Res Inst, Dept Internal Med, Amarillo, TX 79106 USA.
[Wright, Stephen E.] Texas Tech Univ, Hlth Sci Ctr, Dept Microbiol & Immunol, Sch Med, Amarillo, TX 79106 USA.
[Wright, Stephen E.; Srivastava, Sanjay K.] Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, Sch Pharm, Amarillo, TX 79106 USA.
[Wright, Stephen E.; Eldridge, Paul W.] Harrington Canc Ctr, Amarillo, TX 79106 USA.
[Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Wright, SE (reprint author), Texas Tech Univ, Hlth Sci Ctr, Womens Hlth Res Inst, Dept Internal Med, 1400 Wallace Blvd, Amarillo, TX 79106 USA.
EM stephen.wright@ttuhsc.edu
FU VA medical research funds [0006]; Harrington Research Foundation
(Amarillo, TX, USA); Women's Health Research Institute; Texas Tech
University Health Sciences Center (Amarillo, TX, USA); Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research
FX The authors are grateful to the Coffee Memorial Blood Center (Amarillo,
TX, USA) and the Harrington Cancer Center (Amarillo, TX, USA) for the
PBMCs, and to those mentioned in the text for materials and/or services.
Gigi O'Connell participated in the initial phase of the studies. This
study was supported in part by VA medical research funds (no. 0006), the
Harrington Research Foundation (Amarillo, TX, USA), the Women's Health
Research Institute, Texas Tech University Health Sciences Center
(Amarillo, TX, USA) and the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 23
TC 0
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U1 1
U2 2
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1792-1074
EI 1792-1082
J9 ONCOL LETT
JI Oncol. Lett.
PD JUN
PY 2014
VL 7
IS 6
BP 2113
EP 2117
DI 10.3892/ol.2014.1969
PG 5
WC Oncology
SC Oncology
GA AI0QY
UT WOS:000336555200073
ER
PT J
AU Wang, Z
Niu, G
Chen, XY
AF Wang, Zhe
Niu, Gang
Chen, Xiaoyuan
TI Polymeric Materials for Theranostic Applications
SO PHARMACEUTICAL RESEARCH
LA English
DT Review
DE drug delivery; imaging; nanoparticle; polymer; theranostics
ID IRON-OXIDE NANOPARTICLES; POLYPEPTIDE-DOXORUBICIN CONJUGATE;
MAGNETIC-RESONANCE ANGIOGRAPHY; TARGETED DRUG-DELIVERY; MRI CONTRAST
AGENTS; IN-VIVO; QUANTUM-DOT; POLY(L-GLUTAMIC ACID); GOLD NANOPARTICLES;
CARBON NANOTUBES
AB Nanotechnology has continuously contributed to the fast development of diagnostic and therapeutic agents. Theranostic nanomedicine has encompassed the ongoing efforts on concurrent molecular imaging of biomarkers, delivery of therapeutic agents, and monitoring of therapy response. Among these formulations, polymer-based theranostic agents hold great promise for the construction of multifunctional agents for translational medicine. In this article, we reviewed the state-of-the-art polymeric nanoparticles, from preparation to application, as potential theranostic agents for diagnosis and therapy. We summarized several major polymer formulas, including polymeric conjugate complexes, nanospheres, micelles, and dendrimers for integrated molecular imaging and therapeutic applications.
C1 [Wang, Zhe; Niu, Gang; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bldg 31,1C22, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
FU Intramural Research Program, National Institute of Biomedical Imaging
and Bioengineering, National Institutes of Health
FX This work was supported by the Intramural Research Program, National
Institute of Biomedical Imaging and Bioengineering, National Institutes
of Health.
NR 177
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U1 6
U2 140
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-8741
EI 1573-904X
J9 PHARM RES-DORDR
JI Pharm. Res.
PD JUN
PY 2014
VL 31
IS 6
BP 1358
EP 1376
DI 10.1007/s11095-013-1103-7
PG 19
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA AI3FK
UT WOS:000336745800002
PM 23765400
ER
PT J
AU Xing, RJ
Liu, G
Zhu, JH
Hou, YL
Chen, XY
AF Xing, Ruijun
Liu, Gang
Zhu, Jinghan
Hou, Yanglong
Chen, Xiaoyuan
TI Functional Magnetic Nanoparticles for Non-Viral Gene Delivery and MR
Imaging
SO PHARMACEUTICAL RESEARCH
LA English
DT Review
DE gene delivery; gene therapy; magnetic nanoparticles (MNPs); magnetic
resonance imaging (MRI)
ID IRON-OXIDE NANOPARTICLES; SMALL INTERFERING RNA; LOW-MOLECULAR-WEIGHT;
IN-VIVO; DRUG-DELIVERY; PAMAM DENDRIMERS; BIOMEDICAL APPLICATIONS;
SURFACE MODIFICATION; DNA DELIVERY; TRANSFECTION EFFICIENCY
AB Gene therapy is becoming a promising strategy to treat various kinds of genetic and acquired diseases. However, the development of safe, efficient, and targetable gene delivery systems remains a major challenge in gene therapy. The unique material characteristics of magnetic nanoparticles (MNPs), including high surface area, facile surface modification, controllable size, and excellent magnetic properties, make them promising candidates for gene delivery. The engineered MNPs with modifiable functional surfaces and bioactive cores can result in several advantageous diagnostic and therapeutic properties including enhanced magnetic resonance imaging (MRI) signal intensity, long permeation and retention in the circulatory system, specific delivery of therapeutic genes to target sites. In this review, the updated research on the preparation and surface modification of MNPs for gene delivery is summarized.
C1 [Xing, Ruijun; Zhu, Jinghan; Hou, Yanglong] Peking Univ, Dept Mat Sci & Engn, Coll Engn, Beijing 100871, Peoples R China.
[Liu, Gang] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361102, Peoples R China.
[Liu, Gang] North Sichuan Med Coll, Sichuan Key Lab Med Imaging, Nanchong 637007, Peoples R China.
[Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
RP Hou, YL (reprint author), Peking Univ, Dept Mat Sci & Engn, Coll Engn, Beijing 100871, Peoples R China.
EM gangliu.cmitm@xmu.edu.cn; hou@pku.edu.cn
RI Hou, Yanglong/B-8688-2012
FU Major State Basic Research Development Program of China (973 Program)
[2010-CB934601, 2013CB733802]; National Nature Science of Foundation of
China (NSFC) [81101101, 51273165, 51125001, 51172005]; National Natural
Science Foundation of China [51250110078]; Fundamental Research Funds
for the Central Universities [2013121039]; Chinese Ministry of Education
[212149]
FX This work was supported by the Major State Basic Research Development
Program of China (973 Program) (2010-CB934601, 2013CB733802); the
National Nature Science of Foundation of China (NSFC) (81101101,
51273165, 51125001, 51172005); the Research Fellowship for International
Young Scientists of the National Natural Science Foundation of China
(51250110078); Fundamental Research Funds for the Central Universities
(2013121039); and the Key Project of Chinese Ministry of Education
(212149).
NR 119
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Z9 8
U1 3
U2 72
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-8741
EI 1573-904X
J9 PHARM RES-DORDR
JI Pharm. Res.
PD JUN
PY 2014
VL 31
IS 6
BP 1377
EP 1389
DI 10.1007/s11095-013-1205-2
PG 13
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA AI3FK
UT WOS:000336745800003
PM 24065595
ER
PT J
AU Ramos, E
Doumatey, A
Elkahloun, AG
Shriner, D
Huang, H
Chen, G
Zhou, J
McLeod, H
Adeyemo, A
Rotimi, CN
AF Ramos, E.
Doumatey, A.
Elkahloun, A. G.
Shriner, D.
Huang, H.
Chen, G.
Zhou, J.
McLeod, H.
Adeyemo, A.
Rotimi, C. N.
TI Pharmacogenomics, ancestry and clinical decision making for global
populations
SO PHARMACOGENOMICS JOURNAL
LA English
DT Article
DE ADME; clinical decision making; global populations; pharmacogenomics
ID NATURAL-SELECTION; GENOMIC MEDICINE; WARFARIN; EIGENANALYSIS;
POLYMORPHISMS; ASSOCIATION; GENOTYPES; CYP2C19; DISEASE; SIGNALS
AB Pharmacogenomically relevant markers of drug response and adverse drug reactions are known to vary in frequency across populations. We examined minor allele frequencies (MAFs), genetic diversity (F-ST) and population structure of 1156 genetic variants (including 42 clinically actionable variants) in 212 genes involved in drug absorption, distribution, metabolism and excretion (ADME) in 19 populations (n=1478). There was wide population differentiation in these ADME variants, reflected in the range of mean MAF (Delta MAF) and F-ST. The largest mean Delta MAF was observed in African ancestry populations (0.10) and the smallest mean AMAF in East Asian ancestry populations (0.04). MAFs ranged widely, for example, from 0.93 for single-nucleotide polymorphism (SNP) rs9923231, which influences warfarin dosing to 0.01 for SNP rs3918290 associated with capecitabine metabolism. ADME genetic variants show marked variation between and within continental groupings of populations. Enlarging the scope of pharmacogenomics research to include multiple global populations can improve the evidence base for clinical translation to benefit all peoples.
C1 [Ramos, E.; Doumatey, A.; Shriner, D.; Huang, H.; Chen, G.; Zhou, J.; Adeyemo, A.; Rotimi, C. N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Elkahloun, A. G.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[McLeod, H.] Univ N Carolina, Inst Pharmacogenom & Individualized Therapy, Chapel Hill, NC USA.
RP Ramos, E (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
EM ramose@mail.nih.gov
OI Adeyemo, Adebowale/0000-0002-3105-3231
FU National Institutes of Health [S06GM008016-320107, S06GM008016-380111];
former National Center for Research Resources [2M01RR010284]; National
Institutes of Health; Intramural Research Program of the Center for
Research on Genomics and Global Health; National Human Genome Research
Institute; National Institute of Diabetes and Digestive and Kidney
Diseases; Center for Information Technology; Office of the Director at
the National Institutes of Health [Z01HG200362]
FX The informatics expertise of Kevin Long, University of North Carolina,
Chapel Hill is greatly appreciated. The study was supported by National
Institutes of Health grants S06GM008016-320107 to CNR and
S06GM008016-380111 to AA. HUFS participants were enrolled at the Howard
University General Clinical Research Center, which is supported by grant
2M01RR010284 from the former National Center for Research Resources,
National Institutes of Health. This research was supported in part by
the Intramural Research Program of the Center for Research on Genomics
and Global Health. The Center for Research on Genomics and Global Health
is supported by the National Human Genome Research Institute, the
National Institute of Diabetes and Digestive and Kidney Diseases, the
Center for Information Technology and the Office of the Director at the
National Institutes of Health (Z01HG200362).
NR 27
TC 14
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U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1470-269X
EI 1473-1150
J9 PHARMACOGENOMICS J
JI Pharmacogenomics J.
PD JUN
PY 2014
VL 14
IS 3
BP 217
EP 222
DI 10.1038/tpj.2013.24
PG 6
WC Genetics & Heredity; Pharmacology & Pharmacy
SC Genetics & Heredity; Pharmacology & Pharmacy
GA AI0SK
UT WOS:000336560000003
PM 23835662
ER
PT J
AU McCracken, JT
Badashova, KK
Posey, DJ
Aman, MG
Scahill, L
Tierney, E
Arnold, LE
Vitiello, B
Whelan, F
Chuang, SZ
Davies, M
Shah, B
McDougle, CJ
Nurmi, EL
AF McCracken, J. T.
Badashova, K. K.
Posey, D. J.
Aman, M. G.
Scahill, L.
Tierney, E.
Arnold, L. E.
Vitiello, B.
Whelan, F.
Chuang, S. Z.
Davies, M.
Shah, B.
McDougle, C. J.
Nurmi, E. L.
TI Positive effects of methylphenidate on hyperactivity are moderated by
monoaminergic gene variants in children with autism spectrum disorders
SO PHARMACOGENOMICS JOURNAL
LA English
DT Article
DE autism spectrum disorders; dopamine; genetics; hyperactivity;
methylphenidate
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL
DISORDERS; DOPAMINE TRANSPORTER GENOTYPE; ABERRANT BEHAVIOR CHECKLIST;
ADHD CHILDREN; DOSE-RESPONSE; RECEPTOR GENE; SCHIZOPHRENIC CHILDREN;
GENOME BROWSER; ASSOCIATION
AB Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P< 0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability.
C1 [McCracken, J. T.; Badashova, K. K.; Whelan, F.; Shah, B.; Nurmi, E. L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci, Los Angeles, CA 90024 USA.
[Posey, D. J.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA.
[Aman, M. G.; Arnold, L. E.] Ohio State Univ, Nisonger Ctr UCEDD, Dept Psychiat, Columbus, OH 43210 USA.
[Aman, M. G.; Arnold, L. E.] Ohio State Univ, Nisonger Ctr UCEDD, Dept Psychol, Columbus, OH 43210 USA.
[Scahill, L.] Yale Univ, Child Study Ctr, New Haven, CT USA.
[Tierney, E.] Johns Hopkins Univ, Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA.
[Vitiello, B.] NIMH, NIH, Bethesda, MD 20892 USA.
[Chuang, S. Z.; Davies, M.] Columbia Univ, Dept Psychiat, New York, NY USA.
[McDougle, C. J.] Massachusetts Gen Hosp, Lurie Autism Ctr, Dept Psychiat, Boston, MA 02114 USA.
RP McCracken, JT (reprint author), UCLA NPI Semel Inst, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90024 USA.
EM jmccracken@mednet.ucla.edu
RI Nurmi, Erika/P-4627-2014;
OI Nurmi, Erika/0000-0003-4893-8957; Scahill, Lawrence/0000-0001-5073-1707
FU NIMH [N01 MH-70070, N01 MH-70009, N01 MH-70001, N01 MH 80011, MH-01805,
MH094613, T32MH073517, MH-68627]; NIH Division of Research Resources
General Clinical Research Center [M01 RR-00750, M01 RR-00052, M01
RR-00034, M01 RR-06022]; Korczak Foundation
FX The RUPP Autism Network comprises the following investigators listed by
role and study site: Ohio State University: principal investigator
Michael G Amen, PhD, co-investigators L Eugene Arnold, MEd, MD, Yaser
Ramadan, MD, Andrea Witwer, MA, Ronald Lindsay, MD and Patricia Nash,
MD; University of California at Los Angeles: principal investigator
James T McCracken, MD, co-investigators Bhavik Shah, MD, James Mc Gough,
MD, Pegeen Cronin, PhD, Lisa Lee, BA; Indiana University: principal
investigator Christopher J McDougle, MD, co-investigators David Posey,
MD, Naomi Swiezy, PhD, Arlene Kohn, BA; Yale University: principal
investigator Lawrence Scahill, MSN, PhD, co-investigators Andres Martin,
MD, Kathleen Koenig, MSN, Fred Volkmar, MD, Deirdre Carroll, MSN,
Allison Lancor, BS; Kennedy Krieger Institute: principal investigator
Elaine Tierney, MD, co-investigators Jaswinder Ghuman, MD, Nilda
Gonzalez, MD, Marco Grados, MD; National Institute of Mental Health:
principal investigator Benedetto Vitiello, MD, co-investigator Louise
Ritz, MBA; statisticians: Shirley Z Chuang, MS, Mark Davies, MPH, of
Columbia University; data management: James Robinson, MEd, Don McMahon,
MS, Nathan Kline Institute. Research supported by NIMH contracts N01
MH-70070 (principal investigator: Dr McCracken), N01 MH-70009 (principal
investigator: Dr Scahill), N01 MH-70001 (principal investigator: Dr
McDougle), and N01 MH 80011 (principal investigator: Dr Amen); by NIH
Division of Research Resources General Clinical Research Center grants
M01 RR-00750 (to Indiana University), M01 RR-00052 (to John Hopkins
University), M01 RR-00034 (to Ohio University) and M01 RR-06022 (to Yale
University); by NIMH grants MH-01805 (to Dr McCracken) NIMH grants
MH094613 and T32MH073517 (Dr Nurmi) and MH-68627 (to Dr Posey); and by
funding from the Korczak Foundation (to Dr Scahill). The opinions and
assertions contained in this report are the private views of the authors
and are not to be construed as official or as reflecting the views of
the National Institute of Mental Health, the National Institutes of
Health, or the Department of Health and Human Services.
NR 67
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U1 3
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1470-269X
EI 1473-1150
J9 PHARMACOGENOMICS J
JI Pharmacogenomics J.
PD JUN
PY 2014
VL 14
IS 3
BP 295
EP 302
DI 10.1038/tpj.2013.23
PG 8
WC Genetics & Heredity; Pharmacology & Pharmacy
SC Genetics & Heredity; Pharmacology & Pharmacy
GA AI0SK
UT WOS:000336560000014
PM 23856854
ER
PT J
AU Holman, DM
Berkowitz, Z
Guy, GP
Hartman, AM
Perna, FM
AF Holman, Dawn M.
Berkowitz, Zahava
Guy, Gery P., Jr.
Hartman, Anne M.
Perna, Frank M.
TI The association between demographic and behavioral characteristics and
sunburn among U.S. adults - National Health Interview Survey, 2010
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Sunburn; Skin neoplasms; Primary prevention; Health behavior; Adult
ID SKIN-CANCER RISK; CUTANEOUS MALIGNANT-MELANOMA; UNITED-STATES; SUN
PROTECTION; WOMEN; METAANALYSIS; POPULATION; PREVALENCE; PREVENTION;
SUNSCREEN
AB Objective. To examine the association between demographic and behavioral characteristics and sunburn among U.S. adults.
Method We used 2010 National Health Interview Survey data (N = 24,970) to conduct multivariable logistic regressions examining associations with having 1 or more sunburns in the past year and having 4 or more sunburns in the past year.
Results. Overall, 37.1% of adults experienced sunburn in the past year. The adjusted prevalence of sunburn was particularly common among adults aged 18-29 years (52.0%), those who repeatedly burn or freckle after 2 weeks in the sun (45.9%), whites (443%), indoor tanners (44.1%), those with a family history of melanoma (43.9%), and those who are US-born (39.5%). Physical activity, alcohol consumption, and overweight/obesity were positively associated with sunburn (all P < 0.001); sun protection behaviors were not significantly associated with sunburn (P = 0.35). Among those who were sunburned in the past year, 12.1% experienced 4 or more sunburns.
Conclusion. Sunburn is common, particularly among younger adults, those with a more sun-sensitive skin type, whites, those with a family history of melanoma, the highly physically active, and indoor tanners. Efforts are needed to facilitate sun-safety during outdoor recreation, improve the consistency of sun protection practices, and prevent sunburn, particularly among these subgroups. Published by Elsevier Inc.
C1 [Holman, Dawn M.; Berkowitz, Zahava; Guy, Gery P., Jr.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA 30341 USA.
[Hartman, Anne M.; Perna, Frank M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Holman, DM (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, 4770 Buford Highway,NE Chamblee Bldg 107,MS F76, Atlanta, GA 30341 USA.
EM dholman@cdc.gov; zab3@cdc.gov; irm2@cdc.gov; hartmana@mail.nih.gov;
pernafm@mail.nih.gov
FU Intramural CDC HHS [CC999999]
NR 39
TC 22
Z9 22
U1 4
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
EI 1096-0260
J9 PREV MED
JI Prev. Med.
PD JUN
PY 2014
VL 63
BP 6
EP 12
DI 10.1016/j.ypmed.2014.02.018
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA AI0TM
UT WOS:000336562900002
PM 24589442
ER
PT J
AU Ursano, RJ
Colpe, LJ
Heeringa, SG
Kessler, RC
Schoenbaum, M
Stein, MB
AF Ursano, Robert J.
Colpe, Lisa J.
Heeringa, Steven G.
Kessler, Ronald C.
Schoenbaum, Michael
Stein, Murray B.
CA Army STARRS Collaborators
TI The Army Study to Assess Risk and Resilience in Servicemembers (Army
STARRS)
SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES
LA English
DT Article
ID ADOLESCENT SUICIDE; PROPENSITY SCORE; VETERANS; BEHAVIOR; AFGHANISTAN;
MILITARY; IRAQ; CARE; MEN
AB Importance/Objective: Although the suicide rate in the U.S. Army has traditionally been below age-gender matched civilian rates, it has climbed steadily since the beginning of the Iraq and Afghanistan conflicts and since 2008 has exceeded the demographically matched civilian rate. The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a multicomponent epidemiological and neurobiological study designed to generate actionable evidence-based recommendations to reduce Army suicides and increase knowledge about risk and resilience factors for suicidality and its psychopathological correlates. This paper presents an overview of the Army STARRS component study designs and of recent findings.
Design/Setting/Participants/Intervention: Army STARRS includes six main component studies: (1) the Historical Administrative Data Study (HADS) of Army and Department of Defense (DoD) administrative data systems (including records of suicidal behaviors) for all soldiers on active duty 2004-2009 aimed at finding administrative record predictors of suicides; (2) retrospective case-control studies of fatal and nonfatal suicidal behaviors (each planned to have n = 150 cases and n = 300 controls); (3) a study of new soldiers (n = 50,765 completed surveys) assessed just before beginning basic combat training (BCT) with self-administered questionnaires (SAQ), neurocognitive tests, and blood samples; (4) a cross-sectional study of approximately 35,000 (completed SAQs) soldiers representative of all other (i.e., exclusive of BCT) active duty soldiers; (5) a pre-post deployment study (with blood samples) of soldiers in brigade combat teams about to deploy to Afghanistan (n = 9,421 completed baseline surveys), with sub-samples assessed again one, three, and nine months after returning from deployment; and (6) a pilot study to follow-up SAQ respondents transitioning to civilian life. Army/DoD administrative data are being linked prospectively to the large-scale survey samples to examine predictors of subsequent suicidality and related mental health outcomes.
Main outcome measures: Measures (self-report and administratively recorded) of suicidal behaviors and their psychopathological correlates.
Results: Component study cooperation rates are comparatively high. Sample biases are relatively small. Inefficiencies introduced into parameter estimates by using nonresponse adjustment weights and time-space clustering are small. Initial findings show that the suicide death rate, which rose over 2004-2009, increased for those deployed, those never deployed, and those previously deployed. Analyses of administrative records show that those deployed or previously deployed were at greater suicide risk. Receiving a waiver to enter the Army was not associated with increased risk. However, being demoted in the past two years was associated with increased risk. Time in current deployment, length of time since return from most recent deployment, total number of deployments, and time interval between most recent deployments (known as dwell time) were not associated with suicide risk. Initial analyses of survey data show that 13.9% of currently active non-deployed regular Army soldiers considered suicide at some point in their lifetime, while 5.3% had made a suicide plan, and 2.4% had attempted suicide. Importantly, 47-60% of these outcomes first occurred prior to enlistment. Prior mental disorders, in particular major depression and intermittent explosive disorder, were the strongest predictors of these self-reported suicidal behaviors. Most onsets of plans-attempts among ideators (58.3-63.3%) occurred within the year of onset of ideation. About 25.1% of non-deployed U.S. Army personnel met 30-day criteria for a DSM-IV anxiety, mood, disruptive behavior, or substance disorder (15.0% an internalizing disorder; 18.4% an externalizing disorder) and 11.1% for multiple disorders. Importantly, three-fourths of these disorders had pre-enlistment onsets.
Conclusions: Integration across component studies creates strengths going well beyond those in conventional applications of the same individual study designs. These design features create a strong methodological foundation from which Army STARRS can pursue its substantive research goals. The early findings reported here illustrate the importance of the study and its approach as a model of studying rare events particularly of national security concern. Continuing analyses of the data will inform suicide prevention for the U.S. Army.
C1 [Ursano, Robert J.] Uniformed Serv Univ Sch Med, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD USA.
[Colpe, Lisa J.; Schoenbaum, Michael] NIMH, Bethesda, MD 20892 USA.
[Heeringa, Steven G.] Univ Michigan Inst Social Res, Ann Arbor, MI USA.
[Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Stein, Murray B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Stein, Murray B.] VA San Diego Healthcare Syst, San Diego, CA USA.
RP Ursano, RJ (reprint author), USUHS, Dept Psychiat, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM robert.ursano@usuhs.edu
FU Eli Lilly Company; EPI-Q; GlaxoSmithKline; Ortho-McNeil Janssen
Scientific Affairs; Sanofi-Aventis Groupe; Shire U.S., Inc.; Walgreens
Co.; Janssen; Department of the Army; U.S. Department of Health and
Human Services, National Institutes of Health, National Institute of
Mental Health (NIH/NIMH) [U01MH087981]
FX Financial Disclosure: In the past five years, Dr. Kessler has been a
consultant for Eli Lilly & Company, Glaxo, Inc., Integrated Benefits
Institute, Ortho-McNeil Janssen Scientific Affairs, Pfizer Inc.,
Sanofi-Aventis Groupe, Shire U.S. Inc., and Transcept Pharmaceuticals
Inc. and has served on advisory boards for Johnson & Johnson. He has had
research support for his epidemiological studies over this time period
from Eli Lilly & Company, EPI-Q, GlaxoSmithKline, Ortho-McNeil Janssen
Scientific Affairs, Sanofi-Aventis Groupe, Shire U.S., Inc., and
Walgreens Co. Dr. Kessler owns a 25% share in DataStat, Inc. Dr. Stein
has in the last three years been a consultant for Healthcare Management
Technologies and had research support for pharmacological imaging
studies from Janssen. The remaining authors report nothing to disclose.;
Funding/Support: Army STARRS was sponsored by the Department of the Army
and funded under cooperative agreement number U01MH087981 with the U.S.
Department of Health and Human Services, National Institutes of Health,
National Institute of Mental Health (NIH/NIMH). The contents are solely
the responsibility of the authors and do not necessarily represent the
views of the Department of Health and Human Services, NIMH, the
Department of the Army, or the Department of Defense.
NR 35
TC 39
Z9 39
U1 3
U2 23
PU GUILFORD PUBLICATIONS INC
PI NEW YORK
PA 72 SPRING STREET, NEW YORK, NY 10012 USA
SN 0033-2747
J9 PSYCHIATRY
JI Psychiatry-Interpers. Biol. Process.
PD SUM
PY 2014
VL 77
IS 2
BP 107
EP 119
PG 13
WC Psychiatry
SC Psychiatry
GA AI1VD
UT WOS:000336642400001
PM 24865195
ER
PT J
AU Wang, HR
Wang, XH
Archer, TK
Zwaka, TP
Cooney, AJ
AF Wang, Hongran
Wang, Xiaohong
Archer, Trevor K.
Zwaka, Thomas P.
Cooney, Austin J.
TI GCNF-Dependent Activation of Cyclin D1 Expression via Repression of
Mir302a During ESC Differentiation
SO STEM CELLS
LA English
DT Article
DE Cyclin D1; GCNF; microRNA; Mir302; ESCs
ID CELL NUCLEAR FACTOR; EMBRYONIC STEM-CELLS; RECEPTOR GCNF; BINDING;
PROTEIN; OCT4; PLURIPOTENCY; PROGENITORS; TRANSITION; INHIBITION
AB Cyclin D1 plays an important role in the regulation of cellular proliferation and its expression is activated during gastrulation in the mouse; however, it remains unknown how cyclin D1 expression is regulated during early embryonic development. Here, we define the role of germ cell nuclear factor (GCNF) in the activation of cyclin D1 expression during embryonic stem cell (ESC) differentiation as a model of early development. During our study of GCNF knockout (GCNF(-/-)) ESC, we discovered that loss of GCNF leads to the repression of cyclin D1 activation during ESC differentiation. This was determined to be an indirect effect of deregulation Mir302a, which is a cyclin D1 suppressor via binding to the 3'UTR of cyclin D1 mRNA. Moreover, we showed that Mir302 is a target gene of GCNF that inhibits Mir302 expression by binding to a DR0 element within its promoter. Inhibition of Mir302a using Mir302 inhibitor during differentiation of GCNF(-/-) ESCs restored cyclin D1 expression. Similarly over-expression of GCNF during differentiation of GCNF(-/-) ESCs rescued the inhibition of Mir302a expression and the activation of cyclin D1. These results reveal that GCNF plays a key role in regulating activation of cyclin D1 expression via inhibition of Mir302a.
C1 [Wang, Hongran; Wang, Xiaohong; Cooney, Austin J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Wang, Hongran; Wang, Xiaohong; Cooney, Austin J.] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA.
[Wang, Xiaohong] Texas Heart Inst, Stem Cell Ctr, Houston, TX 77025 USA.
[Archer, Trevor K.] NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Zwaka, Thomas P.] Icahn Sch Med Mt Sinai, Dept Dev & Regenerat Med, Black Family Stem Cell Inst, New York, NY USA.
RP Cooney, AJ (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA.
EM acooney@bcm.edu
FU NIH [P01 GM081627]
FX This work was supported by a Grant NIH P01 GM081627 to A.J.C.
NR 41
TC 2
Z9 2
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD JUN
PY 2014
VL 32
IS 6
BP 1527
EP 1537
DI 10.1002/stem.1689
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA AI3EE
UT WOS:000336741700017
PM 24578347
ER
PT J
AU Robertson, DJ
Lieberman, DA
Winawer, SJ
Ahnen, DJ
Baron, JA
Schatzkin, A
Cross, AJ
Zauber, AG
Church, TR
Lance, P
Greenberg, ER
Martinez, ME
AF Robertson, Douglas J.
Lieberman, David A.
Winawer, Sidney J.
Ahnen, Dennis J.
Baron, John A.
Schatzkin, Arthur
Cross, Amanda J.
Zauber, Ann G.
Church, Timothy R.
Lance, Peter
Greenberg, E. Robert
Martinez, Maria Elena
TI Colorectal cancers soon after colonoscopy: a pooled multicohort analysis
SO GUT
LA English
DT Article
ID FECAL OCCULT-BLOOD; SOCIETY TASK-FORCE; SCREENING COLONOSCOPY;
ANTIOXIDANT VITAMINS; ASYMPTOMATIC ADULTS; ADENOMATOUS POLYPS;
RANDOMIZED-TRIAL; INCREASED RISK; SURVEILLANCE; POLYPECTOMY
AB Objective Some individuals are diagnosed with colorectal cancer (CRC) despite recent colonoscopy. We examined individuals under colonoscopic surveillance for colonic adenomas to assess possible reasons for diagnosing cancer after a recent colonoscopy with complete removal of any identified polyps.
Design Primary data were pooled from eight large (>800 patients) North American studies in which participants with adenoma(s) had a baseline colonoscopy (with intent to remove all visualised lesions) and were followed with subsequent colonoscopy. We used an algorithm based on the time from previous colonoscopy and the presence, size and histology of adenomas detected at prior exam to assign interval cancers as likely being new, missed, incompletely resected (while previously an adenoma) or due to failed biopsy detection.
Results 9167 participants (mean age 62) were included in the analyses, with a median follow-up of 47.2 months. Invasive cancer was diagnosed in 58 patients (0.6%) during follow-up (1.71 per 1000 person-years follow-up). Most cancers (78%) were early stage (I or II); however, 9 (16%) resulted in death from CRC. We classified 30 cancers (52%) as probable missed lesions, 11 (19%) as possibly related to incomplete resection of an earlier, non-invasive lesion and 14 (24%) as probable new lesions. The cancer diagnosis may have been delayed in three cases (5%) because of failed biopsy detection.
Conclusions Despite recent colonoscopy with intent to remove all neoplasia, CRC will occasionally be diagnosed. These cancers primarily seem to represent lesions that were missed or incompletely removed at the prior colonoscopy and might be avoided by increased emphasis on identifying and completely removing all neoplastic lesions at colonoscopy.
C1 [Robertson, Douglas J.] Dept Vet Affairs Med Ctr, White River Jct, VT USA.
[Robertson, Douglas J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA.
[Robertson, Douglas J.] Dartmouth Inst, Hanover, NH USA.
[Lieberman, David A.] Dept Vet Affairs Med Ctr, Portland, OR USA.
[Winawer, Sidney J.; Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Ahnen, Dennis J.] Univ Colorado, Dept Vet Affairs Med Ctr, Denver, CO 80202 USA.
[Ahnen, Dennis J.] Univ Colorado, Ctr Canc, Denver, CO 80262 USA.
[Baron, John A.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Schatzkin, Arthur; Cross, Amanda J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Church, Timothy R.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA.
[Lance, Peter; Martinez, Maria Elena] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA.
[Lance, Peter; Martinez, Maria Elena] Univ Arizona, Mel & Enid Zuckerman Arizona Coll Publ Hlth, Tucson, AZ USA.
[Lance, Peter] Univ Arizona, Dept Med, Tucson, AZ USA.
[Greenberg, E. Robert] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Robertson, DJ (reprint author), VA Med Ctr, 215 N Main St,Sect Gastroenterol 111E, White River Jct, VT 05009 USA.
EM douglas.robertson@va.gov
RI Lance, Peter/I-2196-2014;
OI Lance, Peter/0000-0003-2944-1881; Church, Timothy R./0000-0003-3292-5035
FU Public Health Service from the National Cancer Institute [CA-41108,
CA-23074, CA95060, CA37287, CA104869, CA23108, CA59005, CA26852];
Cooperative Studies Program, Department of Veterans Affairs; Department
of Veterans Affairs, Veterans Health Administration, Office of Research
and Development, Health Services Research and Development Career
Development Award
FX This work was supported by Public Health Service grants CA-41108,
CA-23074, CA95060, CA37287, CA104869, CA23108, CA59005 and CA26852 from
the National Cancer Institute. Funding for the Veteran's Affairs Study
was supported by the Cooperative Studies Program, Department of Veterans
Affairs. Dr Robertson's work supported in part by the Department of
Veterans Affairs, Veterans Health Administration, Office of Research and
Development, Health Services Research and Development Career Development
Award.
NR 57
TC 79
Z9 81
U1 0
U2 10
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
EI 1468-3288
J9 GUT
JI Gut
PD JUN
PY 2014
VL 63
IS 6
BP 949
EP 956
DI 10.1136/gutjnl-2012-303796
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA AG4AB
UT WOS:000335360000014
PM 23793224
ER
PT J
AU Naluyima, P
Eller, MA
Laeyendecker, O
Quinn, TC
Serwadda, D
Sewankambo, NK
Gray, RH
Michael, NL
Wabwire-Mangen, F
Robb, ML
Sandberg, JK
AF Naluyima, Prossy
Eller, Michael A.
Laeyendecker, Oliver
Quinn, Thomas C.
Serwadda, David
Sewankambo, Nelson K.
Gray, Ronald H.
Michael, Nelson L.
Wabwire-Mangen, Fred
Robb, Merlin L.
Sandberg, Johan K.
TI Impaired natural killer cell responses are associated with loss of the
highly activated NKG2AR CD57 R CD56 dim subset in HIV-1 subtype D
infection in Uganda
SO AIDS
LA English
DT Article
DE AIDS; CD57; HIV-1; immune activation; natural killer cells; NKG2A;
subtype D
ID VIRUS TYPE-1 INFECTION; KIR3DL1(+) NK CELLS; DENDRITIC CELLS; INNATE
IMMUNITY; RAKAI DISTRICT; T-CELLS; HLA-B; EXPRESSION; DIVERSITY;
PATTERNS
AB Objective:Of the predominant HIV-1 subtypes in Uganda, subtype D infection confers a worse prognosis. HIV-1 infection causes perturbations to natural killer (NK) cells, and yet these cells can exert immune pressure on the virus and influence clinical outcome. Here, we studied NK cell activation and function in Ugandans with chronic untreated HIV-1 subtype D infection in comparison to uninfected community matched controls.Methods:Cryopreserved peripheral blood mononuclear cells (PBMCs) from 42 HIV-infected individuals and 28 HIV-negative controls were analysed using eight-colour flow cytometry. NK cell surface expression of CD16, CD56, CD57, HLA-DR and NKG2A were used to investigate activation, maturation and differentiation status. NK cell function was evaluated by measuring interferon-gamma (IFN) production in response to K562 cells, or interleukin (IL)-12 and IL-18.Results:CD56(dim) NK cells from HIV-infected individuals produced less IFN in response to IL-12 and IL-18 than did CD56(dim) NK cells from uninfected controls. Infected individuals had lower levels of CD56(dim) NK cells coexpressing the differentiation markers NKG2A and CD57 than controls. In addition, their NKG2A(+)CD57(+) CD56(dim) NK cells displayed elevated activation levels as assessed by HLA-DR expression. Cytokine-induced IFN production correlated directly with coexpression of CD57 and NKG2A on CD56(dim) NK cells.Conclusion:HIV-1 subtype D infection is associated with impaired NK cell responsiveness to cytokines, decline of the NKG2A(+)CD57(+) CD56(dim) NK cell subset, as well as elevated activation in this subset. These alterations within the NK cell compartment may contribute to immunopathogenesis of HIV-1 subtype D infection in Ugandans.
C1 [Naluyima, Prossy; Wabwire-Mangen, Fred] Makerere Univ Walter Reed Project, Kampala, Uganda.
[Naluyima, Prossy; Sandberg, Johan K.] Karolinska Univ Hosp Huddinge, Karolinska Inst, Ctr Infect Med, Dept Med, S-14186 Stockholm, Sweden.
[Eller, Michael A.; Michael, Nelson L.; Robb, Merlin L.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.
[Eller, Michael A.; Robb, Merlin L.] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA.
[Laeyendecker, Oliver; Quinn, Thomas C.] NIAID, Div Intramural Res, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Laeyendecker, Oliver; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Serwadda, David; Wabwire-Mangen, Fred] Makerere Univ, Coll Hlth Sci, Sch Publ Hlth, Kampala, Uganda.
[Serwadda, David; Sewankambo, Nelson K.] Uganda Virus Res Inst, Rakai Hlth Sci Program, Entebbe, Uganda.
[Sewankambo, Nelson K.] Makerere Univ, Coll Hlth Sci, Fac Med, Kampala, Uganda.
[Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Sandberg, JK (reprint author), Karolinska Univ Hosp Huddinge, Karolinska Inst, Ctr Infect Med, Dept Med, F59, S-14186 Stockholm, Sweden.
EM johan.sandberg@ki.se
FU Henry M. Jackson Foundation for the Advancement of Military Medicine,
Inc. [W81XWH-07-2-0067]; U.S. Department of Defense; National Institute
of Allergy and Infectious Diseases (NIAID) [R01 AI34826, R01 AI34265];
National Institute of Child and Health Development [5P30HD06826];
Fogarty Foundation [5D43TW00010]; Swedish Research Council; Swedish
Cancer Society; Stockholm County Council; Karolinska Institutet;
Division of Intramural Research, NIAID, NIH
FX Primary support was provided by a cooperative agreement
(W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the
Advancement of Military Medicine, Inc., and the U.S. Department of
Defense. Data collection was supported, in part, by grants R01 AI34826
and R01 AI34265 from the National Institute of Allergy and Infectious
Diseases (NIAID); grant 5P30HD06826 from the National Institute of Child
and Health Development; grant 5D43TW00010 from the Fogarty Foundation.
Additional support was provided by the Swedish Research Council, the
Swedish Cancer Society, the Stockholm County Council, Karolinska
Institutet and the Division of Intramural Research, NIAID, NIH.
NR 39
TC 4
Z9 4
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
EI 1473-5571
J9 AIDS
JI Aids
PD JUN 1
PY 2014
VL 28
IS 9
BP 1273
EP 1278
DI 10.1097/QAD.0000000000000286
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA AH2SX
UT WOS:000335972500004
PM 24959961
ER
PT J
AU Kapetanovic, S
Dass-Brailsford, P
Nora, D
Talisman, N
AF Kapetanovic, Suad
Dass-Brailsford, Priscilla
Nora, Diana
Talisman, Nicholas
TI Mental Health of HIV-Seropositive Women During Pregnancy and Postpartum
Period: A Comprehensive Literature Review
SO AIDS AND BEHAVIOR
LA English
DT Review
DE HIV; Pregnancy; Mental health; Perinatal depression; Women
ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTIMATE PARTNER VIOLENCE;
QUALITY-OF-LIFE; DEPRESSIVE SYMPTOMS; POSITIVE WOMEN; INFECTED WOMEN;
SOUTH-AFRICA; PRENATAL DEPRESSION; EMOTIONAL DISTRESS; SUBSTANCE USE
AB With growing numbers of HIV-seropositive (HIV+) women of child-bearing age and increased access to effective clinical protocols for preventing mother-to-child transmission (MTCT) of HIV, mental health-related factors have become increasingly relevant due to their potential to affect the women's quality of life, obstetric outcomes and risk of MTCT. This review synthesizes evidence from 53 peer-reviewed publications examining mental health-related variables in pregnant and postpartum HIV+ women. The presentation of results is organized by the level of socioeconomic resources in the countries where studies were conducted (i.e., high-, middle-, and low-income countries). It is concluded that psychiatric symptoms, particularly depression, and mental health vulnerabilities (e.g., inadequate coping skills) are widespread among pregnant HIV+ women globally and have a potential to affect psychological well-being, quality of life and salient clinical outcomes. The current body of evidence provides rationale for developing and evaluating clinical and structural interventions aimed at improving mental health outcomes and their clinical correlates in pregnant HIV+ women.
C1 [Kapetanovic, Suad; Nora, Diana] NIMH, NIH, Bethesda, MD 20892 USA.
[Kapetanovic, Suad] NIMH, Off Clin Director, Bethesda, MD 20892 USA.
[Dass-Brailsford, Priscilla] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA.
[Talisman, Nicholas] Georgetown Univ, Sch Med, Washington, DC USA.
RP Kapetanovic, S (reprint author), NIMH, Off Clin Director, 10 CRC,Room 6-5340,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA.
EM suad.kapetanovic@nih.gov
FU Intramural NIH HHS [Z99 MH999999]; NIAID NIH HHS [P30 AI087714,
P30AI087714]
NR 72
TC 10
Z9 10
U1 0
U2 16
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
EI 1573-3254
J9 AIDS BEHAV
JI AIDS Behav.
PD JUN
PY 2014
VL 18
IS 6
BP 1152
EP 1173
DI 10.1007/s10461-014-0728-9
PG 22
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA AH5YF
UT WOS:000336206400019
PM 24584458
ER
PT J
AU Prizment, AE
Yatsuya, H
Lutsey, PL
Lubin, JH
Woodward, M
Folsom, AR
Huxley, RR
AF Prizment, Anna E.
Yatsuya, Hiroshi
Lutsey, Pamela L.
Lubin, Jay H.
Woodward, Mark
Folsom, Aaron R.
Huxley, Rachel R.
TI Smoking Behavior and Lung Cancer in a Biracial Cohort The
Atherosclerosis Risk in Communities Study
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID UNITED-STATES; RACIAL-DIFFERENCES; AFRICAN-AMERICANS; CIGARETTE-SMOKING;
INTERVAL ESTIMATION; MENTHOL CIGARETTES; WHITE SMOKERS; CARCINOMA;
CESSATION; WOMEN
AB Background: In the U.S., the incidence of lung cancer varies by race, with rates being highest among black men. There are marked differences in smoking behavior between blacks and whites, but little is known regarding how these differences contribute to the racial disparities in lung cancer.
Purpose: To compare the lung cancer risk associated with smoking in 14,610 blacks and whites in the prospective cohort Atherosclerosis Risk in Communities study.
Methods: Smoking characteristics were ascertained at baseline and three follow-up visits in 1990-1992, 1993-1995, and 1996-1998 (response rates were 93%, 86%, and 80%, respectively), as well as from annual telephone interviews. Data Were analyzed in the fall of 2012. Multivariable-adjusted proportional hazards models were used to calculate hazard ratios and 95% CIs for lung cancer.
Results: Over 20 years of follow-up (1987-2006), 470 incident cases of lung cancer occurred. Lung cancer incident rates were highest in black men and lowest in black women. However, there was no evidence to support racial differences in the associations of smoking status, intensity, or age at initiation with lung cancer risk (all p(interaction) >= 0.25). The hazard ratio for those who started smoking at age <= 12 versus >22 years was 3.03 (95% CI =1.62, 5.67). Prolonged smoking cessation ( >= 10 years) was associated with a decrease in lung cancer risk, with equivalent benefits in whites and blacks, 84% and 74%, respectively (P-interaction=0.25).
Conclusions: Smoking confers similar lung cancer risk in blacks and whites. (C) 2014 American Journal of Preventive Medicine
C1 [Prizment, Anna E.; Lutsey, Pamela L.; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
[Yatsuya, Hiroshi] Fujita Hlth Univ, Sch Med, Dept Publ Hlth, Toyoake, Aichi 47011, Japan.
[Lubin, Jay H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Woodward, Mark] Univ Sydney, George Inst Global Hlth, Sydney, NSW 2006, Australia.
[Huxley, Rachel R.] Univ Queensland, Sch Populat Hlth, Brisbane, Qld, Australia.
RP Prizment, AE (reprint author), Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, 1300 South Second St,Suite 300, Minneapolis, MN 55454 USA.
EM prizm001@umn.edu
RI Huxley, Rachel/J-4638-2013; Woodward, Mark/D-8492-2015; Huxley,
Rachel/C-7032-2013
OI Huxley, Rachel/0000-0002-2705-6616; Huxley, Rachel/0000-0002-2705-6616
FU Intramural NIH HHS; NCATS NIH HHS [KL2 TR000113]; NCI NIH HHS [T32
CA132670, T32CA132670, U01 CA164975, U01 CA164975-01]; NCRR NIH HHS [UL1
RR025005, UL1RR025005]; NHLBI NIH HHS [HHSN268201100006C,
HHSN268201100005C, HHSN268201100005G, HHSN268201100005I,
HHSN268201100007C, HHSN268201100007I, HHSN268201100008C,
HHSN268201100008I, HHSN268201100009C, HHSN268201100009I,
HHSN268201100010C, HHSN268201100011C, HHSN268201100011I,
HHSN268201100012C]
NR 41
TC 4
Z9 4
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUN
PY 2014
VL 46
IS 6
BP 624
EP 632
DI 10.1016/j.amepre.2014.01.017
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA AH5SC
UT WOS:000336190400010
PM 24842739
ER
PT J
AU Wira, CR
Veronese, F
AF Wira, Charles R.
Veronese, Fulvia
TI Hormone Regulation of the Mucosal Environment in the Reproductive Tract
and the Prevention of HIV Infection
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Letter
C1 [Wira, Charles R.] Geisel Sch Med Dartmouth, Dept Physiol & Neurobiol, Lebanon, NH 03756 USA.
[Veronese, Fulvia] NIAID, Prevent Sci Program, DAIDS, NIH,DHHS, Bethesda, MD 20892 USA.
RP Wira, CR (reprint author), Geisel Sch Med Dartmouth, Dept Physiol & Neurobiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
EM Charles.R.Wira@Dartmouth.edu; veronesf@niaid.nih.gov
FU NIAID NIH HHS [R01 AI102838]
NR 1
TC 3
Z9 3
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
EI 1600-0897
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD JUN
PY 2014
VL 71
IS 6
SI SI
BP 487
EP 489
DI 10.1111/aji.12269
PG 3
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA AH1YK
UT WOS:000335917600001
PM 24832616
ER
PT J
AU Barreto-de-Souza, V
Arakelyan, A
Margolis, L
Vanpouille, C
AF Barreto-de-Souza, Victor
Arakelyan, Anush
Margolis, Leonid
Vanpouille, Christophe
TI HIV-1 Vaginal Transmission: Cell- Free or Cell- Associated Virus?
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Review
DE Cell; HIV-1; mucosa; semen; transmission
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN LYMPHOID-TISSUE;
SEXUALLY-TRANSMITTED-DISEASES; ACTIVE ANTIRETROVIRAL THERAPY; FEMALE
REPRODUCTIVE-TRACT; GENITAL EPITHELIAL-CELLS; TROJAN HORSE LEUKOCYTES;
MATURE DENDRITIC CELLS; CD4(+) T-CELLS; IN-VITRO
AB The vast majority of new HIV infections in male-to-female transmission occurs through semen, where HIV-1 is present in two different forms: as free and as cell-associated virus. In the female lower genital tract, semen mixes with female genital secretions that contain various factors, some of which facilitate or inhibit HIV-1 transmission. Next, HIV-1 crosses the genital epithelia, reaches the regional lymph nodes, and disseminates through the female host. Cervico-vaginal mucosa contains multiple barriers, resulting in a low probability of vaginal transmission. However, in some cases, HIV-1 is able to break these barriers. Although the exact mechanisms of how these barriers function remain unclear, their levels of efficiency against cell-free and cell-associated HIV-1 are different, and both cell-free and cell-associated virions seem to use different strategies to overcome these barriers. Understanding the basic mechanisms of HIV-1 vaginal transmission is required for the development of new antiviral strategies to contain HIV-1 epidemics.
C1 [Barreto-de-Souza, Victor; Arakelyan, Anush; Margolis, Leonid; Vanpouille, Christophe] NICHHD, Sect Intercellular Interact, Program Phys Biol, Bethesda, MD 20892 USA.
RP Margolis, L (reprint author), NICHHD, Program Phys Biol, Bldg 10,Room 9D58,10 Ctr Dr,MSC 1855, Bethesda, MD 20892 USA.
EM margolis@helix.nih.gov
FU NICHD; Brazilian Ministry of Education/CAPES; Brazilian Ministry of
Science and Technology/CNPq
FX This work was supported by the NICHD intramural program. VBS was
partially supported by fellowships from the Brazilian Ministry of
Education/CAPES and the Brazilian Ministry of Science and
Technology/CNPq. We are also grateful to Dr. Jean-Charles Grivel for his
critical review of the manuscript and helpful suggestions.
