FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Jonas, MM
Balistreri, WF
Gonzalez-Peralta, RP
Haber, B
Mohan, P
Molleston, JP
Murray, KF
Narkewicz, M
Rosenthal, P
Schwarz, KB
Smith, LJ
Barton, B
Shepherd, JA
Robuck, PR
Duggan, C
AF Jonas, Maureen M.
Balistreri, William F.
Gonzalez-Peralta, Regino P.
Haber, Barbara
Mohan, Parvathi
Molleston, Jean P.
Murray, Karen F.
Narkewicz, Michael
Rosenthal, Philip
Schwarz, Kathleen B.
Smith, Lesley J.
Barton, Bruce
Shepherd, John A.
Robuck, Patricia R.
Duggan, Christopher
TI CHANGES IN BODY MASS INDEX AND BODY COMPOSITION IN CHILDREN TREATED WITH
PEGINTERFERON FOR CHRONIC HEPATITIS C IN THE PEDS-C TRIAL
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Jonas, Maureen M.; Duggan, Christopher] Childrens Hosp, Boston, MA 02115 USA.
[Balistreri, William F.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Gonzalez-Peralta, Regino P.] Univ Florida, Gainesville, FL USA.
[Haber, Barbara] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Mohan, Parvathi] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Molleston, Jean P.] Indiana Univ, Indianapolis, IN 46204 USA.
[Murray, Karen F.] Seattle Childrens Hosp, Seattle, WA USA.
[Narkewicz, Michael] Univ Colorado, Denver, CO 80202 USA.
[Rosenthal, Philip; Shepherd, John A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Schwarz, Kathleen B.] Johns Hopkins Univ, Baltimore, MD USA.
[Smith, Lesley J.] Univ Miami, Miami, FL USA.
[Barton, Bruce] Maryland Med Res Inst, Baltimore, MD USA.
[Robuck, Patricia R.] NIDDK, Bethesda, MD USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 708
BP 636A
EP 637A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000707
ER
PT J
AU Ananthanarayanan, M
Li, YF
Walsh, M
Surapureddi, S
Goldstein, J
Suchy, FJ
AF Ananthanarayanan, Meena
Li, Yanfeng
Walsh, Martin
Surapureddi, Sailesh
Goldstein, Joyce
Suchy, Frederick J.
TI IDENTIFICATION OF NUCLEAR RECEPTOR COACTIVATOR 6 (NCOA6/ASC-2) AND MIXED
MYELOID LINEAGE LEUKEMIA 3 (MLL3), A HISTONE H3K4 METHYL TRANSFERASE, AS
PARTNERS OF THE ASCOM COMPLEX IN FXR TRANSACTIVATION OF BSEP PROMOTER
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Ananthanarayanan, Meena; Li, Yanfeng; Walsh, Martin; Suchy, Frederick J.] Mt Sinai Sch Med, Dept Pediat, New York, NY USA.
[Surapureddi, Sailesh; Goldstein, Joyce] NIEHS, Pharmacol Lab, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 763
BP 662A
EP 662A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000762
ER
PT J
AU Katsounas, A
Frank, AC
Yang, J
Lempicki, RA
Neumann, AU
Polis, MA
Kottilil, S
AF Katsounas, Antonios
Frank, Astrid C.
Yang, Jun
Lempicki, Richard A.
Neumann, Avidan U.
Polis, Michael A.
Kottilil, Shyam
TI DIFFERENTIAL SPECIFICITY OF INNATE HOST GENE EXPRESSION ON
INTERFERON-MEDIATED ANTIVIRAL EFFECT ON HCV AND HIV
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Katsounas, Antonios; Yang, Jun; Lempicki, Richard A.] NCI, SAIC, Frederick, MD 21701 USA.
[Frank, Astrid C.; Polis, Michael A.; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Neumann, Avidan U.] Bar Ilan Univ, Ramat Dan, Israel.
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 797
BP 678A
EP 678A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000796
ER
PT J
AU Lempicki, RA
Yang, J
Masur, H
Polis, MA
Kottilil, S
AF Lempicki, Richard A.
Yang, Jun
Masur, Henry
Polis, Michael A.
Kottilil, Shyam
TI EXHAUSTION OF TYPE-I INTERFERON SIGNALING PATHWAY AS A MAJOR MECHANISM
FOR LACK OF RESPONSE TO PEG-INTERFERON AND RIBAVIRIN THERAPY IN HIV/HCV
CO-INFECTED SUBJECTS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Polis, Michael A.; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Lempicki, Richard A.; Yang, Jun] SAIC Frederick, Frederick, MD USA.
[Masur, Henry] NIH, CCMD, CC, Bethesda, MD 20892 USA.
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 804
BP 681A
EP 681A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000803
ER
PT J
AU Wang, HH
Schlaak, JF
Masur, H
Polis, MA
Suffredini, AF
Kottilil, S
AF Wang, Honghui
Schlaak, Joerg F.
Masur, Henry
Polis, Michael A.
Suffredini, Anthony F.
Kottilil, Shyam
TI APPLIED PROTEOMICS IN HCV CO-INFECTION: DIFFERENTIAL EXPRESSION OF SERUM
PROTEINS PRIOR TO TREATMENT IS ASSOCIATED WITH RESPONSE TO HCV THERAPY
IN HIV CO-INFECTED INDIVIDUALS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Polis, Michael A.; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Wang, Honghui; Masur, Henry; Suffredini, Anthony F.] NIH, CCMD, CC, Bethesda, MD 20892 USA.
[Schlaak, Joerg F.] Univ Essen Gesamthsch, Essen, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 809
BP 683A
EP 683A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000808
ER
PT J
AU Lempicki, RA
Schlaak, JF
Masur, H
Polis, MA
Kottilil, S
AF Lempicki, Richard A.
Schlaak, Joerg F.
Masur, Henry
Polis, Michael A.
Kottilil, Shyam
TI GENOME-WIDE SINGLE NUCLEOTIDE POLYMORPHISM ANALYSIS IDENTIFIES A UNIQUE
CCL-5 HALPLOTYPE IN HIV/HCV CO-INFECTED NON-RESPONDERS TO
PEGYLATED-INTERFERON (PEG-IFN) AND RIBAVIRIN (RBV) THERAPY
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Polis, Michael A.; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Masur, Henry] NIH, CCMD, CC, Bethesda, MD 20892 USA.
[Lempicki, Richard A.] SAIC Frederick, Frederick, MD USA.
[Schlaak, Joerg F.] Univ Essen Gesamthsch, Essen, Germany.
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
NR 0
TC 2
Z9 2
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 824
BP 690A
EP 690A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000823
ER
PT J
AU Noureddin, M
Rotman, Y
Feld, J
Koh, C
Abdalla, A
Thomas, E
Park, Y
Heller, T
Ghany, MG
Hoofnagle, JH
Liang, TJ
AF Noureddin, Mazen
Rotman, Yaron
Feld, Jordan
Koh, Christopher
Abdalla, Adil
Thomas, Emmanuel
Park, Yoon
Heller, Theo
Ghany, Marc G.
Hoofnagle, Jay H.
Liang, T. Jake
TI THE EFFECTS OF RIBAVIRIN ON SERUM HCV LEVELS BEFORE AND DURING
COMBINATION TREATMENT WITH PEGINTERFERON
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Noureddin, Mazen; Rotman, Yaron; Feld, Jordan; Koh, Christopher; Abdalla, Adil; Thomas, Emmanuel; Park, Yoon; Heller, Theo; Ghany, Marc G.; Hoofnagle, Jay H.; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 835
BP 695A
EP 695A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000834
ER
PT J
AU Murphy, A
Daucher, M
Subramanian, M
Polis, MA
Kottilil, S
AF Murphy, Alison
Daucher, Marybeth
Subramanian, Mani
Polis, Michael A.
Kottilil, Shyam
TI COMPARATIVE ANALYSIS OF IN VIVO ANTIVIRAL EFFECTS AND INDUCTION OF
INTERFERON-INDUCIBLE GENES BY PEGYLATED-INTERFERON AND ALBINTERFERON
ALFA-2B IN HIV/HCV CO-INFECTED SUBJECTS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Murphy, Alison; Daucher, Marybeth; Polis, Michael A.; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Subramanian, Mani] Human Genome Sci, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 846
BP 701A
EP 701A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000845
ER
PT J
AU Burbelo, P
Kovacs, JA
Schlaak, JF
Masur, H
Polis, MA
Kottilil, S
AF Burbelo, Peter
Kovacs, Joseph A.
Schlaak, Joerg F.
Masur, Henry
Polis, Michael A.
Kottilil, Shyam
TI PROTEOME-WIDE ANTI-HCV AND ANTI-HIV ANTIBODY PROFILING USING A NOVEL
HIGH THROUGHPUT LUCIFERASE IMMUNOPRECIPITATION SYSTEM FOR PREDICTING AND
MONITORING RESPONSE TO HCV TREATMENT IN HIV CO-INFECTED PATIENTS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Polis, Michael A.; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Burbelo, Peter] NIDCR, NIH, DHHS, Bethesda, MD USA.
[Schlaak, Joerg F.] Univ Essen Gesamthsch, Essen, Germany.
[Kovacs, Joseph A.; Masur, Henry] NIH, CCMD, CC, Bethesda, MD 20892 USA.
RI Burbelo, Peter/B-1027-2009
NR 0
TC 0
Z9 0
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 864
BP 710A
EP 710A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000863
ER
PT J
AU Herrmann, E
Subramanian, M
Polis, MA
Kottilil, S
AF Herrmann, Eva
Subramanian, Mani
Polis, Michael A.
Kottilil, Shyam
TI COMPARATIVE SAFETY TOLERABILITY, VIRAL AND PHARMACODYNAMIC EFFICACY OF
PEGYLATED-INTERFERONS AND ALBINTERFERON ALFA-2B IN HIV/HCV GENOTYPE-1
INFECTED PATIENTS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Herrmann, Eva] Goethe Univ Frankfurt, Dept Med, Inst Biostat, Frankfurt, Germany.
[Subramanian, Mani] Human Genome Sci Inc, Rockville, MD USA.
[Polis, Michael A.] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 870
BP 714A
EP 714A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000869
ER
PT J
AU Murphy, A
Polis, MA
Neumann, AU
Kottilil, S
AF Murphy, Alison
Polis, Michael A.
Neumann, Avidan U.
Kottilil, Shyam
TI TWICE WEEKLY PEG IFN-ALPHA-2A WITH RIBAVIRIN IMPROVES EARLY VIRAL
KINETICS OVER STANDARD THERAPY AMONG HIV/HCV CO-INFECTED AFRICAN
AMERICAN PATIENTS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Murphy, Alison; Polis, Michael A.; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Neumann, Avidan U.] Bar Ilan Univ, Ramat Dan, Israel.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 905
BP 731A
EP 731A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000904
ER
PT J
AU Heller, T
Rotman, Y
Haynes-Williams, V
Kleiner, DE
Ghany, MG
Liang, TJ
Hoofnagle, JH
AF Heller, Theo
Rotman, Yaron
Haynes-Williams, Vanessa
Kleiner, David E.
Ghany, Marc G.
Liang, T. Jake
Hoofnagle, Jay H.
TI LONG-TERM, HIGH-DOSE PEGINTERFERON ALFA-2A IS AN EFFECTIVE TREATMENT FOR
CHRONIC HEPATITIS D
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Heller, Theo; Rotman, Yaron; Haynes-Williams, Vanessa; Ghany, Marc G.; Liang, T. Jake; Hoofnagle, Jay H.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 3
Z9 3
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 911
BP 734A
EP 734A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000910
ER
PT J
AU Aouizerat, BE
Bambha, K
Unalp-Arida, A
Ferrell, L
Bass, NM
AF Aouizerat, Bradley E.
Bambha, Kiran
Unalp-Arida, Aynur
Ferrell, Linda
Bass, Nathan M.
TI GENETIC VARIATION IN HORMONE SENSITIVE LIPASE AND ADIPONECTIN CONFERS
SUSCEPTIBILITY TO NONALCOHOLIC FATTY LIVER DISEASE
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Aouizerat, Bradley E.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA.
[Bambha, Kiran; Bass, Nathan M.] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA.
[Unalp-Arida, Aynur] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Ferrell, Linda] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA.
[Aouizerat, Bradley E.; Bambha, Kiran; Unalp-Arida, Aynur; Ferrell, Linda; Bass, Nathan M.] NIDDK, NASH Clin Res Network, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 1
U2 2
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 987
BP 768A
EP 768A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000985
ER
PT J
AU Bambha, K
Aouizerat, BE
Unalp-Arida, A
Ferrell, L
Bass, NM
AF Bambha, Kiran
Aouizerat, Bradley E.
Unalp-Arida, Aynur
Ferrell, Linda
Bass, Nathan M.
TI GENETIC VARIATION IN ADIPONECTIN CONFERS SUSCEPTIBILITY TO NONALCOHOLIC
FATTY LIVER DISEASE IN LATINO CAUCASIANS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Bambha, Kiran; Bass, Nathan M.] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA.
[Aouizerat, Bradley E.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA.
[Unalp-Arida, Aynur] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Ferrell, Linda] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA.
[Bambha, Kiran; Aouizerat, Bradley E.; Unalp-Arida, Aynur; Ferrell, Linda; Bass, Nathan M.] NIDDK, NASH Clin Res Network, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 995
BP 771A
EP 772A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000992
ER
PT J
AU Kleiner, DE
Berk, PD
Hsu, JY
Belle, SH
Courcoulas, AP
Pomp, A
Roerig, JL
Smith, MD
Wolfe, BM
AF Kleiner, David E.
Berk, Paul D.
Hsu, Jesse Y.
Belle, Steven H.
Courcoulas, Anita P.
Pomp, Alfons
Roerig, James L.
Smith, Mark D.
Wolfe, Bruce M.
TI SPECTRUM OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) IN BARIATRIC
SURGERY PATIENTS WITH NORMAL ALANINE AMINOTRANSFERASE (ALT)
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Berk, Paul D.] Columbia Univ, New York, NY USA.
[Hsu, Jesse Y.; Belle, Steven H.; Courcoulas, Anita P.] Univ Pittsburgh, Pittsburgh, PA USA.
[Pomp, Alfons] Cornell Univ, New York, NY 10021 USA.
[Roerig, James L.] Univ N Dakota, Fargo, ND USA.
[Smith, Mark D.] Oregon Weight Loss Surg, Portland, OR USA.
[Wolfe, Bruce M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 994
BP 771A
EP 771A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456000991
ER
PT J
AU Katsounas, A
Trippler, M
Wang, B
Lempicki, RA
Bein, S
Gerken, G
Schlaak, JF
AF Katsounas, Antonios
Trippler, Martin
Wang, Bo
Lempicki, Richard A.
Bein, Sabine
Gerken, Guido
Schlaak, Joerg F.
TI CCL5 EXPRESSION IS A MARKER FOR THE STAGE OF LIVER FIBROSIS IN CHRONIC
HEPATITIS C AND IS REGULATED BY THE INNATE IMMUNE SYSTEM
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Katsounas, Antonios; Trippler, Martin; Wang, Bo; Bein, Sabine; Gerken, Guido; Schlaak, Joerg F.] Univ Hosp Essen, Dept Gastroenterol & Hepatol, Essen, Germany.
[Katsounas, Antonios; Lempicki, Richard A.] NIAID, Lab Bioinformat & Immunopathogenesis, SAIC Frederick Inc, Frederick, MD USA.
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1087
BP 813A
EP 813A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001084
ER
PT J
AU Modi, AA
Feld, JJ
Park, Y
Kleiner, DE
Everhart, JE
Liang, JT
Hoofnagle, JH
AF Modi, Apurva A.
Feld, Jordan J.
Park, Yoon
Kleiner, David E.
Everhart, James E.
Liang, Jake T.
Hoofnagle, Jay H.
TI REDUCED LIVER FIBROSIS: COFFEE OR CAFFEINE?
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Modi, Apurva A.; Park, Yoon; Liang, Jake T.; Hoofnagle, Jay H.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
[Feld, Jordan J.] Univ Toronto, Div Gastroenterol, Toronto, ON, Canada.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1097
BP 817A
EP 817A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001094
ER
PT J
AU Marquardt, JU
Raggi, C
Andersen, JB
Seo, D
Avital, I
Holczbauer, A
Factor, VM
Thorgeirsson, SS
AF Marquardt, Jens U.
Raggi, Chiara
Andersen, Jesper B.
Seo, Deakwan
Avital, Itzhak
Holczbauer, Agnes
Factor, Valentina M.
Thorgeirsson, Snorri S.
TI GENE EXPRESSION SIGNATURE OF PUTATIVE CANCER STEM CELLS PREDICTS
SURVIVAL OF HCC PATIENTS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Marquardt, Jens U.; Raggi, Chiara; Andersen, Jesper B.; Seo, Deakwan; Holczbauer, Agnes; Factor, Valentina M.; Thorgeirsson, Snorri S.] NCI, LEC, NIH, Bethesda, MD 20892 USA.
[Avital, Itzhak] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1182
BP 854A
EP 855A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001179
ER
PT J
AU Zeissig, S
Murata, K
Hu, ZY
Kaser, A
Dougan, SK
Scapa, E
Cohen, DE
Liang, JT
Blumberg, RS
AF Zeissig, Sebastian
Murata, Kazumoto
Hu, Zongyi
Kaser, Arthur
Dougan, Stephanie K.
Scapa, Erez
Cohen, David E.
Liang, Jake T.
Blumberg, Richard S.
TI MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN REGULATES CD1D-RESTRICTED
ANTIGEN PRESENTATION OF HEPATOCYTES AND CONTROLS NKT CELL HOMEOSTASIS
VIA CD1D-MEDIATED APOPTOSIS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Zeissig, Sebastian; Dougan, Stephanie K.; Scapa, Erez; Cohen, David E.; Blumberg, Richard S.] Dept Med, Div Gastroenterol, Boston, MA USA.
[Kaser, Arthur] Innsbruck Med Univ, Div Gastroenterol, Innsbruck, Austria.
[Murata, Kazumoto; Hu, Zongyi; Liang, Jake T.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
RI Zeissig, Sebastian/B-6297-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1202
BP 863A
EP 864A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001199
ER
PT J
AU Wang, H
Park, O
Lafdil, F
Shen, KZ
Horiguchi, N
Yin, S
Fu, XY
Kunos, G
Gao, B
AF Wang, Hua
Park, Ogyi
Lafdil, Fouad
Shen, Kezhen
Horiguchi, Norio
Yin, Shi
Fu, Xin-Yuan
Kunos, George
Gao, Bin
TI INTERPLAY OF HEPATIC AND MYELOID STAT3 IN FACILITATING LIVER
REGENERATION VIA TEMPERING INNATE IMMUNITY
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Wang, Hua; Park, Ogyi; Lafdil, Fouad; Shen, Kezhen; Horiguchi, Norio; Yin, Shi; Kunos, George; Gao, Bin] NIAAA, NIH, Bethesda, MD 46202 USA.
[Fu, Xin-Yuan] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1220
BP 871A
EP 871A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001217
ER
PT J
AU Horiguchi, N
Lafdil, F
Park, O
Wang, H
Mukhopadhyay, P
Pacher, P
Gao, B
AF Horiguchi, Norio
Lafdil, Fouad
Park, Ogyi
Wang, Hua
Mukhopadhyay, Partha
Pacher, Pal
Gao, Bin
TI DISSOCIATION OF LIVER INFLAMMATION AND NECROSIS INDUCED BY HEPATOTOXIN
CARBON TETRACHLORIDE IN MYELOID CELL-SPECIFIC STAT3 KNOCKOUT MICE
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Horiguchi, Norio; Lafdil, Fouad; Park, Ogyi; Wang, Hua; Mukhopadhyay, Partha; Pacher, Pal; Gao, Bin] NIAAA, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1244
BP 881A
EP 881A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001241
ER
PT J
AU Lafdil, F
Wang, H
Park, O
Zhang, WC
Moritoki, Y
Yin, S
Gershwin, ME
Lian, ZX
Gao, B
AF Lafdil, Fouad
Wang, Hua
Park, Ogyi
Zhang, Weici
Moritoki, Yuki
Yin, Shi
Gershwin, M. Eric
Lian, Zhe-Xiong
Gao, Bin
TI MYELOID STAT3 DEFICIENCY EXACERBATES T CELL HEPATITIS VIA PROMOTING
PREFERENTIALLY TH1 RESPONSE AND TH17 TO A LESSER EXTENT
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Lafdil, Fouad; Wang, Hua; Park, Ogyi; Yin, Shi; Gao, Bin] NIAAA, Sect Liver Biol, NIH, Rockville, MD 20852 USA.
[Zhang, Weici; Moritoki, Yuki; Gershwin, M. Eric; Lian, Zhe-Xiong] Univ Calif Davis, Div Rheumatol, Davis, CA 95616 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1252
BP 884A
EP 885A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001249
ER
PT J
AU Katsounas, A
Rasimas, JJ
Lempicki, RA
Yang, J
Kottilil, S
AF Katsounas, Antonios
Rasimas, Joseph J.
Lempicki, Richard A.
Yang, Jun
Kottilil, Shyam
TI PSYCHIATRIC SIDE EFFECTS TO INTERFERON-alpha/RIBAVIRIN ARE ASSOCIATED
WITH DISTINCT ISG20 AND FNBP-1 EXPRESSION PROFILES IN THERAPEUTIC
RESPONDERS (SVR) AND NON-RESPONDERS (NR) IN HIV AND HCV CO-INFECTION
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Katsounas, Antonios; Lempicki, Richard A.; Yang, Jun] NCI Frederick, SAIC, Bethesda, MD USA.
[Rasimas, Joseph J.] NIMH, NIH, Bethesda, MD 20892 USA.
[Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1329
BP 917A
EP 918A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001326
ER
PT J
AU Kottilil, S
Zhang, XZ
Yang, J
Lempicki, RA
Sneller, M
AF Kottilil, Shyam
Zhang, Xiaozhen
Yang, Jun
Lempicki, Richard A.
Sneller, Michael
TI WHOLE GENOME TRANSCRIPTIONAL PROFILING IN PBMC ILLUSTRATES UNIQUE
PATHOGENIC CHARACTERISTICS OF B CELL DEPLETION THERAPY IN HCV MIXED
CRYOGLOBULINEMIC VASCULITIS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Kottilil, Shyam; Zhang, Xiaozhen; Sneller, Michael] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Yang, Jun; Lempicki, Richard A.] SAIC Frederick, Frederick, MD USA.
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1342
BP 923A
EP 923A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001339
ER
PT J
AU Kottilil, S
Migone, T
Rao, K
Subramanian, M
Sneller, M
AF Kottilil, Shyam
Migone, Thi
Rao, Koneti
Subramanian, Mani
Sneller, Michael
TI CHANGES IN PLASMA BLYS LEVELS IN PATIENTS WITH HCV MIXED
CRYOGLOBULINEMIC VASCULITIS DURING TREATMENT WITH RITUXIMAB
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Kottilil, Shyam; Sneller, Michael] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Rao, Koneti] NIAID, LCID, NIH, Bethesda, MD 20892 USA.
[Migone, Thi; Subramanian, Mani] Human Genome Sci, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1345
BP 924A
EP 925A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001342
ER
PT J
AU Derbala, MF
Shebl, FM
Rashid, AH
Amer, AM
Bener, A
AF Derbala, Moutaz F.
Shebl, Fatma M.
Rashid, Awad H.
Amer, Aliaa M.
Bener, Abdulbari
TI MICROALBUMINURIA IN HEPATITIS C GENOTYPE 4: RELATION TO LIVER HISTOLOGY,
VIRAL LOAD, AND EFFECT OF TREATMENT
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Shebl, Fatma M.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Rashid, Awad H.] Hamad Med Corp, Dept Nephrol, Doha, Qatar.
[Amer, Aliaa M.] Hamad Med Corp, Dept Lab Med & Histopathol, Hematol Sect, Doha, Qatar.
[Bener, Abdulbari] Hamad Med Corp, Dept Med Stat & Epidemiol, Doha, Qatar.
[Derbala, Moutaz F.] Hamad Med Corp, Dept Gastroenterol & Hepatol, Doha, Qatar.
[Derbala, Moutaz F.] Weill Cornell Med Coll Qatar, Doha, Qatar.
[Shebl, Fatma M.] Natioal Liver Inst, Dept Epidemiol, Menoufia, Egypt.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1352
BP 927A
EP 927A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001348
ER
PT J
AU Katsounas, A
Lempicki, RA
Schlaak, JF
Gerken, G
Polis, MA
Kottilil, S
AF Katsounas, Antonios
Lempicki, Richard A.
Schlaak, Joerg F.
Gerken, Guido
Polis, Michael A.
Kottilil, Shyam
TI HIGH ISG-15 EXPRESSION 15 CORRELATED WITH NON-RESPONSE (NR) IN HIV/HCV
CO-INFECTED SUBJECTS TREATED WITH PEG-INTERFERON AND RIBAVIRIN
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Katsounas, Antonios; Lempicki, Richard A.] SAIC, NCI Frederick, Bethesda, MD USA.
[Polis, Michael A.] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Katsounas, Antonios; Schlaak, Joerg F.; Gerken, Guido; Kottilil, Shyam] Univ Essen Gesamthsch, Dept Gastroenterol & Hepatol, Essen, Germany.
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1377
BP 938A
EP 939A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001373
ER
PT J
AU Natarajan, V
Hazen, A
Polis, MA
Kovacs, JA
Kottilil, S
AF Natarajan, Ven
Hazen, Allison
Polis, Michael A.
Kovacs, Joseph A.
Kottilil, Shyam
TI HCV IN PERIPHERAL BLOOD MONONUCLEAR CELLS ARE PREDOMINANTLY CARRIED ON
THE SURFACE OF NATURAL KILLER CELLS IN HIV/HCV CO-INFECTED INDIVIDUALS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Polis, Michael A.; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Natarajan, Ven; Hazen, Allison] SAIC Frederick, Mol Cell Biol Lab, Frederick, MD USA.
[Kovacs, Joseph A.] NIH, CCMD, CC, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1384
BP 941A
EP 942A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001380
ER
PT J
AU Lempicki, RA
Schlaak, JF
Murphy, A
Kottilil, S
AF Lempicki, Richard A.
Schlaak, Joerg F.
Murphy, Alison
Kottilil, Shyam
TI GENOME-WIDE SINGLE NUCLEOTIDE POILYMORPHISM ANALYSIS IDENTIFIES A UNIQUE
INTEGRIN BETA 5 (ITGB5) HAPLOTYPE IN ADVANCED LIVER FIBROSIS PATIENTS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Murphy, Alison; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Lempicki, Richard A.] SAIC Frederick, Frederick, MD USA.
[Schlaak, Joerg F.] Univ Essen Hosp, Essen, Germany.
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
NR 0
TC 2
Z9 2
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1385
BP 942A
EP 942A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001381
ER
PT J
AU Zhang, XZ
Daucher, M
Kottilil, S
AF Zhang, Xiaozhen
Daucher, Marybeth
Kottilil, Shyam
TI HIV ENHANCES HCV REPLICATION BY ITS INTERACTION WITH MADCAM EXPRESSING
HEPATOCELLULAR CARCINOMA CELLS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Zhang, Xiaozhen; Daucher, Marybeth; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1397
BP 947A
EP 948A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001393
ER
PT J
AU Li, QS
Brass, AL
Ng, A
Xavier, R
Liang, TJ
Elledge, SJ
AF Li, Qisheng
Brass, Abraham L.
Ng, Aylwin
Xavier, Ramnik
Liang, T. Jake
Elledge, Stephen J.
TI A GENOME-WIDE GENETIC SCREEN FOR HOST FACTORS REQUIRED FOR HEPATITIS C
VIRUS PROPAGATION
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Li, Qisheng; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
[Brass, Abraham L.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA.
[Brass, Abraham L.] Harvard Univ, Sch Med, Boston, MA USA.
[Brass, Abraham L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA.
[Ng, Aylwin; Xavier, Ramnik] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA USA.
[Elledge, Stephen J.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet,Div Genet,Brigham & Womens Hosp, Boston, MA 02115 USA.
RI Li, Qisheng/K-1909-2013
NR 0
TC 0
Z9 0
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1404
BP 950A
EP 951A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001400
ER
PT J
AU Zhang, XZ
Daucher, M
Yang, J
Lempicki, RA
Kottilil, S
AF Zhang, Xiaozhen
Daucher, Marybeth
Yang, Jun
Lempicki, Richard A.
Kottilil, Shyam
TI GENOME WIDE TRANSRIPTIONAL PROFILING OF HEPATOMA CELLS IDENTIFIES GENES
SIGNIFICANT FOR HCV ENTRY, PATHOGENESIS AND RESPONSE TO INTERFERON
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Zhang, Xiaozhen; Daucher, Marybeth; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Yang, Jun; Lempicki, Richard A.] SAIC Frederick, Frederick, MD USA.
RI Lempicki, Richard/E-1844-2012
OI Lempicki, Richard/0000-0002-7059-409X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1407
BP 951A
EP 952A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001403
ER
PT J
AU Zeremski, M
Hooker, G
Shu, MA
Brown, Q
Des Jarlais, DC
Tobler, LH
Rehermann, B
Busch, MP
Edlin, BR
Talal, A
AF Zeremski, Marija
Hooker, Giles
Shu, Marla A.
Brown, Queenie
Des Jarlais, Don C.
Tobler, Leslie H.
Rehermann, Barbara
Busch, Michael P.
Edlin, Brian R.
Talal, Andrew
TI INDUCTION OF CXCR3-AND CCR5-ASSOCIATED CHEMOKINES DURING ACUTE HEPATITIS
C VIRUS (HCV) INFECTION
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Zeremski, Marija; Brown, Queenie; Talal, Andrew] Weill Cornell Med Coll, Ctr Study Hepatitis C, Med GI, New York, NY USA.
[Hooker, Giles] Cornell Univ, Ithaca, NY USA.
[Shu, Marla A.; Edlin, Brian R.] SUNY Downstate Coll Med, Brooklyn, NY USA.
[Des Jarlais, Don C.] Beth Israel Deaconess Med Ctr, Baron Edmond de Rothschild Chem Dependency Inst, New York, NY 10003 USA.
[Tobler, Leslie H.; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA.
[Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD USA.
[Busch, Michael P.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
SU S
MA 1408
BP 952A
EP 952A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001404
ER
PT J
AU Lagaye, S
Nascimbeni, M
Triyatni, M
Bourdoncle, P
Pol, S
Saunier, B
AF Lagaye, Sylvie
Nascimbeni, Michelina
Triyatni, Miriam
Bourdoncle, Pierre
Pol, Stanislas
Saunier, Bertrand
TI EVIDENCE FOR REPLICATION AND RELEASE OF HEPATITIS C VIRUS FOLLOWING THE
EX VIVO INFECTION OF CULTURED HUMAN LIVER SLICES WITH VIRAL STRAINS OF
GENOTYPES 1 AND 2
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Lagaye, Sylvie; Nascimbeni, Michelina; Bourdoncle, Pierre; Pol, Stanislas; Saunier, Bertrand] Inst Cochin, Paris, France.
[Triyatni, Miriam] NIAID, MSS, LVD, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1419
BP 957A
EP 957A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001415
ER
PT J
AU Frank, AC
Katsounas, A
Bharucha, J
Imamichi, T
Kottilil, S
AF Frank, Astrid C.
Katsounas, Antonios
Bharucha, Jennifer
Imamichi, Tomozumi
Kottilil, Shyam
TI AN INTERLEUKIN-12 FAMILY CYTOKINE, IL-27 INHIBITS HEPATITIS C VIRUS
REPLICATION IN VITRO BOTH DIRECTLY AND SYNERGISTICALLY WITH INTERFeRON
ALPHA
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Katsounas, Antonios; Bharucha, Jennifer; Imamichi, Tomozumi] NCI, SAIC, Bethesda, MD 20892 USA.
[Frank, Astrid C.; Kottilil, Shyam] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1423
BP 959A
EP 959A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001419
ER
PT J
AU Zhang, XZ
Daucher, M
Kottilil, S
AF Zhang, Xiaozhen
Daucher, Marybeth
Kottilil, Shyam
TI IDENTIFICATION OF HOST MICRORNAS THAT BLOCK HCV REPLICATION IN VITRO AS
POTENTIAL TARGETS FOR TREATMENT OF HCV
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Zhang, Xiaozhen; Daucher, Marybeth; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1430
BP 962A
EP 962A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001426
ER
PT J
AU Mi, LJ
Karsdon, J
Huang, WM
Chiang, B
Ghany, MG
Del Priore, G
Poon, E
Leong, M
Brown, RS
AF Mi, Li-Jun
Karsdon, Jeffrey
Huang, William M.
Chiang, Betty
Ghany, Marc G.
Del Priore, Giuseppe
Poon, Eric
Leong, Michelle
Brown, Robert S.
TI HEPATITIS B VIRUS (HBV) TRANSMISSION RATE AMONG CHILDREN BORN TO
CHINESE-AMERICAN MOTHERS WITH CHRONIC HEPATITIS B (CHB) IN THE NEW YORK
DOWNTOWN AREA
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Mi, Li-Jun] New York Downtown Hosp, Dept Med, Out Patient Div, New York, NY USA.
[Karsdon, Jeffrey; Poon, Eric] New York Downtown Hosp, Dept Pediat, New York, NY USA.
[Huang, William M.] New York Downtown Hosp, Dept Obstet & Gynecol, New York, NY USA.
[Chiang, Betty] Gilead Sci Inc, Hepatitis Med Sci, Foster City, CA 94404 USA.
[Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
[Del Priore, Giuseppe] New York Downtown Hosp, Dept Obstet & Gynecol, New York, NY USA.
[Poon, Eric; Leong, Michelle] Chinese Community Partnership Hlth, New York, NY USA.
[Brown, Robert S.] Columbia Univ, Med Ctr, Div Liver Dis & Transplantat, New York, NY 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 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
SU S
MA 1438
BP 966A
EP 966A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001434
ER
PT J
AU Pati, NT
Daucher, M
Murphy, A
Sarin, SK
Davey, RT
Kottilil, S
AF Pati, Nirupma Trehan
Daucher, Marybeth
Murphy, Alison
Sarin, Shiv K.
Davey, Richard T.
Kottilil, Shyam
TI IL-15 STIMULATION WITH PD-1/PD-L1/2 BLOCKADE ENHANCES HBV-SPECIFIC
EFFECTOR CD8+T CELL IMMUNITY IN HIV POSITIVE AND NEGATIVE HBEAG NEGATIVE
CHRONIC HEPATITIS B PATIENTS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Daucher, Marybeth; Murphy, Alison; Davey, Richard T.; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA.
[Pati, Nirupma Trehan; Sarin, Shiv K.] Inst Liver & Biliary Sci, New Delhi, India.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1455
BP 974A
EP 974A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001451
ER
PT J
AU Curto, TM
Lok, AS
Lagier, RJ
Rowland, CM
Sninsky, J
Everhart, JE
AF Curto, Teresa M.
Lok, Anna S.
Lagier, Robert J.
Rowland, Charles M.
Sninsky, John
Everhart, James E.
TI VALIDATION OF A PANEL OF GENETIC MARKERS (CRS7) IN PREDICTING CIRRHOSIS,
FIBROSIS PROGRESSION (FP) AND CLINICAL OUTCOMES IN PATIENTS WITH CHRONIC
HEPATITIS C (CHC) IN THE HALT-C TRIAL
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA.
[Lok, Anna S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA.
[Everhart, James E.] NIDDK, Bethesda, MD USA.
[Lagier, Robert J.; Rowland, Charles M.; Sninsky, John] Celera, Alameda, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1620
BP 1054A
EP 1054A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001615
ER
PT J
AU Fontana, RJ
Lok, AS
Dienstag, JL
Naishadham, D
Bonkovsky, HL
Wright, EC
Goodman, ZD
Sterling, RK
AF Fontana, Robert J.
Lok, Anna S.
Dienstag, Jules L.
Naishadham, Deepa
Bonkovsky, Herbert L.
Wright, Elizabeth C.
Goodman, Zachary D.
Sterling, Richard K.
TI SERUM FIBROSIS MARKERS ARE ASSOCIATED WITH CLINICAL OUTCOMES AND
HISTOLOGICAL PROGRESSION IN PATIENTS WITH CHRONIC HEPATITIS C (CHC) AND
ADVANCED FIBROSIS
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Fontana, Robert J.; Lok, Anna S.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Bonkovsky, Herbert L.] Carolina Med Ctr, Dept Med, Charlotte, NC USA.
[Goodman, Zachary D.] Armed Forces Inst Pathol, Dept Pathol, Washington, DC 20306 USA.
[Sterling, Richard K.] Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA.
[Dienstag, Jules L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Naishadham, Deepa] New England Res Inst, Boston, MA USA.
[Wright, Elizabeth C.] NIH, Liver Dis Res Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1625
BP 1056A
EP 1057A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001620
ER
PT J
AU Everson, GT
Hoefs, JC
Shiffman, ML
Morgan, TR
Sterling, RK
Curto, TM
Wagner, D
Wright, EC
Everhart, JE
AF Everson, Gregory T.
Hoefs, John C.
Shiffman, Mitchell L.
Morgan, Timothy R.
Sterling, Richard K.
Curto, Teresa M.
Wagner, David
Wright, Elizabeth C.
Everhart, James E.
TI HEPATIC IMPAIRMENT MEASURED BY QUANTITATIVE TESTS OF LIVER FUNCTION
(QLFTS) PREDICTS CLINICAL OUTCOME IN PATIENTS WITH ADVANCED FIBROSIS:
RESULTS FROM THE HEPATITIS C ANTIVIRAL LONG-TERM TREATMENT AGAINST
CIRRHOSIS (HALT-C) TRIAL
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Everson, Gregory T.] Univ Colorado, Transplant Ctr & Hepatol, Aurora, CO USA.
[Hoefs, John C.; Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol & Hepatol, Irvine, CA USA.
[Shiffman, Mitchell L.; Sterling, Richard K.] VCU, Sect Hepatol, Richmond, VA USA.
[Wagner, David] Metab Solut, Nashua, NH USA.
[Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA.
[Wright, Elizabeth C.; Everhart, James E.] NIDDK, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1627
BP 1057A
EP 1058A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001622
ER
PT J
AU Marrero, J
Schwartz, ME
Nguyen, MH
Befeler, A
Reddy, KR
Roberts, LR
Harnois, DM
Wang, YH
Wagner, P
Feng, ZD
AF Marrero, Jorge
Schwartz, Myron E.
Nguyen, Mindie H.
Befeler, Alex
Reddy, K. Rajender
Roberts, Lewis R.
Harnois, Denise M.
Wang, Yinghui
Wagner, Paul
Feng, Ziding
TI ALPHA-FETOPROTEIN AND DES-GAMMA CARBOXYPROTHROMBIN ARE INDEPENDENT
PREDICTORS OF EARLY STAGE HEPATOCELLULAR CARCINOMA
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Marrero, Jorge] Univ Michigan, Ann Arbor, MI 48109 USA.
[Schwartz, Myron E.] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Nguyen, Mindie H.] Stanford Univ, Palo Alto, CA 94304 USA.
[Befeler, Alex] St Louis Univ, St Louis, MO 63103 USA.
[Reddy, K. Rajender] Univ Penn, Philadelphia, PA 19104 USA.
[Roberts, Lewis R.] Mayo Clin, Rochester, MN USA.
[Harnois, Denise M.] Mayo Clin, Jacksonville, FL 32224 USA.
[Wang, Yinghui; Feng, Ziding] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Wagner, Paul] Natl Canc Inst, Bethesda, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1699
BP 1091A
EP 1092A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001693
ER
PT J
AU Rabenhorst, U
Beinoraviciute-Kellner, R
Brezniceanu, ML
Joos, S
Devens, F
Lichter, P
Rieker, RJ
Trojan, J
Chung, HJ
Levens, DL
Zornig, M
AF Rabenhorst, Uta
Beinoraviciute-Kellner, Rasa
Brezniceanu, Marie-Luise
Joos, Stefan
Devens, Frauke
Lichter, Peter
Rieker, Ralf J.
Trojan, Joerg
Chung, Hye-Jung
Levens, David L.
Zoernig, Martin
TI Overexpression of the Far Upstream Element Binding Protein 1 in
Hepatocellular Carcinoma Is Required for Tumor Growth
SO HEPATOLOGY
LA English
DT Article
ID C-MYC EXPRESSION; CELL-DEATH; DNA; CANCER; MECHANISM; APOPTOSIS;
RESECTION; TARGETS; VIRUS; TFIIH
AB We identified the far upstream element binding protein 1 (FBP1), an activator of transcription of the proto-oncogene c-myc, in a functional yeast survival screen for tumor-related antiapoptotic proteins and demonstrated strong overexpression of FBP1 in human hepatocellular carcinoma (HCC). Knockdown of the protein in HCC cells resulted in increased sensitivity to apoptotic stimuli, reduced cell proliferation, and impaired tumor formation in a mouse xenograft transplantation model. Interestingly, analysis of gene regulation in these cells revealed that c-myc levels were not influenced by FBP1 in HCC cells. Instead, we identified the cell cycle inhibitor p21 as a direct target gene repressed by FBP1, and in addition, expression levels of the proapoptotic genes tumor necrosis factor a, tumor necrosis factor-related apoptosis-inducing ligand, Noxa, and Bik were elevated in the absence of FBP1. Conclusion: Our data establish FBP1 as an important oncoprotein overexpressed in HCC that induces tumor propagation through direct or indirect repression of cell cycle inhibitors and proapoptotic target genes. (HEPATOLOGY 2009;50:1121-1129.)
C1 [Rabenhorst, Uta; Beinoraviciute-Kellner, Rasa; Brezniceanu, Marie-Luise; Zoernig, Martin] Chemotherapeut Forschungsinst Georg Speyer Haus, D-60596 Frankfurt, Germany.
[Joos, Stefan; Devens, Frauke; Lichter, Peter] German Canc Res Ctr, Div Mol Genet, D-6900 Heidelberg, Germany.
[Rieker, Ralf J.] Univ Hosp, Dept Pathol, Heidelberg, Germany.
[Rieker, Ralf J.] Med Univ Innsbruck, Dept Pathol, Innsbruck, Austria.
[Trojan, Joerg] Goethe Univ Frankfurt, Dept Internal Med 1, Frankfurt, Germany.
[Chung, Hye-Jung; Levens, David L.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Zornig, M (reprint author), Chemotherapeut Forschungsinst Georg Speyer Haus, Paul Ehrlich Str 42-44, D-60596 Frankfurt, Germany.
EM zoernig@em.uni-frankfurt.de
RI Levens, David/C-9216-2009
OI Levens, David/0000-0002-7616-922X
FU Intramural NIH HHS [ZIA SC009144-26]
NR 31
TC 42
Z9 46
U1 0
U2 5
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
BP 1121
EP 1129
DI 10.1002/hep.23098
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JU
UT WOS:000270455800019
PM 19637194
ER
PT J
AU Jeannot, E
Boorman, GA
Shymonyak, S
Kosyk, O
Rusyn, I
AF Jeannot, Emmanuelle
Boorman, Gary A.
Shymonyak, Svitlana
Kosyk, Oksana
Rusyn, Ivan
TI INCIDENCE OF AFLATOXIN B1-INDUCED HEPATIC TUMORS IS INCREASED IN
HEPATITIS VIRUS C TRANSGENIC MICE AS COMPARED TO WILD TYPE C57BL/6J
STRAIN
SO HEPATOLOGY
LA English
DT Meeting Abstract
CT 60th Annual Meeting of the
American-Association-for-the-Study-of-Liver-Diseases
CY OCT 30-NOV 03, 2009
CL Boston, MA
SP Amer Assoc Study Liver Dis
C1 [Jeannot, Emmanuelle; Shymonyak, Svitlana; Kosyk, Oksana; Rusyn, Ivan] UNC, ESE, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Boorman, Gary A.] Natl Inst Environm Hlth Sci, Environm Toxicol Program, Res Triangle Pk, NC USA.
RI Rusyn, Ivan/S-2426-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
MA 1812
BP 1141A
EP 1141A
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JV
UT WOS:000270456001806
ER
PT J
AU Hikita, H
Takehara, T
Shimizu, S
Kodama, T
Li, W
Miyagi, T
Hosui, A
Ishida, H
Ohkawa, K
Kanto, T
Hiramatsu, N
Yin, XM
Hennighausen, L
Tatsumi, T
Hayashi, N
AF Hikita, Hayato
Takehara, Tetsuo
Shimizu, Satoshi
Kodama, Takahiro
Li, Wei
Miyagi, Takuya
Hosui, Atsushi
Ishida, Hisashi
Ohkawa, Kazuyoshi
Kanto, Tatsuya
Hiramatsu, Naoki
Yin, Xiao-Ming
Hennighausen, Lothar
Tatsumi, Tomohide
Hayashi, Norio
TI Mcl-1 and Bcl-xL Cooperatively Maintain Integrity of Hepatocytes in
Developing and Adult Murine Liver
SO HEPATOLOGY
LA English
DT Article
ID HUMAN HEPATOCELLULAR CARCINOMAS; DEFICIENT MICE; CELL-DEATH; PROTEIN
FAMILY; APOPTOSIS; FAS; SUPPRESSION; DISRUPTION; INJURY; HAIR
AB Anti-apoptotic members of the Bd-2 family, including Bcl-2, Bcl-xL, Mcl-1, Bd-w and Bfl-1, inhibit the mitochondrial pathway of apoptosis. Bd-xL and Mcl-1 are constitutively expressed in the liver. Although previous research established Bcl-xL as a critical apoptosis antagonist in differentiated hepatocytes, the significance of Mcl-1 in the liver, especially in conjunction with Bcl-xL, has not been clear. To examine this question, we generated hepatocyte-specific Mcl-1-deficient mice by crossing mcl-1(flox/flox) mice and AlbCre mice and further crossed them with bcl-x(flox/flox) mice, giving Mcl-1/Bcl-xL-deficient mice. The mcl-1(flox/flox) mice showed spontaneous apoptosis of hepatocytes after birth, as evidenced by elevated levels of serum alanine aminotransferase (ALT) and caspase-3/7 activity and an increased number of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling (TUNEL)positive cells in the liver; these phenotypes were very close to those previously found in hepatocyte-specific Bcl-xL-deficient mice. Although mcl-1(flox/+) AlbCre mice did not display apoptosis, their susceptibility to Fas-mediated liver injury significantly increased. Further crossing of Mcl-1 mice with Bd-xL mice showed that bcl-x(flox+) mcl-1(flox)/(+) AlbCre mice also showed spontaneous hepatocyte apoptosis similar to Bcl-xL-deficient or Mcl-1-deficient mice. In contrast, bcl-x(flox/flox) mcl-1(flox/+) AlbCre, bcl-x(flox/+) mcl-1(flox/flox) AlbCre, and bcl-x(flox/flox) mcl-1(flox/flox) AlbCre mice displayed a decreased number of hepatocytes and a reduced volume of the liver on day 18.5 of embryogenesis and rapidly died within I day after birth, developing hepatic failure evidenced by increased levels of blood ammonia and bilirubin. Conclusion: Mcl-1 is critical for blocking apoptosis in adult liver and, in the absence of Bcl-xL, is essential for normal liver development. Mcl-1 and Bcl-xL are two major anti-apoptotic Bd-2 family proteins expressed in the liver and cooperatively control hepatic integrity during liver development and in adult liver homeostasis in a gene dose-dependent manner. (HEPATOLOGY 2009;50:1217-1226.)
C1 [Hikita, Hayato; Takehara, Tetsuo; Shimizu, Satoshi; Kodama, Takahiro; Li, Wei; Miyagi, Takuya; Hosui, Atsushi; Ishida, Hisashi; Ohkawa, Kazuyoshi; Kanto, Tatsuya; Hiramatsu, Naoki; Tatsumi, Tomohide; Hayashi, Norio] Osaka Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, Suita, Osaka 5650871, Japan.
[Yin, Xiao-Ming] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA.
[Hennighausen, Lothar] NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA.
RP Hayashi, N (reprint author), Osaka Univ, Grad Sch Med, Dept Gastroenterol & Hepatol, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM hayashin@gh.med.osaka-u.ac.jp
OI Kodama, Takahiro/0000-0002-6250-1324
FU Ministry of Educatin, Culture, Sports, and Technology, Japan
FX Supported in part by a Grant-in-Aid for Scientific Research from the
Ministry of Educatin, Culture, Sports, and Technology, Japan (to T.
Tak).
NR 34
TC 41
Z9 42
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD OCT
PY 2009
VL 50
IS 4
BP 1217
EP 1226
DI 10.1002/hep.23126
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 502JU
UT WOS:000270455800029
PM 19676108
ER
PT J
AU Rutter, L
Carver, FW
Holroyd, T
Nadar, SR
Mitchell-Francis, J
Apud, J
Weinberger, DR
Coppola, R
AF Rutter, Lindsay
Carver, Frederick W.
Holroyd, Tom
Nadar, Sreenivasan Rajamoni
Mitchell-Francis, Judy
Apud, Jose
Weinberger, Daniel R.
Coppola, Richard
TI Magnetoencephalographic Gamma Power Reduction in Patients with
Schizophrenia During Resting Condition
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE default network; synthetic aperture magnetometry; baseline; precuneus;
cuneus; SAM; magnetoencephalography; unaffected siblings; default mode
ID VISUOSPATIAL WORKING-MEMORY; TASK-INDUCED DEACTIVATION; MEDIAL
PREFRONTAL CORTEX; FALSE DISCOVERY RATE; DEFAULT-MODE;
ALZHEIMERS-DISEASE; FUNCTIONAL CONNECTIVITY; BRAIN-FUNCTION; CORTICAL
NETWORKS; STATE FMRI
AB Objective: The "default network" represents a baseline condition of brain function and is of interest in schizophrenia research because its component brain regions are believed to be aberrant in the disorder. We hypothesized that magnetoencephalographic (MEG) source localization analysis would reveal abnormal resting activity within particular frequency bands in schizophrenia. Experimental Design: Eyes-closed resting state MEG signals were collected for two comparison groups. Patients with schizophrenia (N = 38) were age-gender matched with healthy control subjects (N = 38), and with a group of unmedicated unaffected siblings of patients with schizophrenia (N = 38). To localize 3D-brain regional differences, svnthetic aperture magnetometry was calculated across established frequency bands as follows: delta (0.9-4 Hz), theta (4-8 Hz), alpha (8-14 Hz), beta (14-30 Hz), gamma (30-80 Hz), and super-gamma (80-150 Hz). Principle Observations: Patients with schizophrenia showed significantly reduced activation in the gamma frequency band in the posterior region of the medial parietal cortex. As a group, unaffected siblings of schizophrenia patients also showed significantly reduced activation in the gamma bandwidth across similar brain regions. Moreover, using the significant region for the patients and examining the gamma band power gave an odds ratio of 6:1 for reductions of two standard deviations from the mean. This suggests that the measure might be the basis of an intermediate phenotype. Conclusions: MEG resting state analysis adds to the evidence that schizophrenic patients experience this condition very differently than healthy controls. Whether this baseline difference relates to network abnormalities remains to be seen. Hum Brain Mapp 30:3254-3264, 2009. (C) 2009 Wile-Liss, Inc.
C1 [Rutter, Lindsay; Carver, Frederick W.; Holroyd, Tom; Nadar, Sreenivasan Rajamoni; Mitchell-Francis, Judy; Coppola, Richard] NIMH, MEG Core Facil, Bethesda, MD 20892 USA.
[Apud, Jose; Weinberger, Daniel R.; Coppola, Richard] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
RP Coppola, R (reprint author), NIH, 301-402-7345,Bldg 10 Magnuson CC,4S235,9000 Rockv, Bethesda, MD 20892 USA.
EM coppolar@mail.nih.gov
FU NIMH Intramural Research program
FX Contract Grant sponsor: NIMH Intramural Research program.
NR 59
TC 49
Z9 50
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD OCT
PY 2009
VL 30
IS 10
BP 3254
EP 3264
DI 10.1002/hbm.20746
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 507LB
UT WOS:000270853700014
PM 19288463
ER
PT J
AU Yerys, BE
Jankowski, KF
Shook, D
Rosenberger, LR
Barnes, KA
Berl, MM
Ritzl, EK
VanMeter, J
Vaidya, CJ
Gaillard, WD
AF Yerys, Benjamin E.
Jankowski, Kathryn F.
Shook, Devon
Rosenberger, Lisa R.
Barnes, Kelly Anne
Berl, Madison M.
Ritzl, Eva K.
VanMeter, John
Vaidya, Chandan J.
Gaillard, William D.
TI The fMRI Success Rate of Children and Adolescents: Typical Development,
Epilepsy, Attention Deficit/Hyperactivity Disorder, and Autism Spectrum
Disorders
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE autism; epilepsy; ADHD; children; success
ID INTERVIEW
AB Functional magnetic resonance imaging (fMRI) in children is increasingly used in clinical application and in developmental research; however, little is known how pediatric patient and typically developing populations successfully complete studies. We examined pediatric Success rates with epilepsy, attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and typically developing children (TYP). We also examined the affect of age, and, for ADHD populations, medication status On success rates. We defined a successful fMRI individual run when the data were interpretable and included in group statistics. For unsuccessful runs, datasets with excessive motion or floor task performance were categorized when possible. All clinical groups scanned less successfully than controls; medication status did not affect ADHD success (epilepsy, 80%; ADHD (off methylphenidate), 77%; ADHD (on methylphenidate), 81%; ASD, 70%; TYP, 87%). Ten to 18-year-old had a significantly greater scan success rate than 4- to 6-year-old; adolescents (13- to 18-year-old) demonstrated greater scan success rates than 7- to 9-year-old. Success rate for completing an entire battery of experimental runs (n = 2-6), varied between 50-59%, for patient populations and 69% for TYP (79%, when excluding 4- to 6-year-old). Success rate for completing one run from a battery was greater than 90% for all groups, except for ASD (81%). These data Suggest 20-30% more children should be recruited in these patient groups, but only 10-20% for TYP for research studies. Studies with 4- to 6-year-olds may require 20-40% additional participants; studies with 10- to 18-year-olds may require 10-15% additional participants. Hum Brain Mapp 30:3426-3435, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Yerys, Benjamin E.] George Washington Univ, Childrens Natl Med Ctr, Sch Med, Dept Neurosci,Childrens Res Inst, Washington, DC 20052 USA.
[Yerys, Benjamin E.; Jankowski, Kathryn F.] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Washington, DC 20010 USA.
[Shook, Devon; Barnes, Kelly Anne; Vaidya, Chandan J.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA.
[Ritzl, Eva K.] Johns Hopkins Univ Hosp, Dept Neurol, Washington, DC USA.
[Ritzl, Eva K.; Gaillard, William D.] NINDS, Clin Epilepsy Sect, NIH, Washington, DC USA.
[VanMeter, John; Gaillard, William D.] Georgetown Univ, Dept Neurol, Washington, DC USA.
RP Yerys, BE (reprint author), George Washington Univ, Childrens Natl Med Ctr, Sch Med, Dept Neurosci,Childrens Res Inst, Washington, DC 20052 USA.
EM byerys@cnmc.org
FU National Institute of Neurological Disorders and Stroke [R01-NS44280];
National Institute of Mental Health [R01-MH65395]; Studies for the
Advancement of Autism Research and Treatment (STAART) [NIMH U54 MH0664
17]; Intellectual and Developmental Disabilities Research Center
(Children's National Medical Center) [NIH IDDRC P30HD40677]; General
Clinic Research Center [NIH GCRC M01-RR13297]; IDDRC T-32 Fellowship
[NIH T32HD046388]; Frederick and Elizabeth Singer Foundation
FX Contract grant sponsor: National Institute of Neurological Disorders and
Stroke; Contract grant number: R01-NS44280; Contract grant sponsor:
National Institute of Mental Health; Contract grant number: R01-MH65395;
Contract grant sponsor: Studies for the Advancement of Autism Research
and Treatment (STAART); Contract grant number: NIMH U54 MH0664 17;
Contract grant sponsor: Intellectual and Developmental Disabilities
Research Center (Children's National Medical Center); Contract grant
number: NIH IDDRC P30HD40677; Contract grant sponsor: General Clinic
Research Center; Contract grant number: NIH GCRC M01-RR13297; Contract
grant sponsor: IDDRC T-32 Fellowship; Contract grant number: NIH
T32HD046388; Contractgrant sponsors: Frederick and Elizabeth Singer
Foundation, Avery Scholar Award.
NR 9
TC 43
Z9 43
U1 2
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD OCT
PY 2009
VL 30
IS 10
BP 3426
EP 3435
DI 10.1002/hbm.20767
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 507LB
UT WOS:000270853700029
PM 19384887
ER
PT J
AU Kraynyak, KA
Kutzler, MA
Cisper, NJ
Laddy, DJ
Morrow, MP
Waldmann, TA
Weiner, DB
AF Kraynyak, Kimberly A.
Kutzler, Michele A.
Cisper, Neil J.
Laddy, Dominick J.
Morrow, Matthew P.
Waldmann, Thomas A.
Weiner, David B.
TI Plasmid-Encoded Interleukin-15 Receptor alpha Enhances Specific Immune
Responses Induced by a DNA Vaccine In Vivo
SO HUMAN GENE THERAPY
LA English
DT Article
ID CD8(+) T-CELLS; VIRUS TYPE-1 INFECTION; MARROW-DERIVED CELLS; LONG-TERM
SURVIVORS; IL-15 PLASMID; NATURAL-KILLER; TRANS-PRESENTATION;
CARBOXYL-TERMINUS; DENDRITIC CELLS; CUTTING EDGE
AB Plasmid-encoded DNA vaccines appear to be a safe and effective method for delivering antigen; however, the immunogenicity of such vaccines is often suboptimal. Cytokine adjuvants including interleukin (IL)-12, RANTES, granulocyte-macrophage colony-stimulating factor, IL-15, and others have been used to augment the immune response against DNA vaccines. In particular, IL-15 binds to a unique high-affinity receptor, IL-15R alpha; is trans-presented to CD8(+) T cells expressing the common beta gamma chain; and has been shown to play a role in the generation, maintenance, and proliferation of antigen-specific CD8(+) T cells. In this study, we took the unique approach of using both a cytokine and its receptor as an adjuvant in an HIV-1 vaccine strategy. To study IL-15R alpha expression, a unique monoclonal antibody (KK1.23) was generated to confirm receptor expression in vitro. Coimmunization of IL-15 and IL-15R alpha plasmids with HIV-1 antigenic plasmids in mice enhanced the antigen-specific immune response 2-fold over IL-15 immunoadjuvant alone. Furthermore, plasmid-encoded IL-15R alpha augments immune responses in the absence of IL-15, suggesting its role as a novel adjuvant. Moreover, pIL-15R alpha enhanced the cellular, but not the humoral, immune response as measured by antigen-specific IgG antibody. This is the first report describing that IL-15R alpha itself can act as an adjuvant by enhancing an antigen-specific T cell response. Uniquely, pIL-15 and pIL-15R alpha adjuvants combined, but not the receptor a chain alone, may be useful as a strategy for generating and maintaining memory CD8(+) T cells in a DNA vaccine.
C1 [Kraynyak, Kimberly A.; Cisper, Neil J.; Laddy, Dominick J.; Morrow, Matthew P.; Weiner, David B.] Univ Penn, Dept Pathol & Lab Med, Sch Med, Philadelphia, PA 19104 USA.
[Kutzler, Michele A.] Drexel Univ, Coll Med, Div Infect Dis & HIV Med, Philadelphia, PA 19102 USA.
[Waldmann, Thomas A.] NCI, NIH, Bethesda, MD 20892 USA.
RP Weiner, DB (reprint author), Univ Penn, Dept Pathol & Lab Med, Sch Med, 422 Curie Blvd,505 Stellar Chance Labs, Philadelphia, PA 19104 USA.
EM dbweiner@mail.med.upenn.edu
RI Weiner, David/H-8579-2014
FU NIH [1-T32-A107632]; HIVRAD
FX The authors acknowledge helpful discussions with Jean Boyer, Ph.D. (
University of Pennsylvania, Philadelphia, PA), and Julia Conicello of
the Wistar Institute Hybridoma Facility ( Philadelphia, PA) for help in
generating and purifying the KK1.23 monoclonal antibody. The authors
also thank the Penn Pathology Flow Cytometry and Biomedical Imaging core
facilities. K. A. K. acknowledges the support of NIH grants
1-T32-A107632. D. B. W. acknowledges support from the NIH, including
HIVRAD funding.
NR 63
TC 15
Z9 16
U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD OCT
PY 2009
VL 20
IS 10
BP 1143
EP 1156
DI 10.1089/hum.2009.025
PG 14
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 509OH
UT WOS:000271026800006
PM 19530914
ER
PT J
AU Luo, M
Simons, SS
AF Luo, Min
Simons, S. Stoney, Jr.
TI Modulation of glucocorticoid receptor induction properties by cofactors
in peripheral blood mononuclear cells
SO HUMAN IMMUNOLOGY
LA English
DT Article
DE Glucocorticoid hormone action; Modulation of induction parameters;
Steroid potency vs. efficacy; Antisteroids; Gene-selective responses
ID TRANSACTIVATION; RESISTANCE; SENSITIVITY; MUTATION; MICE
AB Glucocorticoids are widely used for their anti-inflammatory and immumosuppressive properties. Changing concentrations of transcriptional cofactors or chemicals in transiently transfected tissue culture cells modify several properties of glucocorticoid receptor-regulated gene expression including total activity (A(max)), agonist steroid potency (EC(50)), and the percentage of full agonist activity for antisteroids (percent partial agonist activity). However, no reports exist for endogenous genes in primary human cells. Here we document that reduced concentrations of TIF2, a p160 coactivator, in peripheral blood mononuclear cells modulate these parameters for endogenous genes in a gene-selective manner, thus establishing the physiological relevance of this behavior. Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics.
C1 [Luo, Min; Simons, S. Stoney, Jr.] NIDDKD, Steroid Hormones Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
RP Simons, SS (reprint author), NIDDKD, Steroid Hormones Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
EM steroids@helix.nih.gov
FU Intramural Research Program of the NIH, National Institute of Diabetes
and Digestive and Kidney Diseases
FX We thank Christian Grant [National Institute of Neurological Disorders
and Stroke, National Institutes of Health (NIH)] for assistance with the
transfection of PBMCs and Jon Ashwell (National Cancer Institute, NIH)
for constructive criticism. This research was supported by the
Intramural Research Program of the NIH, National Institute of Diabetes
and Digestive and Kidney Diseases.
NR 19
TC 15
Z9 15
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
J9 HUM IMMUNOL
JI Hum. Immunol.
PD OCT
PY 2009
VL 70
IS 10
BP 785
EP 789
DI 10.1016/j.humimm.2009.07.029
PG 5
WC Immunology
SC Immunology
GA 503YI
UT WOS:000270577900004
PM 19665040
ER
PT J
AU Ahn, J
Schumacher, FR
Berndt, SI
Pfeiffer, R
Albanes, D
Andriole, GL
Ardanaz, E
Boeing, H
Bueno-de-Mesquita, B
Chanock, SJ
Clavel-Chapelon, F
Diver, WR
Feigelson, HS
Gaziano, JM
Giovannucci, E
Haiman, CA
Henderson, BE
Hoover, RN
Kolonel, LN
Kraft, P
Ma, J
Le Marchand, L
Overvad, K
Palli, D
Stattin, P
Stampfer, M
Stram, DO
Thomas, G
Thun, MJ
Travis, RC
Trichopoulos, D
Virtamo, J
Weinstein, SJ
Yeager, M
Kaaks, R
Hunter, DJ
Hayes, RB
AF Ahn, Jiyoung
Schumacher, Fredrick R.
Berndt, Sonja I.
Pfeiffer, Ruth
Albanes, Demetrius
Andriole, Gerald L.
Ardanaz, Eva
Boeing, Heiner
Bueno-de-Mesquita, Bas
Chanock, Stephen J.
Clavel-Chapelon, Francoise
Diver, W. Ryan
Feigelson, Heather Spencer
Gaziano, J. Michael
Giovannucci, Edward
Haiman, Christopher A.
Henderson, Brian E.
Hoover, Robert N.
Kolonel, Laurence N.
Kraft, Peter
Ma, Jing
Le Marchand, Loic
Overvad, Kim
Palli, Domenico
Stattin, Paer
Stampfer, Meir
Stram, Daniel O.
Thomas, Gilles
Thun, Michael J.
Travis, Ruth C.
Trichopoulos, Dimitrios
Virtamo, Jarmo
Weinstein, Stephanie J.
Yeager, Meredith
Kaaks, Rudolf
Hunter, David J.
Hayes, Richard B.
TI Quantitative trait loci predicting circulating sex steroid hormones in
men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3)
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ESTROGEN-RECEPTOR-ALPHA; SERUM ANDROGENS; RISK; GENE; POLYMORPHISMS;
ASSOCIATION
AB Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N = 4720), testosterone (N = 4678), 3 alpha-androstanediol-glucuronide (N = 4767) and 17 beta-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 x 10(-21)), consistent with previous studies, and testosterone (P = 7.54 x 10(-15)), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 x 10(-6)) and SRD5A2 with 3 alpha-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 x 10(-6)). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones.
C1 [Ahn, Jiyoung; Berndt, Sonja I.; Pfeiffer, Ruth; Albanes, Demetrius; Chanock, Stephen J.; Hoover, Robert N.; Thomas, Gilles; Weinstein, Stephanie J.; Yeager, Meredith; Hayes, Richard B.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Ahn, Jiyoung; Hayes, Richard B.] NYU, Sch Med, Dept Environm Med, Div Epidemiol, New York, NY 10016 USA.
[Schumacher, Fredrick R.; Haiman, Christopher A.; Henderson, Brian E.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO USA.
[Ardanaz, Eva] Publ Hlth Inst Navarra, Pamplona, Spain.
[Ardanaz, Eva] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
[Boeing, Heiner] German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany.
[Bueno-de-Mesquita, Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Clavel-Chapelon, Francoise] INSERM, ERI 20, Paris EA 4045, Paris, France.
[Clavel-Chapelon, Francoise] Inst Gustave Roussy, F-94805 Villejuif, France.
[Diver, W. Ryan; Feigelson, Heather Spencer; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30303 USA.
[Gaziano, J. Michael; Giovannucci, Edward; Ma, Jing; Stampfer, Meir; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Dept Epidemiol, Boston, MA 02115 USA.
[Gaziano, J. Michael; Giovannucci, Edward; Ma, Jing; Stampfer, Meir; Trichopoulos, Dimitrios] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Gaziano, J. Michael; Giovannucci, Edward; Ma, Jing; Stampfer, Meir; Trichopoulos, Dimitrios] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA.
[Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Dept Clin Epidemiol & Cardiol, Aalborg, Denmark.
[Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Stattin, Paer] Umea Univ, Umea, Sweden.
[Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, FIN-00300 Helsinki, Finland.
[Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany.
RP Hayes, RB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM richard.b.hayes@nyumc.org
RI Pfeiffer, Ruth /F-4748-2011; Perez , Claudio Alejandro/F-8310-2010;
Clavel-Chapelon, Francoise/G-6733-2014; Albanes, Demetrius/B-9749-2015;
OI Perez , Claudio Alejandro/0000-0001-9688-184X; Hayes,
Richard/0000-0002-0918-661X; PALLI, Domenico/0000-0002-5558-2437
FU Intramural NIH HHS; NCI NIH HHS [R01 CA097193, UO1-CA98216, UO1-CA98233,
UO1-CA98710, UO1-CA98758]
NR 25
TC 27
Z9 27
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD OCT 1
PY 2009
VL 18
IS 19
BP 3749
EP 3757
DI 10.1093/hmg/ddp302
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 505PZ
UT WOS:000270707900019
PM 19574343
ER
PT J
AU Choi, BY
Alper, SL
Griffith, AJ
AF Choi, Byung Yoon
Alper, Seth L.
Griffith, Andrew J.