NR 139
TC 7
Z9 7
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
EI 1600-0897
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD JUN
PY 2014
VL 71
IS 6
SI SI
BP 589
EP 599
DI 10.1111/aji.12240
PG 11
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA AH1YK
UT WOS:000335917600013
PM 24730358
ER
PT J
AU Mestecky, J
Wei, Q
Alexander, R
Raska, M
Novak, J
Moldoveanu, Z
AF Mestecky, Jiri
Wei, Qing
Alexander, Rashada
Raska, Milan
Novak, Jan
Moldoveanu, Zina
TI Humoral Immune Responses to HIV in the Mucosal Secretions and Sera of
HIV- Infected
SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
LA English
DT Review
DE Antibody responses; human immunodeficiency virus; mucosal immunity;
secretory IgA and IgG
ID IMMUNODEFICIENCY-VIRUS TYPE-1; GENITAL-TRACT; NEUTRALIZING ANTIBODIES;
IGA ANTIBODIES; 1-INFECTED INDIVIDUALS; ENVELOPE-GLYCOPROTEIN; EXTERNAL
SECRETIONS; MONOCLONAL-ANTIBODY; IMMUNOGLOBULIN-G; IN-VITRO
AB Although sera and all external secretions contain antibodies to human immunodeficiency virus (HIV), their levels, specificity, isotypes, and relevant effector functions display a great degree of variability. Antibodies that bind HIV antigens and neutralize the virus are predominantly associated with the IgG isotype in sera and in all external secretions, even where total levels of IgG are much lower than those of IgA. Rectal fluid that contains high IgA, but low IgG levels, displayed low neutralizing activity independent of antibodies. Therefore, external secretions should be evaluated before and after selective depletion of Ig. At the systemic level, HIV-specific IgA may interfere with the effector functions of IgG, as suggested by recent studies of individuals systemically immunized with an experimental HIV vaccine. Although HIV-specific IgG and IgA antibodies may exhibit their protective activities at mucosal surfaces through interference with viral entry and local neutralization at the systemic level, such antibodies may display discordant effector functions.
C1 [Mestecky, Jiri; Wei, Qing; Alexander, Rashada; Raska, Milan; Novak, Jan; Moldoveanu, Zina] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Mestecky, Jiri] Charles Univ Prague, Fac Med, Inst Microbiol & Immunol, Prague, Czech Republic.
[Alexander, Rashada] NIH, Off Director, Bethesda, MD 20892 USA.
[Raska, Milan] Palacky Univ, Fac Med, Dept Immunol, CR-77147 Olomouc, Czech Republic.
RP Mestecky, J (reprint author), Univ Alabama Birmingham, BBRB 757,845 19th St South, Birmingham, AL 35294 USA.
EM mestecky@uab.edu
FU NIH-NIAID [PO1 AI083027, R21 AI083613]; University of Alabama at
Birmingham (UAB) School of Medicine; UAB Immunology, Autoimmunity, and
Transplantation Strategic Planning; UAB CFAR [P30 AI027767]
FX This work was supported by grants from NIH-NIAID (PO1 AI083027; R21
AI083613), a Pilot Grant from the University of Alabama at Birmingham
(UAB) School of Medicine, a grant from UAB Immunology, Autoimmunity, and
Transplantation Strategic Planning and a Developmental Grant from UAB
CFAR (P30 AI027767).
NR 69
TC 4
Z9 4
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1046-7408
EI 1600-0897
J9 AM J REPROD IMMUNOL
JI Am. J. Reprod. Immunol.
PD JUN
PY 2014
VL 71
IS 6
SI SI
BP 600
EP 607
DI 10.1111/aji.12203
PG 8
WC Immunology; Reproductive Biology
SC Immunology; Reproductive Biology
GA AH1YK
UT WOS:000335917600014
PM 24494997
ER
PT J
AU Aladjem, MI
Fu, HQ
AF Aladjem, Mirit I.
Fu, Haiqing
TI A new light on DNA replication from the inactive X chromosome
SO BIOESSAYS
LA English
DT Article
DE cell cycle; chromatin; DNA replication; epigenetics; inactive X
chromosome
ID HBO1 HISTONE ACETYLASE; ALLELE-SPECIFIC REPLICATION; BETA-GLOBIN LOCUS;
MAMMALIAN-CELLS; ASYNCHRONOUS REPLICATION; TRANSCRIPTION-FACTOR; DELAYED
REPLICATION; GENE-EXPRESSION; S-PHASE; ORIGIN
AB While large portions of the mammalian genome are known to replicate sequentially in a distinct, tissue-specific order, recent studies suggest that the inactive X chromosome is duplicated rapidly via random, synchronous DNA synthesis at numerous adjacent regions. The rapid duplication of the inactive X chromosome was observed in high-resolution studies visualizing DNA replication patterns in the nucleus, and by allele-specific DNA sequencing studies measuring the extent of DNA synthesis. These studies conclude that inactive X chromosomes complete replication earlier than previously thought and suggest that the strict order of DNA replication detected in the majority of genomic regions is not preserved in non-transcribed, silent chromatin. These observations alter current concepts about the regulation of DNA replication in non-transcribed portions of the genome in general and in the inactive X-chromosome in particular.
C1 [Aladjem, Mirit I.; Fu, Haiqing] NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Aladjem, MI (reprint author), NCI, Dev Therapeut Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM aladjemm@mail.nih.gov
RI Aladjem, Mirit/G-2169-2010
OI Aladjem, Mirit/0000-0002-1875-3110
FU CCR; National Cancer Institute; National Institutes of Health
FX We thank Drs. Eric Bouhassira, Carl Schildkraut and Mathew Thayer for
helpful discussions and Owen Smith for critical reading of the
manuscript. We apologize to colleagues whose work could not be cited
directly due to space limitations. Studies at our lab are supported by
the intramural program of the CCR, National Cancer Institute, National
Institutes of Health.
NR 84
TC 1
Z9 1
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0265-9247
EI 1521-1878
J9 BIOESSAYS
JI Bioessays
PD JUN
PY 2014
VL 36
IS 6
BP 591
EP 597
DI 10.1002/bies.201400021
PG 7
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA AI0IH
UT WOS:000336529800011
PM 24706495
ER
PT J
AU Yanik, GA
Horowitz, MM
Weisdorf, DJ
Logan, BR
Ho, VT
Soiffer, RJ
Carter, SL
Wu, J
Wingard, JR
Difronzo, NL
Ferrara, JL
Giralt, S
Madtes, DK
Drexler, R
White, ES
Cooke, KR
AF Yanik, Gregory A.
Horowitz, Mary M.
Weisdorf, Daniel J.
Logan, Brent R.
Ho, Vincent T.
Soiffer, Robert J.
Carter, Shelly L.
Wu, Juan
Wingard, John R.
Difronzo, Nancy L.
Ferrara, James L.
Giralt, Sergio
Madtes, David K.
Drexler, Rebecca
White, Eric S.
Cooke, Kenneth R.
TI Randomized, Double-Blind, Placebo-Controlled Trial of Soluble Tumor
Necrosis Factor Receptor: Enbrel (Etanercept) for the Treatment of
Idiopathic Pneumonia Syndrome after Allogeneic Stem Cell
Transplantation: Blood and Marrow Transplant Clinical Trials Network
Protocol
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Bone marrow transplantation; IPS; TNF; Pneumonia; Pulmonary
ID LUNG INJURY; RISK
AB Idiopathic pneumonia syndromes (IPS) is a diffuse, noninfectious lung injury that occurs acutely after allogeneic hematopoietic cell transplantation (HCT). JPS-related mortality has been historically high (>50%) despite treatment with systemic corticosteroids and supportive care measures. We have now examined the role of tumor necrosis factor inhibition in a randomized, double-blind, placebo-controlled trial of corticosteroids with etanercept or placebo. Thirty-four subjects (>= 18 years) with IPS after HCT were randomized to receive methylprednisolone (2 mg/kg/day) plus etanercept (0.4 mg/kg twice weekly X 4 weeks; n = 16) or placebo (n = 18). No active infections and a pathogen-negative bronchoscopy were required at study entry. Response (alive, with complete discontinuation of supplemental oxygen support) and overall survival were examined. This study, originally planned to accrue 120 patients, was terminated prematurely due to slow accrual. In the limited number of patients examined, there were no differences in response rates at day 28 of study. Ten of 16 patients (62.5% [95%,confidence interval {CI}, 35.4% to 84.8%]) receiving etanercept and 12 of 18 patients (66.7% [95% CI, 41,0% to 86.7%]) receiving placebo met the day 28 response definition (P = 1.00). The median survival was 170 days (95% CI, 11 to 362) with etanercept versus 64 days (95% CI, 26 to 209) with placebo (P = .51). Among responders, the-median time to discontinuation of supplemental oxygen was 9 days (etanercept) versus 7 days (placebo). Therapy was well tolerated, With 1 toxicity-related death froth infectious pneumonia in the placebo arm. The treatment of IPS with corticosteroids in adult HCT recipients was associated with high early response rates (>60%) compared with historical reports, with poor overall survival. The addition of etanercept did not lead to further increases in response, although the sample size of this truncated trial preclude a definitive conclusion. (C) 2014 Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation.
C1 [Yanik, Gregory A.; Ferrara, James L.] Univ Michigan, Blood & Marrow Transplant Program, Med Ctr, Dept Pediat & Internal Med, Ann Arbor, MI 48109 USA.
[Horowitz, Mary M.; Logan, Brent R.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Weisdorf, Daniel J.] Univ Minnesota, Dept Internal Med, Blood & Marrow Transplantat Program, Minneapolis, MN USA.
[Ho, Vincent T.; Soiffer, Robert J.] Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA.
[Carter, Shelly L.; Wu, Juan] EMMES Corp, Rockville, MD USA.
[Wingard, John R.] Univ Florida, Dept Med, Gainesville, FL USA.
[Difronzo, Nancy L.] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
[Giralt, Sergio] Mem Sloan Kettering Canc Ctr, Dept Stem Cell Transplantat, New York, NY 10021 USA.
[Madtes, David K.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98195 USA.
[Madtes, David K.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
[Drexler, Rebecca] Natl Marrow Donor Program, Minneapolis, MN USA.
[Drexler, Rebecca] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[White, Eric S.] Univ Michigan, Med Ctr, Dept Internal Med Pulm & Crit Care Med, Ann Arbor, MI 48109 USA.
[Cooke, Kenneth R.] Johns Hopkins Univ, Sch Med, Dept Oncol, Sidney Kimmel Canc Ctr, Baltimore, MD 21205 USA.
RP Yanik, GA (reprint author), Univ Michigan, Blood & Marrow Transplant Program, Med Ctr, 5310 Canc Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
EM gyanik@umich.edu
FU National Heart, Lung, and Blood Institute [U10HL069294]; Leukemia and
Lymphoma Society; Burroughs Welcome Fund; National Cancer Institute
FX Support for this study was provided by grant U10HL069294 from the
National Heart, Lung, and Blood Institute and the National Cancer
Institute, The Leukemia and Lymphoma Society (to K.R.C.), and the
Burroughs Welcome Fund (to K.R.C.). Immunex Corporation, a wholly owned
subsidiary of Amgen Inc., provided study drug and central pharmacy
support for the trial.
NR 17
TC 13
Z9 13
U1 0
U2 32
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUN
PY 2014
VL 20
IS 6
BP 858
EP 864
DI 10.1016/j.bbmt.2014.02.026
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA AH8WH
UT WOS:000336418400019
PM 24607553
ER
PT J
AU Koethe, Y
Mannes, AJ
Wood, BJ
AF Koethe, Yilun
Mannes, Andrew J.
Wood, Bradford J.
TI Image-guided Nerve Cryoablation for Post-thoracotomy Pain Syndrome
SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
DE Cryoablation; Clinical practice; Pain management; Spine/nervous system;
Experimental IR
ID FEASIBILITY; ABLATION; ACCURACY; FUSION; TUMORS
AB Chronic post-thoracotomy pain syndrome (PTPS) can cause significant patient distress and is frequently difficult to manage. Percutaneous intercostal nerve (ICN) cryoablation by palpation of surface landmarks can be risky, as inaccurate probe placement can lead to hemo- or pneumothorax. Experience with image-guided ICN cryoablation with treatment planning and device navigation is limited. A patient with intractable PTPS was treated with ICN cryoablation under cone-beam computed tomography guidance with software-assisted needle trajectory planning and ablation zone simulation. This procedure provided the patient similar to 8 weeks of relief. This case demonstrated that ICN cryoablation is feasible under image guidance with device navigation and ablation simulation and may result in a few months of pain relief in cases of intractable PTPS.
C1 [Koethe, Yilun; Wood, Bradford J.] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Koethe, Yilun] Duke Univ, Sch Med, Durham, NC 27710 USA.
[Mannes, Andrew J.] NIH, Perioperat Med Clin Ctr, Bethesda, MD 20892 USA.
RP Koethe, Y (reprint author), NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr,MSC 1182,Bldg 10, Bethesda, MD 20892 USA.
EM yilun.koethe@gmail.com; bwood@cc.nih.gov
OI Mannes, Andrew/0000-0001-5834-5667
FU [ZIA BC 011242-03CCRO]
FX The authors wish to thank Dr. Nadine Abi-Jaoudeh for contributing the
images used in this publication. Grant #No. ZIA BC 011242-03CCRO
NR 14
TC 3
Z9 3
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0174-1551
EI 1432-086X
J9 CARDIOVASC INTER RAD
JI Cardiovasc. Interv. Radiol.
PD JUN
PY 2014
VL 37
IS 3
BP 843
EP 846
DI 10.1007/s00270-013-0718-8
PG 4
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA AH7RM
UT WOS:000336331300041
PM 23954965
ER
PT J
AU Amalou, H
Wood, BJ
AF Amalou, Hayet
Wood, Bradford J.
TI Beware Catheter Breakdown During Alcohol Sclerosis of Lymphoceles
SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Letter
ID POSTOPERATIVE LYMPHOCELES; RENAL-TRANSPLANTATION; SCLEROTHERAPY;
MANAGEMENT
C1 [Amalou, Hayet; Wood, Bradford J.] NIH, Ctr Intervent Oncol Radiol & Imaging Sci, Bethesda, MD 20892 USA.
RP Wood, BJ (reprint author), NIH, Ctr Intervent Oncol Radiol & Imaging Sci, MSC 1182,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bwood@nih.gov
FU Intramural NIH HHS
NR 5
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0174-1551
EI 1432-086X
J9 CARDIOVASC INTER RAD
JI Cardiovasc. Interv. Radiol.
PD JUN
PY 2014
VL 37
IS 3
BP 850
EP 851
DI 10.1007/s00270-013-0774-0
PG 2
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA AH7RM
UT WOS:000336331300043
PM 24190637
ER
PT J
AU Solier, S
Pommier, Y
AF Solier, Stephanie
Pommier, Yves
TI The nuclear gamma-H2AX apoptotic ring: implications for cancers and
autoimmune diseases
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Chromatin; Epigenetics; Biomarkers
ID DOUBLE-STRAND BREAKS; HISTONE H2AX PHOSPHORYLATION; DNA-DAMAGE RESPONSE;
DEPENDENT PROTEIN-KINASE; PROGRAMMED CELL-DEATH; ATM ACTIVATION;
CHROMOSOME CONDENSATION; CYCLE PHASE; SERINE 139; S-PHASE
AB Apoptosis is a fundamental process for metazoan development. It is also relevant to the pathophysiology of immune diseases and cancers and to the outcome of cancer chemotherapies, as well as being a target for cancer therapies. Apoptosis involves intrinsic pathways typically initiated by DNA damaging agents and engaging mitochondria, and extrinsic pathways typically initiated by "death receptors" and their ligands TRAIL and TNF at the cell surface. Recently, we discovered the apoptotic ring, which microscopically looks like a nuclear annular staining early in apoptosis. This ring is, in three-dimensional space, a thick intranuclear shell consisting of epigenetic modifications including histone H2AX and DNA damage response (DDR) proteins. It excludes the DNA repair factors usually associated with gamma-H2AX in the DDR nuclear foci. Here, we summarize our knowledge of the apoptotic ring, and discuss its biological and pathophysiological relevance, as well as its value as a potential pharmacodynamic biomarker for anticancer therapies.
C1 [Solier, Stephanie; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU NCI Intramural Program, Center for Cancer Research, NIH
FX We wish to thank our close laboratory colleagues for their commitment to
gamma-H2AX basic research: Dr. William Bonner, Dr. Christophe Redon, Dr.
James H. Doroshow, and Dr. Kurt W. Kohn. We also wish to thank our NCI
colleagues from the DCTD, PADIS, for the development of gamma-H2AX
pharmacodynamics biomarker assays: Dr. James H. Doroshow, Dr. Joseph E.
Tomaszewski, Dr. Raph E. Parchment, and Dr. Robert Kinders. Our studies
are supported by the NCI Intramural Program, Center for Cancer Research,
NIH.
NR 68
TC 16
Z9 16
U1 1
U2 10
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
EI 1420-9071
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD JUN
PY 2014
VL 71
IS 12
BP 2289
EP 2297
DI 10.1007/s00018-013-1555-2
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA AH8SJ
UT WOS:000336408200007
PM 24448903
ER
PT J
AU Case, ED
Chong, A
Wehrly, TD
Hansen, B
Child, R
Hwang, S
Virgin, HW
Celli, J
AF Case, Elizabeth Di Russo
Chong, Audrey
Wehrly, Tara D.
Hansen, Bryan
Child, Robert
Hwang, Seungmin
Virgin, Herbert W.
Celli, Jean
TI The Francisella O-antigen mediates survival in the macrophage cytosol
via autophagy avoidance
SO CELLULAR MICROBIOLOGY
LA English
DT Article
ID LIPID-A; TULARENSIS; LIPOPOLYSACCHARIDE; REPLICATION; ESCAPE;
RECOGNITION; MUTANTS; PATHOGENICITY; STRAINS; ATG5
AB Autophagy is a key innate immune response to intracellular parasites that promotes their delivery to degradative lysosomes following detection in the cytosol or within damaged vacuoles. Like Listeria and Shigella, which use specific mechanisms to avoid autophagic detection and capture, the bacterial pathogen Francisella tularensis proliferates within the cytosol of macrophages without demonstrable control by autophagy. To examine how Francisella evades autophagy, we screened a library of F.tularensis subsp. tularensisSchu S4 HimarFT transposon mutants in GFP-LC3-expressing murine macrophages by microscopy for clones localized within autophagic vacuoles after phagosomal escape. Eleven clones showed autophagic capture at 6h post-infection, whose HimarFT insertions clustered to fourgenetic loci involved in lipopolysaccharidic and capsular O-antigen biosynthesis. Consistent with the HimarFT mutants, in-frame deletion mutants of two representative loci, FTT1236 and FTT1448c (manC), lacking both LPS and capsular O-antigen, underwent phagosomal escape but were cleared from the host cytosol. Unlike wild-type Francisella, the O-antigen deletion mutants were ubiquitinated, and recruited the autophagy adaptor p62/SQSTM1 and LC3 prior to cytosolic clearance. Autophagy-deficient macrophages partially supported replication of both mutants, indicating that O-antigen-lacking Francisella are controlled by autophagy. These data demonstrate the intracellular protective role of this bacterial surface polysaccharide against autophagy.
C1 [Case, Elizabeth Di Russo; Chong, Audrey; Wehrly, Tara D.; Child, Robert; Celli, Jean] NIAID, Lab Intracellular Parasites, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Hansen, Bryan] NIAID, Electron Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Hwang, Seungmin; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Hwang, Seungmin; Virgin, Herbert W.] Washington Univ, Sch Med, Midwest Reg Ctr Excellence Biodef & Emerging Infe, St Louis, MO 63110 USA.
RP Celli, J (reprint author), Washington State Univ, Coll Vet Med, Paul G Allen Sch Global Anim Hlth, Pullman, WA 99164 USA.
EM jcelli@vetmed.wsu.edu
OI Hwang, Seungmin/0000-0003-0846-5462; Case, Elizabeth/0000-0002-9129-3894
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases; NIAID [U54 AI057160]
FX We thank members of the lab for their assistance with generating the
Francisella-HimarFT insertion library, Michael Apicella for the
monoclonal 11B7 antibody against Francisella capsule, helpful
suggestions and critical reading of the manuscript, Thomas Zahrt for the
pHimarH3, Jacques Peschon and Ed Miao for pBMN-Z-v-mycMC29,
and Leigh Knodler for critical reading of the manuscript. We also thank
Stephanie Lathrop and Olivia Steele-Mortimer for providing human
peripheral blood monocytes. This work was supported by the Intramural
Research Program of the National Institutes of Health, National
Institute of Allergy and Infectious Diseases and by NIAID Grant U54
AI057160 to H.W. Virgin. The authors declare that they have no conflict
of interest.
NR 37
TC 20
Z9 20
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-5814
EI 1462-5822
J9 CELL MICROBIOL
JI Cell Microbiol.
PD JUN
PY 2014
VL 16
IS 6
BP 862
EP 877
DI 10.1111/cmi.12246
PG 16
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA AH2DF
UT WOS:000335930200006
PM 24286610
ER
PT J
AU Den Linger, CS
Meropol, NJ
Li, T
Lewis, NL
Engstrom, PF
Weiner, LM
Cheng, JD
Alpaugh, RK
Cooper, H
Wright, JJ
Cohen, SJ
AF Den Linger, Crystal S.
Meropol, Neal J.
Li, Tianyu
Lewis, Nancy L.
Engstrom, Paul F.
Weiner, Louis M.
Cheng, Jonathan D.
Alpaugh, R. Katherine
Cooper, Harry
Wright, John J.
Cohen, Steven J.
TI A Phase II Trial of the Proteasome Inhibitor Bortezomib in Patients With
Advanced Biliary Tract Cancers
SO CLINICAL COLORECTAL CANCER
LA English
DT Article
DE Biliary tract cancers; Bortezomib; Cholangiocarcinoma; Proteosome
inhibition
ID HUMAN CHOLANGIOCARCINOMA CELLS; DIAGNOSED MULTIPLE-MYELOMA; SINGLE-AGENT
GEMCITABINE; INTRAHEPATIC CHOLANGIOCARCINOMA; GALLBLADDER CARCINOMA;
P27(KIP1) EXPRESSION; PLUS DEXAMETHASONE; HISTOLOGIC TYPES; SURVIVAL
RATES; KAPPA-B
AB Therapeutic options in advanced biliary tract cancers are limited. We evaluated bortezomib in 20 patients with advanced biliary tract cancers in a single-arm phase H study. Although no objective responses were seen, 9 patients achieved stable disease with encouraging median time to progression and survival rates, suggesting that evaluation of bortezomib in combination with other therapies is warranted in this disease. Background: Patients with advanced biliary tract cancers have limited therapeutic options. Preclinical data suggest that proteasome inhibition may be an effective therapeutic strategy. We thus evaluated the clinical efficacy of bortezomib in advanced biliary tract cancers. Patients and Methods: Patients with locally advanced or metastatic cholangiocarcinoma or gallbladder adenocarcinoma who had received 0 to 2 previous therapies received bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 of a 21-day cycle. The primary end point was objective response rate. A Simon 2-stage design was used (null response rate of < 5% and response rate of >= 20% of interest). Results: Twenty patients enrolled (bile duct/gallbladder cancer [14/6] and previous treatments 0/1/2 [10/6/3]). The trial was discontinued early because of lack of confirmed partial responses. No unanticipated adverse events were noted. There was 1 unconfirmed partial response. Ten patients achieved stable disease as best response. Median time to progression was 5.8 months (95% confidence interval [CI], 0.7-77.6 months). Median survival was 9 months (95% CI, 4.6-18.5 months). The 6-month and 1-year survival rates were 70% and 38%, respectively. There was no difference in survival based on primary disease site. Conclusion: Single-agent bortezomib does not result in objective responses in biliary tract cancers. However, the rate of stable disease and time to progression benchmark is encouraging. Further development of bortezomib in combination with other therapies in this disease setting should be considered.(C) 2014 Elsevier Inc. All rights reserved.
C1 [Den Linger, Crystal S.; Engstrom, Paul F.; Cheng, Jonathan D.; Alpaugh, R. Katherine; Cohen, Steven J.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA.
[Meropol, Neal J.] Case Western Reserve Univ, Univ Hosp, Case Med Ctr, Case Comprehens Canc Ctr,Seidman Canc Ctr,Div Hem, Cleveland, OH 44106 USA.
[Li, Tianyu] Fox Chase Canc Ctr, Dept Biostat, Philadelphia, PA 19111 USA.
[Lewis, Nancy L.] Thomas Jefferson Univ Hosp, Dept Med Oncol, Philadelphia, PA 19107 USA.
[Weiner, Louis M.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA.
[Cooper, Harry] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA.
[Wright, John J.] Natl Canc Inst, Canc Therapy Evaluat Program, Invest Drug Branch, Rockville, MD USA.
RP Den Linger, CS (reprint author), Fox Chase Canc Ctr, 333 Cottman Ave, Philadelphia, PA 19111 USA.
EM crystal.denlinger@fccc.edu
FU National Cancer Institute [P30 CA006927]; Cancer Therapy Evaluation
Program NCI [6135]
FX This study was supported by the National Cancer Institute P30 CA006927
(Fisher) and the Cancer Therapy Evaluation Program NCI # 6135 (SJC). The
content of this article is solely the responsibility of the authors and
does not necessarily represent the official views of the National Cancer
Institute.
NR 48
TC 4
Z9 4
U1 0
U2 3
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1533-0028
EI 1938-0674
J9 CLIN COLORECTAL CANC
JI Clin. Colorectal Canc.
PD JUN
PY 2014
VL 13
IS 2
BP 81
EP 86
DI 10.1016/j.clcc.2013.12.005
PG 6
WC Oncology
SC Oncology
GA AH5UO
UT WOS:000336196800002
PM 24512954
ER
PT J
AU Huang, J
Nair, SG
Mahoney, MR
Nelson, GD
Shields, AF
Chan, E
Goldberg, RM
Gill, S
Kahlenberg, MS
Quesenberry, JT
Thibodeau, SN
Smyrk, TC
Grothey, A
Sinicrope, FA
Webb, TA
Farr, GH
Pockaj, BA
Berenberg, JL
Mooney, M
Sargent, DJ
Alberts, SR
AF Huang, Jocelin
Nair, Suresh G.
Mahoney, Michelle R.
Nelson, Garth D.
Shields, Anthony F.
Chan, Emily
Goldberg, Richard M.
Gill, Sharlene
Kahlenberg, Morton S.
Quesenberry, James T.
Thibodeau, Stephen N.
Smyrk, Thomas C.
Grothey, Axel
Sinicrope, Frank A.
Webb, Thomas A.
Farr, Gist H., Jr.
Pockaj, Barbara A.
Berenberg, Jeffrey L.
Mooney, Margaret
Sargent, Daniel J.
Alberts, Steven R.
CA Alliance Clinical Trials Oncology
TI Comparison of FOLFIRI With or Without Cetuximab in Patients With
Resected Stage III Colon Cancer; NCCTG (Alliance) Intergroup Trial N0147
SO CLINICAL COLORECTAL CANCER
LA English
DT Article
DE Adjuvant therapy; Disease free survival; Overall survival; Response rate
ID METASTATIC COLORECTAL-CANCER; 1ST-LINE TREATMENT; ADJUVANT TREATMENT;
RANDOMIZED-TRIAL; FLUOROURACIL; LEUCOVORIN; CHEMOTHERAPY; IRINOTECAN;
KRAS; OXALIPLATIN
AB In the randomized phase III trial N0147 for resected colon cancer, the early trial versions included treatment arms of FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) with and without cetuximab, in addition to FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) with and without cetuximab. In the small group receiving FOLFIRI plus cetuximab evidence of possible benefit was noted. However, pending results of a randomized trial, FOLFIRI plus cetuximab should not be considered as an option for adjuvant therapy. Background: Two arms with FOLFIRI, with or without cetuximab, were initially included in the randomized phase III intergroup clinical trial NCCTG (North Central Cancer Treatment Group) N0147. When other contemporary trials demonstrated no benefit to using irinotecan as adjuvant therapy, the FOLFIRI-containing arms were discontinued. We report the clinical outcomes for patients randomized to FOLFIRI with or without cetuximab. Patients and Methods: After resection, patients were randomized to 12 biweekly cycles of FOLFIRI, with or without cetuximab. KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation status was retrospectively determined in a central lab. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS) and toxicity. Results: One hundred and six patients received FOLFIRI and 40 received FOLFIRI plus cetuximab. Median follow-up was 5.95 years (range, 0.1-7.0 years). The addition of cetuximab showed a trend toward improved DFS (hazard ratio [HR], 0.53; 95% CI, 0.26-1.1; P = .09) and OS (HR, 0.45; 95% CI, 0.17-1.16; P = .10) in the overall group, regardless of KRAS status, and in patients with wild type KRAS. Grade >= 3 nonhematologic adverse effects were significantly increased in the cetuximab versus FOLFIRI-alone arm (68% vs. 46%; P = .02). Adjuvant FOLFIRI resulted in a 3-year DFS less than that expected for FOLFOX. Conclusion: In this small randomized subset of patients with resected stage III colon cancer, the addition of cetuximab to FOLFIRI was associated with a nonsignificant trend toward improved DFS and OS. Nevertheless, considering the limitations of this analysis, FOLFOX without the addition of a biologic agent remains the standard of care for adjuvant therapy in resected stage Ill colon cancer. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Huang, Jocelin; Thibodeau, Stephen N.; Smyrk, Thomas C.; Grothey, Axel; Sinicrope, Frank A.; Alberts, Steven R.] Mayo Clin, Dept Oncol, Rochester, MN 55905 USA.
[Nair, Suresh G.] Lehigh Valley Hosp, Allentown, PA USA.
[Mahoney, Michelle R.; Nelson, Garth D.; Sargent, Daniel J.] Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN 55905 USA.
[Shields, Anthony F.] Karmanos Canc Inst, Dept Oncol, Detroit, MI USA.
[Chan, Emily] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, Nashville, TN USA.
[Goldberg, Richard M.] Ohio State Univ, Wexner Med Ctr, Dept Oncol, Columbus, OH 43210 USA.
[Gill, Sharlene] British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada.
[Kahlenberg, Morton S.] Surg Oncol Assoc South Texas, San Antonio, TX USA.
[Quesenberry, James T.] Siouxland Hematol Oncol Assoc, Sioux City, IA USA.
[Webb, Thomas A.] Illinois Oncol Res Assoc Community Clin Oncol Pro, Peoria, IL USA.
[Farr, Gist H., Jr.] Ochsner Community Clin Oncol Program, New Orleans, LA USA.
[Pockaj, Barbara A.] Mayo Clin Arizona, Scottsdale, AZ USA.
[Berenberg, Jeffrey L.] Univ Hawaii, Ctr Canc, Community Clin Oncol Program, Honolulu, HI 96822 USA.
[Mooney, Margaret] Natl Canc Inst, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Clin Invest Branch, Bethesda, MD USA.
RP Alberts, SR (reprint author), Mayo Clin, Div Med Oncol, Go-10,200 First St SW, Rochester, MN 55905 USA.
EM alberts.steven@mayo.edu
OI Sargent, Daniel/0000-0002-2684-4741
FU NCCTG; Mayo Clinic; Public Health Service from NCI - Department of
Health and Human Services [CA-25224, CA-37404, CA-35103, CA-35113,
CA-35272, CA-114740, CA-32102, CA-14028, CA49957, CA21115, CA31946,
CAl2027, CA37377]; Canadian Cancer Society Research Institute [021039,
015469]; US NCI [CA077202]
FX This study was conducted as a collaborative trial of the NCCTG, Mayo
Clinic, and was supported in part by Public Health Service grants
CA-25224, CA-37404, CA-35103, CA-35113, CA-35272, CA-114740, CA-32102,
CA-14028, CA49957, CA21115, CA31946, CAl2027, CA37377 from the NCI,
Department of Health and Human Services. National Cancer Institute of
Canada Clinical Trials Group participation in this trial was supported
by funding received from the Canadian Cancer Society Research Institute
(Grant #021039 and #015469) and the US NCI (Grant #CA077202). The
content is solely the responsibility of the authors and does not
necessarily represent the views of the NCI or the National Institutes of
Health.
NR 18
TC 15
Z9 17
U1 0
U2 5
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1533-0028
EI 1938-0674
J9 CLIN COLORECTAL CANC
JI Clin. Colorectal Canc.
PD JUN
PY 2014
VL 13
IS 2
BP 100
EP 109
DI 10.1016/j.clcc.2013.12.002
PG 10
WC Oncology
SC Oncology
GA AH5UO
UT WOS:000336196800005
PM 24512953
ER
PT J
AU Keller, SP
Fessler, HE
AF Keller, Steven P.
Fessler, Henry E.
TI Monitoring of oesophageal pressure
SO CURRENT OPINION IN CRITICAL CARE
LA English
DT Review
DE respiratory monitoring; dead space; volumetric capnography; mechanical
ventilation
ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; ACUTE LUNG
INJURY; RANDOMIZED CONTROLLED-TRIAL; TRANSPULMONARY PRESSURE; PLEURAL
PRESSURE; MECHANICS; EXCHANGE; BALLOONS; SUPINE
AB Purpose of review Volumetric capnography (VCap) measures the kinetics of carbon dioxide (CO2) elimination on a breath-by-breath basis. A volumetric capnogram contains extensive physiological information about metabolic production, circulatory transport and CO2 elimination within the lungs. VCap is also the best clinical tool to measure dead spaces allowing a detailed analysis of the functional components of each tidal volume, thereby providing clinically useful hints about the lung's efficiency of gas exchange. Difficulties in its bedside measurement, oversimplifications of its interpretation along with prevailing misconceptions regarding dead space analysis have, however, limited its adoption as a routine tool for monitoring mechanically ventilated patients. Recent findings Improvements in CO2 measuring technologies and more advanced algorithms for faster and more accurate analysis of volumetric capnograms have increased our physiological understanding and thus the clinical usefulness of VCap. The recently validated VCap-based method for estimating alveolar partial pressure of CO2 provided a breakthrough for a fully noninvasive breath-by-breath measurement of physiological dead space. Recent advances in VCap and our improved understanding of its clinical implications may help in overcoming the known limitations and reluctances to include expired CO2 kinetics and dead space analysis in routine bedside monitoring. It is about time to start using this powerful monitoring tool to support decision making in the intensive care environment.
C1 [Keller, Steven P.] NIH, Dept Crit Care, Bethesda, MD 20892 USA.
[Keller, Steven P.; Fessler, Henry E.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA.
RP Fessler, HE (reprint author), Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, 1830 E Monument St,5th Floor, Baltimore, MD 21205 USA.
EM hfessler@jhmi.ed
NR 29
TC 5
Z9 7
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1070-5295
EI 1531-7072
J9 CURR OPIN CRIT CARE
JI Curr. Opin. Crit. Care
PD JUN
PY 2014
VL 20
IS 3
BP 340
EP 346
DI 10.1097/MCC.0000000000000095
PG 7
WC Critical Care Medicine
SC General & Internal Medicine
GA AH2TK
UT WOS:000335973800017
PM 24751808
ER
PT J
AU Clark, NA
Mumford, SL
Segars, JH
AF Clark, Natalie A.
Mumford, Sunni L.
Segars, James H.
TI Reproductive impact of MRI-guided focused ultrasound surgery for
fibroids: a systematic review of the evidence
SO CURRENT OPINION IN OBSTETRICS & GYNECOLOGY
LA English
DT Review
DE fertility; fibroids; HIFU; MRgFUS; pregnancy
ID UTERINE FIBROIDS; PREGNANCY; ABLATION; MRGFUS; LEIOMYOMAS; HYPERINTENSE;
IMPROVEMENT; PREDICTORS; EXPERIENCE; EFFICACY
AB Purpose of reviewMagnetic-resonance-guided focused ultrasound surgery (MRgFUS) is a minimally invasive technique for the treatment of uterine fibroids. The purpose of this review is to highlight the impact of MRgFUS on fertility and reproductive outcomes.Recent findingsThe role of MRgFUS in the treatment of fibroids has been evolving since its introduction in 2004. Several new devices and techniques including location-specific treatment, volumetric therapy, and vessel-targeted therapy have been introduced over the last few years. Several case series report uncomplicated pregnancy following MRgFUS; however, results of the ongoing studies will further elucidate the utility of MRgFUS in patients planning future fertility. A systematic review of the literature was completed and studies that reported quality of life at baseline and after 6 months were included in a meta-analysis.SummaryMRgFUS represents a minimally invasive treatment for uterine fibroids that is able to improve the quality of life and fibroid size with durability. It is possible that MRgFUS could be the treatment of choice for patients desiring future fertility; however, further investigation is needed.
C1 [Clark, Natalie A.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Mumford, Sunni L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA.
[Segars, James H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Segars, JH (reprint author), CRC, Bldg 10,Room 1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
FU Intramural Research Program of Reproductive and Adult Endocrinology,
NICHD, NIH [ZIA HD-008737-12]; Division of Intramural Population Health
Research, NICHD, NIH
FX This research was supported, in part, by the Intramural Research Program
of Reproductive and Adult Endocrinology, NICHD, NIH (ZIA HD-008737-12)
and the Division of Intramural Population Health Research, NICHD, NIH.
NR 50
TC 13
Z9 14
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-872X
EI 1473-656X
J9 CURR OPIN OBSTET GYN
JI Curr. Opin. Obstet. Gynecol.
PD JUN
PY 2014
VL 26
IS 3
BP 151
EP 161
DI 10.1097/GCO.0000000000000070
PG 11
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA AH1PF
UT WOS:000335892600005
PM 24751998
ER
PT J
AU Tan, IS
Ramamurthi, KS
AF Tan, Irene S.
Ramamurthi, Kumaran S.
TI Spore formation in Bacillus subtilis
SO ENVIRONMENTAL MICROBIOLOGY REPORTS
LA English
DT Review
ID DEVELOPMENTAL TRANSCRIPTION FACTOR; PENICILLIN-BINDING PROTEINS;
BACTERIAL ENDOSPORE FORMATION; CELL-SPECIFIC TRANSCRIPTION; ACID-SOLUBLE
PROTEINS; HEAT-RESISTANCE; SUBCELLULAR-LOCALIZATION; MORPHOGENETIC
PROTEIN; SPORULATION PROTEIN; HISTIDINE KINASE
AB Although prokaryotes ordinarily undergo binary fission to produce two identical daughter cells, some are able to undergo alternative developmental pathways that produce daughter cells of distinct cell morphology and fate. One such example is a developmental programme called sporulation in the bacterium Bacillus subtilis, which occurs under conditions of environmental stress. Sporulation has long been used as a model system to help elucidate basic processes of developmental biology including transcription regulation, intercellular signalling, membrane remodelling, protein localization and cell fate determination. This review highlights some of the recent work that has been done to further understand prokaryotic cell differentiation during sporulation and its potential applications.
C1 [Tan, Irene S.; Ramamurthi, Kumaran S.] NCI, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
[Tan, Irene S.] Johns Hopkins Univ, NIH, Grad Partnerships Program, Baltimore, MD 21218 USA.
RP Ramamurthi, KS (reprint author), NCI, Lab Mol Biol, NIH, Bethesda, MD 20892 USA.
EM ramamurthiks@mail.nih.gov
RI Ramamurthi, Kumaran/P-3516-2015
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute; Center for Cancer Research
FX We thank P. Eswaramoorthy for comments on the manuscript. This work was
funded by the Intramural Research Program of the National Institutes of
Health, National Cancer Institute and Center for Cancer Research.
NR 157
TC 40
Z9 42
U1 12
U2 85
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1758-2229
J9 ENV MICROBIOL REP
JI Environ. Microbiol. Rep.
PD JUN
PY 2014
VL 6
IS 3
BP 212
EP 225
DI 10.1111/1758-2229.12130
PG 14
WC Environmental Sciences; Microbiology
SC Environmental Sciences & Ecology; Microbiology
GA AG9VQ
UT WOS:000335768400002
PM 24983526
ER
PT J
AU Williams, TH
Mendelson, TC
AF Williams, Tory H.
Mendelson, Tamra C.
TI Quantifying Reproductive Barriers in a Sympatric Pair of Darter Species
SO EVOLUTIONARY BIOLOGY
LA English
DT Review
DE Behavioral isolation; Coloration; Etheostoma; Reproductive barrier;
Sexual selection; Speciation
ID SEXUAL SELECTION; PERCIDAE ETHEOSTOMATINAE; BEHAVIORAL ISOLATION; MALE
COLORATION; VISUAL SIGNALS; SPECIATION; DIVERSIFICATION; EVOLUTION;
PATTERNS; GENUS
AB Quantifying and comparing the strengths of different reproductive barriers between diverging lineages is especially useful for determining the evolutionary mechanisms driving speciation. Etheostoma barrenense and Etheostoma zonale are closely related sympatric species of darters that are sexually dimorphic and exhibit clear differences in male nuptial coloration. Prior studies demonstrated that these species exhibit complete behavioral isolation, and that both intraspecific and interspecific variation in male coloration play a role in female choice, all consistent with speciation by sexual selection on male nuptial color. Remaining unclear, however, is whether behavioral isolation is the strongest reproductive barrier between these species or, alternatively, whether additional reproductive barriers are equally strong, which could implicate mechanisms other than sexual selection in speciation. Here, we compare the relative strengths of multiple reproductive barriers between the two focal species, measuring: (1) ecological isolation, (2) gametic incompatibility, (3) hybrid inviability, (4) conspecific sperm precedence, and comparing these measures to a previously estimated strength of behavioral isolation. We find that behavioral isolation is the strongest reproductive barrier measured to date and suggest it may be the only barrier that has evolved to completion. This result provides additional empirical evidence for speciation driven by sexual selection and provides insight into the maintenance of sympatric species in nature.
C1 [Williams, Tory H.] NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
[Mendelson, Tamra C.] Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA.
RP Williams, TH (reprint author), NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
EM tory.williams@nih.gov
FU National Science Foundation [DEB-0718987, IOS-0919271]
FX We thank J.M. Gumm and M. D. Martin for help during fish capture and
ecological data collection, P.J. Ciccotto for aid in fish care, and C.
F. O'Rourke for assistance with microsatellite protocols. We thank our
anonymous reviewers for their time and suggestions. The authors have no
conflict of interest regarding this work. This research was partially
funded by National Science Foundation grants DEB-0718987 and IOS-0919271
to TCM.
NR 34
TC 4
Z9 4
U1 3
U2 24
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0071-3260
EI 1934-2845
J9 EVOL BIOL
JI Evol. Biol.
PD JUN
PY 2014
VL 41
IS 2
BP 212
EP 220
DI 10.1007/s11692-013-9259-y
PG 9
WC Evolutionary Biology
SC Evolutionary Biology
GA AH7QG
UT WOS:000336327800004
ER
PT J
AU Kaplan, R
Bush, D
Bonnefond, M
Bandettini, PA
Barnes, GR
Doeller, CF
Burgess, N
AF Kaplan, Raphael
Bush, Daniel
Bonnefond, Mathilde
Bandettini, Peter A.
Barnes, Gareth R.
Doeller, Christian F.
Burgess, Neil
TI Medial prefrontal theta phase coupling during spatial memory retrieval
SO HIPPOCAMPUS
LA English
DT Article
DE hippocampus; mPFC; MTL; MEG; oscillations
ID FRONTAL-MIDLINE THETA; HIPPOCAMPAL THETA; GAMMA OSCILLATIONS;
WORKING-MEMORY; EPISODIC MEMORY; TEMPORAL-LOBE; NEURONAL OSCILLATIONS;
DECISION-MAKING; BEHAVING RAT; FREQUENCY
AB Memory retrieval is believed to involve a disparate network of areas, including medial prefrontal and medial temporal cortices, but the mechanisms underlying their coordination remain elusive. One suggestion is that oscillatory coherence mediates inter-regional communication, implicating theta phase and theta-gamma phase-amplitude coupling in mnemonic function across species. To examine this hypothesis, we used non-invasive whole-head magnetoencephalography (MEG) as participants retrieved the location of objects encountered within a virtual environment. We demonstrate that, when participants are cued with the image of an object whose location they must subsequently navigate to, there is a significant increase in 4-8 Hz theta power in medial prefrontal cortex (mPFC), and the phase of this oscillation is coupled both with ongoing theta phase in the medial temporal lobe (MTL) and perceptually induced 65-85 Hz gamma amplitude in medial parietal cortex. These results suggest that theta phase coupling between mPFC and MTL and theta-gamma phase-amplitude coupling between mPFC and neocortical regions may play a role in human spatial memory retrieval. (c) 2014 The Authors. Hippocampus Published by Wiley Periodicals, Inc.
C1 [Kaplan, Raphael] NIMH, NIMH UCL Joint Neurosci Grad Partnership Program, Bethesda, MD 20892 USA.
[Kaplan, Raphael; Bandettini, Peter A.] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Kaplan, Raphael; Bush, Daniel; Burgess, Neil] UCL, Inst Cognit Neurosci, London WC1N 3AR, England.
[Kaplan, Raphael; Bush, Daniel; Barnes, Gareth R.; Burgess, Neil] UCL, Inst Neurol, London WC1N 1PJ, England.
[Bonnefond, Mathilde; Doeller, Christian F.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behaviour, NL-6500 HB Nijmegen, Netherlands.
RP Kaplan, R (reprint author), Wellcome Trust Ctr Neuroimaging, 12 Queen Sq, London WC1N 3BG, England.
EM raphael.kaplan.09@ucl.ac.uk; n.burgess@ucl.ac.uk
RI Burgess, Neil/B-2420-2009;
OI Burgess, Neil/0000-0003-0646-6584; Kaplan, Raphael/0000-0002-5023-1566
FU European Research Council; MRC UK; National Institute of Mental Health;
Wellcome Trust; National Institutes of Health Graduate Partnership
Program; MRC UK MEG Partnership
FX Grant sponsors: European Research Council; MRC UK; National Institute of
Mental Health; Wellcome Trust; National Institutes of Health Graduate
Partnership Program; MRC UK MEG Partnership.
NR 93
TC 19
Z9 19
U1 1
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1050-9631
EI 1098-1063
J9 HIPPOCAMPUS
JI Hippocampus
PD JUN
PY 2014
VL 24
IS 6
BP 656
EP 665
DI 10.1002/hipo.22255
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA AH2IY
UT WOS:000335945900005
PM 24497013
ER
PT J
AU Tu, WZ
Eckert, GJ
Hannon, TS
Liu, H
Pratt, LM
Wagner, MA
DiMeglio, LA
Jung, J
Pratt, JH
AF Tu, Wanzhu
Eckert, George J.
Hannon, Tamara S.
Liu, Hai
Pratt, Linda M.
Wagner, Mary Anne
DiMeglio, Linda A.
Jung, Jeesun
Pratt, J. Howard
TI Racial Differences in Sensitivity of Blood Pressure to Aldosterone
SO HYPERTENSION
LA English
DT Article
DE aldosterone; blood pressure; child; continental population groups;
renin; sodium
ID LEFT-VENTRICULAR MASS; HYPERTENSION; BLACKS; HYPERALDOSTERONISM;
ASSOCIATION; MECHANISMS; DIAGNOSIS; CHILDREN; HEART
AB Blacks in comparison with whites are at risk for a more serious form of hypertension with high rates of complications. Greater sodium retention is thought to underlie the blood pressure (BP)-determining physiology of blacks, but specific mechanisms have not been identified. In a prospective observational study of BP, 226 black children and 314 white children (mean age, 10.6 years) were enrolled initially. Assessments were repeated in 85 blacks and 136 whites after reaching adulthood (mean age, 31 years). The relationship of BP to plasma aldosterone concentration in the context of the prevailing level of plasma renin activity was studied in blacks and whites. In a secondary interventional study, 9-alpha fludrocortisone was administered for 2 weeks to healthy adult blacks and whites to simulate hyperaldosteronism. BP responses in the 2 race groups were then compared. Although black children had lower levels of plasma renin activity and plasma aldosterone, their BP was positively associated with the plasma aldosterone concentration, an effect that increased as plasma renin activity decreased (P=0.004). Data from black adults yielded similar results. No similar relationship was observed in whites. In the interventional study, 9-alpha fludrocortisone increased BP in blacks but not in whites. In conclusion, aldosterone sensitivity is a significant determinant of BP in young blacks. Although its role in establishing the risk of hypertension is not known, it could be as relevant as the actual level of aldosterone.
C1 [Tu, Wanzhu; Eckert, George J.; Liu, Hai; Pratt, Linda M.] Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN 46202 USA.
[Hannon, Tamara S.; DiMeglio, Linda A.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
[Wagner, Mary Anne; Pratt, J. Howard] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA.
[Jung, Jeesun] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Tu, Wanzhu] Indiana Univ Sch Med, Regenstrief Inst, Indianapolis, IN 46202 USA.
[Wagner, Mary Anne; Pratt, J. Howard] VA Med Ctr, Indianapolis, IN USA.
[Jung, Jeesun] NIAAA, Bethesda, MD USA.
RP Pratt, JH (reprint author), 541 Clin Dr,CL 365a, Indianapolis, IN 46202 USA.
EM johpratt@iu.edu
OI DiMeglio, Linda/0000-0002-8033-6078
FU National Institutes of Health [RO1-HL095086, RO1-HL 35795]; Department
of Veterans Affairs Merit Review Award
FX Funded by the National Institutes of Health (RO1-HL095086 and RO1-HL
35795) and by a Department of Veterans Affairs Merit Review Award.
NR 28
TC 14
Z9 14
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD JUN
PY 2014
VL 63
IS 6
BP 1212
EP 1218
DI 10.1161/HYPERTENSIONAHA.113.02989
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AG5XL
UT WOS:000335491900156
PM 24711519
ER
PT J
AU Tabet, F
Lee, S
Torres, LC
Levin, M
Drummond, GR
Remaley, A
Rye, KA
Vickers, K
Sobey, CG
AF Tabet, F.
Lee, S.
Torres, Cuesta L.
Levin, M.
Drummond, G. R.
Remaley, A.
Rye, K. A.
Vickers, K.
Sobey, C. G.
TI TRANSCRIPTIONAL AND POST-TRANSCRIPTIONAL CIRCUITRY IN THE BRAIN AFTER
TRANSIENT AND PERMANENT ISCHEMIA
SO HYPERTENSION
LA English
DT Meeting Abstract
CT 35th Annual Scientific Meeting of the
High-Blood-Pressure-Research-Council-of-Australia (HBPRCA) / 39th Annual
Scientific Meeting of the Australian-Atherosclerosis-Society (AAS)
CY DEC 05-07, 2013
CL Melbourne, AUSTRALIA
SP High Blood Pressure Res Council Australia, Australian Atherosclerosis Soc
C1 [Tabet, F.; Torres, Cuesta L.; Rye, K. A.] Univ New S Wales, Ctr Vasc Res, Sydney, NSW, Australia.
[Lee, S.; Drummond, G. R.; Sobey, C. G.] Monash Univ, Dept Pharmacol, Clayton, Vic 3168, Australia.
[Levin, M.; Remaley, A.; Vickers, K.] NIH, Bethesda, MD 20892 USA.
[Vickers, K.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 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 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD JUN
PY 2014
VL 63
IS 6
BP E157
EP E158
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AG5XL
UT WOS:000335491900076
ER
PT J
AU Chen, G
Wang, XW
Severo, MS
Sakhon, OS
Sohail, M
Brown, LJ
Sircar, M
Snyder, GA
Sundberg, EJ
Ulland, TK
Olivier, AK
Andersen, JF
Zhou, Y
Shi, GP
Sutterwala, FS
Kotsyfakis, M
Pedra, JHF
AF Chen, Gang
Wang, Xiaowei
Severo, Maiara S.
Sakhon, Olivia S.
Sohail, Mohammad
Brown, Lindsey J.
Sircar, Mayukh
Snyder, Greg A.
Sundberg, Eric J.
Ulland, Tyler K.
Olivier, Alicia K.
Andersen, John F.
Zhou, Yi
Shi, Guo-Ping
Sutterwala, Fayyaz S.
Kotsyfakis, Michail
Pedra, Joao H. F.
TI The Tick Salivary Protein Sialostatin L2 Inhibits Caspase-1-Mediated
Inflammation during Anaplasma phagocytophilum Infection
SO INFECTION AND IMMUNITY
LA English
DT Article
ID GRANULOCYTIC EHRLICHIOSIS AGENT; PERIPHERAL-BLOOD LEUKOCYTES;
TUMOR-NECROSIS-FACTOR; CATHEPSIN-L ACTIVITY; IXODES-SCAPULARIS; NLRP3
INFLAMMASOME; NALP3 INFLAMMASOME; GLAND EXTRACTS; MESSENGER-RNA; CUTTING
EDGE
AB Saliva from arthropod vectors facilitates blood feeding by altering host inflammation. Whether arthropod saliva counters inflammasome signaling, a protein scaffold that regulates the activity of caspase-1 and cleavage of interleukin-1 beta (IL-1 beta) and IL-18 into mature molecules, remains elusive. In this study, we provide evidence that a tick salivary protein, sialostatin L2, inhibits inflammasome formation during pathogen infection. We show that sialostatin L2 targets caspase-1 activity during host stimulation with the rickettsial agent Anaplasma phagocytophilum. A. phagocytophilum causes macrophage activation and hemophagocytic syndrome features. The effect of sialostatin L2 in macrophages was not due to direct caspase-1 enzymatic inhibition, and it did not rely on nuclear factor kappa B or cathepsin L signaling. Reactive oxygen species from NADPH oxidase and the Loop2 domain of sialostatin L2 were important for the regulatory process. Altogether, our data expand the knowledge of immunoregulatory pathways of tick salivary proteins and unveil an important finding in inflammasome biology.
C1 [Chen, Gang; Severo, Maiara S.; Sakhon, Olivia S.; Sohail, Mohammad; Pedra, Joao H. F.] Univ Calif Riverside, Ctr Dis Vector Res, Riverside, CA 92521 USA.
[Chen, Gang; Severo, Maiara S.; Sakhon, Olivia S.; Sohail, Mohammad; Pedra, Joao H. F.] Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA.
[Wang, Xiaowei; Brown, Lindsey J.; Sircar, Mayukh; Pedra, Joao H. F.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Snyder, Greg A.] Univ Maryland, Sch Med, Dept Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Sundberg, Eric J.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Inst Human Virol,Dept Med, Baltimore, MD 21201 USA.
[Ulland, Tyler K.; Sutterwala, Fayyaz S.] Univ Iowa, Dept Internal Med, Inflammat Program, Iowa City, IA 52242 USA.
[Ulland, Tyler K.; Sutterwala, Fayyaz S.] Univ Iowa, Dept Internal Med, Div Infect Dis, Iowa City, IA 52242 USA.
[Olivier, Alicia K.] Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA.
[Andersen, John F.] NIAID, Lab Malaria & Vector Res, Rockville, MD USA.
[Zhou, Yi; Shi, Guo-Ping] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02115 USA.
[Kotsyfakis, Michail] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic.
RP Pedra, JHF (reprint author), Univ Calif Riverside, Ctr Dis Vector Res, Riverside, CA 92521 USA.
EM jpedra@som.umaryland.edu
RI Kotsyfakis, Michail/G-9525-2014;
OI Kotsyfakis, Michail/0000-0002-7526-1876; Severo,
Maiara/0000-0001-5972-0035; Pedra, Joao/0000-0001-8740-2667; Ulland,
Tyler/0000-0002-6507-4989
FU Centers for Disease Control and Prevention [K01 CK000101]; National
Institutes of Health [R01 AI093653]; University of California;
University of Maryland, Baltimore School of Medicine; American
Association of University Women
FX This work was supported by the Centers for Disease Control and
Prevention (grant K01 CK000101), the National Institutes of Health
(grant R01 AI093653), an initial complement provided by the University
of California, start-up funds provided by the University of Maryland,
Baltimore School of Medicine, and an international fellowship from the
American Association of University Women.
NR 55
TC 8
Z9 9
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD JUN
PY 2014
VL 82
IS 6
BP 2553
EP 2564
DI 10.1128/IAI.01679-14
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AH8HN
UT WOS:000336378100040
PM 24686067
ER
PT J
AU Truog, RD
Miller, FG
AF Truog, Robert D.
Miller, Franklin G.
TI Defining death: the importance of scientific candor and transparency
SO INTENSIVE CARE MEDICINE
LA English
DT Editorial Material
ID BRAIN-DEATH
C1 [Truog, Robert D.] Boston Childrens Hosp, Div Crit Care Med, Boston, MA 02115 USA.
[Truog, Robert D.] Harvard Univ, Ctr Bioeth, Sch Med, Boston, MA 02115 USA.
[Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Truog, RD (reprint author), Boston Childrens Hosp, Div Crit Care Med, Boston, MA 02115 USA.
EM Robert.Truog@childrens.harvard.edu
NR 11
TC 3
Z9 3
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0342-4642
EI 1432-1238
J9 INTENS CARE MED
JI Intensive Care Med.
PD JUN
PY 2014
VL 40
IS 6
BP 885
EP 887
DI 10.1007/s00134-014-3301-0
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA AH6ZJ
UT WOS:000336281100014
PM 24807081
ER
PT J
AU Lee, SY
Chen, SL
Chang, YH
Chen, SH
Chu, CH
Huang, SY
Tzeng, NS
Wang, CL
Wang, LJ
Lee, IH
Yeh, TL
Yang, YK
Hong, JS
Lu, RB
AF Lee, Sheng-Yu
Chen, Shiou-Lan
Chang, Yun-Hsuan
Chen, Shih-Heng
Chu, Chun-Hsieh
Huang, San-Yuan
Tzeng, Nian-Sheng
Wang, Chen-Lin
Wang, Liang-Jen
Lee, I. Hui
Yeh, Tzung Lieh
Yang, Yen Kuang
Hong, Jau-Shyong
Lu, Ru-Band
TI Genotype variant associated with add-on memantine in bipolar II disorder
(vol 17, pg 189, 2014)
SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
LA English
DT Correction
C1 [Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsieh; Wang, Chen-Lin; Lee, I. Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Dept Psychiat, Tainan 70101, Taiwan.
[Chang, Yun-Hsuan; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med & Hosp, Inst Allied Hlth Sci, Tainan 70101, Taiwan.
[Huang, San-Yuan; Tzeng, Nian-Sheng] Natl Def Med Ctr, Tri Serv Gen Hosp, Dept Psychiat, Taipei, Taiwan.
[Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Inst Behav Med, Tainan 70101, Taiwan.
[Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Addit Res Ctr, Tainan 70101, Taiwan.
[Wang, Liang-Jen] Kaohsiung Chang Gung Mem Hosp, Dept Child & Adolescent Psychiat, Kaohsiung, Taiwan.
[Wang, Liang-Jen] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan.
[Hong, Jau-Shyong] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Lee, SY (reprint author), Natl Cheng Kung Univ, Dept Psychiat, Tainan 70101, Taiwan.
NR 1
TC 0
Z9 0
U1 0
U2 2
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1461-1457
EI 1469-5111
J9 INT J NEUROPSYCHOPH
JI Int. J. Neuropsychopharmacol.
PD JUN
PY 2014
VL 17
IS 6
BP 979
EP 979
DI 10.1017/S1461145714000091
PG 1
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AG6DI
UT WOS:000335508300014
ER
PT J
AU Ziai, WC
Tuhrim, S
Lane, K
McBee, N
Lees, K
Dawson, J
Butcher, K
Vespa, P
Wright, DW
Keyl, PM
Mendelow, AD
Kase, C
Wijman, C
Lapointe, M
John, S
Thompson, R
Thompson, C
Mayo, S
Reilly, P
Janis, S
Awad, I
Hanley, DF
AF Ziai, Wendy C.
Tuhrim, Stanley
Lane, Karen
McBee, Nichol
Lees, Kennedy
Dawson, Jesse
Butcher, Kenneth
Vespa, Paul
Wright, David W.
Keyl, Penelope M.
Mendelow, A. David
Kase, Carlos
Wijman, Christine
Lapointe, Marc
John, Sayona
Thompson, Richard
Thompson, Carol
Mayo, Steven
Reilly, Pat
Janis, Scott
Awad, Issam
Hanley, Daniel F.
CA CLEAR III Investigators
TI A multicenter, randomized, double-blinded, placebo-controlled phase III
study of Clot Lysis Evaluation of Accelerated Resolution of
Intraventricular Hemorrhage (CLEAR III)
SO INTERNATIONAL JOURNAL OF STROKE
LA English
DT Article
DE intracerebral haemorrhage; protocols; thrombolysis; stroke; randomized
clinical trial
ID SPONTANEOUS INTRACEREBRAL HEMORRHAGE; BLOOD-CLOT; PLASMINOGEN-ACTIVATOR;
FIBRINOLYTIC THERAPY; CEREBROSPINAL-FLUID; CANINE MODEL; UROKINASE;
HYDROCEPHALUS; SAFETY; TRIAL
AB Background In adults, intraventricular thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) facilitates resolution of intraventricular haemorrhage (IVH), reduces intracranial pressure, decreases duration of cerebrospinal fluid diversion, and may ameliorate direct neural injury. We hypothesize that patients with small parenchymal haematoma volumes (<30 cc) and relatively large IVH causing acute obstructive hydrocephalus would have improved clinical outcomes when given injections of low-dose rtPA to accelerate lysis and evacuation of IVH compared with placebo. Methods The Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage III trial is an investigator-initiated, phase III, randomized, multicenter, double-blind, placebo-controlled study comparing the use of external ventricular drainage (EVD) combined with intraventricular injection of rtPA to EVD plus intraventricular injection of normal saline (placebo) for the treatment of IVH. Patients with known symptom onset within 24 h of the computed tomography scan confirmed IVH and third or fourth ventricle obstruction, with or without supratentorial intracerebral haemorrhage volume <30 cc, who require EVD are screened with a computed tomography scan at least six hours after EVD placement and, if necessary, at consecutive 12-h intervals until stabilization of any intracranial bleeding has been established. Patients who meet clinical and imaging criteria (no ongoing coagulopathy and no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly) will be randomized to either intraventricular rtPA or placebo. Results The primary outcome measure is dichotomized modified Rankin Scale 0-3 vs. 4-6 at 180 days. Clinical secondary outcomes include additional modified Rankin Scale dichotomizations at 180 days (0-4 vs. 5-6), ordinal modified Rankin Scale (0-6), mortality and safety events at 30 days, mortality at 180 days, functional status measures, type and intensity of intensive care unit management, rate and extent of ventricular blood clot removal, and quality of life measures.
C1 [Ziai, Wendy C.] Johns Hopkins Univ, Sch Med, Dept Neurol, Div Neurosci Crit Care,Johns Hopkins Hosp, Baltimore, MD 21205 USA.
[Tuhrim, Stanley] Mt Sinai Sch Med, Dept Neurol, New York, NY USA.
[Lane, Karen; McBee, Nichol; Keyl, Penelope M.; Hanley, Daniel F.] Johns Hopkins Univ, Sch Med, Div Brain Injury Outcomes, Baltimore, MD USA.
[Lees, Kennedy; Dawson, Jesse] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Butcher, Kenneth] Univ Alberta, Div Neurol, Edmonton, AB, Canada.
[Vespa, Paul] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA.
[Wright, David W.] Emory Univ, Sch Med, Grady Mem Hosp, Dept Emergency Neurosci, Atlanta, GA USA.
[Mendelow, A. David] Newscastle Gen Hosp, Dept Neurosurg, Newcastle Upon Tyne, Tyne & Wear, England.
[Kase, Carlos] Boston Med Ctr, Dept Neurol, Boston, MA USA.
[Wijman, Christine] Stanford Med, Dept Neurol & Neurol Sci, Stanford, CA USA.
[Lapointe, Marc] Med Univ S Carolina, Coll Pharm, Charleston, SC 29425 USA.
[John, Sayona] Rush Univ, Med Ctr, Dept Neurol, Chicago, IL 60612 USA.
[Thompson, Richard; Thompson, Carol] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Mayo, Steven] Emissary Int LLC, Austin, TX USA.
[Reilly, Pat] Genentech Inc, San Francisco, CA 94080 USA.
[Janis, Scott] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Awad, Issam] Univ Chicago, Pritzker Sch Med, Neurosurg Sect, Chicago, IL 60637 USA.
[Awad, Issam] Univ Chicago, Pritzker Sch Med, Neurovasc Surg Program, Chicago, IL 60637 USA.
RP Ziai, WC (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, 600 Wolf St, Baltimore, MD 21231 USA.
EM weziai@jhmi.edu
RI Wright, David/F-1209-2013
OI Wright, David/0000-0002-7145-9105
FU NIH/NINDS [5U01 NS062851, RO1NS046309]; Eleanor Naylor Dana Charitable
Trust [272-2007]; Jeffry and Harriet Legum Endowment; Genentech, Inc.
FX Funding: The CLEAR III trial is supported by a grant (NIH/NINDS 5U01
NS062851 to Dr Hanley). Drs Wendy Ziai and Stanley Tuhrim, Karen Lane,
Nichol McBee, Drs Issam Awad, Kennedy Lees, Jesse Dawson, Kenneth
Butcher, Paul Vespa, Penelope Keyl, A. David Mendelow, Carlos Kase,
Christine Wijman, Marc Lapointe, Sayona John, Richard Thompson, Carol
Thompson, and Steven Mayo receive funding from the same grant (NIH/NINDS
5U01 NS062851 to Dr Daniel F. Hanley). Dr Hanley is also supported by
grants RO1NS046309 from the NIH/NINDS, grant 272-2007 from the Eleanor
Naylor Dana Charitable Trust, the Jeffry and Harriet Legum Endowment,
and materials grants from Genentech, Inc.
NR 37
TC 33
Z9 36
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1747-4930
EI 1747-4949
J9 INT J STROKE
JI Int. J. Stroke
PD JUN
PY 2014
VL 9
IS 4
BP 536
EP 542
DI 10.1111/ijs.12097
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA AG8JP
UT WOS:000335664900029
PM 24033910
ER
PT J
AU Farber, CR
Reich, A
Barnes, AM
Becerra, P
Rauch, F
Cabral, WA
Bae, A
Quinlan, A
Glorieux, FH
Clemens, TL
Marini, JC
AF Farber, Charles R.
Reich, Adi
Barnes, Aileen M.
Becerra, Patricia
Rauch, Frank
Cabral, Wayne A.
Bae, Alison
Quinlan, Aaron
Glorieux, Francis H.
Clemens, Thomas L.
Marini, Joan C.
TI A Novel IFITM5 Mutation in Severe Atypical Osteogenesis Imperfecta Type
VI Impairs Osteoblast Production of Pigment Epithelium-Derived Factor
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE IFITM5; BRIL; SERPINF1; PEDF; OSTEOGENESIS IMPERFECTA; OI
ID INTEGRATIVE GENOMICS VIEWER; BRITTLE BONE-DISEASE; I COLLAGEN;
HYPERPLASTIC CALLUS; NETWORK ANALYSIS; SEQUENCING DATA; PEDF;
MINERALIZATION; ASSOCIATION; EXPRESSION
AB Osteogenesis imperfecta (OI) types V and VI are caused, respectively, by a unique dominant mutation in IFITM5, encoding BRIL, a transmembrane ifitm-like protein most strongly expressed in the skeletal system, and recessive null mutations in SERPINF1, encoding pigment epithelium-derived factor (PEDF). We identified a 25-year-old woman with severe OI whose dermal fibroblasts and cultured osteoblasts displayed minimal secretion of PEDF, but whose serum PEDF level was in the normal range. SERPINF1 sequences were normal despite bone histomorphometry consistent with type VI OI and elevated childhood serum alkaline phosphatase. We performed exome sequencing on the proband, both parents, and an unaffected sibling. IFITM5 emerged as the candidate gene from bioinformatics analysis, and was corroborated by membership in a murine bone co-expression network module containing all currently known OI genes. The de novo IFITM5 mutation was confirmed in one allele of the proband, resulting in a p.S40L substitution in the intracellular domain of BRIL but was absent in unaffected family members. IFITM5 expression was normal in proband fibroblasts and osteoblasts, and BRIL protein level was similar to control in differentiated proband osteoblasts on Western blot and in permeabilized mutant osteoblasts by microscopy. In contrast, SERPINF1 expression was decreased in proband osteoblasts; PEDF was barely detectable in conditioned media of proband cells. Expression and secretion of type I collagen was similarly decreased in proband osteoblasts; the expression pattern of several osteoblast markers largely overlapped reported values from cells with a primary PEDF defect. In contrast, osteoblasts from a typical case of type V OI, with an activating mutation at the 5'-terminus of BRIL, have increased SERPINF1 expression and PEDF secretion during osteoblast differentiation. Together, these data suggest that BRIL and PEDF have a relationship that connects the genes for types V and VI OI and their roles in bone mineralization. (c) 2014 American Society for Bone and Mineral Research.
C1 [Farber, Charles R.; Quinlan, Aaron] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Farber, Charles R.; Quinlan, Aaron] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Farber, Charles R.; Quinlan, Aaron] Univ Virginia, Dept Biochem, Charlottesville, VA 22908 USA.
[Farber, Charles R.; Quinlan, Aaron] Univ Virginia, Dept Mol Genet, Charlottesville, VA USA.
[Reich, Adi; Barnes, Aileen M.; Cabral, Wayne A.; Bae, Alison; Marini, Joan C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA.
[Becerra, Patricia] NEI, Sect Prot Struct & Funct, LRCMB, NIH, Bethesda, MD 20892 USA.
[Rauch, Frank; Glorieux, Francis H.] Shriners Hosp Children, Montreal, PQ, Canada.
[Rauch, Frank; Glorieux, Francis H.] McGill Univ, Montreal, PQ, Canada.
[Clemens, Thomas L.] Johns Hopkins Sch Med, Dept Orthopaed Surg, Baltimore, MD USA.
[Clemens, Thomas L.] Baltimore VA Med Ctr, Baltimore, MD USA.
RP Marini, JC (reprint author), NICHD, Bone & Extracellular Matrix Branch, NIH, Bldg 10 Room 10D39,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM oidoc@helix.nih.gov
OI Quinlan, Aaron/0000-0003-1756-0859; Farber, Charles/0000-0002-6748-4711
FU NICHD; NEI [RO1-AR057759, RO1-AR049410]; VA Merit Review; Shriners
Hospital of North America; Chercheur-Boursier Clinicien program of the
Fonds de Recherche du Quebec-Sante; VA Senior Career Scientist Award
FX We thank the proband and her family for their dedicated long-term
support of OI research. We are grateful to Prof Pierre Moffatt for
communication of unpublished results on BRIL structure in the cell
membrane. We thank the NICHD Microscopy and Imaging Core in which the
confocal microscopy was conducted. This work was supported by NICHD
(JCM) and NEI (PB) intramural funding, extramural RO1-AR057759 (CRF),
RO1-AR049410 (TLC), a VA Merit Review (TLC), and Shriners Hospital of
North America (FR and FHG). FR received salary support from the
Chercheur-Boursier Clinicien program of the Fonds de Recherche du
Quebec-Sante. TLC is also supported by a VA Senior Career Scientist
Award.
NR 52
TC 12
Z9 13
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD JUN
PY 2014
VL 29
IS 6
BP 1402
EP 1411
DI 10.1002/jbmr.2173
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA AH3DJ
UT WOS:000336001500013
PM 24519609
ER
PT J
AU Lee, SY
Chen, SL
Chang, YH
Chen, PS
Huang, SY
Tzeng, NS
Wang, YS
Wang, LJ
Lee, IH
Wang, TY
Yeh, TL
Yang, YK
Hong, JS
Lu, RB
AF Lee, Sheng-Yu
Chen, Shiou-Lan
Chang, Yun-Hsuan
Chen, Po See
Huang, San-Yuan
Tzeng, Nian-Sheng
Wang, Yu-Shan
Wang, Liang-Jen
Lee, I. Hui
Wang, Tzu-Yun
Yeh, Tzung Lieh
Yang, Yen Kuang
Hong, Jau-Shyong
Lu, Ru-Band
TI The Effects of Add-On Low-Dose Memantine on Cytokine Levels in Bipolar
II Depression A 12-Week Double- Blind, Randomized Controlled Trial
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE bipolar II depression; memantine; treatment; cytokines
ID NMDA RECEPTOR ANTAGONISTS; DOUBLE-BLIND; ALCOHOL DEPENDENCE;
AFFECTIVE-DISORDER; LITHIUM TREATMENT; MAJOR DEPRESSION; RATING-SCALE;
HYPOMANIA; BRAIN; MOOD
AB Memantine, a noncompetitive N-methyl-d-aspartate receptor antagonist with a mood-stabilizing effect, and an association between bipolar disorder and proinflammatory cytokine levels have been reported. Whether adding-on memantine would reduce cytokine levels and is more effective than valproic acid (VPA) alone in bipolar II disorder was investigated. A randomized, double-blind, controlled, 12-week study was conducted. Patients undergoing regular VPA treatments were randomly assigned to a group: VPA + memantine (5 mg/d) (n = 106) or VPA + placebo (n = 108). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical response. Symptom severity, plasma tumor necrosis factor (TNF-), interleukin 6 (IL-6), IL-8, and IL-1 levels were examined during weeks 0, 1, 2, 4, 8, and 12. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. Tumor necrosis factor levels were significantly lower in the VPA + memantine group than in the VPA + placebo group (P = 0.013). Posttreatment HDRS and YMRS scores decreased significantly in both groups, but not significant, nor was the other between-group cytokine level difference pretreatment and posttreatment. The HDRS score changes were significantly associated with IL-6 (P = 0.012) and IL-1 (P = 0.005) level changes and changes in YMRS score changes with TNF- (P = 0.005) level changes. Treating bipolar II depression with VPA + memantine may improve the plasma TNF- level. However, adding-on memantine may not improve clinical symptoms or cytokine levels other than TNF-. Clinical symptoms may be correlated with certain cytokines.
C1 [Lee, Sheng-Yu; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Po See; Lee, I. Hui; Wang, Tzu-Yun; Yeh, Tzung Lieh; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med & Hosp, Dept Psychiat, Tainan 70428, Taiwan.
[Chen, Shiou-Lan; Wang, Yu-Shan; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med & Hosp, Inst Behav Med, Tainan 70428, Taiwan.
[Chang, Yun-Hsuan; Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med & Hosp, Inst Allied Hlth Sci, Tainan 70428, Taiwan.
[Huang, San-Yuan; Tzeng, Nian-Sheng] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan.
[Wang, Liang-Jen] Kaohsiung Chang Gung Mem Hosp, Dept Child & Adolescent Psychiat, Kaohsiung, Taiwan.
[Wang, Liang-Jen] Chang Gung Univ, Coll Med, Kaohsiung, Taiwan.
[Wang, Tzu-Yun] Tainan Hosp, Dept Hlth Execut Yuan, Dept Psychiat, Tainan, Taiwan.
[Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 70101, Taiwan.
[Hong, Jau-Shyong] NIH NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC USA.
RP Lu, RB (reprint author), Natl Cheng Kung Univ, Coll Med & Hosp, Addict Ctr, Inst Behav Med,Dept Psychiat, 138 Sheng Li Rd, Tainan 70428, Taiwan.
EM rblu@mail.ncku.edu.tw
FU Taiwan National Science Council [NSC98-2314-B-006-022-MY3,
NSC100-2314-B-006-048-MY3]; Taiwan Department of Health [DOH
95-TD-M-113-055]; Taiwan National Health Research Institute
[NHRI-EX-97-9738NI]; National Cheng Kung University Project for
Promoting Academic Excellence and Developing World Class Research
Centers
FX This work was supported in part by grant NSC98-2314-B-006-022-MY3 (to
R.-B.L.) and NSC100-2314-B-006-048-MY3 (to S.-Y.L.) from the Taiwan
National Science Council, grant DOH 95-TD-M-113-055 (to R.-B.L.) from
the Taiwan Department of Health, grant NHRI-EX-97-9738NI (to R.-B.L.)
from the Taiwan National Health Research Institute, and the National
Cheng Kung University Project for Promoting Academic Excellence and
Developing World Class Research Centers.
NR 65
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U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0271-0749
EI 1533-712X
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD JUN
PY 2014
VL 34
IS 3
BP 337
EP 343
DI 10.1097/JCP.0000000000000109
PG 7
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA AH3AR
UT WOS:000335994100012
PM 24717258
ER
PT J
AU Ferguson, GM
Desir, C
Bornstein, MH
AF Ferguson, Gail M.
Desir, Charlene
Bornstein, Marc H.
TI "Ayiti Cheri": Cultural Orientation of Early Adolescents in Rural Haiti
SO JOURNAL OF EARLY ADOLESCENCE
LA English
DT Article
DE cultural maintenance; globalization; remote acculturation; family
obligations; Caribbean
ID ACCULTURATION; IDENTITY
AB Adolescents are an emerging population in Haiti, particularly after the deadly 2010 earthquake. The steady penetration of U.S. culture into this poor, disaster-prone country begs the question, Do today's adolescents possess a similar fondness for their home country, culture, and traditional family values as did Haitians of old? Or are they more oriented toward U.S. culture? Early adolescents (N = 105, 52% female, M = 12.87 years, SD = .86) in rural Haiti reported their cultural orientation toward Haitian culture and U.S. culture as well as their family obligations beliefs. Findings revealed high Haitian orientation, very high family obligations (boys especially), and very low U.S. orientation, although adolescents who interacted more frequently with U.S. tourists and those who consumed more U.S. fast food had higher U.S. culture orientation. Despite severe challenges, rural Haitian early adolescents demonstrate remarkable allegiance to their home country, culture, and traditional family values.
C1 [Ferguson, Gail M.] Univ Illinois, Urbana, IL 61801 USA.
[Ferguson, Gail M.] Univ Illinois, Ctr Latin Amer & Caribbean Studies, Urbana, IL 61801 USA.
[Desir, Charlene] Novasoutheastern Univ, North Miami Beach, FL USA.
[Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Ferguson, GM (reprint author), Univ Illinois, Doris Kelley Christopher Hall,MC-081, Urbana, IL 61801 USA.
EM gmfergus@illinois.edu
NR 28
TC 0
Z9 0
U1 5
U2 9
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-4316
EI 1552-5449
J9 J EARLY ADOLESCENCE
JI J. Early Adolesc.
PD JUN
PY 2014
VL 34
IS 5
BP 621
EP 637
DI 10.1177/0272431613503214
PG 17
WC Family Studies; Psychology, Developmental
SC Family Studies; Psychology
GA AH6UC
UT WOS:000336265600004
ER
PT J
AU Brooks-Russell, A
Farhat, T
Haynie, D
Simons-Morton, B
AF Brooks-Russell, Ashley
Farhat, Tilda
Haynie, Denise
Simons-Morton, Bruce
TI Trends in Substance Use Among 6th-to 10th-Grade Students From 1998 to
2010: Findings From a National Probability Study
SO JOURNAL OF EARLY ADOLESCENCE
LA English
DT Article
DE adolescent tobacco use; adolescent alcohol use; substance use trends;
national prevalence of substance use
ID DRINKING; SMOKING; ONSET
AB Of the handful of national studies tracking trends in adolescent substance use in the United States, only the Health Behavior in School-Aged Children (HBSC) study collects data from 6th through 10th graders. The purpose of this study was to examine trends from 1998 to 2010 (four time points) in the prevalence of tobacco, alcohol, and marijuana use among 6th through 10th graders. Differences in trends by grade, gender, and race/ethnicity were examined for each substance use behavior, with a primary focus on trends for sixth and seventh graders. Overall, there were significant declines in tobacco, alcohol, and marijuana use from 1998 to 2010. The declines were largest for the younger grades, which suggest promise for future declines among high school students as these cohorts age into high school.
C1 [Brooks-Russell, Ashley; Farhat, Tilda; Haynie, Denise; Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
RP Brooks-Russell, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd Room 7B13, Bethesda, MD 20892 USA.
EM ashley.russell@nih.gov
OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie,
Denise/0000-0002-8270-6079
FU Intramural NIH HHS [ZIA HD002525-18]
NR 14
TC 4
Z9 4
U1 1
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-4316
EI 1552-5449
J9 J EARLY ADOLESCENCE
JI J. Early Adolesc.
PD JUN
PY 2014
VL 34
IS 5
BP 667
EP 680
DI 10.1177/0272431613501409
PG 14
WC Family Studies; Psychology, Developmental
SC Family Studies; Psychology
GA AH6UC
UT WOS:000336265600006
PM 26949282
ER
PT J
AU Goveas, JS
Espeland, MA
Hogan, PE
Tindle, HA
Shih, RA
Kotchen, JM
Robinson, JG
Barnes, DE
Resnick, SM
AF Goveas, Joseph S.
Espeland, Mark A.
Hogan, Patricia E.
Tindle, Hilary A.
Shih, Regina A.
Kotchen, Jane M.
Robinson, Jennifer G.
Barnes, Deborah E.
Resnick, Susan M.
TI Depressive Symptoms and Longitudinal Changes in Cognition: Women's
Health Initiative Study of Cognitive Aging
SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY
LA English
DT Article
DE depression; cognitive decline; vascular risk factors; cardiovascular
disease; women; dementia; depressive symptoms
ID LATE-LIFE DEPRESSION; APOLIPOPROTEIN-E GENOTYPE; PRIMARY-CARE PATIENTS;
GERIATRIC DEPRESSION; VASCULAR DEPRESSION; POSTMENOPAUSAL WOMEN;
ALZHEIMER-DISEASE; IMPAIRMENT; DEMENTIA; RISK
AB Elevated depressive symptoms (DS) are associated with incident mild cognitive impairment and probable dementia in postmenopausal women. We examined the association of elevated DS with domain-specific cognitive changes and the moderating role of cardiovascular risk factor severity and cardiovascular disease (CVD). A total of 2221 elderly women who participated in the Women's Health Initiative Study of Cognitive Aging were separated into those with (N = 204) and without (N = 2017) elevated DS. The DS and multidomain cognitive outcomes were measured annually for an average follow-up of 5.04 years. Women with elevated DS showed baseline multidomain cognitive deficits but longitudinal declines in global cognition only. Persistent DS was related to greater global cognition, verbal knowledge and fluency, and memory declines. Significant DS-CVD interactions were observed cross-sectionally (but not longitudinally) for figural memory and fine motor speed. Future studies should investigate the role of nonvascular mechanisms linking DS and cognitive decline.
C1 [Goveas, Joseph S.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA.
[Espeland, Mark A.; Hogan, Patricia E.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA.
[Tindle, Hilary A.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Shih, Regina A.] RAND Corp, Arlington, VA USA.
[Kotchen, Jane M.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA.
[Kotchen, Jane M.] Med Coll Wisconsin, Clin & Translat Sci Inst, Milwaukee, WI 53226 USA.
[Robinson, Jennifer G.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat & Epidemiol, San Francisco, CA 94143 USA.
[Barnes, Deborah E.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Barnes, Deborah E.] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA.
[Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Goveas, JS (reprint author), Med Coll Wisconsin, Dept Psychiat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM jgoveas@mcw.edu
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, US Department of Health and Human Services [N01WH22110, 24152,
32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
42107-26, 42129-32, 44221]; Department of Health and Human Services;
National Institute on Aging [NO1-AG-1-2106]; Intramural Research
Program, National Institute on Aging; National Institutes of Health;
Alzheimer's Association [NIRG-11-204070]; Extendicare Foundation; Brain
& Behavior Research Foundation (NARSAD); Wyeth Pharmaceuticals; Brain
and Behavior Research Foundation (previously NARSAD) young investigator
award
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: The
Women's Health Initiative (WHI) program is funded by the National Heart,
Lung, and Blood Institute, National Institutes of Health, US Department
of Health and Human Services through contracts N01WH22110, 24152,
32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122,
42107-26, 42129-32, and 44221. The WHI Study of Cognitive Aging (WHISCA)
was supported by the Department of Health and Human Services and the
National Institute on Aging (NO1-AG-1-2106). SMR is supported by the
Intramural Research Program, National Institute on Aging, and National
Institutes of Health. JSG is supported by the Alzheimer's Association
New Investigator NIRG-11-204070 and Extendicare Foundation, and
previously by Brain & Behavior Research Foundation (NARSAD) young
investigator, and Research for a Healthier Tomorrow, a Component of the
Advancing a Healthier Wisconsin Endowment at MCW. The Women's Health
Initiative Memory Study was funded in part by Wyeth Pharmaceuticals as
an ancillary study to the WHI. DB's contributions were supported in part
by Brain and Behavior Research Foundation (previously NARSAD) young
investigator award.
NR 46
TC 11
Z9 11
U1 3
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0891-9887
EI 1552-5708
J9 J GERIATR PSYCH NEUR
JI J. Geriatr. Psychiatry Neurol.
PD JUN
PY 2014
VL 27
IS 2
BP 94
EP 102
DI 10.1177/0891988714522697
PG 9
WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry
SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry
GA AH6DG
UT WOS:000336220300004
PM 24584465
ER
PT J
AU Villarroel, VA
Okiyama, N
Tsuji, G
Linton, JT
Katz, SI
AF Villarroel, Vadim A.
Okiyama, Naoko
Tsuji, Gaku
Linton, Jay T.
Katz, Stephen I.
TI CXCR3-Mediated Skin Homing of Autoreactive CD8 T Cells Is a Key
Determinant in Murine Graft-Versus-Host Disease
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID RHEUMATOID-ARTHRITIS; ALLOGRAFT-REJECTION; CHEMOKINE RECEPTORS;
ALOPECIA-AREATA; CXCR3; EXPRESSION; INFILTRATION; RECRUITMENT;
MIGRATION; CXCL10
AB The pathomechanisms underlying the development of cutaneous graft-versus-host disease (GVHD) are incompletely defined. We previously reported that K14-mOVA mice expressing membrane ovalbumin (mOVA), driven by the keratin 14 (K14) promoter, developed GVHD-like mucocutaneous disease and weight loss following transfer of OVA-specific, CD8(+) OT-I T cells. In this study, we demonstrate that early in the course of disease, the kinetics of epidermal expression of C-X-C motif chemokine ligand 9 (CXCL9) and CXCL10, interferon-gamma-inducible chemokines that bind the C-X-C motif chemokine receptor 3 (CXCR3) receptor, coincides with CXCR3 expression by OT-I cells in secondary lymphoid organs. Recruitment of OT-I cells into the skin began by day 5 with progressive accumulation through day 13 post transfer. Transfer of CXCR3-knockout (CXCR3KO) OT-I cells into K14-mOVA mice resulted in strikingly attenuated skin disease. CXCR3KO OT-I cells retained full activation and effector function, but preferentially accumulated in the spleen, in contrast to wild-type (WT) OT-I cells that accumulated in skin-draining lymph nodes. Moreover, OT-I cells accounted for a significantly reduced percentage of skin-infiltrating lymphocytes in mice receiving CXCR3KO OT-I cells compared with WT OT-I cells. These results identify CXCR3 as being critical to the skin-selective effector T-cell recruitment underlying autoreactive GVHD, suggesting CXCR3 as a potential target in the treatment of GVHD and related skin diseases.
C1 [Villarroel, Vadim A.; Okiyama, Naoko; Tsuji, Gaku; Linton, Jay T.; Katz, Stephen I.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Katz, SI (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM katzs@od.niams.nih.gov
NR 35
TC 8
Z9 8
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD JUN
PY 2014
VL 134
IS 6
BP 1552
EP 1560
DI 10.1038/jid.2014.2
PG 9
WC Dermatology
SC Dermatology
GA AH5TJ
UT WOS:000336193700013
PM 24390137
ER
PT J
AU Turkbey, B
Merino, MJ
Gallardo, EC
Shah, V
Aras, O
Bernardo, M
Mena, E
Daar, D
Rastinehad, AR
Linehan, WM
Wood, BJ
Pinto, PA
Choyke, PL
AF Turkbey, Baris
Merino, Maria J.
Gallardo, Elma Carvajal
Shah, Vijay
Aras, Omer
Bernardo, Marcelino
Mena, Esther
Daar, Dagane
Rastinehad, Ardeshir R.
Linehan, W. Marston
Wood, Bradford J.
Pinto, Peter A.
Choyke, Peter L.
TI Comparison of Endorectal Coil and Nonendorectal Coil T2W and
Diffusion-Weighted MRI at 3 Tesla for Localizing Prostate Cancer:
Correlation With Whole-Mount Histopathology
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE prostate cancer; surface coil; endorectal coil; MRI; 3 Tesla
ID PHASED-ARRAY COIL; STAGING ACCURACY; IMAGE QUALITY; 1.5 T; LOCALIZATION
AB PurposeTo compare utility of T2-weighted (T2W) MRI and diffusion-weighted MRI (DWI-MRI) obtained with and without an endorectal coil at 3 Tesla (T) for localizing prostate cancer.
Materials and MethodsThis Institutional Review Board-approved study included 20 patients (median prostate-specific antigen, 8.4 ng/mL). Patients underwent consecutive prostate MRIs at 3T, first with a surface coil alone, then with combination of surface, endorectal coils (dual coil) followed by robotic assisted radical prostatectomy. Lesions were mapped at time of acquisition on dual-coil T2W, DWI-MRI. To avoid bias, 6 months later nonendorectal coil T2W, DWI-MRI were mapped. Both MRI evaluations were performed by two readers blinded to pathology with differences resolved by consensus. A lesion-based correlation with whole-mount histopathology was performed.
ResultsAt histopathology 51 cancer foci were present ranging in size from 2 to 60 mm. The sensitivity of the endorectal dual-coil, nonendorectal coil MRIs were 0.76, 0.45, respectively. PPVs for endorectal dual-coil, nonendorectal coil MRI were 0.80, 0.64, respectively. Mean size of detected lesions with nonendorectal coil MRI were larger than those detected by dual-coil MRI (22 mm versus 17.4 mm).
ConclusionDual-coil prostate MRI detected more cancer foci than nonendorectal coil MRI. While nonendorectal coil MRI is an attractive alternative, physicians performing prostate MRI should be aware of its limitations. J. Magn. Reson. Imaging 2014;39:1443-1448. (c) 2013 Wiley Periodicals, Inc.
C1 [Turkbey, Baris; Aras, Omer; Bernardo, Marcelino; Mena, Esther; Daar, Dagane; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Gallardo, Elma Carvajal; Wood, Bradford J.] NCI, Ctr Intervent Oncol, Bethesda, MD 20892 USA.
[Gallardo, Elma Carvajal; Wood, Bradford J.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Gallardo, Elma Carvajal] UMC Utrecht, Image Sci Inst, Utrecht, Netherlands.
[Shah, Vijay] VirtualScopics, Rochester, NY USA.
[Bernardo, Marcelino] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Rastinehad, Ardeshir R.; Linehan, W. Marston; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Choyke, PL (reprint author), NCI, Mol Imaging Program, 10 Ctr Dr,MSC 1182 Bldg 10,Room B3B69, Bethesda, MD 20892 USA.
EM pchoyke@mail.nih.gov
RI Shah, Vijay/D-4083-2014
OI Shah, Vijay/0000-0003-3856-156X
FU Intramural NIH HHS [Z01 BC010655-03, ZIA BC010655-08]
NR 20
TC 52
Z9 52
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD JUN
PY 2014
VL 39
IS 6
BP 1443
EP 1448
DI 10.1002/jmri.24317
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AG5LM
UT WOS:000335460500014
PM 24243824
ER
PT J
AU Mattmiller, SA
Carlson, BA
Gandy, JC
Sordillo, LM
AF Mattmiller, Sarah A.
Carlson, Bradley A.
Gandy, Jeff C.
Sordillo, Lorraine M.
TI Reduced macrophage selenoprotein expression alters oxidized lipid
metabolite biosynthesis from arachidonic and linoleic acid
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Selenium; Selenoproteins; Macrophage; Oxylipids; Eicosanoids
ID AORTIC ENDOTHELIAL-CELLS; FACTOR-KAPPA-B; PROLIFERATOR-ACTIVATED
RECEPTOR; SELENIUM DEFICIENCY; GENE-EXPRESSION; FATTY-ACIDS; EICOSANOID
BIOSYNTHESIS; OXIDATIVE STRESS; IMMUNE FUNCTION; UP-REGULATION
AB Uncontrolled inflammation is an underlying etiology for multiple diseases and macrophages orchestrate inflammation largely through the production of oxidized fatty acids known as oxylipids. Previous studies showed that selenium (Se) status altered the expression of oxylipids and magnitude of inflammatory responses. Although selenoproteins are thought to mediate many of the biological effects of Se, the direct effect of selenoproteins on the production of oxylipids is unknown. Therefore, the role of decreased selenoprotein activity in modulating the production of biologically active oxylipids from macrophages was investigated. Thioglycollate-elicited peritoneal macrophages were collected from wild-type and myeloid-cell-specific selenoprotein knockout mice to analyze oxylipid production by liquid chromatography/mass spectrometry as well as oxylipid biosynthetic enzyme and inflammatory marker gene expression by quantitative real-time polymerase chain reaction. Decreased selenoprotein activity resulted in the accumulation of reactive oxygen species, enhanced cyclooxygenase and lipoxygenase expression and decreased oxylipids with known anti-inflammatory properties such as arachidonic acid-derived lipoxin A(4) (LXA(4)) and linoleic acid-derived 9-oxo-octadecadienoic acid (9-oxoODE). Treating RAW 264.7 macrophages with LXA(4) or 9-oxoODE diminished oxidant-induced macrophage inflammatory response as indicated by decreased production of TNF alpha. The results show for the first time that selenoproteins are important for the balanced biosynthesis of pro- and anti-inflammatory oxylipids during inflammation. A better understanding of the Se-dependent control mechanisms governing oxylipid biosynthesis may uncover nutritional intervention strategies to counteract the harmful effects of uncontrolled inflammation due to oxylipids. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Mattmiller, Sarah A.; Gandy, Jeff C.; Sordillo, Lorraine M.] Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA.
[Carlson, Bradley A.] NCI, Mol Biol Selenium Sect, Mouse Canc Genet Program, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Sordillo, LM (reprint author), Michigan State Univ, Coll Vet Med, 748 Wilson Rd,G300 Vet Med Ctr, E Lansing, MI 48824 USA.
EM Sordillo@msu.edu
FU AFRI Animal Health competitive grant from the USDA National Institute of
Food and Agriculture [2011-67015-30179]; Pre-Doctoral Fellowship from
the USDA National Institute of Food and Agriculture [2012-67011-19944]
FX This study was supported by grants from AFRI Animal Health competitive
grant (no. 2011-67015-30179) and for a Pre-Doctoral Fellowship (grant
no. 2012-67011-19944), both from the USDA National Institute of Food and
Agriculture.
NR 41
TC 6
Z9 7
U1 2
U2 14
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD JUN
PY 2014
VL 25
IS 6
BP 647
EP 654
DI 10.1016/j.jnutbio.2014.02.005
PG 8
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA AH8AD
UT WOS:000336355600008
PM 24746836
ER
PT J
AU Murai, J
Zhang, YP
Morris, J
Ji, JP
Takeda, S
Doroshow, JH
Pommier, Y
AF Murai, Junko
Zhang, Yiping
Morris, Joel
Ji, Jiuping
Takeda, Shunichi
Doroshow, James H.
Pommier, Yves
TI Rationale for Poly(ADP-ribose) Polymerase (PARP) Inhibitors in
Combination Therapy with Camptothecins or Temozolomide Based on PARP
Trapping versus Catalytic Inhibition
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID DNA TOPOISOMERASE-I; CANCER CELL-LINES; HOMOLOGOUS RECOMBINATION;
VERTEBRATE CELLS; DRUG-COMBINATION; MAMMALIAN-CELLS; STRAND BREAKS;
L1210 CELLS; REPAIR; DAMAGE
AB We recently showed that poly(ADP-ribose) polymerase (PARP) inhibitors exert their cytotoxicity primarily by trapping PARP-DNA complexes in addition to their NAD(+)-competitive catalytic inhibitory mechanism. PARP trapping is drug-specific, with olaparib exhibiting a greater ability than veliparib, whereas both compounds are potent catalytic PARP inhibitors. Here, we evaluated the combination of olaparib or veliparib with therapeutically relevant DNA-targeted drugs, including the topoisomerase I inhibitor camptothecin, the alkylating agent temozolomide, the cross-linking agent cisplatin, and the topoisomerase II inhibitor etoposide at the cellular and molecular levels. We determined PARP-DNA trapping and catalytic PARP inhibition in genetically modified chicken lymphoma DT40, human prostate DU145, and glioblastoma SF295 cancer cells. For camptothecin, both PARP inhibitors showed highly synergistic effects due to catalytic PARP inhibition, indicating the value of combining either veliparib or olaparib with topoisomerase I inhibitors. On the other hand, for temozolomide, PARP trapping was critical in addition to catalytic inhibition, consistent with the fact that olaparib was more effective than veliparib in combination with temozolomide. For cisplatin and etoposide, olaparib only showed no or a weak combination effect, which is consistent with the lack of involvement of PARP in the repair of cisplatin-and etoposide-induced lesions. Hence, we conclude that catalytic PARP inhibitors are highly effective in combination with camptothecins, whereas PARP inhibitors capable of PARP trapping are more effective with temozolomide. Our study provides insights in combination treatment rationales for different PARP inhibitors.
C1 [Murai, Junko; Doroshow, James H.; Pommier, Yves] NCI, Dev Therapeut Branch, 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.
[Morris, Joel; 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, Dev Therapeut Branch, Mol Pharmacol Lab, Ctr Canc Res,NIH, 37 Convent Dr,Bldg 37,Room 5068, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU John Mung program (Kyoto University); Kyoto University Foundation;
Intramural Research Program of the National Institutes of Health
[National Cancer Institute]; Center for Cancer Research [Z01 BC 006150];
Japan Society for the Promotion of Science KAKENHI program [25740016];
National Institutes of Health National Cancer Institute
[HHSN261200800001E]
FX J.M. is a recipient of fellowships from the John Mung program (Kyoto
University) and the Kyoto University Foundation. This work was supported
by the Intramural Research Program of the National Institutes of Health
[National Cancer Institute]; and the Center for Cancer Research [Grant
Z01 BC 006150]. J.M. was supported by Japan Society for the Promotion of
Science KAKENHI program [Grant 25740016]. J.J. was supported by the
National Institutes of Health National Cancer Institute [Contract no.
HHSN261200800001E].
NR 44
TC 51
Z9 51
U1 2
U2 13
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD JUN
PY 2014
VL 349
IS 3
BP 408
EP 416
DI 10.1124/jpet.113.210146
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AH5GJ
UT WOS:000336156200005
PM 24650937
ER
PT J
AU Pichard, DC
Hensley, JR
Williams, E
Apolo, AB
Klion, AD
DiGiovanna, JJ
AF Pichard, Dominique C.
Hensley, Jennifer R.
Williams, Esther
Apolo, Andrea B.
Klion, Amy D.
DiGiovanna, John J.
TI Rapid development of migratory, linear, and serpiginous lesions in
association with immunosuppression
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Editorial Material
ID STRONGYLOIDES-STERCORALIS HYPERINFECTION; CUTANEOUS LARVA MIGRANS;
PREVENTION; CURRENS
C1 [Pichard, Dominique C.; Hensley, Jennifer R.] Georgetown Univ Hosp, Dept Dermatol, Washington, DC 20007 USA.
[Williams, Esther] NIH, Ctr Clin, Dept Lab Med, Microbiol Serv, Bethesda, MD 20892 USA.
[Apolo, Andrea B.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Klion, Amy D.] NIAID, Eosinophil Pathol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[DiGiovanna, John J.] NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP DiGiovanna, JJ (reprint author), NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res,NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM jdg@nih.gov
OI Klion, Amy/0000-0002-4986-5326
FU Intramural NIH HHS [Z99 CA999999, ZIA BC004517-37]
NR 17
TC 2
Z9 2
U1 0
U2 0
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 JUN
PY 2014
VL 70
IS 6
BP 1130
EP 1134
DI 10.1016/j.jaad.2013.11.036
PG 5
WC Dermatology
SC Dermatology
GA AH3NJ
UT WOS:000336030400034
PM 24831316
ER
PT J
AU Dave, J
Ahlman, MA
Lockshin, BN
Bluemke, DA
Mehta, NN
AF Dave, Jenny
Ahlman, Mark A.
Lockshin, Benjamin N.
Bluemke, David A.
Mehta, Nehal N.