TI Response to: The c.-103T > C Variant in the 5 '-ATR of SLC26A4 Gene: A
Pathogenic Mutation or Coincidental Polymorphism?
SO HUMAN MUTATION
LA English
DT Letter
ID VESTIBULAR AQUEDUCT; PENDRED-SYNDROME; HEARING-LOSS; ENLARGEMENT; DFNB4
C1 [Griffith, Andrew J.] NIDCD, Otolaryngol Branch, NIH, Rockville, MD 20850 USA.
[Alper, Seth L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Choi, Byung Yoon] NIDCD, Mol Genet Lab, NIH, Rockville, MD 20850 USA.
RP Griffith, AJ (reprint author), NIDCD, Otolaryngol Branch, NIH, 5 Res Court,Room 1A-13D, Rockville, MD 20850 USA.
EM griffita@nidcd.nih.gov
NR 6
TC 4
Z9 4
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD OCT
PY 2009
VL 30
IS 10
BP 1471
EP 1471
DI 10.1002/humu.21098
PG 1
WC Genetics & Heredity
SC Genetics & Heredity
GA 507LQ
UT WOS:000270855400014
ER
PT J
AU Roessler, E
El-Jaick, KB
Dubourg, C
Velez, JI
Solomon, BD
Pineda-Alvarez, DE
Lacbawan, F
Zhou, N
Ouspenskaia, M
Paulussen, A
Smeets, HJ
Hehr, U
Bendavid, C
Bale, S
Odent, S
David, V
Muenke, M
AF Roessler, Erich
El-Jaick, Kenia B.
Dubourg, Christele
Velez, Jorge I.
Solomon, Benjamin D.
Pineda-Alvarez, Daniel E.
Lacbawan, Felicitas
Zhou, Nan
Ouspenskaia, Maia
Paulussen, Aimee
Smeets, Hubert J.
Hehr, Ute
Bendavid, Claude
Bale, Sherri
Odent, Sylvie
David, Veronique
Muenke, Maximilian
TI The Mutational Spectrum of Holoprosencephaly-Associated Changes within
the SHH Gene in Humans Predicts Loss-of-Function Through Either Key
Structural Alterations of the Ligand or Its Altered Synthesis
SO HUMAN MUTATION
LA English
DT Article
DE holoprosencephaly; mutation spectrum; SHH; protein processing
ID MAXILLARY CENTRAL INCISOR; SONIC-HEDGEHOG GENE; BRACHYDACTYLY TYPE A1;
HUMAN SIX3 GENE; GONADAL-DYSGENESIS; DESERT-HEDGEHOG; INDIAN HEDGEHOG;
HETEROZYGOUS MUTATION; CRYSTAL-STRUCTURE; TERMINAL DOMAIN
AB Mutations within either the SHH gene or its related pathway components are the most common, and best understood, pathogenetic changes observed in holoprosencephaly patients; this fact is consistent with the essential functions of this gene during forebrain development and patterning. Here we summarize the nature and types of deleterious sequence alterations among over one hundred distinct mutations in the SHH gene (64 novel mutations) and compare these to over a dozen mutations in disease-related Hedgehog family members IHH and DHH. This combined structural analysis suggests that dysfunction of Hedgehog signaling in human forebrain development can occur through truncations or major structural changes to the signaling domain, SHH-N, as well as due to defects in the processing of the mature ligand from its pre-pro-precursor or defective post-translation bi-lipid modifications with palmitate and cholesterol (C) 2009 WileyLiss, Inc.
C1 [Roessler, Erich; El-Jaick, Kenia B.; Velez, Jorge I.; Solomon, Benjamin D.; Pineda-Alvarez, Daniel E.; Lacbawan, Felicitas; Zhou, Nan; Ouspenskaia, Maia; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Dubourg, Christele; Bendavid, Claude; David, Veronique] CHU Pontchaillou, Genet Mol Lab, Rennes, France.
[Dubourg, Christele; Bendavid, Claude; Odent, Sylvie; David, Veronique] Univ Rennes 1, CNRS, Genet & Dev UMR6061, IFR140, F-35014 Rennes, France.
[Paulussen, Aimee; Smeets, Hubert J.] Univ Maastricht, Acad Hosp, Maastricht, Netherlands.
[Paulussen, Aimee; Smeets, Hubert J.] Univ Maastricht, Dept Clin Genet, Maastricht, Netherlands.
[Hehr, Ute] Univ Regensburg, Ctr Human Genet, D-8400 Regensburg, Germany.
[Hehr, Ute] Univ Regensburg, Dept Human Genet, D-8400 Regensburg, Germany.
[Bale, Sherri] GeneDx, Gaithersburg, MD USA.
[Odent, Sylvie] CHU Hop Sud, Serv Genet Clin, Rennes, France.
RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA.
EM mmuenke@nhgri.nih.gov
FU National Human Genome Research Institute, National Institutes of Health;
GIS Institut des Maladies Rares; COREC (CHU, Faculte de Medecine,
Rennes, France)
FX The authors wish to thank the patients who participated in this research
and the many clinicians who referred them. This research was supported
by the Division of Intramural Research of the National Human Genome
Research Institute, National Institutes of Health, and by the GIS
Institut des Maladies Rares, COREC (CHU, Faculte de Medecine, Rennes,
France).
NR 66
TC 32
Z9 34
U1 0
U2 6
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD OCT
PY 2009
VL 30
IS 10
BP E921
EP E935
DI 10.1002/humu.21090
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 626QC
UT WOS:000279980600003
PM 19603532
ER
PT J
AU Mattai, A
Fung, L
Bakalar, J
Overman, G
Tossell, J
Miller, R
Rapoport, J
Gogtay, N
AF Mattai, Anand
Fung, Lawrence
Bakalar, Jennifer
Overman, Gerald
Tossell, Julia
Miller, Rachel
Rapoport, Judith
Gogtay, Nitin
TI Adjunctive use of lithium carbonate for the management of neutropenia in
clozapine-treated children
SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL
LA English
DT Article
DE clozapine; lithium; childhood-onset schizophrenia; neutropenia
ID CHILDHOOD-ONSET SCHIZOPHRENIA; COLONY-STIMULATING FACTOR; INDUCED
AGRANULOCYTOSIS; ADOLESCENTS; RECHALLENGE; OLANZAPINE; EFFICACY;
DISORDER; THERAPY; IRELAND
AB Objective Clozapine, a dibenzodiazepine antipsychotic, is the most effective medication for treatment-resistant schizophrenia. However, its use has been limited by the high risk of neutropenia. In children, the rate of neutropenia is higher when compared to adults. We decided to explore the use of lithium to manage neutropenia in childhood-onset schizophrenia (COS) through a systematic audit of COS cases.
Methods Medical records were reviewed for patients with COS who had been treated with the combination of clozapine and lithium carbonate.
Results Seven patients were found to have been treated with both clozapine and lithium. After initiation of lithium, ANC increased significantly in six out of seven subjects by 29 to 106% with a mean of 66%. In addition, six out of seven subjects continued using both clozapine and lithium for over 2 years (range: 2.0-7.2 years) and do not have immediate plans for discontinuation of either medications.
Conclusions Our study bolsters support for the use of lithium in the management of neutropenia in children treated with clozapine. Although the coadministration of lithium and clozapine appears effective in the management of neutropenia, it is not without its risks and clinicians must be diligent in their joint use of these medications. Published in 2009 by John Wiley & Sons, Ltd.
C1 [Mattai, Anand; Fung, Lawrence; Bakalar, Jennifer; Overman, Gerald; Tossell, Julia; Miller, Rachel; Rapoport, Judith; Gogtay, Nitin] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
RP Mattai, A (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,BN202,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mattaia@mail.nih.gov
RI Gogtay, Nitin/A-3035-2008;
OI Fung, Lawrence/0000-0002-5738-0396
FU Intramural NIH HHS [Z99 MH999999]
NR 36
TC 5
Z9 5
U1 0
U2 3
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0885-6222
J9 HUM PSYCHOPHARM CLIN
JI Hum. Psychopharmacol.-Clin. Exp.
PD OCT
PY 2009
VL 24
IS 7
BP 584
EP 589
DI 10.1002/hup.1056
PG 6
WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry;
Psychology
GA 507XT
UT WOS:000270889900009
PM 19743394
ER
PT J
AU Ohtsubo, T
Matsumura, K
Sakagami, K
Fujii, K
Tsuruya, K
Noguchi, H
Rovira, II
Finkel, T
Iida, M
AF Ohtsubo, Toshio
Matsumura, Kiyoshi
Sakagami, Kanae
Fujii, Koji
Tsuruya, Kazuhiko
Noguchi, Hideko
Rovira, Ilsa I.
Finkel, Toren
Iida, Mitsuo
TI Xanthine Oxidoreductase Depletion Induces Renal Interstitial Fibrosis
Through Aberrant Lipid and Purine Accumulation in Renal Tubules
SO HYPERTENSION
LA English
DT Article
DE xanthine oxidoreductase; lipid; uric acid; xanthine; renal interstitial
fibrosis; epithelial mesenchymal transition; oxidative stress
ID SERUM URIC-ACID; CARDIOVASCULAR-DISEASE; REPERFUSION INJURY;
IMMUNE-SYSTEM; OXIDASE; EXPRESSION; GENE; IDENTIFICATION; HYPERTENSION;
MOUSE
AB Xanthine oxidoreductase (XOR) is an enzyme responsible for purine degradation, reactive oxygen species production, and adipogenesis. XOR gene-disrupted (XOR-/-) mice demonstrate renal failure and early death within several months. The aim of this study was to elucidate the mechanism of renal damage in XOR-/- mice and to determine the physiological role of XOR in the kidney. Histological analysis revealed that renal tubular damage in XOR-/- mice was accompanied by deposition of crystals and lipid-rich substances. Triglyceride content in renal homogenates was significantly increased in XOR-/- mice. The level of lipogenesis-related gene expression was comparable in XOR+/+ and XOR-/- mice, whereas the expression of adipogenesis-related gene expression was significantly elevated in XOR-/- mice. Urinary excretions of xanthine and hypoxanthine were markedly elevated in XOR-/- mice. Immunohistochemical analysis, Western blotting, and real time RT-PCR revealed that various markers of fibrosis, inflammation, ischemia, and oxidative stress were increased in XOR-/- mice. Finally, we demonstrate that primary renal epithelial cells from XOR-/- mice are more readily transformed to myofibroblasts, which is a marker of increased epithelial mesenchymal transition. These results suggest that XOR gene disruption induced the depletion of uric acid and the accumulation of triglyceride-rich substances, xanthine, and hypoxanthine in the renal tubules. We believe that these changes contribute to a complex cellular milieu characterized by inflammation, tissue hypoxia, and reactive oxygen species production, ultimately resulting in renal failure through increased renal interstitial fibrosis. (Hypertension. 2009; 54: 868-876.)
C1 [Ohtsubo, Toshio; Matsumura, Kiyoshi; Sakagami, Kanae; Fujii, Koji; Tsuruya, Kazuhiko; Noguchi, Hideko; Iida, Mitsuo] Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Higashi Ku, Fukuoka 8128582, Japan.
[Rovira, Ilsa I.; Finkel, Toren] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Ohtsubo, T (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan.
EM tohtsubo@intmed2.med.kyushu-u.ac.jp
FU Ministry of Education, Science, Sports, and Culture of Japan [19590954]
FX This work was supported in part by Grants-in-Aid for Scientific Research
from the Ministry of Education, Science, Sports, and Culture of Japan
(No. 19590954).
NR 39
TC 24
Z9 24
U1 0
U2 4
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 OCT
PY 2009
VL 54
IS 4
BP 868
EP U371
DI 10.1161/HYPERTENSIONAHA.109.135152
PG 11
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 494XJ
UT WOS:000269852600033
PM 19667249
ER
PT J
AU Gauthier, KM
Chawengsub, Y
Zeldin, DC
Campbell, WB
AF Gauthier, Kathryn M.
Chawengsub, Yuttana
Zeldin, Darryl C.
Campbell, William B.
TI Role of Soluble Epoxide Hydrolase in Flow-Induced Dilations of Mouse
Mesenteric Arteries
SO HYPERTENSION
LA English
DT Meeting Abstract
CT 63rd High Blood Pressure Research Conference
CY SEP 23-26, 2009
CL Chicago, IL
C1 [Gauthier, Kathryn M.; Chawengsub, Yuttana; Campbell, William B.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Zeldin, Darryl C.] NIEHS, Rsch Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD OCT
PY 2009
VL 54
IS 4
BP E124
EP E125
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 494XJ
UT WOS:000269852600506
ER
PT J
AU Montefusco, MC
Kelley-Hedgepeth, A
Merlo, K
Bryan, CD
Housman, DE
Levy, D
Mendelsohn, ME
Huggins, GS
AF Montefusco, Maria Claudia
Kelley-Hedgepeth, Alyson
Merlo, Kristen
Bryan, Crystal D.
Housman, David E.
Levy, Daniel
Mendelsohn, Michael E.
Huggins, Gordon S.
TI Little ROCK1 Is a Variant of the ROCK1 Gene Expressed in Human Smooth
Muscle Cells
SO HYPERTENSION
LA English
DT Meeting Abstract
CT 63rd High Blood Pressure Research Conference
CY SEP 23-26, 2009
CL Chicago, IL
C1 [Montefusco, Maria Claudia; Kelley-Hedgepeth, Alyson; Merlo, Kristen; Bryan, Crystal D.; Mendelsohn, Michael E.; Huggins, Gordon S.] Tufts Med Cntr, Boston, MA USA.
[Housman, David E.] MIT, Cambridge, MA 02139 USA.
[Levy, Daniel] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD OCT
PY 2009
VL 54
IS 4
BP E62
EP E62
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 494XJ
UT WOS:000269852600207
ER
PT J
AU Westphal, C
Schmidt, C
Konkel, A
Schubert, C
Fischer, R
Dechend, R
Luft, FC
Regitz-Zagrosek, V
Zeldin, DC
Schunck, WH
Muller, DN
AF Westphal, Christina
Schmidt, Cosima
Konkel, Anne
Schubert, Carola
Fischer, Robert
Dechend, Ralf
Luft, Friedrich C.
Regitz-Zagrosek, Vera
Zeldin, Darryl C.
Schunck, Wolf-Hagen
Muller, Dominik N.
TI CYP2J2 Overexpression Improves Cardiac Hypertrophy in Male But Not
Female Mice
SO HYPERTENSION
LA English
DT Meeting Abstract
CT 63rd High Blood Pressure Research Conference
CY SEP 23-26, 2009
CL Chicago, IL
C1 [Westphal, Christina; Schubert, Carola; Regitz-Zagrosek, Vera] Charite, Cntr Gender Med & Cardiovasc Dis Women, D-13353 Berlin, Germany.
[Schmidt, Cosima; Konkel, Anne; Dechend, Ralf; Luft, Friedrich C.; Schunck, Wolf-Hagen; Muller, Dominik N.] Max Delbruck Ctr Mol Med, Berlin, Germany.
[Zeldin, Darryl C.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD OCT
PY 2009
VL 54
IS 4
BP E53
EP E53
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 494XJ
UT WOS:000269852600163
ER
PT J
AU Joshi, RP
Song, J
Schoenbach, KH
Sridhara, V
AF Joshi, R. P.
Song, J.
Schoenbach, K. H.
Sridhara, V.
TI Aspects of Lipid Membrane Bio-responses to Subnanosecond, Ultrahigh
Voltage Pulsing
SO IEEE TRANSACTIONS ON DIELECTRICS AND ELECTRICAL INSULATION
LA English
DT Article
DE Bioelectric phenomena; dielectric breakdown; modeling; biomembranes
ID MOLECULAR-DYNAMICS SIMULATIONS; REVERSIBLE ELECTRICAL BREAKDOWN; PLANAR
BILAYER-MEMBRANES; CELL-MEMBRANES; ELECTROPORATION; ALAMETHICIN; FIELD;
PERMEABILIZATION; VESICLES; CHANNELS
AB Membrane electroporation is probably one of the best-known effects of applying external voltages to biological cells. Reports in the literature have focused on relatively long voltage pulse durations (100 ns-1 ms). Here we probe the very short (< 1 ns), but intense electric field (> 500 kV/cm) regime that is made possible by advances in pulsed power technology. Our analyses based on continuum Smoluchowski and Molecular Dynamics (MD) approaches, predict two new aspects. First, it is shown that pore formation rates would be dramatically lower than predicted by conventional theory due to their dependence on local pore area. Second, such high fields are predicted to affect membrane proteins and ion-channels, without causing electroporation in regions between the proteins. Hence, such high voltage, short duration pulsing should not be associated with electroporation alone, but rather be viewed as a novel vehicle that opens possibilities for a range of new electrically-driven bio-response phenomena.
C1 [Joshi, R. P.; Song, J.; Schoenbach, K. H.] Old Dominion Univ, Dept Elect & Comp Engn, Norfolk, VA 23529 USA.
[Joshi, R. P.; Song, J.; Schoenbach, K. H.] Old Dominion Univ, Frank Reidy Ctr Bioelect, Norfolk, VA 23529 USA.
[Sridhara, V.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Joshi, RP (reprint author), Old Dominion Univ, Dept Elect & Comp Engn, Norfolk, VA 23529 USA.
FU AFOSR-MURI [F49620-02-1-0320]
FX The authors would like to thank J. Weaver (MIT), W. Krassowska (Duke
University), E. Neumann (Univ. of Bielefeld), and A. Pakhomov (ODU) for
useful discussions. This work was sponsored in part by an AFOSR-MURI
grant (#F49620-02-1-0320) on Subcellular Responses to Narrowband and
Wideband Radio Frequency Radiation, managed by Dr. Robert J. Barker.
NR 72
TC 10
Z9 11
U1 0
U2 9
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA
SN 1070-9878
J9 IEEE T DIELECT EL IN
JI IEEE Trns. Dielectr. Electr. Insul.
PD OCT
PY 2009
VL 16
IS 5
BP 1243
EP 1250
PG 8
WC Engineering, Electrical & Electronic; Physics, Applied
SC Engineering; Physics
GA 509MU
UT WOS:000271022800004
ER
PT J
AU Voss, CY
Deola, S
Fleisher, TA
Marincola, FM
AF Voss, Ching Y.
Deola, Sara
Fleisher, Thomas A.
Marincola, Francesco M.
TI Increased effector-target cell conjugate formation due to HLA restricted
specific antigen recognition
SO IMMUNOLOGIC RESEARCH
LA English
DT Article
DE Effector-target conjugate formation; HLA-restricted antigen recognition;
TCR/HLA/epitopes; Intracellular cytokines; Adhesion molecules
ID PARAMETER FLOW-CYTOMETRY; CYTOTOXIC T-LYMPHOCYTES; MELANOMA-CELLS;
ADHESION; ACTIVATION; EXPRESSION; PATHWAYS; VACCINE; LFA-1; CD2
AB The T cell receptor (TCR) orchestrates T cell mediated-cytotoxicity through a complex interaction that results in an antigen-specific effector-target cell conjugate formation. While it is well recognized that specific TCR/antigen interactions generate the immunological synapse, their direct contribution to the effector-target cell conjugate has not been conclusively demonstrated. Moreover, since human cytotoxic T lymphocyte (CTL) clones are also susceptible to antigen-independent adhesion to target cells, it remains unclear whether effector-target cell conjugate formation can serve as an indicator of specific antigen recognition by the TCR. To address this question, a well-characterized epitope-specific CTL clone recognizing the melanoma-associated antigen epitope gp100:209-217 in association with HLA-A*0201 was tested against melanoma cell lines lacking or expressing the HLA-A*0201 allele and/or gp100. In this model, TCR/HLA/antigen interactions cooperated with accessory/adhesion molecules to facilitate effector-target cell conjugate formation. HLA-restricted antigen recognition played a dominant role resulting in up to 2-fold increases in conjugate frequency, and a 50% increase of CTL binding to tumor cells over background. The increased number of CTL contained in conjugates correlated with the number of IFN-gamma producing CTL. These results warrant further investigation to evaluate conjugate assays as a potential tool to detect and isolate viable and functionally active CTL. Since conjugate formation analysis does not require knowledge of the target antigen, this assay could potentially be used for enrichment of CTL directed against novel antigens.
C1 [Deola, Sara; Marincola, Francesco M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Voss, Ching Y.; Fleisher, Thomas A.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Marincola, FM (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM FMarincola@cc.nih.gov
FU NIH
FX This work was supported by the NIH intramural program.
NR 22
TC 1
Z9 1
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0257-277X
J9 IMMUNOL RES
JI Immunol. Res.
PD OCT
PY 2009
VL 45
IS 1
BP 13
EP 24
DI 10.1007/s12026-008-8041-1
PG 12
WC Immunology
SC Immunology
GA 495OV
UT WOS:000269904000002
PM 18696013
ER
PT J
AU Qi, CF
Li, ZY
Raffeld, M
Wang, HS
Kovalchuk, AL
Morse, HC
AF Qi, Chen-Feng
Li, Zhaoyang
Raffeld, Mark
Wang, Hongsheng
Kovalchuk, Alexander L.
Morse, Herbert C., III
TI Differential expression of IRF8 in subsets of macrophages and dendritic
cells and effects of IRF8 deficiency on splenic B cell and macrophage
compartments
SO IMMUNOLOGIC RESEARCH
LA English
DT Article
DE Germinal center; Follicular dendritic cells; B cells; IRF8
ID SEQUENCE-BINDING PROTEIN; IFN REGULATORY FACTOR-4; LEUKEMIA-LIKE
SYNDROME; MARGINAL-ZONE; TRANSCRIPTION FACTORS; GERMINAL-CENTERS;
CUTTING EDGE; ICSBP; GENE; MICE
AB IRF8, a transcription factor restricted primarily to hematopoietic cells, is known to influence the differentiation and function of dendritic cells (DC), macrophages, granulocytes and B cells. In human tonsil, IRF8 is expressed at high levels by intrafollicular macrophages and DC, but at much lower levels by tingible body macrophages in germinal centers (GCs) and little, if at all, by follicular DC. Spleens of IRF8-deficient mice had reduced numbers of white pulp follicles and GCs that were irregular in shape. The frequency of follicular B cells was significantly reduced while the population of marginal zone (MZ) B cells was increased. In addition, MZ macrophages were reduced in number and abnormally distributed, while metallophilic macrophages were normal. These findings demonstrate differential requirements for IRF8 among distinct subsets of B cells, DC, and macrophages.
C1 [Qi, Chen-Feng; Li, Zhaoyang; Wang, Hongsheng; Kovalchuk, Alexander L.; Morse, Herbert C., III] NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA.
[Raffeld, Mark] NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Qi, CF (reprint author), NIAID, Immunopathol Lab, NIH, 5640 Fishers Lane,Twinbrook 1,Room 1528, Rockville, MD 20852 USA.
EM cqi@niaid.nih.gov; hmorse@niaid.nih.gov
OI Morse, Herbert/0000-0002-9331-3705
FU Intramural Research Program of the NIH; National Institute of Allergy
and Infectious Diseases
FX We gratefully acknowledge the editorial assistance of B. Marshall,
photographic support from Rick Dreyfuss, and the provision of mice by K.
Ozato. This work was supported by the Intramural Research Program of the
NIH, National Institute of Allergy and Infectious Diseases.
NR 41
TC 13
Z9 13
U1 0
U2 3
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0257-277X
J9 IMMUNOL RES
JI Immunol. Res.
PD OCT
PY 2009
VL 45
IS 1
BP 62
EP 74
DI 10.1007/s12026-008-8032-2
PG 13
WC Immunology
SC Immunology
GA 495OV
UT WOS:000269904000006
PM 18663414
ER
PT J
AU Simkus, C
Bhattacharyya, A
Zhou, M
Veenstra, TD
Jones, JM
AF Simkus, Carrie
Bhattacharyya, Anamika
Zhou, Ming
Veenstra, Timothy D.
Jones, Jessica M.
TI Correlation between recombinase activating gene 1 ubiquitin ligase
activity and V(D)J recombination
SO IMMUNOLOGY
LA English
DT Article
DE CDC34; recombinase activating gene 1; ubiquitin ligase; V(D)J
recombination
ID POLYUBIQUITIN CHAINS; CONJUGATING ENZYME; PROTEIN BREAKDOWN; RAG
MUTATIONS; CELL-CYCLE; SUBSTRATE; DOMAIN; DEFECTS; COMPLEX; BINDING
AB P>The really interesting new gene (RING) finger ubiquitin ligase domain of the recombinase activating gene 1 (RAG1) V(D)J recombinase protein adopts a standard cross-brace architecture but co-ordinates three zinc ions as opposed to the canonical two. We demonstrated previously that disruption of the conserved zinc co-ordination sites resulted in loss of structural integrity and ubiquitin ligase (E3) activity and interfered with the ability of full-length RAG1 to support recombination. Here we present evidence that amino acids surrounding the third, non-canonical site also contribute to functional interaction with the ubiquitin conjugating (E2) enzyme CDC34, while certain residues on the RING domain's surface important for interaction between other E2-E3 pairs are less critical to the functional RAG1-CDC34 interaction in this assay. Partial reduction of ubiquitin ligase activity was significantly correlated with reduction in the ability of RAG1 to support recombination of extra-chromosomal substrates (r = 0 center dot 805, P = 0 center dot 009). While poly-ubiquitin chains could be generated, RAG1 did not promote rapid chain extension following mono-ubiquitylation of substrate, regardless of the E2 enzyme used. No single ubiquitin lysine mutant disrupted the ability of CDC34 to form ubiquitin chains on RAG1, and mass spectrometric analysis of the poly-ubiquitylated products indicated ubiquitin chain linkages through lysines 48 and 11. These data suggest that RAG1 promotes a mono-ubiquitylation reaction that is required for optimal levels of V(D)J recombination.
C1 [Simkus, Carrie; Bhattacharyya, Anamika; Jones, Jessica M.] Georgetown Univ, Dept Biochem Mol & Cellular Biol, Washington, DC 20057 USA.
[Zhou, Ming; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Jones, JM (reprint author), Georgetown Univ, Dept Biochem Mol & Cellular Biol, Washington, DC 20057 USA.
EM jonesj5@georgetown.edu
FU National Cancer Institute; National Institutes of Health [N01-CO-12400,
P30CA051008, AI062854-01]
FX The authors wish to thank Dr Wei Yang, National Institute for Diabetes,
Digestive and Kidney Diseases, for assistance with preparation of Fig.
2. This project has been funded in whole or in part with federal funds
from the National Cancer Institute, National Institutes of Health, under
Contract N01-CO-12400 and Award Number P30CA051008. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
United States Government. This project was supported in part by a grant
to J.M.J. from the National Institutes of Health (AI062854-01). The
content is solely the responsibility of the authors.
NR 38
TC 12
Z9 12
U1 1
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0019-2805
J9 IMMUNOLOGY
JI Immunology
PD OCT
PY 2009
VL 128
IS 2
BP 206
EP 217
DI 10.1111/j.1365-2567.2009.03101.x
PG 12
WC Immunology
SC Immunology
GA 491LM
UT WOS:000269580300006
PM 19740377
ER
PT J
AU Greenaway, HY
Kurniawan, M
Price, DA
Douek, DC
Davenport, MP
Venturi, V
AF Greenaway, Hui Yee
Kurniawan, Monica
Price, David A.
Douek, Daniel C.
Davenport, Miles P.
Venturi, Vanessa
TI Extraction and characterization of the rhesus macaque T-cell receptor
beta-chain genes
SO IMMUNOLOGY AND CELL BIOLOGY
LA English
DT Article
DE T-cell; T-cell receptor; T-cell receptor repertoire
ID SIMIAN IMMUNODEFICIENCY VIRUS; SIV INFECTION; ANIMAL-MODEL; REPERTOIRE
DIVERSITY; IMMUNE-RESPONSE; INFLUENZA-VIRUS; TCR REPERTOIRE; CTL ESCAPE;
CD8(+); MONKEYS
AB Rhesus macaque models have been instrumental in the development and testing of vaccines before human studies and have provided fundamental insights into the determinants of immune efficacy in a variety of infectious diseases. However, the characterization of antigen-specific T-cell receptor (TCR) repertoires during adaptive immune responses in these models has earlier relied on human TCR gene assignments. Here, we extracted and characterized TCR beta-chain (TRB) genes from the recently sequenced rhesus macaque genome that are homologous to the human TRB genes. Comparison of the rhesus macaque TRB genes with the human TRB genes showed an average best match similarity of 92.9%. Furthermore, we confirmed the usage of most rhesus macaque TRB genes by expressed TCR beta sequences within epitope-specific TCR repertoires. This primary description of the rhesus macaque TRB genes will provide a standardized nomenclature and enable better characterization of TCR usage in studies that use this species. Immunology and Cell Biology (2009) 87, 546-553; doi: 10.1038/icb.2009.38; published online 9 June 2009
C1 [Greenaway, Hui Yee; Kurniawan, Monica; Davenport, Miles P.; Venturi, Vanessa] Univ New S Wales, Ctr Vasc Res, Complex Syst Biol Grp, Kensington, NSW 2052, Australia.
[Price, David A.] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff, S Glam, Wales.
[Price, David A.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Venturi, V (reprint author), Univ New S Wales, Ctr Vasc Res, Complex Syst Biol Grp, Wallace Wurth Bldg, Kensington, NSW 2052, Australia.
EM v.venturi@unsw.edu.au
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
FU James S McDonnell Foundation 21st Century Research Award/Studying
Complex Systems; Australian Research Council (ARC); National Institutes
of Health (NIH); Medical Research Council (UK)
FX We thank Dr Mark Tanaka for assistance with the phylogenetic analysis
and Associate Professor Andrew Collins for helpful discussions. This
work was supported by the James S McDonnell Foundation 21st Century
Research Award/Studying Complex Systems, the Australian Research Council
(ARC) and the National Institutes of Health (NIH). MPD is a Sylvia and
Charles Viertel Senior Medical Research Fellow and DAP is a Medical
Research Council (UK) Senior Clinical Fellow.
NR 50
TC 7
Z9 8
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0818-9641
J9 IMMUNOL CELL BIOL
JI Immunol. Cell Biol.
PD OCT
PY 2009
VL 87
IS 7
BP 546
EP 553
DI 10.1038/icb.2009.38
PG 8
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 506NN
UT WOS:000270782300011
PM 19506572
ER
PT J
AU Newman, ZL
Leppla, SH
Moayeri, M
AF Newman, Zachary L.
Leppla, Stephen H.
Moayeri, Mahtab
TI CA-074Me Protection against Anthrax Lethal Toxin
SO INFECTION AND IMMUNITY
LA English
DT Article
ID INDEPENDENT PHOSPHOLIPASE A(2); TUMOR-NECROSIS-FACTOR; CELL-DEATH
PATHWAY; CATHEPSIN-B; BACILLUS-ANTHRACIS; CASPASE-1 ACTIVATION; NALP3
INFLAMMASOME; METHYL-ESTER; LYSOSOMAL PERMEABILIZATION; MEDIATED
ACTIVATION
AB Anthrax lethal toxin (LT) activates the NLRP1b (NALP1b) inflammasome and caspase-1 in macrophages from certain inbred mouse strains, but the mechanism by which this occurs is poorly understood. We report here that similar to several NLRP3 (NALP3, cryopyrin)-activating stimuli, LT activation of the NLRP1b inflammasome involves lysosomal membrane permeabilization (LMP) and subsequent cytoplasmic cathepsin B activity. CA-074Me, a potent cathepsin B inhibitor, protects LT-sensitive macrophages from cell death and prevents the activation of caspase-1. RNA interference knockdown of cathepsin B expression, however, cannot prevent LT-mediated cell death, suggesting that CA-074Me may also act on other cellular proteases released during LMP. CA-074Me appears to function downstream of LT translocation to the cytosol (as assessed by mitogen-activated protein kinase kinase cleavage), K+ effluxes, and proteasome activity. The initial increase in cytoplasmic activity of cathepsin B occurs at the same time or shortly before caspase-1 activation but precedes a larger-scale lysosomal destabilization correlated closely with cytolysis. We present results suggesting that LMP may be involved in the activation of the NLRP1b inflammasome.
C1 [Newman, Zachary L.; Leppla, Stephen H.; Moayeri, Mahtab] NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
RP Moayeri, M (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, Bldg 33,Room 1W20B, Bethesda, MD 20892 USA.
EM mmoayeri@niaid.nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Allergy and Infectious Diseases
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 64
TC 56
Z9 59
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 OCT
PY 2009
VL 77
IS 10
BP 4327
EP 4336
DI 10.1128/IAI.00730-09
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 496ER
UT WOS:000269952800016
PM 19635822
ER
PT J
AU Zelazny, AM
Ding, L
Elloumi, HZ
Brinster, LR
Benedetti, F
Czapiga, M
Ulrich, RL
Ballentine, SJ
Goldberg, JB
Sampaio, EP
Holland, SM
AF Zelazny, Adrian M.
Ding, Li
Elloumi, Houda Z.
Brinster, Lauren R.
Benedetti, Fran
Czapiga, Meggan
Ulrich, Ricky L.
Ballentine, Samuel J.
Goldberg, Joanna B.
Sampaio, Elizabeth P.
Holland, Steven M.
TI Virulence and Cellular Interactions of Burkholderia multivorans in
Chronic Granulomatous Disease
SO INFECTION AND IMMUNITY
LA English
DT Article
ID RESPIRATORY EPITHELIAL-CELLS; CEPACIA COMPLEX; CYSTIC-FIBROSIS;
HOST-DEFENSE; INTRACELLULAR SURVIVAL; PSEUDOMONAS-CEPACIA; LUNG
INFECTION; GENE-TRANSFER; MURINE MODEL; IN-VITRO
AB Chronic granulomatous disease (CGD) patients are susceptible to life-threatening infections by the Burkholderia cepacia complex. We used leukocytes from CGD and healthy donors and compared cell association, invasion, and cytokine induction by Burkholderia multivorans strains. A CGD isolate, CGD1, showed higher cell association than that of an environmental isolate, Env1, which correlated with cell entry. All B. multivorans strains associated significantly more with cells from CGD patients than with those from healthy donors. Similar findings were observed with another CGD pathogen, Serratia marcescens, but not with Escherichia coli. In a mouse model of CGD, strain CGD1 was virulent while Env1 was avirulent. B. multivorans organisms were found in the spleens of CGD1-infected mice at levels that were 1,000 times higher than those found in Env1-infected mice, which was coincident with higher levels of the proinflammatory cytokine interleukin-1 beta. Taken together, these results may shed light on the unique susceptibility of CGD patients to specific pathogens.
C1 [Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Zelazny, Adrian M.; Ding, Li; Elloumi, Houda Z.; Ballentine, Samuel J.; Sampaio, Elizabeth P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Brinster, Lauren R.; Benedetti, Fran] NIAID, Div Vet Resources, Bethesda, MD 20892 USA.
[Czapiga, Meggan] NIAID, Biol Imaging Sect, Bethesda, MD 20892 USA.
[Ulrich, Ricky L.] USA, Med Res Inst Infect Dis, Bacteriol Div, Ft Detrick, MD 21702 USA.
[Goldberg, Joanna B.] Univ Virginia Hlth Syst, Dept Microbiol, Charlottesville, VA USA.
[Sampaio, Elizabeth P.] Fiocruz MS, Leprosy Lab, Inst Oswaldo Cruz, BR-21045900 Rio De Janeiro, Brazil.
RP Zelazny, AM (reprint author), NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, 10 Ctr Dr,Bldg 10-2C-385, Bethesda, MD 20892 USA.
EM azelazny@mail.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was financially supported by the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health.
NR 46
TC 12
Z9 13
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD OCT
PY 2009
VL 77
IS 10
BP 4337
EP 4344
DI 10.1128/IAI.00259-09
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 496ER
UT WOS:000269952800017
PM 19635825
ER
PT J
AU Wilbur, WJ
Kim, W
AF Wilbur, W. John
Kim, Won
TI The ineffectiveness of within-document term frequency in text
classification
SO INFORMATION RETRIEVAL
LA English
DT Article
DE Within-document frequency; Bag-of-words; Word burstiness
AB For the purposes of classification it is common to represent a document as a bag of words. Such a representation consists of the individual terms making up the document together with the number of times each term appears in the document. All classification methods make use of the terms. It is common to also make use of the local term frequencies at the price of some added complication in the model. Examples are the na < ve Bayes multinomial model (MM), the Dirichlet compound multinomial model (DCM) and the exponential-family approximation of the DCM (EDCM), as well as support vector machines (SVM). Although it is usually claimed that incorporating local word frequency in a document improves text classification performance, we here test whether such claims are true or not. In this paper we show experimentally that simplified forms of the MM, EDCM, and SVM models which ignore the frequency of each word in a document perform about at the same level as MM, DCM, EDCM and SVM models which incorporate local term frequency. We also present a new form of the na < ve Bayes multivariate Bernoulli model (MBM) which is able to make use of local term frequency and show again that it offers no significant advantage over the plain MBM. We conclude that word burstiness is so strong that additional occurrences of a word essentially add no useful information to a classifier.
C1 [Wilbur, W. John; Kim, Won] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Wilbur, WJ (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM wilbur@ncbi.nlm.nih.gov; wonkim@ncbi.nlm.nih.gov
FU NIH, National Library of Medicine
FX The authors are supported by the Intramural Research Program of the NIH,
National Library of Medicine. The authors would like to thank the
anonymous referees for numerous helpful comments which improved the work
reported here.
NR 25
TC 7
Z9 7
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1386-4564
J9 INFORM RETRIEVAL
JI Inf. Retr.
PD OCT
PY 2009
VL 12
IS 5
BP 509
EP 525
DI 10.1007/s10791-008-9069-5
PG 17
WC Computer Science, Information Systems
SC Computer Science
GA 488AF
UT WOS:000269320200001
PM 19802376
ER
PT J
AU Laky, K
Annaert, W
Fowlkes, BJ
AF Laky, Karen
Annaert, Willem
Fowlkes, B. J.
TI Amyloid precursor family proteins are expressed by thymic and lymph node
stromal cells but are not required for lymphocyte development
SO INTERNATIONAL IMMUNOLOGY
LA English
DT Article
DE APP-deficient mice; APLP2-deficient mice; T cells; thymocytes;
gamma-secretase
ID GAMMA-SECRETASE ACTIVITY; HEMATOPOIETIC PROGENITOR CELLS;
RECEPTOR-RELATED PROTEIN; NF-KAPPA-B; INTRACELLULAR DOMAIN;
ALZHEIMERS-DISEASE; THYMOCYTE DEVELOPMENT; NOTCH LIGANDS; IN-VITRO;
PRESENILIN/GAMMA-SECRETASE
AB Pharmacological inhibitors that block amyloid precursor protein (APP) cleavage and the formation of senile plaques are under development for the treatment of familial Alzheimer's disease. Unfortunately, many inhibitors that block gamma-secretase-mediated cleavage of APP also have immunosuppressive side effects. In addition to APP, numerous other proteins undergo gamma-secretase-mediated cleavage. In order to develop safer inhibitors, it is necessary to determine which of the gamma-secretase substrates contribute to the immunosuppressive effects. Because APP family members are widely expressed and are reported to influence calcium flux, transcription and apoptosis, they could be important for normal lymphocyte maturation. We find that APP and amyloid precursor-like protein 2 are expressed by stromal cells of thymus and lymph nodes, but not by lymphocytes. Although signals provided by thymic stromal cells are critical for normal T cell differentiation, lymphocyte development proceeds unperturbed in mice deficient for these APP family members.
C1 [Laky, Karen; Fowlkes, B. J.] NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Annaert, Willem] Ctr Human Genet KULeuven & VIB, Lab Membrane Trafficking, Louvain, Belgium.
RP Fowlkes, BJ (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, 9000 Rockville Pike,Bldg 4,Room 111, Bethesda, MD 20892 USA.
EM bfowlkes@nih.gov
FU NIAID
FX National Institutes of Health Intramural Research Program of the NIAID.
NR 73
TC 4
Z9 4
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0953-8178
J9 INT IMMUNOL
JI Int. Immunol.
PD OCT
PY 2009
VL 21
IS 10
BP 1163
EP 1174
DI 10.1093/intimm/dxp083
PG 12
WC Immunology
SC Immunology
GA 499KH
UT WOS:000270218500008
PM 19710207
ER
PT J
AU Miller, MA
Barr, BC
Nordhausen, R
James, ER
Magargal, SL
Murray, M
Conrad, PA
Toy-Choutka, S
Jessup, DA
Grigg, ME
AF Miller, M. A.
Barr, B. C.
Nordhausen, R.
James, E. R.
Magargal, S. L.
Murray, M.
Conrad, P. A.
Toy-Choutka, S.
Jessup, D. A.
Grigg, M. E.
TI Ultrastructural and molecular confirmation of the development of
Sarcocystis neurona tissue cysts in the central nervous system of
southern sea otters (Enhydra lutris nereis)
SO INTERNATIONAL JOURNAL FOR PARASITOLOGY
LA English
DT Article
DE Sea otter; Sarcocystis neurona; Tissue cyst; Central nervous system;
Brain; Ultrastructure; 18S rDNA; ITS1
ID OPOSSUMS DIDELPHIS-VIRGINIANA; EQUINE PROTOZOAL MYELOENCEPHALITIS;
TOXOPLASMA-GONDII INFECTION; PHOCA-VITULINA-RICHARDSI; N-SP PROTOZOA;
INTERMEDIATE HOST; MEPHITIS-MEPHITIS; PROCYON-LOTOR; LIFE-CYCLE;
MENINGOENCEPHALITIS
AB In 2004, three wild sea otters were diagnosed with putative Sarcocystis neurona-associated meningoencephalitis by histopathology and immunohistochemistry. Schizonts, free merozoites and tissue cysts were observed in the brains of all three infected animals. Tissue cysts walls from sea otter I (SO1) stained positively using anti-S. neurona polyclonal antiserum. However, positive staining does not preclude infection by closely related or cross-reactive tissue cyst-forming coccidian parasites. Two immature tissue cysts in the brain of SO1 were examined using transmission electron microscopy. Ultrastructural features included cyst walls with thin villous projections up to I pm long with tapered ends and a distinctive, electron-dense outer lining layer composed of linearly-arranged, semi-circular structures with a "hob-nailed" surface contour. Small numbers of microtubules extended down through the villi into the underlying granular layer. Metrocytes were short and plump with an anterior apical complex, 22 sub-pellicular microtubules, numerous free ribosomes and no rhoptries. Some metrocytes appeared to be dividing, with two adjacent nuclear profiles. Collectively these ultrastructural features were compatible with developing protozoal cysts and were similar to prior descriptions of S. neurona tissue cysts. Panspecific 18S rDNA primers were utilized to identify protozoa infecting the brains of these otters and DNA amplification and additional sequencing at the ITS1 locus confirmed that all three otters were infected with S. neurona. No other Sarcocystis spp. were detected in the brains or skeletal muscles of these animals by immunohistochemistry or PCR. We believe this is the first ultrastructural and molecular confirmation of the development of S. neurona tissue cysts in the CNS of any animal. Published by Elsevier Ltd. on behalf of Australian Society for Parasitology Inc.
C1 [Miller, M. A.; Toy-Choutka, S.; Jessup, D. A.] Calif Dept Fish & Game, Marine Wildlife Vet Care & Res Ctr, Santa Cruz, CA 95060 USA.
[Barr, B. C.; Nordhausen, R.] Univ Calif Davis, Calif Anim Hlth & Food Safety Serv Lab, Davis, CA 95617 USA.
[James, E. R.] Univ British Columbia, Dept Med, Vancouver, BC V5Z 3J5, Canada.
[Magargal, S. L.; Grigg, M. E.] NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Murray, M.] Monterey Bay Aquarium, Monterey, CA 93940 USA.
[Conrad, P. A.] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
RP Miller, MA (reprint author), Calif Dept Fish & Game, Marine Wildlife Vet Care & Res Ctr, 1451 Shaffer Rd, Santa Cruz, CA 95060 USA.
EM MMiller@ospr.dfg.ca.gov; grggm@niaid.nih.gov
RI James, Erick/D-4725-2012
FU California Department of Fish and Game-Department of Oil Spill
Prevention and Response (CDFG); NIH; NIAID
FX This project was funded and completed by the California Department of
Fish and Game-Department of Oil Spill Prevention and Response (CDFG) and
by the Intramural Research Program of the NIH and NIAID (MEG). Staff and
volunteers of CDFG, Monterey Bay Aquarium, the Marine Mammal Center,
United States Geological Survey and the United States Fish and Wildlife
Service helped recover and transport live and dead sea otters along the
central California coast. We appreciate the assistance of the CDFG
Petroleum Chemistry Laboratory, especially Dr. Susan Sugarman for
completing the petroleum fingerprint testing on otter #3. Technical
staff from CDFG assisted with otter necropsy, specimen collection and
storage and data collection. Bacterial and protozoal cultures and
protozoal serology were completed at the UC Davis School of Veterinary
Medicine. Immunohistochemical stains for S. neurona and T. gondii and
domoic acid testing were prepared at the California Animal Health and
Food Safety (CAHFS) Laboratory.
NR 54
TC 15
Z9 16
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0020-7519
J9 INT J PARASITOL
JI Int. J. Parasit.
PD OCT
PY 2009
VL 39
IS 12
BP 1363
EP 1372
DI 10.1016/j.ijpara.2009.04.014
PG 10
WC Parasitology
SC Parasitology
GA 491RW
UT WOS:000269598100007
PM 19527725
ER
PT J
AU Thomas, KJ
Cookson, MR
AF Thomas, Kelly Jean
Cookson, Mark R.
TI The role of PTEN-induced kinase 1 in mitochondrial dysfunction and
dynamics
SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
LA English
DT Review
DE Parkinsonism; Parkin; Drp1; Fission; Fusion; Oxidative stress
ID EARLY-ONSET PARKINSONISM; CYTOCHROME-C RELEASE; DEPENDENT
PROTEIN-KINASE; SUBSTANTIA-NIGRA NEURONS; PINK1 MUTATIONS; CELL-DEATH;
PERMEABILITY TRANSITION; OXIDATIVE STRESS; SUBCELLULAR-DISTRIBUTION;
RECESSIVE PARKINSONISM
AB Mutations in parkin, PTEN-induced kinase 1 (PINK1) and DJ-1 can all cause autosomal recessive forms of Parkinson's disease. Recent data suggest that these recessive parkinsonism-associated genes converge within a single pathogenic pathway whose dysfunction leads to the loss of substantia nigra pars compacta neurons. The major common functional effects of all three genes relate to mitochondrial and oxidative damage, with a possible additional involvement of the ubiquitin proteasome system. This review highlights the role of the mitochondrial kinase, PINK1, in protection against mitochondrial dysfunction and how this might relate to loss of substaintia nigra neurons in recessive parkinsonism. Published by Elsevier Ltd.
C1 [Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20982 USA.
RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20982 USA.
EM Cookson@mail.nih.gov
FU National Institutes on Aging, Intramural Research Program, NIH
FX This work was supported by the National Institutes on Aging, Intramural
Research Program, NIH.
NR 181
TC 22
Z9 22
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1357-2725
J9 INT J BIOCHEM CELL B
JI Int. J. Biochem. Cell Biol.
PD OCT
PY 2009
VL 41
IS 10
BP 2025
EP 2035
DI 10.1016/j.biocel.2009.02.018
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 501AZ
UT WOS:000270351100029
PM 19703660
ER
PT J
AU Castle, PE
Rodriguez, AC
Burk, RD
Herrero, R
Hildesheim, A
Solomon, D
Sherman, ME
Jeronimo, J
Alfaro, M
Morales, J
Guillen, D
Hutchinson, ML
Wacholder, S
Schiffman, M
AF Castle, Philip E.
Rodriguez, Ana C.
Burk, Robert D.
Herrero, Rolando
Hildesheim, Allan
Solomon, Diane
Sherman, Mark E.
Jeronimo, Jose
Alfaro, Mario
Morales, Jorge
Guillen, Diego
Hutchinson, Martha L.
Wacholder, Sholom
Schiffman, Mark
TI Neither one-time negative screening tests nor negative colposcopy
provides absolute reassurance against cervical cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE cervical cancer; human papillomavirus; cytology; Pap smear; cervical
intraepithelial neoplasia; loop electrosurgical excision procedure;
Guanacaste
ID HUMAN-PAPILLOMAVIRUS DNA; SQUAMOUS INTRAEPITHELIAL LESIONS; LOOP
ELECTROSURGICAL EXCISION; COSTA-RICA; FOLLOW-UP; INCIDENCE TRENDS;
CLINICAL-TRIAL; HIGH-RISK; WOMEN; NEOPLASIA
AB A population sample of 10,049 women living in Guanacaste, Costa Rica, was recruited into a natural history of human papillomavirus (HPV) and cervical neoplasia study in 1993-1994. At the enrollment visit, we applied multiple state-of-the-art cervical cancer screening methods to detect prevalent cervical cancer and to prevent subsequent cervical cancers by the timely detection an treatment of precancerous lesions. Women were screened at enrollment with 3 kinds of cytology (often reviewed by more than one pathologist), visual inspection and cervicography. Any positive screening test led to colposcopic referral and biopsy and/or excisional treatment of CIN2 or worse. We retrospectively tested stored specimens with an early HPV test (hybrid capture tube test) and for >40 HPV genotypes using a research PCR assay. We followed women typically 5-7 years and some up to 11 years. Nonetheless, 16 cases of Invasive cervical cancer were diagnosed during follow-up. Six cancer cases were failures at enrollment to detect abnormalities by cytology screening; 3 of the 6 were also negative at enrollment by sensitive HPV DNA testing. Seven cancers represent failures of colposcopy to diagnose cancer or a precancerous lesion in screen-positive women. Finally, 3 cases arose despite attempted excisional treatment of precancerous lesions. Based on this evidence, we suggest that no current secondary cervical cancer prevention technologies applied once in a previously under-screened population is likely to be 100% efficacious in preventing incident diagnoses of invasive cervical cancer. (C) 2009 UICC
C1 [Castle, Philip E.; Hildesheim, Allan; Sherman, Mark E.; Jeronimo, Jose; Wacholder, Sholom; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Rodriguez, Ana C.; Herrero, Rolando; Morales, Jorge; Guillen, Diego] Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica.
[Burk, Robert D.] Yeshiva Univ, Albert Einstein Coll Med, Dept Pediat, Bronx, NY USA.
[Burk, Robert D.] Yeshiva Univ, Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY USA.
[Burk, Robert D.] Yeshiva Univ, Albert Einstein Coll Med, Dept Obstet & Gynecol, Bronx, NY USA.
[Burk, Robert D.] Yeshiva Univ, Albert Einstein Coll Med, Dept Womens Hlth, Bronx, NY USA.
[Burk, Robert D.] Yeshiva Univ, Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY USA.
[Solomon, Diane] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Jeronimo, Jose] Program Appropriate Technol Hlth, Seattle, WA USA.
[Alfaro, Mario] Caja Costarricense Seguro Social, Lab Nacl Citol, San Jose, Costa Rica.
[Hutchinson, Martha L.] Women & Infants Hosp Rhode Isl, Dept Pathol & Lab Med, Providence, RI 02908 USA.
RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd Room 5030,EPS MSC 7234, Bethesda, MD 20892 USA.
EM castlep@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU NIH/National Cancer Institute
FX This research was supported by the Intramural Research Program of the
NIH/National Cancer Institute.
NR 49
TC 9
Z9 9
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD OCT 1
PY 2009
VL 125
IS 7
BP 1649
EP 1656
DI 10.1002/ijc.24525
PG 8
WC Oncology
SC Oncology
GA 491GB
UT WOS:000269565400018
PM 19569231
ER
PT J
AU Cornfield, J
Haenszel, W
Hammond, EC
Lilienfeld, AM
Shimkin, MB
Wynder, EL
AF Cornfield, Jerome
Haenszel, William
Hammond, E. Cuyler
Lilienfeld, Abraham M.
Shimkin, Michael B.
Wynder, Ernst L.
TI Smoking and lung cancer: recent evidence and a discussion of some
questions
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
ID CIGARETTE-SMOKE; BRONCHIAL EPITHELIUM; AIR POLLUTION; TOBACCO TAR; DEATH
RATES; MORTALITY; CONDENSATE; BENZPYRENE; CARCINOMA
AB This report reviews some of the more recent epidemiologic and experimental findings on the relationship of tobacco smoking to lung cancer, and discusses some criticisms directed against the conclusion that tobacco smoking, especially cigarettes, has a causal role in the increase in broncho-genic carcinoma. The magnitude of the excess lung-cancer risk among cigarette smokers is so great that the results can not be interpreted as arising from an indirect association of cigarette smoking with some other agent or characteristic, since this hypothetical agent would have to be at least as strongly associated with lung cancer as cigarette use; no such agent has been found or suggested. The consistency of all the epidemiologic and experimental evidence also supports the conclusion of a causal relationship with cigarette smoking, while there are serious inconsistencies in reconciling the evidence with other hypotheses which have been advanced. Unquestionably there are areas where more research is necessary, and, of course, no single cause accounts for all lung cancer. The information already available, however, is sufficient for planning and activating public health measures. - J. Nat. Cancer Inst. 22:173-203, 1959.
C1 [Cornfield, Jerome] Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21218 USA.
[Haenszel, William; Shimkin, Michael B.] US PHS, Natl Canc Inst, Dept Hlth Educ & Welf, Bethesda, MD USA.
[Hammond, E. Cuyler] Amer Canc Soc Inc, New York, NY USA.
[Wynder, Ernst L.] Sloan Kettering Inst Canc Res, New York, NY USA.
RP Cornfield, J (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21218 USA.
NR 81
TC 58
Z9 59
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD OCT
PY 2009
VL 38
IS 5
BP 1175
EP 1191
DI 10.1093/ije/dyp289
PG 17
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 510PH
UT WOS:000271101800003
PM 19773415
ER
PT J
AU Hazra, R
Stoszek, SK
Hance, LF
Pinto, J
Marques, H
Peixoto, M
Alarcon, J
Mussi-Pinhata, M
Serchuck, L
AF Hazra, Rohan
Stoszek, Sonia K.
Hance, Laura Freimanis
Pinto, Jorge
Marques, Heloisa
Peixoto, Mario
Alarcon, Jorge
Mussi-Pinhata, Marisa
Serchuck, Leslie
CA NISDI Pediat Study Grp 2008
TI Cohort Profile: NICHD International Site Development Initiative (NISDI):
a prospective, observational study of HIV-exposed and HIV-infected
children at clinical sites in Latin American and Caribbean countries
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
ID INFANT TRANSMISSION; ZIDOVUDINE; WOMEN
C1 [Hazra, Rohan; Serchuck, Leslie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA.
[Stoszek, Sonia K.; Hance, Laura Freimanis] Westat Corp, Rockville, MD USA.
[Pinto, Jorge] Univ Fed Minas Gerais, Dept Pediat, Div Immunol, Belo Horizonte, MG, Brazil.
[Peixoto, Mario] Hosp Femina, Grp Hosp Conceicao, Porto Alegre, RS, Brazil.
[Pinto, Jorge] Univ Nacl Mayor San Marcos, Inst Med Trop Daniel Alcides Carrion, Lima 14, Peru.
[Mussi-Pinhata, Marisa] Univ Sao Paulo, Fac Med Ribeirao Preto, BR-14049 Ribeirao Preto, SP, Brazil.
RP Hazra, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, 6100 Execut Blvd,Room 4B11, Bethesda, MD 20892 USA.
EM hazrar@mail.nih.gov
RI Mussi-Pinhata, Marisa/G-6568-2012;
OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586;
Alarcon, Jorge/0000-0002-0800-2380
FU NICHD NIH HHS [#N01-HD-3-3345]; NIDDK NIH HHS [#N01-DK-8-0001]
NR 8
TC 22
Z9 22
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD OCT
PY 2009
VL 38
IS 5
BP 1207
EP 1214
DI 10.1093/ije/dyn239
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 510PH
UT WOS:000271101800009
PM 19036797
ER
PT J
AU Rice, NE
Bandinelli, S
Corsi, AM
Ferrucci, L
Guralnik, JM
Miller, MA
Kumari, M
Murray, A
Frayling, TM
Melzer, D
AF Rice, Neil E.
Bandinelli, Stefania
Corsi, Anna Maria
Ferrucci, Luigi
Guralnik, Jack M.
Miller, Michelle A.
Kumari, Meena
Murray, Anna
Frayling, Tim M.
Melzer, David
TI The paraoxonase (PON1) Q192R polymorphism is not associated with poor
health status or depression in the ELSA or INCHIANTI studies
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE PON1 Q192R polymorphism; rs662; organophosphates; detoxification;
paraoxonase activity; depression; Mendelian randomization
ID GENOME-WIDE ASSOCIATION; MENDELIAN RANDOMIZATION; GENETIC EPIDEMIOLOGY;
SUSCEPTIBILITY; DISEASE; SHEEP; DISORDER
AB Background The human paraoxonase (PON1) protein detoxifies certain organophosphates, and the PON1 Q192R polymorphism (rs662) affects PON1 activity. Groups with higher dose exposure to organophosphate sheep dips or first Gulf War nerve toxins reported poorer health if they had 192R, and these associations have been used to exemplify Mendelian randomization analysis. However, a reported association of 192R with depression in a population-based study of older women recently cast doubt on the specificity of the higher dose findings. We aimed to examine associations between the PON1 Q192R polymorphism and self-reported poor health and depression in two independent population-based studies.
Methods We used logistic regression models to examine the associations in men and women aged 60-79 years from the English Longitudinal Study of Ageing (ELSA, n = 3158) and InCHIANTI (n = 761) population studies. Outcomes included the Center for Epidemiologic Studies Depression (CES-D) scale, self-rated general health status and (in ELSA only) diagnoses of depression.
Results The PON1 Q192R polymorphism was not associated with self-reported poor health {meta-analysis: odds ratio (OR)= 1.01 [confidence interval (CI) 0.91-1.13], P = 0.801} or depressive symptoms in either study or in meta-analyses [CES-D: OR = 1.01 (CI 0.87-1.17), P = 0.90]. There was also no association with histories of diagnosed depression in ELSA [OR = 1.03 (CI 0.82-1.30), P = 0.80].
Conclusions We found no evidence of an association between the PON1 Q192R polymorphism, and poor general or mental health in two independent population-based studies. Neither the claimed Q192R association with depression in the general population nor its theoretical implications were supported.
C1 [Rice, Neil E.; Murray, Anna; Melzer, David] Peninsula Med Sch, Epidemiol & Publ Hlth Grp, Exeter EX2 5DW, Devon, England.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
[Corsi, Anna Maria] Tuscany Reg Hlth Agcy, Florence, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Miller, Michelle A.] CSB, Clin Sci Res Inst, Warwick Med Sch, Coventry, W Midlands, England.
[Kumari, Meena] UCL, Dept Epidemiol & Publ Hlth, London, England.
RP Melzer, D (reprint author), Peninsula Med Sch, Epidemiol & Publ Hlth Grp, RD&E Site,Barrack Rd, Exeter EX2 5DW, Devon, England.
EM david.melzer@pms.ac.uk
RI Miller, Michelle/D-1840-2009;
OI Murray, Anna/0000-0002-2351-2522; Kumari, Meena/0000-0001-9716-1035;
Melzer, David/0000-0002-0170-3838
FU US National Institute on Aging [R01AG24233, R01AG1764406S1]
FX US National Institute on Aging [grant numbers R01AG24233, R01AG1764406S1
to English Longitudinal Study of Ageing DNA Repository (EDNAR)]; the
Intramural Research Program, US National Institute on Aging, NIH. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 24
TC 8
Z9 8
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD OCT
PY 2009
VL 38
IS 5
BP 1374
EP 1379
DI 10.1093/ije/dyp265
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 510PH
UT WOS:000271101800031
PM 19651761
ER
PT J
AU Stetler-Stevenson, M
Yuan, CM
AF Stetler-Stevenson, M.
Yuan, C. M.
TI Myelodysplastic syndromes: the role of flow cytometry in diagnosis and
prognosis
SO INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
LA English
DT Review
DE Flow cytometry; Myelodysplastic Syndromes; Cytopenia; Idiopathic
Cytopenia of Uncertain Significance; Prognosis
ID BONE-MARROW; ABNORMALITIES; CYTOGENETICS; EXPRESSION; DYSPLASIA; CELLS
AB P>Flow cytometric immunophenotypic analysis is a well-recognized and widely accepted adjuvant test to increase the sensitivity and specificity of diagnosis in potential myelodysplastic syndrome (MDS) cases. In addition, flow cytometric analysis provides prognostic information in MDS that is not available from other sources. The flow cytometric findings indicative of MDS and its value is a diagnostic adjunct are discussed.
C1 [Stetler-Stevenson, M.; Yuan, C. M.] NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20895 USA.
RP Stetler-Stevenson, M (reprint author), NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 2A-33,Mail Stop 1500, Bethesda, MD 20895 USA.
EM stetler@mail.nih.gov
FU NIH; NCI
FX This was supported in part by the Intramural Research Program of the
NIH, NCI.
NR 22
TC 10
Z9 11
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1751-5521
J9 INT J LAB HEMATOL
JI Int. J. Lab. Hematol.
PD OCT
PY 2009
VL 31
IS 5
BP 479
EP 483
DI 10.1111/j.1751-553X.2009.01176.x
PG 5
WC Hematology
SC Hematology
GA 487IQ
UT WOS:000269265900001
PM 19555363
ER
PT J
AU Ando, H
Ichihashi, M
Hearing, VJ
AF Ando, Hideya
Ichihashi, Masamitsu
Hearing, Vincent J.
TI Role of the Ubiquitin Proteasome System in Regulating Skin Pigmentation
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Review
DE fatty acid; melanin; melanocyte; tyrosinase; skin; pigmentation
ID OCULOCUTANEOUS ALBINISM TYPE-1; MOUSE MELANOMA-CELLS; FATTY-ACIDS;
ENDOPLASMIC-RETICULUM; QUALITY-CONTROL; MULTICATALYTIC PROTEINASE;
SECRETORY PATHWAY; MOLECULAR-BASIS; LINOLEIC-ACID; TYROSINASE
AB Pigmentation of the skin, hair and eyes is regulated by tyrosinase, the critical rate-limiting enzyme in melanin synthesis by melanocytes. Tyrosinase is degraded endogenously, at least in part, by the ubiquitin proteasome system ( UPS). Several types of inherited hypopigmentary diseases, such as oculocutaneous albinism and Hermansky-Pudlak syndrome, involve the aberrant processing and/or trafficking of tyrosinase and its subsequent degradation which can occur due to the quality-control machinery. Studies on carbohydrate modifications have revealed that tyrosinase in the endoplasmic reticulum (ER) is proteolyzed via ER-associated protein degradation and that tyrosinase degradation can also occur following its complete maturation in the Golgi. Among intrinsic factors that regulate the UPS, fatty acids have been shown to modulate tyrosinase degradation in contrasting manners through increased or decreased amounts of ubiquitinated tyrosinase that leads to its accelerated or decelerated degradation by proteasomes.
C1 [Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Ando, Hideya; Ichihashi, Masamitsu] Doshisha Univ, Skin Aging & Photoaging Res Ctr, Kyoto 6190225, Japan.
[Ando, Hideya; Ichihashi, Masamitsu] Kobe Skin Res Inst, Kobe, Hyogo 6500047, Japan.
RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM hideyaando@aol.com; mm_ichihashi@hotmail.com; hearingv@nih.gov
FU NIH, National Cancer Institute
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute.
NR 39
TC 15
Z9 17
U1 0
U2 4
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD OCT
PY 2009
VL 10
IS 10
BP 4428
EP 4434
DI 10.3390/ijms10104428
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
SC Biochemistry & Molecular Biology; Chemistry
GA 512UJ
UT WOS:000271276000014
PM 20057953
ER
PT J
AU Hyodo, F
Chandramouli, GVR
Matsumoto, S
Matsumoto, KI
Mitchell, JB
Krishna, MC
Munasinghe, JP
AF Hyodo, Fuminori
Chandramouli, Gadisetti V. R.
Matsumoto, Shingo
Matsumoto, Ken-Ichiro
Mitchell, James B.
Krishna, Murali C.
Munasinghe, Jeeva P.
TI Estimation of tumor microvessel density by MRI using a blood pool
contrast agent
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE angiogenesis; blood volume; microvascular density; MRI; Sunitinib;
tumor; USPIO
ID IRON-OXIDE; ENHANCED MRI; VOLUME; ANGIOGENESIS; BRAIN; MICE; FLOW;
VASCULATURE; CARCINOMA; THERAPY
AB Recognition of importance of angiogenesis to tumor growth, metastasis, and treatment outcome has led to efforts to develop non-invasive methods for longitudinal monitoring of tumor microvasculature. We describe a steady-state MRI technique to determine absolute blood volume (BV) as a marker of microvascular density with improved spatial and temporal resolution using an ultra small super paramagnetic iron oxide (USPIO). A noise reduction scheme for BV imaging was also proposed based on weighting factors derived by pre-contrast signal level as an adjustable additive constant. Gradient echo sequence was used for BV imaging with MRI at 7T. Optimal imaging conditions (USPIO dose and echo time) were determined by USPIO dose-dependent studies ex vivo and in vivo. Improved analysis strategies were at first applied for cerebral BV estimation in mice, which were found in good agreement with the literature values. These methods were then used to determine tumor BV in mice. The optimal concentration of USPIO for BV estimates was found to range from 3.6 to 4.48 mM (estimated as Fe concentration) in ex vivo experiments corresponding to an in vivo dosage of 215-287 mu mol/kg body weight, whereas a USPIO dose of 287 mu mol/kg leads to higher cerebral BV estimate in vivo than the reported values. Application of the BV imaging method to evaluation of anti-angiogenic effect of Sunitinib in squamous cell carcinoma (SCC) tumor bearing mice revealed similar to 46% reduction in tumor BV 4 days after start of Sunitinib treatment. The results show that the MRI. approach using USPIO yields high-resolution absolute BV images and the method can be conveniently applied to monitor longitudinal tumor microvessel density changes as a function of growth or in response to treatment.
C1 [Hyodo, Fuminori; Chandramouli, Gadisetti V. R.; Matsumoto, Shingo; Mitchell, James B.; Krishna, Murali C.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hyodo, Fuminori] Kyushu Univ, Innovat Ctr Med Redox Nav, Fukuoka 812, Japan.
[Matsumoto, Ken-Ichiro] Natl Inst Radiol Sci, Heavy Ion Radiobiol Res Grp, Chiba 260, Japan.
[Munasinghe, Jeeva P.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA.
EM murali@helix.nih.gov
NR 29
TC 16
Z9 16
U1 1
U2 5
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
J9 INT J ONCOL
JI Int. J. Oncol.
PD OCT
PY 2009
VL 35
IS 4
BP 797
EP 804
DI 10.3892/ijo_00000392
PG 8
WC Oncology
SC Oncology
GA 494AD
UT WOS:000269780600015
PM 19724915
ER
PT J
AU Vikram, B
AF Vikram, Bhadrasain
TI CYBERKNIFE AND PROSTATE CANCER. IN REGARD TO KING ET AL. (INT J RADIAT
ONCOL BIOL PHYS 2009;73:1043-1048)
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Letter
ID THERAPY
C1 NCI, Clin Radiat Oncol Branch, Rockville, MD USA.
RP Vikram, B (reprint author), NCI, Clin Radiat Oncol Branch, Rockville, MD USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD OCT 1
PY 2009
VL 75
IS 2
BP 632
EP 632
DI 10.1016/j.ijrobp.2009.05.064
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 496AZ
UT WOS:000269941600045
PM 19735890
ER
PT J
AU Lamm, AS
Khare, A
Conville, P
Lau, PCK
Bergeron, H
Rosazza, JPN
AF Lamm, Andrew S.
Khare, Arshdeep
Conville, Patricia
Lau, Peter C. K.
Bergeron, Helene
Rosazza, John P. N.