TI Vascular inflammation in psoriasis localizes to the arterial wall using
a novel imaging technique
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Letter
ID POSITRON-EMISSION-TOMOGRAPHY; PET/CT
C1 [Dave, Jenny; Mehta, Nehal N.] NHLBI, Bethesda, MD 20892 USA.
[Ahlman, Mark A.; Bluemke, David A.] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Lockshin, Benjamin N.] DermAssociates PC, Silver Spring, MD USA.
RP Mehta, NN (reprint author), NIH, Bldg 10,CRC 5-5140, Bethesda, MD 20892 USA.
EM nehal.mehta@nih.gov
OI Bluemke, David/0000-0002-8323-8086
FU Intramural NIH HHS [Z99 HL999999]; NHLBI NIH HHS [HL-Z-000000]
NR 7
TC 9
Z9 9
U1 0
U2 4
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 JUN
PY 2014
VL 70
IS 6
BP 1137
EP 1138
DI 10.1016/j.jaad.2013.12.043
PG 3
WC Dermatology
SC Dermatology
GA AH3NJ
UT WOS:000336030400037
PM 24641984
ER
PT J
AU Schwartz, SM
Lu, MM
Ohye, RG
Hill, KD
Atz, AM
Naim, MY
Williams, IA
Goldberg, CS
Lewis, A
Pigula, F
Manning, P
Pizarro, C
Chai, P
McCandless, R
Dunbar-Masterson, C
Kaltman, JR
Kanter, K
Sleeper, LA
Schonbeck, JV
Ghanayem, N
AF Schwartz, Steven M.
Lu, Minmin
Ohye, Richard G.
Hill, Kevin D.
Atz, Andrew M.
Naim, Maryam Y.
Williams, Ismee A.
Goldberg, Caren S.
Lewis, Alan
Pigula, Frank
Manning, Peter
Pizarro, Christian
Chai, Paul
McCandless, Rachel
Dunbar-Masterson, Carolyn
Kaltman, Jonathan R.
Kanter, Kirk
Sleeper, Lynn A.
Schonbeck, Julie V.
Ghanayem, Nancy
CA Pediat Heart Network Investigators
TI Risk factors for prolonged length of stay after the stage 2 procedure in
the single-ventricle reconstruction trial
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID LEFT-HEART SYNDROME; BIDIRECTIONAL CAVOPULMONARY SHUNT; PULMONARY-ARTERY
CONDUIT; BLALOCK-TAUSSIG SHUNT; HEMI-FONTAN PROCEDURE; NORWOOD
PROCEDURE; CARDIOPULMONARY BYPASS; GLENN OPERATION; OUTCOMES; PALLIATION
AB Background: The single-ventricle reconstruction trial randomized patients with single right ventricle lesions to a modified Blalock-Taussig or right ventricle-to-pulmonary artery shunt at the Norwood. This analysis describes outcomes at the stage 2 procedure and factors associated with a longer hospital length of stay (LOS).
Methods: We examined the association of shunt type with stage 2 hospital outcomes. Cox regression and bootstrapping were used to evaluate risk factors for longer LOS. We also examined characteristics associated with in-hospital death.
Results: There were 393 subjects in the analytic cohort. Median stage 2 procedure hospital LOS (8 days; interquartile range [IQR], 6-14 days), hospital mortality (4.3%), transplantation (0.8%), median ventilator time (2 days; IQR, 1-3 days), median intensive care unit LOS (4 days; IQR, 3-7 days), number of additional cardiac procedures or complications, and serious adverse events did not differ by shunt type. Longer LOS was associated (R-2 = 0.26) with center, longer post-Norwood LOS (hazard ratio [HR], 1.93 per log day; P <.001), nonelective timing of the stage 2 procedure (HR, 1.78; P <.001), and pulmonary artery (PA) stenosis (HR, 1.56; P <.001). By univariate analysis, nonelective stage 2 (65% vs 32%; P = .009), moderate or greater atrioventricular valve (AVV) regurgitation (75% vs 24%; P <.001), and AVV repair (53% vs 9%; P <.001) were among the risk factors associated with in-hospital death.
Conclusions: Norwood LOS, PA stenoses, and nonelective stage 2 procedure, but not shunt type, are independently associated with longer LOS. Nonelective stage 2 procedure, moderate or greater AVV regurgitation, and need for AVV repair are among the risk factors for death.
C1 [Schwartz, Steven M.] Hosp Sick Children, Dept Crit Care Med, Div Cardiac Crit Care Med, Toronto, ON M5G 1X8, Canada.
[Schwartz, Steven M.] Hosp Sick Children, Dept Crit Care Med, Div Cardiol, Toronto, ON M5G 1X8, Canada.
[Schwartz, Steven M.] Hosp Sick Children, Dept Paediat, Toronto, ON M5G 1X8, Canada.
[Lu, Minmin; Sleeper, Lynn A.; Schonbeck, Julie V.] New England Res Inst, Watertown, MA 02172 USA.
[Ohye, Richard G.] Univ Michigan, Sch Med, Dept Cardiac Surg, Div Pediat Cardiovasc Surg, Ann Arbor, MI USA.
[Goldberg, Caren S.] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Div Pediat Cardiol, Ann Arbor, MI USA.
[Hill, Kevin D.] Duke Univ, Dept Pediat, Div Cardiol, Durham, NC 27706 USA.
[Atz, Andrew M.] Med Univ S Carolina, Dept Pediat, Div Pediat Cardiol, Charleston, SC 29425 USA.
[Naim, Maryam Y.] Childrens Hosp Philadelphia, Dept Anesthesia & Crit Care, Div Crit Care Med, Philadelphia, PA 19104 USA.
[Williams, Ismee A.] Columbia Univ, Dept Pediat, Div Pediat Cardiol, New York, NY 10027 USA.
[Lewis, Alan] Univ Calif Los Angeles, Dept Pediat, Div Cardiol, Los Angeles, CA 90024 USA.
[Pigula, Frank] Childrens Hosp, Dept Cardiac Surg, Boston, MA 02115 USA.
[Dunbar-Masterson, Carolyn] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
[Manning, Peter] Cincinnati Childrens Hosp Med Ctr, Dept Surg, Div Cardiovasc Surg, Cincinnati, OH 45229 USA.
[Pizarro, Christian] Alfred I duPont Hosp Children, Dept Surg, Div Pediat Cardiothorac Surg, Wilmington, DE USA.
[Chai, Paul] All Childrens Hosp, Div Cardiovasc Surg, Tampa, FL USA.
[McCandless, Rachel] Primary Childrens Med Ctr, Dept Pediat, Div Pediat Cardiol, Salt Lake City, UT 84103 USA.
[Kaltman, Jonathan R.] NHLBI, Heart Dev & Struct Dis Branch, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Kanter, Kirk] Emory Univ, Dept Surg, Div Cardiothorac Surg, Atlanta, GA 30322 USA.
[Ghanayem, Nancy] Childrens Hosp Wisconsin, Dept Pediat, Div Crit Care Med, Milwaukee, WI 53201 USA.
RP Schwartz, SM (reprint author), Hosp Sick Children, Dept Crit Care Med, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM steven.schwartz@sickkids.ca
FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279,
HL068281, HL068285, HL068292, HL068290, HL068288, HL085057, HL109781,
HL109737]
FX This study was supported by U01 grants from the National Heart, Lung,
and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285,
HL068292, HL068290, HL068288, HL085057, HL109781, and HL109737). This
work is solely the responsibility of the authors and does not
necessarily represent the official views of the National Heart, Lung,
and Blood Institute or the National Institutes of Health.
NR 30
TC 4
Z9 5
U1 1
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5223
EI 1097-685X
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD JUN
PY 2014
VL 147
IS 6
BP 1791
EP U134
DI 10.1016/j.jtcvs.2013.07.063
PG 12
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA AH9HF
UT WOS:000336452000022
PM 24075564
ER
PT J
AU Rastinehad, AR
Turkbey, B
Salami, SS
Yaskiv, O
George, AK
Fakhoury, M
Beecher, K
Vira, MA
Kavoussi, LR
Siegel, DN
Villani, R
Ben-Levi, E
AF Rastinehad, Ardeshir R.
Turkbey, Baris
Salami, Simpa S.
Yaskiv, Oksana
George, Arvin K.
Fakhoury, Mathew
Beecher, Karin
Vira, Manish A.
Kavoussi, Louis R.
Siegel, David N.
Villani, Robert
Ben-Levi, Eran
TI Improving Detection of Clinically Significant Prostate Cancer: Magnetic
Resonance Imaging/Transrectal Ultrasound Fusion Guided Prostate Biopsy
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostate; prostatic neoplasms; biopsy; magnetic resonance imaging;
ultrasonography
ID ACTIVE SURVEILLANCE; NEGATIVE BIOPSIES; MORTALITY; ACCURACY; MEN
AB Purpose: Given the limitations of prostate specific antigen and standard biopsies for detecting prostate cancer, we evaluated the cancer detection rate and external validity of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system used at the National Institutes of Health.
Materials and Methods: We performed a phase III trial of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system with participants enrolled between 2012 and 2013. A total of 153 men consented to the study and underwent 3 Tesla multiparametric magnetic resonance imaging with an endorectal coil for clinical suspicion of prostate cancer. Lesions were classified as low or moderate/high risk for prostate cancer. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy and standard 12-core prostate biopsy were performed and 105 men were eligible for analysis.
Results: Mean patient age was 65.8 years and mean prostate specific antigen was 9.5 ng/ml. The overall cancer detection rate was 62.9% (66 of 105 patients). The cancer detection rate in those with moderate/high risk on imaging was 72.3% (47 of 65) vs 47.5% (19 of 40) in those classified as low risk for prostate cancer (p < 0.05). Mean tumor core length was 4.6 and 3.7 mm for fusion biopsy and standard 12-core biopsy, respectively (p < 0.05). Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detected prostate cancer that was missed by standard 12-core biopsy in 14.3% of cases (15 of 105), of which 86.7% (13 of 15) were clinically significant. This biopsy upgraded 23.5% of cancers (4 of 17) deemed clinically insignificant on 12-core biopsy to clinically significant prostate cancer necessitating treatment.
Conclusions: Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy can improve prostate cancer detection. The results of this trial support the external validity of this platform and may be the next step in the evolution of prostate cancer management.
C1 [Rastinehad, Ardeshir R.] Hofstra North Shore Jewish Sch Med, Arthur Smith Inst Urol, New Hyde Pk, NY 11040 USA.
Hofstra North Shore Jewish Sch Med, Dept Radiol, New Hyde Pk, NY 11040 USA.
Hofstra North Shore Jewish Sch Med, Dept Intervent Radiol & Pathol, New Hyde Pk, NY 11040 USA.
[Turkbey, Baris] NIH, Mol Imaging Program, Bethesda, MD 20892 USA.
RP Rastinehad, AR (reprint author), Hofstra North Shore Jewish Sch Med, Arthur Smith Inst Urol, 450 Lakeville Rd,Suite M-41, New Hyde Pk, NY 11040 USA.
EM arastine@nshs.edu
NR 20
TC 70
Z9 71
U1 2
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD JUN
PY 2014
VL 191
IS 6
BP 1749
EP 1754
DI 10.1016/j.juro.2013.12.007
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA AI0IS
UT WOS:000336531100028
PM 24333515
ER
PT J
AU Fwu, CW
Eggers, PW
Kirkali, Z
McVary, KT
Burrows, PK
Kusek, JW
AF Fwu, Chyng-Wen
Eggers, Paul W.
Kirkali, Ziya
McVary, Kevin T.
Burrows, Pamela K.
Kusek, John W.
TI Change in Sexual Function in Men with Lower Urinary Tract
Symptoms/Benign Prostatic Hyperplasia Associated with Long-Term
Treatment with Doxazosin, Finasteride and Combined Therapy
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostate; lower urinary tract symptoms; sexual dysfunction;
physiological; doxazosin; finasteride
ID REAL-LIFE PRACTICE; COMBINATION THERAPY; MEDICAL THERAPY; OLMSTED
COUNTY; HEALTH-STATUS; DYSFUNCTION; TRIAL; EFFICACY; DUTASTERIDE; CANCER
AB Purpose: We examined the effects of doxazosin, finasteride and combined therapy in men with lower urinary tract symptoms associated with benign prostatic hyperplasia on sexual function, as assessed by the Brief Male Sexual Function Inventory during 4 years.
Materials and Methods: The MTOPS (Medical Therapy of Prostatic Symptoms) study was a multicenter, randomized, double-blind, placebo controlled clinical trial with a primary outcome of time to benign prostatic hyperplasia progression. Change in sexual function was a secondary outcome. We analyzed the records of 2,783 men enrolled in the study who completed the inventory at baseline and at least once during followup.
Results: In men enrolled in MTOPS sexual function decreased with time. Men assigned to finasteride and combined therapy experienced overall statistically significant but slight worsening of ejaculatory function compared with men on placebo. Men assigned to combined therapy also experienced significant worsening in erectile function and sexual problem assessment. There was no significant difference in changes in any inventory domain in men assigned to doxazosin alone compared to placebo.
Conclusions: This study significantly extends understanding of the effects of long-term treatment with these drugs on sexual function in men with lower urinary tract symptoms associated with benign prostatic hyperplasia. Treatment with finasteride or combined therapy was associated with worsening sexual function while treatment with doxazosin alone was associated with minimal negative impact, if any. Physicians should discuss with their patients the possible long-term effects of these drugs for lower urinary tract symptoms associated with benign prostatic hyperplasia on sexual function.
C1 [Fwu, Chyng-Wen] Social & Sci Syst Inc, Silver Spring, MD 20910 USA.
[Eggers, Paul W.; Kirkali, Ziya; Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA.
[Burrows, Pamela K.] George Washington Univ, Ctr Biostat, Rockville, MD USA.
[McVary, Kevin T.] So Illinois Univ, Sch Med, Div Urol, Springfield, IL USA.
RP Fwu, CW (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA.
EM cfwu@s-3.com
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[HHSN 276201200161U]; NIDDK (MTOPS)
FX Supported by National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) Contract HHSN 276201200161U (CWF) and NIDDK (MTOPS).
NR 30
TC 15
Z9 15
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD JUN
PY 2014
VL 191
IS 6
BP 1828
EP 1834
DI 10.1016/j.juro.2013.12.014
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA AI0IS
UT WOS:000336531100074
PM 24342143
ER
PT J
AU Duyn, JH
AF Duyn, Jeff H.
TI Frequency Shifts in the Myelin Water Compartment
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Letter
ID MAGNETIC-SUSCEPTIBILITY; WHITE-MATTER; BRAIN; ORIENTATION; MRI;
ANISOTROPY; MEMBRANES; SHEATH; NERVE
C1 NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Duyn, JH (reprint author), NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bldg 10,Room B1D118,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jhd@helix.nih.gov
FU Intramural NIH HHS [ZIA NS002990-14]
NR 23
TC 5
Z9 5
U1 1
U2 32
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUN
PY 2014
VL 71
IS 6
BP 1953
EP 1955
DI 10.1002/mrm.24983
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AH6SL
UT WOS:000336260900001
PM 24700549
ER
PT J
AU Gamache, B
Leist, SR
Bard, AD
Logan, DW
Carpanini, SM
AF Gamache, Benjamin
Leist, Sarah R.
Bard, Andrew Daniel
Logan, Darren W.
Carpanini, Sarah M.
TI 27th International Mammalian Genome Conference meeting report
SO MAMMALIAN GENOME
LA English
DT Article
C1 [Gamache, Benjamin] NCI, NIH, Bethesda, MD 20892 USA.
[Leist, Sarah R.] Helmholtz Ctr Infect Res, Dept Infect Genet, Braunschweig, Germany.
[Bard, Andrew Daniel; Logan, Darren W.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
[Bard, Andrew Daniel] Univ Bristol, Sch Biochem, Bristol BS8 1TD, Avon, England.
[Carpanini, Sarah M.] Univ Edinburgh, Div Neurobiol, Roslin Inst, Edinburgh EH25 9RG, Midlothian, Scotland.
RP Carpanini, SM (reprint author), Univ Edinburgh, Div Neurobiol, Roslin Inst, Edinburgh EH25 9RG, Midlothian, Scotland.
EM sarah.carpanini@roslin.ed.ac.uk
OI Logan, Darren /0000-0003-1545-5510
FU NHGRI [2R13HG0002394]; NICHD at NIH; Mouse News Letter Ltd; COST Action
SYSGENET
FX The IMGS wishes to thank the organising committee for arranging this
fantastic conference; Elena de la Casa Esperon, Lluis Montoliu, Fernando
Pardo-Manuel de Villena and Jesus Perez-Losada. The IMGS also wishes to
thank the Secretariat comprising David Beier (President), Teresa Gunn
(Vice-President), David Threadgill (Past President), Klaus Schughart,
Linda Siracusa, Sarah Carpanini, Piero Carninci, Steven Munger, Elena de
la Casa Esperon, Jiri Forejt and Darren Logan for their service. The
society is also indebted to Darla Miller. The meeting was supported by
The Jackson Laboratory, Taconic, Disease Models and Mechanisms, PLOS
Genetics, GeneSeek and MMRRC. Funding for scholarship awards was made
available through 2R13HG0002394 from NHGRI and NICHD at NIH and from
Mouse News Letter Ltd, and through the COST Action SYSGENET.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0938-8990
EI 1432-1777
J9 MAMM GENOME
JI Mamm. Genome
PD JUN
PY 2014
VL 25
IS 5-6
BP 195
EP 201
DI 10.1007/s00335-014-9513-3
PG 7
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA AH8LD
UT WOS:000336388400002
PM 24752582
ER
PT J
AU Sacktor, N
Nakasujja, N
Redd, AD
Manucci, J
Laeyendecker, O
Wendel, SK
Porcella, SF
Martens, C
Bruno, D
Skolasky, RL
Okonkwo, OC
Robertson, K
Musisi, S
Katabira, E
Quinn, TC
AF Sacktor, Ned
Nakasujja, Noeline
Redd, Andrew D.
Manucci, Jordyn
Laeyendecker, Oliver
Wendel, Sarah K.
Porcella, Stephen F.
Martens, Craig
Bruno, Daniel
Skolasky, Richard L.
Okonkwo, Ozioma C.
Robertson, Kevin
Musisi, Seggane
Katabira, Elly
Quinn, Thomas C.
TI HIV subtype is not associated with dementia among individuals with
moderate and advanced immunosuppression in Kampala, Uganda
SO METABOLIC BRAIN DISEASE
LA English
DT Article
DE HIV; Dementia; Subtype; Uganda; Clade
ID SUB-SAHARAN AFRICA; DISEASE PROGRESSION; NEUROPSYCHOLOGICAL PERFORMANCE;
COGNITIVE IMPAIRMENT; RAKAI; SUPERINFECTION; RECEPTORS; INFECTION;
CHILDREN; COHORT
AB HIV-associated neurocognitive disorders (HAND) are a common neurological manifestation of HIV infection. A previous study suggested that HIV dementia may be more common among patients with subtype D virus than among those with subtype A virus among HIV+ individuals with advanced immunosuppression. We conducted a study to evaluate the frequency of HIV dementia, and the association of HIV dementia with HIV subtype and compartmentalization among HIV+ individuals with moderate and advanced immunosuppression (CD4 lymphocyte count > 150 cells/mu L and < 250 cells/mu L). The study enrolled 117 antiretroviral na < ve HIV+ individuals in Kampala, Uganda. HIV+ individuals received neurological, neuropsychological testing, and functional assessments, and gag and gp41 regions were subtyped. Subjects were considered infected with a specific subtype if both regions analyzed were from the same subtype. 41 % of the HIV+ individuals had HIV dementia (mean CD4 lymphocyte count = 233 cells/mu L). 67 individuals had subtype A, 25 individuals had subtype D, 24 individuals were classified as A/D recombinants, and one individual had subtype C. There was no difference in the frequency of HIV dementia when stratified by HIV subtype A and D and no association with compartmentalization between the cerebrospinal fluid and peripheral blood. These results suggest that HIV dementia is common in HIV+ individuals in Uganda. There was no association between HIV subtype and dementia among HIV+ individuals with moderate and advanced immunosuppression. Future studies should be performed to confirm these results.
C1 [Sacktor, Ned] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD 21224 USA.
[Skolasky, Richard L.] Johns Hopkins Univ, Sch Med, Dept Orthoped Surg, Baltimore, MD USA.
[Manucci, Jordyn; Laeyendecker, Oliver; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Nakasujja, Noeline; Musisi, Seggane] Dept Psychiat, Kampala, Uganda.
[Katabira, Elly] Makerere Univ, Dept Med, Kampala, Uganda.
[Redd, Andrew D.; Manucci, Jordyn; Laeyendecker, Oliver; Wendel, Sarah K.; Quinn, Thomas C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Porcella, Stephen F.; Martens, Craig; Bruno, Daniel] NIAID, Genom Unit, Res Technol Branch, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT USA.
[Okonkwo, Ozioma C.] Univ Wisconsin, Dept Med, Madison, WI USA.
[Robertson, Kevin] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA.
RP Sacktor, N (reprint author), Johns Hopkins Bayview Med Ctr, Dept Neurol, 301 Bldg,Suite 2100,4940 Eastern Ave, Baltimore, MD 21224 USA.
EM sacktor@jhmi.edu
OI Laeyendecker, Oliver/0000-0002-6429-4760; Skolasky,
Richard/0000-0002-2598-4427
FU National Institute of Mental Health at the National Institutes of Health
[MH083465]; Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health
FX This work was supported by the National Institute of Mental Health at
the National Institutes of Health (Grant number MH083465). Funding also
was provided in part by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 29
TC 4
Z9 4
U1 1
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0885-7490
EI 1573-7365
J9 METAB BRAIN DIS
JI Metab. Brain Dis.
PD JUN
PY 2014
VL 29
IS 2
SI SI
BP 261
EP 268
DI 10.1007/s11011-014-9498-3
PG 8
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA AH7SU
UT WOS:000336335200007
PM 24515303
ER
PT J
AU Ciucci, T
Bosselut, R
AF Ciucci, Thomas
Bosselut, Remy
TI A ROG(ue) in charge of the (natural) killers
SO NATURE IMMUNOLOGY
LA English
DT Editorial Material
ID REPRESSOR; CELLS; DIFFERENTIATION; REGULATORS; EXPRESSION; EFFECTORS;
LINEAGE; FAMILY; GATA
AB Natural killer (NK) cells are innate lymphocytes that exhibit many features of adaptive immunity, such as long-lived memory. This can now be extended to the transcriptional circuits that control the proliferation of NK cells and lymphocytes.
C1 [Ciucci, Thomas; Bosselut, Remy] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ciucci, T (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM remy@helix.nih.gov
NR 12
TC 1
Z9 1
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUN
PY 2014
VL 15
IS 6
BP 531
EP 532
PG 2
WC Immunology
SC Immunology
GA AH8WQ
UT WOS:000336419300007
PM 24840990
ER
PT J
AU Lee, JH
Halperin-Sheinfeld, M
Baatar, D
Mughal, MR
Tae, HJ
Kim, JW
Carter, A
Lustig, A
Snir, O
Lavie, G
Okun, E
Mattson, MP
Sredni, B
Taub, DD
AF Lee, Jun-Ho
Halperin-Sheinfeld, Meital
Baatar, Dolgar
Mughal, Mohamed R.
Tae, Hyun-Jin
Kim, Jie-Wan
Carter, Arnell
Lustig, Ana
Snir, Omri
Lavie, Gad
Okun, Eitan
Mattson, Mark P.
Sredni, Benjamin
Taub, Dennis D.
TI Tellurium Compound AS101 Ameliorates Experimental Autoimmune
Encephalomyelitis by VLA-4 Inhibition and Suppression of Monocyte and T
Cell Infiltration into the CNS
SO NEUROMOLECULAR MEDICINE
LA English
DT Article
DE Inflammation; Integrin; Macrophages; Multiple sclerosis; Spinal cord;
VLA-4
ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM;
MULTIPLE-SCLEROSIS; CANCER-PATIENTS; IMMUNOMODULATOR AS101;
DEMYELINATING DISEASE; ADHESION MOLECULE-1; DENDRITIC CELLS;
ANIMAL-MODELS; LEWIS RATS
AB Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) involving demyelinating and neurodegenerative processes. Several of the major pathological CNS alterations and behavioral deficits of MS are recapitulated in the experimental autoimmune encephalitis (EAE) mouse model in which the disease process is induced by administration of myelin peptides. Development of EAE requires infiltration of inflammatory cytokine-generating monocytes and macrophages, and auto-reactive T cells, into the CNS. Very late antigen-4 (VLA-4, alpha 4 beta 1) is an integrin molecule that plays a role in inflammatory responses by facilitating the migration of leukocytes across the blood-brain barrier during inflammatory disease, and antibodies against VLA-4 exhibit therapeutic efficacy in mouse and monkey MS models. Here, we report that the tellurium compound AS101 (ammonium trichloro (dioxoethylene-o,o') tellurate) ameliorates EAE by inhibiting monocyte and T cell infiltration into the CNS. CD49d is an alpha subunit of the VLA-4 (alpha 4 beta 1) integrin. During the peak stage of EAE, AS101 treatment effectively ameliorated the disease process by reducing the number of CD49d(+) inflammatory monocyte/macrophage cells in the spinal cord. AS101 treatment markedly reduced the pro-inflammatory cytokine levels, while increasing anti-inflammatory cytokine levels. In contrast, AS101 treatment did not affect the peripheral populations of CD11b(+) monocytes and macrophages. AS101 treatment reduced the infiltration of CD4(+) and CD49(+)/VLA4 T cells. In addition, treatment of T cells from MS patients with AS101 resulted in apoptosis, while such treatment did not affect T cells from healthy donors. These results suggest that AS101 reduces accumulation of leukocytes in the CNS by inhibiting the activity of the VLA-4 integrin and provide a rationale for the potential use of Tellurium IV compounds for the treatment of MS.
C1 [Lee, Jun-Ho; Baatar, Dolgar; Tae, Hyun-Jin; Kim, Jie-Wan; Carter, Arnell; Lustig, Ana; Taub, Dennis D.] NIA, Lab Cell Biol & Immunol, Intramural Res Program, Baltimore, MD 21224 USA.
[Lee, Jun-Ho; Mughal, Mohamed R.; Mattson, Mark P.] NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.
[Halperin-Sheinfeld, Meital; Snir, Omri; Okun, Eitan; Sredni, Benjamin] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel.
[Snir, Omri; Lavie, Gad] Chaim Sheba Med Ctr, Ctr Blood Transfus, IL-52621 Tel Hashomer, Israel.
[Snir, Omri; Lavie, Gad] Chaim Sheba Med Ctr, Multiple Sclerosis Ctr, IL-52621 Tel Hashomer, Israel.
[Mattson, Mark P.] Johns Hopkins Univ Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Taub, DD (reprint author), NIA, Lab Cell Biol & Immunol, Intramural Res Program, Baltimore, MD 21224 USA.
EM mattsonm@grc.nia.nih.gov; srednib@mail.biu.ac.il; taubd@grc.nia.nih.gov
FU National Institute on Aging
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging.
NR 60
TC 4
Z9 4
U1 0
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1535-1084
EI 1559-1174
J9 NEUROMOL MED
JI Neuromol. Med.
PD JUN
PY 2014
VL 16
IS 2
BP 292
EP 307
DI 10.1007/s12017-013-8277-3
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA AH6EW
UT WOS:000336224500005
PM 24272426
ER
PT J
AU Byun, NE
Grannan, M
Bubser, M
Barry, RL
Thompson, A
Rosanelli, J
Gowrishankar, R
Kelm, ND
Damon, S
Bridges, TM
Melancon, BJ
Tarr, JC
Brogan, JT
Avison, MJ
Deutch, AY
Wess, J
Wood, MR
Lindsley, CW
Gore, JC
Conn, PJ
Jones, CK
AF Byun, Nellie E.
Grannan, Michael
Bubser, Michael
Barry, Robert L.
Thompson, Analisa
Rosanelli, John
Gowrishankar, Raajaram
Kelm, Nathaniel D.
Damon, Stephen
Bridges, Thomas M.
Melancon, Bruce J.
Tarr, James C.
Brogan, John T.
Avison, Malcolm J.
Deutch, Ariel Y.
Wess, Juergen
Wood, Michael R.
Lindsley, Craig W.
Gore, John C.
Conn, P. Jeffrey
Jones, Carrie K.
TI Antipsychotic Drug-Like Effects of the Selective M-4 Muscarinic
Acetylcholine Receptor Positive Allosteric Modulator VU0152100
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE M-4; muscarinic; antipsychotic; allosteric; phMRI; VU0152100
ID IN-VIVO VALIDATION; AGONIST XANOMELINE; KNOCKOUT MICE; CHOLINERGIC
INTERNEURONS; FUNCTIONAL CONNECTIVITY; PREPULSE INHIBITION;
PHARMACOLOGICAL MRI; PREFRONTAL CORTEX; OREXIN NEURONS; DOPAMINE
AB Accumulating evidence suggests that selective M-4 muscarinic acetylcholine receptor (mAChR) activators may offer a novel strategy for the treatment of psychosis. However, previous efforts to develop selective M-4 activators were unsuccessful because of the lack of M-4 mAChR subtype specificity and off-target muscarinic adverse effects. We recently developed VU0152100, a highly selective M-4 positive allosteric modulator (PAM) that exerts central effects after systemic administration. We now report that VU01521 00 dose-dependently reverses amphetamine-induced hyperlocomotion in rats and wild-type mice, but not in M-4 KO mice. VU0152100 also blocks amphetamine-induced disruption of the acquisition of contextual fear conditioning and prepulse inhibition of the acoustic startle reflex. These effects were observed at doses that do not produce catalepsy or peripheral adverse effects associated with non-selective mAChR agonists. To further understand the effects of selective potentiation of M-4 on region-specific brain activation, VU0152100 alone and in combination with amphetamine were evaluated using pharmacologic magnetic resonance imaging (phMRI). Key neural substrates of M-4-mediated modulation of the amphetamine response included the nucleus accumbens (NAS), caudate-putamen (CP), hippocampus, and medial thalamus. Functional connectivity analysis of phMRI data, specifically assessing correlations in activation between regions, revealed several brain networks involved in the M4 modulation of amphetamine-induced brain activation, including the NAS and retrosplenial cortex with motor cortex, hippocampus, and medial thalamus. Using in vivo microdialysis, we found that VU0152100 reversed amphetamine-induced increases in extracellular dopamine levels in NAS and CP. The present data are consistent with an antipsychotic drug-like profile of activity for VU0152100. Taken together, these data support the development of selective M-4 PAMs as a new approach to the treatment of psychosis and cognitive impairments associated with psychiatric disorders such as schizophrenia.
C1 [Byun, Nellie E.; Grannan, Michael; Bubser, Michael; Thompson, Analisa; Rosanelli, John; Bridges, Thomas M.; Melancon, Bruce J.; Tarr, James C.; Brogan, John T.; Wood, Michael R.; Lindsley, Craig W.; Conn, P. Jeffrey; Jones, Carrie K.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA.
[Byun, Nellie E.; Grannan, Michael; Bubser, Michael; Thompson, Analisa; Bridges, Thomas M.; Brogan, John T.; Avison, Malcolm J.; Deutch, Ariel Y.; Lindsley, Craig W.; Conn, P. Jeffrey; Jones, Carrie K.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA.
[Byun, Nellie E.; Barry, Robert L.; Kelm, Nathaniel D.; Damon, Stephen; Avison, Malcolm J.; Gore, John C.] Vanderbilt Univ, Med Ctr, Vanderbilt Univ Inst Imaging Sci, Nashville, TN 37232 USA.
[Barry, Robert L.; Avison, Malcolm J.] Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA.
[Gowrishankar, Raajaram] Vanderbilt Univ, Grad Program Neurosci, Nashville, TN 37232 USA.
[Gowrishankar, Raajaram] Vanderbilt Univ, Vanderbilt Brain Inst, Nashville, TN 37232 USA.
[Gowrishankar, Raajaram] Vanderbilt Univ, Vanderbilt Int Scholars Program, Nashville, TN 37232 USA.
[Kelm, Nathaniel D.; Gore, John C.] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37232 USA.
[Bridges, Thomas M.; Brogan, John T.; Wood, Michael R.; Lindsley, Craig W.] Vanderbilt Univ, Med Ctr, Dept Chem, Nashville, TN 37232 USA.
[Deutch, Ariel Y.] Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN 37232 USA.
[Wess, Juergen] Natl Inst Diabet & Digest & Kidney Dis, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA.
RP Jones, CK (reprint author), Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, 418B Preston Res Bldg, Nashville, TN 37232 USA.
EM carrie.jones@vanderbilt.edu
OI Bubser, Michael/0000-0002-0583-5248
FU NovoNordisk; NIH; Bristol Myers Squibb; Johnson Johnson; AstraZeneca;
Michael J Fox Foundation; Thome Foundation; US National Institutes of
Health [MH077298]; Eli Lilly; Barrus Foundation
FX Dr Avison receives funding from NovoNordisk and received funding through
NIH. Dr Conn received research support from Bristol Myers Squibb,
Johnson & Johnson, and AstraZeneca, the Michael J Fox Foundation, the
Thome Foundation and NIH and is an inventor on filed patent applications
protecting M4 PAMs for the treatment of schizophrenia. Dr
Deutch is supported in part by the US National Institutes of Health
(MH077298) and by the Michael J Fox Foundation. He has served as a
consultant for Eli Lilly, for which he has received honoraria and travel
support. In addition, he has received compensation for editorial board
responsibilities on Neuropsychopharmacology (ACNP). He has received
travel support to attend meetings of Medical and Scientific Board of the
National Parkinson Foundation. Dr Gore received funding from Astra
Zeneca and the NIH. Dr Jones received research support from Bristol
Myers Squibb, Johnson & Johnson, and AstraZeneca. Dr Jones also received
funding through the Michael J Fox Foundation, the Barrus Foundation, and
NIH. Dr Lindsley received compensation as a consultant for AbbVie
Pharmaceuticals and research support from AstraZeneca, Johnson &
Johnson, and Bristol Myers Squibb. Dr Lindsley also received funding
through the Michael J Fox Foundation and NIH and is an inventor on filed
patent applications protecting M4 PAMs for the treatment of
schizophrenia. The remaining authors declare no conflict of interest.
NR 70
TC 24
Z9 24
U1 2
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUN
PY 2014
VL 39
IS 7
BP 1578
EP 1593
DI 10.1038/npp.2014.2
PG 16
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AH4OG
UT WOS:000336107300004
PM 24442096
ER
PT J
AU Kramar, CP
Chefer, VI
Wise, RA
Medina, JH
Barbano, MF
AF Kramar, Cecilia P.
Chefer, Vladimir I.
Wise, Roy A.
Medina, Jorge H.
Flavia Barbano, M.
TI Dopamine in the Dorsal Hippocampus Impairs the Late Consolidation of
Cocaine-Associated Memory
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE memory persistence; memory consolidation; hippocampus; dopamine;
cocaine; conditioned behavior
ID LONG-TERM-MEMORY; CONDITIONED PLACE PREFERENCE; VENTRAL TEGMENTAL AREA;
MOLECULAR-MECHANISMS; NUCLEUS-ACCUMBENS; ADENYLYL-CYCLASE;
LITHIUM-CHLORIDE; DRUG-ADDICTION; REWARD; GLUTAMATE
AB Cocaine is thought to be addictive because it elevates dopamine levels in the striatum, reinforcing drug-seeking habits. Cocaine also elevates dopamine levels in the hippocampus, a structure involved in contextual conditioning as well as in reward function. Hippocampal dopamine promotes the late phase of consolidation of an aversive step-down avoidance memory. Here, we examined the role of hippocampal dopamine function in the persistence of the conditioned increase in preference for a cocaine-associated compartment. Blocking dorsal hippocampal DI -type receptors (D1Rs) but not D2-type receptors (D2Rs) 12 h after a single training trial extended persistence of the normally short-lived memory; conversely, a general and a specific phospholipase C-coupled DIR agonist (but not a D2R or adenylyl cyclase-coupled DIR agonist) decreased the persistence of the normally long-lived memory established by three-trial training. These effects of DI agents were opposite to those previously established in a step-down avoidance task, and were here also found to be opposite to those in a lithium chloride-conditioned avoidance task. After returning to normal following cocaine injection, dopamine levels in the dorsal hippocampus were found elevated again at the time when dopamine antagonists and agonists were effective: between 13 and 17 h after cocaine injection. These findings confirm that, long after the making of a cocaine place association, hippocampal activity modulates memory consolidation for that association via a dopamine dependent mechanism. They suggest a dynamic role for dorsal hippocampal dopamine in this late-phase memory consolidation and, unexpectedly, differential roles for late consolidation of memories for places that induce approach or withdrawal because of a drug association.
C1 [Kramar, Cecilia P.; Medina, Jorge H.; Flavia Barbano, M.] Univ Buenos Aires, Fac Med, Inst Biol Celular & Neurociencias CONICET UBA, Buenos Aires, DF, Argentina.
[Chefer, Vladimir I.; Wise, Roy A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Medina, Jorge H.] Univ Buenos Aires, Fac Med, Dept Fisiol, RA-1425 Buenos Aires, DF, Argentina.
RP Barbano, MF (reprint author), NIDA, Intramural Res Program, Neuronal Networks Sect, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM maria.barbano@nih.gov
FU CONICET, Argentina; CONICET, UBA, Foncyt [PICT 2010-1169, PICT
2011-1941]; Intramural Research Program of the National Institute on
Drug Abuse (NIDA/NIH)
FX We gratefully acknowledge Dr Gustavo Murer and Verardo y Cia. laboratory
for their kind donation of quinpirole and cocaine hydrochloride,
respectively. We thank Catherine Schweppe, Fernando Garagoli, Eduardo
Gigante, and Carolina Gonzalez for excellent technical help. CP Kramar
was supported by a doctoral fellowship from CONICET, Argentina. This
work was supported by CONICET, UBA, Foncyt (Grants PICT 2010-1169 to Dr
Medina and PICT 2011-1941 to Dr Barbano) and by the Intramural Research
Program of the National Institute on Drug Abuse (NIDA/NIH).
NR 41
TC 6
Z9 7
U1 2
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUN
PY 2014
VL 39
IS 7
BP 1645
EP 1653
DI 10.1038/npp.2014.11
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AH4OG
UT WOS:000336107300010
PM 24442095
ER
PT J
AU Rose, EJ
Salmeron, BJ
Ross, TJ
Waltz, J
Schweitzer, JB
McClure, SM
Stein, EA
AF Rose, Emma Jane
Salmeron, Betty Jo
Ross, Thomas J.
Waltz, James
Schweitzer, Julie B.
McClure, Samuel M.
Stein, Elliot A.
TI Temporal Difference Error Prediction Signal Dysregulation in Cocaine
Dependence
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE cocaine dependence; temporal difference error prediction; reward;
motivation; fMRI
ID STATE FUNCTIONAL CONNECTIVITY; EVENT-RELATED FMRI; PREFRONTAL CORTEX;
HUMAN BRAIN; DOPAMINE RELEASE; DORSAL STRIATUM; DRUG-ADDICTION;
EMISSION-TOMOGRAPHY; NEURAL RESPONSES; DECISION-MAKING
AB Cocaine dependence impacts drug-related, dopamine-dependent reward processing, yet its influence on non-drug reward processing is unclear. Here, we investigated cocaine-mediated effects on reward learning using a natural food reinforcer. Cocaine-dependent subjects (N =14) and healthy controls (N-= 14) learned to associate a visual cue with a juice reward. In subsequent functional imaging sessions they were exposed to trials where juice was received as learned, withheld (negative temporal difference error (NTDE)), or received unexpectedly (positive temporal difference error (PTDE)). Subjects were scanned twice in sessions that were identical, except that cocaine-dependent participants received cocaine or saline 10 min before task onset In the insula, precentral and postcentral gyri NTDE signals were greater, and PTDE-related function was reduced in cocaine-dependent subjects. Compared with healthy controls, in the cocaine-dependent group PTDE signals were also reduced in medial frontal gyrus and reward-related function, irrespective of predictability, was reduced in the putamen. Group differences in error-related activity were predicted by the time as last selfadministered cocaine use, but TDE function was not influenced by acute cocaine. Thus, cocaine dependence seems to engender increased responsiveness to unexpected negative outcomes and reduced sensitivity to positive events in dopaminergic reward regions. Although it remains to be established if these effects are a consequence of or antecedent to cocaine dependence, they likely have implications for the high-cocaine use recidivism rates by contributing to the drive to consume cocaine, perhaps via influence on dopamine-related reward computations. The fact that these effects do not acquiesce to acute cocaine administration might factor in binge-related escalated consumption.
C1 [Rose, Emma Jane; Salmeron, Betty Jo; Ross, Thomas J.; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD USA.
[Waltz, James] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
[Schweitzer, Julie B.] Univ Calif Davis, Sch Med, MIND Inst, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA.
[McClure, Samuel M.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA.
RP Rose, EJ (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Ctr Translat Res Advers Neurodev & Subst Abuse, 4th Floor,110 S Paca St, Baltimore, MD 21201 USA.
EM ejrose@rti.org
RI Rose, Emma/A-9960-2010; Salmeron, Betty Jo/M-1793-2016;
OI Rose, Emma/0000-0001-5365-4794; Salmeron, Betty Jo/0000-0003-1699-9333;
Ross, Thomas/0000-0002-7745-3572
FU Intramural Research Program of the National Institute on Drug Abuse
(NIDA)
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse (NIDA), We gratefully acknowledge
Kimberley Slater for her invaluable support and assistance in running
this study. We thank Loretta Spurgeon, Eliscia Smith, NIDA-IRP nursing
and recruitment staff, and the individuals who volunteered their time to
participate.
NR 68
TC 6
Z9 7
U1 3
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD JUN
PY 2014
VL 39
IS 7
BP 1732
EP 1742
DI 10.1038/npp.2014.21
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA AH4OG
UT WOS:000336107300019
PM 24569319
ER
PT J
AU Takakura, A
Tessler, HH
Goldstein, DA
Guex-Crosier, Y
Chan, CC
Brown, DM
Thorne, JE
Wang, R
Cunningham, ET
AF Takakura, Ako
Tessler, Howard H.
Goldstein, Debra A.
Guex-Crosier, Yan
Chan, Chi-Chao
Brown, Diane M.
Thorne, Jennifer E.
Wang, Robert
Cunningham, Emmett T., Jr.
TI Viral Retinitis following Intraocular or Periocular Corticosteroid
Administration: A Case Series and Comprehensive Review of the Literature
SO OCULAR IMMUNOLOGY AND INFLAMMATION
LA English
DT Article
DE Acute retinal necrosis; corticosteroid; cytomegalovirus; herpes virus;
injection; retinitis
ID INTRAVITREAL TRIAMCINOLONE ACETONIDE; ACUTE RETINAL NECROSIS;
CYTOMEGALOVIRUS RETINITIS; IMMUNOCOMPETENT PATIENT; CMV RETINITIS;
INJECTION; UVEITIS; AIDS; IMPLANT
AB Purpose: To describe viral retinitis following intravitreal and periocular corticosteroid administration.
Methods: Retrospective case series and comprehensive literature review.
Results: We analyzed 5 unreported and 25 previously published cases of viral retinitis following local corticosteroid administration. Causes of retinitis included 23 CMV (76.7%), 5 HSV (16.7%), and 1 each VZV and unspecified (3.3%). Two of 22 tested patients (9.1%) were HIV positive. Twenty-one of 30 (70.0%) cases followed one or more intravitreal injections of triamcinolone acetonide (TA), 4 (13.3%) after one or more posterior sub-Tenon injections of TA, 3 (10.0%) after placement of a 0.59-mg fluocinolone acetonide implant (Retisert), and 1 (3.3%) each after an anterior subconjunctival injection of TA (together with IVTA), an anterior chamber injection, and an anterior sub-Tenon injection. Mean time from most recent corticosteroid administration to development of retinitis was 4.2 months (median 3.8; range 0.25-13.0). Twelve patients (40.0%) had type II diabetes mellitus. Treatments used included systemic antiviral agents (26/30, 86.7%), intravitreal antiviral injections (20/30, 66.7%), and ganciclovir intravitreal implants (4/30, 13.3%).
Conclusions: Viral retinitis may develop or reactivate following intraocular or periocular corticosteroid administration. Average time to development of retinitis was 4 months, and CMV was the most frequently observed agent. Diabetes was a frequent co-morbidity and several patients with uveitis who developed retinitis were also receiving systemic immunosuppressive therapy.
C1 [Takakura, Ako; Cunningham, Emmett T., Jr.] Calif Pacific Med Ctr, Dept Ophthalmol, San Francisco, CA USA.
[Tessler, Howard H.] Univ Illinois, Dept Ophthalmol, Chicago, IL 60680 USA.
[Goldstein, Debra A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Guex-Crosier, Yan; Chan, Chi-Chao] Univ Lausanne, Jules Gonin Eye Hosp, Lausanne, Switzerland.
[Brown, Diane M.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Thorne, Jennifer E.] Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21287 USA.
[Wang, Robert] Texas Retina Associates, Dallas, TX USA.
[Cunningham, Emmett T., Jr.] Stanford Univ, Dept Ophthalmol, Sch Med, Stanford, CA 94305 USA.
[Cunningham, Emmett T., Jr.] UCSF, Francis I Proctor Fdn, San Francisco, CA USA.
RP Cunningham, ET (reprint author), West Coast Retina Med Grp Inc, 1445 Bush St, San Francisco, CA 94109 USA.
EM emmett_cunningham@yahoo.com
FU Pacific Vision Foundation; Retina Foundation
FX Supported in part by the Pacific Vision Foundation and the Retina
Foundation.
NR 28
TC 9
Z9 9
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0927-3948
EI 1744-5078
J9 OCUL IMMUNOL INFLAMM
JI Ocul. Immunol. Inflamm.
PD JUN
PY 2014
VL 22
IS 3
BP 175
EP 182
DI 10.3109/09273948.2013.866256
PG 8
WC Ophthalmology
SC Ophthalmology
GA AH8ZR
UT WOS:000336428300003
PM 24655372
ER
PT J
AU Weiss, B
Widemann, BC
Wolters, P
Dombi, E
Vinks, AA
Cantor, A
Korf, B
Perentesis, J
Gutmann, DH
Schorry, E
Packer, R
Fisher, MJ
AF Weiss, Brian
Widemann, Brigitte C.
Wolters, Pamela
Dombi, Eva
Vinks, Alexander A.
Cantor, Alan
Korf, Bruce
Perentesis, John
Gutmann, David H.
Schorry, Elizabeth
Packer, Roger
Fisher, Michael J.
TI Sirolimus for Non-Progressive NF1-Associated Plexiform Neurofibromas: An
NF Clinical Trials Consortium Phase II Study
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE clinical trials; mTOR; neurofibromatosis; new agents; solid; tumors
ID VISUAL ANALOG SCALE; QUALITY-OF-LIFE; MAMMALIAN TARGET; CANCER-THERAPY;
FUNCTIONAL ASSESSMENT; PAIN QUESTIONNAIRE; RAPAMYCIN PATHWAY; PEDIATRIC
PAIN; RELIABILITY; POPULATION
AB BackgroundPatients with Neurofibromatosis Type 1 (NF1) have an increased risk of developing tumors of the central and peripheral nervous system, including plexiform neurofibromas (PN), which are benign nerve sheath tumors that are among the most debilitating complications of NF1. There are no standard treatment options for PN other than surgery, which is often difficult due to the extensive growth and invasion of surrounding tissues. Mammalian Target of Rapamcyin (mTOR) acts as a master switch of cellular catabolism and anabolism and controls protein translation, angiogenesis, cell motility, and proliferation. The NF1 tumor suppressor, neurofibromin, regulates the mTOR pathway activity. Sirolimus is a macrolide antibiotic that inhibits mTOR activity.
ProcedureWe conducted a 2-stratum phase II clinical trial. In stratum 2, we sought to determine whether the mTOR inhibitor sirolimus in subjects with NF1 results in objective radiographic responses in inoperable PNs in the absence of documented radiographic progression at trial entry.
ResultsNo subjects had better than stable disease by the end of six courses. However, the children's self-report responses on health-related quality of life questionnaires indicated a significant improvement in the mean scores of the Emotional and School domains from baseline to 6 months of sirolimus.
ConclusionsThis study efficiently documented that sirolimus does not cause shrinkage of non-progressive PNs, and thus should not be considered as a treatment option for these tumors. This study also supports the inclusion of patient-reported outcome measures in clinical trials to assess areas of benefit that are not addressed by the medical outcomes. Pediatr Blood Cancer 2014;61:982-986. (c) 2013 Wiley Periodicals, Inc.
C1 [Weiss, Brian; Perentesis, John] Cincinnati Childrens Hosp Med Ctr, Div Oncol, Cincinnati, OH 45229 USA.
[Widemann, Brigitte C.; Wolters, Pamela; Dombi, Eva] NCI, Dept Pediat Oncol, Bethesda, MD 20892 USA.
[Vinks, Alexander A.] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA.
[Cantor, Alan; Korf, Bruce] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA.
[Gutmann, David H.] Washington Univ, Dept Neurol, St Louis, MO USA.
[Schorry, Elizabeth] Cincinnati Childrens Hosp Med Ctr, Dept Genet, Cincinnati, OH 45229 USA.
[Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Fisher, Michael J.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
RP Weiss, B (reprint author), Div Hematol Oncol, MLC 7015,3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM brian.weiss@cchmc.org
FU Neurofibromatosis Clinical Trials Award [W81XWH-05-1-0615]
FX Grant sponsor: Neurofibromatosis Clinical Trials Award for FY2007; Grant
number: W81XWH-05-1-0615
NR 39
TC 16
Z9 17
U1 3
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUN
PY 2014
VL 61
IS 6
BP 982
EP 986
DI 10.1002/pbc.24873
PG 5
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA AE9IC
UT WOS:000334320100008
PM 24851266
ER
PT J
AU Lee, B
Lee, M
Lefevre, M
Kim, HR
AF Lee, Bonggi
Lee, Minsup
Lefevre, Michael
Kim, Hyeung-Rak
TI Anthocyanins Inhibit Lipogenesis During Adipocyte Differentiation of
3T3-L1 Preadipocytes
SO PLANT FOODS FOR HUMAN NUTRITION
LA English
DT Article
DE Anthocyanins; Lipogenesis; Adipocytes
ID FATTY-ACID SYNTHASE; ISOLATED RAT ADIPOCYTES; LIVER X-RECEPTORS;
GENE-EXPRESSION; MICE; INSULIN; CELLS; ADIPOGENESIS; PERSPECTIVES;
METABOLISM
AB Anthocyanins have been shown to suppress body weight and fat mass in animal studies. However, the effect of anthocyanins on the process of lipid accumulation during adipocyte differentiation is not fully understood and the lipogenic transcription factors regulated by anthocyanins have not been identified. We investigated the effects of anthocyanins on lipogenesis pathways during adipocyte differentiation in 3T3-L1 cells. Anthocyanins reduced triglyceride (TG) accumulation in a dose-dependent manner during adipocyte differentiation. Accumulation of TG was rapidly reversed by anthocyanin withdrawal. Anthocyanins markedly reduced gene and protein expression levels of lipogenic transcription factors such as liver X receptor alpha, sterol regulatory element-binding protein-1c, peroxisome proliferators-activated receptor-gamma, and CCAAT enhancer-binding protein-alpha. In addition, the target gene and protein expression of these lipogenic transcription factors such as fatty acid synthase, stearoyl-CoA desaturase-1, and acetyl-CoA carboxylase alpha were markedly suppressed by anthocyanins. Thus, anthocyanins suppress lipid accumulation in adipocytes due to broad inhibition of the transcription factors regulating lipogenesis. This may partially explain the mechanism by which anthocyanins exert their anti-obesity effect.
C1 [Lee, Bonggi; Lee, Minsup; Kim, Hyeung-Rak] Pukyong Natl Univ, Dept Food Sci & Nutr, Pusan 608737, South Korea.
[Lee, Bonggi] NICHHD, NIH, Bethesda, MD 20892 USA.
[Lefevre, Michael] Utah State Univ, Ctr Adv Nutr, Logan, UT 84322 USA.
RP Kim, HR (reprint author), Pukyong Natl Univ, Dept Food Sci & Nutr, 45 Yongso Ro, Pusan 608737, South Korea.
EM hrkim@pknu.ac.kr
RI Lefevre, Michael/B-5030-2014
OI Lefevre, Michael/0000-0002-2046-3593
FU Pukyong National University Research Abroad Fund [C-D-2013-0915]
FX This work was supported by Pukyong National University Research Abroad
Fund in 2013 (C-D-2013-0915).
NR 34
TC 6
Z9 7
U1 2
U2 25
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0921-9668
EI 1573-9104
J9 PLANT FOOD HUM NUTR
JI Plant Food Hum. Nutr.
PD JUN
PY 2014
VL 69
IS 2
BP 137
EP 141
DI 10.1007/s11130-014-0407-z
PG 5
WC Plant Sciences; Chemistry, Applied; Food Science & Technology; Nutrition
& Dietetics
SC Plant Sciences; Chemistry; Food Science & Technology; Nutrition &
Dietetics
GA AH8NC
UT WOS:000336393700008
PM 24682657
ER
PT J
AU Brotman, MA
Tseng, WL
Olsavsky, AK
Fromm, SJ
Muhrer, EJ
Rutenberg, JG
Deveney, CM
Adleman, NE
Zarate, CA
Pine, DS
Leibenluft, E
AF Brotman, M. A.
Tseng, W. -L.
Olsavsky, A. K.
Fromm, S. J.
Muhrer, E. J.
Rutenberg, J. G.
Deveney, C. M.
Adleman, N. E.
Zarate, C. A., Jr.
Pine, D. S.
Leibenluft, E.
TI Fronto-limbic-striatal dysfunction in pediatric and adult patients with
bipolar disorder: impact of face emotion and attentional demands
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Attention; bipolar disorder; face emotion; fronto-limbic-striatal
dysfunction; imaging; pediatric
ID ANTERIOR CINGULATE CORTEX; SEVERE MOOD DYSREGULATION; FACIAL AFFECT
RECOGNITION; DEPRESSION RATING-SCALE; AMYGDALA ACTIVATION; PREFRONTAL
CORTEX; QUANTITATIVE METAANALYSIS; FUNCTIONAL CONNECTIVITY; FMRI;
CHILDREN
AB Background Research in bipolar disorder (BD) implicates fronto-limbic-striatal dysfunction during face emotion processing but it is unknown how such dysfunction varies by task demands, face emotion and patient age.
Method During functional magnetic resonance imaging (fMRI), 181 participants, including 62 BD (36 children and 26 adults) and 119 healthy comparison (HC) subjects (57 children and 62 adults), engaged in constrained and unconstrained processing of emotional (angry, fearful, happy) and non-emotional (neutral) faces. During constrained processing, subjects answered questions focusing their attention on the face; this was processed either implicitly (nose width rating) or explicitly (hostility; subjective fear ratings). Unconstrained processing consisted of passive viewing.
Results Pediatric BD rated neutral faces as more hostile than did other groups. In BD patients, family-wise error (FWE)-corrected region of interest (ROI) analyses revealed dysfunction in the amygdala, inferior frontal gyrus (IFG), anterior cingulate cortex (ACC) and putamen. Patients with BD showed amygdala hyperactivation during explicit processing (hostility ratings) of fearful faces and passive viewing of angry and neutral faces but IFG hypoactivation during implicit processing of neutral and happy faces. In the ACC and striatum, the direction of dysfunction varied by task demand: BD demonstrated hyperactivation during unconstrained processing of angry or neutral faces but hypoactivation during constrained processing (implicit or explicit) of angry, neutral or happy faces.
Conclusions Findings suggest amygdala hyperactivation in BD while processing negatively valenced and neutral faces, regardless of attentional condition, and BD IFG hypoactivation during implicit processing. In the cognitive control circuit involving the ACC and putamen, BD neural dysfunction was sensitive to task demands.
C1 [Brotman, M. A.; Tseng, W. -L.; Fromm, S. J.; Muhrer, E. J.; Rutenberg, J. G.; Deveney, C. M.; Adleman, N. E.; Pine, D. S.; Leibenluft, E.] NIMH, Emot & Dev Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Olsavsky, A. K.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
[Zarate, C. A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Brotman, MA (reprint author), Bldg 10,Room B1D43C,10 Ctr Dr, Bethesda, MD 20892 USA.
EM brotmanm@mail.nih.gov
RI Brotman, Melissa/H-7409-2013
FU Intramural Research Program of the National Institute of Mental Health
(NIMH), National Institutes of Health (NIH)
FX Funding for this study was provided by the Intramural Research Program
of the National Institute of Mental Health (NIMH), National Institutes
of Health (NIH). We thank the staff of the Emotion and Development and
Experimental Therapeutics and Pathophysiology Branches at NIMH and the
patients and their parents for their participation.
NR 77
TC 8
Z9 8
U1 2
U2 16
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
EI 1469-8978
J9 PSYCHOL MED
JI Psychol. Med.
PD JUN
PY 2014
VL 44
IS 8
BP 1639
EP 1651
DI 10.1017/S003329171300202X
PG 13
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA AG6DG
UT WOS:000335508100010
PM 23930595
ER
PT J
AU Rhebergen, D
van der Steenstraten, IM
Sunderland, M
de Graaf, R
ten Have, M
Lamers, F
Penninx, BWJH
Andrews, G
AF Rhebergen, D.
van der Steenstraten, I. M.
Sunderland, M.
de Graaf, R.
ten Have, M.
Lamers, F.
Penninx, B. W. J. H.
Andrews, G.
TI An examination of generalized anxiety disorder and dysthymic disorder by
latent class analysis
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Dysthymia; generalized anxiety disorder; latent class analysis; nosology
ID INTERNATIONAL DIAGNOSTIC INTERVIEW; NATIONAL-COMORBIDITY-SURVEY;
DEPRESSIVE SYMPTOMATOLOGY IDS; WORLD-HEALTH-ORGANIZATION; COMMON
MENTAL-DISORDERS; PSYCHOMETRIC PROPERTIES; SURVEY REPLICATION; MAJOR
DEPRESSION; INVENTORY; CIDI
AB Background The nosological status of generalized anxiety disorder (GAD) versus dysthymic disorder (DD) has been questioned. The aim of this study was to examine qualitative differences within (co-morbid) GAD and DD symptomatology.
Method Latent class analysis was applied to anxious and depressive symptomatology of respondents from three population-based studies (2007 Australian National Survey of Mental Health and Wellbeing; National Comorbidity Survey Replication; and Netherlands Mental Health Survey and Incidence Study-2; together known as the Triple study) and respondents from a multi-site naturalistic cohort [Netherlands Study of Depression and Anxiety (NESDA)]. Sociodemographics and clinical characteristics of each class were examined.
Results A three-class (Triple study) and two-class (NESDA) model best fitted the data, reflecting mainly different levels of severity of symptoms. In the Triple study, no division into a predominantly GAD or DD co-morbidity subtype emerged. Likewise, in spite of the presence of pure GAD and DD cases in the NESDA sample, latent class analysis did not identify specific anxiety or depressive profiles in the NESDA study. Next, sociodemographics and clinical characteristics of each class were examined. Classes only differed in levels of severity.
Conclusions The absence of qualitative differences in anxious or depressive symptomatology in empirically derived classes questions the differentiation between GAD and DD.
C1 [Rhebergen, D.; van der Steenstraten, I. M.; Penninx, B. W. J. H.] VU Univ Med Ctr Amsterdam, Dept Psychiat, Amsterdam, Netherlands.
[Rhebergen, D.; van der Steenstraten, I. M.; Penninx, B. W. J. H.] VU Univ Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Rhebergen, D.; Penninx, B. W. J. H.] GGZ inGeest, Amsterdam, Netherlands.
[Sunderland, M.; Andrews, G.] Univ New S Wales, CRUfAD, Sydney, NSW, Australia.
[de Graaf, R.; ten Have, M.] Netherlands Inst Mental Hlth & Addict, Utrecht, Netherlands.
[Lamers, F.] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
RP Rhebergen, D (reprint author), VU Univ Med Ctr Amsterdam, Amsterdam, Netherlands.
EM d.rhebergen@ggzingeest.nl
OI Sunderland, Matthew/0000-0001-8452-364X
FU Australian Department of Health and Ageing; Ministry of Health, Welfare
and Sport; Geestkracht program of the Netherlands Organization for
Health Research and Development (ZonMw) [10-000-1002]; VU University
Medical Center; GGZ inGeest; Arkin; Leiden University Medical Center;
GGZ Rivierduinen; University Medical Center Groningen; Lentis; GGZ
Friesland; GGZ Drenthe; IQ Healthcare; Netherlands Institute for Health
Services Research (NIVEL); Netherlands Institute of Mental Health and
Addiction; Dr Catharine van Tussenbroek Fonds; National Health and
Medical Research Council (NHMRC) Capacity Building Grant [568940];
Netherlands Organization for Scientific Research (NWO)
FX We greatly acknowledge the National Comorbidity Survey Replication for
releasing a public use version of their dataset. The 2007 Australian
National Survey of Mental Health and Wellbeing was funded by the
Australian Department of Health and Ageing and conducted by the
Australian Bureau of Statistics. NEMESIS-2 is conducted by the
Netherlands Institute of Mental Health and Addiction (Trimbos Institute)
in Utrecht with financial support from the Ministry of Health, Welfare
and Sport. The infrastructure for the NESDA study (www.nesda.nl) is
funded through the Geestkracht program of the Netherlands Organization
for Health Research and Development (ZonMw, grant no. 10-000-1002) and
is supported by participating universities and mental health care
organizations [VU University Medical Center, GGZ inGeest, Arkin, Leiden
University Medical Center, GGZ Rivierduinen, University Medical Center
Groningen, Lentis, GGZ Friesland, GGZ Drenthe, IQ Healthcare,
Netherlands Institute for Health Services Research (NIVEL) and
Netherlands Institute of Mental Health and Addiction]. D. R. was
supported by a grant from the Dr Catharine van Tussenbroek Fonds. M. S.
was supported by a National Health and Medical Research Council (NHMRC)
Capacity Building Grant (no.568940). F. L. was supported by a Rubicon
Fellowship from the Netherlands Organization for Scientific Research
(NWO).
NR 46
TC 1
Z9 1
U1 4
U2 9
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
EI 1469-8978
J9 PSYCHOL MED
JI Psychol. Med.
PD JUN
PY 2014
VL 44
IS 8
BP 1701
EP 1712
DI 10.1017/S0033291713002225
PG 12
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA AG6DG
UT WOS:000335508100015
PM 24020863
ER
PT J
AU Dunbar-Jacob, J
McCloskey, DJ
Weglicki, LS
Grady, PA
AF Dunbar-Jacob, Jacqueline
McCloskey, Donna Jo
Weglicki, Linda S.
Grady, Patricia A.
TI The Contributions and Challenges of NINR Centers: Perspectives of
Directors
SO RESEARCH IN NURSING & HEALTH
LA English
DT Editorial Material
DE Nursing research; research productivity; research centers;
interprofessional research; research mentoring
ID TRANSLATIONAL SCIENCE
C1 [Dunbar-Jacob, Jacqueline] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA.
[McCloskey, Donna Jo; Weglicki, Linda S.; Grady, Patricia A.] NINR, NIH, Bethesda, MD 20892 USA.
RP Dunbar-Jacob, J (reprint author), Univ Pittsburgh, Sch Nursing, 3500 Victoria St,Room 350, Pittsburgh, PA 15261 USA.
EM dunbar@pitt.edu
NR 10
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0160-6891
EI 1098-240X
J9 RES NURS HEALTH
JI Res. Nurs. Health
PD JUN
PY 2014
VL 37
IS 3
BP 174
EP 181
DI 10.1002/nur.21598
PG 8
WC Nursing
SC Nursing
GA AH2PF
UT WOS:000335962700002
PM 24797436
ER
PT J
AU Bloodworth, RF
Ward, KD
Relyea, GE
Cashion, AK
AF Bloodworth, Robin F.
Ward, Kenneth D.
Relyea, George E.
Cashion, Ann K.
TI Food Availability as a Determinant of Weight Gain Among Renal Transplant
Recipients
SO RESEARCH IN NURSING & HEALTH
LA English
DT Article
DE food availability; obesity; BMI; renal transplant; post-transplant
weight gain
ID KIDNEY-TRANSPLANTATION; OBESITY; IMMUNOSUPPRESSION; ENVIRONMENTS;
THERAPY; RISK
AB Excessive weight gain is common after renal transplantation, but it is unknown whether environmental factors, such as food availability, contribute to this important clinical problem. We evaluated the effects of food availability (fast food restaurants, convenience stores, and grocery stores within 1, 2, and 3 mile buffers of transplant recipients' residences) on body mass index (BMI) change during the first year post-transplant. Participants (n=299) resided in Memphis, Tennessee. BMI increased by 1.42 units (p<.001) corresponding to an average weight gain of 9.25lbs (5.43%) during the first year post-transplant. The number of grocery stores within 1 mile of recipient's residence was associated with an increase in BMI (p<.05), but fast food restaurants and convenience stores were not significantly associated with BMI change. (c) 2014 Wiley Periodicals, Inc.
C1 [Bloodworth, Robin F.] Univ Maryland, Dept Hlth Serv Adm, College Pk, MD 20742 USA.
[Bloodworth, Robin F.] Univ Memphis, Sch Publ Hlth, Memphis, TN 38152 USA.
[Bloodworth, Robin F.] Univ Tennessee, Ctr Hlth Sci, Coll Nursing, Memphis, TN 38163 USA.
[Ward, Kenneth D.] Univ Memphis, Sch Publ Hlth, Div Social & Behav Sci, Memphis, TN 38152 USA.
[Relyea, George E.] Univ Memphis, Sch Publ Hlth, Dept Epidemiol & Biostat, Memphis, TN 38152 USA.
[Cashion, Ann K.] NINR, NIH, Bethesda, MD 20892 USA.
RP Bloodworth, RF (reprint author), Univ Maryland, Dept Hlth Serv Adm, 1222 Sch Publ Hlth Bldg, College Pk, MD 20742 USA.
EM rbloodwo@umd.edu
FU Intramural NIH HHS [Z99 NR999999]
NR 24
TC 5
Z9 5
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0160-6891
EI 1098-240X
J9 RES NURS HEALTH
JI Res. Nurs. Health
PD JUN
PY 2014
VL 37
IS 3
BP 253
EP 259
DI 10.1002/nur.21599
PG 7
WC Nursing
SC Nursing
GA AH2PF
UT WOS:000335962700011
PM 24805885
ER
PT J
AU Albert, PS
Shih, JH
AF Albert, Paul S.
Shih, Joanna H.
TI Modelling batched Gaussian longitudinal weight data in mice subject to
informative dropout
SO STATISTICAL METHODS IN MEDICAL RESEARCH
LA English
DT Article
DE Missing data; pattern mixture models; repeated measures; shared random
parameter models
ID TO-EVENT DATA; LIKELIHOOD APPROACH; SURVIVAL-DATA; LINEAR-MODEL; JOINT;
ALGORITHMS; TIMES
AB Modelling longitudinal data subject to informative dropout is an active area in statistical research. This article focuses on modelling such longitudinal data when the outcome at each follow-up time is collected in batches rather than individually collected. The problem occurred in a study that compared the weight of mice over time between a control and a treatment group, where animal weight was measured in batches of five animals per cage. We develop both a shared parameter and a pattern mixture modelling approach for accounting for potentially informative dropout due to an animal's death. Our methodology suggests that animals receiving the treatment have a lower weight in mid-life, and have a slower decline in weight in the later period of life. Our simulations suggest that both the shared random parameter and pattern mixture modelling approaches work well under a correctly specified model. However, the pattern mixture model is more robust against model misspecification than the shared random parameter model, but the shared random parameter model parameters have a more direct interpretation than those of the pattern mixture modelling approach.
C1 [Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
[Shih, Joanna H.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Albert, PS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
EM albertp@mail.nih.gov
FU NIH, Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX We thank two referees for their constructive comments which lead to a
substantially improved manuscript. We thank Dr John Mitchell and Dr John
Cook for collaborations which has led to the development of this
methodology. We also thank them for allowing us access to the data and
for reviewing the manuscript. This research was supported in part by the
Intramural Research Program of the NIH, Eunice Kennedy Shriver National
Institute of Child Health and Human Development. We thank the Center for
Information Technology, NIH, for providing access to the
high-performance computational capabilities of the Biowulf cluster
computer system.
NR 23
TC 0
Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0962-2802
EI 1477-0334
J9 STAT METHODS MED RES
JI Stat. Methods Med. Res.
PD JUN
PY 2014
VL 23
IS 3
BP 203
EP 217
DI 10.1177/0962280210397886
PG 15
WC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Statistics & Probability
SC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Mathematics
GA AH7SZ
UT WOS:000336335800001
PM 21300625
ER
PT J
AU Phipps, KM
Devlin, M
AF Phipps, Karl M.
Devlin, Mark
TI Dr. Mark Devlin
SO TRIBOLOGY & LUBRICATION TECHNOLOGY
LA English
DT Editorial Material
C1 [Devlin, Mark] Afton Chem Corp, Richmond, VA USA.
[Devlin, Mark] NIH, Bethesda, MD 20892 USA.
EM mark.devlin@aftonchemical.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SOC TRIBOLOGISTS & LUBRICATION ENGINEERS
PI PARK RIDGE
PA 840 BUSSE HIGHWAY, PARK RIDGE, IL 60068 USA
SN 1545-858X
J9 TRIBOL LUBR TECHNOL
JI Tribol. Lubr. Technol.
PD JUN
PY 2014
VL 70
IS 6
BP 20
EP 23
PG 4
WC Engineering, Mechanical
SC Engineering
GA AH8BY
UT WOS:000336360300006
ER
PT J
AU Pan, WL
Wong, JH
Fang, EF
Chan, YS
Ng, TB
Cheung, RCF
AF Pan, Wen Liang
Wong, Jack Ho
Fang, Evandro Fei
Chan, Yau Sang
Ng, Tzi Bun
Cheung, Randy Chi Fai
TI Preferential cytotoxicity of the type I ribosome inactivating protein
alpha-momorcharin on human nasopharyngeal carcinoma cells under normoxia
and hypoxia
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE alpha-Momorcharin; Unfolded protein response; Ribosome inactivating
protein; Nasopharyngeal carcinoma; Hypoxic tumors
ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-CELLS; INDUCIBLE FACTOR-1; CYCLIN D1;
ACTIVATION; SURVIVAL; CANCER; STRESS; RADIOTHERAPY; APOPTOSIS
AB All primary nasopharyngeal carcinoma (NPC) tumors contain hypoxic regions which are implicated in decreased local control and increased distant metastases, as well as resistance to chemotherapy in advanced NPC patients. One of the promising therapeutic approaches for NPC is to use drugs that can target hypoxic factors in tumors. In the present investigation, the type I ribosome inactivating protein alpha-momorcharin (alpha-MMC), isolated from seeds of the bitter gourd Momordica charantia, reduced cell viability and inhibited clonogenic formation of human NPC CNE2 and HONE1 cells under normoxia and cobalt chloride-induced hypoxia. By comparison, alpha-MMC exhibited only slight cytotoxicity on human nasopharyngeal epithelial NP69 cells under normoxia. Interestingly, alpha-MMC suppressed the expression levels of hypoxia-inducible factor 1-alpha (HIF1 alpha) and vascular endothelial growth factor (VEGF) in hypoxic NPC, as well as the growth of human umbilical vein endothelial cells. Further study disclosed that alpha-MMC targeted endoplasmic reticulum and down-regulated unfolded protein response (UPR) in NPC cells. Moreover, alpha-MMC induced apoptosis in NPC cells in a dose- and time-dependent manner. It initiated mitochondrial- and death receptor-mediated apoptotic signaling in CNE2 cells, but there was hardly any effect on HONE1 cells. In addition, alpha-MMC brought about G0/G1 phase cell cycle arrest in CNE2 cells and S phase arrest in HONE1 cells. Collectively, alpha-MMC preferentially exhibited inhibitory effect on normoxic and hypoxic NPC cells partly by blocking survival signaling (e.g. HIFI alpha, VEGF and UPR), and triggering apoptotic pathways mediated by mitochondria or death receptor. These observations indicate the potential utility of alpha-MMC for prophylaxis and therapy of NPC. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Pan, Wen Liang; Wong, Jack Ho; Chan, Yau Sang; Ng, Tzi Bun; Cheung, Randy Chi Fai] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
[Fang, Evandro Fei] NIA, NIH, Baltimore, MD 21224 USA.
RP Ng, TB (reprint author), Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
EM tzibunng@cuhk.edu.hk
FU Intramural Research Program of the NIH, National Institute on Aging
[Z01-AG000723-02]
FX EFF is supported by the Intramural Research Program (Grant number:
Z01-AG000723-02) of the NIH, National Institute on Aging.
NR 53
TC 11
Z9 13
U1 1
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
EI 1873-2968
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD JUN 1
PY 2014
VL 89
IS 3
BP 329
EP 339
DI 10.1016/j.bcp.2014.03.004
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AH3GZ
UT WOS:000336013000004
PM 24637239
ER
PT J
AU Spruiell, K
Jones, DZ
Cullen, JM
Awumey, EM
Gonzalez, FJ
Gyamfi, MA
AF Spruiell, Krisstonia
Jones, Dominique Z.
Cullen, John M.
Awumey, Emmanuel M.
Gonzalez, Frank J.
Gyamfi, Maxwell A.
TI Role of human pregnane X receptor in high fat diet-induced obesity in
pre-menopausal female mice
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Obesity; High-fat diet; Pregnane X receptor; Nuclear receptors; Type 2
diabetes; Females
ID UNCOUPLING PROTEIN GENE; BROWN ADIPOSE-TISSUE; ESTROGEN-RECEPTOR;
INSULIN-RESISTANCE; BODY-FAT; NUCLEAR RECEPTOR; GLUCOSE-HOMEOSTASIS;
DIABETES-MELLITUS; CROSS-TALK; ANDROSTANE RECEPTOR
AB Obesity is a complex metabolic disorder that is more prevalent among women. Until now, the only relevant rodent models of diet-induced obesity were via the use of ovariectomized ("postmenopausal") females. However, recent reports suggest that the xenobiotic nuclear receptor pregnane X receptor (PXR) may contribute to obesity. Therefore, we compared the roles of mouse and human PXRs in diet-induced obesity between wild type (WT) and PXR-humanized (hPXR) transgenic female mice fed either control or high-fat diets (HFD) for 16 weeks. HFD-fed hPXR mice gained weight more rapidly than controls, exhibited hyperinsulinemia, and impaired glucose tolerance. Fundamental differences were observed between control-fed hPXR and WT females: hPXR mice possessed reduced estrogen receptor alpha (ER alpha) but enhanced uncoupling protein 1 (UCP1) protein expression in white adipose tissue (WAT); increased protein expression of the hepatic cytochrome P450 3A11 (CYP3A11) and key gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, and increased total cholesterol. Interestingly, HFD ingestion induced both UCP1 and glucokinase protein expression in WT mice, but inhibited these enzymes in hPXR females. Unlike WT mice, CYP3A1 l protein, serum 17 beta-estradiol levels, and WAT ERa expression were unaffected by HFD in hPXR females. Together, these studies indicate that the hPXR gene promotes obesity and metabolic syndrome by dysregulating lipid and glucose homeostasis while inhibiting UCP1 expression. Furthermore, our studies indicate that the human PXR suppresses the protective role of estrogen in metabolic disorders. Finally, these data identify PXR-humanized mice as a promising in vivo research model for studying obesity and diabetes in women. Published by Elsevier Inc.
C1 [Spruiell, Krisstonia; Jones, Dominique Z.; Awumey, Emmanuel M.; Gyamfi, Maxwell A.] N Carolina Cent Univ, Julius L Chambers Biomed Biotechnol Res Inst, Cardiovasc & Metab Dis Res Program, Durham, NC 27707 USA.
[Spruiell, Krisstonia; Awumey, Emmanuel M.] N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA.
[Cullen, John M.] N Carolina State Univ, North Carolina Coll Vet Med, Raleigh, NC 27607 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Gyamfi, MA (reprint author), N Carolina Cent Univ, Julius L Chambers Biomed Biotechnol Res Inst, Cardiovasc & Metab Dis Res Program, 700 George St, Durham, NC 27707 USA.
EM mgyamfi@nccu.edu
FU National Institutes of Health (NIH) [U54 AA019765, SC1 HL099139, P20
MD000175, RO1 HL064761, R25HL059868]; National Cancer Institute
Intramural Research Program, NIH
FX The authors are grateful to Drs. Thomas Pazdernik and Susan T. Yeyeodu
for critical reading of the manuscript. This work was supported by the
National Institutes of Health (NIH) grants U54 AA019765, SC1 HL099139,
P20 MD000175, RO1 HL064761, and R25HL059868 and the National Cancer
Institute Intramural Research Program, NIH.
NR 101
TC 9
Z9 10
U1 2
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
EI 1873-2968
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD JUN 1
PY 2014
VL 89
IS 3
BP 399
EP 412
DI 10.1016/j.bcp.2014.03.019
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA AH3GZ
UT WOS:000336013000010
PM 24721462
ER
PT J
AU Lissek, S
Kaczkurkin, AN
Rabin, S
Geraci, M
Pine, DS
Grillon, C
AF Lissek, Shmuel
Kaczkurkin, Antonia N.
Rabin, Stephanie
Geraci, Marilla
Pine, Daniel S.
Grillon, Christian
TI Generalized Anxiety Disorder Is Associated With Overgeneralization of
Classically Conditioned Fear
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the Association-for-Behavioral-and-Cognitive-Therapies
CY NOV, 2012
CL National Harbor, MD
SP Assoc Behav & Cognit Therapies
DE Fear conditioning; fear-potentiated startle; generalized; anxiety
disorder; interpretation bias; pathophysiology; stimulus generalization
ID STIMULUS-GENERALIZATION; DISCRIMINATION; CORTEX; MODEL; RATS;
VALIDATION; LESIONS
AB Background: Meta-analytic results of fear-conditioning studies in the anxiety disorders implicate generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of anxiety pathology. Due to the absence of conditioning studies assessing generalization in generalized anxiety disorder (GAD), results of this meta-analysis do not reveal whether such generalization abnormalities also apply to GAD. The current study fills this gap by behaviorally and psychophysiologically assessing levels of conditioned fear generalization across adults with and without GAD.
Methods: Twenty-two patients with a DSM-IV-Text Revision diagnosis of GAD and 26 healthy comparison subjects were recruited and tested. The employed generalization paradigm consisted of quasi-randomly presented rings of gradually increasing size, with extreme sizes serving as conditioned danger cues (CS+) and conditioned safety cues. The rings of intermediary size served as generalization stimuli, creating a continuum of similarity between CS+ and conditioned safety cues across which to assess response slopes, referred to as generalization gradients. Primary outcome variables included slopes for fear-potentiated startle (electromyography) and self-reported risk ratings.
Results: Behavioral and psychophysiological findings demonstrated overgeneralization of conditioned fear among patients with GAD. Specifically, generalization gradients were abnormally shallow among GAD patients, reflecting less degradation of the conditioned fear response as the presented stimulus differentiated from the CS+.
Conclusions: Overgeneralization of conditioned fear to safe encounters resembling feared situations may contribute importantly to the psychopathology of GAD by proliferating anxiety cues in the individual's environment that are then capable of evoking and maintaining anxiety and worry associated with GAD.
C1 [Lissek, Shmuel; Geraci, Marilla; Pine, Daniel S.; Grillon, Christian] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Lissek, Shmuel; Kaczkurkin, Antonia N.] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
[Rabin, Stephanie] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA.
RP Lissek, S (reprint author), Univ Minnesota, Dept Psychol, Elliott Hall,75 East River Rd, Minneapolis, MN 55455 USA.
EM smlissek@umn.edu
OI Rabin, Stephanie/0000-0002-8282-0867
FU Intramural NIH HHS; NIMH NIH HHS [K99 MH080130, R00 MH080130]
NR 23
TC 56
Z9 59
U1 8
U2 28
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUN 1
PY 2014
VL 75
IS 11
BP 909
EP 915
DI 10.1016/j.biopsych.2013.07.025
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA AH1SX
UT WOS:000335902400014
PM 24001473
ER
PT J
AU Thompson, PM
Stein, JL
Medland, SE
Hibar, DP
Vasquez, AA
Renteria, ME
Toro, R
Jahanshad, N
Schumann, G
Franke, B
Wright, MJ
Martin, NG
Agartz, I
Alda, M
Alhusaini, S
Almasy, L
Almeida, J
Alpert, K
Andreasen, NC
Andreassen, OA
Apostolova, LG
Appel, K
Armstrong, NJ
Aribisala, B
Bastin, ME
Bauer, M
Bearden, CE
Bergmann, O
Binder, EB
Blangero, J
Bockholt, HJ
Boen, E
Bois, C
Boomsma, DI
Booth, T
Bowman, IJ
Bralten, J
Brouwer, RM
Brunner, HG
Brohawn, DG
Buckner, RL
Buitelaar, J
Bulayeva, K
Bustillo, JR
Calhoun, VD
Cannon, DM
Cantor, RM
Carless, MA
Caseras, X
Cavalleri, GL
Chakravarty, MM
Chang, KD
Ching, CRK
Christoforou, A
Cichon, S
Clark, VP
Conrod, P
Coppola, G
Crespo-Facorro, B
Curran, JE
Czisch, M
Deary, IJ
de Geus, EJC
den Braber, A
Delvecchio, G
Depondt, C
de Haan, L
de Zubicaray, GI
Dima, D
Dimitrova, R
Djurovic, S
Dong, HW
Donohoe, G
Duggirala, R
Dyer, TD
Ehrlich, S
Ekman, CJ
Elvsashagen, T
Emsell, L
Erk, S
Espeseth, T
Fagerness, J
Fears, S
Fedko, I
Fernandez, G
Fisher, SE
Foroud, T
Fox, PT
Francks, C
Frangou, S
Frey, EM
Frodl, T
Frouin, V
Garavan, H
Giddaluru, S
Glahn, DC
Godlewska, B
Goldstein, RZ
Gollub, RL
Grabe, HJ
Grimm, O
Gruber, O
Guadalupe, T
Gur, RE
Gur, RC
Goring, H
Hagenaars, S
Hajek, T
Hall, GB
Hall, J
Hardy, J
Hartman, CA
Hass, J
Hatton, SN
Haukvik, UK
Hegenscheid, K
Heinz, A
Hickie, IB
Ho, BC
Hoehn, D
Hoekstra, PJ
Hollinshead, M
Holmes, AJ
Homuth, G
Hoogman, M
Hong, LE
Hosten, N
Hottenga, JJ
Pol, HEH
Hwang, KS
Jack, CR
Jenkinson, M
Johnston, C
Jonsson, E
Kahn, R
Kasperaviciute, D
Kelly, S
Kim, S
Kochunov, P
Koenders, L
Kramer, B
Kwok, JBJ
Lagopoulos, J
Laje, G
Landen, M
Landman, BA
Lauriello, J
Lawrie, SM
Lee, PH
Le Hellard, S
Lemaitre, H
Leonardo, CD
Li, CS
Liberg, B
Liewald, DC
Liu, XM
Lopez, LM
Loth, E
Lourdusamy, A
Luciano, M
Macciardi, F
Machielsen, MWJ
MacQueen, GM
Malt, UF
Mandl, R
Manoach, DS
Martinot, JL
Matarin, M
Mather, KA
Mattheisen, M
Mattingsdal, M
Meyer-Lindenberg, A
McDonald, C
McIntosh, AM
McMahon, FJ
McMahon, KL
Meisenzahl, E
Melle, I
Milaneschi, Y
Mohnke, S
Montgomery, GW
Morris, DW
Moses, EK
Mueller, BA
Munoz Maniega, S
Muhleisen, T
Muller-Myhsok, B
Mwangi, B
Nauck, M
Nho, K
Nichols, TE
Nilsson, LG
Nugent, AC
Nyberg, L
Olvera, RL
Oosterlaan, J
Ophoff, RA
Pandolfo, M
Papalampropoulou-Tsiridou, M
Papmeyer, M
Paus, T
Pausova, Z
Pearlson, GD
Penninx, BW
Peterson, CP
Pfennig, A
Phillips, M
Pike, GB
Poline, JB
Potkin, SG
Putz, B
Ramasamy, A
Rasmussen, J
Rietschel, M
Rijpkema, M
Risacher, SL
Roffman, JL
Roiz-Santianez, R
Romanczuk-Seiferth, N
Rose, EJ
Royle, NA
Rujescu, D
Ryten, M
Sachdev, PS
Salami, A
Satterthwaite, TD
Savitz, J
Saykin, AJ
Scanlon, C
Schmaal, L
Schnack, HG
Schork, AJ
Schulz, SC
Schur, R
Seidman, L
Shen, L
Shoemaker, JM
Simmons, A
Sisodiya, SM
Smith, C
Smoller, JW
Soares, JC
Sponheim, SR
Sprooten, E
Starr, JM
Steen, VM
Strakowski, S
Strike, L
Sussmann, J
Samann, PG
Teumer, A
Toga, AW
Tordesillas-Gutierrez, D
Trabzuni, D
Trost, S
Turner, J
Van den Heuvel, M
Van der Wee, NJ
van Eijk, K
van Erp, TGM
van Haren, NEM
Van 't Ent, D
van Tol, MJ
Hernandez, MCV
Veltman, DJ
Versace, A
Volzke, H
Walker, R
Walter, H
Wang, L
Wardlaw, JM
Weale, ME
Weiner, MW
Wen, W
Westlye, LT
Whalley, HC
Whelan, CD
White, T
Winkler, AM
Wittfeld, K
Woldehawariat, G
Wolf, C
Zilles, D
Zwiers, MP
Thalamuthu, A
Schofield, PR
Freimer, NB
Lawrence, NS
Drevets, W
AF Thompson, Paul M.
Stein, Jason L.
Medland, Sarah E.
Hibar, Derrek P.
Vasquez, Alejandro Arias
Renteria, Miguel E.
Toro, Roberto
Jahanshad, Neda
Schumann, Gunter
Franke, Barbara
Wright, Margaret J.
Martin, Nicholas G.
Agartz, Ingrid
Alda, Martin
Alhusaini, Saud
Almasy, Laura
Almeida, Jorge
Alpert, Kathryn
Andreasen, Nancy C.
Andreassen, Ole A.
Apostolova, Liana G.
Appel, Katja
Armstrong, Nicola J.
Aribisala, Benjamin
Bastin, Mark E.
Bauer, Michael
Bearden, Carrie E.
Bergmann, Orjan
Binder, Elisabeth B.
Blangero, John
Bockholt, Henry J.
Boen, Erlend
Bois, Catherine
Boomsma, Dorret I.
Booth, Tom
Bowman, Ian J.
Bralten, Janita
Brouwer, Rachel M.
Brunner, Han G.
Brohawn, David G.
Buckner, Randy L.
Buitelaar, Jan
Bulayeva, Kazima
Bustillo, Juan R.
Calhoun, Vince D.
Cannon, Dara M.
Cantor, Rita M.
Carless, Melanie A.
Caseras, Xavier
Cavalleri, Gianpiero L.
Chakravarty, M. Mallar
Chang, Kiki D.
Ching, Christopher R. K.
Christoforou, Andrea
Cichon, Sven
Clark, Vincent P.
Conrod, Patricia
Coppola, Giovanni
Crespo-Facorro, Benedicto
Curran, Joanne E.
Czisch, Michael
Deary, Ian J.
de Geus, Eco J. C.
den Braber, Anouk
Delvecchio, Giuseppe
Depondt, Chantal
de Haan, Lieuwe
de Zubicaray, Greig I.
Dima, Danai
Dimitrova, Rali
Djurovic, Srdjan
Dong, Hongwei
Donohoe, Gary
Duggirala, Ravindranath
Dyer, Thomas D.
Ehrlich, Stefan
Ekman, Carl Johan
Elvsashagen, Torbjorn
Emsell, Louise
Erk, Susanne
Espeseth, Thomas
Fagerness, Jesen
Fears, Scott
Fedko, Iryna
Fernandez, Guillen
Fisher, Simon E.
Foroud, Tatiana
Fox, Peter T.
Francks, Clyde
Frangou, Sophia
Frey, Eva Maria
Frodl, Thomas
Frouin, Vincent
Garavan, Hugh
Giddaluru, Sudheer
Glahn, David C.
Godlewska, Beata
Goldstein, Rita Z.
Gollub, Randy L.
Grabe, Hans J.
Grimm, Oliver
Gruber, Oliver
Guadalupe, Tulio
Gur, Raquel E.
Gur, Ruben C.
Goering, Harald H. H.
Hagenaars, Saskia
Hajek, Tomas
Hall, Geoffrey B.
Hall, Jeremy
Hardy, John
Hartman, Catharina A.
Hass, Johanna
Hatton, Sean N.
Haukvik, Unn K.
Hegenscheid, Katrin
Heinz, Andreas
Hickie, Ian B.
Ho, Beng-Choon
Hoehn, David
Hoekstra, Pieter J.
Hollinshead, Marisa
Holmes, Avram J.
Homuth, Georg
Hoogman, Martine
Hong, L. Elliot
Hosten, Norbert
Hottenga, Jouke-Jan
Pol, Hilleke E. Hulshoff
Hwang, Kristy S.
Jack, Clifford R., Jr.
Jenkinson, Mark
Johnston, Caroline
Joensson, Erik G.
Kahn, Rene S.
Kasperaviciute, Dalia
Kelly, Sinead
Kim, Sungeun
Kochunov, Peter
Koenders, Laura
Kraemer, Bernd
Kwok, John B. J.
Lagopoulos, Jim
Laje, Gonzalo
Landen, Mikael
Landman, Bennett A.
Lauriello, John
Lawrie, Stephen M.
Lee, Phil H.
Le Hellard, Stephanie
Lemaitre, Herve
Leonardo, Cassandra D.
Li, Chiang-shan
Liberg, Benny
Liewald, David C.
Liu, Xinmin
Lopez, Lorna M.
Loth, Eva
Lourdusamy, Anbarasu
Luciano, Michelle
Macciardi, Fabio
Machielsen, Marise W. J.
MacQueen, Glenda M.
Malt, Ulrik F.
Mandl, Rene
Manoach, Dara S.
Martinot, Jean-Luc
Matarin, Mar
Mather, Karen A.
Mattheisen, Manuel
Mattingsdal, Morten
Meyer-Lindenberg, Andreas
McDonald, Colm
McIntosh, Andrew M.
McMahon, Francis J.
McMahon, Katie L.
Meisenzahl, Eva
Melle, Ingrid
Milaneschi, Yuri
Mohnke, Sebastian
Montgomery, Grant W.
Morris, Derek W.
Moses, Eric K.
Mueller, Bryon A.
Munoz Maniega, Susana
Muehleisen, Thomas W.
Mueller-Myhsok, Bertram
Mwangi, Benson
Nauck, Matthias
Nho, Kwangsik
Nichols, Thomas E.
Nilsson, Lars-Goeran
Nugent, Allison C.
Nyberg, Lars
Olvera, Rene L.
Oosterlaan, Jaap
Ophoff, Roel A.
Pandolfo, Massimo
Papalampropoulou-Tsiridou, Melina
Papmeyer, Martina
Paus, Tomas
Pausova, Zdenka
Pearlson, Godfrey D.
Penninx, Brenda W.
Peterson, Charles P.
Pfennig, Andrea
Phillips, Mary
Pike, G. Bruce
Poline, Jean-Baptiste
Potkin, Steven G.
Puetz, Benno
Ramasamy, Adaikalavan
Rasmussen, Jerod
Rietschel, Marcella
Rijpkema, Mark
Risacher, Shannon L.
Roffman, Joshua L.
Roiz-Santianez, Roberto
Romanczuk-Seiferth, Nina
Rose, Emma J.
Royle, Natalie A.
Rujescu, Dan
Ryten, Mina
Sachdev, Perminder S.
Salami, Alireza
Satterthwaite, Theodore D.
Savitz, Jonathan
Saykin, Andrew J.
Scanlon, Cathy
Schmaal, Lianne
Schnack, Hugo G.
Schork, Andrew J.
Schulz, S. Charles
Schuer, Remmelt
Seidman, Larry
Shen, Li
Shoemaker, Jody M.
Simmons, Andrew
Sisodiya, Sanjay M.
Smith, Colin
Smoller, Jordan W.
Soares, Jair C.
Sponheim, Scott R.
Sprooten, Emma
Starr, John M.
Steen, Vidar M.
Strakowski, Stephen
Strike, Lachlan
Sussmann, Jessika
Saemann, Philipp G.
Teumer, Alexander
Toga, Arthur W.
Tordesillas-Gutierrez, Diana
Trabzuni, Daniah
Trost, Sarah
Turner, Jessica
Van den Heuvel, Martijn
van der Wee, Nic J.
van Eijk, Kristel
van Erp, Theo G. M.
van Haren, Neeltje E. M.
van 't Ent, Dennis
van Tol, Marie-Jose
Hernandez, Maria C. Valdes
Veltman, Dick J.
Versace, Amelia
Voelzke, Henry
Walker, Robert
Walter, Henrik
Wang, Lei
Wardlaw, Joanna M.
Weale, Michael E.
Weiner, Michael W.
Wen, Wei
Westlye, Lars T.
Whalley, Heather C.
Whelan, Christopher D.
White, Tonya
Winkler, Anderson M.
Wittfeld, Katharina
Woldehawariat, Girma
Wolf, Christiane
Zilles, David
Zwiers, Marcel P.
Thalamuthu, Anbupalam
Schofield, Peter R.
Freimer, Nelson B.
Lawrence, Natalia S.
Drevets, Wayne
CA Alzheimer's Dis Neuroimaging
EPIGEN Consortium
IMAGEN Consortium
Saguenay Youth Study SYS Grp
TI The ENIGMA Consortium: large-scale collaborative analyses of
neuroimaging and genetic data
SO BRAIN IMAGING AND BEHAVIOR
LA English
DT Article
DE Genetics; MRI; GWAS; Consortium; Meta-analysis; Multi-site
ID GENOME-WIDE ASSOCIATION; CORTICAL SURFACE-AREA; WHITE-MATTER
MICROSTRUCTURE; MULTIVARIATE PARALLEL ICA; TENSOR-BASED MORPHOMETRY;
QUANTITATIVE TRAIT LOCI; VOXEL-BASED MORPHOMETRY; HUMAN BRAIN STRUCTURE;
DISEASE RISK VARIANT; BODY-MASS INDEX
AB The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
C1 [Thompson, Paul M.; Hibar, Derrek P.; Jahanshad, Neda; Bowman, Ian J.; Ching, Christopher R. K.; Dong, Hongwei; Leonardo, Cassandra D.; Toga, Arthur W.] Univ So Calif, Imaging Genet Ctr, Inst Neuroimaging & Informat, Keck Sch Med, Los Angeles, CA 90033 USA.
[Montgomery, Grant W.; Strike, Lachlan] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Lee, Phil H.; Smoller, Jordan W.] Broad Inst Harvard & MIT, Boston, MA USA.
[Vasquez, Alejandro Arias; Franke, Barbara; Bralten, Janita; Brunner, Han G.; Hoogman, Martine] Radboud Univ Nijmegen Med Ctr, Dept Human Genet, Nijmegen, Netherlands.
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[Toro, Roberto] Inst Pasteur, Human Genet & Cognit Funct, Paris, France.
[Toro, Roberto] Inst Pasteur, CNRS URA Genes Synapses & Cognit 2182, Paris, France.
[Toro, Roberto] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.
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[Glahn, David C.; Li, Chiang-shan; Pearlson, Godfrey D.; Winkler, Anderson M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Appel, Katja; Grabe, Hans J.] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany.
[Andreassen, Ole A.; Christoforou, Andrea; Djurovic, Srdjan; Espeseth, Thomas; Giddaluru, Sudheer; Haukvik, Unn K.; Le Hellard, Stephanie; Mattingsdal, Morten; Melle, Ingrid; Steen, Vidar M.; Westlye, Lars T.] Univ Oslo, NORMENT, KG Jebsen Ctr Psychosis Res, Oslo Univ Hosp, Oslo, Norway.
[Andreassen, Ole A.; Christoforou, Andrea; Djurovic, Srdjan; Espeseth, Thomas; Giddaluru, Sudheer; Haukvik, Unn K.; Le Hellard, Stephanie; Mattingsdal, Morten; Melle, Ingrid; Steen, Vidar M.; Westlye, Lars T.] Univ Oslo, Inst Clin Med, Oslo, Norway.
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[Aribisala, Benjamin; Munoz Maniega, Susana; Wardlaw, Joanna M.] Scottish Imaging Network, St Andrews, Fife, Scotland.
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[Binder, Elisabeth B.; Czisch, Michael; Hoehn, David; Mueller-Myhsok, Bertram; Puetz, Benno; Saemann, Philipp G.; Wolf, Christiane] Max Planck Inst Psychiat, D-80804 Munich, Germany.
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[Giddaluru, Sudheer] Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, N-5021 Bergen, Norway.
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[Cichon, Sven; Muehleisen, Thomas W.] Forschungszentrum Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany.
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RP Thompson, PM (reprint author), Univ So Calif, Imaging Genet Ctr, Inst Neuroimaging & Informat, Keck Sch Med, 2001 N Soto St, Los Angeles, CA 90033 USA.