TI Nocardia iowensis sp nov., an organism rich in biocatalytically
important enzymes and nitric oxide synthase
SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY
LA English
DT Article
ID RIBOSOMAL-RNA GENE; ALDEHYDE OXIDOREDUCTASE; PHYLOGENETIC TREES;
IDENTIFICATION; SEQUENCES; PURIFICATION; ACIDS; METABOLISM; EXPRESSION;
NRRL-5646
AB Nocardia strain NRRL 5646, isolated from a garden soil sample in Osceola, Iowa, USA, was initially of interest as an antibiotic producer. It contained biocatalytically important enzymes and represented the first described nitric oxide synthase enzyme system in bacteria. The present polyphasic taxonomic study was undertaken to differentiate strain NRRL 5646 T from related species of the genus Nocardia. Chemotaxonomic analyses included determinations of the fatty acid methyl ester profile (C(16:1)omega 6c/C(16:1)omega 7c, C(16:0), C(18:1)omega 9c and C(18:0) 10-methyl as major components), quinone [cyclo, MK-8(H(4)) as the major component], polar lipid (diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside as major components) and mycolic acid. These results supported its placement within the genus Nocardia. Biochemical testing and 16S rRNA, 65-kDa heat-shock protein (hsp65) and preprotein translocase (secA1) gene sequence analyses differentiated strain NRRL 5646(T) from recognized Nocardia species. Previous studies have demonstrated that other genetic sequences (carboxylic acid reductase, Nocardia phosphopantetheinyl transferase and GTP cyclohydrolase I) from strain NRRL 5646(T) can also be used to substantiate its uniqueness. The level of 16S rRNA gene sequence similarity between strain NRRL 5646(T) and the type strains of Nocardia tenerifensis and Nocardia brasiliensis was 98.8 %. However, strain NRRL 5646 T could be clearly distinguished from these Nocardia species based on DNA-DNA hybridization data. Consequently, strain NRRL 5646(T) is considered to represent a novel species of the genus Nocardia, for which the name Nocardia iowensis sp. nov. is proposed. The type strain is NRRL 5646(T) (=UI 122540(T) =NRRL B-24671(T) =DSM 45197(T)).
C1 [Lamm, Andrew S.; Khare, Arshdeep; Rosazza, John P. N.] Univ Iowa, Ctr Biocatalysis & Bioproc, Iowa City, IA 52242 USA.
[Conville, Patricia] NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,US Dept Hlth & Human S, Bethesda, MD 20892 USA.
[Lau, Peter C. K.; Bergeron, Helene] Natl Res Council Canada, Biotechnol Res Inst, Montreal, PQ H4P 2R2, Canada.
RP Rosazza, JPN (reprint author), Univ Iowa, Ctr Biocatalysis & Bioproc, 2501 Crosspk Rd,Suite C100,Oakdale Res Pk, Iowa City, IA 52242 USA.
EM john-rosazza@uiowa.edu
FU Iowa Biotechnology Byproducts Consortium; US Department of Agriculture
[2002-34188-12035, 2004-34188-15067]; NIH Warren G. Magnuson Clinical
Center
FX We acknowledge the assistance of Claude Pujol and Jean Ross at the
University of Iowa. This work was supported by the Iowa Biotechnology
Byproducts Consortium, through the Cooperative State Research, Education
and Extension Service, US Department of Agriculture, under Agreement nos
2002-34188-12035 and 2004-34188-15067. Any opinions, findings,
conclusions or recommendations expressed in this publication are those
of the authors and do not necessarily reflect the views of the US
Department of Agriculture. In addition, this research was supported in
part by the Intramural Research Program of the NIH Warren G. Magnuson
Clinical Center. The views expressed herein are those of the authors and
should not be construed as those of the US Department of Health and
Human Services.
NR 39
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U1 0
U2 5
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 1466-5026
J9 INT J SYST EVOL MICR
JI Int. J. Syst. Evol. Microbiol.
PD OCT
PY 2009
VL 59
BP 2408
EP 2414
DI 10.1099/ijs.0.007427-0
PG 7
WC Microbiology
SC Microbiology
GA 511ZL
UT WOS:000271211000006
PM 19622667
ER
PT J
AU Gericke, A
Mayer, VGA
Steege, A
Patzak, A
Neumann, U
Grus, FH
Joachim, SC
Choritz, L
Wess, J
Pfeiffer, N
AF Gericke, Adrian
Mayer, Veronique G. A.
Steege, Andreas
Patzak, Andreas
Neumann, Ulrike
Grus, Franz H.
Joachim, Stephanie C.
Choritz, Lars
Wess, Juergen
Pfeiffer, Norbert
TI Cholinergic Responses of Ophthalmic Arteries in M(3) and M(5) Muscarinic
Acetylcholine Receptor Knockout Mice
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ISCHEMIC OPTIC NEUROPATHY; OCULAR BLOOD-FLOW; ENDOTHELIAL DYSFUNCTION;
MACULAR DEGENERATION; CHOROIDAL CIRCULATION; DIABETIC-RETINOPATHY;
RETROBULBAR HEMODYNAMICS; ISOMETRIC-EXERCISE; NITRIC-OXIDE; NERVE HEAD
AB PURPOSE. To determine the functional role of M(3) and M(5) muscarinic acetylcholine receptor subtypes in ophthalmic arteries using gene-targeted mice.
METHODS. Muscarinic receptor gene expression was quantified in murine ophthalmic arteries using real-time PCR. To test the functional relevance of M(3) and M(5) receptors, ophthalmic arteries from mice deficient in either subtype (M3R(-/-), M5R(-/-), respectively) and wild-type controls were isolated, cannulated with micropipettes, and pressurized. Changes in luminal vessel diameter in response to muscarinic and nonmuscarinic receptor agonists were measured by video microscopy.
RESULTS. With the use of real-time PCR, all five muscarinic receptor subtypes were detected in ophthalmic arteries. However, mRNA levels of M(1), M(3), and M(5) receptors were higher than those of M(2) and M(4) receptors. In functional studies, after preconstriction with phenylephrine, acetylcholine and carbachol produced concentration-dependent dilations of ophthalmic arteries that were similar in M5R(-/-) and wild-type mice. Strikingly, cholinergic dilation of ophthalmic arteries was almost completely abolished in M3R(-/-) mice. Deletion of either M(3) or M(5) receptor did not affect responses to nonmuscarinic vasodilators such as bradykinin or nitroprusside.
CONCLUSIONS. These findings provide the first evidence that M(3) receptors are critically involved in cholinergic regulation of diameter in murine ophthalmic arteries. (Invest Ophthalmol Vis Sci.2009;50:4822-4827) DOI: 10.1167/iovs.09-3600
C1 [Gericke, Adrian; Mayer, Veronique G. A.; Grus, Franz H.; Joachim, Stephanie C.; Choritz, Lars; Pfeiffer, Norbert] Johannes Gutenberg Univ Mainz, Univ Med, Dept Ophthalmol, D-55101 Mainz, Germany.
[Steege, Andreas; Patzak, Andreas; Neumann, Ulrike] Charite Univ Med Berlin, Inst Vegetat Physiol, Berlin, Germany.
[Wess, Juergen] NIDDKD, Mol Signalling Lab, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Gericke, A (reprint author), Johannes Gutenberg Univ Mainz, Univ Med, Dept Ophthalmol, D-55101 Mainz, Germany.
EM adrian.gericke@gmx.net
RI Steege, Andreas/F-3885-2010; Choritz, Lars/G-1859-2013
FU Ernst und Berta Grimmke Stiftung [5/08]
FX Supported by Grant 5/08 from the Ernst und Berta Grimmke Stiftung.
NR 50
TC 8
Z9 8
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD OCT
PY 2009
VL 50
IS 10
BP 4822
EP 4827
DI 10.1167/iovs.09-3600
PG 6
WC Ophthalmology
SC Ophthalmology
GA 497XE
UT WOS:000270097200040
PM 19407017
ER
PT J
AU Ding, XY
Patel, M
Shen, DF
Herzlich, AA
Cao, XG
Villasmil, R
Klupsch, K
Tuo, JS
Downward, J
Chan, CC
AF Ding, Xiaoyan
Patel, Mrinali
Shen, Defen
Herzlich, Alexandra A.
Cao, Xiaoguang
Villasmil, Rafael
Klupsch, Kristina
Tuo, Jingsheng
Downward, Julian
Chan, Chi-Chao
TI Enhanced HtrA2/Omi Expression in Oxidative Injury to Retinal Pigment
Epithelial Cells and Murine Models of Neurodegeneration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID HTRA1 PROMOTER POLYMORPHISM; SERINE-PROTEASE OMI/HTRA2; MACULAR
DEGENERATION; NEUROPROTECTIVE ROLE; FAMILY PROTEINS; APOPTOSIS; DISEASE;
DEATH; RPE; MITOCHONDRIA
AB PURPOSE. To investigate the role of HtrA2/Omi, a nuclear-encoded mitochondrial serine protease with a proapoptosis function, under H(2)O(2)-induced oxidative stress in human RPE, in the Ccl2(-/-) Cx3cr1(-/-) double-knockout (DKO) mouse retina, and the HtrA2/Omi-deficient mice.
METHODS. Oxidative stress was induced in ARPE-19 cells by 1 mM H(2)O(2) for 2 hours. HtrA2/Omi and caspase-3 expression was evaluated using RQ-PCR, immunohistochemistry, or Western blot. Cell viability was detected by MTT assay. HtrA2/Omi expression in the subcellular components and activated caspase-3 were measured. These processes were also evaluated in cells treated with UCF-101, an HtrA2/Omi inhibitor or in cells subjected to RNAi against HtrA2/Omi. Oxidative stress was assayed and compared in retinas of DKO and wild-type (WT) mice by determining serum NADPH oxidase subunits and nitrite levels. Transmission electron microscopy was used to view the retinal ultrastructure of the HtrA2/Omi-deficient mice.
RESULTS. H(2)O(2)-induced oxidative damage resulted in HtrA2/Omi translocation from mitochondria to cytosol, leading to RPE cell apoptosis via a caspase-mediated pathway. Treatment of RPE cells with UCF-101 reduced the cytosolic translocation of HtrA2/Omi, attenuated caspase-3 activation, and decreased apoptosis. After specific HtrA2 downregulation, increased cell viability was measured in H(2)O(2)-treated ARPE-19 cells. Retina of DKO mice exhibit increased oxidative stress and upregulation of HtrA2/Omi. Fewer and abnormal mitochondria were found in HtrA2/Omi(-/-) photoreceptors and RPE.
CONCLUSIONS. These findings suggest that HtrA2/Omi is related to RPE apoptosis due to oxidative stress, which may play an important role in the integrity of mitochondria and the pathogenesis of AMD. (Invest Ophthalmol Vis Sci. 2009; 50: 4957-4966) DOI: 10.1167/iovs.09-3381
C1 [Ding, Xiaoyan; Patel, Mrinali; Shen, Defen; Herzlich, Alexandra A.; Cao, Xiaoguang; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Ding, Xiaoyan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China.
[Patel, Mrinali] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Cao, Xiaoguang] Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100871, Peoples R China.
[Klupsch, Kristina; Downward, Julian] Canc Res UK London Res Inst, Signal Transduct Lab, London, England.
RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
OI Tuo, Jingsheng/0000-0002-1372-7810; Downward, Julian/0000-0002-2331-4729
FU National Institutes of Health Intramural Research Foundation
FX Supported by the National Institutes of Health Intramural Research
Foundation.
NR 51
TC 20
Z9 20
U1 1
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD OCT
PY 2009
VL 50
IS 10
BP 4957
EP 4966
DI 10.1167/iovs.09-3381
PG 10
WC Ophthalmology
SC Ophthalmology
GA 497XE
UT WOS:000270097200057
PM 19443712
ER
PT J
AU Blum, A
Costello, R
Samsel, L
Zalos, G
McCoy, P
Csako, G
Waclawiw, MA
Cannon, RO
AF Blum, Arnon
Costello, Rene
Samsel, Leigh
Zalos, Gloria
McCoy, Phil
Csako, Gyorgy
Waclawiw, Myron A.
Cannon, Richard O., III
TI Variability of C-Reactive Protein Levels among Patients with Stable
Coronary Artery Disease and on Statin Therapy
SO ISRAEL MEDICAL ASSOCIATION JOURNAL
LA English
DT Article
DE C-reactive protein; coronary artery disease; statin therapy; vascular
inflammation; risk stratification
ID MIDDLE-AGED MEN; HEART-DISEASE; CARDIOVASCULAR-DISEASE; FUTURE RISK;
MYOCARDIAL-INFARCTION; CHOLESTEROL LEVELS; HEALTHY-MEN; INFLAMMATION;
MARKERS; EVENTS
AB Background: High sensitivity C-reactive protein, a marker of inflammation, has been proposed to stratify coronary artery disease risk and is lowered by HMG-CoA reductase (statin) therapy. However, the reproducibility of persistently elevated hs-CRP levels and association with other markers of inflammation in patients with stable CAD on aggressive statin therapy is unknown.
Objectives: To determine the reproducibility of hs-CRP levels measured within 2 weeks in patients with documented CAD with stable symptoms and to identify associations with other markers of inflammation.
Methods: Levels of hs-CRP were measured twice within 14 days (7 +/- 4) in 23 patients (22 mates and 1 female, average age 66 +/- 10 years) with stable CAD and hs-CRP >= 2.0 mg/L but <= 10 mg/L at visit 1. All patients had received statins for cholesterol management (low density lipoprotein-cholesterol 84 +/- 25 mg/dl) with no dose change for > 3 months. None had a history or evidence of malignancy, chronic infection or inflammation, or recent trauma. There was no change in medications between visits 1 and 2, and no patient reported a change in symptoms or general health during this interval. White blood cell count and pro- and anti-inflammatory cytokines were measured at both visits.
Results: hs-CRP levels tended to be lower at visit 2 (median 2.4 mg/L, range 0.8-11 mg/L) than at visit 1 (median 3.3 mg/L, range 2.0-9.7; P = 0.1793). However, between the two visits hs-CRP levels decreased by more than 1.0 mg/L in 10 patients and increased by more than 1.0 mg/L in 4 patients. Changes in hs-CRP levels were unrelated to changes in levels of white blood cells (P= 0.4353). Of the cytokines tested, only the anti-inflammatory cytokine interleukin-1 receptor antagonist and the pro-inflammatory cytokine interleukin-8 were above tower limits of detection, but there were no correlations between changes in these values and changes in hs-CRP (both P > 0.5).
Conclusions: In stable CAD patients on aggressive statin therapy, hs-CRP levels may fluctuate over brief periods in the absence of changes in health, cardiac symptom status and medications, and without corroboration with other measures of inflammation. Accordingly, elevated hs-CRP levels should be interpreted with caution in this setting.
C1 [Blum, Arnon; Zalos, Gloria; Cannon, Richard O., III] NIH, Ctr Clin, Translat Med Branch, Bethesda, MD 20892 USA.
[Samsel, Leigh; McCoy, Phil] NIH, Ctr Clin, Flow Cytometry Core Facil, Bethesda, MD 20892 USA.
[Waclawiw, Myron A.] NHLBI, Off Biostat Res, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Costello, Rene; Csako, Gyorgy] NIH, Ctr Clin, Med Lab, Bethesda, MD 20892 USA.
RP Blum, A (reprint author), Baruch Padeh Poria Med Ctr, Dept Internal Med, IL-15208 Galilee, Israel.
EM navablum@hotmail.com
NR 25
TC 2
Z9 3
U1 0
U2 0
PU ISRAEL MEDICAL ASSOC JOURNAL
PI RAMAT GAN
PA 2 TWIN TOWERS, 11TH FL, 35 JABOTINSKY ST, PO BOX 3604, RAMAT GAN 52136,
ISRAEL
SN 1565-1088
J9 ISR MED ASSOC J
JI Isr. Med. Assoc. J.
PD OCT
PY 2009
VL 11
IS 10
BP 602
EP 605
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 545SU
UT WOS:000273757900005
PM 20077946
ER
PT J
AU Galliher-Beckley, AJ
Cidlowski, JA
AF Galliher-Beckley, Amy J.
Cidlowski, John A.
TI Emerging Roles of Glucocorticoid Receptor Phosphorylation in Modulating
Glucocorticoid Hormone Action in Health and Disease
SO IUBMB LIFE
LA English
DT Review
DE CDK; glucocorticoid receptor; ERK; GSK-3 beta; JNK; p38 MAPK;
phosphorylation
ID N-TERMINAL KINASE; GENE-EXPRESSION; PROTEIN-KINASE; TRANSCRIPTIONAL
ACTIVATION; CELLS; SITES; CROSSTALK; APOPTOSIS; ISOFORMS
AB Glucocorticoids (GCs) are hormones naturally released when the body perceives stress and function to return homeostatic balance within various tissues. Synthetic GCs are widely prescribed therapeutics for the treatment of numerous inflammatory disorders and cancers. The effects of GCs are mediated by their binding and activation of the GC receptor (GR), a transcription factor that is subject to hormone-dependent and -independent phosphorylation on several serine and threonine residues. The GR is phosphorylated by kinases such as MAPKs, CDKs, and GSK-3 beta, and these modifications modulate the transcriptional activity of the GR within cells. Here, we discuss the phosphorylation status of the GR as a mechanism to dictate how cells will ultimately respond to GCs. In doing so, we will review current knowledge about each phosphorylated residue within the GR and their contributions to modulating GC signaling in normal homeostatic physiology and during the progression of disease. (C) 2009 IUBMB IUBMB Life, 61(10): 979-986, 2009
C1 [Galliher-Beckley, Amy J.; Cidlowski, John A.] NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, Dept Hlth & Human Serv,NIH, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, Dept Hlth & Human Serv,NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
FU NIH National Institute of Environmental Health Sciences [Z01E5090057-12]
FX We would like to thank Carl Bortner, Robert H. Oakley, arid Harriet
Kinyarnu for their critical reading of this review. This research was
Supported by the Intramural Research Program of the NIH National
Institute of Environmental Health Sciences (Z01E5090057-12). The authors
declare no conflicts of interest.
NR 35
TC 66
Z9 70
U1 1
U2 6
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1521-6543
J9 IUBMB LIFE
JI IUBMB Life
PD OCT
PY 2009
VL 61
IS 10
BP 979
EP 986
DI 10.1002/iub.245
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 507DX
UT WOS:000270832600006
PM 19787703
ER
PT J
AU Aissani, B
Ogwaro, KM
Shrestha, S
Tang, JM
Breen, EC
Wong, HL
Jacobson, LP
Rabkin, CS
Ambinder, RF
Martinez-Maza, O
Kaslow, RA
AF Aissani, Brahim
Ogwaro, Kisani M.
Shrestha, Sadeep
Tang, Jianming
Breen, Elizabeth C.
Wong, Hui-lee
Jacobson, Lisa P.
Rabkin, Charles S.
Ambinder, Richard F.
Martinez-Maza, Otoniel
Kaslow, Richard A.
TI The Major Histocompatibility Complex Conserved Extended Haplotype 8.1 in
AIDS-Related Non-Hodgkin Lymphoma
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE CD4; human leukocyte antigen; HIV; NHL; TNF
ID TUMOR-NECROSIS-FACTOR; ACTIVE ANTIRETROVIRAL THERAPY; TNF-ALPHA
PRODUCTION; GENETIC POLYMORPHISMS; MULTIPLE-SCLEROSIS; HIV-1 INFECTION;
MHC HAPLOTYPES; RISK-FACTORS; ASSOCIATION; IMMUNODEFICIENCY
AB Background: Two single nucleotide polymorphisms (SNPs) in adjacent genes, lymphotoxin alpha (LTA + 252G, rs909253 A>G) and tumor necrosis factor (TNF - 308A, rs1800629 G>A), form the G-A haplotype repeatedly associated with increased risk of non-Hodgkin lymphoma (NHL) in individuals uninfected with HTV-1. This association has been observed alone or in combination with human leukocyte antigens HLA-B*08 or HLA-DRB1*03 in the major histocompatibility complex (MHC). Which gene variant on this highly conserved extended haplotype (CEH 8.1) in whites most likely represents a true etiologic factor remains uncertain.
Objective: We aimed to determine whether the reported association of the G-A haplotype of LTA-TNF with non-AIDS NHL also occurs with AIDS-related NHL.
Methods: SNPs in LTA and TNF and in 6 other genes nearby were typed in 140 non-Hispanic European American pairs of AIDS-NHL cases and matched controls selected from HIV-infected men in the Multicenter AIDS Cohort Study.
Results: The G-A haplotype and a 4-SNP haplotype in the neighboring gene cluster (rs537160 (A) rs1270942 (G), rs2072633 (A), and rs6467 (C)) were associated with AIDS-NHL (odds ratio = 2.7, 95% confidence interval: 1.5 to 4.8, P = 0.0009; and odds ratio = 3.2, 95% confidence interval: 1.6 to 6.6, P = 0.0008; respectively). These 2 haplotypes occur in strong linkage disequilibrium with each other on CEH 8.1.
Conclusion: The CEH 8.1-specific haplotype association of MHC class HI variants with AIDS-NHL closely resembles that observed for non-AIDS NHL. Corroboration of an MHC determinant of AIDS and non-AIDS NHL alike would imply an important pathogenetic mechanism common to both.
C1 [Aissani, Brahim] Univ Alabama, Program Epidemiol Infect & Immun, Dept Epidemiol, Birmingham, AL 35294 USA.
[Ogwaro, Kisani M.] Univ Alabama, Dept Psychiat, Birmingham, AL 35294 USA.
[Tang, Jianming; Kaslow, Richard A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Wong, Hui-lee; Rabkin, Charles S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Jacobson, Lisa P.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Ambinder, Richard F.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA.
[Breen, Elizabeth C.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA.
RP Aissani, B (reprint author), Univ Alabama, Program Epidemiol Infect & Immun, Dept Epidemiol, 1665 Univ Blvd,RPHB Room 220A, Birmingham, AL 35294 USA.
EM baissani@uab.edu; rkaslow@uab.edu
RI Martinez-Maza, Otoniel/B-2667-2009;
OI Martinez-Maza, Otoniel/0000-0003-1364-0675; Tang,
Jianming/0000-0003-0137-7486
FU NCI NIH HHS [P50 CA096888, P50 CA096888-01, P50-CA96888, R01 CA073475,
R01 CA073475-03, R01 CA106168, R01 CA106168-01A1, R01-CA106168,
R01-CA73475]; NCRR NIH HHS [5-M01-RR-00722, M01 RR000722]; NIAID NIH HHS
[U01 AI037613, P30 AI 045008, P30 AI045008, P30 AI045008-01, U01
AI035039, U01 AI035040, U01 AI035041, U01 AI035042, U01 AI035043, U01
AI037984, UO1-AI-35039, UO1-AI-35040,, UO1-AI-35041, UO1-AI-35042,
UO1-AI-35043, UO1-AI-37613, UO1-AI-37984]
NR 53
TC 12
Z9 13
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD OCT 1
PY 2009
VL 52
IS 2
BP 170
EP 179
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 499GQ
UT WOS:000270206500004
PM 19654554
ER
PT J
AU Busse, KH
Hadigan, C
Chairez, C
Alfaro, RM
Formentini, E
Kovacs, JA
Penzak, SR
AF Busse, Kristin H.
Hadigan, Colleen
Chairez, Cheryl
Alfaro, Raul M.
Formentini, Elizabeth
Kovacs, Joseph A.
Penzak, Scott R.
TI Gemfibrozil Concentrations Are Significantly Decreased in the Presence
of Lopinavir-Ritonavir
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article; Proceedings Paper
CT 48th Annual Interscience Conference on Antimicrobial Agents and
Chemotherapy/46th Annual Meeting of the
Infectious-Diseases-Society-of-America
CY OCT 25, 2008
CL Washington, DC
SP Infect Dis Soc Amer
DE drug interaction; lopinavir-ritonavir; gemfibrozil; HIV
ID INHIBITOR-ASSOCIATED HYPERTRIGLYCERIDEMIA; FIBRIC ACID-DERIVATIVES;
CLINICAL PHARMACOKINETICS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK;
LOPINAVIR/RITONAVIR; THERAPY; DISEASE; ABNORMALITIES; DYSLIPIDEMIA
AB Objective: The objective of this study was to determine the influence of a 2-week course of lopinavir-ritonavir on the pharmacokinetics of the triglyceride-lowering agent, gemfibrozil.
Methods: The study was conducted as an open label, single-sequence pharmacokinetic. study in healthy human volunteers. Gemfibrozil pharmacokinetic parameter values were compared using a Student t test after a single 600-mg dose was administered to healthy volunteers before and after 2 weeks of lopinavir-ritonavir (400/100 mg) twice daily.
Results: Fifteen healthy volunteers (eight males) completed the study. All study drugs were generally well tolerated and no subjects withdrew participation. The geometric mean ratio (90% confidence interval) for gemfibrozil area under the plasma concentration-time curve after 14 days of lopinavir-ritonavir compared with baseline was 0.59 (0.52, 0.67) (P < 0.001). All 15 study subjects experienced a reduction in gemfibrozil area under the plasma concentration-time curve after lopinavir-ritonavir (range, - 6% to - 74%). The geometric mean ratios for gemfibrozil apparent oral clearance and maximum concentration were 1.69 (1.41, 1.97) and 0.67 (0.49, 0.86) after 14 days of lopinavir-ritonavir versus baseline, respectively (P < 0.0001 and 0.01, respectively). Gemfibrozil elimination half-life did not change after lopinavir-ritonavir administration (P = 0.60).
Conclusion: Lopinavir-ritonavir significantly reduced the systemic exposure of gemfibrozil by reducing gemfibrozil absorption. Clinicians treating HIV-infected patients with hypertriglyceridemia should be aware of this drug interaction.
C1 [Busse, Kristin H.; Alfaro, Raul M.; Penzak, Scott R.] NIH, Clin Pharmacokinet Res Lab, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA.
[Hadigan, Colleen; Chairez, Cheryl] NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA.
[Formentini, Elizabeth; Kovacs, Joseph A.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Penzak, SR (reprint author), 9000 Rockville Pike,Bldg 10,Room 1N257, Bethesda, MD 20892 USA.
EM spenzak@cc.nih.gov
FU Intramural NIH HHS [Z01 CL006000-01]
NR 37
TC 7
Z9 8
U1 0
U2 0
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 OCT 1
PY 2009
VL 52
IS 2
BP 235
EP 239
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 499GQ
UT WOS:000270206500010
PM 19648824
ER
PT J
AU Giedd, JN
AF Giedd, Jay N.
TI Linking Adolescent Sleep, Brain Maturation, and Behavior
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Editorial Material
ID PREFRONTAL CORTEX; SCHIZOPHRENIA
C1 NIMH, Brain Imaging Unit, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Giedd, JN (reprint author), NIMH, Brain Imaging Unit, Child Psychiat Branch, Bethesda, MD 20892 USA.
RI Sanguansri, Luz/B-6630-2011; Giedd, Jay/A-3080-2008; Giedd,
Jay/B-7302-2012; Giedd, Jay/J-9644-2015
OI Sanguansri, Luz/0000-0003-1908-7604; Giedd, Jay/0000-0003-0827-3460;
Giedd, Jay/0000-0003-2002-8978
FU Intramural NIH HHS [Z99 MH999999]
NR 10
TC 15
Z9 15
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD OCT
PY 2009
VL 45
IS 4
BP 319
EP 320
DI 10.1016/j.jadohealth.2009.07.007
PG 2
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 502AM
UT WOS:000270426200001
PM 19766933
ER
PT J
AU Wang, J
Iannotti, RJ
Nansel, TR
AF Wang, Jing
Iannotti, Ronald J.
Nansel, Tonja R.
TI School Bullying Among Adolescents in the United States: Physical,
Verbal, Relational, and Cyber
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE School bullying; Cyber bullying; Relational bullying; Parental support;
Peers; Sociodemographic characteristics
ID PEER VICTIMIZATION; INDIRECT AGGRESSION; PERCEIVED FAMILY; INVOLVEMENT;
ADJUSTMENT; FRIENDSHIP; PREVALENCE; VICTIMS; BULLIES; GENDER
AB Purpose: Four forms of school bullying behaviors among US adolescents and their association with sociodemographic characteristics, parental support, and friends were examined.
Methods: Data were obtained from the Health Behavior in School-Aged Children (HBSC) 2005 Survey, a nationally representative sample of grades 6-10 (N = 7,182). The revised Olweus Bully/Victim Questionnaire was used to measure physical, verbal, and relational forms of bullying. Two items were added using the same format to measure cyber bullying. For each form, four categories were created: bully, victim, bully-victim, and not involved. Multinomial logistic regressions were applied, with sociodemographic variables, parental support, and number of friends as predictors.
Results: Prevalence rates of having bullied others or having been bullied at school for at least once in the last 2 months were 20.8% physically, 53.6% verbally, 51.4% socially, or 13.6% electronically. Boys were more involved in physical or verbal bullying, whereas girls were more involved in relational bullying. Boys were more likely to be cyber bullies, whereas girls were more likely to be cyber victims. African-American adolescents were involved in more bullying (physical, verbal, or cyber) but less victimization (verbal or relational). Higher parental support was associated with less involvement across all forms and classifications of bullying. Having more friends was associated with more bullying and less victimization for physical, verbal, and relational forms but was not associated with cyber bullying.
Conclusions: Parental support may protect adolescents from all four forms of bullying. Friends associate differentially with traditional and cyber bullying. Results indicate that cyber bullying is a distinct nature from that of traditional bullying. (C) 2009 Society for Adolescent Medicine. All rights reserved.
C1 [Wang, Jing; Iannotti, Ronald J.; Nansel, Tonja R.] NIH, Bethesda, MD 20892 USA.
RP Wang, J (reprint author), NIH, 6100 Execut Blvd, Bethesda, MD 20892 USA.
EM wangji2@mail.nih.gov
OI Nansel, Tonja/0000-0002-8298-7595
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; Maternal and Child
Health Bureau of the Health Resources and Services Administration
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development and the Maternal and Child Health Bureau of the Health
Resources and Services Administration.
NR 24
TC 401
Z9 421
U1 36
U2 201
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD OCT
PY 2009
VL 45
IS 4
BP 368
EP 375
DI 10.1016/j.jadohealth.2009.03.021
PG 8
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 502AM
UT WOS:000270426200009
PM 19766941
ER
PT J
AU Metcalfe, DD
Peavy, RD
Gilfillan, AM
AF Metcalfe, Dean D.
Peavy, Richard D.
Gilfillan, Alasdair M.
TI Mechanisms of mast cell signaling in anaphylaxis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Anaphylaxis; mast cells; Fc is an element of RI; signal transduction
ID FC-EPSILON-RI; AFFINITY IGE RECEPTOR; ALLERGIC RESPONSES; NEGATIVE
REGULATION; TYROSINE KINASE; CHANNEL FUNCTION; DEFICIENT MICE; FYN
KINASE; LYN KINASE; ACTIVATION
AB The recent development of a consensus definition and proposed diagnostic criteria for anaphylaxis offers promise for research efforts and a better understanding of the epidemiology and pathogenesis of this enigmatic and life-threatening disease. This review examines basic principles and recent research advances in the mechanisms of mast cell signaling believed to underlie anaphylaxis. The unfolding complexity of mast cell signaling suggests that the system is sensitive to regulation by any of several individual signaling pathways and intermediates and that complementary pathways regulate mast cell activation by amplified signals. The signaling events underlying anaphylactic reactions have largely been identified through experiments in genetically modified mice and supported by biochemical studies of mast cells derived from these mice. These studies have revealed that signaling pathways exist to both upregulate and downregulate mast cell responses. In this review we will thus describe the key molecular players in these pathways in the context of anaphylaxis. (J Allergy Clin Immunol 2009;124:639-46.)
C1 [Metcalfe, Dean D.; Peavy, Richard D.; Gilfillan, Alasdair M.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Metcalfe, DD (reprint author), Bldg 10-11C207,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA.
EM dmetcalfe@niaid.nih.gov
FU Merck Co., Inc.; National Institute of Allergy anti Infectious Diseases,
National Institutes of Health
FX Supported by the Intramural Research Program of the National Institute
of Allergy anti Infectious Diseases, National Institutes of Health.
NR 71
TC 92
Z9 94
U1 2
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD OCT
PY 2009
VL 124
IS 4
BP 639
EP 646
DI 10.1016/j.jaci.2009.08.035
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 506UV
UT WOS:000270802800002
PM 19815110
ER
PT J
AU Plaut, M
Sawyer, RT
Fenton, MJ
AF Plaut, Marshall
Sawyer, Richard T.
Fenton, Matthew J.
TI Summary of the 2008 National Institute of Allergy and Infectious
Diseases-US Food and Drug Administration Workshop on Food Allergy
Clinical Trial Design
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Food allergy; clinical trials; clinical trial design; oral food
challenge; precautions; prevention; treatment; tolerance;
desensitization
ID COWS MILK ALLERGY; ORAL TOLERANCE INDUCTION; 1ST 3 YEARS; PEANUT
ALLERGY; EGG ALLERGY; SUBLINGUAL IMMUNOTHERAPY; NATURAL-HISTORY;
DOUBLE-BLIND; CHILDREN; SENSITIZATION
AB This article summarizes the proceedings of a 2008 Workshop on Food Allergy Clinical Trials Design co-organized by the National Institute of Allergy and Infectious Diseases and the US Food and Drug Administration. The use of food allergens both as therapy and for oral food challenges is associated with a risk of anaphylaxis. Investigators are strongly encouraged to address regulatory considerations by discussing proposed studies with the US Food and Drug Administration. Food allergen administration through the oral or sublingual routes might be less risky than through the subcutaneous route, but this hypothesis has not been proved, and subjects with food allergy might still be at high risk of allergic reactions to such allergen administration. Two distinct mechanisms might lead to beneficial clinical outcomes: desensitization (reversible when food allergen therapy is stopped) and tolerance (persistent benefit even after allergen therapy is stopped). There are important clinical distinctions between desensitization and tolerance. The efficacy of a therapy for food allergy can be evaluated by assessing changes in the dose response to double-blind, placebo-controlled oral food challenges before and after therapy and also by assessing changes in the number of allergic episodes during a longitudinal natural history/exposure study; both approaches have strengths and limitations. (,J Allergy Clin Immunol 2009;124:671-78.)
C1 [Plaut, Marshall; Sawyer, Richard T.; Fenton, Matthew J.] NIAID, DAIT, NIH, Bethesda, MD 20892 USA.
RP Plaut, M (reprint author), NIAID, DAIT, NIH, 6610 Rockledge Dr,Room 3069, Bethesda, MD 20892 USA.
EM mplaut@niaid.nih.gov
NR 45
TC 14
Z9 14
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD OCT
PY 2009
VL 124
IS 4
BP 671
EP 678
DI 10.1016/j.jaci.2009.05.027
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 506UV
UT WOS:000270802800007
PM 19560803
ER
PT J
AU Salo, PM
Zeldin, DC
AF Salo, Paeivi M.
Zeldin, Darryl C.
TI Does exposure to cats and dogs decrease the risk of allergic
sensitization and disease?
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Editorial Material
DE Cats; dogs; allergic sensitization; domestic pets
ID FEL D 1; ASTHMA; PETS; ENVIRONMENT; PREVALENCE; CHILDHOOD; CHILDREN;
CENTERS; CD14; IGE
C1 [Salo, Paeivi M.; Zeldin, Darryl C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
RP Zeldin, DC (reprint author), NIEHS, NIH, 111 TW Alexander Dr,Room A222, Res Triangle Pk, NC 27709 USA.
EM zeldin@niehs.nih.gov
FU Intramural NIH HHS [Z01 ES025041-11]; NIEHS NIH HHS [Z01 ES025041]
NR 18
TC 2
Z9 2
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD OCT
PY 2009
VL 124
IS 4
BP 751
EP 752
DI 10.1016/j.jaci.2009.08.012
PG 2
WC Allergy; Immunology
SC Allergy; Immunology
GA 506UV
UT WOS:000270802800020
PM 19815117
ER
PT J
AU Komarow, HD
Hu, ZH
Brittain, E
Uzzaman, A
Gaskins, D
Metcalfe, DD
AF Komarow, Hirsh D.
Hu, Zonghui
Brittain, Erica
Uzzaman, Ashraf
Gaskins, Donna
Metcalfe, Dean D.
TI Serum tryptase levels in atopic and nonatopic children
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID ANAPHYLAXIS; DEFICIENCY
C1 [Komarow, Hirsh D.; Uzzaman, Ashraf; Gaskins, Donna; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Hu, Zonghui; Brittain, Erica] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Komarow, HD (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM komarowh@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI000951-06, NIH0010049406, Z01 AI000951-03]
NR 8
TC 22
Z9 22
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD OCT
PY 2009
VL 124
IS 4
BP 845
EP 848
DI 10.1016/j.jaci.2009.06.040
PG 4
WC Allergy; Immunology
SC Allergy; Immunology
GA 506UV
UT WOS:000270802800034
PM 19665778
ER
PT J
AU Cohen, SG
Mazzullo, JC
AF Cohen, Sheldon G.
Mazzullo, Joy C.
TI The allergy archives: Pioneers and milestones Discovering anaphylaxis:
Elucidation of a shocking phenomenon
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
C1 [Cohen, Sheldon G.; Mazzullo, Joy C.] NIAID, Natl Lib Med, NIH, Bethesda, MD 20892 USA.
RP Cohen, SG (reprint author), NIAID, Natl Lib Med, NIH, 8600 Rockville Pike,Bldg 38,Room 1E21, Bethesda, MD 20892 USA.
EM scohen@niaid.nih.gov
NR 14
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 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD OCT
PY 2009
VL 124
IS 4
BP 866
EP 869
PG 4
WC Allergy; Immunology
SC Allergy; Immunology
GA 506UV
UT WOS:000270802800046
PM 19830893
ER
PT J
AU Abraham, TT
Barnes, AJ
Lowe, RH
Spargo, EAK
Milman, G
Pirnay, SO
Gorelick, DA
Goodwin, RS
Huestis, MA
AF Abraham, Tsadik T.
Barnes, Allan J.
Lowe, Ross H.
Spargo, Erin A. Kolbrich
Milman, Garry
Pirnay, Stephane O.
Gorelick, David A.
Goodwin, Robert S.
Huestis, Marilyn A.
TI Urinary MDMA, MDA, HMMA, and HMA Excretion Following Controlled MDMA
Administration to Humans
SO JOURNAL OF ANALYTICAL TOXICOLOGY
LA English
DT Article
ID CHROMATOGRAPHY-MASS SPECTROMETRY; GAS-CHROMATOGRAPHY;
3,4-METHYLENEDIOXYMETHAMPHETAMINE ECSTASY; METABOLITES;
PHARMACOKINETICS; PLASMA; AMPHETAMINE; PH; QUANTIFICATION; PHARMACOLOGY
C1 [Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Spargo, Erin A. Kolbrich] SW Inst Forens Sci, Dallas, TX 75235 USA.
[Pirnay, Stephane O.] Univ Paris 05, Fac Pharm, INSERM, U705, F-75010 Paris, France.
[Gorelick, David A.] NIDA, Off Sci Director, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Room 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program; National Institutes of Health; National
Institute on Drug Abuse (NIDA/IRP)
FX This research was supported by the Intramural Research Program, National
Institutes of Health, National Institute on Drug Abuse (NIDA/IRP). The
authors wish to thank Janeen Nichels, John Etter, Kathleen Demuth, and
David Darwin for assistance with study procedures.
NR 30
TC 21
Z9 21
U1 1
U2 4
PU PRESTON PUBL INC
PI NILES
PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA
SN 0146-4760
J9 J ANAL TOXICOL
JI J. Anal. Toxicol.
PD OCT
PY 2009
VL 33
IS 8
BP 439
EP 446
PG 8
WC Chemistry, Analytical; Toxicology
SC Chemistry; Toxicology
GA 502ZN
UT WOS:000270500000006
PM 19874650
ER
PT J
AU Karschner, EL
Schwilke, EW
Lowe, RH
Darwin, WD
Herning, RI
Cadet, JL
Huestis, MA
AF Karschner, Erin L.
Schwilke, Eugene W.
Lowe, Ross H.
Darwin, W. David
Herning, Ronald I.
Cadet, Jean Lud
Huestis, Marilyn A.
TI Implications of Plasma Delta(9)-Tetrahydrocannabinol, 11-Hydroxy-THC,
and 11-nor-9-Carboxy-THC Concentrations in Chronic Cannabis Smokers
SO JOURNAL OF ANALYTICAL TOXICOLOGY
LA English
DT Article
ID FIELD SOBRIETY TESTS; MARIJUANA USE; DELTA-9-TETRAHYDROCANNABINOL THC;
BLOOD CANNABINOIDS; HALF-LIFE; USERS; METABOLISM; SMOKING; THCCOOH; TIME
C1 [Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Suite 200,251 Bayview Blvd,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse;
National Institutes of Health
FX The authors would like to thank Allan J. Barnes for data analysis
support and Kathleen Demuth, Janeen Nichels, and John Etter for clinical
research assistance. This research was supported by the Intramural
Research Program of the National Institute on Drug Abuse, National
Institutes of Health.
NR 44
TC 36
Z9 37
U1 3
U2 16
PU PRESTON PUBL INC
PI NILES
PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA
SN 0146-4760
J9 J ANAL TOXICOL
JI J. Anal. Toxicol.
PD OCT
PY 2009
VL 33
IS 8
BP 469
EP 477
PG 9
WC Chemistry, Analytical; Toxicology
SC Chemistry; Toxicology
GA 502ZN
UT WOS:000270500000010
PM 19874654
ER
PT J
AU Demner-Fushman, D
Chapman, WW
McDonald, CJ
AF Demner-Fushman, Dina
Chapman, Wendy W.
McDonald, Clement J.
TI What can natural language processing do for clinical decision support?
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Review
DE Natural language processing; Decision support techniques; Clinical
decision support systems; Review
ID PART-OF-SPEECH; ELECTRONIC MEDICAL-RECORD; NAMED-ENTITY RECOGNITION;
PATIENT SAFETY RESEARCH; BIOMEDICAL LITERATURE; INFORMATION; DOCUMENTS;
TEXT; PERFORMANCE; EXTRACTION
AB Computerized clinical decision support (CDS) aims to aid decision making of health care providers and the public by providing easily accessible health-related information at the point and time it is needed. natural language processing (NLP) is instrumental in using free-text information to drive CDS, representing clinical knowledge and CDS interventions in standardized formats, and leveraging clinical narrative. The early innovative NLP research of clinical narrative was followed by a period of stable research conducted at the major clinical centers and a shift of mainstream interest to biomedical NLP. This review primarily focuses on the recently renewed interest in development of fundamental NLP methods and advances in the NLP systems for CDS. The current solutions to challenges posed by distinct sublanguages, intended user groups, and support goals are discussed. Published by Elsevier Inc.
C1 [Demner-Fushman, Dina; McDonald, Clement J.] NIH, Lister Hill Natl Ctr Biomed Commun, Commun Engn Branch, US Natl Lib Med, Bethesda, MD 20894 USA.
[Chapman, Wendy W.] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA 15260 USA.
RP Demner-Fushman, D (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Commun Engn Branch, US Natl Lib Med, Bldg 38A,Room 10S-1020,8600 Rockville Pike MSC-38, Bethesda, MD 20894 USA.
EM ddemner@mail.nih.gov
OI Chapman, Wendy/0000-0001-8702-4483
FU National Library of Medicine, National Institutes of Health
FX This work was partially supported by the Intramural Research Program of
the National Library of Medicine, National Institutes of Health. We also
thank Kevin Bretonnel Cohen for inspiration and valuable comments, and
the anonymous reviewers for the detailed analysis and helpful comments.
NR 132
TC 110
Z9 116
U1 3
U2 23
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD OCT
PY 2009
VL 42
IS 5
BP 760
EP 772
DI 10.1016/j.jbi.2009.08.007
PG 13
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 507QV
UT WOS:000270870500002
PM 19683066
ER
PT J
AU Fiszman, M
Demner-Fushman, D
Kilicoglu, H
Rindflesch, TC
AF Fiszman, Marcelo
Demner-Fushman, Dina
Kilicoglu, Halil
Rindflesch, Thomas C.
TI Automatic summarization of MEDLINE citations for evidence-based medical
treatment: A topic-oriented evaluation
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Natural language processing; Semantic processing; Automatic
summarization; Evidence-based medicine; Knowledge representation;
Artificial intelligence; Evaluation
ID CLINICAL QUESTIONS; BIOMEDICAL TEXT; RETRIEVAL; KNOWLEDGE; FRAMEWORK;
QUALITY; SYSTEM
AB As the number of electronic biomedical textual resources increases, it becomes harder for physicians to find useful answers at the point of care. Information retrieval applications provide access to databases; however, little research has been done on using automatic summarization to help navigate the documents returned by these systems. After presenting a semantic abstraction automatic summarization system for MEDLINE citations, we concentrate on evaluating its ability to identify useful drug interventions for 53 diseases. The evaluation methodology uses existing sources of evidence-based medicine as surrogates for a physician-annotated reference standard. Mean average precision (MAP) and a clinical usefulness score developed for this study were computed as performance metrics. The automatic summarization system significantly outperformed the baseline in both metrics. The MAP gain was 0.17 (p < 0.01) and the increase in the overall score of clinical usefulness was 0.39 (p < 0.05). Published by Elsevier Inc.
C1 [Fiszman, Marcelo; Demner-Fushman, Dina; Kilicoglu, Halil; Rindflesch, Thomas C.] NIH, Natl Lib Med, Bethesda, MD 20894 USA.
[Kilicoglu, Halil] Concordia Univ, Dept Comp Sci & Software Engn, Montreal, PQ, Canada.
RP Fiszman, M (reprint author), NIH, Natl Lib Med, 8600 Rockville Pike,Bldg 38A,Rm B1N-28J, Bethesda, MD 20894 USA.
EM fiszmanm@mail.nih.gov
FU National Institutes of Health; National Library of Medicine
FX We would like to thank Charles Sneiderman and Jimmy Lin for valuable
discussions about the evaluation methodology and available resources.
This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Library of Medicine.
NR 45
TC 19
Z9 22
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 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD OCT
PY 2009
VL 42
IS 5
BP 801
EP 813
DI 10.1016/j.jbi.2008.10.002
PG 13
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 507QV
UT WOS:000270870500006
PM 19022398
ER
PT J
AU Neveol, A
Shooshan, SE
Humphrey, SM
Mork, JG
Aronson, AR
AF Neveol, Aurelie
Shooshan, Sonya E.
Humphrey, Susanne M.
Mork, James G.
Aronson, Alan R.
TI A recent advance in the automatic indexing of the biomedical literature
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Abstracting and Indexing as Topic/methods/statistics & numerical data;
Artificial Intelligence; Dictionaries, Medical; Evaluation Studies as
Topic; MEDLINE; Medical Subject Headings; Natural Language Processing
ID TEXT CATEGORIZATION; DOCUMENTS; ARTICLES; KEYWORDS; MEDLINE
AB The volume of biomedical literature has experienced explosive growth in recent years. This is reflected in the corresponding increase in the size of MEDLINE(R), the largest bibliographic database of biomedical citations. Indexers at the US National Library of Medicine (NLM) need efficient tools to help them accommodate the ensuing workload. After reviewing issues in the automatic assignment of Medical Subject Headings (MeSH(R) terms) to biomedical text, we focus more specifically on the new subheading attachment feature for NLM's Medical Text Indexer (MTI). Natural Language Processing, statistical, and machine learning methods of producing automatic MeSH main heading/subheading pair recommendations were assessed independently and combined. The best combination achieves 48% precision and 30% recall. After validation by NLM indexers, a suitable combination of the methods presented in this paper was integrated into MTI as a subheading attachment feature producing MeSH indexing recommendations compliant with current state-of-the-art indexing practice. (C) 2008 Elsevier Inc. All rights reserved.
C1 [Neveol, Aurelie; Shooshan, Sonya E.; Humphrey, Susanne M.; Mork, James G.; Aronson, Alan R.] NIH, US Natl Lib Med, Bethesda, MD 20894 USA.
RP Neveol, A (reprint author), NIH, US Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM neveola@nlm.nih.gov; sonya@nlm.nih.gov; humphrey@nlm.nih.gov;
mork@nlm.nih.gov; alan@nlm.nih.gov
FU NIH; National Library of Medicine; Oak Ridge Institute for Science and
Education
FX This work was supported in part by the Intramural Research Program of
the NIH, National Library of Medicine and by an appointment of A. Neveol
to the NLM Research Participation Program sponsored by the National
Library of Medicine and administered by the Oak Ridge Institute for
Science and Education. The authors thank James Marcetich and Joe Thomas
of NLM's Indexing Section for their interest and feedback on this work.
The authors also acknowledge Willie J. Rogers for his technical help
with implementing and running the JDI method.
NR 24
TC 27
Z9 27
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD OCT
PY 2009
VL 42
IS 5
BP 814
EP 823
DI 10.1016/j.jbi.2008.12.007
PG 10
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 507QV
UT WOS:000270870500007
PM 19166973
ER
PT J
AU Lu, ZY
Wilbur, WJ
AF Lu, Zhiyong
Wilbur, W. John
TI Improving accuracy for identifying related PubMed queries by an
integrated approach
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE PubMed distance; Related query; PubMed query log; Session segmentation;
Lexical similarity; Contextual similarity
ID ENDOPLASMIC-RETICULUM; SEARCH ENGINE; LOGS; COPII
AB PubMed is the most widely used tool for searching biomedical literature online. As with many other online search tools, a user often types a series of multiple related queries before retrieving satisfactory results to fulfill a single information need. Meanwhile, it is also a common phenomenon to see a user type queries on unrelated topics in a single session. In order to study PubMed users' search strategies, it is necessary to be able to automatically separate unrelated queries and group together related queries. Here, we report a novel approach combining both lexical and contextual analyses for segmenting PubMed query sessions and identifying related queries and compare its performance with the previous approach based solely on concept mapping.
We experimented with our integrated approach on sample data consisting of 1539 pairs of consecutive user queries in 351 user sessions. The prediction results of 1396 pairs agreed with the gold-standard annotations, achieving an overall accuracy of 90.7%. This demonstrates that our approach is significantly better than the previously published method. By applying this approach to a one day query log of PubMed, we found that a significant proportion of information needs involved more than one PubMed query, and that most of the consecutive queries for the same information need are lexically related. Finally, the proposed PubMed distance is shown to be an accurate and meaningful measure for determining the contextual similarity between biological terms. The integrated approach can play a critical role in handling real-world PubMed query log data as is demonstrated in our experiments. Published by Elsevier Inc.
C1 [Lu, Zhiyong; Wilbur, W. John] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Lu, ZY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM luzh@ncbi.nlm.nih.gov
FU NIH; National Library of Medicine
FX The authors thank Jorge R. Herskovic and Elmer V. Bernstam for their
previous work that motivated this study and their kindness for providing
the test data and results used in their work for us to compare with. We
are grateful to Larry Hunter for bringing the Google distance metric to
our attention and Kevin B. Cohen for his critical review of this
manuscript. We also thank Bill Baumgartner for proofreading this
manuscript. This research was funded by the Intramural Research Program
of the NIH, National Library of Medicine.
NR 22
TC 6
Z9 6
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
EI 1532-0480
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD OCT
PY 2009
VL 42
IS 5
SI SI
BP 831
EP 838
DI 10.1016/j.jbi.2008.12.006
PG 8
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 507QV
UT WOS:000270870500009
PM 19162232
ER
PT J
AU Smith, LH
Wilbur, WJ
AF Smith, Larry H.
Wilbur, W. John
TI The value of parsing as feature generation for gene mention recognition
SO JOURNAL OF BIOMEDICAL INFORMATICS
LA English
DT Article
DE Natural language processing; Named entity recognition; Biological text;
Gene mention recognition; Parsers; Machine learning; Support vector
machines
ID TEXT
AB We measured the extent to which information surrounding a base noun phrase reflects the presence of a gene name, and evaluated seven different parsers in their ability to provide information for that purpose. Using the GENETAG corpus as a gold standard, we performed machine learning to recognize from its context when a base noun phrase contained a gene name. Starting with the best lexical features, we assessed the gain of adding dependency or dependency-like relations from a full sentence parse. Features derived from parsers improved performance in this partial gene mention recognition task by a small but statistically significant amount. There were virtually no differences between parsers in these experiments. Published by Elsevier Inc.
C1 [Smith, Larry H.; Wilbur, W. John] Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA.
RP Smith, LH (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Room 6S614-N,Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA.
EM lsmith@ncbi.nlm.nih.gov; wilbur@ncbi.nlm.nih.gov
FU NIH; NLM; NCBI
FX We thank Dr. D. Comeau and Dr. L. Tanabe for their contributions in
annotation. This research was supported by the Intramural Research
Program of the NIH, NLM, and NCBI.
NR 42
TC 1
Z9 1
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1532-0464
J9 J BIOMED INFORM
JI J. Biomed. Inform.
PD OCT
PY 2009
VL 42
IS 5
BP 895
EP 904
DI 10.1016/j.jbi.2009.03.011
PG 10
WC Computer Science, Interdisciplinary Applications; Medical Informatics
SC Computer Science; Medical Informatics
GA 507QV
UT WOS:000270870500015
PM 19345281
ER
PT J
AU Norton, JT
Titus, SA
Dexter, D
Austin, CP
Zheng, W
Huang, S
AF Norton, John T.
Titus, Steven A.
Dexter, Dwayne
Austin, Christopher P.
Zheng, Wei
Huang, Sui
TI Automated High-Content Screening for Compounds That Disassemble the
Perinucleolar Compartment
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE high-content screening; nucleus; cancer; perinucleolar compartment;
small molecules
ID POLYMERASE-III TRANSCRIPTS; TRACT-BINDING-PROTEIN; RNA; PREVALENCE
AB All solid malignancies share characteristic traits, including unlimited cellular proliferation, evasion of immune regulation, and the propensity to metastasize. The authors have previously described that a subnuclear structure, the perinucleolar compartment (PNC), is associated with the metastatic phenotype in solid tumor cancer cells. The percentage of cancer cells that contain PNCs (PNC prevalence) is indicative of the malignancy of a tumor both in vitro and in vivo, and thus PNC prevalence is a marker that reflects metastatic capability in a population of tumor cells. Although the function of the PNC remains to be determined, the PNC is highly enriched with small RNAs and RNA binding proteins. The initial chemical biology studies using a set of anticancer drugs that disassemble PNCs revealed a direct association of the structure with DNA. Therefore, PNC prevalence reduction as a phenotypic marker can be used to identify compounds that target cellular processes required for PNC maintenance and hence used to elucidate the nature of the PNC function. Here the authors report the development of an automated high-content screening assay that is capable of detecting PNC prevalence in prostate cancer cells (PC-3M) stably expressing a green fluorescent protein (GFP)-fusion protein that localizes to the PNC. The assay was optimized using known PNC-reducing drugs and non-PNC-reducing cytotoxic drugs. After optimization, the fidelity of the assay was probed with a collection of 8284 compounds and was shown to be robust and capable of detecting known and novel PNC-reducing compounds, making it the first reported high-content phenotypic screen for small changes in nuclear structure. (Journal of Biomolecular Screening 2009:1045-1053)
C1 [Norton, John T.; Huang, Sui] Northwestern Univ, Feinberg Sch Med Cell & Mol Biol, Chicago, IL 60611 USA.
[Titus, Steven A.; Austin, Christopher P.; Zheng, Wei] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Dexter, Dwayne] GE Healthcare, Piscataway, NJ USA.
RP Huang, S (reprint author), Northwestern Univ, Feinberg Sch Med Cell & Mol Biol, 303 E Chicago Ave, Chicago, IL 60611 USA.
EM s-huang2@northwestern.edu
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU Intramural NIH HHS [NIH0012490817]; PHS HHS [NIH0012490817]
NR 15
TC 6
Z9 7
U1 1
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD OCT
PY 2009
VL 14
IS 9
BP 1045
EP 1053
DI 10.1177/1087057109343120
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA 514LL
UT WOS:000271396100002
PM 19762548
ER
PT J
AU Boden, BP
Breit, I
Sheehan, FT
AF Boden, Barry P.
Breit, Ilan
Sheehan, Frances T.
TI Tibiofemoral Alignment: Contributing Factors to Noncontact Anterior
Cruciate Ligament Injury
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID DEFICIENT STIFLE JOINT; VIDEO ANALYSIS; TIBIAL SLOPE; KNEE; MECHANISMS;
TRANSLATION; STABILITY; RUPTURE; BIOMECHANICS; ASSOCIATION
AB Background: The mechanisms of noncontact anterior cruciate ligament injury remain undefined. The purpose of this study was to identify the tibiofemoral alignment in the lateral compartment of the knee for three variations of a one-limb landing in noncontact sports activities: the safe, provocative, and exaggerated provocative positions. These positions were chosen on the basis of a previous study that measured the average joint angles of the limb at the point of ground contact for athletes who landed without injury (safe) and those who sustained an anterior cruciate ligament injury (provocative). It was hypothesized that, in the provocative positions, altered tibiofemoral alignment predisposes the knee to possible subluxation, potentially leading to an anterior cruciate ligament injury.
Methods: Magnetic resonance images were acquired for a single knee in twenty-five noninjured athletes for the three landing positions. The angle between the posterior tibial slope and the femur along with three distances (from the tibiofemoral point of contact to [1] the femoral sulcus point, [2] the posterior tibial point, and [3] the most anterior point of the circular posterior aspect of the condyle) were measured for each acquisition.
Results: The tibial slope relative to the femur was directed significantly more inferior to superior in the provocative and exaggerated positions than in the safe landing position. Similarly, as the limb transitioned from the safe to the provocative positions, the tibiofemoral joint contact point was significantly closer to the femoral sulcus point and to the most anterior point of the circular posterior portion of the lateral femoral condyle.
Conclusions: As the limb moves toward the provocative landing position, the anatomical alignment based on slope and contact characteristics places the knee at possible risk for noncontact anterior cruciate ligament injury. An enhanced understanding of the mechanism of anterior cruciate ligament injury may lead to improved preventative strategies.
C1 [Boden, Barry P.] Orthopaed Ctr, Rockville, MD 20850 USA.
Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
NIH, Funct & Appl Biomechan Lab, Bethesda, MD 20892 USA.
RP Boden, BP (reprint author), Orthopaed Ctr, 9711 Med Ctr Dr,Suite 201, Rockville, MD 20850 USA.
EM bboden@starpower.net
RI sheehan, frances/B-6962-2009
NR 34
TC 27
Z9 32
U1 3
U2 12
PU JOURNAL BONE JOINT SURGERY INC
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02192 USA
SN 0021-9355
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD OCT
PY 2009
VL 91A
IS 10
BP 2381
EP 2389
DI 10.2106/JBJS.H.01721
PG 9
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 503FV
UT WOS:000270519700010
PM 19797573
ER
PT J
AU Giallauria, F
Lucci, R
D'Agostino, M
Vitelli, A
Maresca, L
Mancini, M
Aurino, M
Del Forno, D
Giannuzzi, P
Vigorito, C
AF Giallauria, Francesco
Lucci, Rosa
D'Agostino, Mariantonietta
Vitelli, Alessandra
Maresca, Luigi
Mancini, Maria
Aurino, Mario
Del Forno, Domenico
Giannuzzi, Pantaleo
Vigorito, Carlo
TI Two-year multicomprehensive secondary prevention program: favorable
effects on cardiovascular functional capacity and coronary risk profile
after acute myocardial infarction
SO JOURNAL OF CARDIOVASCULAR MEDICINE
LA English
DT Article
DE cardiac rehabilitation; cardiopulmonary exercise testing; exercise
training; lipid profile; long-term multi-comprehensive cardiac
rehabilitation; multi-comprehensive approach; myocardial infarction;
oxygen consumption; secondary prevention
ID RANDOMIZED CONTROLLED-TRIAL; HEART-RATE RECOVERY; BODY-MASS INDEX;
CARDIAC REHABILITATION; ARTERY-DISEASE; PHYSICAL-ACTIVITY;
EUROPEAN-SOCIETY; CLINICAL-TRIAL; BLOOD-LIPIDS; TASK-FORCE
AB Background Cardiac rehabilitation includes interventions aimed at facilitating physical, psychological and emotional recovery following the acute phase of myocardial infarction (AMI). To date, optimal cardiac rehabilitation program duration and frequency of patient contact has yet to be identified.
Objective The present study was performed to evaluate the effects of two different strategies of secondary prevention (2 years, multifactorial continued educational and behavioral intervention versus usual care) implemented into a cardiac rehabilitation setting on several cardiovascular endpoints indicating cardiovascular functional exercise capacity and coronary risk profile in patients with recent AMI.
Methods This was a prospective randomized study including 52 postinfarction patients. Initially, all patients were enrolled in a 3-month outpatient cardiac rehabilitation program. Thereafter, they were randomly subdivided into two groups (I = intervention group; C = control group), each composed of 26 patients, and followed for 24 months.
Results At the end of the 3-month outpatient cardiac rehabilitation program, both groups showed a significant (P<0.05) improvement in cardiopulmonary parameters (maximal oxygen consumption, maximal workload) and in cardiovascular risk profile (BMI, lipid profile). During the 24-month study period, group I showed stabilization or even improvement (P<0.05) of both cardiopulmonary parameters and cardiovascular risk profile, whereas group C patients showed a deterioration or significant impairment (P<0.05) of the same parameters. Clinical events occurred in 27% of patients in the control group (n = 7) and in 11% in the training group (n = 3) (P< 0.05).
Conclusion Long-term, multifactorial educational and behavioral intervention maintained for 2 years in a multicomprehensive cardiac rehabilitation setting represents a valid strategy for improving long-term cardiovascular functional capacity and cardiovascular risk profile in postinfarction patients. J Cardiovasc Med 10:772-780 (C) 2009 Italian Federation of Cardiology.
C1 [Giallauria, Francesco; Lucci, Rosa; D'Agostino, Mariantonietta; Vitelli, Alessandra; Maresca, Luigi; Mancini, Maria; Aurino, Mario; Del Forno, Domenico; Vigorito, Carlo] Univ Naples Federico 2, Cardiac Rehabil Unit, Dept Clin Med Cardiovasc & Immunol Sci, I-80131 Naples, Italy.
[Giallauria, Francesco] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Giannuzzi, Pantaleo] Med Ctr Rehabil, IRCCS, Salvatore Maugeri Fdn, Div Cardiol, Veruno, Italy.
RP Giallauria, F (reprint author), Univ Naples Federico 2, Cardiac Rehabil Unit, Dept Clin Med Cardiovasc & Immunol Sci, Via Pansini5, I-80131 Naples, Italy.
EM giallauria@libero.it
RI Giallauria, Francesco/B-5681-2013; Giannuzzi, Pantaleo/K-2797-2016
OI Giallauria, Francesco/0000-0003-4119-9397; Giannuzzi,
Pantaleo/0000-0002-2313-9115
FU University of Naples "Federico II"; NIH, National Institute on Aging
FX This research is supported by University of Naples "Federico II" and in
part by the Intramural Research Program of the NIH, National Institute
on Aging.
NR 44
TC 15
Z9 15
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1558-2027
J9 J CARDIOVASC MED
JI J. Cardiovasc. Med.
PD OCT
PY 2009
VL 10
IS 10
BP 772
EP 780
DI 10.2459/JCM.0b013e32832d55fe
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 497GN
UT WOS:000270046400006
PM 19531961
ER
PT J
AU Heymann, JAW
Hinshaw, JE
AF Heymann, Juergen A. W.
Hinshaw, Jenny E.
TI Dynamins at a glance
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
ID PLECKSTRIN HOMOLOGY DOMAIN; MARIE-TOOTH DISEASE; MITOCHONDRIAL
MORPHOLOGY; MEMBRANE FISSION; CENTRONUCLEAR MYOPATHY; PEROXISOMAL
FISSION; ACTIN CYTOSKELETON; ALZHEIMERS-DISEASE; CRYSTAL-STRUCTURE;
PLASMA-MEMBRANE
C1 [Heymann, Juergen A. W.; Hinshaw, Jenny E.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
RP Heymann, JAW (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA.
EM heymannj@mail.nih.gov
FU NIDDK; National Institutes of Health
FX The laboratory is supported by the intramural research program of the
NIDDK, National Institutes of Health. Deposited in PMC for release after
12 months.
NR 59
TC 45
Z9 46
U1 0
U2 5
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD OCT
PY 2009
VL 122
IS 19
BP 3427
EP 3431
DI 10.1242/jcs.051714
PG 5
WC Cell Biology
SC Cell Biology
GA 494TK
UT WOS:000269839900001
PM 19759282
ER
PT J
AU Boheler, KR
AF Boheler, Kenneth R.
TI Stem Cell Pluripotency: A Cellular Trait That Depends on Transcription
Factors, Chromatin State and a Checkpoint Deficient Cell Cycle
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Review
ID NANOG GENE-EXPRESSION; EMBRYONIC STEM; B-MYB; SELF-RENEWAL; EPIGENETIC
REGULATION; ES CELLS; DEVELOPMENTAL REGULATORS; NUCLEAR ARCHITECTURE;
FORCED EXPRESSION; HUMAN FIBROBLASTS
AB Embryonic stem (ES) and induced pluripotent stem (iPS) cells self-renew and are pluripotent. Differentiation of these cells can yield over 200 somatic cell types, making pluripotent cells an obvious source for regenerative medicine. Before the potential of these cells can be maximally harnessed for clinical applications, it will be necessary to understand the processes that maintain pluripotentiality and signal differentiation. Currently, three unique molecular properties distinguish pluripotent stem cells from somatic cells. These include a unique transcriptional hierarchy that sustains the pluripotent state during the process of self-renewal; a poised epigenetic state that maintains chromatin in a form ready for rapid cell fate decisions; and a cell cycle characterized by an extremely short gap I (G 1) phase and the near absence of normal somatic cell checkpoint controls. Recently, B-MYB (MYBL2) was implicated in the gene regulation of two pluripotency factors and normal cell cycle progression. In this article, the three pluripotency properties and the potential role of B-Myb to regulate these processes will be discussed. J. Cell. Physiol. 221: 10-17, 2009. (C) 2009 Wiley-Liss, Inc.
C1 NIA, NIH, GRC, LCS, Baltimore, MD 21224 USA.
RP Boheler, KR (reprint author), NIA, NIH, GRC, LCS, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM bohelerk@grc.nia.nih.gov
FU Research Program of the NIH; National Institute on Aging
FX This research was supported entirely by the Research Program of the NIH,
National Institute on Aging.
NR 95
TC 43
Z9 44
U1 2
U2 24
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0021-9541
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD OCT
PY 2009
VL 221
IS 1
BP 10
EP 17
DI 10.1002/jcp.21866
PG 8
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 491IZ
UT WOS:000269573400003
PM 19562686
ER
PT J
AU Benton, G
George, J
Kleinman, HK
Arnaoutova, IP
AF Benton, G.
George, J.
Kleinman, H. K.
Arnaoutova, I. P.
TI Advancing Science and Technology Via 3D Culture on Basement Membrane
Matrix
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Review
ID ENDOTHELIAL-CELL INVASION; EXTRACELLULAR-MATRIX; IN-VITRO;
GENE-EXPRESSION; TUMOR-CELLS; BRANCHING MORPHOGENESIS; ACINAR
DIFFERENTIATION; TISSUE MORPHOGENESIS; CHEMOINVASION ASSAY;
BIOLOGICAL-ACTIVITY
AB Many cells in tissues are in contact with a highly specialized extracellular matrix, termed the basement membrane. Basement membranes have certain common components, including collagen IV, laminins, heparan sulfate proteoglycans, and growth factors which have a wide variety of biological activities. Extracts of basement membrane-rich tissue have yielded material suitable for studying cell-basement membrane interactions. Cells cultured in a 3D basement membrane matrix allow the in vitro modeling of cell behavior, including differentiation, apoptosis, steps in capillary formation, cancer growth, invasion, etc. It has also led to the development of widely used assays for invasion and angiogenesis and more recently for tumor cell dormancy. Importantly, stem cell culture in 3D basement membrane matrices has provided important advances that allow for expansion of these cells in feeder layer-free cultures and for studying their differentiation. 3D basement membrane culture has allowed the molecular dissection of pathways and genes important in differentiation, aided in the identification of progenitor cells, and led to the development of tissue constructs which may be models for regenerative medicine. This review will outline how this technology has led to important research assays and findings that have advanced our understanding of tissue development and disease and aided in the preclinical development of various therapeutics. J. Cell. Physiol. 221: 18-25, 2009. (C) Published 2009 Wiley-Liss, Inc.(dagger)
C1 [Kleinman, H. K.] NIDCR, NIH, Bethesda, MD 20892 USA.