EM pthomp@usc.edu; wdrevets@its.jnj.com
RI Winkler, Anderson/P-7773-2016; Luciano, Michelle/F-7277-2010;
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Greig/B-1763-2008; Walter, Henrik/O-2612-2013; Bralten,
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Jessica/H-7282-2015; Rijpkema, Mark/D-1974-2010; Zwiers,
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Hoekstra, Pieter/O-4396-2014; Savitz, Jonathan/C-3088-2009; Fox,
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Sarah/C-7630-2013; Jack, Clifford/F-2508-2010; Laje,
Gonzalo/L-2654-2014; Hardy, John/C-2451-2009; McDonald,
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OI Winkler, Anderson/0000-0002-4169-9781; Luciano,
Michelle/0000-0003-0935-7682; Meyer-Lindenberg,
Andreas/0000-0001-5619-1123; Clark, Vincent/0000-0002-9151-2102;
Almeida, Jorge/0000-0002-1213-1986; Bulayeva,
Kazima/0000-0003-4830-5383; Lemaitre, Herve/0000-0002-5952-076X; Toro,
Roberto/0000-0002-6671-858X; van den Heuvel,
Martijn/0000-0003-1570-1195; Romanczuk-Seiferth,
Nina/0000-0002-6931-269X; Whelan, Christopher/0000-0003-0308-5583;
Montgomery, Grant/0000-0002-4140-8139; Mattheisen,
Manuel/0000-0002-8442-493X; Wright, Margaret/0000-0001-7133-4970; Arias
Vasquez, Alejandro/0000-0002-4786-0169; McMahon,
Katie/0000-0002-6357-615X; Macciardi, Fabio/0000-0003-0537-4266; Li,
Chiang-Shan/0000-0002-9393-1212; Matarin, Mar/0000-0002-4717-5735;
Melle, Ingrid /0000-0002-9783-548X; Karen, Mather/0000-0003-4143-8941;
Putz, Benno/0000-0002-2208-209X; Nyberg, Lars/0000-0002-3367-1746;
Weale, Michael/0000-0003-4593-1186; de Zubicaray,
Greig/0000-0003-4506-0579; Hoogman, Martine/0000-0002-1261-7628;
Roiz-Santianez, Roberto/0000-0002-5176-2983; Tordesillas-Gutierrez,
Diana/0000-0003-1458-3932; Turner, Jessica/0000-0003-0076-8434;
Rijpkema, Mark/0000-0002-8495-4703; Zwiers, Marcel/0000-0001-5483-2935;
Alda, Martin/0000-0001-9544-3944; Rose, Emma/0000-0001-5365-4794;
Savitz, Jonathan/0000-0001-8143-182X; Fox, Peter/0000-0002-0465-2028;
Fisher, Simon/0000-0002-3132-1996; Ho, Beng-Choon/0000-0003-3976-1555;
Franke, Barbara/0000-0003-4375-6572; Ramasamy,
Adaikalavan/0000-0002-7598-2892; Medland, Sarah/0000-0003-1382-380X;
Jack, Clifford/0000-0001-7916-622X; Laje, Gonzalo/0000-0003-2763-3329;
Dima, Danai/0000-0002-2598-0952; Hulshoff Pol,
Hilleke/0000-0002-2038-5281; Munoz Maniega, Susana/0000-0001-5185-6384;
Fernandez, Guillen/0000-0002-5522-0604; Simmons,
Andrew/0000-0003-2306-5811; Pike, Bruce/0000-0001-8924-683X; Delvecchio,
Giuseppe/0000-0003-4750-1980; Jenkinson, Mark/0000-0001-6043-0166;
Gollub, Randy L./0000-0002-9434-4044; McMahon,
Francis/0000-0002-9469-305X; Cannon, Dara/0000-0001-7378-3411; Agartz,
Ingrid/0000-0002-9839-5391; Kwok, John/0000-0001-9574-6195; Lourdusamy,
Anbarasu/0000-0002-1978-6301; Morris, Derek/0000-0002-3413-570X;
Andreassen, Ole A./0000-0002-4461-3568; Martin,
Nicholas/0000-0003-4069-8020; McIntosh, Andrew/0000-0002-0198-4588;
Cavalleri, Gianpiero/0000-0002-9802-0506; Nugent,
Allison/0000-0003-2569-2480; Lawrence, Natalia/0000-0003-1969-6637;
Donohoe, Gary/0000-0003-3037-7426; Sachdev,
Perminder/0000-0002-9595-3220; Mwangi, Benson/0000-0002-1717-4395; Shen,
Li/0000-0002-5443-0503; Schur, Remmelt/0000-0002-2840-2592; Hatton,
Sean/0000-0002-9149-8726; Westlye, Lars T./0000-0001-8644-956X; de Geus,
Eco/0000-0001-6022-2666; Emsell, Louise/0000-0003-0011-4158; Potkin,
Steven/0000-0003-1028-1013; Trabzuni, Daniah/0000-0003-4826-9570; Stein,
Jason/0000-0003-4829-0513; Frodl, Thomas/0000-0002-8113-6959; Caseras,
Xavier/0000-0002-8490-6891; Jonsson, Erik/0000-0001-8368-6332
FU Biotechnology and Biological Sciences Research Council [BB/F019394/1];
Medical Research Council [G0600429, G0700704, G0701120, G0802462,
G0901254, G1001245, MR/J006742/1, MR/K01417X/1, MR/K026992/1,
MR/L010305/1, MR/L016400/1]; NCATS NIH HHS [UL1 TR001108]; NIA NIH HHS
[P50 AG005134, P30 AG010133, R01 AG019771, R01 AG040770, U01 AG024904,
U19 AG010483, U24 AG021886]; NIBIB NIH HHS [P41 EB015922, R01 EB005846,
R01 EB015611, U54 EB020403]; NIMH NIH HHS [K01 MH099232, K99 MH101367];
NLM NIH HHS [K99 LM011384, R00 LM011384, R01 LM011360]; Parkinson's UK
[G-0907]; Wellcome Trust [100309, 104036]
NR 195
TC 84
Z9 85
U1 10
U2 83
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1931-7557
EI 1931-7565
J9 BRAIN IMAGING BEHAV
JI Brain Imaging Behav.
PD JUN
PY 2014
VL 8
IS 2
SI SI
BP 153
EP 182
DI 10.1007/s11682-013-9269-5
PG 30
WC Neuroimaging
SC Neurosciences & Neurology
GA AG9UP
UT WOS:000335765700003
PM 24399358
ER
PT J
AU Kutsenko, A
de Gonzalez, AB
Curtis, RE
Rajaraman, P
AF Kutsenko, Alina
de Gonzalez, Amy Berrington
Curtis, Rochelle E.
Rajaraman, Preetha
TI Risk of second benign brain tumors among cancer survivors in the
surveillance, epidemiology, and end results program
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Meningioma; Radiotherapy; SEER; Brain neoplasm; Second primary neoplasm
ID CENTRAL-NERVOUS-SYSTEM; ACUTE LYMPHOBLASTIC-LEUKEMIA; LONG-TERM
SURVIVORS; CHILDHOOD-CANCER; MALIGNANT NEOPLASMS; GENETIC-STRUCTURE;
UNITED-STATES; FOLLOW-UP; MENINGIOMA; ASSOCIATION
AB To assess risk of developing a second benign brain tumor in a nationwide population of cancer survivors.
We evaluated the risk of developing second benign brain tumors among 2,038,074 1-year minimum cancer survivors compared to expected risk in the general population between 1973 and 2007 in nine population-based cancer registries in the NCI's surveillance, epidemiology, and end results program. Excess risk was estimated using standardized incidence ratios (SIRs) for all second benign brain tumors and specifically for second meningiomas and acoustic neuromas diagnosed during 2004-2008.
1,025 patients were diagnosed with a second primary benign brain tumor, of which second meningiomas composed the majority (n = 745). Statistically significant increases in risk of developing a second meningioma compared to the general population were observed following first cancers of the brain [SIR = 19.82; 95 % confidence interval (CI) 13.88-27.44], other central nervous system (CNS) (SIR = 9.54; CI 3.10-22.27), thyroid (SIR = 2.05; CI 1.47-2.79), prostate (SIR = 1.21; CI 1.02-1.43), and acute lymphocytic leukemia (ALL) (SIR = 42.4; CI 23.18-71.13). Statistically significant decreases in risk were observed following first cancers of the uterine corpus (SIR = 0.63; CI 0.42-0.91) and colon (SIR = 0.56; CI 0.37-0.82). Differences in risk between patients initially treated with radiotherapy versus non-irradiated patients were statistically significant for second meningioma after primary cancers of the brain (p (Het) < 0.001) and ALL (p (Het) = 0.02). No statistically significant increased risks were detected for second acoustic neuromas (n = 114) following any first primary tumor.
Risk of second benign brain tumors, particularly meningioma, is increased following first primary cancers of the brain/CNS, thyroid, prostate, and ALL. Radiation exposure likely contributes to these excess risks.
C1 [Kutsenko, Alina; de Gonzalez, Amy Berrington; Curtis, Rochelle E.; Rajaraman, Preetha] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Kutsenko, A (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,MSC 9778, Bethesda, MD 20892 USA.
EM alk2022@med.cornell.edu; berringtona@mail.nih.gov; rcurtis@mail.nih.gov;
rajarama@mail.nih.gov
NR 36
TC 1
Z9 1
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUN
PY 2014
VL 25
IS 6
BP 659
EP 668
DI 10.1007/s10552-014-0367-5
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA AH3LA
UT WOS:000336023600002
PM 24682745
ER
PT J
AU Colloca, L
Grillon, C
AF Colloca, Luana
Grillon, Christian
TI Understanding Placebo and Nocebo Responses for Pain Management
SO CURRENT PAIN AND HEADACHE REPORTS
LA English
DT Review
DE Brain Imaging; Cannabinoids; Conditioning; Dopamine; Expectation;
Genetics; Interpersonal interactions; Learning; Psychological traits;
Opioids; Social observation; Oxytocin
ID DISPOSITIONAL OPTIMISM; SOCIAL-BEHAVIOR; OPIOID ACTIVITY; SPINAL-CORD;
ANALGESIA; ACTIVATION; MECHANISMS; SYSTEM; EXPECTATION; PERSONALITY
AB Placebo analgesia makes individuals experience relief of their pain simply by virtue of the anticipation of a benefit. A reduction of pain can occur also when placebos follow the administration of active and effective painkillers. In fact, studies indicate that placebos mimic the action of active treatments and promote the endogenous release of opioids in both humans and animals. Finally, social support and observational learning also lead to analgesic effects. Thus, different psychological factors and situations induce expectations of analgesia facilitating the activation of the top-down systems for pain control along with the release of endogenous mediators crucially involved in placebo-induced benefits. Recent scientific investigation in the field of brain imaging is opening new avenues to understanding the cognitive mechanisms and neurobiological substrates of expectation-induced pain modulation. Gaining deeper knowledge of top-down mechanisms of pain modulation has enormous implications for personalizing and optimizing pain management.
C1 [Colloca, Luana; Grillon, Christian] NIMH, NIH, Bethesda, MD 20892 USA.
[Colloca, Luana] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Colloca, L (reprint author), NIH, Ctr Clin, Bldg 10,Room 1C154, Bethesda, MD 20892 USA.
EM luana.colloca@nih.gov
OI Colloca, Luana/0000-0002-6503-4709
FU NIMH; NCCAM [11-M-0104, NCT:01328561]
FX This research was funded by intramural NIMH and NCCAM (11-M-0104;
NCT:01328561). The authors thank Catherine M. Bushnell for helpful
comments on this article.
NR 68
TC 7
Z9 7
U1 2
U2 41
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1531-3433
EI 1534-3081
J9 CURR PAIN HEADACHE R
JI Curr. Pain Headache Rep.
PD JUN
PY 2014
VL 18
IS 6
AR 419
DI 10.1007/s11916-014-0419-2
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA AG8QF
UT WOS:000335682600004
PM 24771206
ER
PT J
AU Andrulis, M
Bauerle, T
Goldschmidt, H
Delorme, S
Landgren, O
Schirmacher, P
Hillengass, J
AF Andrulis, Mindaugas
Baeuerle, Tobias
Goldschmidt, Hartmut
Delorme, Stefan
Landgren, Ola
Schirmacher, Peter
Hillengass, Jens
TI Infiltration patterns in monoclonal plasma cell disorders: correlation
of magnetic resonance imaging with matched bone marrow histology
SO EUROPEAN JOURNAL OF RADIOLOGY
LA English
DT Article
DE Paraproteinemias; Multiple myeloma; Plasma cells; Magnetic resonance
imaging; Bone marrow; Histology
ID UNDETERMINED SIGNIFICANCE MGUS; MULTIPLE-MYELOMA; WHOLE-BODY;
PROGNOSTIC-SIGNIFICANCE; GAMMOPATHY; MRI; CLASSIFICATION; SURVIVAL;
DISEASE; SALMON
AB Objectives: To investigate how plasma cell infiltration patterns detected by MRI match the plasma cell distribution in bone marrow biopsy.
Methods: We assessed 50 patients with monoclonal plasma cell disorders of all clinical stages. MRI infiltration pattern was compared with matched BM histology from the same anatomic region.
Results: MRI revealed a minimal (n = 11, 22%), focal (n = 5,10%), diffuse (n = 14, 28%) and mixed (n= 20,40%) infiltration pattern. Diffuse MRI pattern was predominant in smoldering myeloma patients whereas the MRI patterns with "focal component" (i.e. focal and mixed) were most common in symptomatic myeloma (p < 0.01). In histology an interstitial (n = 13, 26%), nodular (n = 23,46%) and packed marrow (n = 14, 28%) was found respectively. All three histological types of infiltration were observed in patients with diffuse and mixed MRI patterns. Minimal MRI pattern was found in all MGUS patients and was associated with an interstitial BM infiltration. In two patients with minimal MRI pattern an extensive micro-nodular BM infiltration was found in histology.
Conclusions: Infiltration patterns in MRI represent different histological growth patterns of plasma cells, but the MRI resolution is not sufficient to visualize micro-nodular aggregates of plasma cells. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Andrulis, Mindaugas; Schirmacher, Peter] Heidelberg Univ, Inst Pathol, D-69120 Heidelberg, Germany.
[Baeuerle, Tobias] Univ Hamburg, Dept Diagnost & Intervent Radiol, Hamburg, Germany.
[Goldschmidt, Hartmut; Hillengass, Jens] Heidelberg Univ, Dept Hematol & Oncol, D-69120 Heidelberg, Germany.
[Delorme, Stefan; Hillengass, Jens] German Canc Res Ctr, Dept Radiol, Heidelberg, Germany.
[Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch, Bethesda, MD 20892 USA.
RP Hillengass, J (reprint author), Heidelberg Univ, Dept Hematol & Oncol, Neuenheimer Feld 410D, D-69120 Heidelberg, Germany.
EM jens.hillengass@med.uni-heidelberg.de
OI Delorme, Stefan/0000-0002-1000-2582
FU International Myeloma Foundation; German Research Foundation
FX This work was supported by grants from the International Myeloma
Foundation and from the German Research Foundation: grant for
"initiation of bilateral cooperation" and Transregio 79.
NR 23
TC 3
Z9 3
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0720-048X
EI 1872-7727
J9 EUR J RADIOL
JI Eur. J. Radiol.
PD JUN
PY 2014
VL 83
IS 6
BP 970
EP 974
DI 10.1016/j.ejrad.2014.03.005
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AH1UJ
UT WOS:000335906400016
PM 24725673
ER
PT J
AU Wang, LL
Cummings, RD
Smith, DF
Huflejt, M
Campbell, CT
Gildersleeve, JC
Gerlach, JQ
Kilcoyne, M
Joshi, L
Serna, S
Reichardt, NC
Pera, NP
Pieters, RJ
Eng, W
Mahal, LK
AF Wang, Linlin
Cummings, Richard D.
Smith, David F.
Huflejt, Margaret
Campbell, Christopher T.
Gildersleeve, Jeffrey C.
Gerlach, Jared Q.
Kilcoyne, Michelle
Joshi, Lokesh
Serna, Sonia
Reichardt, Niels-Christian
Pera, Nuria Parera
Pieters, Roland J.
Eng, William
Mahal, Lara K.
TI Cross-platform comparison of glycan microarray formats
SO GLYCOBIOLOGY
LA English
DT Article
DE comparison; glycan microarray; lectin; presentation
ID WHEAT-GERM-AGGLUTININ; CARBOHYDRATE-PROTEIN INTERACTIONS; LECTIN
MICROARRAY; BINDING-PROTEINS; CELL-BINDING; ARRAY DATA; SURFACE;
RECOGNITION; DENSITY; SPECIFICITIES
AB Carbohydrates participate in almost every aspect of biology from protein sorting to modulating cell differentiation and cell-cell interactions. To date, the majority of data gathered on glycan expression has been obtained via analysis with either anti-glycan antibodies or lectins. A detailed understanding of the specificities of these reagents is critical to the analysis of carbohydrates in biological systems. Glycan microarrays are increasingly used to determine the binding specificity of glycan-binding proteins (GBPs). In this study, six different glycan microarray platforms with different modes of glycan presentation were compared using five well-known lectins; concanavalin A, Helix pomatia agglutinin, Maackia amurensis lectin I, Sambucus nigra agglutinin and wheat germ agglutinin. A new method (universal threshold) was developed to facilitate systematic comparisons across distinct array platforms. The strongest binders of each lectin were identified using the universal threshold across all platforms while identification of weaker binders was influenced by platform-specific factors including presentation of determinants, array composition and self-reported thresholding methods. This work compiles a rich dataset for comparative analysis of glycan array platforms and has important implications for the implementation of microarrays in the characterization of GBPs.
C1 [Wang, Linlin; Eng, William; Mahal, Lara K.] NYU, Dept Chem, Biomed Chem Inst, New York, NY 10003 USA.
[Cummings, Richard D.; Smith, David F.] Emory Univ, Dept Biochem, Glyc Ctr, Sch Med, Atlanta, GA 30322 USA.
[Huflejt, Margaret] NYU, Div Thorac Surg & Thorac Oncol, Dept Cardiothorac Surg, Sch Med, New York, NY 10016 USA.
[Campbell, Christopher T.; Gildersleeve, Jeffrey C.] NCI, Chem Biol Lab, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Gerlach, Jared Q.; Kilcoyne, Michelle; Joshi, Lokesh] Natl Univ Ireland Galway, Glycosci Grp, Natl Ctr Biomed Engn Sci, Galway, Ireland.
[Serna, Sonia; Reichardt, Niels-Christian] CICbiomaGUNE, Biofunct Nanomat Unit, San Sebastian 20009, Spain.
[Pera, Nuria Parera; Pieters, Roland J.] Univ Utrecht, Dept Med Chem & Chem Biol, Utrecht Inst Pharmaceut Sci, NL-3508 TB Utrecht, Netherlands.
RP Mahal, LK (reprint author), NYU, Dept Chem, Biomed Chem Inst, 100 Washington Sq East,Room 1001, New York, NY 10003 USA.
EM lkmahal@nyu.edu
RI Serna, Sonia/K-5795-2014; Gildersleeve, Jeffrey/N-3392-2014; biomaGUNE,
CIC/J-9136-2014; Pieters, Roland/A-9254-2008; Gerlach,
Jared/K-2698-2013;
OI Serna, Sonia/0000-0002-2085-4412; biomaGUNE, CIC/0000-0001-7690-0660;
Pieters, Roland/0000-0003-4723-3584; Gerlach, Jared/0000-0001-7343-7201;
Kilcoyne, Michelle/0000-0002-8870-1308
FU NIH [GM62116, GM098791]; National Center for Functional Glycomics
[P41-GM103694]; National Cancer Institute, National Institutes of
Health; Consortium for Functional Glycomics (Scripps Research Institute)
[GM62116]; Pharmacology Research Associate Training (PRAT) program of
the NIGMS; Science Foundation Ireland [08/SRC/B1393]; European Union
[260600]; Ministerio de Ciencia e Innovacion [CTQ2008-04444/BQA,
CTQ2011-27874]; Government of the Basque Country; Etortek grant;
European Union; Dutch Technology Foundation STW; applied science
division of NWO; Ministry of Economic Affairs; National Institutes of
Health [5 U54 GM062116-09]; MacCracken Fellowship (NYU)
FX R.D.C. and D.F.S.: The Protein-Glycan Interaction Resource (Core H) of
the Consortium for Functional Glycomics is supported by NIH Grants
GM62116 GM098791 and the National Center for Functional Glycomics
P41-GM103694. J.C.G.: This work was supported in part by the intramural
research program of the National Cancer Institute, National Institutes
of Health and the Consortium for Functional Glycomics (GM62116; The
Scripps Research Institute). C. T. C. received fellowship support
through the Pharmacology Research Associate Training (PRAT) program of
the NIGMS. L.J.: This work was supported by Science Foundation Ireland
(grant 08/SRC/B1393) in support of the Alimentary Glycoscience Research
Cluster (AGRC) and the European Union FP7 program (grant 260600) in
support of GlycoHIT. N.C.R.: This work was supported by Ministerio de
Ciencia e Innovacion, projects CTQ2008-04444/BQA and CTQ2011-27874,
Government of the Basque Country, Etortek grant and the European Union,
ITN-EuroGlycoArrays grant is gratefully acknowledged. R.J.P.: This work
was supported by the Dutch Technology Foundation STW, applied science
division of NWO and the Technology Program of the Ministry of Economic
Affairs. L. K. M.: This work was supported by the National Institutes of
Health Grant No. 5 U54 GM062116-09. L. W. was supported by a MacCracken
Fellowship (NYU).
NR 55
TC 36
Z9 36
U1 2
U2 47
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD JUN
PY 2014
VL 24
IS 6
BP 507
EP 517
DI 10.1093/glycob/cwu019
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA AH2CO
UT WOS:000335928500004
PM 24658466
ER
PT J
AU Beare, PA
Sandoz, KM
Larson, CL
Howe, D
Kronmiller, B
Heinzen, RA
AF Beare, Paul A.
Sandoz, Kelsi M.
Larson, Charles L.
Howe, Dale
Kronmiller, Brent
Heinzen, Robert A.
TI Essential Role for the Response Regulator PmrA in Coxiella burnetii Type
4B Secretion and Colonization of Mammalian Host Cells
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID LEGIONELLA-PNEUMOPHILA; SIGNAL-TRANSDUCTION; HUMAN MACROPHAGES;
INTRACELLULAR MULTIPLICATION; ACANTHAMOEBA-CASTELLANII; VESICULAR
TRAFFICKING; ESCHERICHIA-COLI; EUKARYOTIC CELLS; EFFECTOR PROTEIN;
SYSTEM
AB Successful host cell colonization by the Q fever pathogen, Coxiella burnetii, requires translocation of effector proteins into the host cytosol by a Dot/Icm type 4B secretion system (T4BSS). In Legionella pneumophila, the two-component system ( TCS) PmrAB regulates the Dot/Icm T4BSS and several additional physiological processes associated with pathogenesis. Because PmrA consensus regulatory elements are associated with some dot/icm and substrate genes, a similar role for PmrA in regulation of the C. burnetii T4BSS has been proposed. Here, we constructed a C. burnetii pmrA deletion mutant to directly probe PmrA-mediated gene regulation. Compared to wild-type bacteria, C. burnetii Delta pmrA exhibited severe intracellular growth defects that coincided with failed secretion of effector proteins. Luciferase gene reporter assays demonstrated PmrA-dependent expression of 5 of 7 dot/icm operons and 9 of 11 effector-encoding genes with a predicted upstream PmrA regulatory element. Mutational analysis verified consensus sequence nucleotides required for PmrA-directed transcription. RNA sequencing and whole bacterial cell mass spectrometry of wild-type C. burnetii and the Delta pmrA mutant uncovered new components of the PmrA regulon, including several genes lacking PmrA motifs that encoded Dot/Icm substrates. Collectively, our results indicate that the PmrAB TCS is a critical virulence factor that regulates C. burnetii Dot/Icm secretion. The presence of PmrA-responsive genes lacking PmrA regulatory elements also suggests that the PmrAB TCS controls expression of regulatory systems associated with the production of additional C. burnetii proteins involved in host cell parasitism.
C1 [Beare, Paul A.; Sandoz, Kelsi M.; Larson, Charles L.; Howe, Dale; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Kronmiller, Brent] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA.
RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
EM rheinzen@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Allergy and Infectious Diseases
FX We thank Renee Olano of the Research Technologies Branch, National
Institute of Allergy and Infectious Diseases, for mass spectrometry.;
This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 76
TC 9
Z9 9
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
EI 1098-5530
J9 J BACTERIOL
JI J. Bacteriol.
PD JUN
PY 2014
VL 196
IS 11
BP 1925
EP 1940
DI 10.1128/JB.01532-14
PG 16
WC Microbiology
SC Microbiology
GA AH1VM
UT WOS:000335909500002
PM 24610709
ER
PT J
AU Machado, ES
Krauss, MR
Megazzini, K
Coutinho, CM
Kreitchmann, R
Melo, VH
Pilotto, JH
Ceriotto, M
Hofer, CB
Siberry, GK
Watts, DH
AF Machado, Elizabeth Stankiewicz
Krauss, Margot R.
Megazzini, Karen
Coutinho, Conrado Milani
Kreitchmann, Regis
Melo, Victor Hugo
Pilotto, Jose Henrique
Ceriotto, Mariana
Hofer, Cristina B.
Siberry, George K.
Watts, D. Heather
CA NICHD Int Site Dev Initiative NISD
TI Hypertension, preeclampsia and eclampsia among HIV-infected pregnant
women from Latin America and Caribbean countries
SO JOURNAL OF INFECTION
LA English
DT Article
DE HIV-infected women; Pregnancy; Hypertensive disorders
ID ACTIVE ANTIRETROVIRAL THERAPY; INCREASED RISK; BLOOD-VOLUME; INFANTS;
METAANALYSIS; ZIDOVUDINE; OUTCOMES; WEIGHT; CITY; AIDS
AB Objectives: To evaluate the incidence of and risk factors for hypertensive disorders in a cohort of HIV-infected pregnant women.
Methods: Hypertensive disorders ( HD) including preeclampsia/eclampsia (PE/E) and pregnancy induced hypertension, and risk factors were evaluated in a cohort of HIV-infected pregnant women from Latin America and the Caribbean enrolled between 2002 and 2009. Only pregnant women enrolled for the first time in the study and delivered at >= 20 weeks gestation were analyzed.
Results: HD were diagnosed in 73 (4.8%, 95% CI: 3.8%-6.0%) of 1513 patients; 35 (47.9%) had PE/E. HD was significantly increased among women with a gestational age-adjusted body mass index (gBMI) >= 25 kg/m(2) (OR = 3.1; 95% CI: 1.9-5.0), hemoglobin (Hg) >= 11 g/dL at delivery (OR = 2.1; 95% CI: 1.2-3.6) and age >= 35 years (OR = 1.8; 95% CI: 1.1-3.2). PE/E was increased among women with a gBMI >= 25 kg/m(2) (OR = 3.0; 95% CI: 1.5-6.0)and Hg >= 11 g/dL at delivery (OR = 2.8; 95% CI: 1.2-6.5). A previous history of PE/E increased the risk of PE/E 6.7 fold (95% CI: 1.8-25.5). HAART before conception was associated with PE/E (OR = 2.3; 95% CI: 1.1-4.9).
Conclusions: HIV-infected women, with a previous history of PE/E, a gBMI >= 25 kg/m(2), Hg at delivery >= 11 g/dL and in use of HAART before conception are at an increased risk of developing PE/E during pregnancy. (C) 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
C1 [Machado, Elizabeth Stankiewicz; Hofer, Cristina B.] Univ Fed Rio de Janeiro, Inst Puericultura & Pediat Martagao Gesteira, Rio De Janeiro, Brazil.
[Krauss, Margot R.; Megazzini, Karen] WESTAT Corp, Rockville, MD 20850 USA.
[Coutinho, Conrado Milani] Univ Sao Paulo, Fac Med Ribeirao Preto, Hosp Clin, BR-05508 Sao Paulo, Brazil.
[Kreitchmann, Regis] Irmandade Santa Casa de Misericordia Porto Alegre, Porto Alegre, RS, Brazil.
[Melo, Victor Hugo] Univ Fed Minas Gerais, Fac Med, Belo Horizonte, MG, Brazil.
[Pilotto, Jose Henrique] Fiocruz IOC, Lab AIDS & Imunol Mol, Rio De Janeiro, Brazil.
[Pilotto, Jose Henrique] Hosp Geral Nova Iguacu, Rio De Janeiro, Brazil.
[Ceriotto, Mariana] Dr Cecilia Grierson Hosp, Infect Dis Unit, Buenos Aires, MD, Argentina.
[Siberry, George K.; Watts, D. Heather] NICHD, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD USA.
RP Machado, ES (reprint author), IPPMG UFRJ, Serv Prenatal, Av Bruno Lobo 50,Cidade Univ, BR-21941912 Rio De Janeiro, RJ, Brazil.
EM emachado@infolink.com.br
FU Eunice Kennedy ShriverNational Institute of Child Health and Human
Development, Bethesda, Maryland, USA (NICHD) [N01-HD-3-3345]; NICHD
[HHSN267200800001C, N01-HD-8-0001]
FX Supported by Eunice Kennedy ShriverNational Institute of Child Health
and Human Development, Bethesda, Maryland, USA (NICHD) Contract #
N01-HD-3-3345 (2002-2007) and by NICHD Contract # HHSN267200800001C
(NICHD Control #: N01-HD-8-0001) (2007-2012). NICHD was involved in all
aspects of study design, data analysis and interpretation, and
manuscript writing/ editing.
NR 46
TC 5
Z9 5
U1 0
U2 5
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0163-4453
EI 1532-2742
J9 J INFECTION
JI J. Infect.
PD JUN
PY 2014
VL 68
IS 6
BP 572
EP 580
DI 10.1016/j.jinf.2013.12.018
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA AG9XL
UT WOS:000335773200008
PM 24462561
ER
PT J
AU Alonso, WJ
McCormick, BJJ
Schuck-Paim, C
AF Alonso, Wladimir J.
McCormick, Benjamin J. J.
Schuck-Paim, Cynthia
TI Influenza and specific humidity in French Guiana: When analytical
simplicity is golden
SO JOURNAL OF INFECTION
LA English
DT Letter
C1 [Alonso, Wladimir J.; McCormick, Benjamin J. J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Schuck-Paim, Cynthia] Origem Sci, BR-03337 Sao Paulo, Brazil.
RP Alonso, WJ (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr,Bldg 16, Bethesda, MD 20892 USA.
EM alonsow@mail.nih.gov
NR 6
TC 1
Z9 1
U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0163-4453
EI 1532-2742
J9 J INFECTION
JI J. Infect.
PD JUN
PY 2014
VL 68
IS 6
BP 604
EP 605
DI 10.1016/j.jinf.2014.02.002
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA AG9XL
UT WOS:000335773200012
PM 24513392
ER
PT J
AU Mahamat, A
Viboud, C
AF Mahamat, A.
Viboud, C.
TI Influenza and specific humidity in French Guiana: When analytical
simplicity is golden Response
SO JOURNAL OF INFECTION
LA English
DT Letter
ID SEASONALITY; EPIDEMICS
C1 [Mahamat, A.] Cayenne Gen Hosp, Infect Dis & Trop Med Unit, Cayenne, French Guiana.
[Mahamat, A.] Univ Antilles Guyane, EA 3595, Cayenne, French Guiana.
[Viboud, C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Mahamat, A (reprint author), CH Andree Rosemon, Unite Malad Infect & Trop, Ave Flamboyants, Cayenne 97306, French Guiana.
EM mahamataba@gmail.com
NR 14
TC 0
Z9 0
U1 0
U2 2
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0163-4453
EI 1532-2742
J9 J INFECTION
JI J. Infect.
PD JUN
PY 2014
VL 68
IS 6
BP 605
EP 606
DI 10.1016/j.jinf.2014.02.004
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA AG9XL
UT WOS:000335773200013
PM 24530373
ER
PT J
AU Schulz, KS
Liu, XQ
Klupp, BG
Granzow, H
Cohen, JI
Mettenleiter, TC
AF Schulz, Katharina S.
Liu, XueQiao
Klupp, Barbara G.
Granzow, Harald
Cohen, Jeffrey I.
Mettenleiter, Thomas C.
TI Pseudorabies Virus pUL46 Induces Activation of ERK1/2 and Regulates
Herpesvirus-Induced Nuclear Envelope Breakdown
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CELL-CYCLE PROGRESSION; TEGUMENT PROTEIN US2; FAMILY KINASE LCK;
DELETION MUTANTS; GENE-PRODUCT; MAP KINASES; TYPE-1 UL46; SIMPLEX;
PHOSPHORYLATION; EGRESS
AB Herpesvirus capsid morphogenesis occurs in the nucleus, while final maturation takes place in the cytosol, requiring translocation of capsids through the nuclear envelope. The nuclear egress complex, consisting of homologs of herpes simplex virus pUL31 and pUL34, is required for efficient nuclear egress via primary envelopment and de-envelopment. Recently, we described an alternative mode of nuclear escape by fragmentation of the nuclear envelope induced by replication-competent pUL31 and pUL34 deletion mutants of the alphaherpesvirus pseudorabies virus (PrV), which had been selected by serial passaging in cell culture. Both passaged viruses carry congruent mutations in seven genes, including UL46, which encodes one of the major tegument proteins. Herpesvirus pUL46 homologs have recently been shown to activate the PI3K-Akt and ERK1/2 signaling pathways, which are involved in regulation of mitosis and apoptosis. Since in uninfected cells fragmentation of the nuclear envelope occurs during mitosis and apoptosis, we analyzed whether pUL46 of PrV is involved in signaling events impairing the integrity of the nuclear envelope. We show here that PrV pUL46 is able to induce phosphorylation of ERK1/2 and, thus, expression of ERK1/2 target genes but fails to activate the PI3K-Akt pathway. Deletion of UL46 from PrV-Delta UL34Pass and PrV-Delta UL31Pass or replacement by wild-type UL46 resulted in enhanced nuclear envelope breakdown, indicating that the mutations in pUL46 may limit the extent of NEBD. Thus, although pUL46 induces ERK1/2 phosphorylation, controlling the integrity of the nuclear envelope is independent of the ERK1/2 signaling pathway.
C1 [Schulz, Katharina S.; Klupp, Barbara G.; Mettenleiter, Thomas C.] Friedrich Loeffler Inst, Inst Mol Biol, Greifswald, Germany.
[Granzow, Harald] Friedrich Loeffler Inst, Inst Infectol, Greifswald, Germany.
[Liu, XueQiao; Cohen, Jeffrey I.] NIH, Med Virol Sect, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Mettenleiter, TC (reprint author), Friedrich Loeffler Inst, Inst Mol Biol, Greifswald, Germany.
EM thomas.mettenleiter@fli.bund.de
FU Deutsche Forschungsgemeinschaft [DFG Me 854/12-1]; intramural research
program of the National Institute of Allergy and Infectious Diseases
FX This work was supported by the Deutsche Forschungsgemeinschaft (DFG Me
854/12-1) and the intramural research program of the National Institute
of Allergy and Infectious Diseases.
NR 42
TC 4
Z9 4
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2014
VL 88
IS 11
BP 6003
EP 6011
DI 10.1128/JVI.00501-14
PG 9
WC Virology
SC Virology
GA AH2SB
UT WOS:000335970300010
PM 24623429
ER
PT J
AU Grohman, JK
Gorelick, RJ
Kottegoda, S
Allbritton, NL
Rein, A
Weeks, KM
AF Grohman, Jacob K.
Gorelick, Robert J.
Kottegoda, Sumith
Allbritton, Nancy L.
Rein, Alan
Weeks, Kevin M.
TI An Immature Retroviral RNA Genome Resembles a Kinetically Trapped
Intermediate State
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MURINE-LEUKEMIA-VIRUS; SELECTIVE 2'-HYDROXYL ACYLATION; SINGLE
NUCLEOTIDE RESOLUTION; PRIMER EXTENSION SHAPE; SECONDARY STRUCTURE;
HIV-1 VIRIONS; VIRAL-RNA; WILD-TYPE; GAG; DIMERIZATION
AB Retroviral virions initially assemble in an immature form that differs from that of the mature infectious particle. The RNA genomes in both immature and infectious particles are dimers, and interactions between the RNA dimer and the viral Gag protein ensure selective packaging into nascent immature virions. We used high-sensitivity selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) to obtain nucleotide-resolution structural information from scarce, femtomole quantities of Moloney murine leukemia virus (MuLV) RNA inside authentic virions and from viral RNA extracted from immature (protease-minus) virions. Our secondary structure model of the dimerization and packaging domain indicated that a stable intermolecular duplex known as PAL2, previously shown to be present in mature infectious MuLV particles, was sequestered in an alternate stem-loop structure inside immature virions. The intermediate state corresponded closely to a late-folding intermediate that we detected in time-resolved studies of the free MuLV RNA, suggesting that the immature RNA structure reflects trapping of the intermediate folding state by interactions in the immature virion. We propose models for the RNA-protein interactions that trap the RNA in the immature state and for the conformational rearrangement that occurs during maturation of virion particles.
C1 [Grohman, Jacob K.; Kottegoda, Sumith; Allbritton, Nancy L.; Weeks, Kevin M.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
[Gorelick, Robert J.] Leidos Biomedical Res Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
[Allbritton, Nancy L.] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC USA.
[Allbritton, Nancy L.] N Carolina State Univ, Raleigh, NC 27695 USA.
[Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
RP Weeks, KM (reprint author), Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
EM weeks@unc.edu
FU U. S. National Institutes of Health [GM064803]
FX This work was supported by a grant from the U. S. National Institutes of
Health (GM064803 to K.M.W.); in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research (A.
R.); and under contract number HHSN261200800001E with Leidos Biomedical
Research, Inc. (R.J.G.).
NR 40
TC 5
Z9 5
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2014
VL 88
IS 11
BP 6061
EP 6068
DI 10.1128/JVI.03277-13
PG 8
WC Virology
SC Virology
GA AH2SB
UT WOS:000335970300015
PM 24623442
ER
PT J
AU Walsh, KB
Teijaro, JR
Brock, LG
Fremgen, DM
Collins, PL
Rosen, H
Oldstone, MBA
AF Walsh, Kevin B.
Teijaro, John R.
Brock, Linda G.
Fremgen, Daniel M.
Collins, Peter L.
Rosen, Hugh
Oldstone, Michael B. A.
TI Animal Model of Respiratory Syncytial Virus: CD8(+) T Cells Cause a
Cytokine Storm That Is Chemically Tractable by Sphingosine-1-Phosphate 1
Receptor Agonist Therapy
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PNEUMONIA VIRUS; INFLUENZA-VIRUS; MICE; INFECTION; ANALOG; RESPONSES;
DISEASE; FTY720; INNATE; INJURY
AB The cytokine storm is an intensified, dysregulated, tissue-injurious inflammatory response driven by cytokine and immune cell components. The cytokine storm during influenza virus infection, whereby the amplified innate immune response is primarily responsible for pulmonary damage, has been well characterized. Now we describe a novel event where virus-specific T cells induce a cytokine storm. The paramyxovirus pneumonia virus of mice (PVM) is a model of human respiratory syncytial virus (hRSV). Unexpectedly, when C57BL/6 mice were infected with PVM, the innate inflammatory response was undetectable until day 5 postinfection, at which time CD8(+) T cells infiltrated into the lung, initiating a cytokine storm by their production of gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). Administration of an immunomodulatory sphingosine-1-phosphate (S1P) receptor 1 (S1P1R) agonist significantly inhibited PVM-elicited cytokine storm by blunting the PVM-specific CD8(+) T cell response, resulting in diminished pulmonary disease and enhanced survival.
C1 [Walsh, Kevin B.; Teijaro, John R.; Fremgen, Daniel M.; Oldstone, Michael B. A.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Brock, Linda G.; Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Rosen, Hugh] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA.
RP Oldstone, MBA (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
EM hrosen@scripps.edu; mbaobo@scripps.edu
FU USPHS [AI074564, AI009484, AI055509, MH084512]; NIH training [NS041219,
AI007244, AI007364]; American Heart Association [11POST7430106];
Intramural Program of NIAID, NIH
FX This work was supported in part by USPHS grants AI074564 (to M.B.A.O.,
H.R., K.B.W., and J.R.T.), AI009484 (to M.B.A.O.), AI055509 (to H.R.),
and MH084512 (to H.R.), NIH training grants NS041219 (to K.B.W.),
AI007244 (to K.B.W.), and AI007364 (to J.R.T.), and American Heart
Association grant 11POST7430106 (to J.R.T.). L.G.B. and P.L.C. were
supported by the Intramural Program of NIAID, NIH.
NR 41
TC 13
Z9 13
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2014
VL 88
IS 11
BP 6281
EP 6293
DI 10.1128/JVI.00464-14
PG 13
WC Virology
SC Virology
GA AH2SB
UT WOS:000335970300035
PM 24672024
ER
PT J
AU Le Nouen, C
Hillyer, P
Brock, LG
Winter, CC
Rabin, RL
Collins, PL
Buchholz, UJ
AF Le Nouen, Cyril
Hillyer, Philippa
Brock, Linda G.
Winter, Christine C.
Rabin, Ronald L.
Collins, Peter L.
Buchholz, Ursula J.
TI Human Metapneumovirus SH and G Glycoproteins Inhibit
Macropinocytosis-Mediated Entry into Human Dendritic Cells and Reduce
CD4(+) T Cell Activation
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNOSUPPRESSION IN-VITRO; RESPIRATORY-TRACT DISEASE; VIRAL
GLYCOPROTEINS; FLOW-CYTOMETRY; VIRUS ENTRY; ADULTS; INFECTION; CHILDREN;
SURFACE; MEMORY
AB Human metapneumovirus (HMPV) is a major etiologic agent of respiratory disease worldwide. HMPV reinfections are common in healthy adults and children, suggesting that the protective immune response to HMPV is incomplete and short-lived. We used gene-deletion viruses to evaluate the role of the attachment G and small hydrophobic SH glycoproteins on virus uptake by primary human monocyte-derived dendritic cells (MDDC) in vitro and on subsequent MDDC maturation and activation of autologous T cells. HMPV with deletion of G and SH (Delta SHG) exhibited increased infectivity but had little effect on MDDC maturation. However, MDDC stimulated with Delta SHG induced increased proliferation of autologous Th1-polarized CD4(+) T cells. This effect was independent of virus replication. Increased T cell proliferation was strictly dependent on contact between virus-stimulated MDDC and CD4(+) T cells. Confocal microscopy revealed that deletion of SH and G was associated with an increased number of immunological synapses between memory CD4(+) T cells and virus-stimulated MDDC. Uptake of HMPV by MDDC was found to be primarily by macropinocytosis. Uptake of wild-type (WT) virus was reduced compared to that of Delta SHG, indicative of inhibition by the SH and G glycoproteins. In addition, DC-SIGN-mediated endocytosis provided a minor alternative pathway that depended on SH and/or G and thus operated only for WT. Altogether, our results show that SH and G glycoproteins reduce the ability of HMPV to be internalized by MDDC, resulting in a reduced ability of the HMPV-stimulated MDDC to activate CD4(+) T cells. This study describes a previously unknown mechanism of virus immune evasion.
C1 [Le Nouen, Cyril; Brock, Linda G.; Winter, Christine C.; Collins, Peter L.; Buchholz, Ursula J.] NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Hillyer, Philippa; Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
RP Le Nouen, C (reprint author), NIAID, RNA Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lenouenc@niaid.nih.gov
FU Intramural Research Program of the NIAID, NIH
FX This research was supported by the Intramural Research Program of the
NIAID, NIH. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 58
TC 9
Z9 9
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD JUN
PY 2014
VL 88
IS 11
BP 6453
EP 6469
DI 10.1128/JVI.03261-13
PG 17
WC Virology
SC Virology
GA AH2SB
UT WOS:000335970300050
PM 24672038
ER
PT J
AU Kreimer, AR
AF Kreimer, Aimee R.
TI Prospects for prevention of HPV-driven oropharynx cancer
SO ORAL ONCOLOGY
LA English
DT Article
DE Prevention; Human papillomavirus; HPV; Oropharyngeal cancer
ID HUMAN-PAPILLOMAVIRUS INFECTION; SQUAMOUS-CELL CARCINOMA; YOUNG-WOMEN;
INTRAEPITHELIAL NEOPLASIA; VACCINATION COVERAGE; UNITED-STATES;
COSTA-RICA; TRIAL; MEN; PREVALENCE
AB Prevention of HPV-associated cancers can take two forms-one through prevention of infection via prophylactic HPV vaccination, and one through interruption of disease progression through early identification (i.e.: screening) and treatment. Primary prevention via vaccination seems promising, as a proof-of-principal study demonstrated high vaccine efficacy against one-time detection of oral HPV16/18 infection. In addition to the direct benefit of vaccination, indirect protection from reduced genital HPV infection should also reduce oral HPV exposure at the individual level. Yet, for the current unvaccinated cohorts who will bear the burden of non-cervical HPV-associated cancers for the foreseeable future, no secondary prevention opportunities exist, as the field has not yet validated any screening methods for non-cervical HPV associated cancers. Serum HPV16 E6 antibody data suggest that this test might one day be able to detect many of the at-risk patients prior to tumor development. For any biomarker that proves valid and reliable, transitioning into clinical practice will require additional research focused on (1) diagnostics, (2) effective intervention, and (3) observed reductions in cancer mortality. (C) 2013 The Author. Published by Elsevier Ltd. All rights reserved.
C1 NCI, NIH, Bethesda, MD 20892 USA.
RP Kreimer, AR (reprint author), NCI, NIH, 9609 Med Ctr Dr,RM 6-E104,MSC 9767, Bethesda, MD 20892 USA.
EM kreimera@mail.nih.gov
RI Kreimer, Aimee/H-1687-2015
FU Intramural NIH HHS [ZIA CP010209-01]
NR 41
TC 18
Z9 18
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
EI 1879-0593
J9 ORAL ONCOL
JI Oral Oncol.
PD JUN
PY 2014
VL 50
IS 6
BP 555
EP 559
DI 10.1016/j.oraloncolgy.2013.06.007
PG 5
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA AH1NY
UT WOS:000335889000005
PM 23876626
ER
PT J
AU Klinger, R
Colloca, L
Bingel, U
Flor, H
AF Klinger, Regine
Colloca, Luana
Bingel, Ulrike
Flor, Herta
TI Placebo analgesia: Clinical applications
SO PAIN
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIAL; IRRITABLE-BOWEL-SYNDROME; LOW-BACK-PAIN;
MECHANISMS; EXPECTATIONS; RESPONSES; EFFICACY; DISEASE
C1 [Klinger, Regine] Univ Hamburg, Dept Psychol, Psychotherapeut Univ Outpatient Clin Behav Therap, D-20146 Hamburg, Germany.
[Colloca, Luana] NIMH, NCCAM, Bethesda, MD 20892 USA.
[Colloca, Luana] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
[Bingel, Ulrike] Univ Duisburg Essen, Univ Hosp Essen, Dept Neurol, Essen, Germany.
[Flor, Herta] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Health, Dept Cognit & Clin Neurosci, D-68159 Mannheim, Germany.
RP Klinger, R (reprint author), Univ Hamburg, Dept Psychol, Psychotherapeut Univ Outpatient Clin Behav Therap, Von Melle Pk 5, D-20146 Hamburg, Germany.
EM rklinger@uni-hamburg.de
OI Colloca, Luana/0000-0002-6503-4709; Flor, Herta/0000-0003-4809-5398
FU National Center for Complementary and Alternative Medicine (NCCAM);
National Institute of Mental Health (NIMH); Deutsche
Forschungsgemeinschaft [FOR 1328/1, Kl 1350/3-1, Fl 156/33-1, BI
789/2-1]; Federal Ministry of Education and Research [01GQ0808]
FX This research was funded by an intramural grant from the National Center
for Complementary and Alternative Medicine (NCCAM) and National
Institute of Mental Health (NIMH) (L.C.), and grants by the Deutsche
Forschungsgemeinschaft (FOR 1328/1) to R.K. (Kl 1350/3-1), H.F. (Fl
156/33-1), and U.B. (BI 789/2-1), and the Federal Ministry of Education
and Research (01GQ0808) (U.B.).
NR 41
TC 20
Z9 21
U1 4
U2 27
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
EI 1872-6623
J9 PAIN
JI Pain
PD JUN
PY 2014
VL 155
IS 6
BP 1055
EP 1058
DI 10.1016/j.pain.2013.12.007
PG 4
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA AH1SY
UT WOS:000335902500005
PM 24333780
ER
PT J
AU Yeung, STA
Colagiuri, B
Lovibond, PF
Colloca, L
AF Yeung, Siu Tsin Au
Colagiuri, Ben
Lovibond, Peter F.
Colloca, Luana
TI Partial reinforcement, extinction, and placebo analgesia
SO PAIN
LA English
DT Article
DE Conditioning; Expectancy; Extinction; Pain; Partial reinforcement;
Placebo effect
ID IRRITABLE-BOWEL-SYNDROME; DOSE REDUCTION; EXPECTANCY; MECHANISMS;
EXPERIENCE; RESPONSES; NALOXONE; NOCEBO
AB Numerous studies indicate that placebo analgesia can be established via conditioning procedures. However, these studies have exclusively involved conditioning under continuous reinforcement. Thus, it is currently unknown whether placebo analgesia can be established under partial reinforcement and how durable any such effect would be. We tested this possibility using electrocutaneous pain in healthy volunteers. Sixty undergraduates received placebo treatment (activation of a sham electrode) under the guise of an analgesic trial. The participants were randomly allocated to different conditioning schedules, namely continuous reinforcement (CRF), partial reinforcement (PRF), or control (no conditioning). Conditioning was achieved by surreptitiously reducing pain intensity during training when the placebo was activated compared with when it was inactive. For the CRF group, the placebo was always followed by a surreptitious reduction in pain during training. For the PRF group, the placebo was followed by a reduction in pain stimulation on 62.5% of trials only. In the test phase, pain stimulation was equivalent across placebo and no placebo trials. Both CRF and PRF produced placebo analgesia, with the magnitude of initial analgesia being larger after CRF. However, although the placebo analgesia established under CRF extinguished during test phase, the placebo analgesia established under PRF did not. These findings indicate that PRF can induce placebo analgesia and that these effects are more resistant to extinction than those established via CRF. PRF may therefore reflect a novel way of enhancing clinical outcomes via the placebo effect. (C) 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
C1 [Yeung, Siu Tsin Au; Colagiuri, Ben] Univ Sydney, Sch Psychol, Sydney, NSW 2006, Australia.
[Colagiuri, Ben; Lovibond, Peter F.] Univ New S Wales, Sch Psychol, Sydney, NSW, Australia.
[Colloca, Luana] NIMH, Bethesda, MD USA.
[Colloca, Luana] NCCAM, NIH, Bethesda, MD USA.
RP Colagiuri, B (reprint author), Univ Sydney, Sch Psychol, A18, Sydney, NSW 2006, Australia.
EM ben.colagiuri@sydney.edu.au
OI Colloca, Luana/0000-0002-6503-4709; Lovibond, Peter/0000-0003-2146-9054
FU Intramural Research Program of the National Institute of Mental Health;
National Center for Complementary and Alternative Medicine
FX The authors thank Professor Justin Harris, University of Sydney, for his
useful advice on the current project. Dr. Luana Colloca is supported by
the Intramural Research Program of the National Institute of Mental
Health and National Center for Complementary and Alternative Medicine.
NR 44
TC 7
Z9 7
U1 0
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
EI 1872-6623
J9 PAIN
JI Pain
PD JUN
PY 2014
VL 155
IS 6
BP 1110
EP 1117
DI 10.1016/j.pain.2014.02.022
PG 8
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA AH1SY
UT WOS:000335902500012
ER
PT J
AU Forsythe, LP
Arora, N
Alfano, CM
Weaver, KE
Hamilton, AS
Aziz, N
Rowland, JH
AF Forsythe, Laura P.
Arora, Neeraj K.
Alfano, Catherine M.
Weaver, Kathryn E.
Hamilton, Ann S.
Aziz, Noreen
Rowland, Julia H.