[Benton, G.; George, J.; Arnaoutova, I. P.] Trevigen Inc, Gaithersburg, MD USA.
[Benton, G.] Georgetown Univ, Washington, DC USA.
RP Kleinman, HK (reprint author), NIDCR, NIH, 30-402,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA.
EM hkleinman@dir.nidcr.nih.gov
OI Benton, Gabriel/0000-0003-4244-5764
NR 53
TC 55
Z9 56
U1 0
U2 27
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0021-9541
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD OCT
PY 2009
VL 221
IS 1
BP 18
EP 25
DI 10.1002/jcp.21832
PG 8
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 491IZ
UT WOS:000269573400004
PM 19492404
ER
PT J
AU Aid, S
Silva, AC
Candelario-Jalil, E
Choi, SH
Rosenberg, GA
Bosetti, F
AF Aid, S.
Silva, A. C.
Candelario-Jalil, E.
Choi, S. -H.
Rosenberg, G. A.
Bosetti, F.
TI Cyclooxygenase-1 and 2 differently modulate lipopolysaccharide-induced
blood-brain barrier disruption via a matrix metalloproteinase mechanism
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Aid, S.; Choi, S. -H.; Bosetti, F.] NIA, BPMS, NIH, Bethesda, MD 20892 USA.
[Silva, A. C.] NINDS, Cerebral Microcirculat Unit, NIH, Bethesda, MD 20892 USA.
[Candelario-Jalil, E.; Rosenberg, G. A.] Univ New Mexico, Dept Neurol, Hlth Sci Ctr, Albuquerque, NM 87131 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S479
EP S479
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900584
ER
PT J
AU Bishu, S
Schmidt, K
Unterman, A
Zametkin, A
Channing, M
Liu, ZH
Qin, M
Kammerer, W
Herscovitch, P
Quezado, Z
Smith, CB
AF Bishu, S.
Schmidt, K.
Unterman, A.
Zametkin, A.
Channing, M.
Liu, Z. -H.
Qin, M.
Kammerer, W.
Herscovitch, P.
Quezado, Z.
Smith, C. Beebe
TI Propofol anesthesia alters tissue clearance of leucine but not regional
rates of cerebral protein synthesis
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Bishu, S.; Schmidt, K.; Unterman, A.; Zametkin, A.; Liu, Z. -H.; Qin, M.; Smith, C. Beebe] NIMH, Sect Neuroadaptat & Prot Metab, Bethesda, MD 20892 USA.
[Channing, M.; Herscovitch, P.] NIH, PET Dept, Bethesda, MD 20892 USA.
[Kammerer, W.; Quezado, Z.] NIH, Dept Anesthesia, Bethesda, MD 20892 USA.
RI Quezado, Zenaide/O-4860-2016
OI Quezado, Zenaide/0000-0001-9793-4368
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S11
EP S11
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900012
ER
PT J
AU Fujimura, Y
Yasuno, F
Farris, A
Liow, JS
Geraci, M
Drevets, W
Pine, D
Ghose, S
Lerner, A
Hargreaves, R
Bruns, D
Morse, C
Pike, V
Innis, R
AF Fujimura, Y.
Yasuno, F.
Farris, A.
Liow, J. -S.
Geraci, M.
Drevets, W.
Pine, D.
Ghose, S.
Lerner, A.
Hargreaves, R.
Bruns, D.
Morse, C.
Pike, V.
Innis, R.
TI Decreased neurokinin(1) (substance P) receptor binding in patients with
panic disorder: positron emission tomographic study with [F-18]SPA-RQ
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Fujimura, Y.; Yasuno, F.; Farris, A.; Liow, J. -S.; Lerner, A.; Morse, C.; Pike, V.; Innis, R.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Geraci, M.; Drevets, W.; Pine, D.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Ghose, S.] UT SW Med Ctr, Dept Psychiat, Dallas, TX USA.
[Hargreaves, R.; Bruns, D.] Merck Res Labs, West Point, PA USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
SU S1
BP S585
EP S586
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900719
ER
PT J
AU Fujimura, Y
Zoghbi, S
Simeon, F
Taku, A
Victor, P
Innis, R
Fujita, M
AF Fujimura, Y.
Zoghbi, S.
Simeon, F.
Taku, A.
Victor, P.
Innis, R.
Fujita, M.
TI Quantification of peripheral benzodiazepine receptors in human brain
with F-18-PBR06
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Fujimura, Y.; Zoghbi, S.; Simeon, F.; Taku, A.; Victor, P.; Innis, R.; Fujita, M.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
NR 2
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
SU S1
BP S360
EP S360
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900434
ER
PT J
AU Fujita, M
Zoghbi, S
Zarate, C
Mallinger, A
Hong, J
Ozaki, H
Pike, V
Innis, R
Drevets, W
AF Fujita, M.
Zoghbi, S.
Zarate, C.
Mallinger, A.
Hong, J.
Ozaki, H.
Pike, V.
Innis, R.
Drevets, W.
TI Changes of brain phosphodiesterase 4 in major depression
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Fujita, M.; Zoghbi, S.; Hong, J.; Ozaki, H.; Pike, V.; Innis, R.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Zarate, C.; Mallinger, A.] NIMH, Mood & Anxiety Disorders Res Unit, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S582
EP S582
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900715
ER
PT J
AU Henning, E
Martin, A
Warach, S
Latour, L
AF Henning, E.
Martin, A.
Warach, S.
Latour, L.
TI Flair of early BBB disruption in acute experimental stroke
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Henning, E.; Martin, A.; Warach, S.; Latour, L.] NINDS, Stroke Diagnost & Therapeut Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S482
EP S482
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900588
ER
PT J
AU Hirano, Y
Liu, J
Stefanovic, B
Silva, A
AF Hirano, Y.
Liu, J.
Stefanovic, B.
Silva, A.
TI Spatiotemporal investigation of the bold and CBV response to brief
somatosensory stimulation in awake marmosets
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Hirano, Y.; Liu, J.; Silva, A.] NINDS, CMU LFMI, NIH, Bethesda, MD 20892 USA.
[Stefanovic, B.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S603
EP S604
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900739
ER
PT J
AU Honda, M
Sanchez-Lemus, E
Saavedra, JM
AF Honda, M.
Sanchez-Lemus, E.
Saavedra, J. M.
TI Clarification of the anti-stress effects of angiotensin II AT1 receptor
blockers and their mechanisms of action
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
ID ISOLATION STRESS; DECREASES; PITUITARY
C1 [Honda, M.; Sanchez-Lemus, E.; Saavedra, J. M.] NIMH, Pharmacol Sect, NIH, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S425
EP S426
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900514
ER
PT J
AU Itoh, T
Abe, K
Inoue, O
Hong, J
Pike, VW
Innis, RB
Fujita, M
AF Itoh, T.
Abe, K.
Inoue, O.
Hong, J.
Pike, V. W.
Innis, R. B.
Fujita, M.
TI The effect of cAMP dependent protein kinase activator and inhibitor on
[C-11]rolipram binding to phosphodiesterase 4 in conscious rats
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Itoh, T.; Hong, J.; Pike, V. W.; Innis, R. B.; Fujita, M.] NIMH, Bethesda, MD 20892 USA.
[Itoh, T.; Abe, K.] Shionogi & Co Ltd, Osaka, Japan.
[Abe, K.; Inoue, O.] Osaka Univ, Grad Sch Med, Osaka, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
SU S1
BP S13
EP S14
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900015
ER
PT J
AU Kannan, S
Saadani-Makki, F
Dai, H
Chakraborthy, P
Muzik, O
Romero, R
Chugani, D
AF Kannan, S.
Saadani-Makki, F.
Dai, H.
Chakraborthy, P.
Muzik, O.
Romero, R.
Chugani, D.
TI Brain tryptophan metabolism using small animal pet in a neonatal rabbit
model of maternal inflammation induced cerebral palsy
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Kannan, S.; Saadani-Makki, F.; Dai, H.; Chakraborthy, P.; Muzik, O.; Chugani, D.] Wayne State Univ, Detroit, MI USA.
[Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S97
EP S98
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900107
ER
PT J
AU Kocharyan, A
Stefanovic, B
Silva, AC
AF Kocharyan, A.
Stefanovic, B.
Silva, A. C.
TI Neuronal PGE(2) is involved in cerebral blood flow response to
somatosensory stimulation in chloralose anesthetized rats
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Kocharyan, A.; Silva, A. C.] Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA.
[Stefanovic, B.] Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada.
[Stefanovic, B.] Univ Toronto, Toronto, ON, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
SU S1
BP S191
EP S192
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900227
ER
PT J
AU Kreisl, WC
Fujimura, Y
Kimura, N
Hong, JS
Morse, CL
Zoghbi, SS
Gladding, RL
Pike, VW
Fujita, M
Innis, RB
AF Kreisl, W. C.
Fujimura, Y.
Kimura, N.
Hong, J. S.
Morse, C. L.
Zoghbi, S. S.
Gladding, R. L.
Pike, V. W.
Fujita, M.
Innis, R. B.
TI Identification of human 'non-binders' and measurement of specific
binding with [C-11](R)-PK 11195: implications for PET imaging of brain
inflammation
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
ID RADIOLIGAND
C1 [Kreisl, W. C.; Fujimura, Y.; Kimura, N.; Hong, J. S.; Morse, C. L.; Zoghbi, S. S.; Gladding, R. L.; Pike, V. W.; Fujita, M.; Innis, R. B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
SU S1
BP S70
EP S70
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900077
ER
PT J
AU Leoni, R
Paiva, FF
de Araujo, DB
Silva, AC
AF Leoni, R.
Paiva, F. F.
de Araujo, D. B.
Silva, A. C.
TI Reduced cerebrovascular reactivity to CO2 induced by hypertension and
age: an arterial spin labeling study in rats
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
ID CEREBRAL BLOOD-FLOW
C1 [Leoni, R.; Paiva, F. F.; Silva, A. C.] NINDS, Cerebral Microcirculat Unit, NIH, Bethesda, MD 20892 USA.
[Leoni, R.; de Araujo, D. B.] Univ Sao Paulo, Dept Math & Phys, BR-14049 Ribeirao Preto, Brazil.
RI Paiva, Fernando/C-1429-2012; Leoni, Renata/J-3182-2012; Araujo,
Draulio/I-6038-2012
OI Paiva, Fernando/0000-0002-8989-9707; Leoni, Renata/0000-0002-4568-0746;
Araujo, Draulio/0000-0002-6934-2485
NR 5
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
SU S1
BP S132
EP S133
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900151
ER
PT J
AU Liu, J
Bock, N
Kocharyan, A
Hirano, Y
Silva, A
AF Liu, J.
Bock, N.
Kocharyan, A.
Hirano, Y.
Silva, A.
TI Structural MRI-measured T-1 map reflects functional topography in
primary somatosensory cortex of a non-human primate
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Liu, J.; Bock, N.; Kocharyan, A.; Hirano, Y.; Silva, A.] NINDS, CMU LFMI, NIH, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
SU S1
BP S602
EP S603
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900738
ER
PT J
AU Mazzetto-Betti, KC
Leoni, RF
Pontes-Neto, OM
Santos, AC
Silva, AC
De Araujo, DB
AF Mazzetto-Betti, K. C.
Leoni, R. F.
Pontes-Neto, O. M.
Santos, A. C.
Silva, A. C.
De Araujo, D. B.
TI Mapping the hemodynamic response function in the primary auditory cortex
under normo- and hypercapnia
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Mazzetto-Betti, K. C.; Pontes-Neto, O. M.; Santos, A. C.; De Araujo, D. B.] Univ Sao Paulo, Dept Neurol Psychiat & Med Psycol, FMRP, BR-14049 Ribeirao Preto, Brazil.
[Leoni, R. F.; De Araujo, D. B.] Univ Sao Paulo, Dept Math & Phys, FFCLRP, BR-14049 Ribeirao Preto, Brazil.
[Leoni, R. F.; Silva, A. C.] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA.
RI Pontes-Neto, Octavio/G-4294-2012; Leoni, Renata/J-3182-2012; Araujo,
Draulio/I-6038-2012
OI Pontes-Neto, Octavio/0000-0003-0317-843X; Leoni,
Renata/0000-0002-4568-0746; Araujo, Draulio/0000-0002-6934-2485
NR 2
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S569
EP S570
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900701
ER
PT J
AU Miller, DS
Wang, X
AF Miller, D. S.
Wang, X.
TI Upregulation of blood-brain barrier drug efflux pumps by the
constitutive-androstane receptor (CAR, NR1I3): a xenobiotic-activated
nuclear receptor
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
ID P-GLYCOPROTEIN
C1 [Miller, D. S.; Wang, X.] NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S82
EP S82
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900090
ER
PT J
AU Ozaki, H
Zoghbi, S
Hong, J
Pike, V
Innis, R
Fujita, M
AF Ozaki, H.
Zoghbi, S.
Hong, J.
Pike, V.
Innis, R.
Fujita, M.
TI Protoporphyrin IX interaction with peripheral type benzodiazepine
receptor in rats
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Ozaki, H.; Zoghbi, S.; Hong, J.; Pike, V.; Innis, R.; Fujita, M.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S365
EP S365
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900440
ER
PT J
AU Palumbo, S
Toscano, CD
Silva, A
Bosetti, F
AF Palumbo, S.
Toscano, C. D.
Silva, A.
Bosetti, F.
TI Brain arachidonic acid metabolic pathway is altered during
cuprizone-induced demyelination
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
ID REMYELINATION
C1 [Palumbo, S.; Bosetti, F.] NIA, BPMS, NIH, Bethesda, MD 20892 USA.
[Toscano, C. D.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Neurol Prod,Off Drug Evaluat 1, Silver Spring, MD USA.
[Silva, A.] NINDS, NIH, Bethesda, MO USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S281
EP S282
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900342
ER
PT J
AU Piknova, B
Schechter, AN
Silva, AC
AF Piknova, B.
Schechter, A. N.
Silva, A. C.
TI Exogenously administered nitric oxide does not recover the attenuation
of the CBF response to somatosensory stimulation after nNOS inhibition
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Piknova, B.; Schechter, A. N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
[Silva, A. C.] NINDS, Cerebral Microcirculat Unit, NIH, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S133
EP S134
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900152
ER
PT J
AU Seneca, N
Zoghbi, SS
Liow, JS
Kreisl, W
Herscovitch, P
Jenko, K
Gladding, RL
Taku, A
Pike, VW
Innis, RB
AF Seneca, N.
Zoghbi, S. S.
Liow, J. -S.
Kreisl, W.
Herscovitch, P.
Jenko, K.
Gladding, R. L.
Taku, A.
Pike, V. W.
Innis, R. B.
TI Human brain imaging and radiation dosimetry of
[C-11]-N-desmethyl-loperamide, a positron emission tomographic
radiotracer to measure the function of P-glycoprotein
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Seneca, N.] F Hoffmann La Roche Ltd, Clin Res & Exploratory Dev, Basl, Switzerland.
[Seneca, N.; Zoghbi, S. S.; Liow, J. -S.; Kreisl, W.; Jenko, K.; Gladding, R. L.; Taku, A.; Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Herscovitch, P.] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
SU S1
BP S480
EP S481
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900586
ER
PT J
AU Simonyan, K
Herscovitch, P
AF Simonyan, K.
Herscovitch, P.
TI Striatal dopaminergic function during speech production
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Simonyan, K.] NINDS, Laryngeal & Speech Sect, NIH, Bethesda, MD 20892 USA.
[Herscovitch, P.] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S587
EP S588
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900721
ER
PT J
AU Sojkova, J
Zhou, Y
Kraut, M
Brasic, J
Ferrucci, L
Wong, D
Resnick, S
AF Sojkova, J.
Zhou, Y.
Kraut, M.
Brasic, J.
Ferrucci, L.
Wong, D.
Resnick, S.
TI Spatial patterns of longitudinal changes in amyloid deposition in
nondemented older adults
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Sojkova, J.; Ferrucci, L.] NIA, NIH, Baltimore, MD 21224 USA.
[Sojkova, J.; Zhou, Y.; Kraut, M.; Brasic, J.; Wong, D.; Resnick, S.] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA.
RI Brasic, James/B-3503-2008
OI Brasic, James/0000-0002-3948-4853
NR 0
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 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
BP S44
EP S44
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900050
ER
PT J
AU Terry, G
Liow, JS
Zoghbi, S
Hirvonen, J
Farris, A
Lerner, A
Tauscher, J
Schaus, J
Phebus, L
Felder, C
Morse, C
Hong, J
Halldin, C
Pike, V
Innis, R
AF Terry, G.
Liow, J. -S.
Zoghbi, S.
Hirvonen, J.
Farris, A.
Lerner, A.
Tauscher, J.
Schaus, J.
Phebus, L.
Felder, C.
Morse, C.
Hong, J.
Halldin, C.
Pike, V.
Innis, R.
TI Imaging and quantitation of cannabinoid CB1 receptors in healthy human
brain using the inverse agonist radioligand [C-11]MePPEP
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Terry, G.; Liow, J. -S.; Zoghbi, S.; Hirvonen, J.; Farris, A.; Lerner, A.; Morse, C.; Hong, J.; Pike, V.; Innis, R.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Terry, G.; Halldin, C.] Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden.
[Tauscher, J.; Schaus, J.; Phebus, L.; Felder, C.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA.
NR 2
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
SU S1
BP S364
EP S364
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900439
ER
PT J
AU Tomasi, G
Bertoldo, A
Bishu, S
Unterman, A
Smith, CB
Schmidt, K
AF Tomasi, G.
Bertoldo, A.
Bishu, S.
Unterman, A.
Smith, C. Beebe
Schmidt, K.
TI Voxel-based quantification of L-[1-C-11] leucine kinetics for
determination of regional rates of cerebral protein synthesis
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
ID TISSUE AMINO-ACIDS; PET
C1 [Tomasi, G.] Yale Univ, Dept Diagnost Radiol, New Haven, CT 06510 USA.
[Bertoldo, A.] Univ Padua, Dept Informat Engn, Padua, Italy.
[Bishu, S.; Unterman, A.; Smith, C. Beebe; Schmidt, K.] NIMH, Sect Neuroadaptat & Prot Metab, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
SU S1
BP S312
EP S312
PG 1
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900381
ER
PT J
AU Veronese, M
Bertoldo, A
Bishu, S
Unterman, A
Tomasi, G
Smith, CB
Schmidt, KC
AF Veronese, M.
Bertoldo, A.
Bishu, S.
Unterman, A.
Tomasi, G.
Smith, C. B.
Schmidt, K. C.
TI A new spectral analysis method for measuring regional rates of cerebral
protein synthesis in L-[1-C-11]leucine PET studies
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Meeting Abstract
CT 24th International Symposium on Cerebral Blood Flow and Metabolism/9th
International Conference on Quantification of Brain Function with PET
CY JUN 29-JUL 03, 2009
CL Chicago, IL
SP Int Soc Cerebral Blood Flow & Metabolism
C1 [Veronese, M.; Bertoldo, A.] Univ Padua, Dept Informat Engn, Padua, Italy.
[Bishu, S.; Unterman, A.; Smith, C. B.; Schmidt, K. C.] NIMH, Sect Neuroadaptat & Prot Metab, Bethesda, MD 20892 USA.
[Tomasi, G.] Yale Univ, Dept Diagnost Radiol, New Haven, CT 06510 USA.
NR 3
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD OCT
PY 2009
VL 29
SU S1
BP S318
EP S319
PG 2
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 500UB
UT WOS:000270329900388
ER
PT J
AU Dror, O
Schneidman-Duhovny, D
Inbar, Y
Nussinov, R
Wolfson, HJ
AF Dror, Oranit
Schneidman-Duhovny, Dina
Inbar, Yuval
Nussinov, Ruth
Wolfson, Haim J.
TI Novel Approach for Efficient Pharmacophore-Based Virtual Screening:
Method and Applications
SO JOURNAL OF CHEMICAL INFORMATION AND MODELING
LA English
DT Article
ID DRUG DESIGN; MOLECULAR DOCKING; IDENTIFICATION; SUPERPOSITION; 3D;
ALGORITHM; SEARCH; SUBSTRUCTURES; RECEPTORS; DATABASES
AB Virtual screening is emerging as a productive and cost-effective technology in rational drug design for the identification of novel lead compounds. An important model for virtual screening is the pharmacophore. Pharmacophore is the spatial configuration of essential features that enable a ligand molecule to interact with a specific target receptor. In the absence of a known receptor structure, a pharmacophore can be identified from a set of ligands that have been observed to interact with the target receptor. Here, we present a novel computational method for pharmacophore detection and virtual screening. The pharmacophore detection module is able to (i) align multiple flexible ligands in a deterministic manner without exhaustive enumeration of the conformational space, (ii) detect subsets of input ligands that may bind to different binding sites or have different binding modes, (iii) address cases where the input ligands have different affinities by defining weighted pharmacophores based on the number of ligands that share them, and (iv) automatically select the most appropriate pharmacophore candidates for virtual screening. The algorithm is highly efficient, allowing a fast exploration of the chemical space by virtual screening of huge compound databases. The performance of PharmaGist was successfully evaluated on a commonly used data set of G-Protein Coupled Receptor alpha]A. Additionally,a large-scale evaluation using the DUD (directory of useful decoys) data set was performed. DUD contains 2950 active ligands for 40 different receptors, with 36 decoy compounds for each active ligand. PharmaGist enrichment rates are comparable with other state-of-the-art tools for virtual screening.
C1 [Dror, Oranit; Schneidman-Duhovny, Dina; Inbar, Yuval; Wolfson, Haim J.] Tel Aviv Univ, Blavatnik Sch Comp Sci, Raymond Fac Exact Sci, IL-69978 Tel Aviv, Israel.
[Nussinov, Ruth] Tel Aviv Univ, Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel.
Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
[Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
RP Wolfson, HJ (reprint author), Tel Aviv Univ, Blavatnik Sch Comp Sci, Raymond Fac Exact Sci, IL-69978 Tel Aviv, Israel.
EM wolfson@tau.ac.il
RI Wolfson, Haim/A-1837-2011
FU Intramural NIH HHS [Z01 BC010442-06]; NCI NIH HHS [N01-CO-12400,
N01CO12400]; NIAID NIH HHS [1UC1AI067231, UC1 AI067231]
NR 52
TC 44
Z9 44
U1 1
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9596
J9 J CHEM INF MODEL
JI J. Chem Inf. Model.
PD OCT
PY 2009
VL 49
IS 10
BP 2333
EP 2343
DI 10.1021/ci900263d
PG 11
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science,
Information Systems; Computer Science, Interdisciplinary Applications
SC Pharmacology & Pharmacy; Chemistry; Computer Science
GA 509JJ
UT WOS:000271011500017
PM 19803502
ER
PT J
AU Kratochvil, CJ
May, DE
Silva, SG
Madaan, V
Puumala, SE
Curry, JF
Walkup, J
Kepley, H
Vitiello, B
March, JS
AF Kratochvil, Christopher J.
May, Diane E.
Silva, Susan G.
Madaan, Vishal
Puumala, Susan E.
Curry, John F.
Walkup, John
Kepley, Hayden
Vitiello, Benedetto
March, John S.
TI Treatment Response in Depressed Adolescents With and Without Co-Morbid
Attention-Deficit/Hyperactivity Disorder in the Treatment for
Adolescents with Depression Study
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID DEFICIT HYPERACTIVITY DISORDER; SEROTONIN REUPTAKE INHIBITORS;
COGNITIVE-BEHAVIORAL THERAPY; MAJOR DEPRESSION; CASE SERIES; CHILDREN;
COMORBIDITY; FLUOXETINE; ADHD; SAFETY
AB Objective: In the Treatment for Adolescents with Depression Study (TADS), fluoxetine (FLX) and the combination of fluoxetine with cognitive-behavioral therapy (COMB) had superior improvement trajectories compared to pill placebo (PBO), whereas cognitive-behavioral therapy (CBT) was not significantly different from PBO. Because attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) frequently co-exist, we examined whether ADHD moderated these outcomes in TADS.
Method: A total of 439 adolescents with MDD, 12-17 years old, were randomized to FLX, CBT, COMB, or PBO. Random coefficients regression models examined depression improvement in 377 depressed youths without ADHD and 62 with ADHD, including 20 who were treated with a psychostimulant.
Results: Within the ADHD group, the improvement trajectories of the three active treatments were similar, all with rates of improvement greater than PBO. For those without ADHD, only COMB had a rate of improvement that was superior to PBO.
Conclusions: Co-morbid ADHD moderated treatment of MDD. CBT alone or FLX alone may offer benefits similar to COMB in the treatment of MDD in youths with co-morbid MDD and ADHD, whereas monotherapy may not match the benefits of COMB for those without ADHD. The ADHD subgroup analysis presented in this paper is exploratory in nature because of the small number of youths with ADHD in the sample.
C1 [Kratochvil, Christopher J.; May, Diane E.; Madaan, Vishal; Puumala, Susan E.] Univ Nebraska Med Ctr, Dept Psychiat, Omaha, NE USA.
[Silva, Susan G.; Curry, John F.; March, John S.] Duke Univ, Med Ctr, Durham, NC USA.
[Walkup, John] Johns Hopkins Univ, Baltimore, MD USA.
[Kepley, Hayden] Univ N Carolina, Wilmington, NC 28401 USA.
[Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA.
RP Kratochvil, CJ (reprint author), 985581 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM ckratoch@unmc.edu
FU National Institute of Mental Health to Duke University Medical Center
[N01 MH80008]
FX TADS was supported by contract N01 MH80008 from the National Institute
of Mental Health to Duke University Medical Center (John S. March,
Principal Investigator). Eli Lilly provided fluoxetine and matching
placebo under an independent educational grant to Duke University. Eli
Lilly had no role in the design or implementation of this study and did
not participate in the analysis of the data or in authoring this
manuscript. The opinions and assertions contained in this publication
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 34
TC 15
Z9 15
U1 2
U2 7
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD OCT
PY 2009
VL 19
IS 5
BP 519
EP 527
DI 10.1089/cap.2008.0143
PG 9
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA 514KC
UT WOS:000271392100006
PM 19877976
ER
PT J
AU Mueller, SC
Temple, V
Cornwell, B
Grillon, C
Pine, DS
Ernst, M
AF Mueller, Sven C.
Temple, Veronica
Cornwell, Brian
Grillon, Christian
Pine, Daniel S.
Ernst, Monique
TI Impaired spatial navigation in pediatric anxiety
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Pediatric; anxiety; hippocampus; water maze; spatial navigation
ID MORRIS WATER MAZE; SEX-DIFFERENCES; DEPRESSIVE-DISORDERS;
HIPPOCAMPAL-LESIONS; SOCIAL PHOBIA; CHILDREN; MEMORY; ADOLESCENTS;
INDIVIDUALS; PERFORMANCE
AB Background:
Previous theories implicate hippocampal dysfunction in anxiety disorders. Most of the data supporting these theories stem from animal research, particularly lesion studies. The generalization of findings from rodent models to human function is hampered by fundamental inter-species differences. The present work uses a task of spatial orientation, which is known to rely on hippocampal function. Deficits in spatial navigation in anxious children suggest that the hippocampal network involved in spatial orientation is also implicated in anxiety disorders.
Methods:
Thirty-four treatment-naive children with an anxiety disorder (mean 11.00 years +/- 2.54) are compared to 35 healthy age- and IQ-matched healthy children (mean 11.95 years +/- 2.36) on a virtual, computer-based equivalent of the Morris Water Maze task.
Results:
Results indicate that children with anxiety disorder exhibit overall impaired performance relative to the comparison group. Anxious children made more heading direction errors and had worse accuracy in completing trials relative to controls.
Conclusions:
The results present novel evidence that spatial orientation deficits occur in pediatric anxiety.
C1 [Mueller, Sven C.; Temple, Veronica; Cornwell, Brian; Grillon, Christian; Pine, Daniel S.; Ernst, Monique] NIMH, MAP, NIH, Bethesda, MD 20892 USA.
RP Mueller, SC (reprint author), NIMH, MAP, NIH, 15K N Dr, Bethesda, MD 20892 USA.
EM msven@mail.nih.gov
FU Intramural Research Programme of the NIMH; NIH
FX This research was supported, in part, by the Intramural Research
Programme of the NIMH, NIH. We would like to thank the three anonymous
reviewers for their helpful comments in improving this manuscript.
NR 52
TC 13
Z9 13
U1 6
U2 12
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9630
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD OCT
PY 2009
VL 50
IS 10
BP 1227
EP 1234
DI 10.1111/j.1469-7610.2009.02112.x
PG 8
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 496MH
UT WOS:000269977800005
PM 19594834
ER
PT J
AU de Castro, A
Concheiro, M
Shakleya, DM
Huestis, MA
AF de Castro, Ana
Concheiro, Marta
Shakleya, Diaa M.
Huestis, Marilyn A.
TI Development and validation of a liquid chromatography mass spectrometry
assay for the simultaneous quantification of methadone, cocaine, opiates
and metabolites in human umbilical cord
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE Methadone; Cocaine; Opiates; Umbilical cord; LCMS; In utero
ID DRUG-DEPENDENT MOTHERS; FETAL EXPOSURE; AMNIOTIC-FLUID; ILLICIT DRUGS;
BIRTH-WEIGHT; MECONIUM; ABUSE; INFANTS; TISSUE; PREGNANCY
AB A liquid chromatography mass spectrometric selected reaction monitoring mode (SRM) method for methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine (BE), 6-acetylmorphine, morphine and codeine quantification in human umbilical cord was developed and fully validated. Analytes were extracted from homogenized tissue (1 g) by solid phase extraction. Linearity was 2.5-500 ng/g, except for methadone (10-2000 ng/g). Method imprecision was <12.7%CV with analytical recovery 85.9-112.7%, extraction efficiency >59.2%, matrix effect 4.5-39.5%, process efficiency 48.6-92.6% and stability >84.6%. Analysis of an umbilical cord following controlled methadone administration and illicit drug use contained in ng/g, 40.3 morphine, 3.6 codeine, 442 BE, 186 methadone and 45.9 EDDP. Published by Elsevier B.V.
C1 [de Castro, Ana; Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[de Castro, Ana] Univ Santiago Compostela, Inst Legal Med, Forens Toxicol Serv, Santiago De Compostela 15782, Spain.
RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Biomed Res Ctr, NIH, 251 Bayview Blvd Suite 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
RI DE CASTRO, ANA/M-5159-2015
OI DE CASTRO, ANA/0000-0002-9832-012X
FU National Institutes of Health; Intramural Research Program of the
National Institute on Drug Abuse; Direccion Xeral de Investigacion,
Desenvolvemento a Innovacion (Conselleria de Innovacion a Industria),
Galicia, Spain
FX The authors would like to thank Dr. Askin, March and Ruan from the
Department of Pathology, Johns Hopkins Bayview Medical Center, for
providing us with anonymous human blank umbilical cord tissue for the
development of this method. This research was supported by the National
Institutes of Health, Intramural Research Program of the National
Institute on Drug Abuse, and from Direccion Xeral de Investigacion,
Desenvolvemento a Innovacion (Conselleria de Innovacion a Industria),
Galicia, Spain.
NR 35
TC 15
Z9 15
U1 2
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD OCT 1
PY 2009
VL 877
IS 27
BP 3065
EP 3071
DI 10.1016/j.jchromb.2009.07.028
PG 7
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 499SS
UT WOS:000270246400019
PM 19656745
ER
PT J
AU Munzer, T
Harman, SM
Sorkin, JD
Blackman, MR
AF Muenzer, Thomas
Harman, S. Mitchell
Sorkin, John D.
Blackman, Marc R.
TI Growth Hormone and Sex Steroid Effects on Serum Glucose, Insulin, and
Lipid Concentrations in Healthy Older Women and Men
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; IMPROVES BODY-COMPOSITION;
PLACEBO-CONTROLLED TRIAL; ESTROGEN PLUS PROGESTIN;
CORONARY-HEART-DISEASE; GH-DEFICIENT ADULTS; MIDDLE-AGED MEN;
REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; ELDERLY-WOMEN
AB Context: With aging, GH, IGF-I, and sex steroid concentrations and glucose tolerance decrease, and body fat and serum lipids increase.
Objective: The aim of the study was to assess GH and/or sex steroid administration effects on serum glucose, insulin, insulin sensitivity, and lipids in older individuals.
Design: A double-masked, 2 x 2 factorial, placebo-controlled, double-dummy design was used for the study.
Intervention: GH and/or sex steroid [transdermal estradiol plus oral medroxyprogesterone acetate in women (HRT); testosterone enanthate (T) in men] were administered for 6 months.
Participants: Healthy, community-dwelling women (n = 57) and men (n = 74) ages 65-88 yr (mean, 72 yr) participated in the study.
Main Outcome Measures: We measured serum glucose, insulin, and insulin sensitivity [quantitative insulin sensitivity check index (QUICKI) and insulin sensitivity index (ISI)] before and during an oral glucose tolerance test and lipid profiles. Results: In women, GH did not alter oral glucose tolerance test 120 min or 2-h area under the curve (AUC) glucose values, but it increased 120 min insulin and AUC insulin. There were no significant effects of HRT or GH + HRT. ISI and QUICKI decreased after GH. In men, GH increased 120 min and AUC glucose and insulin AUC. GH + T increased 120 min glucose and glucose and insulin AUCs. T alone did not affect glucose or insulin. ISI decreased after GH and GH + T, whereas QUICKI decreased after GH. GH in women and men and GH + T in men decreased QUICKI by 4 wk. In women, HRT decreased total cholesterol and low-density lipoprotein (LDL)-cholesterol, and GH decreased LDL-cholesterol. In men, total cholesterol decreased after T and GH + T. LDL-cholesterol decreased after GH and GH + T. GH increased serum triglycerides.
Conclusions: GH administration to healthy older individuals for 6 months increased insulin resistance with moderately beneficial effects on lipids. (J Clin Endocrinol Metab 94: 3833-3841, 2009)
C1 [Blackman, Marc R.] Vet Affairs Med Ctr, Res Serv, Washington, DC 20422 USA.
[Muenzer, Thomas; Harman, S. Mitchell; Blackman, Marc R.] NIA, Endocrine Sect, Clin Invest Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Sorkin, John D.] NIA, Metab Sect, Clin Invest Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Muenzer, Thomas] Geriatr Klin, CH-9000 St Gallen, Switzerland.
[Harman, S. Mitchell] Kronos Longev Res Inst, Phoenix, AZ 85016 USA.
[Sorkin, John D.; Blackman, Marc R.] Ctr Geriatr Res Educ & Clin, Baltimore Vet Affairs Med Ctr, Dept Vet Affairs, Baltimore, MD 21201 USA.
[Sorkin, John D.] Univ Maryland, Sch Med, Claude D Pepper Older Amer Independence Ctr, Baltimore, MD 21201 USA.
[Blackman, Marc R.] Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Baltimore, MD 21218 USA.
RP Blackman, MR (reprint author), VA Med Ctr, Res Serv 151, 50 Irving St NW, Washington, DC 20422 USA.
EM marc.blackman@va.gov
FU National Institute on Aging (NIA); National Center for Research
Resources, National Institutes of Health (Bethesda, MD) [RO-1 AG11005,
MO-1-RR-02719]; Department of Veterans Affairs and Veterans Affairs
Medical Center Baltimore Geriatrics Research, Education, and Clinical
Center; Claude D. Pepper Older Americans Independence Center
[P60-AG-12583]; National Institutes of Health; Robert Bosch Foundation,
Stuttgart, Germany
FX This work was supported by the Intramural Research Program of the
National Institute on Aging (NIA); National Institutes of Health
Research Grant RO-1 AG11005 (to M. R. B.) and General Clinical Research
Center Grant MO-1-RR-02719, from the National Center for Research
Resources, National Institutes of Health (Bethesda, MD); Department of
Veterans Affairs and Veterans Affairs Medical Center Baltimore
Geriatrics Research, Education, and Clinical Center; Claude D. Pepper
Older Americans Independence Center Grant P60-AG-12583 at the University
of Maryland; and the Research Service, Washington, D. C., Veterans
Affairs Medical Center. T. M. was supported in part by the Fogarty
International Fellowship Program of the National Institutes of Health.
T. M. now receives grant support from the Robert Bosch Foundation,
Stuttgart, Germany.
NR 60
TC 16
Z9 17
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD OCT
PY 2009
VL 94
IS 10
BP 3833
EP 3841
DI 10.1210/jc.2009-1275
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 503IE
UT WOS:000270526500028
PM 19602554
ER
PT J
AU Baid, SK
Rubino, D
Sinaii, N
Ramsey, S
Frank, A
Nieman, LK
AF Baid, Smita K.
Rubino, Domenica
Sinaii, Ninet
Ramsey, Sheila
Frank, Arthur
Nieman, Lynnette K.
TI Specificity of Screening Tests for Cushing's Syndrome in an Overweight
and Obese Population
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; DEXAMETHASONE-SUPPRESSION TEST; SALIVARY
CORTISOL-LEVELS; URINARY FREE CORTISOL; DIAGNOSTIC-TESTS;
HYPERCORTISOLISM
AB Context: Recent reports suggest a higher prevalence (1-5%) of Cushing's syndrome in certain patient populations with features of the disorder (e. g., diabetes), but the prevalence in the overweight and obese population is not known.
Objective: The aim of the study was to evaluate the diagnostic performance of screening tests for Cushing's syndrome in overweight and obese subjects with at least two other features of the disorder.
Design and Setting: We conducted a cross-sectional prospective study.
Subjects and Methods: A total of 369 subjects (73% female) completed two or three tests: a 24-h urine cortisol, and/or late-night salivary cortisol, and/or 1 mg dexamethasone suppression test (DST). If any result was abnormal [based on laboratory reference range or cortisol after DST >= 1.8 mu g/dl (50 nmol/liter)], tests were repeated and/or a dexamethasone-CRH test was performed. Subjects with abnormal DST results and a low dexamethasone level were asked to repeat the test with 2 mg of dexamethasone.
Results: In addition to obesity, subjects had a mean of five to six features of Cushing's syndrome. None was found to have Cushing's syndrome. Test specificities to exclude Cushing's syndrome for subjects who completed three tests were: urine cortisol, 96% [95% confidence interval (CI), 93-98%]; DST, 90% (95% CI, 87-93%); salivary cortisol, 84% by RIA (95% CI, 79-89%) and 92% by liquid chromatography-tandem mass spectrometry (95% CI, 88-95%). The combined specificity (both tests normal) for all combinations of two tests was 84 to 90%, with overlapping CIs.
Conclusion: These data do not support widespread screening of overweight and obese subjects for Cushing's syndrome; test results for such patients may be falsely abnormal. (J Clin Endocrinol Metab 94: 3857-3864, 2009)
C1 [Baid, Smita K.; Nieman, Lynnette K.] Eunice Kennedy Shriver NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Rubino, Domenica; Ramsey, Sheila; Frank, Arthur] George Washington Univ, Weight Management Program, Washington, DC 20037 USA.
[Rubino, Domenica; Ramsey, Sheila] Washington Ctr Weight Management & Res, Arlington, VA 22201 USA.
[Sinaii, Ninet] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA.
RP Nieman, LK (reprint author), Clin Res Ctr, Bldg 10,1 E,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM NiemanL@nih.gov
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Development
FX This research was supported (in part) by the Intramural Research Program
of the National Institutes of Health, The Eunice Kennedy Shriver
National Institute of Child Health and Development.
NR 20
TC 43
Z9 47
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD OCT
PY 2009
VL 94
IS 10
BP 3857
EP 3864
DI 10.1210/jc.2008-2766
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 503IE
UT WOS:000270526500031
PM 19602562
ER
PT J
AU Robinson-White, AJ
Bossis, I
Hsiao, HP
Nesterova, M
Leitner, WW
Stratakis, CA
AF Robinson-White, Audrey J.
Bossis, Ioannis
Hsiao, Hui-Pin
Nesterova, Maria
Leitner, Wolfgang W.
Stratakis, Constantine A.
TI 8-Cl-Adenosine Inhibits Proliferation and Causes Apoptosis in
B-Lymphocytes via Protein Kinase A-Dependent and Independent Effects:
Implications for Treatment of Carney Complex-Associated Tumors
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID SPOTTY SKIN PIGMENTATION; ALPHA REGULATORY SUBUNIT; MULTIPLE-MYELOMA
CELLS; NUCLEOSIDE TRANSPORTERS; ENDOCRINE OVERACTIVITY;
S-ADENOSYLHOMOCYSTEINE; ACTIVE METABOLITE; GROWTH-INHIBITION;
DOWN-REGULATION; LEUKEMIA-CELLS
AB Context: Carney complex, a multiple neoplasia syndrome, characterized primarily by spotty skin pigmentation and a variety of endocrine and other tumors, is caused by mutations in PRKAR1A, the gene that codes for the RI alpha subunit of protein kinase A (PKA). PKA controls cell proliferation in many cell types. The cAMP analogue 8-Cl-adenosine (8-Cl-ADO) is thought to inhibit cancer cell proliferation.
Objective: The objective of the study was to study the antiproliferative effects of 8-Cl-ADO on growth and proliferation in B-lymphocytes of Carney complex patients that have PKA defects and to determine whether 8-CL-ADO could be used as a therapeutic agent in the treatment of Carney complex-associated tumors.
Design: We used a multiparametric approach (i.e. growth and proliferation assays, PKA, and PKA subunit assays, cAMP and (3)H-cAMP binding assays, and apoptosis assays) to understand the growth and proliferative effects of 8-Cl-ADO on human B-lymphocytes.
Results: 8-Cl-ADO inhibited proliferation, mainly through its intracellular transport and metabolism, which induced apoptosis. PKA activity, cAMP levels, and (3)H-cAMP binding were increased or decreased, respectively, by 8-Cl-ADO, whereas PKA subunit levels were differentially affected. 8-Cl-ADO also inhibited proliferation induced by G protein-coupled receptors for isoproterenol and adenosine, as well as proliferation induced by tyrosine kinase receptors.
Conclusions: 8-Cl-ADO in addition to unambiguously inhibiting proliferation and inducing apoptosis in a PKA-independent manner also has PKA-dependent effects that are unmasked by a mutant PRKAR1A. Thus, 8-Cl-ADO could serve as a therapeutic agent in patients with Carney complex-related tumors. (J Clin Endocrinol Metab 94: 4061-4069, 2009)
C1 [Robinson-White, Audrey J.; Hsiao, Hui-Pin; Nesterova, Maria; Stratakis, Constantine A.] NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Leitner, Wolfgang W.] NCI, Dermatol Branch, Bethesda, MD 20892 USA.
[Bossis, Ioannis] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA.
[Hsiao, Hui-Pin] Kaohsiung Med Univ, Dept Pediat, Kaohsiung Municipal Hsiao Kang Hosp, Kaohsiung 807, Taiwan.
RP Robinson-White, AJ (reprint author), NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, Natl Inst Hlth, Bldg 10,Room 1-3330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM robinsoa@mail.nih.gov
RI Hsiao, Hui-Pin/B-3892-2010; Leitner, Wolfgang/F-5741-2011
OI Leitner, Wolfgang/0000-0003-3125-5922
FU National Institutes of Health, National Institute of Child Health and
Human Development intramural project [Z01-HD-000642-04]
FX This work was supported by the National Institutes of Health, National
Institute of Child Health and Human Development intramural project
Z01-HD-000642-04 ( to C. A. S.).
NR 40
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U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD OCT
PY 2009
VL 94
IS 10
BP 4061
EP 4069
DI 10.1210/jc.2009-0759
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 503IE
UT WOS:000270526500058
PM 19773399
ER
PT J
AU Berger, VW
AF Berger, Vance William
TI Valid, adaptive, data-driven comparisons of binary end points
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Letter
C1 [Berger, Vance William] NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
[Berger, Vance William] Univ Maryland Baltimore Cty, Bethesda, MD USA.
RP Berger, VW (reprint author), NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
EM vb78c@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 3
TC 2
Z9 2
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-4356
J9 J CLIN EPIDEMIOL
JI J. Clin. Epidemiol.
PD OCT
PY 2009
VL 62
IS 10
BP 1112
EP 1112
DI 10.1016/j.jclinepi.2009.04.009
PG 1
WC Health Care Sciences & Services; Public, Environmental & Occupational
Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 499UB
UT WOS:000270250500016
PM 19699055
ER
PT J
AU Weir, MR
Yeh, F
Silverman, A
Devereux, RB
Galloway, JM
Henderson, JA
Howard, WJ
Russell, M
Wilson, C
Ratner, R
Sorkin, J
Umans, JG
Fleg, JL
Stylianou, M
Lee, E
Howard, BV
AF Weir, Matthew R.
Yeh, Fawn
Silverman, Angela
Devereux, Richard B.
Galloway, James M.
Henderson, Jeffrey A.
Howard, William J.
Russell, Marie
Wilson, Charlton
Ratner, Robert
Sorkin, John
Umans, Jason G.
Fleg, Jerome L.
Stylianou, Mario
Lee, Elisa
Howard, Barbara V.
TI Safety and Feasibility of Achieving Lower Systolic Blood Pressure Goals
in Persons With Type 2 Diabetes: The SANDS Trial
SO JOURNAL OF CLINICAL HYPERTENSION
LA English
DT Article
ID CORONARY-HEART-DISEASE; RANDOMIZED-TRIAL; AMERICAN-INDIANS; LOWER
TARGETS; CHOLESTEROL; ATHEROSCLEROSIS; COMMITTEE
AB The Stop Atherosclerosis in Native Diabetics Study (SANDS) was a randomized open-label clinical trial in type 2 diabetics designed to examine the effects of intensive reduction of blood pressure, aggressive vs standard goals (< 115/75 mm Hg vs < 130/80 mm Hg), and low-density lipoprotein (LDL) cholesterol on the composite outcome of change in carotid intimal-medial thickness and cardiovascular events. The study demonstrated that in conjunction with a lower LDL cholesterol target of 70 mg/dL, aggressive systolic blood pressure-lowering resulted in a reduction in carotid intimal-medial thickness and left ventricular mass without measurable differences in cardiovascular events. The blood pressure treatment algorithm included renin-angiotensin system blockade, with other agents added if necessary. The authors conclude that both standard and more aggressive systolic blood pressure reduction can be achieved with excellent safety and good tolerability in patients with type 2 diabetes mellitus.
C1 [Weir, Matthew R.] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA.
[Yeh, Fawn; Lee, Elisa] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Silverman, Angela; Howard, William J.; Ratner, Robert; Umans, Jason G.; Howard, Barbara V.] MedStar Res Inst, Hyattsville, MD USA.
[Devereux, Richard B.] Weill Cornell Med Coll, New York, NY USA.
[Galloway, James M.] Univ Arizona, Hlth Sci Ctr, Tucson, AZ USA.
[Henderson, Jeffrey A.] Black Hills Ctr Amer Indian Hlth, Rapid City, SD USA.
[Russell, Marie; Wilson, Charlton] Phoenix Indian Med Ctr, Phoenix, AZ USA.
[Fleg, Jerome L.; Stylianou, Mario] NHLBI, Bethesda, MD 20892 USA.
RP Weir, MR (reprint author), Univ Maryland, Sch Med, Div Nephrol, 22 S Greene St,Room N3W143, Baltimore, MD 21201 USA.
EM mweir@medicine.umaryland.edu
FU First Horizon Pharmacy (Triglide); Merck and Co (Cozaar/Hyzaar); Pfizer,
Inc (Lipitor)
FX We thank the Indian Health Services facilities, SANDS participants, and
participating tribal communities for extraordinary cooperation and
involvement without which this study would not have been possible. We
also acknowledge the valuable contributions of the following SANDS study
staff: Tauqeer Ali, PhD; Collen Begay; Stephanie Big Crow; Verna Cable;
Damon Davis, RN; Joanne Detwiler, PA-C; Lynne Dobrovolny, PA; Verdell
Kanuho; Tanya Molina; Missy Oines; Maria Ramos, PA-C; Corinne Wills,
CNP; and Jackie Yotter, RN, for coordination of study centers and Tia A.
Paul, University of Maryland School of Medicine, Baltimore, MD, for
editing the manuscript. We also gratefully acknowledge donations of
pharmacologic agents by First Horizon Pharmacy (Triglide); Merck and Co
(Cozaar/Hyzaar); and Pfizer, Inc (Lipitor), and we thank Dr John Lachin
for providing advice on statistical methods.
NR 16
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U1 0
U2 1
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 OCT
PY 2009
VL 11
IS 10
BP 540
EP 548
DI 10.1111/j.1751-7176.2009.00121.x
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 504BP
UT WOS:000270588700003
PM 19817934
ER
PT J
AU Nabel, EG
AF Nabel, Elizabeth G.
TI Linking biomedical research to health care
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
C1 NHLBI, Bethesda, MD 20892 USA.
RP Nabel, EG (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
EM directornhlbi@mail.nih.gov
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD OCT
PY 2009
VL 119
IS 10
BP 2858
EP 2858
DI 10.1172/JCI41035
PG 1
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 503HA
UT WOS:000270523100012
PM 20069715
ER
PT J
AU Doi, K
Leelahavanichkul, A
Yuen, PST
Star, RA
AF Doi, Kent
Leelahavanichkul, Asada
Yuen, Peter S. T.
Star, Robert A.
TI Animal models of sepsis and sepsis-induced kidney injury
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Review
ID ACUTE-RENAL-FAILURE; TUMOR-NECROSIS-FACTOR; TOLL-LIKE RECEPTORS;
PERITUBULAR CAPILLARY DYSFUNCTION; CRITICALLY-ILL PATIENTS; IN-VIVO
EXPRESSION; SEPTIC SHOCK; CECAL LIGATION; BLOOD-FLOW; POLYMICROBIAL
SEPSIS
AB Sepsis is characterized by a severe inflammatory response to infection, and its complications, including acute kidney injury, can be fatal. Animal models that correctly mimic human disease are extremely valuable because they hasten the development of clinically useful therapeutics. Too often, however, animal models do not properly mimic human disease. In this Review, we outline a bedside-to-bench-to-bedside approach that has resulted in improved animal models for the study of sepsis - a complex disease for which preventive and therapeutic strategies are unfortunately lacking. We also highlight a few of the promising avenues for therapeutic advances and biomarkers for sepsis and sepsis-induced acute kidney injury. Finally, we review how the study of drug targets and biomarkers are affected by and in turn have influenced these evolving animal models.
C1 [Yuen, Peter S. T.] NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA.
[Doi, Kent] Univ Tokyo, Dept Nephrol & Endocrinol, Tokyo, Japan.
[Leelahavanichkul, Asada] Chulalongkorn Univ, Dept Med, Div Nephrol, Bangkok, Thailand.
RP Yuen, PST (reprint author), NIDDK, Renal Diagnost & Therapeut Unit, NIH, 10 Ctr Dr,Room 3N108, Bethesda, MD 20892 USA.
EM py@nih.gov
RI Yuen, Peter/B-1954-2008
OI Yuen, Peter/0000-0001-9557-3909
FU Intramural Research Program of the NIH; NIDDK
FX This research was supported by the Intramural Research Program of the
NIH, NIDDK. We apologize to all the authors whose. work we could not
cover due to space limitations.
NR 126
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U2 29
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD OCT
PY 2009
VL 119
IS 10
BP 2868
EP 2878
DI 10.1172/JCI39421
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 503HA
UT WOS:000270523100019
PM 19805915
ER
PT J
AU Gress, RE
Deeks, SG
AF Gress, Ronald E.
Deeks, Steven G.
TI Reduced thymus activity and infection prematurely age the immune system
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID T-CELL SUBSETS; REPERTOIRE; RISK; THYMOPOIESIS; ACTIVATION; EXPANSION;
ADULTS; LIFE
AB The aging process affects all aspects of the immune system, particularly the T cells. The immune system in older individuals is often characterized by lower T cell numbers, lower naive/memory T cell ratios, and lower T cell diversity. Most measures of inflammation increase with age. Why this happens, and why there is so much person-to-person variability in these changes, is not known. In this issue of the JCI, Sauce and colleagues show that removal of the thymus during infancy results in premature onset of many of these age-associated changes to the immune system (see the related article beginning on page 3070). The effect of thymectomy was particularly notable in those individuals who acquired CMV infection. Data from this study, as well as data from other observational settings, suggest that reduced thymic function and persistent viral infections combine to accelerate a decline in immunologic function.
C1 [Deeks, Steven G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Gress, Ronald E.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Deeks, SG (reprint author), Univ Calif San Francisco, Ward 84,Bldg 80,995 Potero Ave, San Francisco, CA 94143 USA.
EM sdeeks@php.ucsf.edu
NR 20
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U1 1
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PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD OCT
PY 2009
VL 119
IS 10
BP 2884
EP 2887
DI 10.1172/JCI40855
PG 4
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 503HA
UT WOS:000270523100022
PM 19770512
ER
PT J
AU Snow, AL
Marsh, RA
Krummey, SM
Roehrs, P
Young, LR
Zhang, KJ
van Hoff, J
Dhar, D
Nichols, KE
Filipovich, AH
Su, HC
Bleesing, JJ
Lenardo, MJ
AF Snow, Andrew L.
Marsh, Rebecca A.
Krummey, Scott M.
Roehrs, Philip
Young, Lisa R.
Zhang, Kejian
van Hoff, Jack
Dhar, Deepali
Nichols, Kim E.
Filipovich, Alexandra H.
Su, Helen C.
Bleesing, Jack J.
Lenardo, Michael J.
TI Restimulation-induced apoptosis of T cells is impaired in patients with
X-linked lymphoproliferative disease caused by SAP deficiency
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID HUMORAL IMMUNE-RESPONSES; MICE DEFICIENT; ENCODING GENE; XLP SYNDROME;
SH2 DOMAIN; ACTIVATION; RECEPTOR; DEATH; SLAM; LYMPHOCYTES
AB X-linked lymphoproliferative disease (XLP) is a rare congenital immunodeficiency that leads to an extreme, usually fatal increase in the number of lymphocytes upon infection with EBV. It is most commonly defined molecularly by loss of expression of SLAM-associated protein (SAP). Despite this, there is little understanding of how SAP deficiency causes lymphocytosis following EBV infection. Here we show that T cells from individuals with XLP are specifically resistant to apoptosis mediated by TCR restimulation, a process that normally constrains T cell expansion during immune responses. Expression of SAP and the SLAM family receptor NK, T, and B cell antigen (NTB-A) were required for TCR-induced upregulation of key pro-apoptotic molecules and subsequent apoptosis. Further, SAP/NTB-A signaling augmented the strength of the proximal TCR signal to achieve the threshold required for restimulation-induced cell death (RICD). Strikingly, TCR ligation in activated T cells triggered increased recruitment of SAP to NTB-A, dissociation of the phosphatase SHP-1, and colocalization of NTB-A with CD aggregates. In contrast, NTB-A and SHP-1 contributed to RICD resistance in XLP T cells. Our results reveal what we believe to be novel roles for NTB-A and SAP in regulating T cell homeostasis through apoptosis and provide mechanistic insight into the pathogenesis of lymphoproliferative disease in XLP.
C1 [Snow, Andrew L.; Krummey, Scott M.; Dhar, Deepali; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Zhang, Kejian] Cincinnati Childrens Hosp, Med Ctr, Div Human Genet, Cincinnati, OH USA.
[Young, Lisa R.] Cincinnati Childrens Hosp, Med Ctr, Div Pulm Med, Cincinnati, OH USA.
[Marsh, Rebecca A.; Roehrs, Philip; Filipovich, Alexandra H.; Bleesing, Jack J.] Cincinnati Childrens Hosp, Med Ctr, Div Bone Marrow Transplantat Immune Deficiency, Cincinnati, OH USA.
[van Hoff, Jack] Dartmouth Hitchcock Med Ctr, Dept Hematol Oncol, Lebanon, NH 03766 USA.
[Nichols, Kim E.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Su, Helen C.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
RP Lenardo, MJ (reprint author), Bldg 10,Rm 11N311,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lenardo@nih.gov
RI Su, Helen/H-9541-2015;
OI Su, Helen/0000-0002-5582-9110; Snow, Andrew/0000-0002-8728-6691
FU NIH; National Institute of Allergy and Infectious Diseases; National
Institute of General Medical Sciences
FX We thank the patients and their families, as well as Lewis Silverman at
Dana Farber Cancer Institute for providing blood samples on XLP PtS. We
also thank Juraj Kabat for help with confocal microscopy analysis and
Pamela Schwartzberg for critical reading of the manuscript. We
acknowledge the clinical laboratory testing performed by the Cincinnati
Children's Hospital Diagnostic Immunology Laboratory as well as care for
the patients provided by the bone marrow transplant physicians, nurses,
and staff at Cincinnati Children's Hospital. This research was supported
by the Intramural Research Program of the NIH, National Institute of
Allergy and Infectious Diseases. A.L. Snow was supported by a
Pharmacology Research Associate Training Program Fellowship from the
National Institute of General Medical Sciences.
NR 45
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U2 0
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD OCT
PY 2009
VL 119
IS 10
BP 2976
EP 2989
DI 10.1172/JCI39518
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 503HA
UT WOS:000270523100032
PM 19759517
ER
PT J
AU Li, JH
Chou, CL
Li, B
Gavrilova, O
Eisner, C
Schnermann, J
Anderson, SA
Deng, CX
Knepper, MA
Wess, J
AF Li, Jian Hua
Chou, Chung-Lin
Li, Bo
Gavrilova, Oksana
Eisner, Christoph
Schnermann, Juergen
Anderson, Stasia A.
Deng, Chu-Xia
Knepper, Mark A.
Wess, Juergen
TI A selective EP4 PGE(2) receptor agonist alleviates disease in a new
mouse model of X-linked nephrogenic diabetes insipidus
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID MEDULLARY COLLECTING DUCT; RAT-KIDNEY; WATER PERMEABILITY; PROSTAGLANDIN
E-2; KNOCKOUT MICE; VASOPRESSIN; AQUAPORIN-2; GENE; MUTATIONS;
PATHOGENESIS
AB X-linked nephrogenic diabetes insipidus (XNDI) is a severe kidney disease caused by inactivating mutations in the V2 vasopressin receptor (V2R) gene that result in the loss of renal urine-concentrating ability. At present, no specific pharmacological therapy has been developed for XNDI, primarily due to the lack of suitable animal models. To develop what we believe to be the first viable animal model of XNDI, we generated mice in which the V2R gene could be conditionally deleted during adulthood by administration of 4-OH-tamoxifen. Radioligand-binding studies confirmed the lack of V2R-binding sites in kidneys following 4-OH-tamoxifen treatment, and further analysis indicated that upon V2R deletion, adult mice displayed all characteristic symptoms of XNDI, including polyuria, polydipsia, and resistance to the antidiuretic actions of vasopressin. Gene expression analysis suggested that activation of renal EP4 PGE(2) receptors might compensate for the lack of renal V2R activity in XNDI mice. Strikingly, both acute and chronic treatment of the mutant mice with a selective EP4 receptor agonist greatly reduced all major manifestations of XNDI, including changes in renal morphology. These physiological improvements were most likely due to a direct action on EP4 receptors expressed on collecting duct cells. These findings illustrate the usefulness of the newly generated V2R mutant mice for elucidating and testing new strategies for the potential treatment of humans with XNDI.
C1 [Wess, Juergen] NIDDK, Bioorgan Chem Lab, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA.
[Chou, Chung-Lin; Knepper, Mark A.] NIDDK, Kidney & Electrolyte Metab Lab, NHLBI, NIH, Bethesda, MD 20892 USA.
[Gavrilova, Oksana] NIDDK, Mouse Metab Core Facil, NIH, Bethesda, MD 20892 USA.
[Eisner, Christoph; Schnermann, Juergen] NIDDK, Renal Funct & Injury Sect, NIH, Bethesda, MD 20892 USA.
[Anderson, Stasia A.] NIDDK, Anim MRI Imaging Core, NHLBI, NIH, Bethesda, MD 20892 USA.
[Deng, Chu-Xia] NIDDK, Mammalian Genet Sect, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Wess, J (reprint author), NIDDK, Bioorgan Chem Lab, Mol Signaling Sect, NIH, Bldg 8A,Room B1A-05,8 Ctr Dr, Bethesda, MD 20892 USA.
EM jwess@helix.nih.gov
RI Li, Jianhua/B-7671-2011
OI Li, Jianhua/0000-0002-5744-3182
FU National Institute of Diabetes and Digestive and Kidney Disorders
(NIDDK); National Heart, Lung, and Blood Institute (NHLBI)
[ZO1-HL-001285]
FX This research was supported by the Intramural Research Program budgets
of the National Institute of Diabetes and Digestive and Kidney Disorders
(NIDDK) and the National Heart, Lung, and Blood Institute (NHLBI)
(project number ZO1-HL-001285). We thank Brenda Klaunberg and Vivian
Diaz (In Vivo NMR Center, National Institute of Neurological Disorders
and Stroke) for their help with the blood pressure measurements, Shawn
Kozlov (NHLBI) for analyzing urine and serum samples, and Cuiling Li and
Yinghong Cui (NIDDK) for expert technical assistance.
NR 49
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U2 1
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD OCT
PY 2009
VL 119
IS 10
BP 3115
EP 3126
DI 10.1172/JCI39680
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 503HA
UT WOS:000270523100044
PM 19729836
ER
PT J
AU Mandinova, A
Kolev, V
Neel, V
Hu, B
Stonely, W
Lieb, J
Wu, XW
Colli, C
Han, R
Pazin, M
Ostano, P
Dummer, R
Brissette, JL
Dotto, GP
AF Mandinova, Anna
Kolev, Vihren
Neel, Victor
Hu, Bing
Stonely, Wesley
Lieb, Jocelyn
Wu, Xunwei
Colli, Claudia
Han, Rong
Pazin, Mike
Ostano, Paola
Dummer, Reinhard
Brissette, Janice L.
Dotto, G. Paolo
TI A positive FGFR3/FOXN1 feedback loop underlies benign skin keratosis
versus squamous cell carcinoma formation in humans
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; EPITHELIAL TERMINAL DIFFERENTIATION; SEBORRHEIC
KERATOSES; C-JUN; MULTIPLE-MYELOMA; FGFR3 MUTATIONS; NUDE GENE;
EPIDERMAL-GROWTH; EXPRESSION; PROTEIN
AB Seborrheic keratoses (SKs) are common, benign epithelial tumors of the skin that do not, or very rarely, progress into malignancy, for reasons that are not understood. We investigated this by gene expression profiling of human SKs and cutaneous squamous cell carcinomas (SCCs) and found that several genes previously connected with keratinocyte tumor development were similarly modulated in SKs and SCCs, whereas the expression of others differed by only a few fold. In contrast, the tyrosine kinase receptor FGF receptor-3 (FGFR3) and the transcription factor forkhead box N1 (FOXN1) were highly expressed in SKs, and close to undetectable in SCCs. We also showed that increased FGFR3 activity was sufficient to induce FOXN1 expression, counteract the inhibitory effect of EGFR signaling on FOXN1 expression and differentiation, and induce differentiation in a FOXN1-dependent manner. Knockdown of FOXN1 expression in primary human keratinocytes cooperated with oncogenic RAS in the induction of SCC-like tumors, whereas increased FOXN1 expression triggered the SCC cells to shift to a benign SK-like tumor phenotype, which included increased FGFR3 expression. Thus, we have uncovered a positive regulatory loop between FGFR3 and FOXN1 that underlies a benign versus malignant skin tumor phenotype.
C1 [Hu, Bing; Dotto, G. Paolo] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland.
[Neel, Victor; Dotto, G. Paolo] MGH, Dept Dermatol, Boston, MA USA.
[Mandinova, Anna; Kolev, Vihren; Stonely, Wesley; Lieb, Jocelyn; Wu, Xunwei; Colli, Claudia; Han, Rong; Brissette, Janice L.; Dotto, G. Paolo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA.
[Pazin, Mike] NIA, NIH, Baltimore, MD 21224 USA.
[Ostano, Paola] Fondo Edo Tempia, Lab Canc Pharmacogenom, Biella, Italy.
[Dummer, Reinhard] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland.
RP Dotto, GP (reprint author), Univ Lausanne, Dept Biochem, Chemin Boveresses 155, CH-1066 Epalinges, Switzerland.
EM gian-paolo.dotto@unil.ch
OI Han, Rong/0000-0002-5766-8277; Pazin, Michael/0000-0002-7561-3640
FU NIH [AR39190, AR054856, AR04S284, CA16038, CA73796]; Swiss National
Foundation; European Union [LSHB-CT-2005-019067]; Cutaneous Biology
Research Center through the MGH/Shiseido Co. Ltd. Agreement
FX We thank W. Austen for human skin material, D. Prowse for the FOXN1-ER
retrovirus, D. Ornitz for FGFR3 constructs, and V. Rajashekara for
skillful technical help. This work was supported by NIH grants AR39190,
AR054856, AR04S284, CA16038, and CA73796; by the Swiss National
Foundation; by a grant from the European Union (Epistem, Sixth Framework
Program, LSHB-CT-2005-019067); and in part by the Cutaneous Biology
Research Center through the MGH/Shiseido Co. Ltd. Agreement.
NR 61
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Z9 33
U1 0
U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD OCT
PY 2009
VL 119
IS 10
BP 3127
EP 3137
DI 10.1172/JCI38543
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 503HA
UT WOS:000270523100045
PM 19729838
ER
PT J
AU Iwasawa, M
Miyazaki, T
Nagase, Y
Akiyama, T
Kadono, Y
Nakamura, M
Oshima, Y
Yasui, T
Matsumoto, T
Nakamura, T
Kato, S
Hennighausen, L
Nakamura, K
Tanaka, S
AF Iwasawa, Mitsuyasu
Miyazaki, Tsuyoshi
Nagase, Yuichi
Akiyama, Toru
Kadono, Yuho
Nakamura, Masaki
Oshima, Yasushi
Yasui, Tetsuro
Matsumoto, Takumi
Nakamura, Takashi
Kato, Shigeaki
Hennighausen, Lothar
Nakamura, Kozo
Tanaka, Sakae
TI The antiapoptotic protein Bcl-xL negatively regulates the bone-resorbing
activity of osteoclasts in mice
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID CELL-DEATH; C-SRC; ENDOPLASMIC-RETICULUM; CONDITIONAL DELETION;
NUCLEAR-ENVELOPE; IN-VIVO; APOPTOSIS; FAMILY; RECEPTOR; EXPRESSION
AB The B cell lymphoma 2 (Bcl-2) family member Bcl-xL has a well-characterized antiapoptotic function in lymphoid cells. However, its functions in other cells - including osteoclasts, which are of hematopoietic origin and other cellular processes remain unknown. Here we report an unexpected function of Bcl-xL in attenuating the bone-resorbing activity of osteoclasts in mice. To investigate the role of Bcl-xL in osteoclasts, we generated mice with osteoclast-specific conditional deletion of Bcl-x (referred to herein as Bcl-x cKO mice) by mating Bcl-x(fl/fl) mice with mice in which the gene encoding the Cre recombinase has been knocked into the cathepsin K locus and specifically expressed in mature osteoclasts. Although the Bcl-x cKO mice grew normally with no apparent morphological abnormalities, they developed substantial osteopenia at 1 year of age, which was caused by increased bone resorption. Bcl-x deficiency increased the bone-resorbing activity of osteoclasts despite their high susceptibility to apoptosis, whereas Bcl-xL overexpression produced the opposite effect. In addition, Bcl-x cKO osteoclasts displayed increased c-Src activity, which was linked to increased levels of vitronectin and fibronectin expression. These results suggest that Bcl-xL attenuates osteoclastic bone-resorbing activity through the decreased production of ECM proteins, such as vitronectin and fibronectin, and thus provide evidence for what we believe to be a novel cellular function of Bcl-xL.
C1 [Tanaka, Sakae] Univ Tokyo, Fac Med, Dept Orthopaed Surg, Bunkyo Ku, Tokyo 1130033, Japan.
[Miyazaki, Tsuyoshi] Tokyo Metropolitan Geriatr Hosp, Dept Geriatr Med, Tokyo 173, Japan.
[Miyazaki, Tsuyoshi] Inst Gerontol, Tokyo, Japan.
[Nakamura, Takashi; Kato, Shigeaki] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo, Japan.
[Hennighausen, Lothar] NIH, Lab Genet & Physiol, Bethesda, MD 20892 USA.
RP Tanaka, S (reprint author), Univ Tokyo, Fac Med, Dept Orthopaed Surg, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.
EM TANAKAS-ORT@h.u-tokyo.ac.jp
OI Akiyama, Toru/0000-0001-9493-4768
FU Ministry of Education, Culture, Sports, Science, and Technology of
Japan; Ministry of Health, Labor, and Welfare of Japan; National
Institute of Diabetes and Digestive and Kidney Diseases, NIH
FX The authors thank R. Yamaguchi (Department of Orthopaedic Surgery,
University of Tokyo) for providing expert technical assistance. ABT-737
was provided by Abbott Laboratories. This work was supported in part by
Grants-in-Aid from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan and by Health Science research grants from the
Ministry of Health, Labor, and Welfare of Japan to S. Tanaka. The
research of L. Hennighausen was funded through the Intramural Program of
the National Institute of Diabetes and Digestive and Kidney Diseases,
NIH. Pacific Edit reviewed the manuscript prior to submission.
NR 41
TC 18
Z9 21
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
J9 J CLIN INVEST
JI J. Clin. Invest.
PD OCT
PY 2009
VL 119
IS 10
BP 3149
EP 3159
DI 10.1172/JCI39819
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 503HA
UT WOS:000270523100047
PM 19759519
ER
PT J
AU Chang, SW
Biswas, K
Martin, BK
Stauffer, S
Sharan, SK
AF Chang, Suhwan
Biswas, Kajal
Martin, Betty K.
Stauffer, Stacey
Sharan, Shyam K.
TI Expression of human BRCA1 variants in mouse ES cells allows functional
analysis of BRCA1 mutations
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID BREAST-CANCER SUSCEPTIBILITY; EARLY-ONSET BREAST; OVARIAN-CANCER;
EMBRYONIC LETHALITY; MISSENSE MUTATIONS; GERMLINE MUTATIONS; SEQUENCE
VARIANTS; GENE BRCA1; IN-VIVO; PHOSPHORYLATION
AB To date, inheritance of a mutant BRCA1 or BRCA2 gene is the best-established indicator of an increased risk of developing breast cancer. Sequence analysis of these genes is being used to identify BRCA1/2 mutation carriers, though these efforts are hampered by the high frequency of variants of unknown clinical significance (VUSs). Functional evaluation of such variants has been restricted due to lack of a physiologically relevant assay. In this study we developed a functional assay using mouse ES cells to study variants of BRCA1. We introduced BAC clones with human wild-type BRCA1 or variants into Brca1-null ES cells and confirmed that only wild-type and a known neutral variant rescued cell lethality. The same neutral variant was also able to rescue embryogenesis in Brca1-null mice. A test of several BRCT domain mutants revealed all to be deleterious, including a VUS. Furthermore, we used this assay to determine the effects of BRCA1 variants on cell cycle regulation, differentiation, and genomic stability. Importantly, we discovered that ES cells rescued by S1497A BRCA1 exhibited significant hypersensitivity after gamma-irradiation. Our results demonstrate that this ES cell-based assay is a powerful and reliable method for analyzing the functional impact of BRCA1 variants, which we believe could be used to determine which patients may require preventative treatments.
C1 [Chang, Suhwan; Biswas, Kajal; Stauffer, Stacey; Sharan, Shyam K.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Ft Detrick, MD 21702 USA.
[Martin, Betty K.] NCI, SAIC Frederick, Ft Detrick, MD 21702 USA.
RP Sharan, SK (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Bldg 560,Room 32-31C,1050 Boyles St, Ft Detrick, MD 21702 USA.
EM sharans@mail.nih.gov
FU Center for Cancer Research, NCI, NIH
FX We thank J. Acharya, I. Daar, K. Reilly, and L. Tessarollo for helpful
discussions and critical review of the manuscript. We also thank
Kyung-Ae Kim and Susan Lynn North for technical assistance; Deborah
Swing, Yongping Yang, Prajakta Varadkar, and Lionel Feigenbaum for help
with BAC transgenic mice; Sandra Burkett for cytogenetic analysis; Allen
Kane, Jiro Wada, and Richard Frederickson (NCI-Frederick Publications
Department) for illustracions; Serguei Kozlov for help with in vitro ES
cell differentiation; and Diana Haines for histolopathological analysis.
The research was sponsored by the Center for Cancer Research, NCI, NIH.
NR 47
TC 41
Z9 41
U1 0
U2 4
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD OCT
PY 2009
VL 119
IS 10
BP 3160
EP 3171
DI 10.1172/JCI39836
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 503HA
UT WOS:000270523100048
PM 19770520
ER
PT J
AU Howard, WJ
Russell, M
Fleg, JL
Mete, M
Ali, T
Devereux, RB
Galloway, JM
Otvos, JD
Ratner, RE
Roman, MJ
Silverman, A
Umans, JG
Weissman, NJ
Wilson, C
Howard, BV
AF Howard, Wm. James
Russell, Marie
Fleg, Jerome L.
Mete, Mihriye
Ali, Tauqeer
Devereux, Richard B.
Galloway, James M.
Otvos, James D.
Ratner, Robert E.
Roman, Mary J.
Silverman, Angela
Umans, Jason G.
Weissman, Neil J.
Wilson, Charlton
Howard, Barbara V.
TI Prevention of atherosclerosis with low-density lipoprotein cholesterol
lowering-lipoprotein changes and interactions: the SANDS study
SO JOURNAL OF CLINICAL LIPIDOLOGY
LA English
DT Article
DE Atherosclerosis; Cardiovascular disease; Carotid arteries; Cholesterol;
Lipoproteins
ID CORONARY-HEART-DISEASE; METAANALYSIS; EFFICACY; TRIALS; RISK
AB BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) with statins reduces atherosclerosis. LDL and high-density lipoprotein (HDL) are commonly measured by their cholesterol content, but non-HDL cholesterol, LDL particle number (LDL-P), or total apolipoprotein B (apoB) may be better predictors of cardiovascular risk. Few studies have examined the relationship arnong lipoprotein levels and composition before and after interventions to lower LDL-C and non-HDL-C.
OBJECTIVE: We sought to measure changes in carotid artery intimal media thickness (CIMT) and lipid concentration and composition during 36 months of statin therapy.
METHODS: Analyses were conducted on 418 diabetic individuals, with complete data and no previous cardiovascular events, who were randomized to aggressive (AG) versus standard treatment for LDL-C, non-HDL-C, and systolic blood pressure as part of the Stop Atherosclerosis in Native Diabetics Study (SANDS).
RESULTS: The AG group achieved average LDL-C and non-HDL-C of 71 mg/dL and 100 mg/dL and a decrease in CIMT. No significant interactions were observed between treatment effect and initial levels of LDL-C, non-HDL-C, HDL-C, triglycerides, apoB, or LDL-P. Decreases in LDL-C (P < .005) and non-HDL-C (P < .001) were independently correlated with CIMT regression in the AG group. Changes in apoB and LDL-P demonstrated borderline correlations with CIMT regression (P = .07 and P = .09).
CONCLUSIONS: In diabetic adults with no previous cardiovascular events, treatment to current targets for lipids and systolic blood pressure reduces atherosclerosis progression and when more aggressive targets are met, atherosclerosis regresses. The aggressive targets for LDL-C and non-HDL-C appeared to be the main determinants of CIMT regression and were more predictive of this outcome than changes in LDL-P or apoB. (C) 2009 National Lipid Association. All rights reserved.
C1 [Howard, Wm. James] Washington Hosp Ctr, Lipid Clin, Washington, DC 20010 USA.
[Howard, Wm. James] Washington Hosp Ctr, Consultat Serv, Washington, DC 20010 USA.
[Russell, Marie; Wilson, Charlton] Phoenix Indian Med Ctr, Phoenix, AZ USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
[Mete, Mihriye; Ratner, Robert E.; Silverman, Angela; Umans, Jason G.; Weissman, Neil J.; Howard, Barbara V.] MedStar Res Inst, Hyattsville, MD USA.
[Ali, Tauqeer] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
[Devereux, Richard B.; Roman, Mary J.] Weill Cornell Med Coll, New York, NY USA.
[Galloway, James M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Otvos, James D.] LipoSci Inc, Raleigh, NC USA.
RP Howard, WJ (reprint author), Washington Hosp Ctr, Lipid Clin, Rm 6A-126,110 Irving St NW, Washington, DC 20010 USA.
EM wm.james.howard@medstar.net
FU NHLBI NIH HHS [U01 HL067031, U01 HL067031-01A1]
NR 17
TC 15
Z9 15
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1933-2874
J9 J CLIN LIPIDOL
JI J. Clin. Lipidol.
PD OCT
PY 2009
VL 3
IS 5
BP 322
EP 331
DI 10.1016/j.jacl.2009.09.001
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 511LF
UT WOS:000271165900004
PM 20161568
ER
PT J
AU Hickey, PW
Sutton, DA
Fothergill, AW
Rinaldi, MG
Wickes, BL
Schmidt, HJ
Walsh, TJ
AF Hickey, Patrick W.
Sutton, Deanna A.
Fothergill, Annette W.
Rinaldi, Michael G.
Wickes, Brian L.
Schmidt, Howard J.
Walsh, Thomas J.
TI Trichosporon mycotoxinivorans, a Novel Respiratory Pathogen in Patients
with Cystic Fibrosis
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID CHRONIC GRANULOMATOUS-DISEASE; OF-THE-LITERATURE; AMPHOTERICIN-B;
PULLULANS INFECTION; GENUS TRICHOSPORON; EMERGING PATHOGEN;
IDENTIFICATION; LOUBIERI; BEIGELII; THERAPY
AB This report describes the molecular epidemiology, in vitro susceptibility, colonial and microscopic morphologies, and biochemical features of Trichosporon mycotoxinivorans, a newly recognized pathogen that appears to have a propensity for patients with cystic fibrosis. The index patient died with histologically documented Trichosporon pneumonia complicating cystic fibrosis. This is also the first report of disease caused by a Trichosporon species in a nontransplant patient with cystic fibrosis. As T. mycotoxinivorans has not previously been recognized as a respiratory pathogen, the significance of its recovery from sputum samples was not initially appreciated. Genetic analysis of archived clinical samples found three additional cases of T. mycotoxinivorans infection which had previously been identified as other members of the genus. An additional isolate of T. mycotoxinivorans was identified from a clinical sample on initial testing. Three of these four cases were also patients with cystic fibrosis. All isolates had MICs at 48 h of amphotericin B of >= 1 mu g/ml and of echinocandins of >= 16 mu g/ml, but they displayed various susceptibilities to the triazoles. In summary, Trichosporon mycotoxinivorans is a newly recognized human pathogen that is associated with cystic fibrosis.
C1 [Hickey, Patrick W.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA.
[Hickey, Patrick W.] Walter Reed Army Med Ctr, Div Pediat Infect Dis, Washington, DC 20307 USA.
[Schmidt, Howard J.] Walter Reed Army Med Ctr, Div Pediat Pulmonol, Washington, DC 20307 USA.
[Sutton, Deanna A.; Fothergill, Annette W.; Rinaldi, Michael G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78229 USA.
[Wickes, Brian L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol, San Antonio, TX 78229 USA.
[Schmidt, Howard J.] Virginia Commonwealth Univ, Div Pediat Pulmonol, Richmond, VA USA.
[Walsh, Thomas J.] NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA.
RP Hickey, PW (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM phickey@usuhs.mil
FU U. S. Army Medical Research and Materiel Command, Office of
Congressionally Directed Medical Research Programs [PR054228]; National
Cancer Institute
FX B. L. W. is supported by grant PR054228 from the U. S. Army Medical
Research and Materiel Command, Office of Congressionally Directed
Medical Research Programs. This work was supported in part by the
intramural research program of the National Cancer Institute.
NR 34
TC 30
Z9 30
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD OCT
PY 2009
VL 47
IS 10
BP 3091
EP 3097
DI 10.1128/JCM.00460-09
PG 7
WC Microbiology
SC Microbiology
GA 501BC
UT WOS:000270351700003
PM 19656976
ER
PT J
AU Pfaller, MA
Diekema, DJ
Ghannoum, MA
Rex, JH
Alexander, BD
Andes, D
Brown, SD
Chaturvedi, V
Espinel-Ingroff, A
Fowler, CL
Johnson, EM
Knapp, CC
Motyl, MR
Ostrosky-Zeichner, L
Sheehan, DJ
Walsh, TJ
AF Pfaller, M. A.
Diekema, D. J.
Ghannoum, M. A.
Rex, J. H.
Alexander, B. D.
Andes, D.
Brown, S. D.
Chaturvedi, V.
Espinel-Ingroff, A.
Fowler, C. L.
Johnson, E. M.
Knapp, C. C.
Motyl, M. R.
Ostrosky-Zeichner, L.
Sheehan, D. J.
Walsh, T. J.
CA Clinical Lab Stand Inst Antifungal
TI Wild-Type MIC Distribution and Epidemiological Cutoff Values for
Aspergillus fumigatus and Three Triazoles as Determined by the Clinical
and Laboratory Standards Institute Broth Microdilution Methods
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID CELL TRANSPLANT RECIPIENTS; 14-ALPHA-STEROL DEMETHYLASE CYP51A; INVASIVE
ASPERGILLOSIS; CROSS-RESISTANCE; IN-VITRO; ITRACONAZOLE RESISTANCE;
REDUCED SUSCEPTIBILITY; AZOLE RESISTANCE; AMPHOTERICIN-B; RISK-FACTORS
AB Antifungal susceptibility testing of Aspergillus species has been standardized by both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Recent studies suggest the emergence of strains of Aspergillus fumigatus with acquired resistance to azoles. The mechanisms of resistance involve mutations in the cyp51A (sterol demethylase) gene, and patterns of azole cross-resistance have been linked to specific mutations. Studies using the EUCAST broth microdilution (BMD) method have defined wild-type (WT) MIC distributions, epidemiological cutoff values (ECVs), and cross-resistance among the azoles. We tested a collection of 637 clinical isolates of A. fumigatus for which itraconazole MICs were <= 2 mu g/ml against posaconazole and voriconazole using the CLSI BMD method. An ECV of <= 1 mu g/ml encompassed the WT population of A. fumigatus for itraconazole and voriconazole, whereas an ECV of <= 0.25 mu g/ml was established for posaconazole. Our results demonstrate that the WT distribution and ECVs for A. fumigatus and the mold-active triazoles were the same when determined by the CLSI or the EUCAST BMD method. A collection of 43 isolates for which itraconazole MICs fell outside of the ECV were used to assess cross-resistance. Cross-resistance between itraconazole and posaconazole was seen for 53.5% of the isolates, whereas cross-resistance between itraconazole and voriconazole was apparent in only 7% of the isolates. The establishment of the WT MIC distribution and ECVs for the azoles and A. fumigatus will be useful in resistance surveillance and is an important step toward the development of clinical breakpoints.
C1 [Pfaller, M. A.; Diekema, D. J.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA.
[Pfaller, M. A.] Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA.
[Ghannoum, M. A.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Rex, J. H.] AstraZeneca, Macclesfield, Cheshire, England.
[Alexander, B. D.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
[Andes, D.] Univ Wisconsin, Madison, WI 53792 USA.
[Brown, S. D.] Inst Clin Microbiol, Wilsonville, OR 97070 USA.
[Chaturvedi, V.] New York State Dept Hlth, Albany, NY 12201 USA.
[Espinel-Ingroff, A.] Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA.
[Fowler, C. L.] BioMerieux Inc, Durham, NC 27712 USA.
[Johnson, E. M.] HPA Ctr Infect, Bristol, Avon, England.
[Knapp, C. C.] Trek Diagnost Syst, Cleveland, OH 44131 USA.
[Motyl, M. R.] Merck & Co Inc, Rahway, NJ 07065 USA.
[Ostrosky-Zeichner, L.] Univ Texas Houston, Sch Med, Houston, TX 77030 USA.
[Sheehan, D. J.] Pfizer Inc, New York, NY 10017 USA.
[Walsh, T. J.] NCI, Bethesda, MD 20892 USA.
RP Pfaller, MA (reprint author), Univ Iowa, Coll Med, Dept Pathol, Div Microbiol, C606 GH, Iowa City, IA 52242 USA.
EM michael-pfaller@uiowa.edu
OI Diekema, Daniel/0000-0003-1273-0724
FU Pfizer Pharmaceuticals; Schering- Plough Research Institute
FX This study was supported in part by research and educational grants from
Pfizer Pharmaceuticals and the Schering- Plough Research Institute.
NR 50
TC 72
Z9 76
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD OCT
PY 2009
VL 47
IS 10
BP 3142
EP 3146
DI 10.1128/JCM.00940-09
PG 5
WC Microbiology
SC Microbiology
GA 501BC
UT WOS:000270351700010
PM 19692559
ER
PT J
AU Baddley, JW
Marr, KA
Andes, DR
Walsh, TJ
Kauffman, CA
Kontoyiannis, DP
Ito, JI
Balajee, SA
Pappas, PG
Moser, SA
AF Baddley, John W.
Marr, Kieren A.
Andes, David R.
Walsh, Thomas J.
Kauffman, Carol A.
Kontoyiannis, Dimitrios P.
Ito, James I.
Balajee, S. Arunmozhi
Pappas, Peter G.
Moser, Stephen A.
TI Patterns of Susceptibility of Aspergillus Isolates Recovered from
Patients Enrolled in the Transplant-Associated Infection Surveillance
Network
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID AMPHOTERICIN-B; IN-VITRO; INVASIVE ASPERGILLOSIS; CROSS-RESISTANCE;
AZOLE RESISTANCE; FUMIGATUS; ITRACONAZOLE; VORICONAZOLE; TERREUS;
RAVUCONAZOLE
AB We analyzed antifungal susceptibilities of 274 clinical Aspergillus isolates from transplant recipients with proven or probable invasive aspergillosis collected as part of the Transplant-Associated Infection Surveillance Network (TRANSNET) and examined the relationship between MIC and mortality at 6 or 12 weeks. Antifungal susceptibility testing was performed by the Clinical and Laboratory Standards Institute (CLSI) M38-A2 broth dilution method for amphotericin B (AMB), itraconazole (ITR), voriconazole (VOR), posaconazole (POS), and ravuconazole (RAV). The isolate collection included 181 Aspergillus fumigatus, 28 Aspergillus niger, 27 Aspergillus flavus, 22 Aspergillus terreus, seven Aspergillus versicolor, five Aspergillus calidoustus, and two Aspergillus nidulans isolates and two isolates identified as Aspergillus spp. Triazole susceptibilities were <= 4 mu g/ml for most isolates (POS, 97.6%; ITR, 96.3%; VOR, 95.9%; RAV, 93.5%). The triazoles were not active against the five A. calidoustus isolates, for which MICs were >= 4 mu g/ml. AMB inhibited 93.3% of isolates at an MIC of 1 mu g/ml. The exception was A. terreus, for which 15 (68%) of 22 isolates had MICs of >1 mu g/ml. One of 181 isolates of A. fumigatus showed resistance (MIC > 4 mu g/ml) to two of three azoles tested. Although there appeared to be a correlation of higher VOR MICs with increased mortality at 6 weeks, the relationship was not statistically significant (R(2) = 0.61; P = 0.065). Significant relationships of in vitro MIC to all-cause mortality at 6 and 12 weeks for VOR or AMB were not found.
C1 [Baddley, John W.; Pappas, Peter G.] Univ Alabama, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA.
[Baddley, John W.] Birmingham Vet Affairs Med Ctr, Infect Dis Sect, Dept Med, Birmingham, AL USA.
[Marr, Kieren A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
[Andes, David R.] Univ Wisconsin, Dept Med, Div Infect Dis, Madison, WI USA.
[Walsh, Thomas J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Kauffman, Carol A.] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Kauffman, Carol A.] Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA.
[Ito, James I.] City Hope Natl Med Ctr, Dept Med, Div Infect Dis, Duarte, CA 91010 USA.
[Balajee, S. Arunmozhi] Ctr Dis Control & Prevent, Div Mycot Dis, Atlanta, GA USA.
[Moser, Stephen A.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA.
RP Baddley, JW (reprint author), Univ Alabama, Dept Med, Div Infect Dis, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA.
EM jbaddley@uab.edu
RI Moser, Stephen/A-1168-2008
FU NIH [K23AI064613]
FX J.W.B. is sponsored in part by NIH grant K23AI064613.
NR 30
TC 86
Z9 88
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD OCT
PY 2009
VL 47
IS 10
BP 3271
EP 3275
DI 10.1128/JCM.00854-09
PG 5
WC Microbiology
SC Microbiology
GA 501BC
UT WOS:000270351700029
PM 19692558
ER
PT J
AU Castle, PE
Sadorra, M
Lau, T
Aldrich, C
Garcia, FAR
Kornegay, J
AF Castle, Philip E.
Sadorra, Mark
Lau, Tiffany
Aldrich, Carrie
Garcia, Francisco A. R.
Kornegay, Janet
TI Evaluation of a Prototype Real-Time PCR Assay for Carcinogenic Human
Papillomavirus (HPV) Detection and Simultaneous HPV Genotype 16 (HPV16)
and HPV18 Genotyping
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID CERVICAL INTRAEPITHELIAL NEOPLASIA; LINEAR-ARRAY; SCREENING-TESTS;
CANCER; DNA; WOMEN; PRECANCER; RISK; CYTOLOGY; HYBRID-CAPTURE-2
AB Results from a prototype real-time PCR assay that separately detected human papillomavirus genotype 16 (HPV16), HPV18, and 12 other carcinogenic HPV genotypes in aggregate (cobas 4800 HPV test) and results from a PCR assay that detects 37 HPV genotypes individually (Linear Array) were compared using a convenience sample of cervical specimens (n = 531). The percentage of total agreement between the two assays was 94.7% (95% confidence interval, 92.5 to 96.5%). The Linear Array test was more likely than cobas 4800 HPV test to test positive for the 12 other carcinogenic HPV genotypes among women without evidence of cervical disease (P = 0.004).
C1 [Castle, Philip E.] NCI, Div Canc Epidemiol, DHHS, NIH, Bethesda, MD 20892 USA.
[Sadorra, Mark; Lau, Tiffany; Aldrich, Carrie; Kornegay, Janet] Roche Mol Syst, Alameda, CA USA.
[Garcia, Francisco A. R.] Univ Arizona, Hlth Sci Ctr, Tucson, AZ USA.
RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 5030,MSC 7234, Bethesda, MD 20892 USA.
EM castlep@mail.nih.gov
FU NIH/NCI
FX This work was supported in part by the intramural research program of
the NIH/NCI.
NR 27
TC 29
Z9 33
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD OCT
PY 2009
VL 47
IS 10
BP 3344
EP 3347
DI 10.1128/JCM.00725-09
PG 4
WC Microbiology
SC Microbiology
GA 501BC
UT WOS:000270351700043
PM 19675214
ER
PT J
AU Gianni, L
Norton, L
Wolmark, N
Suter, TM
Bonadonna, G
Hortobagyi, GN
AF Gianni, Luca
Norton, Larry
Wolmark, Norman
Suter, Thomas M.
Bonadonna, Gianni
Hortobagyi, Gabriel N.
TI Role of Anthracyclines in the Treatment of Early Breast Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID TOPOISOMERASE-II-ALPHA; DOXORUBICIN PLUS CYCLOPHOSPHAMIDE; TRIAL
COMPARING DOXORUBICIN; DENSE SEQUENTIAL CHEMOTHERAPY; MAMMARY
EPITHELIAL-CELLS; SURGICAL ADJUVANT BREAST; CONGESTIVE HEART-FAILURE;
LEUKEMIA GROUP-B; NCIC CTG MA.5; RANDOMIZED-TRIAL
AB Purpose To review data relating to anthracyclines in the adjuvant treatment of early breast cancer.
Design This is a report from a seminar in which the future of anthracyclines in the adjuvant treatment of breast cancer was considered. In particular, the question of whether anthracyclines should now be discarded and replaced by taxanes was addressed.
Results Accumulating data from large randomized trials indicate that genetic markers may have a role in predicting sensitivity to cytotoxic drugs. However, no reliable, validated test is available for predicting sensitivity to anthracyclines in particular. Topoisomerase II alpha amplification and/or deletion, especially in conjunction with human epidermal growth factor receptor-2 amplification, has been proposed to fulfill this role but more data are needed. Currently, only one published trial has shown that a taxane-based regimen may be superior to an anthracycline-based regimen, but several trials indicate that combinations including both anthracyclines and taxanes may be better still. Further studies aimed at optimizing anthracyclines and taxanes in combination, and integrating biologic agents, seem to be the way forward. There is no validated test that can determine whether anthracyclines can be of greater benefit than other agents for individual patients.
Conclusion Anthracyclines have been extensively tested in clinical trials spanning several decades; currently, there are insufficient data to recommend replacing them in the adjuvant treatment of breast cancer.
C1 [Hortobagyi, Gabriel N.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA.
Fdn Michelangelo, Milan, Italy.
Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
Swiss Cardiovasc Ctr, Bern, Switzerland.
RP Hortobagyi, GN (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, 1515 Holcombe Blvd,Unit 1354, Houston, TX 77030 USA.
EM ghortoba@mdanderson.org
OI Norton, Larry/0000-0003-3701-9250
NR 100
TC 52
Z9 53
U1 1
U2 8
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD OCT 1
PY 2009
VL 27
IS 28
BP 4798
EP 4808
DI 10.1200/JCO.2008.21.4791
PG 11
WC Oncology
SC Oncology
GA 500LS
UT WOS:000270304100027
PM 19687331
ER
PT J
AU Murty, VP
Sambataro, F
Das, S
Tan, HY
Callicott, JH
Goldberg, TE
Meyer-Lindenberg, A
Weinberger, DR
Mattay, VS
AF Murty, Vishnu P.
Sambataro, Fabio
Das, Saumitra
Tan, Hao-Yang
Callicott, Joseph H.
Goldberg, Terry E.
Meyer-Lindenberg, Andreas
Weinberger, Daniel R.
Mattay, Venkata S.
TI Age-related Alterations in Simple Declarative Memory and the Effect of
Negative Stimulus Valence
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID MILD COGNITIVE IMPAIRMENT; EVENT-RELATED FMRI; EMOTIONAL MEMORY;
FUNCTIONAL CONNECTIVITY; RECOGNITION MEMORY; EPISODIC RETRIEVAL;
ALZHEIMERS-DISEASE; NEURAL MECHANISMS; WORKING-MEMORY; OLDER-ADULTS
AB Healthy aging has been shown to modulate the neural circuitry underlying simple declarative memory; however, the functional impact of negative stimulus valence on these changes has not been fully investigated. Using BOLD fMRI, we explored the effects of aging on behavioral performance, neural activity, and functional coupling during the encoding and retrieval of novel aversive and neutral scenes. Behaviorally, there was a main effect of valence with better recognition performance for aversive greater than neutral stimuli in both age groups. There was also a main effect of age with better recognition performance in younger participants compared to older participants. At the imaging level, there was a main effect of valence with increased activity in the medial-temporal lobe ( amygdala and hippocampus) during both encoding and retrieval of aversive relative to neutral stimuli. There was also a main effect of age with older participants showing decreased engagement of medial-temporal lobe structures and increased engagement of prefrontal structures during both encoding and retrieval sessions. Interestingly, older participants presented with relatively decreased amygdalar-hippocampal coupling and increased amygdalar prefrontal coupling when compared to younger participants. Furthermore, older participants showed increased activation in prefrontal cortices and decreased activation in the amygdala when contrasting the retrieval of aversive and neutral scenes. These results suggest that although normal aging is associated with a decline in declarative memory with alterations in the neural activity and connectivity of brain regions underlying simple declarative memory, memory for aversive stimuli is relatively better preserved than for neutral stimuli, possibly through greater compensatory prefrontal cortical activity.
C1 [Mattay, Venkata S.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Goldberg, Terry E.] Hillside Zucker Hosp, Glen Oaks, NJ USA.
[Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, D-6800 Mannheim, Germany.
RP Mattay, VS (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
EM vsm@mail.nih.gov
RI Sambataro, Fabio/E-3426-2010; Callicott, Joseph/C-9102-2009;
Meyer-Lindenberg, Andreas/H-1076-2011
OI Sambataro, Fabio/0000-0003-2102-416X; Callicott,
Joseph/0000-0003-1298-3334; Meyer-Lindenberg,
Andreas/0000-0001-5619-1123
FU Intramural NIH HHS [Z01 MH002734-12]
NR 57
TC 35
Z9 35
U1 2
U2 5
PU M I T PRESS
PI CAMBRIDGE
PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA
SN 0898-929X
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD OCT
PY 2009
VL 21
IS 10
BP 1920
EP 1933
DI 10.1162/jocn.2009.21130
PG 14
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 505ZK
UT WOS:000270741100006
PM 18823239
ER
PT J
AU Carroll, KM
Martino, S
Ball, SA
Nich, C
Frankforter, T
Anez, LM
Paris, M
Suarez-Morales, L
Szapocznik, J
Miller, WR
Rosa, C
Matthews, J
Farentinos, C
AF Carroll, Kathleen M.
Martino, Steve
Ball, Samuel A.
Nich, Charla
Frankforter, Tami
Anez, Luis M.
Paris, Manuel
Suarez-Morales, Lourdes
Szapocznik, Jose
Miller, William R.
Rosa, Carmen
Matthews, Julie
Farentinos, Chris
TI A Multisite Randomized Effectiveness Trial of Motivational Enhancement
Therapy for Spanish-Speaking Substance Users
SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE motivational interviewing; randomized clinical trials; Spanish-speaking;
drug dependence
ID DRUG-ABUSE; ETHNIC-MINORITIES; DISPARITIES; HISPANICS; SERVICES; ISSUES
AB Hispanic individuals are underrepresented in clinical and research populations and are often excluded from clinical trials in the United States. Hence, there are few data on the effectiveness of most empirically validated therapies for Hispanic substance users. The authors conducted a multisite randomized trial comparing the effectiveness of 3 individual sessions of motivational enhancement therapy with that of 3 individual sessions of counseling as usual on treatment retention and frequency of substance use; all assessment and treatment sessions were conducted in Spanish among 405 individuals seeking treatment for any type of current substance use. Treatment exposure was good, with 66% of participants completing all 3 protocol sessions. Although both interventions resulted in reductions in substance use during the 4-week therapy phase, there were no significant Treatment Condition X Time interactions nor Site X Treatment Condition interactions. Results suggest that the individual treatments delivered in Spanish were both attractive to and effective with this heterogeneous group of Hispanic adults, but the differential effectiveness of motivational enhancement therapy may be limited to those whose primary substance use problem is alcohol and may be fairly modest in magnitude.
C1 [Carroll, Kathleen M.] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06519 USA.
[Suarez-Morales, Lourdes; Szapocznik, Jose] Univ Miami, Dept Psychiat & Behav Studies, Coral Gables, FL 33124 USA.
[Miller, William R.] Univ New Mexico, Dept Psychiat & Psychol, Albuquerque, NM 87131 USA.
[Rosa, Carmen] Natl Inst Drug Abuse, Bethesda, MD 20892 USA.
[Matthews, Julie] Adv Behav Hlth, Middletown, CT USA.
[Farentinos, Chris] Changepoint Inc, Portland, OR USA.
RP Carroll, KM (reprint author), Yale Univ, Sch Med, Dept Psychiat, 950 Campbell Ave,151D, West Haven, CT 06519 USA.
EM kathleen.carroll@yale.edu
OI Carroll, Kathleen/0000-0003-3263-3374
FU NIDA NIH HHS [U10 DA015833, K05 DA000457, K05 DA000457-08, K05
DA000457-09, K05 DA000457-10, U10 DA013035, U10 DA013035-01A1, U10
DA013036, U10 DA013036-04, U10 DA013038, U10 DA013038-01, U10 DA013716,
U10 DA013716-02, U10 DA013720, U10 DA013720-01, U10 DA015833-01, U10
DA13035, U10 DA13036, U10 DA13038, U10 DA13716, U10 DA13720]
NR 17
TC 55
Z9 56
U1 0
U2 8
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-006X
J9 J CONSULT CLIN PSYCH
JI J. Consult. Clin. Psychol.
PD OCT
PY 2009
VL 77
IS 5
BP 993
EP 999
DI 10.1037/a0016489
PG 7
WC Psychology, Clinical
SC Psychology
GA 503TX
UT WOS:000270564400019
PM 19803579
ER
PT J
AU Valenti, G
Ferrucci, L
Lauretani, F
Ceresini, G
Bandinelli, S
Luci, M
Ceda, G
Maggio, M
Schwartz, RS
AF Valenti, G.
Ferrucci, L.
Lauretani, F.
Ceresini, G.
Bandinelli, S.
Luci, M.
Ceda, G.
Maggio, M.
Schwartz, R. S.
TI Dehydroepiandrosterone sulfate and cognitive function in the elderly:
The InCHIANTI Study
SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
LA English
DT Article
DE Cognitive function; DHEAS; elderly
ID MINI-MENTAL-STATE; DECLARATIVE MEMORY; OLDER MEN; CORTISOL; DHEA; MICE;
WOMEN; RECEPTOR; STRESS; AGE
AB DHEA and its sulfate derivative (DHEAS) decline with age. The decline in DHEAS levels has been associated with many physiological impairments in older persons including cognitive dysfunction. However, data regarding the possible relationship between DHEAS and cognition are scant. We investigated whether DHEAS levels are associated with presence and development of lower cognitive function measured by the Mini Mental State Examination (MMSE) in older men and women. One thousand and thirty-four residents aged >= 65 yr of the InCHIANTI Study with data available on DHEAS and MMSE were randomly selected. MMSE was administered at baseline and 3 yr later. Among these, 841 completed a 3-yr follow-up. Parsimonious models obtained by backward selection from initial fully-adjusted models were used to identify independent factors associated with MMSE and DHEAS. The final analysis was performed in 755 participants (410 men and 345 women) with MMSE score >= 21. A significant age-related decline of both DHEAS levels (p<0.001) and MMSE score (p<0.001) was found over the 3-yr follow-up. At enrolment, DHEAS was significantly and positively associated with MMSE score, independently of age and other potential confounders (beta +/- SE 0.003 +/- 0.001, p<0.005). Low baseline DHEAS levels were predictive of larger decline of MMSE and this relationship was significant after adjusting for covariates (beta +/- SE -0.004 +/- 0.002, p<0.03). Our data show a significant and positive association between DHEAS and cognitive function, assessed by MMSE test. Low DHEAS levels predict accelerated decline in MMSE score during the 3-yr follow-up period. (J. Endocrinol. Invest. 32: 766-772, 2009) (C) 2009, Editrice Kurtis
C1 [Valenti, G.; Ceresini, G.; Luci, M.; Ceda, G.; Maggio, M.] Univ Parma, Dept Internal Med & Med Sci, Sect Geriatr, I-43100 Parma, Italy.
[Ferrucci, L.] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
[Lauretani, F.] Univ Hosp Parma, Geriatr Rehabil Dept, Parma, Italy.
[Bandinelli, S.] AUSL 10 Florence, Geriatr Unit, Florence, Italy.
[Schwartz, R. S.] Univ Colorado, Div Geriatr Med, Denver, CO 80202 USA.
RP Valenti, G (reprint author), Azienda Osped Univ, Clin Geriatr, Via Gramsci 14, I-43100 Parma, Italy.
EM giorgiovalenti@libero.it
RI Lauretani, Fulvio/K-5115-2016;
OI Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian
Paolo/0000-0002-9648-8295
FU Italian Ministry of Health [ICS 110.1/RS97.71]; U.S. National Institute
on Aging [N01-AG-916413, N01-AG-821336, 263 MD 9164 13, 263 MD 821 336]
FX The InCHIANTI Study was supported as a "targeted project" (ICS
110.1/RS97.71) by the Italian Ministry of Health and in part by the U.S.
National Institute on Aging (Contracts N01-AG-916413 and N01-AG-821336)
and by the Intramural Research Program of the U.S. National Institute on
Aging (Contracts 263 MD 9164 13 and 263 MD 821336).
NR 52
TC 17
Z9 17
U1 0
U2 3
PU EDITRICE KURTIS S R L
PI MILAN
PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY
SN 0391-4097
J9 J ENDOCRINOL INVEST
JI J. Endocrinol. Invest.
PD OCT
PY 2009
VL 32
IS 9
BP 766
EP 772
DI 10.3275/6438
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 537RX
UT WOS:000273132600009
PM 19620821
ER
PT J
AU Ganiban, JM
Ulbricht, JA
Spotts, EL
Lichtenstein, P
Reiss, D
Hansson, K
Neiderhiser, JA
AF Ganiban, Jody M.
Ulbricht, Jennifer A.
Spotts, Erica L.
Lichtenstein, Paul
Reiss, David
Hansson, Kjell
Neiderhiser, Jenae A.
TI Understanding the Role of Personality in Explaining Associations Between
Marital Quality and Parenting
SO JOURNAL OF FAMILY PSYCHOLOGY
LA English
DT Article
DE marriage; parenting; personality; twins
ID GENETIC-ANALYSIS; ENVIRONMENTAL-INFLUENCES; TEMPERAMENT; SATISFACTION;
CONFLICT; ADJUSTMENT; STABILITY; FAMILIES; BEHAVIOR; MODEL
AB Analyses assessed the degrees to which personality accounts for associations between marital quality and parenting and mediates genetic contributions to these relationships. Participants included 318 male and 544 female same-sex twin pairs from the Twin and Offspring Study in Sweden. All twins completed self-report measures of marital quality and personality (anxiousness, aggression, sociability). Composite measures of parent negativity and warmth were derived from the twins' and their adolescent children's ratings of the twins' disciplinary styles and the emotional tone of the parent-child relationship. Observational ratings of marital quality and parenting were also obtained for a subset of twins. Personality characteristics explained 33% to 42% of the covariance between reported marital quality and parenting and 26% to 28% of the covariance between observed marital quality and parenting. For both sets of analyses, personality accounted for more than half of the genetic contributions to covariance between marital quality and parenting. Results indicate that personality significantly contributes to associations between marital quality and parenting and that personality is an important path through which genetic factors contribute to family relationships.
C1 [Ganiban, Jody M.; Ulbricht, Jennifer A.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA.
[Spotts, Erica L.] NIA, Behav & Social Res Program, Bethesda, MD 20892 USA.
[Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Reiss, David] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA.
[Hansson, Kjell] Lund Univ, Sch Social Work, Lund, Sweden.
[Neiderhiser, Jenae A.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA.
RP Ganiban, JM (reprint author), George Washington Univ, Dept Psychol, 2121 1st St NW, Washington, DC 20052 USA.
EM ganiban@gwu.edu
OI lichtenstein, paul/0000-0003-3037-5287
FU NIMH NIH HHS [R01MH54601, R01 MH054610-04, R01 MH054610]
NR 67
TC 13
Z9 13
U1 2
U2 7
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0893-3200
J9 J FAM PSYCHOL
JI J. Fam. Psychol.
PD OCT
PY 2009
VL 23
IS 5
BP 646
EP 660
DI 10.1037/a0016091
PG 15
WC Psychology, Clinical; Family Studies
SC Psychology; Family Studies
GA 506SL
UT WOS:000270796200004
PM 19803601
ER
PT J
AU Lee, YC
Cook, M
Bhatia, S
Chow, WH
Goto, H
Lin, JT
Li, YQ
Rhee, PL
Sharma, P
Sung, JJ
Wong, J
Wu, JCY
Ho, KY
AF Lee, Y. C.
Cook, M.
Bhatia, S.
Chow, W. H.
Goto, H.
Lin, J. T.
Li, Y. Q.
Rhee, P. L.
Sharma, P.
Sung, J. J.
Wong, J.
Wu, J. C. Y.
Ho, K. Y.
CA ASIAN BARRETT'S CONSORTIUM
TI Inter-observer agreement in the diagnosis of endoscopically suspected
Barrett's esophagus: an Asian multinational study
SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Meeting Abstract
C1 [Lee, Y. C.; Lin, J. T.] Natl Taiwan Univ, Dept Internal Med, Taipei, Taiwan.
[Cook, M.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Chow, W. H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Goto, H.] Nagoya Univ, Dept Gastroenterol, Grad Sch Med, Nagoya, Aichi 4648601, Japan.
[Lin, J. T.] I Shou Univ, Kaohsiung Cty, Taiwan.
[Lin, J. T.] E DA Hosp, Dept Internal Med, Kaohsiung Cty, Taiwan.
[Li, Y. Q.] Shandong Univ, Dept Gastroenterol, Qilu Hosp, Jinan, Peoples R China.
[Rhee, P. L.] Sungkyunkwan Univ, Dept Med, Sch Med, Samsung Med Ctr, Seoul, South Korea.
[Sharma, P.] Univ Kansas, Sch Med, Div Gastroenterol & Hepatol, Lawrence, KS 66045 USA.
[Sung, J. J.; Wu, J. C. Y.] Chinese Univ Hong Kong, Dept Med & Therapeut, Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China.
[Sung, J. J.; Wu, J. C. Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore.
RI Wu, Justin/N-6916-2015
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0815-9319
J9 J GASTROEN HEPATOL
JI J. Gastroenterol. Hepatol.
PD OCT
PY 2009
VL 24
BP A121
EP A121
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 497QI
UT WOS:000270075200321
ER
PT J
AU Rastgou, M
Habibi, MK
Izadpanah, K
Masenga, V
Milne, RG
Wolf, YI
Koonin, EV
Turina, M
AF Rastgou, M.
Habibi, M. K.
Izadpanah, K.
Masenga, V.
Milne, R. G.
Wolf, Y. I.
Koonin, E. V.
Turina, M.
TI Molecular characterization of the plant virus genus Ourmiavirus and
evidence of inter-kingdom reassortment of viral genome segments as its
possible route of origin
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID DOUBLE-STRANDED RNAS; MOVEMENT PROTEINS; MAXIMUM-LIKELIHOOD;
MELON-VIRUS; EVOLUTION; DISEASE; CHERRY; RANUNCULUS; ALGORITHM; SEQUENCE
AB Ourmia melon virus (OuMV), Epirus cherry virus (EpCV) and Cassava virus C (CsVC) are three species placed in the genus Ourmiavirus. We cloned and sequenced their RNA genomes. The sizes of the three genomic RNAs of OuMV, the type member of the genus, were 2814, 1064 and 974 nt and each had one open reading frame. RNA1 potentially encoded a 97.5 kDa protein carrying the GDD motif typical of RNA-dependent RNA polymerases (RdRps). The putative RdRps of ourmiaviruses are distantly related to known viral RdRps, with the closest similarity and phylogenetic affinity observed with fungal viruses of the genus Narnaviridae. RNA2 encoded a 31.6 kDa. protein which, expressed in bacteria as a His-tag fusion protein and in plants through agroinfiltration, reacted specifically with antibodies made against tubular structures found in the cytoplasm. The ORF2 product is significantly similar to movement proteins of the genus Tombusviridae, and phylogenetic analysis supported this evolutionary relationship. The product of OuMV ORF3 is a 23.8 kDa protein. This protein was also expressed in bacteria and plants, and reacted specifically with antisera. against the OuMV coat protein. The sequence of the ORF3 protein showed limited but significant similarity to capsid proteins of several plant and animal viruses, although phylogenetic analysis failed to reveal its most likely origin. Taken together, these results indicate that ourmiaviruses comprise a unique group of plant viruses that might have evolved by reassortment of genomic segments of RNA viruses infecting hosts belonging to different eukaryotic kingdoms, in particular, fungi and plants.
C1 [Masenga, V.; Milne, R. G.; Turina, M.] CNR, Ist Virol Vegetale, I-10135 Turin, Italy.
[Wolf, Y. I.; Koonin, E. V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Rastgou, M.; Habibi, M. K.] Univ Tehran, Dept Plant Protect, Fac Hort Sci & Plant Protect, Coll Agr & Nat Resources, Karaj, Iran.
[Rastgou, M.] Urmia Univ, Dept Plant Protect, Coll Agr, Orumiyeh, Iran.
[Izadpanah, K.] Shiraz Univ, Plant Virol Res Ctr, Shiraz, Iran.
RP Turina, M (reprint author), CNR, Ist Virol Vegetale, Str Cacce 73, I-10135 Turin, Italy.
EM m.turina@ivv.cnr.it
RI Turina, Massimo/B-7550-2015
OI Turina, Massimo/0000-0002-9659-9470
FU Iran Ministry of Science, Research and Technology
FX We thank Maud Swanson (formerly Aiton), Scottish Crop Research
Institute, for kindly providing isolates of CsVC, and Caterina Perrone
for skilful technical assistance in the greenhouse. M. R. was recipient
of a scholarship from the Iran Ministry of Science, Research and
Technology, as part of her PhD project.
NR 51
TC 29
Z9 33
U1 1
U2 10
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD OCT
PY 2009
VL 90
BP 2525
EP 2535
DI 10.1099/vir.0.013086-0
PG 11
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 502ZL
UT WOS:000270499700026
PM 19535502
ER
PT J
AU Hossain, MM
Chowdhury, NA
Shirin, M
Saha, SK
Miller-Bell, M
Edwards, D
Aranda, J
Coffey, P
Darmstadt, GL
AF Hossain, M. Monir
Chowdhury, Nazma A.
Shirin, Mahfuza
Saha, Samir K.
Miller-Bell, Mary
Edwards, David
Aranda, Jacob
Coffey, Patricia
Darmstadt, Gary L.
TI Simplified Dosing of Gentamicin for Treatment of Sepsis in Bangladeshi
Neonates
SO JOURNAL OF HEALTH POPULATION AND NUTRITION
LA English
DT Article
DE Aminoglycoside; Antibiotics; Gentamicin; Infection; Newborns;
Observational studies; Pharmacokinetics; Prospective studies; Sepsis;
Bangladesh
ID ANTIBACTERIAL ACTIVITY; DEVELOPING-COUNTRIES; RURAL BANGLADESH;
CONTROLLED-TRIAL; PHARMACOKINETICS; INFANTS; AMINOGLYCOSIDES;
STRATEGIES; INFECTION; TOXICITY
AB Extended-interval dosing of gentamicin has several advantages over conventional multiple-daily dosing for the treatment of sepsis. The study was conducted to evaluate the pharmacokinetics of gentamicin for the treatment of neonatal sepsis in predetermined doses at 24- or 48-hour intervals, according to weight category, and to develop a simplified protocol for use in peripheral healthcare settings in developing countries. This prospective observational study was conducted among 59 neonates admitted to the Special Care Nursery at Dhaka Shishu Hospital, Bangladesh, with suspected sepsis and treated with antibiotics, including gentamicin. Intravenous dosing of gentamicin according to weight category was: 10 mg every 48 hours if the infant weighed < 2,000 g (n=23), 10 mg every 24 hours if the infant weighed 2,000-2,249 g (n=12), or 13.5 mg every 24 hours if the infant weighed 2,500-3,000 g (n=24). Peak and trough concentrations of gentamicin and the presence of signs of nephrotoxicity and ototoxicity were determined. The mean +/- standard deviation peak concentration of gentamicin was 12.3 +/- 3.7 mu g/mL in infants weighing < 2,000 g, 9.6 +/- 3.1 mu g/mL in infants 2,000-2,249 g, and 10.0 +/- 3.4 mu g/mL in infants 2,500-3,000 g. Initial peak concentration of gentamicin was > 12 mu g/mL in 28.8% and initial trough concentration was > 2 mu g/mL in 6.8% of the subjects. No signs of nephrotoxicity or ototoxicity were detected. Favourable pharmacokinetic parameters found with the simplified dosing regimen suggest that it is safe for the treatment of neonatal sepsis.
C1 [Hossain, M. Monir; Chowdhury, Nazma A.; Shirin, Mahfuza] Dhaka Shishu Childrens Hosp, Bangladesh Inst Child Hlth, Dept Neonatol, Dhaka 1207, Bangladesh.
[Saha, Samir K.] Dhaka Shishu Childrens Hosp, Bangladesh Inst Child Hlth, Dept Microbiol, Dhaka 1207, Bangladesh.
[Miller-Bell, Mary] Duke Univ, Dept Pharmacol, Durham, NC USA.
[Edwards, David] Wayne State Univ, Dept Pharm Practice, Detroit, MI USA.
[Edwards, David; Aranda, Jacob] Wayne State Univ, Childrens Hosp Michigan, NIH, NICHD,Pediat Pharmacol Res Unit Network, Detroit, MI USA.
[Coffey, Patricia] PATH, Seattle, WA USA.
[Darmstadt, Gary L.] Johns Hopkins Univ, Bloomberg Sch Med, Dept Int Hlth, Int Ctr Advancing Neonatal Hlth, Baltimore, MD 21205 USA.
RP Darmstadt, GL (reprint author), Johns Hopkins Univ, Bloomberg Sch Med, Dept Int Hlth E8153, Int Ctr Advancing Neonatal Hlth, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM gdarmsta@jhsph.edu
FU Bill & Melinda Gates Foundation; United States Agency for International
Development (USAID) [GPH-A-0001-00005]
FX This study was supported by Save the Children-USA through a grant from
the Bill & Melinda Gates Foundation and by PATH. PATH's contribution to
this study was made possible through support provided by the Office of
Health, United States Agency for International Development (USAID) under
the HealthTech Cooperative Agreement No. GPH-A-0001-00005. The opinions
expressed herein are those of the authors and do not necessarily reflect
the views of USAID. The authors thank Additional Professor Vinod Paul of
All-India Institute of Medical Sciences, Delhi, for serving on the Data
and Safety Monitoring Board. The authors also thankfully acknowledge Dr.
Shaheen Akter and Dr. Manifa Afreen of Dhaka Shishu Hospital for their
technical assistance.
NR 29
TC 8
Z9 8
U1 1
U2 2
PU ICDDR B
PI DHAKA
PA MOHAKHALI, 1212 DHAKA, BANGLADESH
SN 1606-0997
EI 2072-1315
J9 J HEALTH POPUL NUTR
JI J. Heatlh Popul. Nutr.
PD OCT
PY 2009
VL 27
IS 5
BP 640
EP 645
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 514LF
UT WOS:000271395500006
PM 19902799
ER
PT J
AU Maximova, OA
Faucette, LJ
Ward, JM
Murphy, BR
Pletnev, AG
AF Maximova, Olga A.
Faucette, Lawrence J.
Ward, Jerrold M.
Murphy, Brian R.
Pletnev, Alexander G.
TI Cellular Inflammatory Response to Flaviviruses in the Central Nervous
System of a Primate Host
SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
LA English
DT Article
DE flaviviruses; non-human primates; central nervous system; cellular
inflammatory response; immunohistochemistry; digital whole-tissue
section slides; computerized morphometric analysis
ID WEST-NILE-VIRUS; TICK-BORNE ENCEPHALITIS; JAPANESE ENCEPHALITIS;
INTERFERON-GAMMA; IMMUNE-RESPONSES; T-CELLS; INFECTION; BRAIN;
NEUROVIRULENCE; PROTECTION
AB Flaviviruses such as tick-borne encephalitis virus, Japanese encephalitis virus, West Nile virus, and St. Louis encephalitis virus are important neurotropic human pathogens, typically causing a devastating and often fatal neuroinfection. Flaviviruses induce neuroinflammation with typical features of viral encephalitides, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. Development of safe and effective live-virus vaccines against neurotropic flavivirus infections demands a detailed knowledge of their neuropathogenesis in a primate host that is evolutionarily close to humans. Here, we used computerized morphometric analysis to quantitatively assess the cellular inflammatory responses in the central nervous system (CNS) of rhesus monkeys infected with three antigenically divergent attenuated flaviviruses. The kinetics, spatial pattern, and magnitude of microglial activation, trafficking of T and B cells, and changes in T cell subsets within the CNS define unique phenotypic signatures for each of the three viruses. Our results provide a benchmark for investigation of cellular inflammatory responses induced by attenuated flaviviruses in the CNS of primate hosts and provide insight into the neuropathogenesis of flavivirus encephalitis that might guide the development of safe and effective live-virus vaccines. (J Histochem Cytochem 57:973-989, 2009)
C1 [Maximova, Olga A.; Murphy, Brian R.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Faucette, Lawrence J.; Ward, Jerrold M.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Maximova, OA (reprint author), NIAID, Infect Dis Lab, NIH, 33 N Dr,Room 3W10A,MSC 3203, Bethesda, MD 20892 USA.
EM maximovao@niaid.nih.gov; apletnev@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases (NIAID)
FX This work was supported by funds provided by the National Institute of
Allergy and Infectious Diseases (NIAID) Intramural Research Program.
NR 37
TC 10
Z9 11
U1 0
U2 3
PU HISTOCHEMICAL SOC INC
PI SEATTLE
PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA
SN 0022-1554
J9 J HISTOCHEM CYTOCHEM
JI J. Histochem. Cytochem.
PD OCT
PY 2009
VL 57
IS 10
BP 973
EP 989
DI 10.1369/jhc.2009.954180
PG 17
WC Cell Biology
SC Cell Biology
GA 499TT
UT WOS:000270249500008
PM 19581627
ER
PT J
AU Liu, XP
Zuo, YM
Zhang, WN
Yang, DG
Xiong, CY
Zhang, XZ
AF Liu, Xiuping
Zuo, Yumei
Zhang, Weina
Yang, Deguang
Xiong, Changyun
Zhang, Xiaozhou
TI Expression of Interleukin-15 and Its Receptor on the Surface of
Stimulated Human Umbilical Vein Endothelial Cells
SO JOURNAL OF HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY-MEDICAL
SCIENCES
LA English
DT Article
DE endothelial cells; interleukin-15; interleukin-15 receptor; cytokines
ID IL-15/IL-15R-ALPHA INTRACELLULAR TRAFFICKING; ALPHA-CHAIN; IL-2
RECEPTOR; HUMAN-DISEASE; KILLER-CELLS; GAMMA-CHAIN; TNF-ALPHA; IN-VITRO;
IL-15R-ALPHA; APOPTOSIS
AB Human interleukin-15 (hIL-15) is an important cytokine to activate endothelial cells and can be regulated by many other cytokines. The aim of this study is to examine the ability of interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) to induce the production of human interleukin-15 (hIL-15) and IL-15 receptor (IL-15R alpha) by human umbilical vein endothelial cells (HUVECs). The data are summarized as follows: 1. Northern blot revealed that IL-15 mRNA was up-regulated by IFN-gamma and TNF-alpha. 2. Intracellular IL-15 protein was visualized by fluorescence microscopy, whereas the expression of IL-15 on the surface of HUVECs was detected by fluorescence activated cell sorting (FACS), and no detectable IL-15 in the medium was verified by ELISA. 3. IL-15R alpha was detected on the surface of HUVECs by FACS after IFN-gamma and TNF-alpha stimulation, whereas Western blotting revealed that the elevated expression on surface IL-15R alpha was not due to the increased protein expression. The conclusion demonstrated from our results is that IFN-gamma and TNF-alpha play an important role in regulating the expression of IL-15 and IL-15R alpha on the surface of HUVECs.
C1 [Zhang, Xiaozhou] Huazhong Univ Sci & Technol, Xianggan Med Coll Hosp, Xiaogan 432000, Peoples R China.
[Liu, Xiuping] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China.
[Liu, Xiuping] Hubei Vocat & Tech Coll, Xiaogan 432000, Peoples R China.
[Zuo, Yumei] Third Mil Med Univ, Dept Cardiol, Southwest Hosp, Chongqing 400038, Peoples R China.
[Zhang, Weina] Huazhong Univ Sci & Technol, Minist Educ,Minist Hlth, Inst Organ Transplantat,Tongji Med Coll, Tongji Hosp,Key Lab Organ Transplantat, Wuhan 430030, Peoples R China.
[Yang, Deguang] NE Agr Univ, Coll Agr, Harbin 150030, Peoples R China.
[Xiong, Changyun] NCI, Mol Targets Dev Program, NIH, Frederick, MD 21702 USA.
RP Zhang, XZ (reprint author), Huazhong Univ Sci & Technol, Xianggan Med Coll Hosp, Xiaogan 432000, Peoples R China.
EM Liuxiuping2006@gmail.com
FU NIH of USA [HL42550]
FX This project was supported by NIH grant HL42550 of USA.
NR 35
TC 2
Z9 4
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1672-0733
J9 J HUAZHONG U SCI-MED
JI J. Huazhong Univ. Sci. Tech.-Med.
PD OCT
PY 2009
VL 29
IS 5
BP 527
EP 534
DI 10.1007/s11596-009-0501-x
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 505HA
UT WOS:000270681700001
PM 19821081
ER
PT J
AU Peter, I
Kelley-Hedgepeth, A
Huggins, GS
Housman, DE
Mendelsohn, ME
Vita, JA
Vasan, RS
Levy, D
Benjamin, EJ
Mitchell, GF
AF Peter, I.
Kelley-Hedgepeth, A.
Huggins, G. S.
Housman, D. E.
Mendelsohn, M. E.
Vita, J. A.
Vasan, R. S.
Levy, D.
Benjamin, E. J.
Mitchell, G. F.
TI Association between arterial stiffness and variations in
oestrogen-related genes
SO JOURNAL OF HUMAN HYPERTENSION
LA English
DT Article
DE arterial stiffness; tonometry; oestrogen receptor; polymorphism
ID RECEPTOR-ALPHA GENE; CORONARY-HEART-DISEASE; PREMATURE OVARIAN FAILURE;
FLOW-MEDIATED DILATION; LEFT-VENTRICULAR MASS; SMOOTH-MUSCLE-CELLS; WAVE
REFLECTION; NITRIC-OXIDE; POSTMENOPAUSAL WOMEN; ENDOTHELIAL FUNCTION
AB Increased arterial stiffness and wave reflection have been identified as cardiovascular disease risk factors. In light of significant sex differences and the moderate heritability of vascular function measures, we hypothesized that variation in the genes coding for oestrogen receptors alpha (ESR1) and beta (ESR2) and aromatase (CYP19A1) is associated with aortic stiffness and pressure wave reflection as measured by non-invasive arterial tonometry. In all, 1261 unrelated Framingham Offspring Study participants who attended the seventh examination cycle (mean age 62 +/- 10 years, 52% women) and had arterial tonometry and genotyping data were included in the study. Analysis of covariance was used to assess the association of polymorphisms with forward wave amplitude, augmented pressure, augmentation index (AI), carotid-femoral pulse wave velocity and mean arterial pressure with adjustment for potential confounders. In the sex-pooled analysis, those homozygous for the minor allele at any of four ESR1 variants that were in strong linkage disequilibrium ((TA)(n), rs2077647, rs2234693 and rs9340799) had on an average 18% higher augmented pressure and 16% greater AI compared with carriers of one or two major alleles (P = 0.0002-0.01). A similar magnitude of association was detected in those homozygous for the common allele at two ESR2 single-nucleotide polymorphisms (P = 0.007-0.02). Our results are consistent with the hypothesis that variation in ESR1 and ESR2, but not CYP19A1, is associated with an increased wave reflection that may contribute to associations between these variants and adverse clinical events demonstrated earlier. Our findings will need to be replicated in additional cohorts. Journal of Human Hypertension (2009) 23, 636-644; doi:10.1038/jhh.2009.1; published online 5 February 2009
C1 [Peter, I.] NYU, Dept Genet & Genom Sci, Mt Sinai Sch Med, New York, NY 10029 USA.
[Kelley-Hedgepeth, A.; Huggins, G. S.; Mendelsohn, M. E.] Tufts Med Ctr, Dept Med, Mol Cardiol Res Inst, Boston, MA USA.
[Housman, D. E.] MIT, Dept Biol, Cambridge, MA USA.
[Vita, J. A.; Vasan, R. S.; Levy, D.; Benjamin, E. J.] NHLBI, Framingham Heart Study, NIH, Framingham, MA USA.
[Vita, J. A.; Vasan, R. S.; Benjamin, E. J.] Boston Univ, Sch Med, Dept Prevent Med & Cardiol, Boston, MA 02118 USA.
[Levy, D.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA.
[Benjamin, E. J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Mitchell, G. F.] Cardiovasc Engn Inc, Norwood, MA USA.
RP Peter, I (reprint author), NYU, Dept Genet & Genom Sci, Mt Sinai Sch Med, 1425 Madison Ave, New York, NY 10029 USA.
EM inga.peter@mssm.edu
OI Vita, Joseph/0000-0001-5607-1797; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU NHLBI NIH HHS [P01 HL077378, P01 HL077378-02, P01 HL077378-05, T32
HL069770, T32 HL069770-05]
NR 46
TC 18
Z9 18
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9240
J9 J HUM HYPERTENS
JI J. Hum. Hypertens.
PD OCT
PY 2009
VL 23
IS 10
BP 636
EP 644
DI 10.1038/jhh.2009.1
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 495DU
UT WOS:000269871500002
PM 19194457
ER
PT J
AU Duffield, RM
Snelling, RR
Fales, HM
Blum, MS
AF Duffield, Richard M.
Snelling, Roy R.
Fales, Henry M.
Blum, Murray S.
TI Mandibular Gland Chemistry of Two Nearctic Species of Camponotus
(Colobopsis) (Hymenoptera: Formicidae)
SO JOURNAL OF HYMENOPTERA RESEARCH
LA English
DT Article
ID ALARM-DEFENCE SYSTEM; CARPENTER ANTS; TRAIL PHEROMONE; WEAVER ANT;
IDENTIFICATION; CONSTITUENTS; SECRETION; MELLEIN
AB The chemistry of the mandibular gland secretions of three Nearctic species of carpenter ants of the subgenus Colobopsis was studied. No volatile compound was detected in worker mandibular secretions of C. itnpressus and C. etiolates. Worker secretions of C. mississippiensis were dominated by 2,6-dimethyl-5-heptene-1-ol and citronellol. Male head extracts of C. impressus and C. mississippiensis exhibited these two compounds and an additional volatile which was identified as mellein. Citronellol constituted 50% of the volatile components in each of these species.
C1 [Duffield, Richard M.] Howard Univ, Dept Biol, Washington, DC 20059 USA.
[Snelling, Roy R.] Nat Hist Museum Los Angeles Cty, Entomol Sect, Los Angeles, CA 90007 USA.
[Fales, Henry M.] NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA.
[Blum, Murray S.] Univ Georgia, Dept Entomol, Athens, GA 30602 USA.
RP Duffield, RM (reprint author), Howard Univ, Dept Biol, Washington, DC 20059 USA.
EM rduffield@howard.edu
NR 31
TC 1
Z9 1
U1 1
U2 6
PU PENSOFT PUBL
PI SOFIA
PA GEO MILEV STR 13A, SOFIA, 1111, BULGARIA
SN 1070-9428
EI 1314-2607
J9 J HYMENOPT RES
JI J. Hymenopt. Res.
PD OCT
PY 2009
VL 18
IS 2
BP 140
EP 144
PG 5
WC Entomology
SC Entomology
GA 700WR
UT WOS:000285775500004
ER
PT J
AU Lev, A
Dimberu, P
Das, SR
Maynard, JC
Nicchitta, CV
Bennink, JR
Yewde, JW
AF Lev, Avital
Dimberu, Peniel
Das, Suman R.
Maynard, Jason C.
Nicchitta, Christopher V.
Bennink, Jack R.
Yewde, Jonathan W.
TI Efficient Cross-Priming of Antiviral CD8(+) T Cells by Antigen Donor
Cells Is GRP94 Independent
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HEAT-SHOCK PROTEINS; CLASS-I MOLECULES; ENDOPLASMIC-RETICULUM; MAJOR
HISTOCOMPATIBILITY; CYTOSOLIC PEPTIDES; SCAVENGER RECEPTOR; PRESENTING
CELLS; GP96; INNATE; VIVO
AB Cross-priming, the activation of naive CD8(+) T cells by dendritic cells presenting Ags synthesized by other cells, is believed to play an important role in the generation of antiviral and antitumor responses. The molecular mechanism(s) underlying cross-priming remain poorly defined and highly controversial. GRP94 (gp96), an abundant endoplasmic reticulum chaperone with innate immune-activating capacity, has been widely reported to play a major role in cross-priming. In this study, we show that cells whose expression of GRP94 is silenced via transient or stable transfection with GRP94-directed small interfering RNAs demonstrate no reduction in their abilities to generate class I peptide complexes in cultured cells or to prime antiviral CD8(+) T cell responses in vivo. In demonstrating the dispensability of GRP94, our finding points to the importance of alternative mechanisms for generation of class I peptide complexes from endogenous and exogenous Ags and immunogens. The Journal of Immunology, 2009, 183: 4205-4210.
C1 [Yewde, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Maynard, Jason C.; Nicchitta, Christopher V.] Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA.
RP Yewde, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 33, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
RI yewdell, jyewdell@nih.gov/A-1702-2012; Das, Suman/C-8760-2009
FU Division of Intramural Research; National Institute of Allergy and
Infectious Diseases; National Institutes of Health [CA 104392]
FX J.R.B. and J.W.Y. are supported by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases. C.V.N. is
supported by Grant CA 104392 from the National Institutes of Health.
NR 42
TC 9
Z9 11
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 1
PY 2009
VL 183
IS 7
BP 4205
EP 4210
DI 10.4049/jimmunol.0901828
PG 6
WC Immunology
SC Immunology
GA 503GU
UT WOS:000270522500012
PM 19752220
ER
PT J
AU Ishizuka, J
Grebe, K
Shenderov, E
Peters, B
Chen, QY
Peng, Y
Wang, LL
Dong, T
Pasquetto, V
Oseroff, C
Sidney, J
Hickman, H
Cerundolo, V
Sette, A
Bennink, JR
McMichael, A
Yewdell, JW
AF Ishizuka, Jeffrey
Grebe, Kristie
Shenderov, Eugene
Peters, Bjoern
Chen, Qiongyu
Peng, YanChun
Wang, Lili
Dong, Tao
Pasquetto, Valerie
Oseroff, Carla
Sidney, John
Hickman, Heather
Cerundolo, Vincenzo
Sette, Alessandro
Bennink, Jack R.
McMichael, Andrew
Yewdell, Jonathan W.
TI Quantitating T Cell Cross-Reactivity for Unrelated Peptide Antigens
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TRANSGENIC MICE; INFLUENZA NUCLEOPROTEIN; REPERTOIRE DIVERSITY;
HIGH-AFFINITY; RESPONSES; RECEPTOR; LYMPHOCYTES; VIRUS; CYTOMEGALOVIRUS;
SPECIFICITY
AB Quantitating the frequency of T cell cross-reactivity to unrelated peptides is essential to understanding T cell responses in infectious and autoimmune diseases. Here we used 15 mouse or human CD8(+) T cell clones (11 antiviral, 4 anti-self) in conjunction with a large library of defined synthetic peptides to examine nearly 30,000 TCR-peptide MHC class I interactions for cross-reactions. We identified a single cross-reaction consisting of an anti-self TCR recognizing a poxvirus peptide at relatively low sensitivity. We failed to identify any cross-reactions between the synthetic peptides in the panel and polyclonal. CD8(+) T cells raised to viral or alloantigens. These findings provide the best estimate to date of the frequency of T cell cross-reactivity to unrelated peptides (similar to 1/30,000), explaining why cross-reactions between unrelated pathogens are infrequently encountered and providing a critical parameter for understanding the scope of self-tolerance. The Journal of Immunology, 2009, 183: 4337-4345.