TI Role of oncologists and primary care physicians in providing follow-up
care to non-Hodgkin lymphoma survivors within 5 years of diagnosis: a
population-based study
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Cancer; Non-Hodgkin lymphoma; Survivor; Follow-up care; Patient-centered
ID QUALITY-OF-LIFE; CANCER SURVIVORS; BREAST-CANCER; OUTCOMES RESEARCH;
PATIENT; ADULT; EXPECTATIONS; SYMPTOMS; RISK
AB The growing population of non-Hodgkin lymphoma (NHL) survivors living longer with high physical and psychological treatment burden, in combination with the projected shortage of medical professionals, necessitates redesigning cancer follow-up care. This study examined follow-up care patterns, factors associated with follow-up care, and attitudes towards follow-up care among NHL survivors.
We surveyed survivors of aggressive NHL 2 to 5 years post-diagnosis (N = 363) using a population-based sample from the Los Angeles County Surveillance Epidemiology and End Results registry.
Most survivors (82 %) received cancer-related follow-up care in the past year from an oncologist. History of recurrence, more comorbidities, more symptoms, and a shorter survivor-oncologist relationship were associated with high-frequency care with the oncologist [(a parts per thousand yen5 visits in the past year), p < 0.05]. Many survivors followed up by oncologists (71 %) also saw a primary care provider (PCP) and 47 % also saw both a PCP and other specialists. Factors associated with seeing a PCP in addition to an oncologist included more symptoms, more health information needs, no history of recurrence, perceived excellent quality of cancer follow-up care, and fewer visits with the oncologist (p < 0.05). Survivors generally reported high reassurance from, and low negative anticipation towards, follow-up care.
The high proportion of NHL survivors receiving care from multiple physicians, and the sizable proportion (similar to 30 %) who have not recently seen a PCP, suggests that coordinating care across specialties is critical to ensure comprehensive, non-duplicative care. Understanding factors associated with cancer-related follow-up is a first step towards more effective, efficient, patient-centered care.
C1 [Forsythe, Laura P.] PCORI, Washington, DC 20036 USA.
[Forsythe, Laura P.; Alfano, Catherine M.; Rowland, Julia H.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH DHHS, Bethesda, MD 20892 USA.
[Forsythe, Laura P.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, NIH DHHS, Bethesda, MD 20892 USA.
[Arora, Neeraj K.] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH DHHS, Bethesda, MD 20892 USA.
[Weaver, Kathryn E.] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Social Sci & Hlth Policy, Winston Salem, NC USA.
[Hamilton, Ann S.] Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA.
[Aziz, Noreen] NINR, Off Extramural Programs, Bethesda, MD 20892 USA.
RP Forsythe, LP (reprint author), PCORI, 1828 L St,NW,Suite 900, Washington, DC 20036 USA.
EM lforsythe@pcori.org
FU California Department of Health Services [103885]; National Cancer
Institute Surveillance, Epidemiology, and End Results Program
[N01-PC-35139, N02-PC-15105]; Centers for Disease Control and Prevention
[U55/CCR921930-02]
FX This study was supported in part by the California Department of Health
Services as part of the statewide cancer reporting program mandated by
California Health and Safety Code Section 103885; by National Cancer
Institute Surveillance, Epidemiology, and End Results Program Contract
No. N01-PC-35139 awarded to the University of Southern California and
Contract No. N02-PC-15105 awarded to the Public Health Institute; and by
Centers for Disease Control and Prevention National Program of Cancer
Registries Agreement No. U55/CCR921930-02 awarded to the Public Health
Institute. Selected findings from this manuscript were presented in
abstract form at the Annual Meeting of the American Society of Clinical
Oncology in June 2001 in Chicago, IL.
NR 39
TC 3
Z9 3
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD JUN
PY 2014
VL 22
IS 6
BP 1509
EP 1517
DI 10.1007/s00520-013-2113-z
PG 9
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA AG9YC
UT WOS:000335775000009
PM 24414999
ER
PT J
AU Madeo, AC
Tercyak, KP
Tarini, BA
McBride, CM
AF Madeo, Anne C.
Tercyak, Kenneth P.
Tarini, Beth A.
McBride, Colleen M.
TI Effects of Undergoing Multiplex Genetic Susceptibility Testing on Parent
Attitudes towards Testing Their Children
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Genetic Predisposition to Disease; Genetic Testing/Psychology; Health
Knowledge; Attitudes; Practice; Parents; Psychology
ID RISK INFORMATION; PEDIATRICS; BEHAVIORS
AB Parents may pursue common disease risk information about themselves via multiplex genetic susceptibility testing (MGST) for their children.
To prospectively assess whether parents who received MGST disclosed their test results to their child, intended to change the child's health habits, or have the child tested.
Eighty parents who opted for free MGST completed an online survey about a child in their household before undergoing MGST and a follow-up telephone survey 3 months after receiving results.
Few parents (21 %) disclosed results to the child. Undergoing MGST was unrelated to intentions to change the child's health habits but did increase parental willingness to test the child. Greater willingness to test a child was associated with positive attitudes toward pediatric genetic testing and intentions to change the child's health habits.
The experience of receiving MGST had little impact on parents' perceptions or behaviors related to their minor child.
C1 [Madeo, Anne C.; McBride, Colleen M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Tercyak, Kenneth P.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Tercyak, Kenneth P.] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA.
[Tarini, Beth A.] Univ Michigan, Dept Pediat, Child Hlth Evaluat & Res CHEAR Unit, Ann Arbor, MI 48109 USA.
[Madeo, Anne C.] George E Whalen Dept Vet Affairs Med Ctr, Genom Med Serv, Salt Lake City, UT 84148 USA.
RP Madeo, AC (reprint author), George E Whalen Dept Vet Affairs Med Ctr, Genom Med Serv, 500 Foothill Dr,151Z, Salt Lake City, UT 84148 USA.
EM acmadeo@gmail.com
FU Intramural NIH HHS [ZIA HG200344-07]; NCI NIH HHS [R01 CA137625,
R01CA137625, U19CA079689, U19 CA079689]; NHGRI NIH HHS [K18 HG006754,
HHSN268200782096C, K18HG006754]; NICHD NIH HHS [K23 HD057994,
K23HD057994]
NR 18
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
EI 1532-4796
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD JUN
PY 2014
VL 47
IS 3
BP 388
EP 394
DI 10.1007/s12160-013-9553-z
PG 7
WC Psychology, Multidisciplinary
SC Psychology
GA AG8EV
UT WOS:000335652500016
PM 24338635
ER
PT J
AU Shepperd, JA
Novell, CA
O'Neill, SC
Docherty, SL
Sanderson, SC
McBride, CM
Lipkus, IM
AF Shepperd, James A.
Novell, Corinne A.
O'Neill, Suzanne C.
Docherty, Sharron L.
Sanderson, Saskia C.
McBride, Colleen M.
Lipkus, Isaac M.
TI Contemplating Genetic Feedback Regarding Lung Cancer Susceptibility
SO ANNALS OF BEHAVIORAL MEDICINE
LA English
DT Article
DE Lung cancer; Genes; Expectations; Consistency theory; Self-enhancement
theory
ID S-TRANSFERASE M1; SELF-ENHANCEMENT; RISK; SMOKING; POLYMORPHISMS;
INDIVIDUALS; INVOLVEMENT; MUTATIONS; RESPONSES; SMOKERS
AB We examined three theoretical models (self-enhancement theory, consistency theory, and a combined model) for understanding how expectations and test result favorability influence smokers' desire for a retest following hypothetical genetic test results.
College smokers (N = 128) read a brochure describing a biomarker for lung cancer (the GSTM1 gene) then reported whether they thought they had the gene (indicating lower lung cancer risk) or were missing the gene (indicating higher lung cancer risk). Participants then reported whether they would get retested if they received favorable GSTM1 results versus unfavorable GSTM1 results.
Participants were most likely to want a retest, suggesting rejection of the results, if they expected favorable news yet received unfavorable news.
The findings supported the combined model such that smokers expressed greatest interest in a retest when they imagined genetic risk feedback that challenges both enhancement and consistency motives.
C1 [Shepperd, James A.; Novell, Corinne A.] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA.
[O'Neill, Suzanne C.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Docherty, Sharron L.; Lipkus, Isaac M.] Duke Univ, Sch Nursing, Durham, NC USA.
[Sanderson, Saskia C.] Icahn Sch Med Mt Sinai, New York, NY USA.
[McBride, Colleen M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
RP Shepperd, JA (reprint author), Univ Florida, Dept Psychol, POB 112250, Gainesville, FL 32611 USA.
EM shepperd@ufl.edu
FU NCI NIH HHS [R01 CA121922-01A2, R01 CA121922]
NR 30
TC 1
Z9 1
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0883-6612
EI 1532-4796
J9 ANN BEHAV MED
JI Ann. Behav. Med.
PD JUN
PY 2014
VL 47
IS 3
BP 395
EP 403
DI 10.1007/s12160-013-9561-z
PG 9
WC Psychology, Multidisciplinary
SC Psychology
GA AG8EV
UT WOS:000335652500017
PM 24222509
ER
PT J
AU Napolitano, C
Johnson, WE
Sanderson, J
O'Brien, SJ
Hoelzel, AR
Freer, R
Dunstone, N
Ritland, K
Ritland, CE
Poulin, E
AF Napolitano, Constanza
Johnson, Warren E.
Sanderson, Jim
O'Brien, Stephen J.
Hoelzel, A. Rus
Freer, Rachel
Dunstone, Nigel
Ritland, Kermit
Ritland, Carol E.
Poulin, Elie
TI Phylogeography and population history of Leopardus guigna, the smallest
American felid
SO CONSERVATION GENETICS
LA English
DT Article
DE Leopardus guigna; Felid; Phylogeography; Demographic history; Dispersal
barriers
ID SOUTHERN SOUTH-AMERICA; QUATERNARY CLIMATE-CHANGE; CHILEAN LAKE
DISTRICT; OLIGORYZOMYS-LONGICAUDATUS RODENTIA; LAST GLACIAL MAXIMUM; DNA
CONTROL REGION; MITOCHONDRIAL-DNA; GENETIC-STRUCTURE; ONCIFELIS-GUIGNA;
POSTGLACIAL RECOLONIZATION
AB The guigna (Leopardus guigna) is the smallest and most-restricted New World cat species, inhabiting only around 160,000 km(2) of temperate rain forests in southern South America and is currently threatened by habitat loss, fragmentation and human persecution. We investigated phylogeographic patterns of genetic diversity, demographic history and barriers to gene flow with 116 individuals sampled across the species geographic range by analyzing 1,798 base pairs of the mtDNA (496 bp HVSI region, 720 bp NADH-5 gene, 364 bp from 16S gene and 218 bp from ATP-8 gene) and 15 microsatellite loci. Mitochondrial DNA data revealed a clear phylogeographic pattern with moderate separation between northern and southern Chilean populations supporting recognized subspecific partitions based on morphology. A recent demographic expansion was inferred for the southern-most group (San Rafael Lake), presumably due to the complete coverage of this area during the last glacial period, 28000-16000 years BP. Geographical barriers such as the Andes Mountains and the Chacao Channel have partially restricted historic and more-recent gene flow and the Chilo, Island population has diverged genetically since being separated from the mainland 7000 years BP. This is the first study of the genetic structure of this threatened species throughout its whole geographic range.
C1 [Napolitano, Constanza; Poulin, Elie] Univ Chile, Lab Ecol Mol, Santiago, Chile.
[Napolitano, Constanza; Poulin, Elie] Univ Chile, Inst Ecol & Biodiversidad, Dept Ciencias Ecol, Fac Ciencias, Santiago, Chile.
[Johnson, Warren E.] NCI, Lab Genom Div, Frederick, MD 21701 USA.
[Sanderson, Jim] Small Wild Cat Conservat Fdn, Campbell, CA USA.
[O'Brien, Stephen J.] St Petersburg State Univ, Theodosius Dobzhansky Ctr Genome Bioinformat, St Petersburg 199034, Russia.
[Hoelzel, A. Rus; Freer, Rachel; Dunstone, Nigel] Univ Durham, Sch Biol & Biomed Sci, Durham, England.
[Freer, Rachel] FPCR Environm & Design Ltd, Derby, England.
[Dunstone, Nigel] Nat Hist New Zealand, Dunedin, Otago, New Zealand.
[Ritland, Kermit; Ritland, Carol E.] Univ British Columbia, Dept Forest & Conservat Sci, Vancouver, BC V6T 1Z4, Canada.
RP Napolitano, C (reprint author), Univ Chile, Lab Ecol Mol, Las Palmeras 3425, Santiago, Chile.
EM cnapolit@uchile.cl
RI Poulin, Elie/C-2654-2012; Johnson, Warren/D-4149-2016;
OI Poulin, Elie/0000-0001-7736-0969; Johnson, Warren/0000-0002-5954-186X;
O'Brien, Stephen J./0000-0001-7353-8301
FU Instituto de Ecologia y Biodiversidad (IEB, Facultad de Ciencias,
Universidad de Chile) [ICM P05-002]; Emerging Leaders in The Americas
Program (ELAP, Canadian Bureau for International Education, Government
of Canada); CONICYT, Chile; Instituto de Ecologia y Biodiversidad
(Facultad de Ciencias, Universidad de Chile); Panthera Kaplan Awards
Program (Panthera Foundation, New York, USA); Scott Neotropical Fund
Award (Cleveland Metroparks Zoo & the Cleveland Zoological Society,
Cleveland, USA); Eric York Scholarship (Felidae Conservation Fund,
California, USA); Intramural Research Program of the NCI, NIH
FX Guignas were captured with permission from the Agriculture and Livestock
Service (SAG) in Chile, capture permit numbers 814/13-Feb-2008,
109/9-Jan-2009, 1220/22-Feb-2010 and 1708/26-Mar-2010. Samples were
obtained in Argentina with permission from the National Parks
Administration (APN), permit number 1002/8-May-2009. Samples were
imported with permission from the Agriculture and Livestock Service
(SAG) in Chile, permit number 30/09. C.N. acknowledges support from the
doctoral fellowship ICM P05-002 from the Instituto de Ecologia y
Biodiversidad (IEB, Facultad de Ciencias, Universidad de Chile), the
Emerging Leaders in The Americas Program (ELAP, Canadian Bureau for
International Education, Government of Canada) and Becas Chile para
pasantias doctorales 2010 (CONICYT, Chile). This study was funded by the
Instituto de Ecologia y Biodiversidad (Facultad de Ciencias, Universidad
de Chile), Panthera Kaplan Awards Program (Panthera Foundation, New
York, USA), Scott Neotropical Fund Award (Cleveland Metroparks Zoo & the
Cleveland Zoological Society, Cleveland, USA) and the Eric York
Scholarship (Felidae Conservation Fund, California, USA). This research
was supported in part by the Intramural Research Program of the NCI,
NIH. We wish to thank Benito Gonzalez, Emma Elgueta, Milton Gallardo
(Universidad Austral), Jaime Rau (Universidad de Los Lagos), Oscar
Skewes (Universidad de Concepcion), Barbara Zentilli (CODEFF), Denise
Donoso, Nicolas Galvez, Felipe Hernandez, Elke Schuttler, Cristian
Bonacic, Martin Monteverde (Centro de Ecologia Aplicada del
Neuquen-Argentina), Jose Luis Brito (Museo Municipal de Ciencias
Naturales y Arqueologia de San Antonio), Juan Carlos Torres (Museo de
Historia Natural Santiago), Jose Yanez (Museo de Historia Natural
Santiago), Osvaldo Rojas (Museo de Historia Natural Calama), Fernando
Soto (Museo de Historia Natural de Valparaiso), Elvira Solar (Museo de
Zoologia Universidad de Concepcion), Franklin Troncoso (Museo de
Historia Natural de Concepcion), Luis Villanueva (SAG VII Region),
Cecilia Gonzalez (SAG RM), David Flores (Museo de Ciencias Naturales
Bernardino Rivadavia-Argentina), Diego Verzi (Museo de La
Plata-Argentina), Manuel Valdes (Parque Tantauco), Bernardita Silva,
Lito Quezada, Maximiliano Sepulveda, Javier Cabello, Alejandro Bravo
(Universidad Austral), Jorge Valenzuela (CECPAN), Andres Charrier, Juan
Luis Celis, Buin Zoo and Fidel Ovidio Castro (Banco de Recursos
Geneticos, Facultad de Ciencias Veterinarias, Universidad de Concepcion,
Campus Chillan) for generous collaboration with samples for this study.
We specially thank Magdalena Bennett for map elaboration. We thank
Sylvain Faugeron and Juliana Vianna de Abreu for help with molecular
markers. Special thanks to Jennifer Hetz, Monica Mora, Valentina
Sanchez, Tatiana Vuskovic, Veronica Sole, Rousset Palou, Yuri Zuniga and
Juan Vidal for assisting in the capture of guignas. We thank Raleigh
International for logistical support in collection of samples at San
Rafael Lake. We thank Parque Ahuenco, especially to Alberto Carvacho,
for kindly letting us work in their lands. We thank the Sindicato de
Pescadores Mar Adentro from Chepu, especially to Carlos Villarroel, for
their kind help during field work. We thank Parque Tantauco, especially
to Alan Bannister, for their kind support and for letting us work in
their lands. We thank the Senda Darwin Foundation, Ines Hanning from
Caulin, and many other local land owners in Chiloe Island who kindly let
us work in their lands.
NR 154
TC 4
Z9 4
U1 2
U2 47
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1566-0621
EI 1572-9737
J9 CONSERV GENET
JI Conserv. Genet.
PD JUN
PY 2014
VL 15
IS 3
BP 631
EP 653
DI 10.1007/s10592-014-0566-3
PG 23
WC Biodiversity Conservation; Genetics & Heredity
SC Biodiversity & Conservation; Genetics & Heredity
GA AG8MB
UT WOS:000335671500011
ER
PT J
AU Shui, IM
Lindstrom, S
Kibel, AS
Berndt, SI
Campa, D
Gerke, T
Penney, KL
Albanes, D
Berg, C
Bueno-de-Mesquita, HB
Chanock, S
Crawford, ED
Diver, WR
Gapstur, SM
Gaziano, JM
Giles, GG
Henderson, B
Hoover, R
Johansson, M
Le Marchand, L
Ma, J
Navarro, C
Overvad, K
Schumacher, FR
Severi, G
Siddiq, A
Stampfer, M
Stevens, VL
Travis, RC
Trichopoulos, D
Vineis, P
Mucci, LA
Yeager, M
Giovannucci, E
Kraft, P
AF Shui, Irene M.
Lindstroem, Sara
Kibel, Adam S.
Berndt, Sonja I.
Campa, Daniele
Gerke, Travis
Penney, Kathryn L.
Albanes, Demetrius
Berg, Christine
Bueno-de-Mesquita, H. Bas
Chanock, Stephen
Crawford, E. David
Diver, W. Ryan
Gapstur, Susan M.
Gaziano, J. Michael
Giles, Graham G.
Henderson, Brian
Hoover, Robert
Johansson, Mattias
Le Marchand, Loic
Ma, Jing
Navarro, Carmen
Overvad, Kim
Schumacher, Fredrick R.
Severi, Gianluca
Siddiq, Afshan
Stampfer, Meir
Stevens, Victoria L.
Travis, Ruth C.
Trichopoulos, Dimitrios
Vineis, Paolo
Mucci, Lorelei A.
Yeager, Meredith
Giovannucci, Edward
Kraft, Peter
TI Prostate Cancer (PCa) Risk Variants and Risk of Fatal PCa in the
National Cancer Institute Breast and Prostate Cancer Cohort Consortium
SO EUROPEAN UROLOGY
LA English
DT Article
DE Prostate cancer; Risk single nucleotide polymorphisms; Prostate cancer
mortality; Genetic epidemiology
ID GENOME-WIDE ASSOCIATION; GENETIC-VARIANTS; MORTALITY; LOCI;
SUSCEPTIBILITY; DISEASE; DEATH; 8Q24; MEN
AB Background: Screening and diagnosis of prostate cancer (PCa) is hampered by an inability to predict who has the potential to develop fatal disease and who has indolent cancer. Studies have identified multiple genetic risk loci for PCa incidence, but it is unknown whether they could be used as biomarkers for PCa-specific mortality (PCSM). Objective: To examine the association of 47 established PCa risk single-nucleotide polymorphisms (SNPs) with PCSM.
Design, setting, and participants: We included 10 487 men who had PCa and 11 024 controls, with a median follow-up of 8.3 yr, during which 1053 PCa deaths occurred.
Outcome measurements and statistical analysis: The main outcome was PCSM. The risk allele was defined as the allele associated with an increased risk for PCa in the literature. We used Cox proportional hazards regression to calculate the hazard ratios of each SNP with time to progression to PCSM after diagnosis. We also used logistic regression to calculate odds ratios for each risk SNP, comparing fatal PCa cases to controls.
Results and limitations: Among the cases, we found that 8 of the 47 SNPs were significantly associated (p < 0.05) with time to PCSM. The risk allele of rs11672691 (intergenic) was associated with an increased risk for PCSM, while 7 SNPs had risk alleles inversely associated (rs13385191 [C2orf43], rs17021918 [PDLIM5], rs10486567 [JAZF1], rs6465657 [LMTK2], rs7127900 (intergenic), rs2735839 [KLK3], rs10993994 [MSMB], rs13385191 [C2orf43]). In the case-control analysis, 22 SNPs were associated (p < 0.05) with the risk of fatal PCa, but most did not differentiate between fatal and nonfatal PCa. Rs11672691 and rs10993994 were associated with both fatal and nonfatal PCa, while rs6465657, rs7127900, rs2735839, and rs13385191 were associated with nonfatal PCa only.
Conclusions: Eight established risk loci were associated with progression to PCSM after diagnosis. Twenty-two SNPs were associated with fatal PCa incidence, but most did not differentiate between fatal and nonfatal PCa. The relatively small magnitudes of the associations do not translate well into risk prediction, but these findings merit further follow-up, because they may yield important clues about the complex biology of fatal PCa.
Patient summary: In this report, we assessed whether established PCa risk variants could predict PCSM. We found eight risk variants associated with PCSM: One predicted an increased risk of PCSM, while seven were associated with decreased risk. Larger studies that focus on fatal PCa are needed to identify more markers that could aid prediction. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
C1 [Shui, Irene M.; Lindstroem, Sara; Gerke, Travis; Penney, Kathryn L.; Gaziano, J. Michael; Ma, Jing; Stampfer, Meir; Trichopoulos, Dimitrios; Mucci, Lorelei A.; Giovannucci, Edward; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Kibel, Adam S.] Brigham & Womens Hosp, Dept Surg, Div Urol, Boston, MA 02115 USA.
[Kibel, Adam S.; Penney, Kathryn L.; Ma, Jing; Stampfer, Meir] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Berndt, Sonja I.; Albanes, Demetrius; Chanock, Stephen; Hoover, Robert; Yeager, Meredith] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Campa, Daniele] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
[Penney, Kathryn L.; Ma, Jing; Stampfer, Meir] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Berg, Christine] Johns Hopkins Med, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD USA.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Chanock, Stephen; Yeager, Meredith] Frederick Natl Lab Canc Res, Canc Genom Res Lab, Gaithersburg, MD USA.
[Crawford, E. David] Univ Colorado, Denver, CO 80202 USA.
[Diver, W. Ryan; Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Gaziano, J. Michael] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham G.] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia.
[Henderson, Brian; Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Johansson, Mattias] Int Agcy Res Canc, F-69372 Lyon, France.
[Johansson, Mattias] Umea Univ, Dept Biobank Res, Umea, Sweden.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA.
[Navarro, Carmen] Murcia Reg Hlth Author, Dept Epidemiol, Murcia, Spain.
[Navarro, Carmen] Univ Murcia, Dept Hlth & Social Sci, Murcia, Spain.
[Overvad, Kim] Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark.
[Severi, Gianluca] HuGeF Fdn, Turin, Italy.
[Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, London, England.
[Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens, Greece.
[Bueno-de-Mesquita, H. Bas; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
RP Shui, IM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM ishui@hsph.harvard.edu
RI Albanes, Demetrius/B-9749-2015; Campa, Daniele/K-1617-2016;
OI Campa, Daniele/0000-0003-3220-9944; Giles, Graham/0000-0003-4946-9099
FU NIH NCI [U19 CA148537-01]; American Cancer Society; NCI [5U01CA098710];
Danish Cancer Society; Hellenic Health Foundation; Health Research Fund;
regional government of Andalucia; regional government of Asturias;
regional government of Basque Country; regional government of Murcia
[6236]; Navarra; ISCIII RETIC (Spain) [RD06/0020]; intramural program of
the Division of Cancer Epidemiology and Genetics, NCI; Cancer Council
Victoria
FX This work was supported by the NIH NCI (cooperative agreement U19
CA148537-01). The maintenance of the Cancer Prevention Study II is
supported by the American Cancer Society, and genotyping of the CPS-II
samples was supported by a grant from the NCI (5U01CA098710). The Danish
study Diet, Cancer and Health was funded by the Danish Cancer Society.
EPIC-Greece was supported through the Hellenic Health Foundation.
EPIC-Spain was supported by Health Research Fund; the regional
governments of Andalucia, Asturias, Basque Country, Murcia (No. 6236),
and Navarra; and ISCIII RETIC (RD06/0020; Spain). PLCO was supported by
the intramural program of the Division of Cancer Epidemiology and
Genetics, NCI. The Melbourne Collaborative Cohort Study recruitment was
funded and its follow-up supported by Cancer Council Victoria.
NR 29
TC 17
Z9 17
U1 3
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD JUN
PY 2014
VL 65
IS 6
BP 1069
EP 1075
DI 10.1016/j.eururo.2013.12.058
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA AG4JV
UT WOS:000335386700025
PM 24411283
ER
PT J
AU Ward, MM
Guthrie, LC
Alba, M
AF Ward, Michael M.
Guthrie, Lori C.
Alba, Maria
TI Dependence of the minimal clinically important improvement on the
baseline value is a consequence of floor and ceiling effects and not
different expectations by patients
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article
DE Minimal clinically important difference; Responsiveness; Ceiling effect;
Floor effect; Outcome measures; Rheumatoid arthritis
ID LOW-BACK-PAIN; VISUAL ANALOG SCALE; QUALITY-OF-LIFE; HEALTH-STATUS
MEASURES; RHEUMATOID-ARTHRITIS; REPORTED OUTCOMES; INTENSITY;
QUESTIONNAIRE; MEANINGFUL; SENSITIVITY
AB Objective: Estimates of minimal clinically important improvements (MCIIs) are larger among patients with higher values at baseline, suggesting that these patients require larger changes to appreciate improvements. We examined if baseline dependency of MCIIs was associated with specific patients across three measures, or was owing to floor and ceiling effects.
Study Design and Setting: We prospectively examined 250 outpatients with active rheumatoid arthritis (RA). We used an anchor-based approach to estimate MCIIs for three measures of RA activity (patient global assessment, swollen joint count, and walking time). We examined if the same patients constituted the baseline subgroups with high MOTs across measures.
Results: The MCIIs were greater for those with higher baseline values of all three measures. At the ceiling, there was little opportunity to improve, and judgments were unrelated to measured changes. At midrange, improvements were balanced by worsenings, including some judged as improvements. At the floor, improvements were not similarly balanced. Patients in subgroups with high MCII for patient global assessment were not also predominantly in subgroups with high MCII for the swollen joint count or walking time, and vice versa.
Conclusion: Variation in MCII by baseline values is because of floor and ceiling effects rather than expectations of particular patients. Published by Elsevier Inc.
C1 [Ward, Michael M.; Guthrie, Lori C.; Alba, Maria] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Ward, MM (reprint author), NIAMSD, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
OI Alba, Maria/0000-0002-2131-6325
FU Intramural Research Program, National Institute of Arthritis;
Musculoskeletal and Skin Diseases, National Institutes of Health; U.S.
Public Health Service grant [AR45177]
FX This study was supported by the Intramural Research Program, National
Institute of Arthritis and Musculoskeletal and Skin Diseases, National
Institutes of Health, and U.S. Public Health Service grant AR45177.
NR 36
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 0895-4356
EI 1878-5921
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD JUN
PY 2014
VL 67
IS 6
BP 689
EP 696
DI 10.1016/j.jclinepi.2013.10.025
PG 8
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA AG7PL
UT WOS:000335610000013
PM 24556220
ER
PT J
AU Ungerleider, LG
Galkin, TW
Desimone, R
Gattass, R
AF Ungerleider, Leslie G.
Galkin, Thelma W.
Desimone, Robert
Gattass, Ricardo
TI Subcortical Projections of Area V2 in the Macaque
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID SUPERIOR TEMPORAL SULCUS; MONKEY VISUAL-CORTEX; OLD-WORLD MONKEYS;
RHESUS-MONKEY; CEBUS MONKEY; CORTICAL PROJECTIONS; INFERIOR PULVINAR;
STRIATE CORTEX; MACACA-MULATTA; NEUROCHEMICAL SUBDIVISIONS
AB To investigate the subcortical efferent connections of visual area V2, we injected tritiated amino acids under electrophysiological control into 15 V2 sites in 14 macaques. The injection sites included the fovea representation as well as representations ranging from central to far peripheral eccentricities in both the upper and lower visual fields. The results indicated that V2 projects topographically to different portions of the inferior and lateral pulvinar and to the superficial and intermediate layers of the superior colliculus. Within the pulvinar, the V2 projections terminated in fields P1, P2, and P4, with the strongest projection being in P2. Central visual field injections in V2 labeled projection zones in P1 and P2, whereas peripheral field injections labeled P1, P2, and P4. No projections were found in P3. Both central and peripheral field injections in V2 projected topographically to the superficial and intermediate layers of the superior colliculus. Projections from V2 to the pulvinar and the superior colliculus constituted cortical-subcortical loops through which circuits serving spatial attention are activated.
C1 [Ungerleider, Leslie G.; Galkin, Thelma W.] NIH, Bethesda, MD 20892 USA.
[Desimone, Robert] MIT, Cambridge, MA 02139 USA.
[Gattass, Ricardo] Univ Fed Rio de Janeiro, BR-21941 Rio De Janeiro, Brazil.
RP Ungerleider, LG (reprint author), Lab Brain & Cognit, NIMH Bldg 10,Room 4C104,10 Ctr Dr, Bethesda, MD 20892 USA.
EM ungerlel@mail.nih.gov
FU CNPq; FAPERJ; [EY017292]
FX We thank Charles G. Gross for his support during several phases of this
work, Juliana Soares for her valuable comments on the manuscript, and
John N. Sewell III and Joanna Lawrence for their skillful technical
assistance. The injections into V2 were made at the Laboratory of
Professor Charles Gross in Princeton, in the late 1970s. L. G. U., R.
D., and R. G. planned the experiment and placed the injections, and T.
W. G. plotted the data. R. G., R. D., and L. G. U. reviewed the data,
prepared the illustrations, and wrote the manuscript. R. D. was
supported by EY017292, and R. G. was supported by CNPq and FAPERJ.
NR 80
TC 4
Z9 4
U1 0
U2 3
PU MIT PRESS
PI CAMBRIDGE
PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA
SN 0898-929X
EI 1530-8898
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD JUN
PY 2014
VL 26
IS 6
SI SI
BP 1220
EP 1233
DI 10.1162/jocn_a_00571
PG 14
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA AG6CM
UT WOS:000335506100004
PM 24456395
ER
PT J
AU De Pisapia, N
Serra, M
Rigo, P
Jager, J
Papinutto, N
Esposito, G
Venuti, P
Bornstein, MH
AF De Pisapia, Nicola
Serra, Mauro
Rigo, Paola
Jager, Justin
Papinutto, Nico
Esposito, Gianluca
Venuti, Paola
Bornstein, Marc H.
TI Interpersonal Competence in Young Adulthood and Right Laterality in
White Matter
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID DIFFUSION TENSOR TRACTOGRAPHY; MIRROR NEURON SYSTEM; RIGHT-HEMISPHERE;
HUMAN BRAIN; SOCIAL COGNITION; EMOTIONAL INTELLIGENCE;
LEARNING-DISABILITIES; CONFLICT-RESOLUTION; SPATIAL STATISTICS;
CHILDHOOD
AB The right hemisphere of the human brain is known to be involved in processes underlying emotion and social cognition. Clinical neuropsychology investigations and brain lesion studies have linked a number of personality and social disorders to abnormal white matter (WM) integrity in the right hemisphere. Here, we tested the hypothesis that interpersonal competencies are associated with integrity of WM tracts in the right hemisphere of healthy young adults. Thirty-one participants underwent diffusion tensor imaging scanning. Fractional anisotropy was used to quantify water diffusion. After the scanning session, participants completed the Adolescent Interpersonal Competence Questionnaire. Fractional anisotropy was subsequently correlated with Adolescent Interpersonal Competence Questionnaire scores using tract-based spatial statistics. Higher interpersonal competencies are related to higher WM integrity in several major tracts of the right hemisphere, in specific the uncinate fasciculus, the cingulum, the forceps minor, the infero-fronto occipital fasciculus, the inferior longitudinal fasciculus, and the superior longitudinal fasciculus. These results provide the first direct analysis of the neuroanatomical basis of interpersonal competencies and young adult self-reported skills in social contexts.
C1 [De Pisapia, Nicola; Serra, Mauro; Rigo, Paola; Esposito, Gianluca; Venuti, Paola] Univ Trento, Rovereto, TN, Italy.
[Jager, Justin] Arizona State Univ, Tempe, AZ 85287 USA.
[Papinutto, Nico] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Esposito, Gianluca] RIKEN Brain Sci Inst, Saitama, Japan.
[Bornstein, Marc H.] NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP De Pisapia, N (reprint author), Univ Trento, Dept Psychol & Cognit Sci, Rovereto, TN, Italy.
EM nicola.depisapia@unitn.it
OI De Pisapia, Nicola/0000-0002-1089-8841
FU Intramural Research Program of the NIH, NICHD; Center for Mind/Brain
Sciences of the University of Trento (Italy); Department of Psychology
and Cognitive Science of the University of Trento (Italy)
FX This research was supported by the Intramural Research Program of the
NIH, NICHD, by the Center for Mind/Brain Sciences of the University of
Trento (Italy), and by the Department of Psychology and Cognitive
Science of the University of Trento (Italy). For Charles G. Gross with
admiration and affection in equal measure.
NR 88
TC 5
Z9 5
U1 2
U2 10
PU MIT PRESS
PI CAMBRIDGE
PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA
SN 0898-929X
EI 1530-8898
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD JUN
PY 2014
VL 26
IS 6
SI SI
BP 1257
EP 1265
DI 10.1162/jocn_a_00534
PG 9
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA AG6CM
UT WOS:000335506100006
PM 24345175
ER
PT J
AU Liu, JT
Fan, WW
Liu, MH
Lin, XD
Wang, YB
Wang, F
Chen, XY
Cao, F
Liang, JM
AF Liu, Junting
Fan, Weiwei
Liu, Muhan
Lin, Xiuduan
Wang, Yabin
Wang, Fu
Chen, Xiaoyuan
Cao, Feng
Liang, Jimin
TI Spatial Vascular Volume Fraction Imaging for Quantitative Assessment of
Angiogenesis
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE Angiogenesis; Mesenchymal stem cells; SVVF; Quantitative assessment;
Hybrid micro-CTA/BLT
ID MESENCHYMAL STEM-CELLS; IN-VIVO; BIOLUMINESCENCE TOMOGRAPHY; STROMAL
CELLS; BONE-MARROW; MICE; PERFUSION; ISCHEMIA; PROLIFERATION;
REGENERATION
AB The purpose of this study is to set up a quantitative imaging strategy for therapeutic angiogenesis and monitoring the spatial distribution and survival of the transplanted mesenchymal stem cells (MSCs) in vivo simultaneously.
Mouse adipose-derived MSCs (AD-MSCs) were isolated from firefly luciferase and enhanced green fluorescent protein positive transgenic mice, and implanted intramuscularly into hindlimbs of C57BL/6 mice. Serial spatial vascular volume fraction (SVVF) imaging was performed to quantitatively assess angiogenesis by calculating the spatially explicit vascular volume. The hybrid microcomputed tomography angiography/bioluminescence tomography (micro-CTA/BLT) was used to track the fate of AD-MSCs in vivo. Laser Doppler perfusion imaging (LDPI) was used to evaluate blood perfusion. Ex vivo conventional methods were performed to cross-validate the therapeutic angiogenesis.
There was a linear correlation relation between the cell number and Fluc/Fluc protein signal intensity in AD-MSCs via BLT. LDPI showed improved perfusion rate in mice treated with cytotherapy, compared to control mice. Furthermore, angiogenesis assessed by SVVF was 10.67 +/- 0.41 %, 13.99 +/- 0.28 %, and 23.50 +/- 1.23 % on days 7, 14, and 28 post-transplantation of AD-MSCs, respectively. Vascular densities of the longitudinally monitored ischemic hindlimbs were significantly higher than those at early time points and controls, which was also confirmed by vascular corrosion casting, scanning electron microscopic imaging, and histological analysis.
Hybrid high-resolution micro-CTA/BLT enabled monitoring and quantitative assessment of cytotherapeutically induced angiogenesis in vivo.
C1 [Liu, Junting; Liu, Muhan; Lin, Xiuduan; Wang, Fu; Liang, Jimin] Xidian Univ, Sch Life Sci & Technol, Xian 710071, Peoples R China.
[Fan, Weiwei; Wang, Yabin; Cao, Feng] Fourth Mil Med Univ, Xijing Hosp, Dept Cardiol, Xian 710032, Peoples R China.
[Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
RP Cao, F (reprint author), Fourth Mil Med Univ, Xijing Hosp, Dept Cardiol, 127 West Changle Rd, Xian 710032, Peoples R China.
EM wind8828@gmail.com; jiminliang@gmail.com
RI Liu, Junting/F-3550-2010; Liang, Jimin/B-5394-2014;
OI Liu, Junting/0000-0002-2099-0190; Wang, Fu/0000-0001-9222-0833
FU National Basic Research and Development Program of China (973 program)
[2011CB707702, 2013CB733802]; National Nature Science Foundation of
China [81227901, 81090270, 81090272, 81090274, 31371006]; Ministry of
Science and Technology of China (863 program) [2012AA02A603]; National
Institute of Biomedical Imaging and Bioengineering, National Institutes
of Health
FX We would like to thank Dr. Robert Gillies from Moffitt Cancer Center and
Research Institute for scientific insight. This work was supported in
part by the National Basic Research and Development Program of China
(973 program nos. 2011CB707702 and 2013CB733802), the National Nature
Science Foundation of China (81227901, 81090270, 81090272, 81090274, and
31371006), the Ministry of Science and Technology of China (863 program
2012AA02A603), and the Intramural Research Program of the National
Institute of Biomedical Imaging and Bioengineering, National Institutes
of Health.
NR 35
TC 1
Z9 1
U1 0
U2 16
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
EI 1860-2002
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD JUN
PY 2014
VL 16
IS 3
BP 362
EP 371
DI 10.1007/s11307-013-0694-z
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AG9JH
UT WOS:000335734900008
PM 24158404
ER
PT J
AU Peterson, LM
Kurland, BF
Schubert, EK
Link, JM
Gadi, VK
Specht, JM
Eary, JF
Porter, P
Shankar, LK
Mankoff, DA
Linden, HM
AF Peterson, Lanell M.
Kurland, Brenda F.
Schubert, Erin K.
Link, Jeanne M.
Gadi, V. K.
Specht, Jennifer M.
Eary, Janet F.
Porter, Peggy
Shankar, Lalitha K.
Mankoff, David A.
Linden, Hannah M.
TI A Phase 2 Study of 16 alpha-[F-18]-fluoro-17 beta-estradiol Positron
Emission Tomography (FES-PET) as a Marker of Hormone Sensitivity in
Metastatic Breast Cancer (MBC)
SO MOLECULAR IMAGING AND BIOLOGY
LA English
DT Article
DE FES-PET; FDG-PET; Metastatic breast cancer; ER expression; Endocrine
therapy; Response
ID ESTROGEN-RECEPTOR STATUS; FDG-PET; SYSTEMIC THERAPY; AFRICAN-AMERICAN;
SOLID TUMORS; EXPRESSION; WOMEN; F-18-FLUOROESTRADIOL; FLUOROESTRADIOL;
SURVIVAL
AB 16 alpha-[F-18]-fluoro-17 beta-estradiol positron emission tomography (FES-PET) quantifies estrogen receptor (ER) expression in tumors and may provide diagnostic benefit.
Women with newly diagnosed metastatic breast cancer (MBC) from an ER-positive primary tumor were imaged before starting endocrine therapy. FES uptake was evaluated qualitatively and quantitatively, and associated with response and with ER expression.
Nineteen patients underwent FES imaging. Fifteen had a biopsy of a metastasis and 15 were evaluable for response. Five patients had quantitatively low FES uptake, six had at least one site of qualitatively FES-negative disease. All patients with an ER-negative biopsy had both low uptake and at least one site of FES-negative disease. Of response-evaluable patients, 2/2 with low FES standard uptake value tumors had progressive disease within 6 months, as did 2/3 with qualitatively FES-negative tumors.
Low/absent FES uptake correlates with lack of ER expression. FES-positron emission tomography can help identify patients with endocrine resistant disease and safely measures ER in MBC.
C1 [Peterson, Lanell M.; Schubert, Erin K.; Gadi, V. K.; Specht, Jennifer M.; Mankoff, David A.; Linden, Hannah M.] Univ Washington, Med Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA.
[Kurland, Brenda F.; Gadi, V. K.; Specht, Jennifer M.; Porter, Peggy; Linden, Hannah M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Kurland, Brenda F.] Univ Pittsburgh, Pittsburgh, PA USA.
[Schubert, Erin K.; Mankoff, David A.] Univ Penn, Philadelphia, PA 19104 USA.
[Link, Jeanne M.; Eary, Janet F.] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Shankar, Lalitha K.] NCI, Canc Imaging Program, Bethesda, MD 20892 USA.
RP Peterson, LM (reprint author), Univ Washington, Med Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA.
EM lanell@uw.edu
OI Specht, Jennifer/0000-0003-1484-2113
FU NCI [N01-CM-37008, 8052]; UPCI Biostatistics Shared Resource
[P30CA047904]
FX The authors would like to thank Eunice How, the radiochemistry staff,
nuclear medicine technologists, and physicists in the UW Department of
Radiology as well as the staff of the Fred Hutchinson Breast Cancer
Research Center Cancer Biology lab. This study was sponsored by the NCI
Phase I and II Cancer Imaging Program (Contract #N01-CM-37008, Protocol
8052) and was supported by the UPCI Biostatistics Shared Resource
(P30CA047904).
NR 35
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Z9 25
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1536-1632
EI 1860-2002
J9 MOL IMAGING BIOL
JI Mol. Imaging. Biol.
PD JUN
PY 2014
VL 16
IS 3
BP 431
EP 440
DI 10.1007/s11307-013-0699-7
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA AG9JH
UT WOS:000335734900015
PM 24170452
ER
PT J
AU Zhang, W
Yan, ZF
Gao, JH
Sun, L
Huang, XY
Liu, Z
Yu, SY
Cao, CJ
Zuo, LJ
Chen, ZJ
Hu, Y
Wang, F
Hong, JS
Wang, XM
AF Zhang, Wei
Yan, Zhao-fen
Gao, Jun-hua
Sun, Li
Huang, Xi-yan
Liu, Zhuo
Yu, Shu-yang
Cao, Chen-Jie
Zuo, Li-jun
Chen, Ze-Jie
Hu, Yang
Wang, Fang
Hong, Jau-shyong
Wang, Xiao-min
TI Role and Mechanism of Microglial Activation in Iron-Induced Selective
and Progressive Dopaminergic Neurodegeneration
SO MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE Dopaminergic neurodegeneration; Iron; Microglial activation;
Neuroinflammation; beta-nicotinamide adenine dinucleotide phosphate
oxidase 2; Parkinson's disease; Mechanism
ID PROTEIN-KINASE-C; PARKINSONS-DISEASE; NADPH OXIDASE; OXIDATIVE STRESS;
ALPHA-SYNUCLEIN; HUMAN MONOCYTES; LEWY BODIES; CELL-DEATH; METABOLISM;
BRAIN
AB Parkinson's disease (PD) patients have excessive iron depositions in substantia nigra (SN). Neuroinflammation characterized by microglial activation is pivotal for dopaminergic neurodegeneration in PD. However, the role and mechanism of microglial activation in iron-induced dopaminergic neurodegeneration in SN remain unclear yet. This study aimed to investigate the role and mechanism of microglial beta-nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) activation in iron-induced selective and progressive dopaminergic neurodegeneration. Multiple primary midbrain cultures from rat, NOX2(+/+) and NOX2(-/-) mice were used. Dopaminergic neurons, total neurons, and microglia were visualized by immunostainings. Cell viability was measured by MTT assay. Superoxide (O-2(center dot-)) and intracellular reactive oxygen species (iROS) were determined by measuring SOD-inhibitable reduction of tetrazolium salt WST-1 and DCFH-DA assay. mRNA and protein were detected by real-time PCR and Western blot. Iron induces selective and progressive dopaminergic neurotoxicity in rat neuron-microglia-astroglia cultures and microglial activation potentiates the neurotoxicity. Activated microglia produce a magnitude of O-2(center dot-) and iROS, and display morphological alteration. NOX2 inhibitor diphenylene iodonium protects against iron-elicited dopaminergic neurotoxicity through decreasing microglial O-2(center dot-) generation, and NOX2(-/-) mice are resistant to the neurotoxicity by reducing microglial O-2(center dot-) production, indicating that iron-elicited dopaminergic neurotoxicity is dependent of NOX2, a O-2(center dot-)-generating enzyme. NOX2 activation is indicated by the increased mRNA and protein levels of subunits P47 and gp91. Molecules relevant to NOX2 activation include PKC-sigma, P38, ERK1/2, JNK, and NF-KBP65 as their mRNA and protein levels are enhanced by NOX2 activation. Iron causes selective and progressive dopaminergic neurodegeneration, and microglial NOX2 activation potentiates the neurotoxicity. PKC-sigma, P38, ERK1/2, JNK, and NF-KBP65 are the potential molecules relevant to microglial NOX2 activation.
C1 [Zhang, Wei; Yan, Zhao-fen; Gao, Jun-hua; Sun, Li; Huang, Xi-yan; Liu, Zhuo; Yu, Shu-yang; Cao, Chen-Jie; Zuo, Li-jun; Chen, Ze-Jie; Hu, Yang; Wang, Fang] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing 100050, Peoples R China.
[Zhang, Wei] Beijing Inst Brain Disorders, Parkinsons Dis Ctr, Beijing 100053, Peoples R China.
[Zhang, Wei] Beijing Key Lab Parkinsons Dis, Beijing 100053, Peoples R China.
[Hong, Jau-shyong] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA.
[Wang, Xiao-min] Capital Med Univ, Dept Physiol, Beijing 100069, Peoples R China.
[Wang, Xiao-min] Capital Med Univ, Dept Neurobiol, Beijing 100069, Peoples R China.
[Wang, Xiao-min] Minist Educ, Key Lab Neurodegenerat Disorders, Beijing 100069, Peoples R China.
[Wang, Xiao-min] Beijing Inst Brain Disorders, Beijing 100069, Peoples R China.
RP Zhang, W (reprint author), Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing 100050, Peoples R China.
EM ttyyzw@163.com
FU National Basic Research Program of China [2011CB504100]; National
Natural Science Foundation of China [81071015, 30770745, 81030062];
Natural Science Foundation of Beijing, China [7082032]; High Level
Technical Personnel Training Project of Beijing Health System, China
[2009-3-26]; Excel lent Personnel Training Project of Beijing, China
[20071D0300400076]; Capital Clinical Characteristic Application Research
Project [Z121107001012161]; Important National Science and Technology
Specific Project [2011ZX09102-003-01]; Beijing Natural Science
Foundation [kz200910025001]; Basic-Clinical Research Cooperation Funding
of Capital Medical University [10JL49]
FX This work is supported by the National Basic Research Program of China
(2011CB504100); the National Natural Science Foundation of China
(81071015, 30770745, and 81030062), the Natural Science Foundation of
Beijing, China (7082032), High Level Technical Personnel Training
Project of Beijing Health System, China (2009-3-26), Excel lent
Personnel Training Project of Beijing, China (20071D0300400076), Capital
Clinical Characteristic Application Research (Z121107001012161),
Important National Science and Technology Specific Projects (
2011ZX09102-003-01), Key Project of Beijing Natural Science Foundation
(kz200910025001), and Basic-Clinical Research Cooperation Funding of
Capital Medical University (10JL49). We thank Dr. Yang Du for her
efforts of editing the manuscript.
NR 58
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Z9 14
U1 2
U2 13
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0893-7648
EI 1559-1182
J9 MOL NEUROBIOL
JI Mol. Neurobiol.
PD JUN
PY 2014
VL 49
IS 3
BP 1153
EP 1165
DI 10.1007/s12035-013-8586-4
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA AG8KE
UT WOS:000335666500004
PM 24277523
ER
PT J
AU Choi, K
Forster, JL
AF Choi, Kelvin
Forster, Jean L.
TI Context on Use Is Needed Before Public Health Recommendations Are Made
About E-Cigarettes Response
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Letter
C1 [Choi, Kelvin] Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, Bethesda, MD USA.
[Forster, Jean L.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
RP Choi, K (reprint author), Natl Inst Minor Hlth & Hlth Dispar, Div Intramural Res, Bethesda, MD USA.
RI Choi, Kelvin/H-1544-2015
NR 5
TC 8
Z9 8
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUN
PY 2014
VL 46
IS 6
BP E58
EP E59
DI 10.1016/j.amepre.2014.02.013
PG 3
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA V43UN
UT WOS:000209706400004
PM 24842747
ER
PT J
AU Renvoise, B
Chang, J
Singh, R
Yonekawa, S
FitzGibbon, EJ
Mankodi, A
Vanderver, A
Schindler, AB
Toro, C
Gahl, WA
Mahuran, DJ
Blackstone, C
Pierson, TM
AF Renvoise, Benoit
Chang, Jaerak
Singh, Rajat
Yonekawa, Sayuri
FitzGibbon, Edmond J.
Mankodi, Ami
Vanderver, Adeline
Schindler, Alice B.
Toro, Camilo
Gahl, William A.
Mahuran, Don J.