C1 [Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Ishizuka, Jeffrey; Shenderov, Eugene; Chen, Qiongyu; Peng, YanChun; Wang, Lili; Dong, Tao; Cerundolo, Vincenzo; McMichael, Andrew] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England.
[Peters, Bjoern; Pasquetto, Valerie; Oseroff, Carla; Sidney, John; Sette, Alessandro] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Room 2E13C1,Bldg 33,33 North Dr, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
RI yewdell, jyewdell@nih.gov/A-1702-2012;
OI Cerundolo, Vincenzo/0000-0003-0040-3793
FU Intramural Research, National Institute of Allergy and Infectious
Diseases; Medical Research Council Human Immunology Unit; Cancer
Research UK [C399/A2291]
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases (to J.R.B. and J.W.Y.), by
the Medical Research Council Human Immunology Unit (to T.D. and A.M.),
and by Cancer Research UK (Grant C399/A2291) (to V.C.).
NR 38
TC 28
Z9 28
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 1
PY 2009
VL 183
IS 7
BP 4337
EP 4345
DI 10.4049/jimmunol.0901607
PG 9
WC Immunology
SC Immunology
GA 503GU
UT WOS:000270522500026
PM 19734234
ER
PT J
AU Chen, Q
Davidson, TS
Huter, EN
Shevach, EM
AF Chen, Qian
Davidson, Todd S.
Huter, Eva N.
Shevach, Ethan M.
TI Engagement of TLR2 Does not Reverse the Suppressor Function of Mouse
Regulatory T Cells, but Promotes Their Survival
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTORS; IMMUNE-RESPONSES; CUTTING EDGE; IN-VITRO;
EXPRESSION; TRANSCRIPTION; LYMPHOCYTES; FOXP3; IL-2; VIVO
AB TLRs are a class of conserved pattern recognition receptors that are used by cells of the innate immune system. Recent studies have demonstrated the expression of TLRs on both human and mouse T cells raising the possibility that TLRs play a direct role in adaptive immunity. TLR2 is activated primarily by bacterial wall components including peptidoglycan and lipoproteins. Several studies have shown that mouse regulatory T (Treg) cells express TLR2 and claimed that engagement of TLR2 by synthetic ligands reversed their suppressive function. In contrary, enhancement of Treg function was observed following engagement of TLR2 on human Treg. We have reexamined the expression and function of TLR2 on mouse Treg purified from Foxp3-GFP knock-in mice. TLR2 ligation by TLR2 agonist, the synthetic bacterial lipoprotein Pam3CSK4, enhanced the proliferative responses of both conventional T cells and Treg in response to TLR stimulation in the absence of APC. Treatment of Foxp(3+) Treg with Pam3CSK4 did not alter their suppressive function in vitro or in vivo and did not reduce their level of Foxp3 expression. An additional effect of TLR2 stimulation of Treg was induction of Bcl-x(L) resulting in enhanced survival in vitro. Treatment of mice with the TLR2 agonist enhanced the Ag-driven proliferation of Treg in vivo, but did not abolish their ability to suppress the development of experimental autoimmune encephalomyelitis. Development of methods to selectively stimulate TLR2 on Treg may lead to a novel approaches for the treatment of autoimmune diseases. The Journal of Immunology, 2009, 183: 4458-4466.
C1 [Chen, Qian; Davidson, Todd S.; Huter, Eva N.; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA.
EM eshevach@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health
FX These studies were supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 33
TC 60
Z9 64
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 1
PY 2009
VL 183
IS 7
BP 4458
EP 4466
DI 10.4049/jimmunol.0901465
PG 9
WC Immunology
SC Immunology
GA 503GU
UT WOS:000270522500039
PM 19748987
ER
PT J
AU Crane, DD
Warner, SL
Bosio, CM
AF Crane, Deborah D.
Warner, Shayna L.
Bosio, Catharine M.
TI A Novel Role for Plasmin-Mediated Degradation of Opsonizing Antibody in
the Evasion of Host Immunity by Virulent, but Not Attenuated,
Francisella tularensis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID OUTER-MEMBRANE PROTEINS; YERSINIA-PESTIS; STREPTOCOCCUS-PNEUMONIAE;
STAPHYLOCOCCUS-AUREUS; BORRELIA-BURGDORFERI; CELL ACTIVATION; FC
RECEPTOR; SURFACE; INFECTION; BINDING
AB Opsonization by Abs represents a critical component of the host immune response against many pathogens. The mechanisms by which virulent microbes evade this protective response are not completely understood. In disease mediated by Francisella tularensis, Ab can effectively protect against infections with attenuated strains, for example, LVS, but not virulent strains such as SchuS4. Thus, it is likely that SchuS4 has mechanisms, which are not present in INS, that allow evasion of opsonization by Ab, dampening the protective effects of these host molecules. Here we demonstrate that evasion of Ab-mediated opsonization and phagocytosis by the highly virulent SchuS4 is associated with its ability to bind the host serine protease plasmin. SchuS4, but not the closely related LVS, bound active plasmin. Plasmin bound SchuS4 degraded exogenous and opsonizing Abs, whereas LVS failed to do so. Furthermore, plasmin-mediated inhibition of Ab opsonization by SchuS4 also inhibited Ab-mediated uptake of this bacterium by macrophages. Ab-mediated uptake of uncoated and opsonized SchuS4 elicited a strong proinflammatory response in infected macrophages. However, plasmin-coated, opsonized SchuS4 poorly elicited production of these protective proinflammatory cytokines. This unique host-pathogen interplay is a novel immune evasion strategy utilized by virulent F. tularensis, and it provides one explanation for the ability of Ab to protect against attenuated, but not virulent, strains of F. tularensis. This mechanism may also represent a more common hereto unrecognized strategy by which virulent bacteria evade detection and clearance by Ig. The Journal of Immunology, 2009, 183: 4593-4600.
C1 [Crane, Deborah D.; Warner, Shayna L.; Bosio, Catharine M.] NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Bosio, CM (reprint author), NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
EM bosioc@niaid.nih.gov
RI Bosio, Catharine/D-7456-2015
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases.
NR 36
TC 27
Z9 27
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 1
PY 2009
VL 183
IS 7
BP 4593
EP 4600
DI 10.4049/jimmunol.0901655
PG 8
WC Immunology
SC Immunology
GA 503GU
UT WOS:000270522500054
PM 19752236
ER
PT J
AU Reddy, NM
Suryanarayana, V
Kalvakolanu, DV
Yamamoto, M
Kensler, TW
Hassoun, PM
Kleeberger, SR
Reddy, SP
AF Reddy, Narsal M.
Suryanarayana, Vegiraju
Kalvakolanu, Dhananjaya V.
Yamamoto, Masayuki
Kensler, Thomas W.
Hassoun, Paul M.
Kleeberger, Steven R.
Reddy, Sekhar P.
TI Innate Immunity against Bacterial Infection following Hyperoxia Exposure
Is Impaired in NRF2-Deficient Mice
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ACUTE LUNG INJURY; VENTILATOR-ASSOCIATED PNEUMONIA; PULMONARY
OXYGEN-TOXICITY; TRANSCRIPTION FACTOR NRF2; SCAVENGER RECEPTOR MARCO;
2-RELATED FACTOR-2 GENE; PSEUDOMONAS-AERUGINOSA; PROMOTER POLYMORPHISM;
ALVEOLAR MACROPHAGES; OXIDATIVE STRESS
AB Oxygen supplementation is used as therapy to support critically ill patients with severe respiratory impairment. Although hyperoxia has been shown to enhance the lung susceptibility to subsequent bacterial infection, the mechanisms underlying enhanced susceptibility remain enigmatic. We have reported that disruption of NF-E2-related factor 2 (Nrf2), a master transcription regulator of various stress response pathways, enhances susceptibility to hyperoxia-induced acute lung injury in mice, and have also demonstrated an association between a polymorphism in the NRF2 promoter and increased susceptibility to acute lung injury. In this study, we show that Nrf2-deficient (Nrf2(-/-)) but not wild-type (Nrf2(+/+)) mice exposed to sublethal hyperoxia succumbed to death during recovery after Pseudomonas aeruginosa infection. Nrf2-deficiency caused persistent bacterial pulmonary burden and enhanced levels of inflammatory cell infiltration as well as edema. Alveolar macrophages isolated from Nrf2(-/-) mice exposed to hyperoxia displayed persistent oxidative stress and inflammatory cytokine expression concomitant with diminished levels of antioxidant enzymes, such as Gclc, required for glutathione biosynthesis. In vitro exposure of Nrf2(-/-) macrophages to hyperoxia strongly diminished their antibacterial activity and enhanced inflammatory cytokine expression compared with Nrf2(+/+) cells. However, glutathione supplementation during hyperoxic insult restored the ability of Nrf2(-/-) cells to mount antibacterial response and suppressed cytokine expression. Thus, loss of Nrf2 impairs lung innate immunity and promotes susceptibility to bacterial infection after hyperoxia exposure, ultimately leading to death of the host. The Journal of Immunology, 2009, 183: 4601-4608.
C1 [Reddy, Narsal M.; Suryanarayana, Vegiraju; Kensler, Thomas W.; Reddy, Sekhar P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA.
[Kalvakolanu, Dhananjaya V.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Yamamoto, Masayuki] Tohoku Univ, Dept Med Biochem, Sendai, Miyagi 980, Japan.
[Hassoun, Paul M.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA.
[Kleeberger, Steven R.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA.
RP Reddy, NM (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Room E7610,615 N Wolfe St, Baltimore, MD 21205 USA.
EM nmachire@jhsph.edu; sreddy@jhsph.edu
RI Yamamoto, Masayuki/A-4873-2010; Kensler, Thomas/D-8686-2014
OI Kensler, Thomas/0000-0002-6676-261X
FU NIH [HL66109, ES 11863, HL049441]; SCCOR [P50 HL073994, ES007141,
CA105005, CA94076]; NIH, National Institute of Environmental Health
Sciences
FX This work was funded by NIH Grants HL66109 and ES 11863 (to S.P.R.),
HL049441 (to P.H.), SCCOR P50 HL073994 (to S.P.R. and P.H.), ES007141
(to S.V.), CA105005 (to D.V.K.), and CA94076 (to T.W.K.) and, in part,
by the Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences (to S.RX.).
NR 49
TC 31
Z9 31
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 1
PY 2009
VL 183
IS 7
BP 4601
EP 4608
DI 10.4049/jimmunol.0901754
PG 8
WC Immunology
SC Immunology
GA 503GU
UT WOS:000270522500055
PM 19734219
ER
PT J
AU Anderson, CF
Stumhofer, JS
Hunter, CA
Sacks, D
AF Anderson, Charles F.
Stumhofer, Jason S.
Hunter, Christopher A.
Sacks, David
TI IL-27 Regulates IL-10 and IL-17 from CD4(+) Cells in Nonhealing
Leishmania major Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID AZAR DERMAL LEISHMANIASIS; CENTRAL-NERVOUS-SYSTEM; T-CELLS; KALA-AZAR;
CUTANEOUS LEISHMANIASIS; VISCERAL LEISHMANIASIS; CYTOKINE RESPONSES;
IMMUNE-RESPONSES; INTERFERON-GAMMA; CUTTING EDGE
AB Control of infection caused by Leishmania major requires the development of IFN-gamma(+)CD4(+) lymphocytes for the induction of microbicidal activity in host macrophages. We recently reported on the inability of conventionally resistant C57BL/6 mice to successfully resolve infection by an isolate of L. major, despite a strong IFN-gamma response by the host. Susceptibility was caused by Ag-specific IL-10 from CD4(+) cells that were also producing IFN-gamma. In the present studies, we have explored the role for IL-27 in the regulation of IL-10 from Th1 cells in leishmaniasis. Cytokine analysis of CD4(+) cells in the lesions and draining lymph nodes of infected IL-27R-deficient (WSX-1(-/-)) mice revealed diminished IL-10 from IFN-gamma(+) CD4(+) cells, which was accompanied by a reduction in total IFN-gamma(+)CD4(+) cells and an increase in IL-4. Despite the inhibition of IL-10 from CD4(+) cells, no significant change in parasite numbers was observed, due both to the shift in the Th1/Th2 balance and to residual levels of IL-10. Strikingly, infected WSX-1(-/-) mice developed more severe lesions that were associated with the appearance of IL-17(+) CD4(+) cells, demonstrating a function for IL-27 in blocking the development of inappropriate Th17 cells during L. major infection. The results demonstrate the pleiotropic effects that IL-27 has on L. major-driven Th1, Th2, and Th17 development, and reinforce its function as a key regulatory cytokine that controls the balance between immunity and pathology. The Journal of Immunology, 2009, 183: 4619-4627.
C1 [Anderson, Charles F.; Sacks, David] NIAID, NIH, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Stumhofer, Jason S.; Hunter, Christopher A.] Univ Penn, Dept Pathobiol, Sch Vet Med, Philadelphia, PA 19104 USA.
RP Sacks, D (reprint author), NIAID, NIH, Parasit Dis Lab, Bldg 4,Room 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA.
EM dsacks@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases [142334, D43 TW007127]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Institute of Allergy and
Infectious Diseases, and in part by National Institutes of Health Grants
At 142334 and D43 TW007127.
NR 43
TC 73
Z9 77
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD OCT 1
PY 2009
VL 183
IS 7
BP 4619
EP 4627
DI 10.4049/jimmunol.0804024
PG 9
WC Immunology
SC Immunology
GA 503GU
UT WOS:000270522500057
PM 19748991
ER
PT J
AU Tsuno, T
Mejido, J
Zhao, TM
Schmeisser, H
Morrow, A
Zoon, KC
AF Tsuno, Takaya
Mejido, Josef
Zhao, Tongmao
Schmeisser, Hana
Morrow, Angel
Zoon, Kathryn C.
TI IRF9 is a Key Factor for Eliciting the Antiproliferative Activity of
IFN-alpha
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE IFN-alpha; JAK-STAT pathway; antiproliferative activity; IRF9; TRAIL
ID INTERFERON-ALPHA; MELANOMA-CELLS; SIGNAL TRANSDUCER; START SITES; HUMAN
GENES; FACTOR-I; EXPRESSION; TRAIL; APOPTOSIS; ACTIVATION
AB A number of tumors are still resistant to the antiproliferative activity of human interferon (IFN)-alpha. The Janus kinases/Signal Transducers and Activators of Transcription (JAK-STAT) pathway plays an important role in initial IFN signaling. To enhance the antiproliferative activity of IFN-alpha, it is important to elucidate which factors in the JAK-STAT pathway play a key role in eliciting this activity. In human ovarian adenocarcinoma OVCAR3 cells sensitive to both IFN-alpha and IFN-gamma, only IFN regulatory factor 9 (IRF9)-RNA interference (RNAi) completely inhibited the antiproliferative activity of IFN-alpha among the intracellular JAK-STAT pathway factors. Conversely, Stat1-RNAi did not inhibit the antiproliferative activity of IFN-alpha, whereas it partially inhibited that of IFN-gamma. As a cell death pathway, it is reported that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis through TRAIL-receptor (R) 1 and TRAIL-R2. In IFN-alpha-treated OVCAR3 cells, IRF9-RNAi inhibited transcription of TRAIL whereas Stat1-RNAi did not, suggesting that the transcription of TRAIL induced by IFN-alpha predominantly required IRF9. Furthermore, IFN-stimulated response element-like motifs of TRAIL bound to IFIN-stimulated gene factor 3 (ISGF3) complex after IFN-alpha treatment. Subsequently, TRAIL-R2-RNAi inhibited both antiproliferative activities of IFN-alpha and TRAIL, suggesting that TRAIL-R2 mediated both IFN-alpha and TRAIL signals to elicit their antiproliferative activities. Finally, IRF9 overexpression facilitated IFN-alpha-induced apoptosis in T98G (human glioblastoma multiforme) cells, which were resistant to IFN-alpha. Thus, this study suggests that IRF9 is the key factor for eliciting the antiproliferative activity of IFN-alpha and TRAIL may be one of the potential mediators.
C1 [Zoon, Kathryn C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Zoon, KC (reprint author), NIAID, Div Intramural Res, NIH, Bldg 33,Rm 2N09G 2,33 N Dr, Bethesda, MD 20892 USA.
EM kzoon@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000944-04, Z99 AI999999]
NR 43
TC 26
Z9 26
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2009
VL 32
IS 8
BP 803
EP 816
PG 14
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 500RF
UT WOS:000270321100004
PM 19752753
ER
PT J
AU Zielinski, R
Lyakhov, I
Jacobs, A
Chertov, O
Kramer-Marek, G
Francella, N
Stephen, A
Fisher, R
Blumenthal, R
Capala, J
AF Zielinski, Rafal
Lyakhov, Ilya
Jacobs, Amy
Chertov, Oleg
Kramer-Marek, Gabriela
Francella, Nicholas
Stephen, Andrew
Fisher, Robert
Blumenthal, Robert
Capala, Jacek
TI Affitoxin-A Novel Recombinant, HER2-specific, Anticancer Agent for
Targeted Therapy of HER2-positive Tumors
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE Affibody molecule; HER2; breast cancer; targeted therapy; Pseudomonas
exotoxin A
ID METASTATIC BREAST-CANCER; IMPROVED ANTIGEN-BINDING; DISULFIDE-STABILIZED
FV; PSEUDOMONAS EXOTOXIN-A; ANTITUMOR-ACTIVITY; IN-VITRO; FUSION
PROTEIN; MONOCLONAL-ANTIBODY; AFFIBODY MOLECULES; CARCINOMA-CELLS
AB Expression of the human epidermal growth factor receptor 2 (HER2) is amplified in 25% to 30% of breast cancers and has been associated with an unfavorable prognosis. Here we report the construction, purification, and characterization of Affitoxin-a novel class of HER2-specific cytotoxic molecules combining HER2-specific Affibody molecule as a targeting moiety and PE38KDEL, which is a truncated version of Pseudomonas exotoxin A, as a cell killing agent. It is highly soluble and does not require additional refolding, oxidation, or reduction steps (luring its purification. Using surface plasmon resonance technology and competitive binding assays, we have shown that Affitoxin binds specifically to HER2 with nanomolar affinity. We have also observed a high correlation between HER2 expression and retention of Affitoxin bound to the cell surface. Affitoxin binding and internalization is followed by Pseudomonas exotoxin A activity domain-mediated ADP-ribosylation of translation elongation factor 2 and, consequently, inhibition of protein synthesis as shown by protein expression analysis of HER2-positive cells treated with Affitoxin. Measured IC(50) value for HER2-negative cells MDA-MB468 (65 +/- 2.63 pM) was more than 20 times higher than the value for low HER2 level-expressing MCF7 cells (2.56 +/- 0.1 pM), and almost 3 orders of magnitude higher for its HER2-overexpressing derivative MCF7/HER2 (62.7 +/- 5.9fM). These studies suggest that Affitoxin is an attractive PE38-based candidate for treatment of HER2-positive tumors.
C1 [Zielinski, Rafal; Jacobs, Amy; Kramer-Marek, Gabriela; Francella, Nicholas; Blumenthal, Robert; Capala, Jacek] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lyakhov, Ilya; Chertov, Oleg; Stephen, Andrew; Fisher, Robert] SAIC Frederick Inc, NCI Frederick, Frederick, MD USA.
[Jacobs, Amy] SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA.
RP Capala, J (reprint author), NCI, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room B3B69D, Bethesda, MD 20892 USA.
EM capalaj@mail.nih.gov
FU Center for Cancer Research; National Cancer Institute; Breast Cancer
Research Stamp Fund; National Institutes of Health [N01-CO-12400,
N01-CO-12401]
FX Funded in part with Federal funds from the National Cancer Institute and
National Institutes of Health under contracts N01-CO-12400 and
N01-CO-12401, respectively.
NR 50
TC 32
Z9 32
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2009
VL 32
IS 8
BP 817
EP 825
PG 9
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 500RF
UT WOS:000270321100005
PM 19752752
ER
PT J
AU Smith, FO
Klapper, JA
Wunderlich, JR
Rosenberg, SA
Dudley, ME
AF Smith, Franz O.
Klapper, Jacob A.
Wunderlich, John R.
Rosenberg, Steven A.
Dudley, Mark E.
TI Impact of a Recombinant Fowlpox Vaccine on the Efficacy of Adoptive Cell
Therapy With Tumor Infiltrating Lymphocytes in a Patient With Metastatic
Melanoma
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE recombinant fowlpox vaccine; gp100: 209-217 (210M); metastatic melanoma;
adoptive cell therapy; tumor infiltrating lymphocytes
ID ANTIGEN-4 BLOCKADE; T-CELLS; AUTOIMMUNITY; IMMUNOTHERAPY; REGRESSION;
CANCER; SELF; CTL
AB A patient with metastatic melanoma who had progressive disease after prior surgical resections, high dose interleukin-2. and anti-cytotoxic T lymphocyte antigen-4 antibody received sequential treatments with autologous tumor infiltrating lymphocytes that recognized the gp100 melanocyte differentiation antigen. Although no clinical response was seen when cells were administered alone, an objective clinical response to therapy was seen with tumor infiltrating lymphocytes administered together with a highly immunogenic fowlpox vaccine expressing a gp100: 209-217 (210M) epitope. Persistence of the transferred antigen-specific lymphocytes in the peripheral blood was observed only after adoptive cell therapy plus administration of vaccine. Cell proliferation in vitro was further stimulated by additional vaccine and interleukin-2. The patient has an ongoing partial response at 10 months after the last treatment.
C1 [Smith, Franz O.; Klapper, Jacob A.; Wunderlich, John R.; Rosenberg, Steven A.; Dudley, Mark E.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Dudley, ME (reprint author), NCI, Surg Branch, NIH, CRC 3-5752,10 Ctr Dr, Bethesda, MD 20892 USA.
EM Mark_Dudley@nih.gov
NR 13
TC 11
Z9 11
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2009
VL 32
IS 8
BP 870
EP 874
PG 5
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 500RF
UT WOS:000270321100010
PM 19752747
ER
PT J
AU Goff, SL
Robbins, PF
El-Gamil, M
Rosenberg, SA
AF Goff, Stephanie L.
Robbins, Paul F.
El-Gamil, Mona
Rosenberg, Steven A.
TI No Correlation Between Clinical Response to CTLA-4 Blockade and Presence
of NY-ESO-1 Antibody in Patients With Metastatic Melanoma
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Letter
ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; CANCER; REGRESSION; HYPOPHYSITIS
C1 [Goff, Stephanie L.; Robbins, Paul F.; El-Gamil, Mona; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Goff, SL (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 7
TC 8
Z9 9
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD OCT
PY 2009
VL 32
IS 8
BP 884
EP 885
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 500RF
UT WOS:000270321100012
PM 19752745
ER
PT J
AU Morens, DM
Folkers, GK
Fauci, AS
AF Morens, David M.
Folkers, Gregory K.
Fauci, Anthony S.
TI What Is a Pandemic?
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID INFLUENZA
C1 [Morens, David M.; Folkers, Gregory K.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM dmorens@niaid.nih.gov
NR 27
TC 13
Z9 14
U1 0
U2 3
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD OCT 1
PY 2009
VL 200
IS 7
BP 1018
EP 1021
DI 10.1086/644537
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 490CN
UT WOS:000269475000002
PM 19712039
ER
PT J
AU Nair, N
Moss, WJ
Scott, S
Mugala, N
Ndhlovu, ZM
Lilo, K
Ryon, JJ
Monze, M
Quinn, TC
Cousens, S
Cutts, F
Griffin, DE
AF Nair, Nitya
Moss, William J.
Scott, Susana
Mugala, Nanthalile
Ndhlovu, Zaza M.
Lilo, Kareem
Ryon, Judith J.
Monze, Mwaka
Quinn, Thomas C.
Cousens, Simon
Cutts, Felicity
Griffin, Diane E.
TI HIV-1 Infection in Zambian Children Impairs the Development and Avidity
Maturation of Measles Virus-Specific Immunoglobulin G after Vaccination
and Infection
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID REDUCTION NEUTRALIZATION TEST; B-CELLS; CELLULAR RECEPTOR; UNINFECTED
CHILDREN; THIOCYANATE ELUTION; ANTIBODY-AFFINITY; CD46; IMMUNOGENICITY;
PROTEIN; ELISA
AB Background. Endemic transmission of measles continues in many countries that have a high human immunodeficiency virus (HIV) burden. The effects that HIV infection has on immune responses to measles and to measles vaccine can impact measles elimination efforts. Assays to measure antibody include the enzyme immunoassay (EIA), which measures immunoglobulin G (IgG) to all measles virus (MV) proteins, and the plaque reduction neutralization (PRN) assay, which measures antibody to the hemagglutinin and correlates with protection. Antibody avidity may affect neutralizing capacity.
Methods. HIV-infected and HIV-uninfected Zambian children were studied after measles vaccination (n = 44) or MV infection (n = 57). Laboratory or wild-type MV strains were used to infect Vero or Vero/signaling lymphocyte-activation molecule (SLAM) cells in PRN assays. IgG to MV was measured by EIA, and avidity was determined by ammonium thiocyanate dissociation.
Results. HIV infection impaired EIA IgG responses after vaccination and measles but not PRN responses measured using laboratory-adapted MV. Avidity was lower among HIV-infected children 3 months after vaccination and 1 and 3 months after measles. Neutralization of wild-type MV infection of Vero/SLAM cells correlated with IgG avidity.
Conclusion. Lower antibody quality and quantity in HIV-infected children after measles vaccination raise challenges for assuring the long- term protection of these children. Antibody quality in children receiving antiretroviral therapy requires assessment.
C1 [Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA.
[Nair, Nitya; Moss, William J.; Ndhlovu, Zaza M.; Lilo, Kareem; Ryon, Judith J.; Griffin, Diane E.] Johns Hopkins Univ, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
[Moss, William J.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Scott, Susana; Cousens, Simon; Cutts, Felicity] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England.
[Monze, Mwaka] Univ Teaching Hosp, Virol Lab, Lusaka, Zambia.
[Mugala, Nanthalile] Univ Teaching Hosp, Hlth Serv & Syst Program, Lusaka, Zambia.
RP Griffin, DE (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, 615 N Wolfe St,Rm E5132, Baltimore, MD 21205 USA.
EM dgriffin@jhsph.edu
RI Nair, Nitya/D-2651-2017
OI Nair, Nitya/0000-0002-9524-9313
FU Intramural NIH HHS [ZIA AI000361-28]; NIAID NIH HHS [AI23047, R01
AI023047]; Wellcome Trust [GR059114MA]
NR 45
TC 33
Z9 33
U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD OCT 1
PY 2009
VL 200
IS 7
BP 1031
EP 1038
DI 10.1086/605648
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 490CN
UT WOS:000269475000004
PM 19702505
ER
PT J
AU An, P
Johnson, R
Phair, J
Kirk, GD
Yu, XF
Donfield, S
Buchbinder, S
Goedert, JJ
Winkler, CA
AF An, Ping
Johnson, Randall
Phair, John
Kirk, Gregory D.
Yu, Xiao-Fang
Donfield, Sharyne
Buchbinder, Susan
Goedert, James J.
Winkler, Cheryl A.
TI APOBEC3B Deletion and Risk of HIV-1 Acquisition
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 58th Annual Meeting of the American-Society-of-Human-Genetics
CY NOV 11-15, 2008
CL Philadelphia, PA
SP Amer Soc Human Genet
ID VIF; STRATIFICATION; REPLICATION; INFECTION; GENE; AIDS
AB The human APOBEC3 family of cytidine deaminases provides intrinsic immunity to retroviral infection. A naturally occurring 29.5-kb deletion removes the entire APOBEC3B gene. We examined the impact of the APOBEC3B gene deletion in >4000 individuals from 5 human immunodeficiency virus type 1 (HIV-1) natural history cohorts. The hemizygous genotype had no effect on either acquisition of HIV-1 infection or progression to AIDS. However, the homozygous deletion was significantly associated with unfavorable outcomes for HIV-1 acquisition (odds ratio, 7.37; P = .024), progression to AIDS (relative hazard, 4.01; P = .03) and viral set point (P = .04). These findings suggest that the loss of APOPBEC3B may increase host susceptibility to HIV-1 acquisition and progression to AIDS and warrant further study.
C1 [Winkler, Cheryl A.] NCI, Lab Genom Div, SAIC Frederick, FCRDC, Frederick, MD 21702 USA.
[Kirk, Gregory D.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Yu, Xiao-Fang] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA.
[Phair, John] Northwestern Univ, Chicago, IL 60611 USA.
[Donfield, Sharyne] Rho, Chapel Hill, NC USA.
[Buchbinder, Susan] San Francisco Dept Publ Hlth, San Francisco, CA USA.
RP Winkler, CA (reprint author), NCI, Lab Genom Div, SAIC Frederick, FCRDC, Bldg 560, Frederick, MD 21702 USA.
EM winkler@ncifcrf.gov
RI Johnson, Randall/B-1517-2014
OI Johnson, Randall/0000-0001-7754-0847
FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [Z01 BC010297-11,
ZIA BC010297-15, ZIA BC010297-13, Z01 BC010798-01, Z01 BC010297-10, ZIA
BC010297-12, Z01 BC010798-02, Z99 CA999999, ZIA BC010297-14]; NCI NIH
HHS [N02CP55504, HHSN261200800001E]; NIDA NIH HHS [R56 DA004334, R01
DA004334, R01-DA04334]; PHS HHS [R01-12586]
NR 15
TC 34
Z9 35
U1 0
U2 5
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD OCT 1
PY 2009
VL 200
IS 7
BP 1054
EP 1058
DI 10.1086/605644
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 490CN
UT WOS:000269475000007
PM 19698078
ER
PT J
AU Weinberg, A
Zhang, JH
Oxman, MN
Johnson, GR
Hayward, AR
Caulfield, MJ
Irwin, MR
Clair, J
Smith, JG
Stanley, H
Marchese, RD
Harbecke, R
Williams, HM
Chan, ISF
Arbeit, RD
Gershon, AA
Schodel, F
Morrison, VA
Kauffman, CA
Straus, SE
Schmader, KE
Davis, LE
Levin, MJ
AF Weinberg, Adriana
Zhang, Jane H.
Oxman, Michael N.
Johnson, Gary R.
Hayward, Anthony R.
Caulfield, Michael J.
Irwin, Michael R.
Clair, James
Smith, Jeffrey G.
Stanley, Harold
Marchese, Rocio D.
Harbecke, Ruth
Williams, Heather M.
Chan, Ivan S. F.
Arbeit, Robert D.
Gershon, Anne A.
Schoedel, Florian
Morrison, Vicki A.
Kauffman, Carol A.
Straus, Steve E.
Schmader, Kenneth E.
Davis, Larry E.
Levin, Myron J.
CA US Dept Vet Affairs
TI Varicella-Zoster Virus-Specific Immune Responses to Herpes Zoster in
Elderly Participants in a Trial of a Clinically Effective Zoster Vaccine
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID POSTHERPETIC NEURALGIA; OLDER-ADULTS; LONG-TERM; INFECTION; PAIN;
PERSISTENCE; VALIDATION; PREVENTION; RECIPIENTS; SHIPMENT
AB Background. The objectives of this study were to evaluate the association between varicella-zoster virus (VZV) specific humoral and cell-mediated immunity (CMI) to herpes zoster (HZ) and protection against HZ morbidity and to compare immune responses to HZ and zoster vaccine.
Methods. In 981 elderly persons who developed HZ during a zoster vaccine efficacy trial (321 vaccinees and 660 placebo recipients) and 1362 without HZ (682 vaccinees and 680 placebo recipients), CMI was measured by VZV responder cell frequency and interferon-gamma enzyme-linked immunospot, and antibodies were measured by VZV enzyme-linked immunosorbent assay against affinity-purified VZV glycoproteins (gpELISA).
Results. Robust VZV CMI at HZ onset correlated with reduced HZ morbidity, whereas VZV gpELISA titers did not. Three weeks after HZ onset, gpELISA titers were highest in those with more severe HZ and were slightly increased in placebo recipients (compared with zoster vaccine recipients) and in older individuals. VZV CMI responses to HZ were similar in zoster vaccine and placebo recipients and were not affected by demographic characteristics or antiviral therapy, except for responder cell frequency at HZ onset, which decreased with age. When responses to zoster vaccine and HZ could be compared, VZV CMI values were similar, but antibody titers were lower.
Conclusions. Higher VZV CMI at HZ onset was associated with reduced HZ severity and less postherpetic neuralgia. Higher antibody titers were associated with increased HZ severity and occurrence of postherpetic neuralgia. HZ and zoster vaccine generated comparable VZV CMI.
C1 [Zhang, Jane H.; Johnson, Gary R.] VA Connecticut Healthcare Syst, W Haven Cooperat Studies Program, Coordinating Ctr, West Haven, CT USA.
[Weinberg, Adriana; Levin, Myron J.] Univ Colorado Denver, West Haven, CT USA.
[Oxman, Michael N.; Stanley, Harold; Harbecke, Ruth; Williams, Heather M.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Oxman, Michael N.; Stanley, Harold; Harbecke, Ruth; Williams, Heather M.] VA San Diego Healthcare Syst, San Diego, CA USA.
[Irwin, Michael R.] Univ Calif Los Angeles, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA USA.
[Hayward, Anthony R.; Straus, Steve E.] NIH, Bethesda, MD 20892 USA.
[Caulfield, Michael J.; Clair, James; Smith, Jeffrey G.; Marchese, Rocio D.; Chan, Ivan S. F.; Schoedel, Florian] Merck Res Labs, West Point, PA USA.
[Arbeit, Robert D.] Tufts Univ, Boston, MA 02111 USA.
[Gershon, Anne A.] Columbia Univ, New York, NY USA.
[Morrison, Vicki A.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Morrison, Vicki A.] Vet Adm Med Ctr, Minneapolis, MN 55417 USA.
[Kauffman, Carol A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kauffman, Carol A.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Schmader, Kenneth E.] Durham VA Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA.
[Schmader, Kenneth E.] Duke Univ, Med Ctr, Durham, NC USA.
[Davis, Larry E.] VA Med Ctr, Albuquerque, NM USA.
RP Weinberg, A (reprint author), Res Complex 2,Mail Stop 8604,12700 E 19th Ave, Aurora, CO 80045 USA.
EM Adriana.Weinberg@ucdenver.edu
RI Irwin, Michael/H-4870-2013
OI Irwin, Michael/0000-0002-1502-8431
FU West Haven Cooperative Studies Program Coordinating Center
FX Laboratory assistance for the RCF assay was provided at the San Diego
site by P. Jordan and at the Denver site by L. Enomoto, G. Pott, E.
Ponnuraj, D. Thrasher, and M. Borakove. Clinical assistance was provided
at the San Diego site by P. McCook, D. Beck, J. Guatelli, P. Brooks, and
A. Kendall; at the Denver site by N. Lang and D. Barber; and at Merck by
M. E. Thompson, R. Rutledge, and N. Bundick. Data management and
analysis support at West Haven Cooperative Studies Program Coordinating
Center was provided by K. Dellert. Statistical assistance at Merck was
provided by W. W. B. Wang, J. Xu, J. Heyse, and H. Matthews. Clinical
administration at Merck was provided by F. S., J. Sadoff, S. Manoff, C.
J. White, and R. Vessey. Laboratory assistance at Merck was provided by
R. Kaufhold, M. Wooters, J. Field, H. Joseph for ELISPOT and by O.
Hammond, P. Stump, M. Norris, M. Santo, C. Moyer, M. Constanzer, and J.
Kessler for gpELISA.
NR 29
TC 109
Z9 114
U1 0
U2 9
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD OCT 1
PY 2009
VL 200
IS 7
BP 1068
EP 1077
DI 10.1086/605611
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 490CN
UT WOS:000269475000009
PM 19712037
ER
PT J
AU Hoshino, Y
Pesnicak, L
Dowdell, KC
Burbelo, PD
Knipe, DM
Straus, SE
Cohen, JI
AF Hoshino, Yo
Pesnicak, Lesley
Dowdell, Kennichi C.
Burbelo, Peter D.
Knipe, David M.
Straus, Stephen E.
Cohen, Jeffrey I.
TI Protection from Herpes Simplex Virus (HSV)-2 Infection with
Replication-Defective HSV-2 or Glycoprotein D2 Vaccines in
HSV-1-Seropositive and HSV-1-Seronegative Guinea Pigs
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 27th Annual Meeting of the American-Society-for-Virology
CY JUL 12-18, 2008
CL Ithaca, NY
SP Amer Soc Virol
ID GENITAL HERPES; RECOMBINANT GLYCOPROTEIN; TYPE-2; IMMUNOGENICITY;
VACCINATION; EFFICACY; WOMEN; MEN
AB Background. A herpes simplex virus (HSV)-2 candidate vaccine consisting of glycoprotein D (gD2) in alum and monophosphoryl lipid A (MPL) reduced genital herpes disease in HSV-1-seronegative women but not in men or HSV-1-seropositive women.
Methods. To determine the effect of HSV-1 serostatus on effectiveness of different vaccines, we tested gD2 in alum/MPL, gD2 in Freund's adjuvant, and dl5-29 (a replication-defective HSV-2 mutant) in HSV-1-seropositive or HSV-1-seronegative guinea pigs.
Results. In HSV-1-seronegative animals, dl5-29 induced the highest titers of neutralizing antibody, and after vaginal challenge with wild-type virus, dl5-29 resulted in lower rates of vaginal shedding, lower levels of HSV DNA in ganglia, and a trend for less acute and recurrent genital herpes, compared with the gD2 vaccines. In HSV-1-seropositive animals, all 3 vaccines induced similar titers of neutralizing antibodies and showed similar levels of protection against acute and recurrent genital herpes after vaginal challenge with wild-type virus, but dl5-29 reduced vaginal shedding after challenge more than did the gD2 vaccines.
Conclusions. dl5-29 Is an effective vaccine in both HSV-1-seropositive and HSV-1- seronegative guinea pigs and was superior to gD2 vaccines in reducing virus shedding after challenge in both groups of animals. dl5-29 Might reduce transmission of HSV-2.
C1 [Hoshino, Yo; Pesnicak, Lesley; Dowdell, Kennichi C.; Straus, Stephen E.; Cohen, Jeffrey I.] NIAID, Med Virol Sect, LCID, Bethesda, MD 20892 USA.
[Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA.
[Knipe, David M.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
RP Cohen, JI (reprint author), NIAID, Med Virol Sect, LCID, Bldg 10,Rm 11N234,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jcohen@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999, Z99 DE999999, Z01 AI000548-20]; NCRR
NIH HHS [P51 RR000168]; NIAID NIH HHS [AI057552, R56 AI057552, R01
AI057552]
NR 20
TC 38
Z9 42
U1 0
U2 5
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD OCT 1
PY 2009
VL 200
IS 7
BP 1088
EP 1095
DI 10.1086/605645
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 490CN
UT WOS:000269475000011
PM 19702506
ER
PT J
AU Madhavarao, CN
Arun, P
Anikster, Y
Mog, SR
Staretz-Chacham, O
Moffett, JR
Grunberg, NE
Gahl, WA
Namboodiri, AMA
AF Madhavarao, C. N.
Arun, P.
Anikster, Y.
Mog, S. R.
Staretz-Chacham, O.
Moffett, J. R.
Grunberg, N. E.
Gahl, W. A.
Namboodiri, A. M. A.
TI Glyceryl triacetate for Canavan disease: A low-dose trial in infants and
evaluation of a higher dose for toxicity in the tremor rat model
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Article
ID N-ACETYLASPARTIC ACIDURIA; CENTRAL-NERVOUS-SYSTEM;
MAGNETIC-RESONANCE-SPECTROSCOPY; MYELIN LIPID-SYNTHESIS;
ACETYL-L-ASPARTATE; ASPARTOACYLASE DEFICIENCY; CHAIN TRIGLYCERIDES;
BRAIN; ACETATE; ACETYLASPARTYLGLUTAMATE
AB Canavan disease (CD) is a fatal dysmyelinating genetic disorder associated with aspartoacylase deficiency, resulting in decreased brain acetate levels and reduced myelin lipid synthesis in the developing brain. Here we tested tolerability of a potent acetate precursor, glyceryl triacetate (GTA), at low doses in two infants diagnosed with CD, aged 8 and 13 months. Much higher doses of GTA were evaluated for toxicity in the tremor rat model of CD. GTA was given orally to the infants for up to 4.5 and 6 months, starting at 25 mg/kg twice daily, doubling the dose weekly until a maximum of 250 mg/kg reached. Wild-type and tremor rat pups were given GTA orally twice daily, initially at a dose of 4.2 g/kg from postnatal days 7 through 14, and at 5.8 g/kg from day 15 through 23, and thereafter in food (7.5%) and water (5%). At the end of the trial (similar to 90 to 120 days) sera and tissues from rats were analysed for changes in blood chemistry and histopathology. GTA treatment caused no detectable toxicity and the patients showed no deterioration in clinical status. In the high-dose animal studies, no significant differences in the mean blood chemistry values occurred between treated and untreated groups, and no lesions indicating toxicity were detectable in any of the tissues examined. Lack of GTA toxicity in two CD patients in low-dose trials, as well as in high-dose animal studies, suggests that higher, effective dose studies in human CD patients are warranted.
C1 [Madhavarao, C. N.; Arun, P.; Moffett, J. R.; Namboodiri, A. M. A.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Program Neurosci, Bethesda, MD 20814 USA.
[Madhavarao, C. N.; Arun, P.; Moffett, J. R.; Namboodiri, A. M. A.] Uniformed Serv Univ Hlth Sci, Program Mol & Cell Biol, Bethesda, MD 20814 USA.
[Anikster, Y.] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
[Anikster, Y.] Safra Children Hosp, Metab Dis Unit, Sheba Med Ctr, Tel Hashomer, Israel.
[Mog, S. R.] AFRRI, Div Comparat Pathol, Bethesda, MD USA.
[Staretz-Chacham, O.; Gahl, W. A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Grunberg, N. E.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Program Neurosci, Bethesda, MD 20814 USA.
RP Namboodiri, AMA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Program Neurosci, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM anamboodiri@usuhs.mil
FU Rosalind Poss Rosen Clinical Research Training Fellowship; American
Academy of Neurology Foundation; St Paul; Canavan Foundation, New York;
Jacob's Cure Foundation; NTSAD; Boston; Samueli Institute; NIH
[NS039387]
FX C. N. Madhavarao was supported by the Rosalind Poss Rosen Clinical
Research Training Fellowship sponsored by the American Academy of
Neurology Foundation, St Paul, MN and Canavan Foundation, New York, NY.
The study was supported by Jacob's Cure Foundation, NTSAD, Boston,
Samueli Institute and NIH R56 grant NS039387 for A. M. A. Namboodiri.
GTA for the clinical trials was provided gratis by Cognis Oleo
Chemicals, Germany. The authors thank the National Bio Resource Project
for the Rat, Kyoto University, Kyoto, Japan, for providing breeding
pairs of tremor rats.
NR 39
TC 17
Z9 17
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-8955
J9 J INHERIT METAB DIS
JI J. Inherit. Metab. Dis.
PD OCT
PY 2009
VL 32
IS 5
BP 640
EP 650
DI 10.1007/s10545-009-1155-3
PG 11
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 509AC
UT WOS:000270982100006
PM 19685155
ER
PT J
AU Dacosta, RS
Tang, Y
Kalliomaki, T
Reilly, RM
Weersink, R
Elford, AR
Marcon, NE
Wilson, BC
AF Dacosta, Ralph S.
Tang, Ying
Kalliomaki, Tuula
Reilly, Raymond M.
Weersink, Robert
Elford, Alisha R.
Marcon, Norman E.
Wilson, Brian C.
TI IN VIVO NEAR-INFRARED FLUORESCENCE IMAGING OF HUMAN COLON ADENOCARCINOMA
BY SPECIFIC IMMUNOTARGETING OF A TUMOR-ASSOCIATED MUCIN
SO JOURNAL OF INNOVATIVE OPTICAL HEALTH SCIENCES
LA English
DT Article
DE Autofluorescence imaging; endoscopy; colon adenocarcinoma; TAG72; CC49;
mucin; monoclonal antibody; conjugate; confocal fluorescence microscopy
AB Background and Aims: Accurate endoscopic detection of premalignant lesions and early cancers in the colon is essential for cure, since prognosis is closely related to lesion size and stage. Although it has great clinical potential, autofluorescence endoscopy has limited tumor-to-normal tissue image contrast for detecting small preneoplastic lesions. We have developed a molecularly specific, near-infrared fluorescent monoclonal antibody (CC49) bioconjugate which targets tumor-associated glycoprotein 72 (TAG72), as a contrast agent to improve fluorescence-based endoscopy of colon cancer. Methods: The fluorescent anti-TAG72 conjugate was evaluated in vitro and in vivo in athymic nude mice bearing human colon adenocarcinoma (LS174T) subcutaneous tumors. Autofluorescence, a fluorescent but irrelevant antibody and the free fluorescent dye served as controls. Fluorescent agents were injected intravenously, and in vivo whole body fluorescence imaging was performed at various time points to determine pharmacokinetics, followed by ex vivo tissue analysis by confocal fluorescence microscopy and histology. Results: Fluorescence microscopy and histology confirmed specific LS174T cell membrane targeting of labeled CC49 in vitro and ex vivo. In vivo fluorescence imaging demonstrated significant tumor-to-normal tissue contrast enhancement with labeled-CC49 at three hours post injection, with maximum contrast after 48 h. Accumulation of tumor fluorescence demonstrated that modification of CC49 antibodies did not alter their specific tumor-localizing properties, and was antibody-dependent since controls did not produce detectable tumor fluorescence. Conclusions: These results show proof-of-principle that our near-infrared fluorescent-antibody probe targeting a tumor-associated mucin detects colonic tumors at the molecular level in real time, and offer a basis for future improvement of image contrast during clinical fluorescence endoscopy.
C1 [Dacosta, Ralph S.] Ontario Canc Inst, Div Biophys & Bioimaging, Toronto, ON M5G 2M9, Canada.
[Kalliomaki, Tuula; Wilson, Brian C.] Univ Toronto, Dept Med Biophys, Princess Margaret Hosp, Ontario Canc Inst,Univ Hlth Network, Toronto, ON, Canada.
[Tang, Ying] NCI, NIH, Radiat Oncol Branch, Bethesda, MD USA.
[Reilly, Raymond M.] Toronto Gen Hosp, Div Clin Invest & Human Physiol, Res Inst, Toronto, ON, Canada.
[Reilly, Raymond M.] Univ Toronto, Leslie Dan Fac Pharm Toronto, Toronto, ON, Canada.
[Weersink, Robert] Univ Hlth Network, Lab Appl Biophoton, Toronto, ON, Canada.
[Elford, Alisha R.] Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Univ Hlth Network, Dept Med Biophys & Immunol, Toronto, ON M5G 2M9, Canada.
[Marcon, Norman E.] St Michaels Hosp, Ctr Therapeut Endoscopy & Endoscop Oncol, Toronto, ON M5B 1W8, Canada.
RP Dacosta, RS (reprint author), Ontario Canc Inst, Div Biophys & Bioimaging, 610 Univ Toronto, Toronto, ON M5G 2M9, Canada.
EM rdacosta@uhnres.utoronto.ca
FU Ontario Research and Development Challenge Fund (ORDCF)
FX This work was supported by the Ontario Research and Development
Challenge Fund (ORDCF). The authors wish to thank Anoja Giles, Bob Kuba,
Annie Lin and Kelvin Ho for their technical assistance.
NR 74
TC 3
Z9 3
U1 0
U2 2
PU WORLD SCIENTIFIC PUBL CO PTE LTD
PI SINGAPORE
PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE
SN 1793-5458
J9 J INNOV OPT HEAL SCI
JI J. Innov. Opt. Health Sci.
PD OCT
PY 2009
VL 2
IS 4
BP 407
EP 422
DI 10.1142/S1793545809000759
PG 16
WC Optics; Radiology, Nuclear Medicine & Medical Imaging
SC Optics; Radiology, Nuclear Medicine & Medical Imaging
GA V27YC
UT WOS:000208647500009
ER
PT J
AU Lee, NR
Wallace, GL
Weddle, CR
Liverpool, M
Clasen, LS
Blumenthal, J
Lenroot, RK
Giedd, JN
AF Lee, N. R.
Wallace, G. L.
Weddle, C. R.
Liverpool, M.
Clasen, L. S.
Blumenthal, J.
Lenroot, R. K.
Giedd, J. N.
TI Executive function profiles of males and females with an additional X
chromosome
SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH
LA English
DT Meeting Abstract
DE sex chromosome variation; executive function; CANTAB; BRIEF
C1 [Lee, N. R.; Wallace, G. L.; Weddle, C. R.; Liverpool, M.; Clasen, L. S.; Blumenthal, J.; Lenroot, R. K.; Giedd, J. N.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
RI Lee, Nancy Raitano/F-2565-2011; Giedd, Jay/A-3080-2008; Giedd,
Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Lee,
Nancy/0000-0002-6663-0713
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0964-2633
J9 J INTELL DISABIL RES
JI J. Intell. Disabil. Res.
PD OCT
PY 2009
VL 53
BP 836
EP 836
PG 1
WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry;
Rehabilitation
SC Education & Educational Research; Genetics & Heredity; Neurosciences &
Neurology; Psychiatry; Rehabilitation
GA 499AO
UT WOS:000270189000022
ER
PT J
AU Scharschmidt, TC
List, K
Grice, EA
Szabo, R
Renaud, G
Lee, CCR
Wolfsberg, TG
Bugge, TH
Segre, JA
AF Scharschmidt, Tiffany C.
List, Karin
Grice, Elizabeth A.
Szabo, Roman
Renaud, Gabriel
Lee, Chyi-Chia R.
Wolfsberg, Tyra G.
Bugge, Thomas H.
Segre, Julia A.
CA NISC Comparative Sequencing Progra
TI Matriptase-Deficient Mice Exhibit Ichthyotic Skin with a Selective Shift
in Skin Microbiota
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID EPIDERMAL DIFFERENTIATION COMPLEX; AUTOSOMAL RECESSIVE ICHTHYOSIS;
ATOPIC-DERMATITIS; ANTIMICROBIAL PEPTIDES; BARRIER FUNCTION;
STRATUM-CORNEUM; BACTERIAL BIOTA; DIVERSITY; ENVIRONMENT; ECOLOGY
AB Suppressor of tumorigenicity 14 (St14) encodes matriptase, a serine protease, which regulates processing of profilaggrin to filaggin in vivo. Here, we report that transgenic mice with 1% of wild-type St14 levels (St14(hypo/-)) display aberrant processing of profilaggrin and model human ichthyotic skin phenotypes. Scaling of the skin appears at 1 week of age with underlying epidermal acanthosis and orthohyperkeratosis as well as a CD4+ T-cell dermal infiltrate. Upregulation of antimicrobial peptides occurs when challenged by exposure to the postnatal environment. Direct genomic sequencing of bacterial 16S rRNA genes to query microbial diversity identifies a significant shift in both phylogeny and community structure between St14(hypo/-) mice and control littermates. St14(hypo/-) mice have a selective shift in resident skin microbiota with a decrease of the dominant genus of skin bacteria, Pseudomonas and an accompanying increase of Corynebacterium and Streptococcus. St14(hypo/-) mice provide early evidence that the cutaneous microbiome can be specifically altered by genetic state, which may play an important role in modulating skin disease.
C1 [Segre, Julia A.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Scharschmidt, Tiffany C.] Univ Calif, San Francisco Sch Med, HHMI, NIH,Res Scholars Program, Bethesda, MD USA.
[List, Karin; Szabo, Roman; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[NISC Comparative Sequencing Progra] NIH, Intramural Sequencing Ctr, Rockville, MD USA.
[Lee, Chyi-Chia R.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Segre, JA (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Room 4A26, Bethesda, MD 20892 USA.
EM jsegre@nhgri.nih.gov
RI Lee, Chyi-Chia/I-1938-2013;
OI Lee, Chyi-Chia/0000-0002-5306-7781; Scharschmidt,
Tiffany/0000-0001-5517-089X; Grice, Elizabeth/0000-0003-3939-2200
FU NHGRI; NIDCR; Department of Defense [DAMD-17-02-1-0693]
FX This work was supported by the NHGRI and NIDCR Research Programs and by
a grant from the Department of Defense (DAMD-17-02-1-0693) to Thomas
Bugge. All studies were appropriately reviewed by an NIH Animal Care and
Use Committee. We thank Cherry Yang for genotyping, Dr Maria Turner for
assisting with histological interpretation, Drs Pamela Schwartzberg and
Jennifer Cannons for sharing immunologic expertise, Martha Kirby and
Stacie Anderson for FACs analysis, Dr Peter Elias for intellectual
discussions on skin barrier analysis and the CRTH2 antibody, Histoserv
Inc. for immunohistochemistry services, Alice Young, Robert Blakesly and
Gerard Bouffard from NISC for their sequencing expertise and services,
Julia Fekecs for assistance with figures, and Drs Christina Herrick and
Heidi Kong for reviewing the article. We also thank members of the lab
for their underlying contributions.
NR 45
TC 29
Z9 31
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD OCT
PY 2009
VL 129
IS 10
BP 2435
EP 2442
DI 10.1038/jid.2009.104
PG 8
WC Dermatology
SC Dermatology
GA 498SL
UT WOS:000270163300019
PM 19387477
ER
PT J
AU Subleski, JJ
Ortaldo, JR
AF Subleski, Jeff J.
Ortaldo, John R.
TI NKT cells: to suppress or not to suppress, that is the question
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Editorial Material
DE human NKT cells; suppression; APC
ID KILLER T-CELLS; NATURAL-KILLER; IMMUNOSURVEILLANCE; KRN7000
C1 [Subleski, Jeff J.; Ortaldo, John R.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Ortaldo, JR (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, 560 Chandler St, Frederick, MD 21702 USA.
EM ortaldo@mail.ncifcrf.gov
NR 11
TC 1
Z9 1
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD OCT
PY 2009
VL 86
IS 4
BP 751
EP 752
DI 10.1189/jlb.0309118
PG 2
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 501FS
UT WOS:000270366500002
PM 19797301
ER
PT J
AU Piao, W
Song, C
Chen, HY
Diaz, MAQ
Wahl, LM
Fitzgerald, KA
Li, LW
Medvedev, AE
AF Piao, Wenji
Song, Chang
Chen, Haiyan
Diaz, Marco A. Quevedo
Wahl, Larry M.
Fitzgerald, Katherine A.
Li, Liwu
Medvedev, Andrei E.
TI Endotoxin tolerance dysregulates MyD88-and Toll/IL-1R domain-containing
adapter inducing IFN-beta-dependent pathways and increases expression of
negative regulators of TLR signaling
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE lipopolysaccharide; signal transduction; suppression/anergy; cell
activation; monocytes/macrophages
ID NF-KAPPA-B; TOLL-LIKE RECEPTORS; NECROSIS-FACTOR-ALPHA; CUTTING EDGE;
GENE-EXPRESSION; TRANSCRIPTION FACTORS; BACTERIAL FLAGELLIN;
IMMUNE-RESPONSES; EPITHELIAL-CELLS; INNATE IMMUNITY
AB Endotoxin tolerance reprograms cell responses to LPS by repressing expression of proinflammatory cytokines, while not inhibiting production of anti-inflammatory cytokines and antimicrobial effectors. Molecular mechanisms of induction and maintenance of endotoxin tolerance are incompletely understood, particularly with regard to the impact of endotoxin tolerization on signalosome assembly, activation of adaptor-kinase modules, and expression of negative regulators of TLR signaling in human cells. In this study, we examined LPS-mediated activation of MyD88-dependent and Toll-IL-1R-containing adaptor inducing IFN-beta (TRIF)-dependent pathways emanating from TLR4 and expression of negative regulators of TLR signaling in control and endotoxin-tolerant human monocytes. Endotoxin tolerization suppressed LPS-inducible TLR4-TRIF and TRIF-TANK binding kinase (TBK) 1 associations, induction of TBK1 kinase activity, activation of IFN regulatory factor (IRF)-3, and expression of RANTES and IFN-beta. Tolerance-mediated dysregulation of the TLR4-TRIF-TBK1 signaling module was accompanied by increased levels of suppressor of I kappa B kinase-epsilon (SIKE) and sterile alpha and Armadillo motif-containing molecule (SARM). LPS-tolerant cells showed increased expression of negative regulators Toll-interacting protein (Tollip), suppressor of cytokine signaling (SOCS)-1, IL-1R-associated kinase-M, and SHIP-1, which correlated with reduced p38 phosphorylation, I kappa B-alpha degradation, and inhibited expression of TNF-alpha, IL-6, and IL-8. To examine functional consequences of increased expression of Tollip in LPS-tolerized cells, we overexpressed Tollip in 293/ TLR4/MD-2 transfectants and observed blunted LPS-inducible activation of NF-kappa B and RANTES, while TNF-alpha responses were not affected. These data demonstrate dysregulation of TLR4-triggered MyD88-and TRIF-dependent signaling pathways and increased expression of negative regulators of TLR signaling in endotoxin-tolerant human monocytes. J. Leukoc. Biol. 86: 863-875; 2009.
C1 [Piao, Wenji; Song, Chang; Chen, Haiyan; Diaz, Marco A. Quevedo; Medvedev, Andrei E.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Wahl, Larry M.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Fitzgerald, Katherine A.] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA.
[Li, Liwu] Virginia Tech, Dept Biol, Blacksburg, VA USA.
RP Medvedev, AE (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, 660 W Redwood St,Howard Hall Bldg,Rm HH 324, Baltimore, MD 21201 USA.
EM amedvedev@som.umaryland.edu
OI Li, Liwu/0000-0001-8870-5299
FU National Institutes of Health RO1 [AI-059524, AI067497, AI64414]
FX This work was supported by National Institutes of Health RO1 grants
AI-059524 (A. E. M.), AI067497 (K. A. F.), and AI64414 (L. L.).
NR 75
TC 69
Z9 70
U1 1
U2 6
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD OCT
PY 2009
VL 86
IS 4
BP 863
EP 875
DI 10.1189/jlb.0309189
PG 13
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 501FS
UT WOS:000270366500014
PM 19656901
ER
PT J
AU Hu, K
Doucleff, M
Clore, GM
AF Hu, Kaifeng
Doucleff, Michaeleen
Clore, G. Marius
TI Using multiple quantum coherence to increase the N-15 resolution in a
three-dimensional TROSY HNCO experiment for accurate PRE and RDC
measurements
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE TROSY HNCO; High resolution; RDC; PRE
ID RESIDUAL DIPOLAR COUPLINGS; PARAMAGNETIC RELAXATION ENHANCEMENT; SMALL
ALPHA/BETA PROTEIN; CORRELATED MOTIONS; MOLECULAR-DYNAMICS; ORDER
PARAMETERS; PULSE SEQUENCES; NMR STRUCTURES; BACKBONE; COMPLEXES
AB We present a new version of the 3D TROSY HNCO pulse scheme, referred to as HR-TROSY HNCO, with comparable resolution in the N-15 dimension to a 2D H-1-N-15 HSQC experiment. In the conventional 3D TROSY HNCO, the constant time period (1/2J(NC) similar to 32 ms) severely limits the maximum resolution in the N-15 dimension. In the HR-TROSY HNCO experiment presented here, both constant time periods (similar to 32 ms each) for coherence forward and backward transfer between N-15 and C-13' are utilized to double the N-15 evolution time. This leads to a dramatic enhancement in peak separation along the N-15 dimension, making the HR-TROSY HNCO an ideal pulse scheme for accurate paramagnetic relaxation enhancement and residual dipolar coupling measurements. Published by Elsevier Inc.
C1 [Hu, Kaifeng; Doucleff, Michaeleen; Clore, G. Marius] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM mariusc@intra.niddk.nih.gov
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
FU NIDDK, National Institutes of Health; Office of the Director of the
National Institutes of Health
FX This work was supported by the intramural program of NIDDK, National
Institutes of Health, and the Intramural AIDS Targeted Antiviral Program
of the Office of the Director of the National Institutes of Health (to
G. M. C.).
NR 37
TC 10
Z9 10
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
J9 J MAGN RESON
JI J. Magn. Reson.
PD OCT
PY 2009
VL 200
IS 2
BP 173
EP 177
DI 10.1016/j.jmr.2009.06.019
PG 5
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 526AW
UT WOS:000272260900001
PM 19615926
ER
PT J
AU Shemesh, N
Ozarslan, E
Bar-Shir, A
Basser, PJ
Cohen, Y
AF Shemesh, Noam
Oezarslan, Evren
Bar-Shir, Amnon
Basser, Peter J.
Cohen, Yoram
TI Observation of restricted diffusion in the presence of a free diffusion
compartment: Single- and double-PFG experiments
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE Double-pulsed gradient spin echo; PGSE; Double PGSE; d-PGSE; Diffusion;
White matter phantom; Crossing fibers; Low-q; Pulsed field gradients;
PFG; NMR; Fast; Slow diffusing
ID Q-SPACE DIFFUSION; MAGNETIC-RESONANCE-SPECTROSCOPY; RELAXATION-TIME NMR;
GRADIENT WAVE-FORMS; SPIN-ECHO ANALYSIS; FIELD-GRADIENT; STRUCTURAL
INFORMATION; EXPERIMENTAL PARAMETERS; WATER DIFFUSION; SPHERICAL PORES
AB Theoretical and experimental studies of restricted diffusion have been conducted for decades using single pulsed field gradient (s-PFG) diffusion experiments. In homogenous samples, the diffusion-diffraction phenomenon arising from a single population of diffusing species has been observed experimentally and predicted theoretically. In this study, we introduce a composite bi-compartmental model which superposes restricted diffusion in microcapillaries with free diffusion in an unconfined compartment, leading to fast and slow diffusing components in the NMR signal decay. Although simplified (no exchange), the superposed diffusion modes in this model may exhibit features seen in more complex porous materials and biological tissues. We find that at low q-values the freely diffusing component masks the restricted diffusion component, and that prolongation of the diffusion time shifts the transition from free to restricted profiles to lower q-values. The effect of increasing the volume fraction of freely diffusing water was also studied; we find that the transition in the signal decay from the free mode to the restricted mode occurs at higher q-values when the volume fraction of the freely diffusing water is increased. These findings were then applied to a phantom consisting of crossing fibers, which demonstrated the same qualitative trends in the signal decay. The angular d-PGSE experiment, which has been recently shown to be able to measure small compartmental dimensions even at low q-values, revealed that microscopic anisotropy is lost at low q-values where the fast diffusing component is prominent. Our findings may be of importance in studying realistic systems which exhibit compartmentation. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Shemesh, Noam; Bar-Shir, Amnon; Cohen, Yoram] Tel Aviv Univ, Sch Chem, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel.
[Oezarslan, Evren; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD USA.
RP Cohen, Y (reprint author), Tel Aviv Univ, Sch Chem, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel.
EM ycohen@post.tau.ac.il
RI Ozarslan, Evren/B-4858-2013; Basser, Peter/H-5477-2011;
OI Ozarslan, Evren/0000-0003-0859-1311; Shemesh, Noam/0000-0001-6681-5876
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX P.J.B and E.O. were supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 62
TC 28
Z9 28
U1 2
U2 14
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
J9 J MAGN RESON
JI J. Magn. Reson.
PD OCT
PY 2009
VL 200
IS 2
BP 214
EP 225
DI 10.1016/j.jmr.2009.07.005
PG 12
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 526AW
UT WOS:000272260900006
PM 19656697
ER
PT J
AU Vogel-Claussen, J
Skrok, J
Dombroski, D
Shea, SM
Shapiro, EP
Bohlman, M
Lorenz, CH
Lima, JAC
Bluemke, DA
AF Vogel-Claussen, Jens
Skrok, Jan
Dombroski, David
Shea, Steven M.
Shapiro, Edward P.
Bohlman, Mark
Lorenz, Christine H.
Lima, Joao A. C.
Bluemke, David A.
TI Comprehensive Adenosine Stress Perfusion MRI Defines the Etiology of
Chest Pain in the Emergency Room: Comparison With Nuclear Stress Test
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE adenosine stress perfusion cardiac MRI; emergency room; chest pain;
microvascular disease
ID CORONARY-ARTERY-DISEASE; CARDIAC MAGNETIC-RESONANCE;
EMISSION-COMPUTED-TOMOGRAPHY; CONTRAST-ENHANCED MRI; SMALL VESSEL
DISEASE; MYOCARDIAL-PERFUSION; PROGNOSTIC VALUE; MICROVASCULAR
DYSFUNCTION; SYNDROME-X; ANGIOGRAPHY
AB Purpose: To compare standard of care nuclear SPECT imaging with cardiac magnetic resonance imaging (MRI) for emergency room (ER) patients with chest pain and intermediate probability for coronary artery disease.
Materials and Methods: Thirty-one patients with chest pain, negative electrocardiogram (ECG), and negative cardiac enzymes who underwent cardiac single photon emission tomography (SPECT) within 24 h of ER admission were enrolled. Patients underwent a comprehensive cardiac MRI exam including gated cine imaging, adenosine stress and rest perfusion imaging and delayed enhancement imaging. Patients were followed for 14 +/- 4.7 months.
Results: Of 27 patients, 8 (30%) showed subendocardial hypoperfusion on MRI that was not detected on SPECT. These patients had a higher rate of diabetes (P = 0.01) and hypertension (P = 0.01) and a lower global myocardial perfusion reserve (P = 0.01) compared with patients with a normal cardiac MRI (n = 10). Patients with subendocardial hypoperfusion had more risk factors for cardiovascular disease (mean 4.4) compared with patients with a normal MRI (mean 2.5; P = 0.005). During the follow-up period. patients with subendocardial hypoperfusion on stress MRI were more likely to return to the ER with chest pain compared with patients who had a normal cardiac MRI (P = 0.02). Four patients did not finish the MR exam due to claustrophobia.
Conclusion: In patients with chest pain, diabetes and hypertension, cardiac stress perfusion MRI identified diffuse subendocardial hypoperfusion defects in the ER setting not seen on cardiac SPECT, which is suspected to reflect microvascular disease.
C1 [Vogel-Claussen, Jens; Skrok, Jan; Dombroski, David; Bohlman, Mark; Lima, Joao A. C.; Bluemke, David A.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Sch Med, Baltimore, MD 21287 USA.
[Shapiro, Edward P.; Lima, Joao A. C.] Johns Hopkins Univ, Dept Cardiol, Sch Med, Baltimore, MD 21287 USA.
[Shea, Steven M.; Lorenz, Christine H.] Siemens Corp Res Inc, Imaging & Visualizat, Princeton, NJ USA.
[Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
RP Vogel-Claussen, J (reprint author), Johns Hopkins Univ, Dept Radiol, Nelson Basement MRI 143,600 N Wolfe St, Baltimore, MD 21287 USA.
EM jclauss1@jhmi.edu
OI Bluemke, David/0000-0002-8323-8086
FU Siemens Medical Solutions. Inc. [JHU-2006-MR-27-01]
FX Contract grant sponsor: Siemens Medical Solutions. Inc.; Contract grant
number: numbers; Contract grant number: JHU-2006-MR-27-01.
NR 32
TC 14
Z9 14
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD OCT
PY 2009
VL 30
IS 4
BP 753
EP 762
DI 10.1002/jmri.21899
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 503GY
UT WOS:000270522900008
PM 19787721
ER
PT J
AU Leppert, IR
Almli, CR
McKinstry, RC
Mulkern, RV
Pierpaoli, C
Rivkin, MJ
Pike, GB
AF Leppert, Ilana R.
Almli, C. Robert
McKinstry, Robert C.
Mulkern, Robert V.
Pierpaoli, Carlo
Rivkin, Micheal J.
Pike, G. Bruce
CA Brain Dev Cooperative Grp
TI T2 Relaxometry of Maturing Brains Response
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Letter
C1 [Leppert, Ilana R.; Pike, G. Bruce] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
[Almli, C. Robert] Washington Univ, Sch Med, Dept Neurol, Dev Neuropsychobiol Lab,Program Neurosci, St Louis, MO 63110 USA.