Blackstone, Craig
Pierson, Tyler Mark
TI Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and
SPG11
SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
LA English
DT Article
AB Objective: Hereditary spastic paraplegias (HSPs) are among the most genetically diverse inherited neurological disorders, with over 70 disease loci identified (SPG1-71) to date. SPG15 and SPG11 are clinically similar, autosomal recessive disorders characterized by progressive spastic paraplegia along with thin corpus callosum, white matter abnormalities, cognitive impairment, and ophthalmologic abnormalities. Furthermore, both have been linked to earlyonset parkinsonism. Methods: We describe two new cases of SPG15 and investigate cellular changes in SPG15 and SPG11 patient-derived fibroblasts, seeking to identify shared pathogenic themes. Cells were evaluated for any abnormalities in cell division, DNA repair, endoplasmic reticulum, endosomes, and lysosomes. Results: Fibroblasts prepared from patients with SPG15 have selective enlargement of LAMP1-positive structures, and they consistently exhibited abnormal lysosomal storage by electron microscopy. A similar enlargement of LAMP1-positive structures was also observed in cells from multiple SPG11 patients, though prominent abnormal lysosomal storage was not evident. The stabilities of the SPG15 protein spastizin/ZFYVE26 and the SPG11 protein spatacsin were interdependent. Interpretation: Emerging studies implicating these two proteins in interactions with the late endosomal/lysosomal adaptor protein complex AP-5 are consistent with shared abnormalities in lysosomes, supporting a converging mechanism for these two disorders. Recent work with Zfyve26-/- mice revealed a similar phenotype to human SPG15, and cells in these mice had endolysosomal abnormalities. SPG15 and SPG11 are particularly notable among HSPs because they can also present with juvenile parkinsonism, and this lysosomal trafficking or storage defect may be relevant for other forms of parkinsonism associated with lysosomal dysfunction.
C1 [Renvoise, Benoit; Chang, Jaerak; Singh, Rajat; Mankodi, Ami; Schindler, Alice B.; Blackstone, Craig; Pierson, Tyler Mark] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Yonekawa, Sayuri; Mahuran, Don J.] Hosp Sick Children, Res Inst, Toronto, ON, Canada.
[Yonekawa, Sayuri; Mahuran, Don J.] Univ Toronto, Toronto, ON, Canada.
[FitzGibbon, Edmond J.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
[Vanderver, Adeline] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Toro, Camilo; Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Toro, Camilo; Gahl, William A.] NIH, Undiagnosed Dis Program, Off Rare Dis Res, Bethesda, MD 20892 USA.
[Toro, Camilo; Gahl, William A.] NHGRI, Bethesda, MD 20892 USA.
[Pierson, Tyler Mark] Cedars Sinai Med Ctr, Dept Pediat, 8700 Beverly Blvd,ASHP 8401, Los Angeles, CA 90048 USA.
[Pierson, Tyler Mark] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA.
[Pierson, Tyler Mark] Cedars Sinai Med Ctr, Regenerat Med Inst, Los Angeles, CA 90048 USA.
RP Pierson, TM (reprint author), Cedars Sinai Med Ctr, Dept Pediat, 8700 Beverly Blvd,ASHP 8401, Los Angeles, CA 90048 USA.
EM tyler.pierson@cshs.org
FU Intramural NIH HHS [Z01 NS002992-06, Z01 NS002992-07]
NR 32
TC 15
Z9 15
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2328-9503
J9 ANN CLIN TRANSL NEUR
JI Ann. Clin. Transl. Neurol.
PD JUN
PY 2014
VL 1
IS 6
BP 379
EP 389
DI 10.1002/acn3.64
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA V45KI
UT WOS:000209815100001
PM 24999486
ER
PT J
AU Adeyemo, MA
McDuffie, JR
Brady, S
Condarco, TA
Garcia, RM
Hubbard, VS
Yanovski, JA
AF Adeyemo, Mopelola Adetola
McDuffie, Jennifer R.
Brady, Sheila
Condarco, Tania Andrea
Garcia, Rubi Maricela
Hubbard, Van S.
Yanovski, Jack A.
TI Effect of Orlistat on Ratings of Fat-Containing Foods Among Obese
Adolescents
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Adeyemo, Mopelola Adetola; Garcia, Rubi Maricela; Yanovski, Jack A.] NIH, Bethesda, MD 20892 USA.
[McDuffie, Jennifer R.; Brady, Sheila; Condarco, Tania Andrea] NICHD, NIH, Bethesda, MD USA.
[Hubbard, Van S.] NIH, DNRC, Bethesda, MD 20892 USA.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0938
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103170
ER
PT J
AU Agarwal, N
Iyer, D
Oplt, T
Shenoy, A
Schubert, U
Kopp, JB
Balasubramanyam, A
AF Agarwal, Neeti
Iyer, Dinakar
Oplt, Toni
Shenoy, Akhil
Schubert, Ulrich
Kopp, Jeffrey B.
Balasubramanyam, Ashok
TI Mechanism of HIV-Associated Hepatic Steatosis: Role of HIV-1 Accessory
Protein Vpr, Pparalpha and Lxralpha
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Agarwal, Neeti; Iyer, Dinakar; Oplt, Toni; Shenoy, Akhil; Balasubramanyam, Ashok] Baylor Coll Med, Houston, TX 77030 USA.
[Schubert, Ulrich] Univ Erlangen Nurnberg, Erlangen, Germany.
[Kopp, Jeffrey B.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR21-2
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102266
ER
PT J
AU Allison, MB
Patterson, CM
Krashes, M
Lowell, BB
Olson, DP
Myers, MG
AF Allison, Margaret B.
Patterson, Christa M.
Krashes, Michael
Lowell, Bradford Barr
Olson, David P.
Myers, Martin Grosvenor
TI Translational Profiling Reveals the Transcriptome of Hypothalamic Leptin
Receptor Neurons and Its Regulation By Leptin
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Allison, Margaret B.; Patterson, Christa M.; Olson, David P.; Myers, Martin Grosvenor] Univ Michigan, Ann Arbor, MI 48109 USA.
[Krashes, Michael] NIDDK, NIH, Bethesda, MD 20892 USA.
[Lowell, Bradford Barr] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR45-3
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103151
ER
PT J
AU Alwazeer, MR
Olutoye, O
Margolin, JF
Castro, E
Williams, J
Quezado, MM
Lodish, MB
Stratakis, CA
Balazs, AE
AF Alwazeer, Mouhammad Rateb
Olutoye, Oluyinka
Margolin, Judith F.
Castro, Eumenia
Williams, Jennifer
Quezado, Martha M.
Lodish, Maya Beth
Stratakis, Constantine A.
Balazs, Andrea Erika
TI Cushing Syndrome Secondary to Bronchial Carcinoid Tumor in a 14-Year-
Old Female: Challenges in Diagnosis and Treatment
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Alwazeer, Mouhammad Rateb] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA.
[Olutoye, Oluyinka; Margolin, Judith F.; Castro, Eumenia; Williams, Jennifer; Balazs, Andrea Erika] Baylor Coll Med, Houston, TX 77030 USA.
[Quezado, Martha M.] NCI, Bethesda, MD 20892 USA.
[Lodish, Maya Beth; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0136
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103280
ER
PT J
AU Arduc, A
Yavuz, S
Linderman, JD
Smith, S
Eliseeva, E
Neumann, SE
Celi, FS
AF Arduc, Ayse
Yavuz, Sahzene
Linderman, Joyce D.
Smith, Sheila
Eliseeva, Elena
Neumann, Susanne E.
Celi, Francesco S.
TI Impaired Thyrotroph Dynamics during Thyroid Hormone Withdrawal in a
Patient with Differentiated Thyroid Cancer and Underlying Graves'
Disease
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Arduc, Ayse] NIDDKD, Diabet Endocrine & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Yavuz, Sahzene] Univ Florida, Gainesville, FL 32611 USA.
[Linderman, Joyce D.; Smith, Sheila] NIDDK, Diabet Endocrinol Obes Branch, NIH, Bethesda, MD 20892 USA.
[Eliseeva, Elena; Neumann, Susanne E.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Celi, Francesco S.] Virginia Commonwealth Univ, Richmond, VA USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0497
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805108237
ER
PT J
AU Bernhardt, ML
Williams, CJ
AF Bernhardt, Miranda L.
Williams, Carmen J.
TI Normal Fertilization Is Observed in Oocyte-Specific Stiml Knockout Mice
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Bernhardt, Miranda L.; Williams, Carmen J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0055
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109314
ER
PT J
AU Beuschlein, F
Fassnacht, M
Assie, G
Calebiro, D
Stratakis, CA
Osswald, A
Ronchi, CL
Wielanda, T
Sbiera, S
Faucz, FR
Schaak, K
Schmittfull, A
Schwarzmayr, T
Barreau, O
Vezzosi, D
Rizk-Rabbin, M
Zabel, U
Szarek, E
Salpea, P
Forlino, A
Vetro, A
Zuffardi, O
Kisker, C
Diener, S
Meitinger, T
Lohse, M
Reincke, M
Bertherat, JY
Strom, TM
Allolio, B
AF Beuschlein, Felix
Fassnacht, Martin
Assie, Guillaume
Calebiro, Davide
Stratakis, Constantine A.
Osswald, Andrea
Ronchi, Cristina Lucia
Wielanda, Thomas
Sbiera, Silviu
Faucz, Fabio Rueda
Schaak, Kathrin
Schmittfull, Anett
Schwarzmayr, Thomas
Barreau, Olivia
Vezzosi, Delphine
Rizk-Rabbin, Marthe
Zabel, Ulrike
Szarek, Eva
Salpea, Paraskevi
Forlino, Antonella
Vetro, Annalisa
Zuffardi, Orsetta
Kisker, Caroline
Diener, Susanne
Meitinger, Thomas
Lohse, Martin
Reincke, Martin
Bertherat, Jerome Yves
Strom, Tim M.
Allolio, Bruno
TI Constitutive Activation of Prkaca in Adrenal Cushing's Syndrome
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Beuschlein, Felix; Reincke, Martin] Univ Munich, Munich, Germany.
[Fassnacht, Martin; Calebiro, Davide; Lohse, Martin; Allolio, Bruno] Univ Wurzburg, Wurzburg, Germany.
[Assie, Guillaume; Bertherat, Jerome Yves] Inst Cochin, CNRS, Unite Mixte Rech 8104, INSERM,Unite 1016, Paris, France.
[Stratakis, Constantine A.; Faucz, Fabio Rueda; Szarek, Eva; Salpea, Paraskevi] NIH, Bethesda, MD 20892 USA.
[Osswald, Andrea] Med Klin & Poliklin IV, Munich, Germany.
[Ronchi, Cristina Lucia] Univ Hosp Wuerzburg, Wurzburg, Germany.
[Wielanda, Thomas; Diener, Susanne; Meitinger, Thomas; Strom, Tim M.] Helmholtz Zentrum Munchen, Inst Human Genet, Munich, Germany.
[Sbiera, Silviu; Schaak, Kathrin] Ludwig Maximilians Univ Munchen, Med Klin & Poliklin 4, Munich, Germany.
[Schmittfull, Anett; Schwarzmayr, Thomas] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Barreau, Olivia] Paris Descartes Univ, Inst Cochin, CNRS 8104, Inserm,U1016, Paris, France.
[Vezzosi, Delphine] Hosp Rangueil, Toulouse, France.
[Rizk-Rabbin, Marthe] CNRS, UMR 8104, INSERM, U1016, Paris, France.
[Zabel, Ulrike] Univ Wurzburg, Inst Pharmacol & Toxicol, Wurzburg, Germany.
[Forlino, Antonella; Vetro, Annalisa; Zuffardi, Orsetta] Univ Pavia, Pavia, Italy.
[Kisker, Caroline] Univ Wurzburg, Rudolf Virchow Ctr Expt Biomed, Wurzburg, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR14-3
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102237
ER
PT J
AU Beverly, BEJ
Lambright, C
Furr, J
Sampson, H
Travlos, G
Foster, PM
McIntyre, B
Wilson, V
Gray, LE
AF Beverly, Brandiese E. J.
Lambright, Christy
Furr, Johnathan
Sampson, Hunter
Travlos, Gregory
Foster, Paul M.
McIntyre, Barry
Wilson, Vickie
Gray, L. Earl
TI Simvastatin and Dipentyl Phthalate Display Different Modes of Action but
Exhibit Dose Additive Effects on Fetal Testicular Testosterone
Production in Sprague Dawley Rats
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Beverly, Brandiese E. J.; Lambright, Christy; Furr, Johnathan; Sampson, Hunter; Wilson, Vickie; Gray, L. Earl] US EPA, Washington, DC 20460 USA.
[Travlos, Gregory; Foster, Paul M.; McIntyre, Barry] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR18-4
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100158
ER
PT J
AU Bram, Z
Louiset, E
Ragazzon, B
Renouf, S
Risk-Rabin, M
Libe, R
Young, J
Vantyghem, MC
Martinez, A
Stratakis, CA
Bertherat, JY
Lefebvre, H
AF Bram, Zakariae
Louiset, Estelle
Ragazzon, Bruno
Renouf, Sylvie
Risk-Rabin, Marthe
Libe, Rossella
Young, Jacques
Vantyghem, Marie-Christine
Martinez, Antoine
Stratakis, Constantine A.
Bertherat, Jerome Yves
Lefebvre, Herve
TI Role of Sp1 in cAMP-Dependent Transcriptional Regulation of the
Serotonergic Signaling Pathway in Primary Pigmented Nodular Adrenal
Disease (PPNAD) Tissues Associated with Cushing's Syndrome
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Bram, Zakariae; Louiset, Estelle; Renouf, Sylvie] Univ Rouen, Inst Biomed Res & Innovat, U982, INSERM, Mont St Aignan, France.
[Ragazzon, Bruno; Libe, Rossella; Bertherat, Jerome Yves] CNRS, UMR 8104, Inst Cochin, INSERM,Unite 1016, Paris, France.
[Risk-Rabin, Marthe] Univ Paris 05, Cochin Inst, U1016, INSERM, Paris, France.
[Young, Jacques] Univ Paris 11, Dept Endocrinol, Bicetre Hosp, INSERM,U693, Le Kremlin Bicetre, France.
[Vantyghem, Marie-Christine] Univ Lille 2, INSERM, Lille Reg Univ Hosp, Dept Endocrinol,U859, Lille, France.
[Martinez, Antoine] Clermont Univ, CNRS, UMR6247, INSERM,U931,Gred, Aubiere, France.
[Stratakis, Constantine A.] NICHHD, NIH, Bethesda, MA USA.
[Lefebvre, Herve] Univ Hosp Rouen, Inst Biomed Res & Innovat, Rouen, France.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0774
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103095
ER
PT J
AU Bram, Z
Wils, J
Ragazzon, B
Risk-Rabin, M
Libe, R
Young, J
Vantyghem, MC
Martinez, A
Stratakis, CA
Bertherat, JY
Lefebvre, H
Louiset, E
AF Bram, Zakariae
Wils, Julien
Ragazzon, Bruno
Risk-Rabin, Marthe
Libe, Rossella
Young, Jacques
Vantyghem, Marie-Christine
Martinez, Antoine
Stratakis, Constantine A.
Bertherat, Jerome Yves
Lefebvre, Herve
Louiset, Estelle
TI beta-Estradiol (E2) Stimulates Cortisol Secretion in Primary Pigmented
Nodular Adrenal Disease: An Explanation for the Increased Frequency of
Cushing's Syndrome in Female Patients with Carney Complex
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Bram, Zakariae; Wils, Julien; Louiset, Estelle] Univ Rouen, Inst Biomed Res & Innovat, INSERM, U982, Mont St Aignan, France.
[Ragazzon, Bruno; Libe, Rossella; Bertherat, Jerome Yves] Inst Cochin, CNRS, INSERM, Unite 1016,Unite Mixte Rech 8104, Paris, France.
[Risk-Rabin, Marthe] Univ Paris V, Cochin Inst, INSERM, U1016, Paris, France.
[Young, Jacques] Univ Paris Sud, Dept Endocrinol, Bicetre Hosp, INSERM,U693, Le Kremlin Bicetre, France.
[Vantyghem, Marie-Christine] Lille2 Univ, INSERM, U859, Dept Endocrinol,Lille Reg Univ Hosp, Lille, France.
[Martinez, Antoine] Clermont Univ, Gred, INSERM, U931,CNRS,UMR6247, Aubiere, France.
[Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
[Lefebvre, Herve] Univ Hosp Rouen, Inst Biomed Res & Innovat, Rouen, France.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR14-2
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102227
ER
PT J
AU Brand, MR
Milford, E
Pelch, K
Bromfield, J
Nagel, SC
AF Brand, Mayah Rose
Milford, Emily
Pelch, Katie
Bromfield, John
Nagel, Susan Carol
TI Perinatal Exposure to Xenoestrogens Alters Adult Mammary Gland
Histoarchitecture in the Mouse
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Brand, Mayah Rose; Bromfield, John] Univ Missouri, Columbia, MO USA.
[Milford, Emily] Univer Missouri Columbia, Columbia, MO USA.
[Pelch, Katie] NIEHS, Res Triangle Pk, NC 27709 USA.
[Nagel, Susan Carol] Univ MO Columbia, Columbia, MO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0366
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100185
ER
PT J
AU Cauley, JA
Fluharty, L
Ellenberg, S
Gill, TM
Ensrud, KE
Barrett-Connor, EL
Cifelli, D
Cunningham, GR
Matsumoto, AM
Bhasin, S
Pahor, M
Farrar, JT
Cella, D
Rosen, RC
Resnick, SM
Swerdloff, RS
Lewis, CE
Molitch, ME
Crandall, JP
Stephens, A
Wang, C
Romashkan, S
Hadley, E
Snyder, PJ
AF Cauley, Jane A.
Fluharty, Laura
Ellenberg, Susan
Gill, Thomas M.
Ensrud, Kristine E.
Barrett-Connor, Elizabeth Louise
Cifelli, Denise
Cunningham, Glenn R.
Matsumoto, Alvin M.
Bhasin, Shalender
Pahor, Marco
Farrar, John T.
Cella, David
Rosen, Raymond C.
Resnick, Susan M.
Swerdloff, Ronald S.
Lewis, Cora E.
Molitch, Mark E.
Crandall, Jill P.
Stephens, Alisa
Wang, Christina
Romashkan, Sergei
Hadley, Evan
Snyder, Peter J.
TI Screening and Recruitment for the Testosterone Trials (TTrials)
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Cauley, Jane A.] Univ Pittsburgh, Pittsburgh, PA USA.
[Fluharty, Laura; Cifelli, Denise] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Ellenberg, Susan] Univ Penn, Sch Me, Philadelphia, PA 19104 USA.
[Gill, Thomas M.] Yale Sch Med, New Haven, CT USA.
[Ensrud, Kristine E.] Univ Minnesota, Minneapolis, MN USA.
[Barrett-Connor, Elizabeth Louise] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Cunningham, Glenn R.] Baylor Coll Med, Houston, TX 77030 USA.
[Matsumoto, Alvin M.] VA Puget Sound Hlth Care Sys, Seattle, WA USA.
[Bhasin, Shalender] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA.
[Pahor, Marco] Univ Florida, Gainesville, FL USA.
[Farrar, John T.; Stephens, Alisa] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Cella, David] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA.
[Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA USA.
[Resnick, Susan M.; Romashkan, Sergei; Hadley, Evan] NIA, Baltimore, MD 21224 USA.
[Swerdloff, Ronald S.; Wang, Christina] Harbor UCLA Med Ctr, Torrance, CA 90509 USA.
[Swerdloff, Ronald S.; Wang, Christina] Los Angeles Biomed Res Inst, Torrance, CA USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Molitch, Mark E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Crandall, Jill P.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Snyder, Peter J.] Univ Penn, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0096
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107212
ER
PT J
AU Cedars, MI
Mumford, S
Steiner, AZ
Casson, PR
Coutifaris, C
Diamond, MP
Christman, GM
Schlaff, WD
Alvero, R
Huang, H
Santoro, N
Eisenberg, E
Legro, RS
Zhang, HP
AF Cedars, Marcelle Ivonne
Mumford, Sunni
Steiner, Anne Z.
Casson, Peter Raymond
Coutifaris, Christos
Diamond, Michael P.
Christman, Gregory M.
Schlaff, Wlliam D.
Alvero, Ruben
Huang, Hao
Santoro, Nanette
Eisenberg, Esther
Legro, Richard S.
Zhang, Heping
CA Reproductive Med Network
TI Impact of AMH Level on Chances for Ovulation in Pregnancy in Polycystic
Ovary Syndrome II, a Multi-Center Randomized Clinical Trial
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Cedars, Marcelle Ivonne] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Mumford, Sunni] NICHD, NIH, Bethesda, MD USA.
[Steiner, Anne Z.] Univ N Carolina, Chapel Hill, NC USA.
[Casson, Peter Raymond] Univ Vermont, Burlington, VT USA.
[Coutifaris, Christos] Hosp Univ PA, Philadelphia, PA USA.
[Diamond, Michael P.] Wayne State Univ, Grosse Pointe Shores, MI USA.
[Christman, Gregory M.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Schlaff, Wlliam D.] Jefferson Univ, Philadelphia, PA USA.
[Alvero, Ruben; Santoro, Nanette] Univ Colorado Denver, Aurora, CO USA.
[Huang, Hao] Yale Univ, Sch Med, New Haven, CT USA.
[Eisenberg, Esther] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Legro, Richard S.] Penn State Univ, Hershey, PA USA.
[Zhang, Heping] Yale Univ, New Haven, CT USA.
[Reproductive Med Network] NICHD, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR04-4
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104220
ER
PT J
AU Chia, CW
Egan, JM
AF Chia, Chee Wei
Egan, Josephine Mary
TI Fungiform Papillae Density Is Associated with Age and Markers of Glucose
Metabolism in the Baltimore Longitudinal Study of Aging
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Chia, Chee Wei; Egan, Josephine Mary] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-1005
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106307
ER
PT J
AU Christensen, JD
Lungu, AO
Cochran, E
Collins, MT
Gafni, RI
Reynolds, JC
Gorden, P
Brown, RJ
AF Christensen, John D.
Lungu, Andreea O.
Cochran, Elaine
Collins, Michael T.
Gafni, Rachel I.
Reynolds, James C.
Gorden, Phillip
Brown, Rebecca J.
TI Increased Bone Mineral Content in Patients with Congenital Generalized
Lipodystrophy Is Unaffected By Metreleptin Replacement Therapy
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Christensen, John D.; Cochran, Elaine; Gorden, Phillip; Brown, Rebecca J.] NIDDK, NIH, Bethesda, MD USA.
[Lungu, Andreea O.] Joslin Diabet Ctr, Brookline, MA USA.
[Collins, Michael T.; Gafni, Rachel I.] NIDCR, NIH, Bethesda, MD USA.
[Reynolds, James C.] NIH, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR43-6
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105097
ER
PT J
AU Chrysostomou, P
Lodish, MB
Turkbey, E
Stratakis, CA
AF Chrysostomou, Paola
Lodish, Maya Beth
Turkbey, Evrim
Stratakis, Constantine A.
TI Use of 3-Dimensional Volumetric Modeling of Adrenal Gland Size in
Patients with Primary Pigmented Nodular Adrenocortical Disease
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Chrysostomou, Paola] NICHD, NIH, Bethesda, MD USA.
[Lodish, Maya Beth; Turkbey, Evrim; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0775
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103106
ER
PT J
AU Condarco, TA
McDuffie, JR
Brady, S
Adeyemo, MA
Garcia, RM
Reynolds, J
Hubbard, VS
Calis, KA
Yanovski, JA
AF Condarco, Tania Andrea
McDuffie, Jennifer R.
Brady, Sheila
Adeyemo, Mopelola Adetola
Garcia, Rubi Maricela
Reynolds, James
Hubbard, Van S.
Calis, Karim Anton
Yanovski, Jack A.
TI Differences in Bone Turnover Markers and Bone Mineral Density in
African-American and Caucasian Adolescents Taking Orlistat
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Condarco, Tania Andrea; McDuffie, Jennifer R.; Brady, Sheila] NICHD, NIH, Bethesda, MD USA.
[Adeyemo, Mopelola Adetola; Garcia, Rubi Maricela; Yanovski, Jack A.] NIH, Bethesda, MD 20892 USA.
[Reynolds, James; Calis, Karim Anton] NIH, CC, Bethesda, MD 20892 USA.
[Hubbard, Van S.] NIH, DNRC, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0163
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104047
ER
PT J
AU Correa, RR
Lysikatos-Lyssikatos, C
Belyayskaya, E
Stratakis, CA
AF Correa, Ricardo Rafael
Lysikatos-Lyssikatos, Charalampos
Belyayskaya, Elena
Stratakis, Constantine A.
TI Atypical Presentation of a Ganglioneuroma
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Correa, Ricardo Rafael] NIH, Rockville, MD USA.
[Lysikatos-Lyssikatos, Charalampos; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
[Belyayskaya, Elena] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0753
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105165
ER
PT J
AU Cunningham, GR
Rosen, RC
Wang, C
Stephens, A
Ellenberg, S
Matsumoto, AM
Bhasin, S
Molitch, ME
Farrar, JT
Cella, D
Gill, TM
Barrett-Connor, EL
Cauley, JA
Cifelli, D
Crandall, JP
Ensrud, KE
Fluharty, L
Hadley, E
Lewis, CE
Pahor, M
Resnick, SM
Romashkan, S
Swerdloff, RS
Snyder, PJ
AF Cunningham, Glenn R.
Rosen, Raymond C.
Wang, Christina
Stephens, Alisa
Ellenberg, Susan
Matsumoto, Alvin M.
Bhasin, Shalender
Molitch, Mark E.
Farrar, John T.
Cella, David
Gill, Thomas M.
Barrett-Connor, Elizabeth Louise
Cauley, Jane A.
Cifelli, Denise
Crandall, Jill P.
Ensrud, Kristine E.
Fluharty, Laura
Hadley, Evan
Lewis, Cora E.
Pahor, Marco
Resnick, Susan M.
Romashkan, Sergei
Swerdloff, Ronald S.
Snyder, Peter J.
TI Free Testosterone but Not Total Testosterone or Estradiol Is Associated
with Sexual Function in Symptomatic Older Hypogonadal Men in the Sexual
Function Trial of the Testosterone Trials
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Cunningham, Glenn R.] Baylor Coll Med, Houston, TX 77030 USA.
[Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA USA.
[Wang, Christina] Harbor UCLA Med Ctr, Torrance, CA 90509 USA.
[Wang, Christina; Swerdloff, Ronald S.] Los Angeles Biomed Res Inst, Torrance, CA USA.
[Stephens, Alisa; Ellenberg, Susan; Farrar, John T.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Bhasin, Shalender] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Molitch, Mark E.; Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Gill, Thomas M.] Yale Sch Med, New Haven, CT USA.
[Barrett-Connor, Elizabeth Louise] Univ CA San Diego, La Jolla, CA USA.
[Cauley, Jane A.] Univ Pittsburgh, Pittsburgh, PA USA.
[Cifelli, Denise; Fluharty, Laura] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Crandall, Jill P.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Ensrud, Kristine E.] Univ Minnesota, Minneapolis, MN USA.
[Hadley, Evan; Romashkan, Sergei] NIA, Bethesda, MD 20892 USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Pahor, Marco] Univ Florida, Gainesville, FL USA.
[Resnick, Susan M.] NIA, Baltimore, MD 21224 USA.
[Swerdloff, Ronald S.] Harbor Univ Calif Med Ctr, Torrance, CA USA.
[Snyder, Peter J.] Univ PA, Philadelphia, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0084
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805107199
ER
PT J
AU Del Rivero, J
Madan, R
Marx, SJ
AF Del Rivero, Jaydira
Madan, Ritu
Marx, Stephen J.
TI Uterine Leiomyomas Associated with Multiple Endocrine Neoplasia Type 1
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Del Rivero, Jaydira] NICHHD, NIH, Bethesda, MD 20892 USA.
[Madan, Ritu] NIH, Bethesda, MD 20892 USA.
[Marx, Stephen J.] NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0315
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805108079
ER
PT J
AU Del Rivero, J
Zhuang, ZP
Yang, CZ
Prchal, JT
Lechan, RM
Tischler, AS
Fojo, T
Taieb, D
Popovic, V
Lorenzo, F
Young, JA
Nambuba, J
Adams, KT
Jochmanova, I
Merino, M
Stratakis, CA
Kebebew, E
Pacak, K
AF Del Rivero, Jaydira
Zhuang, Zhengping
Yang, Chunzhang
Prchal, Josef T.
Lechan, Ronald M.
Tischler, Arthur S.
Fojo, Tito
Taieb, David
Popovic, Vera
Lorenzo, Felipe
Young, James A.
Nambuba, Joan
Adams, Karen T.
Jochmanova, Ivana
Merino, Maria
Stratakis, Constantine A.
Kebebew, Electron
Pacak, Karel
TI The NIH Experience of Seven Somatic HIF2A Patients Presenting with
Multiple Paragangliomas and/or Duodenal Somatostatinomas Associated with
Polycythemia
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Del Rivero, Jaydira; Nambuba, Joan; Adams, Karen T.; Jochmanova, Ivana; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Zhuang, Zhengping; Yang, Chunzhang] NINDS, NIH, Bethesda, MD 20892 USA.
[Prchal, Josef T.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Prchal, Josef T.] VAH, Salt Lake City, UT USA.
[Lechan, Ronald M.] Tufts Med Ctr, Boston, MA USA.
[Tischler, Arthur S.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Fojo, Tito; Merino, Maria; Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA.
[Taieb, David] CHU Timone, Marseille 05, France.
[Popovic, Vera] Clin Ctr Serbia, Belgrade, Serbia.
[Lorenzo, Felipe] Univ Utah Hlth Sci, Salt Lake City, UT USA.
[Young, James A.] Rocky Mt Canc Ctr, Denver, CO USA.
[Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0767
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103016
ER
PT J
AU Del Rivero, J
Zhuang, ZP
Yang, CZ
Prchal, JT
Lechan, RM
Tischler, AS
Fojo, T
Taieb, D
Popovic, V
Lorenzo, F
Young, JA
Nambuba, J
Adams, KT
Jochmanova, I
Merino, M
Stratakis, CA
Kebebew, E
Pacak, K
AF Del Rivero, Jaydira
Zhuang, Zhengping
Yang, Chunzhang
Prchal, Josef T.
Lechan, Ronald M.
Tischler, Arthur S.
Fojo, Tito
Taieb, David
Popovic, Vera
Lorenzo, Felipe
Young, James A.
Nambuba, Joan
Adams, Karen T.
Jochmanova, Ivana
Merino, Maria
Stratakis, Constantine A.
Kebebew, Electron
Pacak, Karel
TI The NIH Experience of Seven Somatic HIF2A Patients Presenting with
Multiple Paragangliomas and/or Duodenal Somatostatinomas Associated with
Polycythemia
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Del Rivero, Jaydira; Nambuba, Joan; Adams, Karen T.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Zhuang, Zhengping; Yang, Chunzhang] NINDS, NIH, Bethesda, MD 20892 USA.
[Prchal, Josef T.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Prchal, Josef T.] VAH, Salt Lake City, UT USA.
[Lechan, Ronald M.] Tufts Med Ctr, Boston, MA USA.
[Tischler, Arthur S.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Fojo, Tito] NCI, NIH, Bethesda, MD 20892 USA.
[Taieb, David] CHU Timone, Marseille 05, France.
[Popovic, Vera] Clin Ctr Serbia, Belgrade, Serbia.
[Lorenzo, Felipe] Univ Utah Hlth Sci, Salt Lake City, UT USA.
[Young, James A.] Rocky Mt Canc Ctr, Denver, CO USA.
[Jochmanova, Ivana] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Merino, Maria; Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA.
[Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP35-4
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102005
ER
PT J
AU Delaney, A
Lalonde, FM
Blumenthal, JD
Clasen, LS
Hicks, RL
Denker, AH
Giedd, JN
Crowley, WF
Balasubramanian, R
AF Delaney, Angela
Lalonde, Francois M.
Blumenthal, Jonathan D.
Clasen, Liv S.
Hicks, Rebecca L.
Denker, Alexander H.
Giedd, Jay N.
Crowley, William F.
Balasubramanian, Ravikumar
TI Delayed Sex Hormone Exposure during Puberty Is Associated with
Differences in Brain Cortical Thickness, Spatial Ability, and
Recognition Memory
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Delaney, Angela; Lalonde, Francois M.; Blumenthal, Jonathan D.; Clasen, Liv S.; Hicks, Rebecca L.; Denker, Alexander H.; Giedd, Jay N.] NIH, Bethesda, MD 20892 USA.
[Crowley, William F.; Balasubramanian, Ravikumar] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR11-1
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104109
ER
PT J
AU Deng, Q
Aguilera, G
AF Deng, Qiong
Aguilera, Greti
TI Leucine Repeat 687 to 690 of the Glucocorticoid Receptor (GR) Is
Essential for Ligand Binding and GR Interaction with Heat Shock Protein
90 (HSP90)
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Deng, Qiong; Aguilera, Greti] NICHHD, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0432
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109297
ER
PT J
AU Deng, Q
Aguilera, G
AF Deng, Qiong
Aguilera, Greti
TI Rapid Glucocorticoid Feedback Inhibition of ACTH Secretion Involves
Ligand-Dependent Membrane Association of Glucocorticoid Receptors and
Inhibition of Src Phosphorylation
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Deng, Qiong; Aguilera, Greti] NICHHD, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR48-6
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102042
ER
PT J
AU Desai, SS
Modali, SD
Parekh, VI
Agarwal, SK
AF Desai, Shruti S.
Modali, Sita D.
Parekh, Vaishali I.
Agarwal, Sunita K.
TI Inhibitory Effect of LiCl Treatment on Pancreatic Islet beta-Cell
Tumorigenesis in the Mouse Model of Multiple Endocrine Neoplasia Type 1
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Desai, Shruti S.; Modali, Sita D.; Parekh, Vaishali I.; Agarwal, Sunita K.] NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0305
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805108068
ER
PT J
AU Dogan, BA
Arduc, A
Tuna, MM
Imga, NN
Isik, S
Berker, D
Guler, S
AF Dogan, Bercem Aycicek
Arduc, Ayse
Tuna, Mazhar Muslum
Imga, Narin Nasiroglu
Isik, Serhat
Berker, Dilek
Guler, Serdar
TI Evaluation of Atherosclerosis after Cessation of Cabergoline Therapy in
Patients with Prolactinoma: Preliminary Results of a Prospective Cohort
Study
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Dogan, Bercem Aycicek; Tuna, Mazhar Muslum; Imga, Narin Nasiroglu; Berker, Dilek] Ankara Numune Training & Res Hosp, Ankara, Turkey.
[Arduc, Ayse] NIDDK, Diabet Endocrine & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Isik, Serhat] Ankara Numune Training & Res Hosp, Ankara, Turkey.
[Guler, Serdar] Hitit Univ, Fac Med, Corum, Turkey.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0622
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101058
ER
PT J
AU El-Maouche, D
Kaufmann, M
Gafni, RI
Jones, G
Collins, MT
AF El-Maouche, Diala
Kaufmann, Martin
Gafni, Rachel I.
Jones, Glenville
Collins, Michael T.
TI FGF23-Mediated Vitamin D Metabolism in Tumor-Induced Osteomalacia
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [El-Maouche, Diala] NIH, Bethesda, MD 20892 USA.
[Kaufmann, Martin; Jones, Glenville] Queens Univ, Kingston, ON, Canada.
[Gafni, Rachel I.; Collins, Michael T.] NIDCR, NIH, Bethesda, MD USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR43-2
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105093
ER
PT J
AU Escajadillo, T
Segars, JH
Sewer, MB
AF Escajadillo, Tamara
Segars, James Hugh
Sewer, Marion B.
TI Silencing a-Kinase Anchoring Protein Impairs cAMP Signaling and Steroid
Hormone Biosynthesis in the Adrenal Cortex
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Escajadillo, Tamara] Calif State Univ Dominguez Hills, Carson, CA 90747 USA.
[Segars, James Hugh] NIH, Potomac, MD USA.
[Sewer, Marion B.] Univ Calif San Diego, La Jolla, CA 92093 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0410
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102238
ER
PT J
AU Estrada, A
Venkatesan, A
Wolfgang, CL
Guthrie, L
Fishman, EK
Kamei, I
Ali, SZ
Goggins, M
Hruban, RH
Maitra, A
Gafni, RI
Lennon, AM
Collins, MT
AF Estrada, Andrea
Venkatesan, Aradhana
Wolfgang, Christopher L.
Guthrie, Lori
Fishman, Elliot K.
Kamei, Ihab
Ali, Syed Z.
Goggins, Michael
Hruban, Ralph H.
Maitra, Anirban
Gafni, Rachel I.
Lennon, Anne Marie
Collins, Michael T.
TI Pancreatic Pathology in Mccune Albright Syndrome
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Estrada, Andrea] NICHHD, NIH, Bethesda, MD 20892 USA.
[Venkatesan, Aradhana; Gafni, Rachel I.] NIH, Bethesda, MD 20892 USA.
[Wolfgang, Christopher L.; Fishman, Elliot K.; Kamei, Ihab; Ali, Syed Z.; Goggins, Michael; Hruban, Ralph H.; Lennon, Anne Marie] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Guthrie, Lori] NIH, Bethesda, MD 20892 USA.
[Maitra, Anirban] MD Anderson, Bethesda, MD USA.
[Collins, Michael T.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0314
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805108077
ER
PT J
AU Faucz, FR
Berthon, AS
Zilbermint, M
Assie, G
Lodish, MB
Szarek, E
Trivellin, G
Sinaii, N
Libe, R
Espiard, S
Drougat, L
Ragazzon, B
Feldman, B
Bertherat, JY
Stratakis, CA
AF Faucz, Fabio Rueda
Berthon, Annabel Sophie
Zilbermint, Mihail
Assie, Guillaume
Lodish, Maya Beth
Szarek, Eva
Trivellin, Giampaolo
Sinaii, Ninet
Libe, Rossella
Espiard, Stephanie
Drougat, Ludivine
Ragazzon, Bruno
Feldman, Benjamin
Bertherat, Jerome Yves
Stratakis, Constantine A.
TI Functional Investigation of a New Aimah Suppressor Gene, ARMC5 Using
Animal Models
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Faucz, Fabio Rueda; Berthon, Annabel Sophie; Zilbermint, Mihail; Lodish, Maya Beth; Szarek, Eva; Trivellin, Giampaolo; Sinaii, Ninet; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
[Assie, Guillaume; Espiard, Stephanie; Drougat, Ludivine; Ragazzon, Bruno; Bertherat, Jerome Yves] Inst Cochin, CNRS, UMR 8104, INSERM Unite 1016, Paris, France.
[Libe, Rossella] Inst Cochin, Paris, France.
[Feldman, Benjamin] NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0817
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102197
ER
PT J
AU Feelders, RA
Sharma, ST
Elgarf, R
Ouwerkerk, R
Gharib, AM
Abd-Elmoniem, KZ
Nieman, LK
AF Feelders, Richard A.
Sharma, Susmeeta T.
Elgarf, Reham
Ouwerkerk, Ronald
Gharib, Ahmed M.
Abd-Elmoniem, Khaled Z.
Nieman, Lynnette K.
TI Noninvasive Assessment of the Coronary Artery Vessel Wall in Cushing's
Syndrome Using 3-T Magnetic Resonance Imaging: Evidence for Increased
Atherosclerosis Compared to Risk-Matched Controls
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Feelders, Richard A.] Erasmus MC, Rotterdam, Netherlands.
[Sharma, Susmeeta T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Elgarf, Reham; Ouwerkerk, Ronald; Gharib, Ahmed M.; Abd-Elmoniem, Khaled Z.; Nieman, Lynnette K.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0660
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101282
ER
PT J
AU Fliedner, SMJ
Shankavaram, U
Elkahloun, A
Lehnert, H
Pacak, K
AF Fliedner, Stephanie M. J.
Shankavaram, Uma
Elkahloun, Abdel
Lehnert, Hendrik
Pacak, Karel
TI Characteristic Expression Signature of Hypoxia Inducible Factor 2 Alpha
Mutation-Related Paragangliomas
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Fliedner, Stephanie M. J.; Lehnert, Hendrik] Univ Med Ctr Schleswig Holstein, Lubeck, Germany.
[Shankavaram, Uma] NCI, NIH, Bethesda, MD 20892 USA.
[Elkahloun, Abdel] NHGRI, NIH, Bethesda, MD 20892 USA.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA LBSU-0820
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100026
ER
PT J
AU Fortin, J
Boehm, U
Deng, CX
Treier, M
Bernard, DJ
AF Fortin, Jerome
Boehm, Ulrich
Deng, Chuxia
Treier, Mathias
Bernard, Daniel J.
TI Follicle-Stimulating Hormone Synthesis and Fertility Require the
Independent and Complementary Activities of SMAD4 and FOXL2 in
Gonadotropes
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Fortin, Jerome; Bernard, Daniel J.] McGill Univ, Montreal, PQ, Canada.
[Boehm, Ulrich] Univ Saarland, Sch Med, Homburg, Germany.
[Deng, Chuxia] NIH, Bethesda, MD 20892 USA.
[Treier, Mathias] Max Delbruck Ctr Mol Med, Berlin, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR30-6
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805101193
ER
PT J
AU Gourgari, E
Lodish, MB
Keil, M
Sinai, N
Turkbey, E
Lyssikatos, C
Khurana, D
Crutchfield, C
Nesterova, MV
Sierra, MD
Xekouki, P
Backlund, P
Yergey, A
Ten, SB
Dobs, AS
Stratakis, CA
AF Gourgari, Evgenia
Lodish, Maya Beth
Keil, Margaret
Sinai, Ninet
Turkbey, Evrim
Lyssikatos, Charalampos
Khurana, Divya
Crutchfield, Chris
Nesterova, Maria V.
Sierra, Maria De La Luz
Xekouki, Paraskevi
Backlund, Peter
Yergey, Al
Ten, Svetlana B.
Dobs, Adrian Sandra
Stratakis, Constantine A.
TI Micronodular Adrenal Hyperplasia: A New Mechanism for Hyperandrogenism
in Women with Polycystic Ovarian Syndrome (PCOS)
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Gourgari, Evgenia] Georgetown Univ Hosp, Washington, DC 20007 USA.
[Lodish, Maya Beth; Keil, Margaret; Turkbey, Evrim; Lyssikatos, Charalampos; Nesterova, Maria V.; Sierra, Maria De La Luz; Xekouki, Paraskevi; Stratakis, Constantine A.] NIH, Bethesda, MD 20892 USA.
[Sinai, Ninet] NICHD, Rockville, MD USA.
[Khurana, Divya] MMC, Hicksville, NY USA.
[Crutchfield, Chris] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Backlund, Peter] NICHD, Bethesda, MD USA.
[Yergey, Al] NICHD, NIH, Rockville, MD USA.
[Ten, Svetlana B.] Maimonides Hosp, Brooklyn, NY 11219 USA.
[Dobs, Adrian Sandra] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0087
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805109277
ER
PT J
AU Hein, AC
Vatish, M
Kino, T
Grammatopoulos, D
DeCherney, AH
AF Hein, Anna Caroline
Vatish, Manu
Kino, Tomoshige
Grammatopoulos, Dimitris
DeCherney, Alan H.
TI Novel Role of the Enzyme 11 beta-Hydroxysteroid Dehydrogenase Type 2 (11
beta-HSD2) on Trophoblast Biology
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Hein, Anna Caroline; Kino, Tomoshige] NICHD, NIH, Bethesda, MD USA.
[Vatish, Manu] Univ Oxford, Oxford, England.
[Grammatopoulos, Dimitris] Univ Warwick, Biomed Res Inst, Coventry, W Midlands, England.
[DeCherney, Alan H.] NIH, Potomac, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0076
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105012
ER
PT J
AU Hernandez-Ramirez, LC
Gabrovska, P
Denes, J
Trivellin, G
Radian, S
Tilley, D
Ferrau, F
Akkers, SA
Grossman, AB
Gadelha, M
Korbonits, M
AF Hernandez-Ramirez, Laura C.
Gabrovska, Plamena
Denes, Judit
Trivellin, Giampaolo
Radian, Serban
Tilley, Daniel
Ferrau, Francesco
Akkers, Scott Alexander
Grossman, Ashley B.
Gadelha, MA'nica
Korbonits, Marta
CA Int FIPA Consortium
TI Pituitary Adenomas Harboring AIP Mutations Exhibit Phenotype-Genotype
Correlation, but No Association with the Germline FGFR4 G388R Variant or
Somatic GNAS1 Mutations
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Hernandez-Ramirez, Laura C.] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England.
[Gabrovska, Plamena] Queen Mary Univ London, William Harvey Res Inst, London, England.
[Denes, Judit; Radian, Serban; Tilley, Daniel; Ferrau, Francesco; Korbonits, Marta; Int FIPA Consortium] Queen Mary Univ London, Barts & London Sch Med, London, England.
[Trivellin, Giampaolo] NIH, Bethesda, MD 20892 USA.
[Akkers, Scott Alexander] St Bartholomews Hosp, London, England.
[Grossman, Ashley B.] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Gadelha, MA'nica] Univ Fed Rio de Janeiro, Clementino Fraga Filho Univ Hosp, Rio De Janeiro, Brazil.
RI Radian, Serban/C-3559-2011
OI Radian, Serban/0000-0002-6488-4242
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA OR09-3
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805102034
ER
PT J
AU Ho, TP
Hattenbach, J
Linderman, JD
Smith, S
Simchowitz, L
Celi, FS
AF Ho, Thanh P.
Hattenbach, Jacob
Linderman, Joyce D.
Smith, Sheila
Simchowitz, Louis
Celi, Francesco S.
TI Effects of Inflammation and Adiposity on Bone Density in Non-Elderly
Adults
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Ho, Thanh P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Hattenbach, Jacob; Linderman, Joyce D.; Smith, Sheila; Simchowitz, Louis] NIH, Bethesda, MD 20892 USA.
[Celi, Francesco S.] Virginia Commonwealth Univ, Richmond, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0273
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805105272
ER
PT J
AU Ho, T
Ranganath, K
Kablan, A
Chen, M
Weinstein, LS
AF Ho, Thuy
Ranganath, Khushi
Kablan, Ahmed
Chen, Min
Weinstein, Lee S.
TI Pancreatic alpha Cell-Specific Gsa Deficiency Promotes alpha and beta
Cell Growth
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Ho, Thuy; Ranganath, Khushi; Kablan, Ahmed; Chen, Min; Weinstein, Lee S.] NIDDK, NIH, Bethesda, MD USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SAT-0949
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106150
ER
PT J
AU Huang, CCJ
Forrest, D
AF Huang, Chen-Che Jeff
Forrest, Douglas
TI Thyroid Hormone Receptor beta 1-Mediated Adrenal Remodeling
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Huang, Chen-Che Jeff; Forrest, Douglas] NIDDKD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA SUN-0471
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805108186
ER
PT J
AU Jewell, C
Murphy, L
Cannon, C
Garantziotis, S
Cidlowski, JA
AF Jewell, Christine
Murphy, Lisa
Cannon, Crystal
Garantziotis, Stavros
Cidlowski, John A.
TI The Role of Glucocorticoid Receptor N363S Single Nucleotide Polymorphism
in Receptor Function and Metabolic Disease
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Jewell, Christine; Murphy, Lisa; Cannon, Crystal; Garantziotis, Stavros; Cidlowski, John A.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RI Garantziotis, Stavros/A-6903-2009
OI Garantziotis, Stavros/0000-0003-4007-375X
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0803
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805104074
ER
PT J
AU Jha, S
Nair, G
Patel, J
Bhatia, A
Parseghian, SA
Albert, SG
AF Jha, Smita
Nair, Gopakumar
Patel, Jaymin
Bhatia, Ashmeet
Parseghian, Shant A.
Albert, Stewart Gary
TI Exploring the Benefits of Early Endocrinology Consultation for Diabetic
Ketoacidosis in a Community Hospital Setting
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Jha, Smita] NIH, Bethesda, MD 20892 USA.
[Nair, Gopakumar] Brockton Hosp, Brockton, MA USA.
[Patel, Jaymin; Bhatia, Ashmeet] North Shore Med Ctr, Miami, FL USA.
[Parseghian, Shant A.] NSPG, Winchester, MA USA.
[Albert, Stewart Gary] St Louis Univ, Sch Med, St Louis, MO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0984
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805106271
ER
PT J
AU Kantorovich, V
Arai, AE
Martucci, VL
Adams, KT
Reynolds, JC
Pacak, K
AF Kantorovich, Vitaly
Arai, Andrew E.
Martucci, Victoria L.
Adams, Karen T.
Reynolds, James C.
Pacak, Karel
TI Functional and Structural Cardiac Abnormalities in Patients with
Metastatic Pheochromocytomas and Paragangliomas
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Kantorovich, Vitaly] Univ Connecticut, Ctr Hlth, Farmington, CT USA.
[Arai, Andrew E.] NHLBI, Bethesda, MD 20892 USA.
[Martucci, Victoria L.; Adams, Karen T.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Reynolds, James C.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA MON-0769
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805103038
ER
PT J
AU Kantorovich, V
Arai, AE
Martucci, VL
Adams, KT
Reynolds, JC
Pacak, K
AF Kantorovich, Vitaly
Arai, Andrew E.
Martucci, Victoria L.
Adams, Karen T.
Reynolds, James C.
Pacak, Karel
TI Functional and Structural Cardiac Abnormalities in Patients with
Metastatic Pheochromocytomas and Pa ragangliomas
SO ENDOCRINE REVIEWS
LA English
DT Meeting Abstract
C1 [Kantorovich, Vitaly] Univ Connecticut, Ctr Hlth, Farmington, CT USA.
[Arai, Andrew E.] NHLBI, Bethesda, MD 20892 USA.
[Martucci, Victoria L.; Adams, Karen T.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Reynolds, James C.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD JUN
PY 2014
VL 35
IS 3
SU S
MA PP27-3
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V45GM
UT WOS:000209805100159
ER
EF