[Almli, C. Robert] Washington Univ, Sch Med, Dept Psychol, Dev Neuropsychobiol Lab,Program Neurosci, St Louis, MO 63110 USA.
[Almli, C. Robert] Washington Univ, Sch Med, Program Occupat Therapy, St Louis, MO 63110 USA.
[McKinstry, Robert C.] Washington Univ, Med Ctr, St Louis Childrens Hosp, St Louis, MO 63110 USA.
[McKinstry, Robert C.] Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Mulkern, Robert V.] Harvard Univ, Childrens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA.
[Pierpaoli, Carlo] NICHHD, NIH, Bethesda, MD 20892 USA.
[Rivkin, Micheal J.] Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol Psychiat & Radiol, Boston, MA 02115 USA.
RP Leppert, IR (reprint author), McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
EM ilana@bic.nmi.mcgill.ca
RI Pierpaoli, Carlo/E-1672-2011; Pike, Bruce/K-5562-2014
OI Pike, Bruce/0000-0001-8924-683X
NR 2
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD OCT
PY 2009
VL 30
IS 4
BP 912
EP 912
DI 10.1002/jmri.21928
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 503GY
UT WOS:000270522900032
ER
PT J
AU Miller, FG
AF Miller, F. G.
TI Death and organ donation: back to the future
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
ID BRAIN-DEATH
AB The practice of transplantation of vital organs from "brain-dead'' donors is in a state of theoretical disarray. Although the law and prevailing medical ethics treat patients diagnosed as having irreversible total brain failure as dead, scholars have increasingly challenged the established rationale for regarding these patients as dead. To understand the ethical situation that we now face, it is helpful to revisit the writings of the philosopher Hans Jonas, who forcefully challenged the emerging effort to redefine death in the late 1960s.
C1 NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
FU Intramural Research Program of the Clinical Center; National Institutes
of Health.
FX This research was supported by the Intramural Research Program of the
Clinical Center, National Institutes of Health.
NR 27
TC 10
Z9 10
U1 0
U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
J9 J MED ETHICS
JI J. Med. Ethics
PD OCT
PY 2009
VL 35
IS 10
BP 616
EP 620
DI 10.1136/jme.2009.030627
PG 5
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 501FL
UT WOS:000270365400009
PM 19793942
ER
PT J
AU Chou, WYS
Hunt, YM
Beckjord, EB
Moser, RP
Hesse, BW
AF Chou, Wen-ying Sylvia
Hunt, Yvonne M.
Beckjord, Ellen Burke
Moser, Richard P.
Hesse, Bradford W.
TI Social Media Use in the United States: Implications for Health
Communication
SO JOURNAL OF MEDICAL INTERNET RESEARCH
LA English
DT Article
DE Internet; social media; social networking; demography; population
surveillance; eHealth, new technologies; health communication
ID NATIONAL TRENDS SURVEY; SUPPORT GROUPS; INFORMATION; INTERNET;
PARTICIPATION; HINTS; CARE
AB Background: Given the rapid changes in the communication landscape brought about by participative Internet use and social media, it is important to develop a better understanding of these technologies and their impact on health communication. The first step in this effort is to identify the characteristics of current social media users. Up-to-date reporting of current social media use will help monitor the growth of social media and inform health promotion/communication efforts aiming to effectively utilize social media.
Objective: The purpose of the study is to identify the sociodemographic and health-related factors associated with current adult social media users in the United States.
Methods: Data came from the 2007 iteration of the Health Information National Trends Study (HINTS, N = 7674). HINTS is a nationally representative cross-sectional survey on health-related communication trends and practices. Survey respondents who reported having accessed the Internet (N = 5078) were asked whether, over the past year, they had (1) participated in an online support group, (2) written in a blog, (3) visited a social networking site. Bivariate and multivariate logistic regression analyses were conducted to identify predictors of each type of social media use.
Results: Approximately 69% of US adults reported having access to the Internet in 2007. Among Internet users, 5% participated in an online support group, 7% reported blogging, and 23% used a social networking site. Multivariate analysis found that younger age was the only significant predictor of blogging and social networking site participation; a statistically significant linear relationship was observed, with younger categories reporting more frequent Use. Younger age, poorer subjective health, and a personal cancer experience predicted support group participation. In general, social media are penetrating the US population independent of education, race/ethnicity, or health care access.
Conclusions: Recent growth of social media is not uniformly distributed across age groups; therefore, health communication programs utilizing social media must first consider the age of the targeted population to help ensure that messages reach the intended audience. While racial/ethnic and health status-related disparities exist in Internet access, among those with Internet access, these characteristics do not affect social media use. This finding suggests that the new technologies, represented by social media, may be changing the communication pattern throughout the United States.
C1 [Chou, Wen-ying Sylvia] NCI, Hlth Commun & Informat Res Branch, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
[Beckjord, Ellen Burke] RAND Corp, Pittsburgh, PA USA.
[Moser, Richard P.] NCI, Behav Res Program, Bethesda, MD 20892 USA.
RP Chou, WYS (reprint author), NCI, Hlth Commun & Informat Res Branch, Canc Prevent Fellowship Program, 6130 Execut Blvd EPN,4051A, Bethesda, MD 20892 USA.
EM chouws@mail.nih.gov
OI Hesse, Bradford/0000-0003-1142-1161
FU National Cancer Institute, National Institutes of Health
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health.
NR 29
TC 220
Z9 221
U1 25
U2 164
PU JMIR PUBLICATIONS, INC
PI TORONTO
PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA
SN 1438-8871
J9 J MED INTERNET RES
JI J. Med. Internet Res.
PD OCT-DEC
PY 2009
VL 11
IS 4
AR e48
DI 10.2196/jmir.1249
PG 12
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA 556YW
UT WOS:000274633000009
PM 19945947
ER
PT J
AU Kader, M
Bixler, S
Roederer, M
Veazey, R
Mattapallil, JJ
AF Kader, M.
Bixler, S.
Roederer, M.
Veazey, R.
Mattapallil, J. J.
TI CD4 T cell subsets in the mucosa are CD28+Ki-67-HLA-DR-CD69+but show
differential infection based on alpha 4 beta 7 receptor expression
during acute SIV infection
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Article; Proceedings Paper
CT 26th Annual Symposium on Non-Human Primate Models for AIDS
CY DEC 09-12, 2008
CL San Juan, PR
SP Wisconsin Natl Primate Res Ctr, Caribbean Primate Res Ctr, Natl Inst Hlth, Natl Inst Allergies & Infect Dis, Off AIDS Res
DE acute; CD4; Gut; HIV; IL-17; IL-21; IL-23; immunodeficiency; intestine;
mucosa; simian; SIV; TGF beta
ID SIMIAN IMMUNODEFICIENCY VIRUS; GASTROINTESTINAL-TRACT; TGF-BETA;
ANTIRETROVIRAL THERAPY; VIRAL REPLICATION; RHESUS MACAQUES;
LYMPHOID-TISSUE; DEPLETION; GUT; LYMPHOCYTES
AB Background
CD4 T cell depletion in the mucosa has been well documented during acute HIV and SIV infections. The demonstration the HIV/SIVcan use the alpha 4 beta 7 receptor for viral entry suggests that these viruses selectively target CD4 T cells in the mucosa that express high levels of alpha 4 beta 7 receptor.
Methods
Mucosal samples obtained from SIV infected rhesus macaques during the early phase of infection were used for immunophenotypic analysis. CD4 T cell subsets were sorted based on the expression of beta 7 and CD95 to quantify the level of SIV infection in different subsets of CD4 T cells. Changes in IL-17, IL-21, IL-23 and TGF beta mRNA expression was determined using Taqman PCR.
Results
CD4 T cells in the mucosa were found to harbor two major population of cells; -25% of CD4 T cells expressed the alpha 4+beta 7hi phenotype, whereas the rest of the 75% expressed an alpha 4+beta 7int phenotype. Both the subsets were predominantly CD28+Ki-67-HLA-DR- but CD69+, and expressed detectable levels of CCR5 on their surface. Interestingly, however, alpha 4+beta 7hiCD4 T cells were found to harbor more SIV than the alpha 4+beta 7int subsets at day 10 pi. Early infection was associated with a dramatic increase in the expression of IL-17, and IL-17 promoting cytokines IL-21, IL-23, and TGF beta that stayed high even after the loss of mucosal CD4 T cells.
Conclusions
Our results suggest that the differential expression of the alpha 4 beta 7 receptor contributes to the differences in the extent of infection in CD4 T cell subsets in the mucosa. Early infection is associated dysregulation of the IL-17 network in mucosal tissues involves other non-Th-17 cells that likely contributes to the pro-inflammatory environment in the mucosa during acute stages of SIV infection.
C1 [Mattapallil, J. J.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
[Roederer, M.] Tulane Natl Reg Primate Ctr, Covington, LA USA.
[Veazey, R.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Mattapallil, JJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Room B4098, Bethesda, MD 20814 USA.
EM jmattapallil@usuhs.mil
FU NIAID NIH HHS [K22 AI071812-02, K22AI07812, K22 AI071812-01, K22
AI071812]; NIDCR NIH HHS [R21 DE018339-02, R21 DE018339, R21
DE018339-01, R21DE018339, R21 DE018339-02S1]
NR 30
TC 17
Z9 17
U1 0
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD OCT
PY 2009
VL 38
BP 24
EP 31
DI 10.1111/j.1600-0684.2009.00372.x
PG 8
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 508BJ
UT WOS:000270901500005
PM 19863675
ER
PT J
AU Kader, M
Bixler, S
Piatak, M
Lifson, J
Mattapallil, JJ
AF Kader, M.
Bixler, S.
Piatak, M.
Lifson, J.
Mattapallil, J. J.
TI Anti-retroviral therapy fails to restore the severe Th-17: Tc-17
imbalance observed in peripheral blood during simian immunodeficiency
virus infection
SO JOURNAL OF MEDICAL PRIMATOLOGY
LA English
DT Article; Proceedings Paper
CT 26th Annual Symposium on Non-Human Primate Models for AIDS
CY DEC 09-12, 2008
CL San Juan, PR
SP Wisconsin Natl Primate Res Ctr, Caribbean Primate Res Ctr, Natl Inst Hlth, Natl Inst Allergies & Infect Dis, Off AIDS Res
DE ART; CD4; FTC; Gut; HIV; immunodeficiency; intestine; mucosa; PMPA;
simian; SIV
ID T-CELL DEPLETION; PLASMA VIRAL LOAD; LYMPHOID-TISSUE; HIV-1 INFECTION;
GASTROINTESTINAL-TRACT; SIV INFECTION; TH17 CELLS; GUT; MEMORY; AIDS
AB Background
Human immuno deficiency virus and simian immunodeficiency virus infections are characterized by a severe loss of Th-17 cells (IL-17+CD4+ T cells) that has been associated with disease progression and systemic dissemination of bacterial infections. Anti-retroviral therapy (ART) has led to repopulation of CD4+ T cells in peripheral tissues with little sustainable repopulation in mucosal tissues. Given the central importance of Th-17 cells in mucosal homeostasis, it is not known if the failure of ART to permanently repopulate mucosal tissues is associated with a failure to restore Th-17 cells that are lost during infection.
Methods
Dynamics of alpha 4+beta 7hi CD4+ T cells in peripheral blood of SIV infected rhesus macaques were evaluated and compared to animals that were treated with ART. The frequency of Th-17 and Tc-17 cells was determined following infection and after therapy. Relative expression of IL-21, IL-23, and TGF beta was determined using Taqman PCR.
Results
Treatment of SIV infected rhesus macaques with anti-retroviral therapy was associated with a substantial repopulation of mucosal homing alpha 4+beta 7hiCD4+ T cells in peripheral blood. This repopulation, however, was not accompanied by a restoration of Th-17 responses. Interestingly, SIV infection was associated with an increase in Tc-17 responses (IL-17+CD8+ T cells) suggesting to a skewing in the ratio of Th-17: Tc-17 cells from a predominantly Th-17 phenotype to a predominantly Tc-17 phenotype. Surprisingly, Tc-17 responses remained high during the course of therapy suggesting that ART failed to correct the imbalance in Th-17 : Tc-17 responses induced following SIV infection.
Conclusions
ART was associated with substantial repopulation of alpha 4+beta 7hi CD4+ T cells in peripheral blood with little or no rebound of Th-17 cells. On the other hand, repopulation of alpha 4+beta 7hi CD4+ T cells was accompanied by persistence of high levels of Tc-17 cells in peripheral blood. The dysregulation of Th-17 and Tc-17 responses likely plays a role in disease progression.
C1 [Mattapallil, J. J.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
[Piatak, M.; Lifson, J.] NCI, SAIC, Frederick, MD 21701 USA.
RP Mattapallil, JJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Room B4098, Bethesda, MD 20814 USA.
EM jmattapallil@usuhs.mil
FU NIAID NIH HHS [K22AI07812, K22 AI071812-02, K22 AI071812, K22
AI071812-01]; NIDCR NIH HHS [R21DE018339, R21 DE018339, R21 DE018339-01,
R21 DE018339-02, R21 DE018339-02S1]
NR 31
TC 16
Z9 16
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0047-2565
J9 J MED PRIMATOL
JI J. Med. Primatol.
PD OCT
PY 2009
VL 38
BP 32
EP 38
DI 10.1111/j.1600-0684.2009.00373.x
PG 7
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA 508BJ
UT WOS:000270901500006
PM 19863676
ER
PT J
AU Vinogradova, TM
Lakatta, EG
AF Vinogradova, Tatiana M.
Lakatta, Edward G.
TI Regulation of basal and reserve cardiac pacemaker function by
interactions of cAMP-mediated PKA-dependent Ca2+ cycling with surface
membrane channels
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Review
DE Sinoatrial nodal cells; Local Ca2+ release; Ryanodine receptor; Ionic
channels; Beta-adrenergic receptor stimulation; Phosphodiesterase
ID RABBIT SINOATRIAL NODE; SUSTAINED INWARD CURRENT; PROTEIN-KINASE-A;
RECTIFIER POTASSIUM CURRENT; BETA-ADRENERGIC STIMULATION; NA+-CA2+
EXCHANGE CURRENT; SPONTANEOUS BEATING RATE; ACTIVATED CURRENT IF; CAT
RIGHT ATRIUM; SARCOPLASMIC-RETICULUM
AB Decades of intensive research of primary cardiac pacemaker, the sinoatrial node, have established potential roles of specific membrane channels in the generation of the diastolic depolarization, the major mechanism allowing sinoatrial node cells to generate spontaneous beating. During the last three decades, multiple studies made either in the isolated sinoatrial node or sinoatrial node cells have demonstrated a pivotal role of Ca2+ and, specifically Ca2+ release from sarcoplasmic reticulum, for spontaneous beating of cardiac pacemaker. Recently, spontaneous, rhythmic local subsarcolemmal Ca2+ releases from ryanodine receptors during late half of the diastolic depolarization have been implicated as a vital factor in the generation of sinoatrial node cell spontaneous. ring. Local Ca2+ releases are driven by a unique combination of high basal cAMP production by adenylyl cyclases, high basal cAMP degradation by phosphodiesterases and a high level of cAMP-mediated PKA-dependent phosphorylation. These local Ca2+ releases activate an inward Na+-Ca2+ exchange current which accelerates the terminal diastolic depolarization rate and, thus, controls the spontaneous pacemaker. ring. Both the basal primary pacemaker beating rate and its modulation via beta-adrenergic receptor stimulation appear to be critically dependent upon intact RyR function and local subsarcolemmal sarcoplasmic reticulum generated Ca2+ releases. This review aspires to integrate the traditional viewpoint that has emphasized the supremacy of the ensemble of surface membrane ion channels in spontaneous. ring of the primary cardiac pacemaker, and these novel perspectives of cAMP-mediated PKA-dependent Ca2+ cycling in regulation of the heart pacemaker clock, both in the basal state and during beta-adrenergic receptor stimulation. (C) 2009 Published by Elsevier Inc.
C1 [Vinogradova, Tatiana M.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA.
RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM LakattaE@grc.nia.nih.gov
FU National Institute on Aging, National Institutes of Health
FX This work is supported, in part, by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health.
NR 168
TC 33
Z9 34
U1 0
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD OCT
PY 2009
VL 47
IS 4
BP 456
EP 474
DI 10.1016/j.yjmcc.2009.06.014
PG 19
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 526AX
UT WOS:000272261000006
PM 19573534
ER
PT J
AU Crawford, JR
Santi, MR
Cornelison, R
Sallinen, SL
Haapasalo, H
MacDonald, TJ
AF Crawford, John R.
Santi, Maria Rita
Cornelison, Robbie
Sallinen, Satu-Leena
Haapasalo, Hannu
MacDonald, Tobey J.
TI Detection of human herpesvirus-6 in adult central nervous system tumors:
predominance of early and late viral antigens in glial tumors
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Human herpesvirus-6; Brain tumor; Tissue microarray; HHV-6
ID MULTIPLE-SCLEROSIS PATIENTS; STEM-CELL TRANSPLANTATION;
POLYMERASE-CHAIN-REACTION; HUMAN CYTOMEGALOVIRUS; BRAIN-TUMORS;
INTEGRATED HUMAN-HERPESVIRUS-6; CLINICAL-FEATURES; GENOMIC SEQUENCES;
HUMAN ASTROCYTES; 6 DNA
AB The purpose is to determine the incidence of active and latent human herpesvirus-6 (HHV-6) infection in a large cohort of adult primary and recurrent CNS tumors. We screened a tissue microarray (TMA) containing more than 200 adult primary and recurrent CNS tumors with known clinical information for the presence of HHV-6 DNA by in situ hybridization (ISH) and protein by immunohistochemistry (IHC). One hundred six of 224 (47%) CNS tumors were positive for HHV-6 U57 Major Capsid Protein (MCP) gene by ISH compared to 0/25 non tumor control brain (P = 0.001). Fourteen of 30 (47%) tumors were HHV-6 MCP positive by nested PCR compared to 0/25 non-tumor brain controls (P = 0.001), revealing HHV-6 Variant A in 6 of 14 samples. HHV-6A/B early (p41) and late (gp116/64/54) antigens were detected by IHC in 66 of 277 (24%) (P = 0.003) and 84 of 282 (35%) (P = 0.002) tumors, respectively, suggesting active infection. HHV-6 p41 (P = 0.645) and gp116/64/54 (P = 0.198) antigen detection was independent of recurrent disease. Glial tumors were 3 times more positive by IHC compared to non glial tumors for both HHV-6 gp116/64/54 (P = 0.0002) and HHV-6 p41 (P = 0.004). Kaplan Meier survival analysis showed no effect of HHV-6 gp116/64/54 (P = 0.852) or HHV-6 p41 (P = 0.817) antigen detection on survival. HHV-6 early and late antigens are detected in adult primary and recurrent CNS tumors more frequently in glial tumors. We hypothesize that the glial-tropic features of HHV-6 may play an important modifying role in tumor biology that warrants further investigation.
C1 [Crawford, John R.] Univ Calif San Diego, Dept Neurol, La Jolla, CA 92093 USA.
[Haapasalo, Hannu] Tampere Univ Hosp, Dept Pathol, Tampere 33521, Finland.
[Sallinen, Satu-Leena] Tampere Univ Hosp, Genet Outpatient Clin, Dept Pediat, Tampere 33521, Finland.
[Cornelison, Robbie] NCI, Mol Genet Sect, Bethesda, MD 20892 USA.
[Crawford, John R.] George Washington Univ, Dept Neurol, Washington, DC 20010 USA.
[Santi, Maria Rita] George Washington Univ, Dept Pathol, Washington, DC 20010 USA.
[MacDonald, Tobey J.] George Washington Univ, Dept Hematol Oncol, Washington, DC 20010 USA.
[Crawford, John R.; Santi, Maria Rita; MacDonald, Tobey J.] George Washington Univ, Childrens Natl Med Ctr, Brain Tumor Inst, Washington, DC 20010 USA.
RP Crawford, JR (reprint author), Univ Calif San Diego, Dept Neurol, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM jrcrawford@ucsd.edu
RI MacDonald, Tobey/D-4554-2013
FU National Institutes of Health Neurological Sciences Academic Development
Award (NSADA) [K12NS052159-01A]
FX The authors would like to thank Dr. Juha Kononen for gifting the adult
tissue microarray and Dr. Elisabeth Rushing (Armed Forces Institute of
Pathology, Washington DC) for providing the adult non tumor control
tissue. We thank Dr. Steven Jacobson (National Institute of Neurological
Disorders and Stroke) for providing positive control HHV-6 encephalitis
material and infected cell lysate. This work was supported by the
National Institutes of Health Neurological Sciences Academic Development
Award (NSADA) K12NS052159-01A.
NR 50
TC 12
Z9 15
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD OCT
PY 2009
VL 95
IS 1
BP 49
EP 60
DI 10.1007/s11060-009-9908-2
PG 12
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 495IO
UT WOS:000269884600006
PM 19424665
ER
PT J
AU Sanchez-Ortiz, E
Hahm, BK
Armstrong, DL
Rossie, S
AF Sanchez-Ortiz, Efrain
Hahm, Byoung Kwon
Armstrong, David L.
Rossie, Sandra
TI Protein phosphatase 5 protects neurons against amyloid-beta toxicity
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE Alzheimer's disease; amyloid-beta; neuroprotection; oxidative stress;
protein phosphatase 5
ID STAUROSPORINE-INDUCED APOPTOSIS; CULTURED CORTICAL-NEURONS; RAT
HIPPOCAMPAL-NEURONS; ALZHEIMERS-DISEASE; OXIDATIVE STRESS;
HYDROGEN-PEROXIDE; CELL-DEATH; TRANSGENIC MICE; A-BETA;
NEURODEGENERATIVE DISEASES
AB Amyloid-beta (A beta) is thought to promote neuronal cell loss in Alzheimer's disease, in part through the generation of reactive oxygen species (ROS) and subsequent activation of mitogen-activated protein kinase (MAPK) pathways. Protein phosphatase 5 (PP5) is a ubiquitously expressed serine/threonine phosphatase which has been implicated in several cell stress response pathways and shown to inactivate MAPK pathways through key dephosphorylation events. Therefore, we examined whether PP5 protects dissociated embryonic rat cortical neurons in vitro from cell death evoked by A beta. As predicted, neurons in which PP5 expression was decreased by small-interfering RNA treatment were more susceptible to A beta toxicity. In contrast, over-expression of PP5, but not the inactive mutant, PP5(H304Q), prevented MAPK phosphorylation and neurotoxicity induced by A beta. PP5 also prevented cell death caused by direct treatment with H(2)O(2), but did not prevent A beta-induced production of ROS. Thus, the neuroprotective effect of PP5 requires its phosphatase activity and lies downstream of A beta-induced generation of ROS. In summary, our data indicate that PP5 plays a pivotal neuroprotective role against cell death induced by A beta and oxidative stress. Consequently, PP5 might be an effective therapeutic target in Alzheimer's disease and other neurodegenerative disorders in which oxidative stress is implicated.
C1 [Sanchez-Ortiz, Efrain; Hahm, Byoung Kwon; Rossie, Sandra] Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA.
[Sanchez-Ortiz, Efrain; Hahm, Byoung Kwon; Rossie, Sandra] Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA.
[Armstrong, David L.] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Rossie, S (reprint author), Purdue Univ, Dept Biochem, 175 S Univ St, W Lafayette, IN 47907 USA.
EM rossie@purdue.edu
FU NIH [NS031221]; Indiana University-Indiana Alzheimer Disease Center
(NIH) [P30 AG010133]; NIH Intramural Research Program [Z01-ES080043];
Roy J. Carver Foundation
FX This study was supported by NIH grant NS031221 (SR), Indiana
University-Indiana Alzheimer Disease Center (NIH) grant P30 AG010133
(SR), and the NIH Intramural Research Program at National Institute of
Environmental Health Sciences through Grant Z01-ES080043 (DLA). PP5
adenovirus constructs were prepared at the Gene Transfer Vector Core at
the University of Iowa, supported in part by the NIH and the Roy J.
Carver Foundation.
NR 69
TC 13
Z9 13
U1 1
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD OCT
PY 2009
VL 111
IS 2
BP 391
EP 402
DI 10.1111/j.1471-4159.2009.06337.x
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 498OY
UT WOS:000270152600010
PM 19686245
ER
PT J
AU Cao, DH
Kevala, K
Kim, J
Moon, HS
Jun, SB
Lovinger, D
Kim, HY
AF Cao, Dehua
Kevala, Karl
Kim, Jeffrey
Moon, Hyun-Seuk
Jun, Sang Beom
Lovinger, David
Kim, Hee-Yong
TI Docosahexaenoic acid promotes hippocampal neuronal development and
synaptic function
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE docosahexaenoic acid; hippocampal development; long-term potentiation;
neurite growth; synaptic function; synaptogenesis
ID POLYUNSATURATED FATTY-ACIDS; RETINOID-X-RECEPTOR; LONG-TERM
POTENTIATION; CA3 NMDA RECEPTORS; SYNAPSIN-I; NEURITE OUTGROWTH;
NERVOUS-SYSTEM; AMPA RECEPTORS; RAT-BRAIN; LIGAND
AB Docosahexaenoic acid (DHA, 22:6n-3), the major polyunsaturated fatty acid accumulated in the brain during development, has been implicated in learning and memory, but underlying cellular mechanisms are not clearly understood. Here, we demonstrate that DHA significantly affects hippocampal neuronal development and synaptic function in developing hippocampi. In embryonic neuronal cultures, DHA supplementation uniquely promoted neurite growth, synapsin puncta formation and synaptic protein expression, particularly synapsins and glutamate receptors. In DHA-supplemented neurons, spontaneous synaptic activity was significantly increased, mostly because of enhanced glutamatergic synaptic activity. Conversely, hippocampal neurons from DHA-depleted fetuses showed inhibited neurite growth and synaptogenesis. Furthermore, n-3 fatty acid deprivation during development resulted in marked decreases of synapsins and glutamate receptor subunits in the hippocampi of 18-day-old pups with concomitant impairment of long-term potentiation, a cellular mechanism underlying learning and memory. While levels of synapsins and NMDA receptor subunit NR2A were decreased in most hippocampal regions, NR2A expression was particularly reduced in CA3, suggesting possible role of DHA in CA3-NMDA receptor-dependent learning and memory processes. The DHA-induced neurite growth, synaptogenesis, synapsin, and glutamate receptor expression, and glutamatergic synaptic function may represent important cellular aspects supporting the hippocampus-related cognitive function improved by DHA.
C1 [Cao, Dehua; Kevala, Karl; Kim, Jeffrey; Moon, Hyun-Seuk; Kim, Hee-Yong] NIAAA, Mol Signalling Lab, DICBR, NIH, Bethesda, MD 20892 USA.
[Jun, Sang Beom; Lovinger, David] NIAAA, Lab Integrat Neurosci, DICBR, NIH, Bethesda, MD 20892 USA.
RP Kim, HY (reprint author), NIAAA, Mol Signalling Lab, DICBR, NIH, 5625 Fishers Lane,Rm 3N-07, Bethesda, MD 20892 USA.
EM hykim@nih.gov
RI Moon, Hyun-Seuk/G-8576-2015
OI Moon, Hyun-Seuk/0000-0002-5216-2090
FU NIAAA, NIH
FX This research was supported by the Intramural Research Program of the
NIAAA, NIH.
NR 52
TC 120
Z9 124
U1 0
U2 15
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD OCT
PY 2009
VL 111
IS 2
BP 510
EP 521
DI 10.1111/j.1471-4159.2009.06335.x
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 498OY
UT WOS:000270152600020
PM 19682204
ER
PT J
AU Zhuang, P
Hallett, M
Zhang, X
Li, J
Zhang, Y
Li, Y
AF Zhuang, P.
Hallett, M.
Zhang, X.
Li, J.
Zhang, Y.
Li, Y.
TI Neuronal activity in the globus pallidus internus in patients with tics
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Article
ID DEEP BRAIN-STIMULATION; BASAL GANGLIA; TOURETTES-SYNDROME; SUBTHALAMIC
NUCLEUS; PARKINSONS-DISEASE; SQUIRREL-MONKEY; MOTOR CONTROL; MOVEMENT;
DISORDERS; PALLIDOTOMY
AB Objective: To explore the role of neuronal activity in the globus pallidus internus (GPi) in the generation of tic movements.
Methods: 8 patients with Tourette's syndrome with medically intractable tics who underwent a unilateral pallidotomy for severe tics were studied. They ranged in age from 17 to 24 years; disease duration was 7 19 years. Microelectrode recording was performed in the GPi. The electromyogram (EMG) was simultaneously recorded in muscle groups appropriate for the patient's tics. The relationship between neuronal firing pattern and the EMG was studied.
Results: 232 neurons were recorded during tics from eight trajectories. Of these neurons, in addition to decreased neuronal firing rate and irregular firing pattern, 105 (45%) were tic related showing either a burst of activity or a pause in ongoing tonic activity. They could be synchronous (n = 75), earlier than EMG onset (n = 27) or following EMG onset (n = 3). The GPi neuronal bursts preceded EMG onset with decreased (n = 6) or increased activity (n = 21). The initial change in neural activity occurred about 50 ms to 2 s before the EMG onset.
Conclusions: Although the data are descriptive and preliminary, the tic related neuronal activity observed in GPi appears to indicate that the basal ganglia motor circuit is involved in tic movements. The early neuronal activity seen in GPi may reflect premonitory sensations that precede a tic.
C1 [Zhuang, P.; Zhang, X.; Li, J.; Zhang, Y.; Li, Y.] Capital Med Univ, Xuanwu Hosp, Beijing Inst Funct Neurosurg, Key Lab Neurodegenerat Dis,Minist Educ, Beijing, Peoples R China.
[Hallett, M.] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD USA.
RP Li, Y (reprint author), 45 Changchun St, Beijing 100053, Peoples R China.
EM lyj8828@vip.sina.com
FU NSFC [30370473, 30770746]; NSFB [7042027]; NIH
FX This study was supported by grants NSFC (30370473, 30770746) and NSFB
(7042027) and supported in part by the Intramural Program of the NIH.
NR 37
TC 21
Z9 22
U1 0
U2 5
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD OCT
PY 2009
VL 80
IS 10
BP 1075
EP 1081
DI 10.1136/jnnp.2008.161869
PG 7
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 496BI
UT WOS:000269942600006
PM 19279028
ER
PT J
AU Davis, CD
Milner, JA
AF Davis, Cindy D.
Milner, Jofm A.
TI Gastrointestinal microflora, food components and colon cancer prevention
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Review
DE Prebiotics; Probiotics; Microbiota; Colon cancer
ID ABERRANT CRYPT FOCI; ESTROGEN-RECEPTOR-ALPHA; INTESTINAL
TUMOR-FORMATION; GUT BACTERIAL METABOLISM; CONJUGATED LINOLEIC-ACID;
URINARY EQUOL EXCRETION; RED WINE POLYPHENOLS; INULIN-TYPE FRUCTANS;
IN-VITRO; BIFIDOBACTERIUM-LONGUM
AB Evidence that the intestinal microbiota is intrinsically linked with overall health, including cancer risk, is emerging. Moreover, its composition is not fixed but can be influenced by several dietary components. Dietary modifiers, including the consumption of live bacteria (probiotics) and indigestible or limited digestible food constituents such as oligosaccharides (prebiotics) and polyphenols or both (synbiotics), are recognized modifiers of the numbers and types of microbes and have been reported to reduce colon cancer risk experimentally. Microorganisms also have the ability to generate bioactive compounds from food components. Examples include equol from isoflavones, enterodiol and enterolactone from lignans and urolithins from ellagic acid, which have also been demonstrated to retard experimentally induced cancers. The gastrointestinal microbiota. can also influence both sides of the energy balance equation, namely, as a factor influencing energy utilization from the diet and as a factor that influences host genes that regulate energy expenditure and storage. Because of the link between obesity and cancer incidence and mortality, this complex complexion deserves greater attention. Overall, a dynamic interrelationship exists between the intestinal microbiota and colon cancer risk, which can be modified by dietary components and eating behaviors. Published by Elsevier Inc.
C1 [Davis, Cindy D.] NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD 20892 USA.
RP Davis, CD (reprint author), NCI, Nutr Sci Res Grp, Canc Prevent Div, Rockville, MD 20892 USA.
EM davisci@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 106
TC 129
Z9 136
U1 10
U2 77
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD OCT
PY 2009
VL 20
IS 10
BP 743
EP 752
DI 10.1016/j.jnutbio.2009.06.001
PG 10
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 502EY
UT WOS:000270439400001
PM 19716282
ER
PT J
AU Ponnamperuma, RM
King, KE
Elsir, T
Glick, AB
Wahl, GM
Nister, M
Weinberg, WC
AF Ponnamperuma, Roshini M.
King, Kathryn E.
Elsir, Tamador
Glick, Adam B.
Wahl, Geoffrey M.
Nister, Monica
Weinberg, Wendy C.
TI The transcriptional regulatory function of p53 is essential for
suppression of mouse skin carcinogenesis and can be dissociated from
effects on TGF-beta-mediated growth regulation
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE p53; squamous cell carcinoma; epidermis; senescence; tumour suppression;
TGF-beta; transactivation
ID MUTANT P53; HOMOLOGOUS RECOMBINATION; MALIGNANT PROGRESSION; APOPTOTIC
ACTIVITY; TUMOR-DEVELOPMENT; GENE DOSAGE; IN-VIVO; TRANSACTIVATION;
DEFICIENT; KERATINOCYTES
AB Transcriptional regulation by p53 is critical for p53-mediated tumour suppression; however, p53-mediated transactivation has been dissociated from p53-mediated biological processes including apoptosis, DNA repair, and differentiation. We compared the effects of a mutant allele, p53(QS-val135), containing a double mutation in the amino-terminus abrogating transactivation activity and a modification at amino acid 135 partially affecting DNA binding, to complete loss of p53. We applied in vitro endpoints correlated with epithelial tumourigenesis and an in vivo assay of tumour phenotype to assess whether loss of p53-mediated transcriptional regulation underlies the malignant phenotype of p53(-/-)/v-ras(Ha)-overexpressing keratinocytes. Transactivation deficiency of p53(QS-val135) was confirmed by reporter gene assays in fibroblasts and differentiating keratinocytes. Ras oncogene-induced senescence was lost in both p53(QS-val135/QS-val135) and p53(-/-) keratinocytes. Similarly, p53(QS-val135/QS-val135), like p53(-/-), cooperated with v-ras(Ha) to enhance malignant conversion. The tumours arising in p53(QS-val135/QS-val135) keratinocytes displayed strong nuclear p53 expression; thus, the p53(QS-val135) allele was maintained and the deficient transactivation function of the expressed p53QS mutant protein was supported by absence of p21(waf1) in these tumours. The p53(QS-val135) allele did not confer a dominant-negative phenotype, as p53(+/QS-val135) keratinocytes senesced normally in response to v-ras(Ha) expression and formed benign tumours. While p53(-/-) keratinocytes displayed diminished response to TGF-beta, p53(QS-val135/QS-val135) and p53(+/+) keratinocytes responded equivalently, indicating that the requirement for p53 in maximizing TGF-beta-mediated growth regulation is independent of its transactivation domain and that the ability of keratinocytes to respond to TGF-beta is insufficient to suppress the malignant phenotype in this model. Furthermore, TGF-beta enhances p53QS-induced activation of a dual p53-TGF-beta responsive reporter in a keratinocyte cell line. These findings support an essential role for p53-mediated transcriptional regulation in suppressing malignancies arising from ras-induced skin tumours, consistent with previous findings in spontaneous carcinogenesis in other organs, and highlight the potential importance of senescence for tumour suppression in vivo. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
C1 [Weinberg, Wendy C.] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
[Elsir, Tamador; Nister, Monica] Karolinska Inst, Stockholm, Sweden.
[Glick, Adam B.] Penn State Univ, University Pk, PA 16802 USA.
[Wahl, Geoffrey M.] Salk Inst Biol Studies, La Jolla, CA 92037 USA.
RP Weinberg, WC (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Ctr Drug Evaluat & Res, 29 Lincoln Dr,NIH Bldg 29B,Room 3NN04, Bethesda, MD 20892 USA.
EM wendy.weinberg@fda.hhs.gov
FU FDA Intramural Funds [Z01 BO 04006-06 LIMB]; Swedish Cancer Foundation;
Karolinska Institutet; Karolinska University Hospital; Cancer Society in
Stockholm; Erik and Edith Fernstrom Foundation for Medical Research
FX We wish to acknowledge Michelle Beeche for her assistance in
establishing the p53QS-val135 colony, Dr Kinnimulki
Vijayachandra for help with the in vitro senescence assay, Dr Anna
Eriksson for advice regarding the immunohistochemical analyses, and Dr
Stefano Piccolo for providing the Mix.2 plasmid. We are deeply indebted
to Dr Ulrike Lichti for her advice and guidance in setting up the
grafting model. This work was supported by FDA Intramural Funds for
project Z01 BO 04006-06 LIMB (WCW, RMP, KEK), the Swedish Cancer
Foundation (MN), Karolinska Institutet (MN, TE), Karolinska University
Hospital (MN), the Cancer Society in Stockholm (MN), and the Erik and
Edith Fernstrom Foundation for Medical Research (MN, TE). Tissue
analysis was partly performed at the KI/Karolinska University
Hospital-supported core facility for mouse tissue analysis.
NR 42
TC 3
Z9 3
U1 0
U2 2
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0022-3417
J9 J PATHOL
JI J. Pathol.
PD OCT
PY 2009
VL 219
IS 2
BP 263
EP 274
DI 10.1002/path.2600
PG 12
WC Oncology; Pathology
SC Oncology; Pathology
GA 501YZ
UT WOS:000270421900013
PM 19718706
ER
PT J
AU Goldenberg, AJ
Hull, SC
Botkin, JR
Wilfond, BS
AF Goldenberg, Aaron J.
Hull, Sara Chandros
Botkin, Jeffrey R.
Wilfond, Benjamin S.
TI Pediatric Biobanks: Approaching Informed Consent for Continuing Research
After Children Grow Up
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID GENETIC RESEARCH; CHILDHOOD-CANCER; ETHICAL-ISSUES; TISSUE SAMPLES;
POPULATION; ATTITUDES; DONATION; RESOURCE; STORAGE; COHORT
AB Objective Proposals for pediatric biobanks have prompted questions of whether parental permission is sufficient to continue to use biological samples and data after the children become adults. The objective of this study was to examine adults' attitudes about continued research with their pediatric samples/data, particularly when they could not be located to provide consent.
Study design Telephone interviews were conducted with 1186 patients from 5 academic medical centers by using a hypothetical scenario.
Results Most respondents, 799 (67%), would not be concerned about the use of their sample/data after they reached adulthood. Those respondents who were concerned were more likely to be more private about their medical records, less trusting of medical researchers, or African-American. A total of 543 respondents (46%) believed their consent should be obtained to continue using their sample/data for research. Of these, 407 respondents (75%) would be at least moderately willing to give consent, when asked. Of the 1186 respondents, 310 (26%) would not want researchers to use their sample/data when they could not be located to ask for consent.
Conclusion The data are consistent with the normative view that when feasible, adults should be asked for consent for continued research on their data collected during childhood, but it is generally acceptable to continue to conduct research when adults cannot be located. Further public engagement may help determine how best to balance the potential social value of continued research using pediatric samples/data and the expectations for explicit consent expressed by a minority of respondents that may reflect concerns about privacy and trust. (J Pediatr 2009;155:578-83).
C1 [Goldenberg, Aaron J.] Case Western Reserve Univ, Dept Bioeth, Cleveland, OH 44106 USA.
[Goldenberg, Aaron J.] Case Western Reserve Univ, Ctr Genet Res Eth & Law, Cleveland, OH 44106 USA.
[Hull, Sara Chandros] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Hull, Sara Chandros] NIH, Off Clin Director, NHGRI, Bethesda, MD 20892 USA.
[Botkin, Jeffrey R.] Univ Utah, Salt Lake City, UT USA.
[Wilfond, Benjamin S.] Seattle Childrens Hosp, Treuman Katz Ctr Pediat Bioeth, Seattle, WA USA.
[Wilfond, Benjamin S.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA.
RP Wilfond, BS (reprint author), Metropolitan Pk W,M-S MPW 8-2,1100 Olive Way,Room, Seattle, WA 98101 USA.
EM benjamin.wilfond@seattlechildrens.org
FU National Human Genome Research Institute; National Institutes of Health
[IH P50HG003390]
FX The study was supported by National Human Genome Research Institute (S.H
and B.W.). J.B. received support for the recruitment of subjects. A. G.
was supported by the National Institutes of Health (IH P50HG003390, The
Center for Genetic Research Ethics and Law). No statement in this
article should be construed as an official position of the National
Human Genome Research Institute, National Institutes of Health, or
Department of Health and Human Services. The authors declare no
conflicts of interest.
NR 32
TC 37
Z9 37
U1 0
U2 2
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 OCT
PY 2009
VL 155
IS 4
BP 578
EP 583
DI 10.1016/j.jpeds.2009.04.034
PG 6
WC Pediatrics
SC Pediatrics
GA 502YT
UT WOS:000270497800028
PM 19595370
ER
PT J
AU Ohashi, N
Nomura, W
Kato, M
Narumi, T
Lewin, NE
Blumberg, PM
Tamamura, H
AF Ohashi, Nami
Nomura, Wataru
Kato, Mai
Narumi, Tetsuo
Lewin, Nancy E.
Blumberg, Peter M.
Tamamura, Hirokazu
TI Synthesis of protein kinase C delta C1b domain by native chemical
ligation methodology and characterization of its folding and ligand
binding
SO JOURNAL OF PEPTIDE SCIENCE
LA English
DT Article
DE protein kinase C; native chemical ligation; C1b domain; ligand binding
ID CONFORMATIONALLY CONSTRAINED ANALOGS; PHORBOL ESTER BINDING;
DAG-LACTONES; PK-C; COMPLEX; DIACYLGLYCEROL; ACTIVATION; APOPTOSIS;
PEPTIDE; SITE
AB The C1b domain of protein kinase C delta (PKC delta), a potent receptor for ligands such as diacylglycerol and phorbol esters, was synthesized by utilizing native chemical ligation. With this synthetic strategy, the domain was efficiently constructed and shown to have high affinity ligand binding and correct folding. The C1b domain has been utilized for the development of novel ligands for the control of phosphorylation by PKC family members. This strategy will pave the way for the efficient construction of C1b domains modified with fluorescent dyes, biotin, etc. Copyright (C) 2009 European Peptide Society and John Wiley & Sons, Ltd.
C1 [Ohashi, Nami; Nomura, Wataru; Kato, Mai; Narumi, Tetsuo; Tamamura, Hirokazu] Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Chiyoda Ku, Tokyo 1010062, Japan.
[Lewin, Nancy E.; Blumberg, Peter M.] Natl Canc Inst, Lab Canc Biol & Genet, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Nomura, W (reprint author), Tokyo Med & Dent Univ, Inst Biomat & Bioengn, Chiyoda Ku, 2-3-10 Kandasurugadai, Tokyo 1010062, Japan.
EM nomura.mr@tmd.ac.jp; tamamura.mr@tmd.ac.jp
RI Nomura, Wataru/F-5812-2015
FU Ministry of Education, Culture, Sports, Science, and Technology, Japan;
Ministry of Health, Labour, and Welfare; National Institutes of Health,
Center for Cancer Research, National Cancer Institute
FX This work was supported in part by a Grant-in-aid from the Ministry of
Education, Culture, Sports, Science, and Technology, Japan, and of the
Ministry of Health, Labour, and Welfare. It was also supported in part
by the Intramural Program of the National Institutes of Health, Center
for Cancer Research, National Cancer Institute. The authors thank
Professor Kazunari Akiyoshi, Institute of Biomaterials and
Bioengineering, Tokyo Medical and Dental University, for his assistance
in the CD experiments.
NR 22
TC 3
Z9 3
U1 0
U2 3
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1075-2617
J9 J PEPT SCI
JI J. Pept. Sci.
PD OCT
PY 2009
VL 15
IS 10
BP 642
EP 646
DI 10.1002/psc.1161
PG 5
WC Biochemistry & Molecular Biology; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 498VO
UT WOS:000270173500004
PM 19672879
ER
PT J
AU Lockenhoff, CE
Ironson, GH
O'Cleirigh, C
Costa, PT
AF Loeckenhoff, Corinna E.
Ironson, Gail H.
O'Cleirigh, Conall
Costa, Paul T., Jr.
TI Five-Factor Model Personality Traits, Spirituality/Religiousness, and
Mental Health Among People Living With HIV
SO JOURNAL OF PERSONALITY
LA English
DT Article
ID QUALITY-OF-LIFE; PSYCHOLOGICAL ADJUSTMENT; RELIGION; SPIRITUALITY;
METAANALYSIS; WOMEN; STRATEGIES; MEDIATION; ATTITUDES; DISTRESS
AB We examined the association between five-factor personality domains and facets and spirituality/religiousness as well as their joint association with mental health in a diverse sample of people living with HIV (n=112, age range 18-66). Spirituality/religiousness showed stronger associations with Conscientiousness, Openness, and Agreeableness than with Neuroticism and Extraversion. Both personality traits and spirituality/religiousness were significantly linked to mental health, even after controlling for individual differences in demographic measures and disease status. Personality traits explained unique variance in mental health above spirituality and religiousness. Further, aspects of spirituality and religiousness were found to mediate some of the links between personality and mental health in this patient sample. These findings suggest that underlying personality traits contribute to the beneficial effects of spirituality/religiousness among vulnerable populations.
C1 [Loeckenhoff, Corinna E.; Costa, Paul T., Jr.] NIA, Bethesda, MD 20892 USA.
[Ironson, Gail H.] Univ Miami, Coral Gables, FL 33124 USA.
[O'Cleirigh, Conall] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Fenway Inst, Cambridge, MA 02138 USA.
RP Lockenhoff, CE (reprint author), Cornell Univ, Dept Human Dev, MVR G27-35, Ithaca, NY 14853 USA.
EM CEL72@cornell.edu
OI Costa, Paul/0000-0003-4375-1712; Loeckenhoff,
Corinna/0000-0003-1605-1323
FU Intramural NIH HHS [NIH0011894836, Z01 AG000184-19]; NIMH NIH HHS [R01
MH066697, R01MH066697, R01MH53791]
NR 62
TC 16
Z9 17
U1 0
U2 12
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3506
J9 J PERS
JI J. Pers.
PD OCT
PY 2009
VL 77
IS 5
BP 1411
EP 1436
DI 10.1111/j.1467-6494.2009.00587.x
PG 26
WC Psychology, Social
SC Psychology
GA 490LS
UT WOS:000269503000007
PM 19686457
ER
PT J
AU Ahmet, I
Morrell, C
Lakatta, EG
Talan, MI
AF Ahmet, Ismail
Morrell, Chris
Lakatta, Edward G.
Talan, Mark I.
TI Therapeutic Efficacy of a Combination of a beta 1-Adrenoreceptor (AR)
Blocker and beta 2-AR Agonist in a Rat Model of Postmyocardial
Infarction Dilated Heart Failure Exceeds That of a beta 1-AR Blocker
plus Angiotensin-Converting Enzyme Inhibitor
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR DYSFUNCTION; ISCHEMIC
CARDIOMYOPATHY; CLINICAL-IMPLICATIONS; CARDIAC MYOCYTES; ACE-INHIBITORS;
SURVIVAL; MORTALITY; TRIAL; ENALAPRIL
AB We had proposed previously a novel combination of beta 2-adrenoreceptor (AR) agonist and beta 1-AR blocker that in the rat model of postmyocardial infarction (MI) dilated cardiomyopathy exceeds the therapeutic effectiveness of either monotherapy. In the present study, we compared that treatment with a combination of beta 1-AR blocker and angiotensin-converting enzyme inhibitor (ACEi), a current standard chronic heart failure (CHF) therapy. Two weeks after coronary artery ligation, rats were divided into groups of similar average MI size, measured by echocardiography, and the following 12-month treatments were initiated: fenoterol (250 mu g/kg/day), a beta 2-AR agonist, plus metoprolol (100 mg/kg/day), a beta 1-AR blocker (beta 1-beta 2+); metoprolol plus enalapril (20 mg/kg/day), an ACEi (beta 1-ACEi); and a combination of all three drugs (beta 1-beta 2+ACEi). These treatment groups were compared with each other and with nontreated (nT) and sham groups. The 12-month mortality was significantly reduced in all treatment groups (44% in beta 1-beta 2+, 56% in beta 1-beta 2+ACEi, 59% in beta 1-ACEi versus 81% in nT). Bimonthly echocardiography revealed significant attenuation of the left ventricular (LV) chamber remodeling, LV functional deterioration, and MI expansion in all three treatment groups, but effects were significantly more pronounced when treatment included a beta 2-AR agonist. The results indicated that a combination of beta 1-AR blocker and beta 2-AR agonist is equipotent to a combination of beta 1-AR blocker and ACEi in the treatment of CHF in rats, with the respect to mortality, and exceeds the latter with respect to cardiac remodeling and MI expansion. Thus, this novel therapeutic regimen for CHF warrants detailed clinical investigation.
C1 [Talan, Mark I.] NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA.
RP Talan, MI (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM talanm@grc.nia.nih.gov
FU National Institutes of Health National Institute on Aging
FX This work was supported by the Intramural Research Program of the
National Institutes of Health National Institute on Aging.
NR 40
TC 22
Z9 23
U1 1
U2 5
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD OCT
PY 2009
VL 331
IS 1
BP 178
EP 185
DI 10.1124/jpet.109.157107
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 497SE
UT WOS:000270081500019
PM 19587314
ER
PT J
AU Gonzalez, N
Nakagawa, T
Mantey, SA
Sancho, V
Uehara, H
Katsuno, T
Jensen, RT
AF Gonzalez, Nieves
Nakagawa, Tomoo
Mantey, Samuel A.
Sancho, Veronica
Uehara, Hirotsugu
Katsuno, Tatsuro
Jensen, Robert T.
TI Molecular Basis for the Selectivity of the Mammalian Bombesin Peptide,
Neuromedin B, for Its Receptor
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID GASTRIN-RELEASING-PEPTIDE; 2ND EXTRACELLULAR LOOP; HIGH-AFFINITY
BINDING; AGONIST-BINDING; AMINO-ACIDS; SPECIES SELECTIVITY;
ANTAGONIST-BINDING; SUBTYPES; CHOLECYSTOKININ; IDENTIFICATION
AB The mammalian bombesin (Bn) peptides, neuromedin B (NMB) and gastrin-releasing peptide (GRP), have widespread actions in many tissues, and their effects are mediated by two closely related G-protein-coupled receptors, the NMBR and GRPR. Little is known about the structural determinants of NMBR selectivity for NMB, in contrast to GRP selectivity for the GRPR, which has been extensively studied. To provide insight, chimeric NMBR-GRPR loss-of-affinity and gain-of-affinity mutants were made, as well as NH(2)-terminally truncated NMBR and point mutants using site-directed mutagenesis. Receptors were expressed in Balb-3T3-cells or CHOP cells, and affinities were determined. NMB had 115-fold greater affinity for NMBR than GRPR. Receptor-chimeric studies showed that NMBR selectivity for NMB was primarily determined by differences in the third extracellular (EC3) regions of GRPR-NMBR and adjacent upper-transmembrane-5 (TM5) region. In this region, 24 NMB gain-of-affinity GRPR mutants or NMBR loss-of-affinity point/combination mutants were made. Three gain-of-affinity mutant GRPRs [[A198I] (EC3), [H202Q] (EC3), [S215I] (upper TM5)] had increased NMB affinity (2.4-21-fold), and these results were confirmed with NMBR loss-of-affinity mutants [I199A, Q203H, I215S-NMBR]. The combination mutant [A198I, S215]GRPR had the greatest effect causing a complete NMB gain-of-affinity. The importance of differences at position 199NMBR or 203NMBR was studied by substituting amino acids with various properties. Our results show that NMBR selectivity for NMB is due to differences in the EC3 of NMBR-GRPR and the adjacent upper-TM5 region. Within these regions, isoleucines in NMBR [position 199 ( EC3)] (instead of A198GRPR) and in 215NMBR (TM5) ( instead of S214GRPR), as well as Q203NMBR (instead of H202GRPR) are responsible for high NMB-affinity/selectivity of NMBR. The effect at position 199 is primarily due to differences in hydrophobicity of the substitution, whereas steric factors and charge of the substitution at position 203 were important determinants of NMB selectivity.
C1 [Gonzalez, Nieves; Nakagawa, Tomoo; Mantey, Samuel A.; Sancho, Veronica; Uehara, Hirotsugu; Katsuno, Tatsuro; Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
[Nakagawa, Tomoo; Uehara, Hirotsugu; Katsuno, Tatsuro] Chiba Univ, Grad Sch Med, Dept Clin Cell Biol, Div Gastroenterol, Chiba, Japan.
RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA.
EM robertj@bdg10.niddk.nih.gov
RI Gonzalez, Nieves/N-2199-2014
OI Gonzalez, Nieves/0000-0002-1551-2872
FU National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases
FX This research was supported by the Intramural Research Program of the
National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases.
NR 44
TC 6
Z9 6
U1 0
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD OCT
PY 2009
VL 331
IS 1
BP 265
EP 276
DI 10.1124/jpet.109.154245
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 497SE
UT WOS:000270081500028
PM 19628633
ER
PT J
AU Gorman, GS
Coward, L
Kerstner-Wood, C
Freeman, L
Hebert, CD
Kapetanovic, IM
AF Gorman, Gregory S.
Coward, Lori
Kerstner-Wood, Corenna
Freeman, Lea
Hebert, Charles D.
Kapetanovic, Izet M.
TI In-vitro and in-vivo metabolic studies of the candidate
chemopreventative pentamethylchromanol using liquid
chromatography/tandem mass spectrometry
SO JOURNAL OF PHARMACY AND PHARMACOLOGY
LA English
DT Article
DE CYP450; drug metabolism; liquid chromatography/tandem mass spectrometry;
pentamethylchromanol
ID HUMAN LIVER; VITAMIN-E; UDP-GLUCURONOSYLTRANSFERASES; GLUCURONIDATION;
EXPRESSION; HORMONE; DRUGS
AB Objectives This study focuses on the in-vitro metabolic profiles of pentamethylchromanol in human, rat, dog and non-human primates, and characterizes the associated metabolic kinetics and specific human isozymes responsible for metabolism. Additional investigations compare in-vitro data with in-vivo metabolic data from rats and dogs.
Methods In-vitro metabolites were generated from commercially available microsomes, S9 fractions and cytochrome P450 isozymes. Reaction mixtures were analysed using liquid chromatography/tandem mass spectrometry for metabolite identification, stability, phenotyping and kinetic profiles. Plasma samples were collected from 28-day toxicology studies in rats and dogs, and analysed using the same methodology as for the identification of in-vitro metabolites.
Key findings Samples from in-vitro experiments produced a total of eight identified metabolites while five were observed in the in-vivo samples. Kinetic analysis of metabolites in human microsomes generated Michaelis constants (K(M)) ranging from 10.9 to 104.9 mu m. Pentamethylchromanol metabolic stability varied by species and multiple isozymes were identified for the observed biotransformation pathways. Pentamethylchromanol is susceptible to multiple metabolic pathways and differential metabolic stability, which is species dependent.
Conclusions In-vitro metabolism was not a strong predictor of in-vivo metabolism for the samples assays but showed glucuronidation and sulfation as common biotransformation pathways.
C1 [Gorman, Gregory S.; Coward, Lori; Kerstner-Wood, Corenna; Freeman, Lea; Hebert, Charles D.] So Res Inst, Toxicol & Bioanalyt Sci Dept, Birmingham, AL 35205 USA.
[Kapetanovic, Izet M.] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Gorman, GS (reprint author), So Res Inst, Toxicol & Bioanalyt Sci Dept, 2000 9th Ave S, Birmingham, AL 35205 USA.
EM gorman@southernresearch.org
FU National Cancer Institute [N01-CN-43307]
FX This work was funded by the National Cancer Institute under contract
N01-CN-43307.
NR 20
TC 2
Z9 2
U1 0
U2 1
PU PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN
PI LONDON
PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND
SN 0022-3573
J9 J PHARM PHARMACOL
JI J. Pharm. Pharmacol.
PD OCT
PY 2009
VL 61
IS 10
BP 1309
EP 1318
DI 10.1211/jpp/61.10.0006
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 507RX
UT WOS:000270873400006
PM 19814862
ER
PT J
AU Fishelovitch, D
Shaik, S
Wolfson, HJ
Nussinov, R
AF Fishelovitch, Dan
Shaik, Sason
Wolfson, Haim J.
Nussinov, Ruth
TI Theoretical Characterization of Substrate Access/Exit Channels in the
Human Cytochrome P450 3A4 Enzyme: Involvement of Phenylalanine Residues
in the Gating Mechanism
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID STEERED MOLECULAR-DYNAMICS; BURIED ACTIVE-SITE; POSSIBLE PATHWAY(S);
MEMBRANE-BINDING; PRODUCTS EXIT; FORCE-FIELD; P450CAM; RESOLUTION;
PROTEINS; HYDROXYLATION
AB The human cytochrome P450 3A4 mono-oxygenates similar to 50% of all drugs. Its substrates/products enter/leave the active site by access/exit channels. Here, we perform steered molecular dynamics simulations, pulling the products temazepam and testosterone-6 beta OH out of the P450 3A4 enzyme in order to identify the preferred substrate/product pathways and their gating mechanism. We locate six different egress pathways of products from the active site with different exit preferences for the two products and find that there is more than just one access/exit channel in CYP3A4. The so-called solvent channel manifests the largest opening for both tested products, thereby identifying this channel as a putative substrate channel. Most channels consist of one or two pi-stacked pherylalanine residues that serve as gate keepers. The oxidized drug breaks the hydrophobic interactions of the gating residues and forms mainly hydrophobic contacts with the gate. We argue that product exit preferences in P450s are regulated by protein-substrate specificity.
C1 [Nussinov, Ruth] NCI, CCRNB, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
[Fishelovitch, Dan; Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel.
[Shaik, Sason] Hebrew Univ Jerusalem, Inst Chem, IL-91904 Jerusalem, Israel.
[Shaik, Sason] Hebrew Univ Jerusalem, Lise Meitner Minerva Ctr Computat Quantum Chem, IL-91904 Jerusalem, Israel.
[Wolfson, Haim J.] Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), NCI, CCRNB, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Bldg 469,Rm 149, Frederick, MD 21702 USA.
EM ruthn@ncifcrf.gov
FU National Cancer Institute; National Institutes of Health [N01-CO-12400];
ISF [53/09]
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 No. N01-CO-12400. The content of this publication does not
necessarily reflect the views or policies of the Dept. 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
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. The research of S.S. at the H.U. was supported by all
ISF grant 53/09. This study utilized the high-performance computational
capabilities of the Biowulf PC/Linux cluster at the National Institutes
of Health, Bethesda, MD (http:// biowulf.nih.gov).
NR 57
TC 59
Z9 60
U1 2
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD OCT 1
PY 2009
VL 113
IS 39
BP 13018
EP 13025
DI 10.1021/jp810386z
PG 8
WC Chemistry, Physical
SC Chemistry
GA 496ST
UT WOS:000269999400024
PM 19728720
ER
PT J
AU Boja, ES
Phillips, D
French, SA
Harris, RA
Balaban, RS
AF Boja, Emily S.
Phillips, Darci
French, Stephanie A.
Harris, Robert A.
Balaban, Robert S.
TI Quantitative Mitochondrial Phosphoproteomics Using iTRAQ on an
LTQ-Orbitrap with High Energy Collision Dissociation
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE Quantitative Phosphoproteomics; iTRAQ; HCD; LTO-Orbitrap; Mitochondria
ID PYRUVATE-DEHYDROGENASE; PROTEIN-PHOSPHORYLATION; MASS-SPECTROMETRY;
BOVINE KIDNEY; RAT-HEART; CALCIUM; KINASE; COMPLEX; SITES; BRAIN
AB With the use of iTRAQ labeling and mass spectrometry on an LTQ-Orbitrap with HCD capability, we assessed relative changes in protein phosphorylation in the mitochondria upon physiological perturbation. As a reference reaction, we monitored the well-characterized regulation of pyruvate dehydrogenase (PDH) activity via phosphorylation/dephosphorylation by pyruvate dehydrogenase kinase/pyruvate dehydrogenase phosphatase in response to dichloroacetate, de-energization and Ca(2+). Relative quantification of phosphopeptides of PDH-E1 alpha subunit from porcine heart revealed dephosphorylation at three serine sites (Ser231, Ser292 and Ser299). Dephosphorylation at Ser292 (i.e., the inhibitory site) with DCA correlated with an activation of PDH activity as previously reported, consistent with our deenergization data. Calcium also dephosphorylated (i.e., activated) PDH, thus, confirming calcium activation of PDP. With this approach, we successfully monitored other phosphorylation sites of mitochondrial proteins including adenine nucleotide translocase, malate dehydrogenase and mitochondrial creatine kinase. Among them, four proteins exhibited phosphorylation changes with these physiological stimuli: (1) BCKDH-E1 alpha subunit increased phosphorylation at Ser337 with DCA and deenergization; (2) apoptosis-inducing factor phosphorylation was elevated at Ser345 with calcium; (3) ATP synthase F1 complex alpha subunit and (4) mitofilin dephosphorylated at Ser65 and Ser264 upon deenergization. This screening validated the iTRAQ/HCD technology as a method for functional quantitation of mitochondrial protein phosphorylation as well as providing insight into the regulation of mitochondria via phosphorylation.
C1 [Phillips, Darci; French, Stephanie A.; Balaban, Robert S.] NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Boja, Emily S.] NHLBI, Prote Core Facil, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Harris, Robert A.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, 10 Ctr Dr,Room B1D416, Bethesda, MD 20892 USA.
EM rsb@nih.gov
FU Intramural Funding of the Division of Intramural Research; NHLBI; NIH;
DHHS
FX This work was supported by the Intramural Funding of the Division of
Intramural Research, NHLBI, NIH, DHHS. Supporting
NR 40
TC 64
Z9 67
U1 2
U2 13
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
J9 J PROTEOME RES
JI J. Proteome Res.
PD OCT
PY 2009
VL 8
IS 10
BP 4665
EP 4675
DI 10.1021/pr900387b
PG 11
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 501BM
UT WOS:000270353900024
PM 19694452
ER
PT J
AU Bingham, CO
Pohl, C
Woodworth, TG
Hewlett, SE
May, JE
Rahman, MU
Witter, JP
Furst, DE
Strand, CV
Boers, M
Alten, RE
AF Bingham, Clifton O., III
Pohl, Christoph
Woodworth, Tasia G.
Hewlett, Sarah E.
May, James E.
Rahman, Mahboob U.
Witter, James P.
Furst, Daniel E.
Strand, C. Vibeke
Boers, Maarten
Alten, Rieke E.
TI Developing a Standardized Definition for Disease "Flare" in Rheumatoid
Arthritis (OMERACT 9 Special Interest Group)
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Article; Proceedings Paper
CT 9th International Consensus Conference on Outcome Measures in
Rheumatology Clinical Trails (OMERACT 9)
CY MAY 27-31, 2008
CL Kananaskis, CANADA
DE RHEUMATOID ARTHRITIS; FLARE; WORSENING; DISEASE ACTIVITY; PATIENT
PERSPECTIVE; OUTCOME MEASURES
ID PATIENT PERSPECTIVE; CLINICAL-TRIALS; DOSE TITRATION; DOUBLE-BLIND;
INFLIXIMAB; METHOTREXATE; THERAPY; ETANERCEPT; WITHDRAWAL; OUTCOMES
AB Objective. Traditional outcome measures in randomized controlled trials (RCT) include well-established response criteria its well as ACR EULAR responses using Disease Activity Score 44 (DAS44)/DAS28 to assess improvement; however, a measure to assess worsening of disease has yet to be developed. This special interest group (SIG) was established to develop an evidence-based, consensus-driven standard definition of "flare" in rheumatoid arthritis (RA).
Methods. At OMERACT 8, the need fora standardized definition of RA flare was recognized; interested individuals developed a proposal to form a SIG. A literature review was performed to identify publications and abstracts with flare definitions applied in RA, JIA, and lupus RCT as well as concerning patient perspectives on disease worsening. A SIG was held at OMERACT 9 with breakout sessions for patients and investigators.
Results. The RA flare SIG was attended by about 120 participants, including 11 patients. Patients and investigators held separate breakout sessions to discuss various aspects of disease worsening. The following consensus was obtained at OMERACT 9: it working definition of flare should indicate worsening of disease activity (88%), persistence, and duration its critical elements (77%), and consideration of change or increase in therapy (74%).
Conclusion. A working definition of RA flare was developed based on these votes: flare is any worsening of disease activity that would, if persistent, in most cases lead to initiation or change of therapy; and a flare represents it cluster of symptoms of sufficient duration and intensity to require initiation, change, or increase in therapy. Using this working definition, evaluation of candidate domains will be conducted via Delphi exercise and further informed by patient focus groups. Validation of candidate definitions in appropriate RCT will be required. (First Release August 15 2009; J Rheumatol 2009:36:2335-41; doi: 10.3899/jrheum.090369)
C1 Charite, Schlosspk Klin, D-13353 Berlin, Germany.
Roche Prod Ltd, Welwyn Garden City AL7 3AY, Herts, England.
Univ Calif Los Angeles, Los Angeles, CA USA.
Univ W England, Bristol BS16 1QY, Avon, England.
Univ Penn, Philadelphia, PA 19104 USA.
Centocor Inc, Philadelphia, PA USA.
NIAMS, NIH, Bethesda, MD USA.
Stanford Univ, Portola Valley, CA USA.
Vrije Univ Amsterdam, Amsterdam, Netherlands.
RP Bingham, CO (reprint author), Johns Hopkins Univ, Div Rheumatol, 5200 Eastern Ave,Mason Lord Ctr Tower,Room 404, Baltimore, MD 21224 USA.
EM Clifton.bingham@jhmi.edu
NR 38
TC 47
Z9 47
U1 0
U2 2
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA
SN 0315-162X
J9 J RHEUMATOL
JI J. Rheumatol.
PD OCT
PY 2009
VL 36
IS 10
BP 2335
EP 2341
DI 10.3899/jrheum.090369
PG 7
WC Rheumatology
SC Rheumatology
GA 505KB
UT WOS:000270691200034
PM 19684147
ER
PT J
AU Shumway, S
Wetherby, AM
AF Shumway, Stacy
Wetherby, Amy M.
TI Communicative Acts of Children With Autism Spectrum Disorders in the
Second Year of Life
SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH
LA English
DT Article
DE autism; ASD; social communication; joint attention; early identification
ID PERVASIVE DEVELOPMENTAL DISORDERS; JOINT ATTENTION; EARLY RECOGNITION;
HOME VIDEOTAPES; YOUNG-CHILDREN; FOLLOW-UP; INFANTS; AGE; INSTRUMENT;
STABILITY
AB Purpose: To examine the communicative profiles of children with autism spectrum disorders (ASD) in the second year of life.
Method: Communicative acts were examined in 125 children 18 to 24 months of age: 50 later diagnosed with ASD; 25 with developmental delays (DD); and 50 with typical development (TD). Precise measures of rate, functions, and means of communication were obtained through systematic observation of videotaped behavior samples from the Communication and Symbolic Behavior Scales Developmental Profile (A. Wetherby & B. Prizant, 2002).
Results: Children with ASD communicated at a significantly lower rate than children with DD and TD. The ASD group used a significantly lower proportion of acts for joint attention and a significantly lower proportion of deictic gestures with a reliance on more primitive gestures compared with the DD and TD groups. Children with ASD who did communicate for joint attention were as likely as other children to coordinate vocalizations, eye gaze, and gestures. Rate of communicative acts and joint attention were the strongest predictors of verbal outcome at age 3.
Conclusion: By 18 to 24 months of age, children later diagnosed with ASD showed a unique profile of communication, with core deficits in communication rate, joint attention, and communicative gestures.
C1 [Shumway, Stacy] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA.
[Wetherby, Amy M.] Florida State Univ, Tallahassee, FL 32306 USA.
RP Shumway, S (reprint author), NIMH, Pediat & Dev Neurosci Branch, 10 Ctr Dr,MSC 1255,Bldg 10,Room 4N208, Bethesda, MD 20892 USA.
EM shumways@mail.nih.gov
OI Manwaring, Stacy/0000-0002-0835-9398
FU NIDCD NIH HHS [R01 DC007462-03, R01 DC007462, 1R01 DC007462]
NR 56
TC 42
Z9 45
U1 2
U2 25
PU AMER SPEECH-LANGUAGE-HEARING ASSOC
PI ROCKVILLE
PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA
SN 1092-4388
EI 1558-9102
J9 J SPEECH LANG HEAR R
JI J. Speech Lang. Hear. Res.
PD OCT 1
PY 2009
VL 52
IS 5
BP 1139
EP 1156
DI 10.1044/1092-4388(2009/07-0280)
PG 18
WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
GA 498KX
UT WOS:000270140100003
PM 19635941
ER
PT J
AU Shriberg, LD
Lohmeier, HL
Campbell, TF
Dollaghan, CA
Green, JR
Moore, CA
AF Shriberg, Lawrence D.
Lohmeier, Heather L.
Campbell, Thomas F.
Dollaghan, Christine A.
Green, Jordan R.
Moore, Christopher A.
TI A Nonword Repetition Task for Speakers With Misarticulations: The
Syllable Repetition Task (SRT)
SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH
LA English
DT Review
DE assessment; genetics; memory; speech disorders; endophenotype
ID NON-WORD REPETITION; DEVELOPMENTAL PHONOLOGICAL DISORDERS; SPEECH-SOUND
DISORDER; LANGUAGE IMPAIRMENT; WORKING-MEMORY; 4-YEAR-OLD CHILDREN;
PHONOTACTIC PROBABILITY; KINDERGARTEN-CHILDREN; RECEPTIVE VOCABULARY;
PRESCHOOL-CHILDREN
AB Purpose: Conceptual and methodological confounds occur when non(sense) word repetition tasks are administered to speakers who do not have the target speech sounds in their phonetic inventories or who habitually misarticulate targeted speech sounds. In this article, the authors (a) describe a nonword repetition task, the Syllable Repetiton Task (SRT), that eliminates this confound and (b) report findings from 3 validity studies.
Method: Ninety-five preschool children with speech delay and 63 with typical speech completed an assessment battery that included the Nonword Repetition Task (NRT; C. Dollaghan & T. F. Campbell, 1998) and the SRT. SRT stimuli include only 4 of the earliest occurring consonants and 1 early occurring vowel.
Results: Study 1 findings indicated that the SRT eliminated the speech confound in nonword testing with speakers who misarticulate. Study 2 findings indicated that the accuracy of the SRT to identify expressive language impairment was comparable to findings for the NRT. Study 3 findings illustrated the SRT's potential to interrogate speech processing constraints underlying poor nonword repetition accuracy. Results supported both memorial and auditory-perceptual encoding constraints underlying nonword repetition errors in children with speech-language impairment.
Conclusion: The SRT appears to be a psychometrically stable and substantively informative nonword repetition task for emerging genetic research and other research with speakers who misarticulate.
C1 [Shriberg, Lawrence D.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA.
[Campbell, Thomas F.; Dollaghan, Christine A.] Univ Texas Dallas, Dallas, TX 75230 USA.
[Green, Jordan R.] Univ Nebraska, Lincoln, NE 68583 USA.
[Moore, Christopher A.] Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA.
RP Shriberg, LD (reprint author), Univ Wisconsin, Waisman Ctr, Room 439,1500 Highland Ave, Madison, WI 53705 USA.
EM shriberg@waisman.wisc.edu
RI Green, Jordan/A-7159-2008
OI Green, Jordan/0000-0002-1464-1373
FU NCRR NIH HHS [M01 RR000084, M01 RR00084]; NICHD NIH HHS [HD03352, P30
HD003352]; NIDCD NIH HHS [R01 DC000822-13, DC00496, DC00822, R01
DC000496, R01 DC000496-07, R01 DC000496-21, R01 DC000822]
NR 114
TC 34
Z9 34
U1 4
U2 13
PU AMER SPEECH-LANGUAGE-HEARING ASSOC
PI ROCKVILLE
PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA
SN 1092-4388
J9 J SPEECH LANG HEAR R
JI J. Speech Lang. Hear. Res.
PD OCT 1
PY 2009
VL 52
IS 5
BP 1189
EP 1212
DI 10.1044/1092-4388(2009/08-0047)
PG 24
WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation
GA 498KX
UT WOS:000270140100006
PM 19635944
ER
PT J
AU Lahiri, P
Li, Y
AF Lahiri, P.
Li, Yan
TI A new alternative to the standard F test for clustered data
SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE
LA English
DT Article
DE Clustered data; Intra-cluster correlation; Standard F test; Generalized
least square test; Fuller-Battese transformation
ID VARIANCE
AB The data collection process and the inherent population structure are the main causes for clustered data. The observations in a given duster are correlated, and the magnitude of such correlation is often measured by the intra-cluster correlation coefficient. The intra-cluster correlation can lead to an inflated size of the standard F test in a linear model. In this paper. we propose a solution to this problem. Unlike previous adjustments, our method does not require estimation of the intra-class correlation, which is problematic especially when the number of clusters is small. Our simulation results show that the new method outperforms the existing methods. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Lahiri, P.] Univ Maryland, Joint Program Survey Methodol, College Pk, MD 20742 USA.
[Li, Yan] NCI, Biostat Branch, Rockville, MD 20852 USA.
[Li, Yan] Univ Texas Arlington, Dept Math, Arlington, TX 76019 USA.
RP Lahiri, P (reprint author), Univ Maryland, Joint Program Survey Methodol, College Pk, MD 20742 USA.
EM plahiri@survey.umd.edu; lisherry@mail.nih.gov
NR 19
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-3758
J9 J STAT PLAN INFER
JI J. Stat. Plan. Infer.
PD OCT 1
PY 2009
VL 139
IS 10
BP 3430
EP 3441
DI 10.1016/j.jspi.2009.03.019
PG 12
WC Statistics & Probability
SC Mathematics
GA 480AL
UT WOS:000268703700004
ER
PT J
AU Tian, L
Vexler, A
Yan, L
Schisterman, EF
AF Tian, Lili
Vexler, Albert
Yan, Li
Schisterman, Enrique F.
TI Confidence interval estimation of the difference between paired AUCs
based on combined biomarkers
SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE
LA English
DT Article
DE Receiver operating characteristic (ROC) curve; Optimal linear
combinations; Generalized pivot; Generalized test variable
ID GENERALIZED VARIABLE METHOD; ROC CURVES; LINEAR-COMBINATIONS; DIAGNOSTIC
MARKERS; NORMAL-POPULATIONS; AREAS; INFERENCES; TESTS; DISTRIBUTIONS;
VALUES
AB In many diagnostic studies, multiple diagnostic tests are performed on each subject or multiple disease markers are available. Commonly, the information should be combined to improve the diagnostic accuracy. We consider the problem of comparing the discriminatory abilities between two groups of biomarkers. Specifically, this article focuses on confidence interval estimation of the difference between paired AUCs based on optimally combined markers under the assumption of multivariate normality. Simulation studies demonstrate that the proposed generalized variable approach provides confidence intervals with satisfying coverage probabilities at finite sample sizes. The proposed method can also easily provide P-values for hypothesis testing. Application to analysis of a subset of data from a study on coronary heart disease illustrates the utility of the method in practice. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Tian, Lili; Vexler, Albert; Yan, Li] SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA.
[Schisterman, Enrique F.] NICHD, Div Epidemiol Stat & Prevent, NIH, Bethesda, MD USA.
RP Tian, L (reprint author), SUNY Buffalo, Dept Biostat, 249 Farber Hall,3435 Main St,Bldg 26, Buffalo, NY 14214 USA.
EM ltian@buffalo.edu
OI Schisterman, Enrique/0000-0003-3757-641X
FU Intramural NIH HHS [Z01 HD008761-05]
NR 28
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-3758
EI 1873-1171
J9 J STAT PLAN INFER
JI J. Stat. Plan. Infer.
PD OCT 1
PY 2009
VL 139
IS 10
BP 3725
EP 3732
DI 10.1016/j.jspi.2009.05.001
PG 8
WC Statistics & Probability
SC Mathematics
GA 480AL
UT WOS:000268703700032
PM 19946609
ER
PT J
AU Rodriguez, D
Cheung, MC
Housri, N
Quinones-Hinojosa, A
Camphausen, K
Koniaris, LG
AF Rodriguez, Dayron
Cheung, Michael C.
Housri, Nadine
Quinones-Hinojosa, Alfredo
Camphausen, Kevin
Koniaris, Leonidas G.
TI Outcomes of Malignant CNS Ependymomas: An Examination of 2408 Cases
Through the Surveillance, Epidemiology, and End Results (SEER) Database
(1973-2005)
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article; Proceedings Paper
CT 70th Annual Meeting of the Society-of-University-Surgeons/4th Annual
Academic Surgical Congress
CY FEB 03-06, 2009
CL Ft Myers, FL
SP Soc Univ Surg, Assoc Acad Surg
DE malignancy; cancer; survival; surgery; ependymoma; radiation; outcomes;
SEER
ID GASTROINTESTINAL STROMAL TUMORS; CHILDRENS CANCER GROUP; INTRACRANIAL
EPENDYMOMAS; SPINAL-CORD; PROGNOSTIC-FACTORS; POSTERIOR-FOSSA;
BRAIN-TUMORS; POSTOPERATIVE CHEMOTHERAPY; INFRATENTORIAL EPENDYMOMAS;
CRANIOSPINAL IRRADIATION
AB Background. Determine the role of surgery and radiation therapy for patients with malignant CNS ependymomas.
Methods. The Surveillance, Epidemiology, and End Results (SEER) database (1973-2005) was queried. Results. Overall, a total of 2408 cases of malignant ependymomas were identified. Of these, 2132 cases (88.5%) were identified as WHO grade II ependymomas and 276 cases (11.5%) as WHO grade III (anaplastic) ependymomas. The annual incidence of ependymomas was approximately 1.97 cases per million in 2005. Overall median survival for all patients was 230 mo, with a significant difference between women and men (262 mo versus196 mo, respectively) (P = 0.004). Median age at diagnosis was 37 y among females and 34 y in males. Patients who successfully underwent surgical resection had a considerably longer median survival (237 mo versus 215 mo, P < 0.001) as well as a significantly improved five-year survival (72.4% versus 52.6%, P < 0.001). Univariate analysis demonstrated that age, gender, ethnicity, primary tumor site, WHO grade and surgical resection were significant predictors of improved survival for ependymoma patients. Multivariate analysis identified that a WHO grade III tumor, male gender, patient age, intracranial tumor locations and failure to undergo surgical resection were independent predictors of poorer outcomes. Multivariate analysis of partially resection cases revealed that lack of radiation was a sign of poor prognosis (HR 1.748, P = 0.024).
Conclusion. Surgical extirpation of ependymomas is associated with significantly improved patient survival. For partially resected tumors, radiation therapy provides significant survival benefit. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Rodriguez, Dayron; Cheung, Michael C.; Housri, Nadine; Koniaris, Leonidas G.] Univ Miami, Miller Sch Med, DeWitt Daughtry Family Dept Surg, Div Surg Oncol, Miami, FL 33136 USA.
[Quinones-Hinojosa, Alfredo] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Johns Hopkins Hosp, Baltimore, MD 21205 USA.
[Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Koniaris, LG (reprint author), Univ Miami, Sch Med, Alan Livingstone Chair Surg Oncol, 3550 Sylvester Comprehens Canc Ctr,1475 NW 12th A, Miami, FL 33136 USA.
EM lkoniaris@med.miami.edu
NR 67
TC 43
Z9 47
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
J9 J SURG RES
JI J. Surg. Res.
PD OCT
PY 2009
VL 156
IS 2
BP 340
EP 351
DI 10.1016/j.jss.2009.04.024
PG 12
WC Surgery
SC Surgery
GA 503TW
UT WOS:000270564300026
PM 19577759
ER
PT J
AU Brent, DA
Greenhill, LL
Compton, S
Emslie, G
Wells, K
Walkup, JT
Vitiello, B
Bukstein, O
Stanley, B
Posner, K
Kennard, BD
Cwik, MF
Wagner, A
Coffey, B
March, JS
Riddle, M
Goldstein, T
Curry, J
Barnett, S
Capasso, L
Zelazny, J
Hughes, J
Shen, S
Gugga, SS
Turner, JB
AF Brent, David A.
Greenhill, Laurence L.
Compton, Scott
Emslie, Graham
Wells, Karen
Walkup, John T.
Vitiello, Benedetto
Bukstein, Oscar
Stanley, Barbara
Posner, Kelly
Kennard, Betsy D.
Cwik, Mary F.
Wagner, Ann
Coffey, Barbara
March, John S.
Riddle, Mark
Goldstein, Tina
Curry, John
Barnett, Shannon
Capasso, Lisa
Zelazny, Jamie
Hughes, Jennifer
Shen, Sa
Gugga, S. Sonia
Turner, J. Blake
TI The Treatment of Adolescent Suicide Attempters Study (TASA): Predictors
of Suicidal Events in an Open Treatment Trial
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE suicide attempt; depression; pharmacotherapy; psychotherapy
ID BORDERLINE PERSONALITY-DISORDER; RANDOMIZED CONTROLLED-TRIAL;
SSRI-RESISTANT DEPRESSION; CHILDHOOD SEXUAL-ABUSE;
PSYCHIATRIC-INPATIENTS; RISK-FACTORS; SCALE; SCHIZOPHRENIA; RELIABILITY;
PREVALENCE
AB Objective: To identify the predictors of suicidal events and attempts in adolescent suicide attempters with depression treated in an open treatment trial. Method: Adolescents who had made a recent suicide attempt and had unipolar depression (n = 124) were either randomized (n = 22) or given a choice (n = 102) among three conditions. Two participants withdrew before treatment assignment. The remaining 124 youths received a specialized psychotherapy for suicide attempting adolescents In = 17), a medication algorithm (n = 14), or the combination (n = 93). The participants were followed up 6 months after intake with respect to rate, timing, and predictors of a suicidal event (attempt or acute suicidal ideation necessitating emergency referral). Results: The morbid risks of suicidal events and attempts on 6-month follow-up were 0.19 and 0.12, respectively, with a median time to event of 44 days. Higher self-rated depression, suicidal ideation, family income, greater number of previous suicide attempts, lower maximum lethality of previous attempt, history of sexual abuse, and lower family cohesion predicted the occurrence, and earlier time to event, with similar findings for the outcome of attempts. A slower decline in suicidal ideation was associated with the occurrence of a suicidal event. Conclusions: In this open trial, the 6-month morbid risks for suicidal events and for reattempts were lower than those in other comparable samples, suggesting that this intervention should be studied further. Important treatment targets include suicidal ideation, family cohesion, and sequelae of previous abuse. Because 40% of events occurred with 4 weeks of intake, an emphasis on safety planning and increased therapeutic contact early in treatment may be warranted. J Am. Acad. Child Adolesc. Psychiatry, 2009;48(10):987-996.
C1 [Brent, David A.; Bukstein, Oscar; Goldstein, Tina; Zelazny, Jamie] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA.
[Vitiello, Benedetto; Wagner, Ann] NIMH, Bethesda, MD 20892 USA.
[Greenhill, Laurence L.; Stanley, Barbara; Posner, Kelly; Capasso, Lisa; Shen, Sa; Gugga, S. Sonia; Turner, J. Blake] Columbia Univ, New York Psychiat Inst, New York, NY 10027 USA.
[Emslie, Graham; Kennard, Betsy D.; Hughes, Jennifer] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Compton, Scott; Wells, Karen; March, John S.; Curry, John] Duke Univ, Med Ctr, Durham, NC 27706 USA.
[Coffey, Barbara] NYU, Ctr Child Study, New York, NY 10003 USA.
[Walkup, John T.; Cwik, Mary F.; Riddle, Mark; Barnett, Shannon] Johns Hopkins Univ, Baltimore, MD 21218 USA.
RP Brent, DA (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, 3811 OHara St,Room 311 Bellefield Towers, Pittsburgh, PA 15213 USA.
EM brentda@upmc.edu
RI Stanley, Barbara/J-8736-2013
FU NIMH NIH HHS [U10 MH066778-04, U10 MH066775-04, U10 MH066775-01, U10
MH066769-04, U10 MH066769-01, U10 MH066762-05, U10 MH066762-02, U10
MH066762, U10 MH066750-05, U10 MH066750-02, U10 MH066750, MH66762, U10
MH066778-01, MH66750, U10 MH066778-03, U10 MH066750-01, U10 MH066750-04,
U10 MH066762-01, U10 MH066762-04, U10 MH066769-03, U10 MH066775-03, U10
MH066769-02, MH66769, MH66775, MH66778, U10 MH066750-03, U10
MH066762-02S1, U10 MH066762-03, U10 MH066769, U10 MH066769-05, U10
MH066775, U10 MH066775-02, U10 MH066775-05, U10 MH066778, U10
MH066778-02, U10 MH066778-05]
NR 38
TC 72
Z9 72
U1 2
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD OCT
PY 2009
VL 48
IS 10
BP 987
EP 996
DI 10.1097/CHI.0b013e3181b5dbe4
PG 10
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 499DH
UT WOS:000270196600005
PM 19730274
ER
PT J
AU Vtiello, B
Brent, DA
Greenhill, LL
Emslie, G
Wells, K
Walkup, JT
Stanley, B
Bukstein, O
Kennard, BD
Compton, S
Coffey, B
Cwik, MF
Posner, K
Wagner, A
March, JS
Riddle, M
Goldstein, T
Curry, J
Capasso, L
Mayes, T
Shen, S
Gugga, SS
Turner, JB
Barnett, S
Zelazny, J
AF Vtiello, Benedetto
Brent, David A.
Greenhill, Laurence L.
Emslie, Graham
Wells, Karen
Walkup, John T.
Stanley, Barbara
Bukstein, Oscar
Kennard, Betsy D.
Compton, Scott
Coffey, Barbara
Cwik, Mary F.
Posner, Kelly
Wagner, Ann
March, John S.
Riddle, Mark
Goldstein, Tina
Curry, John
Capasso, Lisa
Mayes, Taryn
Shen, Sa
Gugga, S. Sonia
Turner, J. Blake
Barnett, Shannon
Zelazny, Jamie
TI Depressive Symptoms and Clinical Status During the Treatment of
Adolescent Suicide Attempters (TASA) Study
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE adolescents; suicide; depression; treatment
ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; CHILDREN;
SCALE; TADS; OUTCOMES; METAANALYSIS; RELIABILITY; REMISSION; IDEATION
AB Objective: To examine the course of depression during the treatment of adolescents with depression who had recently attempted suicide. Method: Adolescents (N = 124), ages 12 to 18 years, with a 90-day history of suicide attempt, a current diagnosis of depressive disorder (96.0% had major depressive disorder), and a Children's Depression Rating Scale-Revised (CDRS-R) score of 36 or higher, entered a 6-month treatment with antidepressant medication, cognitive-behavioral therapy focused on suicide prevention, or their combination (Comb), at five academic sites. Treatment assignment could be either random or chosen by study participants. Intent-to-treat, mixed effects regression models of depression and other relevant ratings were estimated. Improvement and remission rates were computed with the last observation carried forward. Results: Most patients (n = 104 or 84%) chose treatment assignment, and overall, three fourths (n = 93) received Comb. In Comb, CDRS-R declined from a baseline adjusted mean of 49.6 (SD 12.3) to 38.3 (8.0) at week 12 and to 27.0 (10.1) at week 24 (p <.0001), with a Clinical Global Impression-defined improvement rate of 58.0% at week 12 and 72.2% at week 24 and a remission (CDRS-R <= 28) rate of 32.5% at week 12 and 50.0% at week 24. The CDRS-R and the Scale for Suicidal Ideation scores were correlated at baseline (r=0.43, p <.0001) and declined in parallel. Conclusions: When vigorously treated with a combination of medication and psychotherapy, adolescents with depression who have recently attempted suicide show rates of improvement and remission of depression that seem comparable to those observed in nonsuicidal adolescents with depression. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(10):997-1004.
C1 [Vtiello, Benedetto; Wagner, Ann] NIMH, Bethesda, MD 20892 USA.
[Brent, David A.; Bukstein, Oscar; Goldstein, Tina; Zelazny, Jamie] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA.
[Greenhill, Laurence L.; Stanley, Barbara; Posner, Kelly; Capasso, Lisa; Shen, Sa; Gugga, S. Sonia; Turner, J. Blake] Columbia Univ, New York State Psychiat Inst, New York, NY 10027 USA.
[Emslie, Graham; Kennard, Betsy D.; Mayes, Taryn] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Wells, Karen; Compton, Scott; March, John S.; Curry, John] Duke Univ, Med Ctr, Durham, NC 27706 USA.
[Coffey, Barbara] NYU, Ctr Child Study, New York, NY 10003 USA.
[Walkup, John T.; Cwik, Mary F.; Riddle, Mark; Barnett, Shannon] Johns Hopkins Univ, Baltimore, MD 21218 USA.
RP Vtiello, B (reprint author), NIMH, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA.
EM bvitiell@mail.nih.gov
FU National Institute of Mental Health [MH66750, MH66769, MH66762, MH66775,
MH66778]; NIMH
FX Funded by the National Institute of Mental Health through cooperative
agreement grants MH66750 (PI: KW, Duke University Medical Center),
MH66769 (PI;J W, Johns Hopkins University), MH66762 (PI: L. G, New York
State Psychiatric Institute), MH66775 (PI: D. B., Universiq of
Pittsburgh), and MH66778 (PI: GE, Univeisity of Texas Southwestern
Medical Center). Data management was funded by an NIMH contract to KAI
Research, Rockville, MD.
NR 26
TC 4
Z9 4
U1 2
U2 6
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 OCT
PY 2009
VL 48
IS 10
BP 997
EP 1004
DI 10.1097/CHI.0b013e3181b5db66
PG 8
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 499DH
UT WOS:000270196600006
ER
PT J
AU Stanley, B
Brown, G
Brent, DA
Wells, K
Poling, K
Curry, J
Kennard, BD
Wagner, A
Cwik, MF
Klomek, AB
Goldstein, T
Vitiello, B
Barnett, S
Daniel, S
Hughes, J
AF Stanley, Barbara
Brown, Gregory
Brent, David A.
Wells, Karen
Poling, Kim
Curry, John
Kennard, Betsy D.
Wagner, Ann
Cwik, Mary F.
Klomek, Anat Brunstein
Goldstein, Tina
Vitiello, Benedetto
Barnett, Shannon
Daniel, Stephanie
Hughes, Jennifer
TI Cognitive-Behavioral Therapy for Suicide Prevention (CBT-SP): Treatment
Model, Feasibility, and Acceptability
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE suicide; psychotherapy; depression
ID PARASUICIDAL BORDERLINE PATIENTS; RANDOMIZED CONTROLLED-TRIAL;
DELIBERATE SELF-HARM; ADOLESCENT SUICIDE; RISK-FACTORS; INTERVENTION;
ATTEMPTERS; PREVALENCE; IDEATION; CHILDREN
AB Objective: To describe the elements of a manual-based cognitive-behavioral therapy for suicide prevention (CBT-SP) and to report its feasibility in preventing the recurrence of suicidal behavior in adolescents who have recently attempted suicide. Method: The CBT-SP was developed using a risk reduction and relapse prevention approach and theoretically grounded in principles of cognitive-behavioral therapy, dialectical behavioral therapy, and targeted therapies for suicidal youths with depression. The CBT-SP consists of acute and continuation phases, each lasting about 12 sessions, and includes a chain analysis of the suicidal event, safety plan development, skill building, psychoeducation, family intervention, and relapse prevention. Results: The CBT-SP was administered to 110 recent suicide attempters with depression aged 13 to 19 years (mean 15.8 years, SD 1.6) across five academic sites. Twelve or more sessions were completed by 72.4% of the sample. Conclusions: A specific intervention for adolescents at high risk for repeated suicide attempts has been developed and manual based, and further testing of its efficacy seems feasible. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(10):1005-1013.
C1 [Stanley, Barbara] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York State Psychiat Inst, New York, NY 10032 USA.
[Brown, Gregory] Univ Penn, Philadelphia, PA 19104 USA.
[Brent, David A.; Poling, Kim; Goldstein, Tina] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Brent, David A.; Poling, Kim; Goldstein, Tina] Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA.
[Wells, Karen; Curry, John] Duke Univ, Durham, NC 27706 USA.
[Wagner, Ann; Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA.
[Kennard, Betsy D.; Hughes, Jennifer] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Cwik, Mary F.; Barnett, Shannon] Johns Hopkins Univ, Baltimore, MD 21218 USA.
[Daniel, Stephanie] Univ N Carolina, Greensboro, NC 27412 USA.
RP Stanley, B (reprint author), Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York State Psychiat Inst, Unit 42 1051,Riverside Dr, New York, NY 10032 USA.
EM bhs2@columbia.edu
RI Stanley, Barbara/J-8736-2013
FU NIAAA NIH HHS [P20 AA015630, P20 AA015630-04]; NIMH NIH HHS [MH66775,
MH66750, MH66762, MH66769, MH66778, R01 MH061017, R01 MH061017-05, U10
MH066750, U10 MH066750-04, U10 MH066762, U10 MH066762-04, U10 MH066769,
U10 MH066769-04, U10 MH066775, U10 MH066775-05, U10 MH066778, U10
MH066778-04]
NR 35
TC 67
Z9 68
U1 9
U2 47
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD OCT
PY 2009
VL 48
IS 10
BP 1005
EP 1013
DI 10.1097/CHI.0b013e3181b5dbfe
PG 9
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 499DH
UT WOS:000270196600007
PM 19730273
ER
PT J
AU Leachman, SA
Carucci, J
Kohlmann, W
Banks, KC
Asgari, MM
Bergman, W
Bianchi-Scarra, G
Brentnall, T
Bressac-de Paillerets, B
Bruno, W
Curiel-Lewandrowski, C
de Snoo, FA
Debniak, T
Demierre, MF
Elder, D
Goldstein, AM
Grant-Kels, J
Halpern, AC
Ingvar, C
Kefford, RF
Lang, J
MacKie, RM
Mann, GJ
Mueller, K
Newton-Bishop, J
Olsson, H
Peterson, GM
Puig, S
Rigel, D
Swetter, SM
Tucker, MA
Yakobson, E
Zitelli, JA
Tsao, H
AF Leachman, Sancy A.
Carucci, John
Kohlmann, Wendy
Banks, Kimberly C.
Asgari, Maryam M.
Bergman, Wilma
Bianchi-Scarra, Giovanna
Brentnall, Teresa
Bressac-de Paillerets, Brigitte
Bruno, William
Curiel-Lewandrowski, Clara
de Snoo, Femke A.
Debniak, Tadeusz
Demierre, Marie-France
Elder, David
Goldstein, Alisa M.
Grant-Kels, Jane
Halpern, Allan C.
Ingvar, Christian
Kefford, Richard F.
Lang, Julie
MacKie, Rona M.
Mann, Graham J.
Mueller, Kurt
Newton-Bishop, Julia
Olsson, Hakan
Peterson, Gloria M.
Puig, Susana
Rigel, Darrell
Swetter, Susan M.
Tucker, Margaret A.
Yakobson, Emanuel
Zitelli, John A.
Tsao, Hensin
TI Selection criteria for genetic assessment of patients with familial
melanoma
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Review
DE CDKN2A; familial; genetic counseling; genetic testing; hereditary;
melanoma; p16
ID GERMLINE CDKN2A MUTATIONS; MULTIPLE PRIMARY MELANOMAS; CUTANEOUS
MALIGNANT-MELANOMA; ATYPICAL-MOLE SYNDROME; PANCREATIC-CARCINOMA
SYNDROME; POPULATION-BASED SAMPLE; NEURAL SYSTEM TUMORS; PRONE FAMILIES;
EARLY-ONSET; CDK4 MUTATIONS
AB Approximately 5% to 10% of melanoma may be hereditary in nature, and about 2% of melanoma can be specifically attributed to pathogenic germline mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A). To appropriately identify the small proportion of patients Who benefit most from referral to a genetics specialist for consideration of genetic testing for CDKN2A, We have reviewed available published studies of CDKN2A mutation analysis in cohorts with invasive, cutaneous melanoma and found variability in the rate of CDKN2A mutations based on geography, ethnicity, and the type of study and eligibility criteria used. Except in regions of high melanoma incidence, such as Australia, we found higher rates of CDKN2A positivity in individuals with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family. The Work summarized in this review should help identify individuals who are appropriate candidates for referral for genetic consultation and possible testing. (J Am Acad Dermatol 2009;61:677-84.)
C1 [Leachman, Sancy A.] Univ Utah, Dept Dermatol, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
[Carucci, John] Cornell Univ, Weill Med Coll, Dept Dermatol, New York, NY 10021 USA.
[Asgari, Maryam M.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Bergman, Wilma; de Snoo, Femke A.] Leiden Univ, Med Ctr, Dept Dermatol & Clin Genet, NL-2300 RA Leiden, Netherlands.
[Bianchi-Scarra, Giovanna; Bruno, William] Univ Genoa, Dept Oncol Biol & Genet, Med Genet Serv, I-16126 Genoa, Italy.
[Brentnall, Teresa] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, Serv Genet, Villejuif, France.
[Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, CNRS, France Genomes & Canc 2939, Villejuif, France.
[Curiel-Lewandrowski, Clara] Univ Arizona, Arizona Canc Ctr, Dermatol Sect, Tucson, AZ 85721 USA.
[Debniak, Tadeusz] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
[Demierre, Marie-France] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02215 USA.
[Elder, David] Hosp Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Goldstein, Alisa M.; Tucker, Margaret A.] Natl Canc Inst, Div Canc Epidemiol & Genet, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD USA.
[Grant-Kels, Jane] Univ Connecticut, Ctr Hlth, Dept Dermatol, Storrs, CT 06269 USA.
[Halpern, Allan C.] Mem Sloan Kettering Canc Ctr, Dermatol Serv, New York, NY 10021 USA.
[Ingvar, Christian] Univ Lund Hosp, Dept Surg, Lund, Sweden.
[Olsson, Hakan] Univ Lund Hosp, Dept Oncol & Canc Epidemiol, Lund, Sweden.
[Kefford, Richard F.; Mann, Graham J.] Univ Sydney, Westmead Millennium Inst, Westmead Inst Canc Res, Sydney, NSW 2006, Australia.
[Kefford, Richard F.; Mann, Graham J.] Univ Sydney, Westmead Millennium Inst, Sydney Melanoma Unit, Sydney, NSW 2006, Australia.
[Lang, Julie] Duncan Guthrie Inst Med Genet, Glasgow G3 8SJ, Lanark, Scotland.
[MacKie, Rona M.] Univ Glasgow, Dept Publ Hlth, Glasgow G12 8QQ, Lanark, Scotland.
[MacKie, Rona M.] Univ Glasgow, Dept Hlth Policy, Glasgow G12 8QQ, Lanark, Scotland.
[MacKie, Rona M.] Univ Glasgow, Dept Med Genet, Glasgow G12 8QQ, Lanark, Scotland.
[Mueller, Kurt] Gundersen Lutheran Med Ctr, Dept Dermatol, La Crosse, WI USA.
[Newton-Bishop, Julia] Univ Leeds, Leeds Inst Mol Med, Div Epidemiol & Biostat, Leeds LS2 9JT, W Yorkshire, England.
[Peterson, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Puig, Susana] Hosp Clin Barcelona, Melanoma Unit, Dept Dermatol, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain.
[Puig, Susana] Ctr Invest Biobedica Red Enfermedades, Barcelona, Spain.
[Rigel, Darrell] NYU, Sch Med, Dept Dermatol, New York, NY 10003 USA.
[Swetter, Susan M.] Stanford Univ, Med Ctr, Dept Dermatol, Pigmented Les & Melanoma Program,Dept Vet Affairs, Stanford, CA 94305 USA.
[Yakobson, Emanuel] Tel Aviv Univ, Sourasky Med Ctr, Lab Clin Biochem, Tel Aviv, Israel.
[Zitelli, John A.] Univ Pittsburgh, Dept Dermatol, Pittsburgh, PA 15260 USA.
[Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
RP Leachman, SA (reprint author), Univ Utah, Dept Dermatol, Huntsman Canc Inst, 2000 Circle Hope Dr, Salt Lake City, UT 84112 USA.
EM sancy.leachman@hci.utah.edu
RI Mann, Graham/G-4758-2014; Bianchi Scarra, Giovanna/G-8933-2014; Tucker,
Margaret/B-4297-2015; Bruno, William/N-7477-2013; Asgari,
Maryam/O-4947-2016;
OI Mann, Graham/0000-0003-1301-405X; Bianchi Scarra,
Giovanna/0000-0002-6127-1192; Bruno, William/0000-0002-0337-0168; Banks,
Kimberly/0000-0002-1290-3114; Newton Bishop, Julia/0000-0001-9147-6802;
Puig, Susana/0000-0003-1337-9745
FU National Institute of Arthritis Musculoskeletal and Skin Diseases [K23
AR 051037]; NCI [P50 CA-93683]; RSG [MG0-112970]; NIH [R01 CA83115]
FX The work of Dr Asgari is supported by the National Institute of
Arthritis Musculoskeletal and Skin Diseases (K23 AR 051037). The work of
Dr Tsao is supported by P50 CA-93683 (NCI), RSG MG0-112970 (American
Cancer Society), NIH R01 CA83115.
NR 96
TC 42
Z9 42
U1 0
U2 6
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 OCT
PY 2009
VL 61
IS 4
BP 677
EP 684
DI 10.1016/j.jaad.2009.03.016
PG 8
WC Dermatology
SC Dermatology
GA 499WU
UT WOS:000270258300015
ER
PT J
AU Boyd, CM
Ricks, M
Fried, LP
Guralnik, JM
Xue, QL
Xia, J
Bandeen-Roche, K
AF Boyd, Cynthia M.
Ricks, Michelle
Fried, Linda P.
Guralnik, Jack M.
Xue, Qian-Li
Xia, Jin
Bandeen-Roche, Karen
TI Functional Decline and Recovery of Activities of Daily Living in
Hospitalized, Disabled Older Women: The Women's Health and Aging Study I
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE hospitalization; activities of daily living; disability; recovery
ID EMOTIONAL VITALITY; MEDICAL ILLNESSES; ELDERLY-PATIENTS; DISABILITY;
INDEPENDENCE; COMMUNITY; ADULTS; FRAILTY; RISK; CARE
AB OBJECTIVES
To determine, in disabled, older, community-dwelling women who were hospitalized, the rates and predictors of functional decline, the probability and time course of subsequent functional recovery, and predictors of functional recovery.
DESIGN
Population-based observational cohort.
SETTING
Woman's Health and Aging Study.
PARTICIPANTS
A subset of the 1,002 moderately to severely disabled community-dwelling older women who were hospitalized over 3 years (N=457).
MEASUREMENTS
Functional decline and complete and partial recovery were defined using a 0 to 6 scale of dependencies in activities of daily living (ADLs) evaluated every 6 months over 3 years. Complete recovery was defined as returning to baseline function (function at visit immediately preceding hospitalization) after functional decline; partial recovery was defined as any improvement in the ADL scale after functional decline. Multiple logistic regression analysis was used to determine predictors of functional decline. Kaplan-Meier curves estimate the proportions recovering as a function of time since hospitalization. Discrete-time proportional hazards models regress the time-to-recovery hazards on the predictor variables.
RESULTS
Thirty-three percent of hospitalized women experienced functional decline at the first visit after hospitalization. Frailty, longer length of stay, and higher education were associated with functional decline. Fifty percent fully recovered over the subsequent 30 months, with 33% recovering within 6 months and an additional 14% over the following 6 months. Younger women were more likely to recover (aged 80 to 70, hazard ratio=0.39, 95% confidence interval=0.24-0.64).
CONCLUSION
Although most recovery of function occurs by 6 months after the first visit after a hospitalization, a substantial proportion of disabled community-dwelling women recover over the following 2 years.
C1 [Boyd, Cynthia M.; Ricks, Michelle; Fried, Linda P.; Xue, Qian-Li; Xia, Jin; Bandeen-Roche, Karen] NIA, Sch Med, Ctr Aging & Hlth, Baltimore, MD 21224 USA.
[Boyd, Cynthia M.; Ricks, Michelle; Fried, Linda P.; Xue, Qian-Li; Xia, Jin; Bandeen-Roche, Karen] NIA, Bloomberg Sch Publ Hlth, Ctr Aging & Hlth, Baltimore, MD 21224 USA.
[Boyd, Cynthia M.; Fried, Linda P.; Xue, Qian-Li; Bandeen-Roche, Karen] NIA, Sch Med, Dept Med, Baltimore, MD 21224 USA.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Dept Epidemiol, Baltimore, MD 21224 USA.
[Bandeen-Roche, Karen] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21224 USA.
RP Boyd, CM (reprint author), Johns Hopkins Univ, Div Geriatr Med & Gerontol, Sch Med, Mason F Lord Bldg,Ctr Tower,7th Floor,5200 Easter, Baltimore, MD 21224 USA.
EM cboyd1@jhmi.edu
FU National Institute on Aging (NIA) through the Older Americans
Independence Center (OAIC); Pfizer/American Geriatrics Society Junior
Faculty Scholars on Health Outcomes Award; NIANO-1AG-1-2112; OAIC [P30
AG021334]; National Institutes of Health
FX Conflict of Interest: The editor in chief has reviewed the conflict of
interest checklist provided by the authors and has determined that the
authors have no financial or any other kind of personal conflicts with
this paper. Dr. Boyd has been supported by the National Institute on
Aging (NIA) through the Older Americans Independence Center (OAIC) and
received a Pfizer/American Geriatrics Society Junior Faculty Scholars on
Health Outcomes Award. Drs. Qian-Li Xue, Karen Bandeen-Roche, and Linda
Fried and Ms. Michelle Ricks and Jin Xia have all received funding from
the NIA and the OAIC (P30 AG021334). None of the authors received
corporate financial support, consultantships, speaker arrangements,
company holdings, or patents related to this research and the materials
described in this article. The Women's Health and Aging Study was funded
by NIA Contract NO-1AG-1-2112. This work was supported, in part, by the
Intramural Research Program, NIA, National Institutes of Health.
NR 46
TC 45
Z9 46
U1 0
U2 9
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD OCT
PY 2009
VL 57
IS 10
BP 1757
EP 1766
DI 10.1111/j.1532-5415.2009.02455.x
PG 10
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 503PV
UT WOS:000270551300003
PM 19694869
ER
PT J
AU Maraldi, C
Harris, TB
Newman, AB
Kritchevsky, SB
Pahor, M
Koster, A
Satterfield, S
Ayonayon, HN
Fellin, R
Volpato, S
AF Maraldi, Cinzia
Harris, Tamara B.
Newman, Anne B.
Kritchevsky, Stephen B.
Pahor, Marco
Koster, Annemarie
Satterfield, Suzanne
Ayonayon, Hilsa N.
Fellin, Renato
Volpato, Stefano
CA Hlth ABC Study
TI Moderate Alcohol Intake and Risk of Functional Decline: The Health,
Aging, and Body Composition Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE alcohol intake; functional decline; aging
ID ACTIVE LIFE EXPECTANCY; CORONARY HEART-DISEASE; CARDIOVASCULAR HEALTH;
PHYSICAL-ACTIVITY; OLDER-ADULTS; INFLAMMATORY MARKERS; MASS INDEX;
CONSUMPTION; WOMEN; DISABILITY
AB OBJECTIVES
To investigate the prospective relationship between alcohol consumption and incident mobility limitation.
DESIGN
Cohort study.
SETTING
The Health Aging and Body Composition study, conducted in Memphis, Tennessee, and Pittsburgh, Pennsylvania.
PARTICIPANTS
Three thousand sixty-one adults aged 70 to 79 without mobility disability at baseline.
MEASUREMENTS
Incidence of mobility limitation, defined as self-report at two consecutive semiannual interviews of any difficulty walking one-quarter of a mile or climbing stairs, and incidence of mobility disability, defined as severe difficulty or inability to perform these tasks at two consecutive reports. Alcohol intake, lifestyle-related variables, diseases, and health status indicators were assessed at baseline.
RESULTS
During a follow-up time of 6.5 years, participants consuming moderate levels of alcohol had the lowest incidence of mobility limitation (total: 6.4 per 100 person-years (person-years); men: 6.4 per 100 person-years; women: 7.3 per 100 person-years) and mobility disability (total: 2.7 per 100 person-years; men: 2.5 per 100 person-years; women: 2.9 per 100 person-years). Adjusting for demographic characteristics, moderate alcohol intake was associated with lower risk of mobility limitation (hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.55-0.89) and mobility disability (HR=0.66, 95% CI=0.45-0.95) than never or occasional consumption. Additional adjustment for lifestyle-related variables substantially reduced the strength of the associations (HR=0.85, 95% CI=0.66-1.08 and HR=0.81, 95% CI=0.56-1.18, respectively). Adjustment for diseases and health status indicators did not affect the strength of the associations, suggesting that lifestyle is most important in confounding this relationship.
CONCLUSION
Lifestyle-related characteristics mainly accounted for the association between moderate alcohol intake and lower risk of functional decline over time. These findings do not support a direct causal effect of alcohol intake on physical function.
C1 [Maraldi, Cinzia; Fellin, Renato; Volpato, Stefano] Univ Ferrara, Sect Internal Med Gerontol & Geriatr, Dept Clin & Expt Med, I-44100 Ferrara, Italy.
[Harris, Tamara B.; Koster, Annemarie] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Med, Pittsburgh, PA USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Pahor, Marco] Univ Florida, Inst Aging, Gainesville, FL USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Ayonayon, Hilsa N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Maraldi, C (reprint author), Univ Ferrara, Sect Internal Med Gerontol & Geriatr, Dept Clin & Expt Med, Via Savonarola 9, I-44100 Ferrara, Italy.
EM mrlcnz@unife.it
RI Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Volpato, Stefano/0000-0003-4335-6034;
Kritchevsky, Stephen/0000-0003-3336-6781
FU National Institute on Aging [N01-AG-6-2106, N01-AG-6-2103,
N01-AG-6-2101, R01 HL72972]; National Institutes of Health
FX This research was supported through National Institute on Aging
Contracts N01-AG-6-2106, N01-AG-6-2103, and N01-AG-6-2101 and in part by
the Intramural Research Program of the National Institutes of Health,
National Institute on Aging Grant R01 HL72972.
NR 41
TC 15
Z9 15
U1 1
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD OCT
PY 2009
VL 57
IS 10
BP 1767
EP 1775
DI 10.1111/j.1532-5415.2009.02479.x
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 503PV
UT WOS:000270551300004
PM 19737328
ER
PT J
AU Maggio, M
Ceda, GP
Lauretani, F
Bandinelli, S
Ruggiero, C
Guralnik, JM
Metter, EJ
Ling, SM
Paolisso, G
Valenti, G
Cappola, AR
Ferrucci, L
AF Maggio, Marcello
Ceda, Gian Paolo
Lauretani, Fulvio
Bandinelli, Stefania
Ruggiero, Carmelinda
Guralnik, Jack M.
Metter, E. Jeffrey
Ling, Shari M.
Paolisso, Giuseppe
Valenti, Giorgio
Cappola, Anne R.
Ferrucci, Luigi
TI Relationship Between Higher Estradiol Levels and 9-Year Mortality in
Older Women: The Invecchiare in Chianti Study
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE estradiol; older postmenopausal women; mortality
ID ENDOGENOUS SEX-HORMONES; ESTROGEN PLUS PROGESTIN; GLUCOSE-TOLERANCE
STATUS; CORONARY-HEART-DISEASE; POSTMENOPAUSAL WOMEN; REPLACEMENT
THERAPY; CARDIOVASCULAR-DISEASE; COLORECTAL-CANCER; RISK; ASSOCIATION
AB OBJECTIVES
To investigate the relationship between total estradiol (E2) levels and 9-year mortality in older postmenopausal women not taking hormone replacement therapy (HRT).
DESIGN
Population-based study of persons living in the Chianti geographic area (Tuscany, Italy).
SETTING
Community.
PARTICIPANTS
A representative sample of 509 women aged 65 and older with measures of total E2.
MEASUREMENTS
Serum total E2 was measured at the University of Parma using ultrasensitive radioimmunoassay (RIA).
RESULTS
Women who died (n=135) during 9 years of follow up were older; had higher total E2 levels; and were more likely to have evidence of stroke, hypertension, diabetes mellitus, and congestive heart failure at baseline than survivors. Higher E2 levels were associated with a greater likelihood of death (hazard ratio (HR)=1.03, 95% confidence interval (CI)=1.01-1.06), and the relationship was independent of age, waist:hip ratio, C-reactive protein, education, cognitive function, physical activity, caloric intake, smoking, and chronic disease (HR=1.08 pg/mL, 95% CI=1.03-1.13, P=.003). The excessive risk of death associated with higher total E2 was not attenuated after adjustment for total testosterone (HR=1.12, 95% CI=1.02-1.18, P <.001) and after further adjustment for insulin resistance evaluated using the homeostasis model assessment (HR=1.07, 95% CI=1.03-1.17, P <.001).
Total E2 was highly predictive of death after more than 5 years (HR=1.42: CI 1.01-1.91, P=.04) and not predictive of death for less than 5 years (P=.78).
CONCLUSION
Higher total E2 concentration predicts mortality in older women not taking HRT.
C1 [Ferrucci, Luigi] Harbor Hosp, NIA, ASTRA Unit, Longitudinal Studies Sect,, Baltimore, MD 21225 USA.
[Ling, Shari M.] NIA, NIH, Clin Res Branch, Intramural Res Program, Baltimore, MD 21225 USA.
[Paolisso, Giuseppe] Univ Naples 2, Unit Internal Med 6, Dept Geriatr Med & Metab Dis, Naples, Italy.
[Cappola, Anne R.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Maggio, Marcello; Ceda, Gian Paolo; Valenti, Giorgio] Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, I-43100 Parma, Italy.
[Maggio, Marcello; Ceda, Gian Paolo; Lauretani, Fulvio] Azienda Osped Univ, Geriatr Rehabil Dept, Parma, Italy.
[Bandinelli, Stefania] Azienda Sanit Firenze, Florence, Italy.
[Ruggiero, Carmelinda] Univ Perugia, Dept Clin & Expt Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21225 USA.
RP Ferrucci, L (reprint author), Harbor Hosp, NIA, ASTRA Unit, Longitudinal Studies Sect,, Harbor Hosp 3001 S Hanover St, Baltimore, MD 21225 USA.
EM ferruccilu@grc.nia.nih.gov
RI Lauretani, Fulvio/K-5115-2016;
OI Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian
Paolo/0000-0002-9648-8295
FU Italian Ministry of Health [ICS 110.1/RS97.71]; U.S. National Institute
on Aging [N01-AG-916413, N01-AG-821336, 263 MD 9164 13, 263 MD 821336]
FX The InCHIANTI Study was supported as a "targeted project" (ICS
110.1/RS97.71) by the Italian Ministry of Health and in part by the U.S.
National Institute on Aging (Contracts N01-AG-916413 and N01-AG-821336)
and by the Intramural Research Program of the U.S. National Institute on
Aging (Contracts 263 MD 9164 13 and 263 MD 821336).
NR 38
TC 17
Z9 18
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD OCT
PY 2009
VL 57
IS 10
BP 1810
EP 1815
DI 10.1111/j.1532-5415.2009.02464.x
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 503PV
UT WOS:000270551300009
PM 19737330
ER
PT J
AU Semba, RD
Bandinelli, S
Sun, K
Guralnik, JM
Ferrucci, L
AF Semba, Richard D.
Bandinelli, Stefania
Sun, Kai
Guralnik, Jack M.
Ferrucci, Luigi
TI Plasma Carboxymethyl-Lysine, an Advanced Glycation End Product, and
All-Cause and Cardiovascular Disease Mortality in Older
Community-Dwelling Adults
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE advanced glycation end products; aging; all-cause mortality;
cardiovascular disease mortality
ID DENSITY-LIPOPROTEIN CHOLESTEROL; DIABETES-MELLITUS; OXIDATIVE STRESS;
SERUM-LEVELS; RISK-FACTOR; ENDPRODUCTS; AGE;
N-EPSILON-(CARBOXYMETHYL)LYSINE; ACCUMULATION; GLYCOTOXINS
AB OBJECTIVES
To determine whether older adults with high plasma carboxymethyl-lysine (CML), an advanced glycation end product, are at higher risk of all-cause and cardiovascular disease (CVD) mortality.
DESIGN
Prospective cohort study.
SETTING
Population-based sample of adults aged 65 and older residing in Tuscany, Italy.
PARTICIPANTS
One thousand thirteen adults participating in the Invecchiare in Chianti study.
MEASUREMENTS
Anthropometric measures, plasma CML, fasting plasma total, high-density and low-density lipoprotein cholesterol, triglycerides, glucose, creatinine. Clinical measures: medical assessment, diabetes mellitus, hypertension, coronary heart disease, heart failure, stroke, cancer. Vital status measures: death certificates and causes of death according to the International Classification of Diseases. Survival methods were used to examine the relationship between plasma CML and all-cause and CVD mortality, adjusting for potential confounders.
RESULTS
During 6 years of follow-up, 227 (22.4%) adults died, of whom 105 died with CVD. Adults with plasma CML in the highest tertile had greater all-cause (hazard ratio (HR)=1.84, 95% confidence interval) CI)=1.30-2.60, P <.001) and CVD (HR=2.11, 95% CI=1.27-3.49, P=.003) mortality than those in the lower two tertiles after adjusting for potential confounders. In adults without diabetes mellitus, those with plasma CML in the highest tertile had greater all-cause (HR=1.68, 95% CI=1.15-2.44, P=.006) and CVD (HR=1.74, 95% CI=1.00-3.01, P=.05) mortality than those in the lower two tertiles after adjusting for potential confounders.
CONCLUSION
Older adults with high plasma CML are at higher risk of all-cause and CVD mortality.
C1 [Semba, Richard D.; Sun, Kai] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Bandinelli, Stefania] Azienda Sanit Firenze, Florence, Italy.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
RP Semba, RD (reprint author), 550 N Broadway,Suite 700, Baltimore, MD 21205 USA.
EM rdsemba@jhmi.edu
FU National Institute on Aging (NIA) [R01 AG027012, R01 AG029148]; National
Institutes of Health (NIH)
FX This work was supported by National Institute on Aging (NIA) Grants R01
AG027012, R01 AG029148 and the Intramural Research Program, NIA,
National Institutes of Health (NIH).
NR 30
TC 42
Z9 44
U1 0
U2 3
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD OCT
PY 2009
VL 57
IS 10
BP 1874
EP 1880
DI 10.1111/j.1532-5415.2009.02438.x
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 503PV
UT WOS:000270551300019
PM 19682127
ER
PT J
AU Park, SK
Kang, D
Kim, Y
Yoo, KY
AF Park, Sue K.
Kang, Daehee
Kim, Yeonju
Yoo, Keun-Young
TI Epidemiologic Characteristics of the Breast Cancer in Korea
SO JOURNAL OF THE KOREAN MEDICAL ASSOCIATION
LA Korean
DT Article
DE Breast cancer; Risk factors; Environment; Gene
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ATOMIC-BOMB SURVIVORS;
RECEPTOR-ALPHA GENE; S-TRANSFERASE M1; BODY-MASS INDEX; LIFE-STYLE;
RISK; WOMEN; POLYMORPHISMS; ASSOCIATION
AB Breast cancer has been the most common cancer among Korean women since 2001 and will continue to increase for the next 20 years, at the least. Many of the established risk factors are linked to the exposure to female hormones: breast cancer risk is increased by early menarche, late menopause, nulliparity and later first full-term pregnancy, and obesity in postmenopausal women. In addition, other established risk factors such as alcohol consumption and family history of breast cancer are associated with an increased risk of breast cancer. Physical activity, breast feeding, higher number of children, and fruit and vegetable consumption seem to reduce breast cancer risk. Smoking also probably increases the risk. Both ora contraceptives in premenopausal women and hormonal replacement therapy in postmenopausal women may increase risk. Above-mentioned risk and protective factors were reported in Korean populations and the breast cancer risk by those factors is similar to that in western population. Currently, a study is being done in Korea to examine the associated risk, and population attributable risk of genetic variants in high penetrance genes including BRCA 1 and 2 and breast cancer risk among Koreans will be reported soon. Other studies conducted in Korea that investigated low penetrance genes have already been published. While the individual risk was small, there was an effect from interaction with environmental factors. Numerous Korean studies about these risk factors helped to establish a model to predict individual breast cancer risk that is utilized in the Personalized Preventive and Predictive medicine.
C1 [Park, Sue K.; Kang, Daehee] Seoul Natl Univ, Dept Prevent Med, Coll Med, Canc Res Ins,WCU, Seoul 151, South Korea.
[Park, Sue K.] Seoul Natl Univ, Inst Hlth Policy & Management, Seoul 151, South Korea.
[Kim, Yeonju] Natl Canc Ctr, Canc Early Detect Branch, Natl Canc Control Inst, Bethesda, MD 20892 USA.
RP Park, SK (reprint author), Seoul Natl Univ, Dept Prevent Med, Coll Med, Canc Res Ins,WCU, Seoul 151, South Korea.
EM suepark@snu.ac.kr; dhkang@snu.ac.kr; yeonju@ncc.re.kr; kyyoo@snu.ac.kr
RI Kang, Dae Hee/E-8631-2012; Park, Sue Kyung/J-2757-2012; Kim,
Yeonju/D-8948-2013
NR 58
TC 8
Z9 8
U1 2
U2 5
PU KOREAN MEDICAL ASSOC
PI SEOUL
PA 302-75 INCHON-1 DONG, YONGSAN-GU, SEOUL, 140-721, SOUTH KOREA
SN 1975-8456
J9 J KOREAN MED ASSOC
JI J. Korean Med. Assoc.
PD OCT
PY 2009
VL 52
IS 10
BP 937
EP 945
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 510DU
UT WOS:000271069000002
ER
PT J
AU Hofman, KJ
Kanyengo, CW
Rapp, BA
Kotzin, S
AF Hofman, Karen J.
Kanyengo, Christine W.
Rapp, Barbara A.
Kotzin, Sheldon
TI Pubmed growth patterns and visibility of journals of Sub-Saharan African
origin Response
SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION
LA English
DT Letter
C1 [Hofman, Karen J.] NIH, Div Int Sci Policy Planning & Evaluat, John E Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Kanyengo, Christine W.] Univ Zambia, Med Lib, Sch Med, Lusaka, Zambia.
[Rapp, Barbara A.] NIH, Off Planning & Anal, Off Hlth Informat Programs Dev, Natl Lib Med, Bethesda, MD 20894 USA.
RP Hofman, KJ (reprint author), NIH, Div Int Sci Policy Planning & Evaluat, John E Fogarty Int Ctr, 16 Ctr Dr,MSC 6705, Bethesda, MD 20892 USA.
EM hofmank@mail.nih.gov; ckanyengo@yahoo.com; rappb@mail.nlm.nih.gov;
kotzins@mail.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MEDICAL LIBRARY ASSOC
PI CHICAGO
PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA
SN 1536-5050
J9 J MED LIBR ASSOC
JI J. Med. Libr. Assoc.
PD OCT
PY 2009
VL 97
IS 4
BP 243
EP 243
DI 10.3163/1536-5050.97.4.005
PG 1
WC Information Science & Library Science
SC Information Science & Library Science
GA 546OO
UT WOS:000273820300005
ER
PT J
AU Dunn, K
Brewer, K
Marshall, JG
Sollenberger, J
AF Dunn, Kathel
Brewer, Karen
Marshall, Joanne Gard
Sollenberger, Julia
TI Measuring the value and impact of health sciences libraries: planning an
update and replication of the Rochester Study
SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION
LA English
DT Article
ID PATIENT-CARE; CLINICAL LIBRARIAN; HOSPITAL LIBRARY; DECISION-MAKING;
SERVICES; SUPPORT
C1 [Dunn, Kathel] Natl Lib Med, Bethesda, MD 20894 USA.
[Brewer, Karen] NYU, Hlth Sci Lib, Ehrman Med Lib, New York, NY 10016 USA.
[Marshall, Joanne Gard] Univ N Carolina, Sch Informat & Lib Sci, Chapel Hill, NC 27599 USA.
[Sollenberger, Julia] Univ Rochester, Med Ctr, Dept Community & Prevent Med, Rochester, NY 14642 USA.
[Sollenberger, Julia] Hlth Sci Lib & Technol, Rochester, NY 14642 USA.
RP Dunn, K (reprint author), Natl Lib Med, Bldg 38,2N-19, Bethesda, MD 20894 USA.
EM Kathel.dunn@gmail.com; Karen.brewer@med.nyu.edu; marshall@ils.unc.edu;
Julia_2sollenberger@urmc.rochester.edu
OI Dunn, Kathel/0000-0002-6967-130X
FU NLM NIH HHS [N01-LM-6-3501]
NR 23
TC 5
Z9 6
U1 3
U2 7
PU MEDICAL LIBRARY ASSOC
PI CHICAGO
PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA
SN 1536-5050
J9 J MED LIBR ASSOC
JI J. Med. Libr. Assoc.
PD OCT
PY 2009
VL 97
IS 4
BP 308
EP 312
DI 10.3163/1536-5050.97.4.016
PG 5
WC Information Science & Library Science
SC Information Science & Library Science
GA 546OO
UT WOS:000273820300017
PM 19851496
ER
PT J
AU Thorner-Bantug, E
Jaszyna-Gasior, M
Schroeder, JR
Collins, CC
Moolchan, ET
AF Thorner-Bantug, Elissa
Jaszyna-Gasior, Maria
Schroeder, Jennifer R.
Collins, Charles C.
Moolchan, Eric T.
TI Weight Gain, Related Concerns, and Treatment Outcomes Among Adolescent
Smokers Enrolled in Cessation Treatment
SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
LA English
DT Article
DE children/adolescents; tobacco; body weight; prevention; treatment
ID NICOTINE DEPENDENCE; SMOKING CESSATION; CIGARETTE-SMOKING; GENDER;
GIRLS; WOMEN
AB We examined associations of weight concerns and weight gain with adolescent tobacco cessation treatment and whether these effects differed by gender or ethnoracial group. Participants were 115 urban adolescents recruited for a randomized clinical trial of nicotine replacement therapy. Baseline weight gain concerns were assessed using the Eating Disorders module from the Diagnostic Interview for the Child and Adolescent DICA-IV). The average weight gain during the trial was 0.59 +/- 2.85 kg among the 43.5% of participants who completed the treatment study. As indicated by the DICA, baseline weight gain concerns were not associated with weight gain during treatment, study completion, or abstinence from smoking at 3-month posttreatment follow-up; these results did not vary by gender or ethnoracial group. Adolescents who quit smoking gained no more weight during the trial than those who smoked.
C1 [Thorner-Bantug, Elissa; Jaszyna-Gasior, Maria; Schroeder, Jennifer R.; Collins, Charles C.; Moolchan, Eric T.] NIDA, Dept Hlth & Human Resources, NIH, Intramural Res Program,Biomed Res Ctr, Baltimore, MD USA.
RP Moolchan, ET (reprint author), Alkermes Inc, Clin Sci, 88 Sidney St, Cambridge, MA 02139 USA.
EM eric.moolchan@alkermes.com
FU National Institutes of Health, National Institute on Drug Abuse,
Intramural Research Program
FX This study was supported in full by funds from the National Institutes
of Health, National Institute on Drug Abuse, Intramural Research
Program.
NR 20
TC 6
Z9 6
U1 2
U2 4
PU NATL MED ASSOC
PI WASHINGON
PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA
SN 0027-9684
J9 J NATL MED ASSOC
JI J. Natl. Med. Assoc.
PD OCT
PY 2009
VL 101
IS 10
BP 1009
EP 1014
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 511XJ
UT WOS:000271204700005
PM 19860300
ER
PT J
AU Ballas, SK
McCarthy, WF
Guo, N
DeCastro, L
Bellevue, R
Barton, BA
Waclawiw, MA
AF Ballas, Samir K.
McCarthy, William F.
Guo, Nan
DeCastro, Laura
Bellevue, Rita
Barton, Bruce A.
Waclawiw, Myron A.
CA Investigators Multictr Study Hydro
TI Exposure to Hydroxyurea and Pregnancy Outcomes in Patients With Sickle
Cell Anemia
SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
LA English
DT Article
DE hydroxyurea; sickle cell anemia; obstetrics/gynecology
ID CHRONIC MYELOID-LEUKEMIA; DISEASE; ADULTS; COMBINATION; MANAGEMENT; RATS
AB The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) was a randomized double-blind placebo-controlled trial to test whether hydroxyurea could reduce the rate of painful crises in adults who had at least 3 painful crises per year. Because hydroxyurea is known to be carcinogenic, mutagenic, and teratogenic in animals, a major inclusion criterion in MSH was the use of contraceptives both by females and males in order to avoid exposure of the fetus to hydroxyurea. Despite this precautionary measure, some women became pregnant while taking hydroxyurea or their male partners were on hydroxyurea. We followed surviving patients who were enrolled in the original MSH trial for up to 17 years postrandomization. Our findings suggest that exposure of the fetus to hydroxyurea does not cause teratogenic changes in those pregnancies that terminate in live birth whether full term or premature. This seems to be true whether the parent taking hydroxyurea was the mother or the father. The same argument seems to apply for exposure to opioids. However, it will take a much longer follow-up of many more hydroxyurea-exposed sickle cell disease subjects to establish the results conclusively.
C1 [Ballas, Samir K.] Thomas Jefferson Univ, Jefferson Med Coll, Cardeza Fdn Hematol Res, Sickle Cell Ctr,Dept Med, Philadelphia, PA 19107 USA.
[McCarthy, William F.; Guo, Nan; Barton, Bruce A.] Maryland Med Res Inst, Baltimore, MD USA.
[DeCastro, Laura] Duke Univ, Med Ctr, Durham, NC USA.
[Bellevue, Rita] New York Methodist Hosp, Brooklyn, NY USA.
[Waclawiw, Myron A.] NHLBI, Bethesda, MD 20892 USA.
RP Ballas, SK (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Cardeza Fdn Hematol Res, Sickle Cell Ctr,Dept Med, 1015 Walnut St, Philadelphia, PA 19107 USA.
EM samir.ballas@jefferson.edu
OI Barton, Bruce/0000-0001-7878-8895
FU National Heart Lung, and Blood Institute [NO1-HB-67129, UO1-HL45696]
FX Funding was provided by the National Heart Lung, and Blood Institute
(NO1-HB-67129 and UO1-HL45696).
NR 32
TC 29
Z9 29
U1 2
U2 6
PU NATL MED ASSOC
PI WASHINGON
PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA
SN 0027-9684
J9 J NATL MED ASSOC
JI J. Natl. Med. Assoc.
PD OCT
PY 2009
VL 101
IS 10
BP 1046
EP 1051
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 511XJ
UT WOS:000271204700010
PM 19860305
ER
PT J
AU Bell, CC
AF Bell, Carl C.
TI Why We Should Still Publish in JNMA More Than 25 Years Later
SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
LA English
DT Editorial Material
DE National Medical Association
ID ISOLATED SLEEP PARALYSIS; STRESS-RELATED DISORDERS; BLACK SUBJECTS;
VICTIMIZATION; NEED; POPULATION; PREVALENCE; HEALTH
C1 [Bell, Carl C.] Community Mental Hlth Council & Fdn, Chicago, IL 60617 USA.
[Bell, Carl C.] Univ Illinois, Inst Juvenile Res, Chicago, IL USA.
[Bell, Carl C.] NIMH, Natl Mental Hlth Advisory Council, Chicago, IL USA.
RP Bell, CC (reprint author), Community Mental Hlth Council & Fdn, 8704 Constance, Chicago, IL 60617 USA.
EM carlcbell@pol.net
NR 31
TC 0
Z9 0
U1 0
U2 0
PU NATL MED ASSOC
PI WASHINGON
PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA
SN 0027-9684
J9 J NATL MED ASSOC
JI J. Natl. Med. Assoc.
PD OCT
PY 2009
VL 101
IS 10
BP 1067
EP 1069
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 511XJ
UT WOS:000271204700014
PM 19860309
ER
PT J
AU Hallett, M
AF Hallett, M.
TI Psychogenic movement disorders
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Meeting Abstract
CT 19th World Congress of Neurology
CY OCT 24-30, 2009
CL Bangkok, THAILAND
C1 [Hallett, M.] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD OCT
PY 2009
VL 285
SU 1
BP S41
EP S41
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 529ML
UT WOS:000272521300146
ER
PT J
AU Koroshetz, W
AF Koroshetz, W.
TI Imaging acute stroke: Perfusion imaging, diffusion imaging and
angiographic guided endovascular procedures
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Meeting Abstract
CT 19th World Congress of Neurology
CY OCT 24-30, 2009
CL Bangkok, THAILAND
C1 [Koroshetz, W.] NINDS, NIH, NINDS Off Director, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD OCT
PY 2009
VL 285
SU 1
BP S10
EP S11
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 529ML
UT WOS:000272521300035
ER
PT J
AU Masdeu, J
AF Masdeu, J.
TI Imaging of dementia
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Meeting Abstract
CT 19th World Congress of Neurology
CY OCT 24-30, 2009
CL Bangkok, THAILAND
C1 [Masdeu, J.] NIH, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA.
RI Masdeu, Joseph/B-5052-2010
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD OCT
PY 2009
VL 285
SU 1
BP S7
EP S7
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 529ML
UT WOS:000272521300023
ER
PT J
AU Saposnik, G
Bayley, M
Cheung, D
Willems, J
Mamdani, M
Cohen, L
Hall, J
Dishaw, A
Thorpe, K
Teasell, R
AF Saposnik, G.
Bayley, M.
Cheung, D.
Willems, J.
Mamdani, M.
Cohen, L.
Hall, J.
Dishaw, A.
Thorpe, K.
Teasell, R.
TI Virtual reality technology in stroke rehabilitation: a pilot randomized
trial using Wii gaming system
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Meeting Abstract
CT 19th World Congress of Neurology
CY OCT 24-30, 2009
CL Bangkok, THAILAND
C1 [Saposnik, G.; Cheung, D.; Willems, J.; Mamdani, M.; Hall, J.; Thorpe, K.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[Bayley, M.] Toronto Rehabil Inst, Toronto, ON, Canada.
[Cohen, L.] NIH, Bethesda, MD 20892 USA.
[Dishaw, A.] Toronto Grace, Toronto, ON, Canada.
[Teasell, R.] Univ Western Ontario, London, ON, Canada.
NR 0
TC 2
Z9 3
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD OCT
PY 2009
VL 285
SU 1
BP S76
EP S76
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 529ML
UT WOS:000272521300265
ER
PT J
AU Yavlovich, A
Singh, A
Tarasov, S
Capala, J
Blumenthal, R
Puri, A
AF Yavlovich, Amichai
Singh, Alok
Tarasov, Sergey
Capala, Jacek
Blumenthal, Robert
Puri, Anu
TI Design of liposomes containing photopolymerizable phospholipids for
triggered release of contents
SO JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
LA English
DT Article
DE Polymerizable lipids; Lipid packing; Triggered drug release; Diacetylene
phospholipids; Light-sensitive liposomes; Lipid modification; Phase
separation
ID POLYMERIZABLE LIPID BILAYERS; THERMOTROPIC PHASE-BEHAVIOR;
PHYSICAL-PROPERTIES; ACYL CHAINS; PHOSPHATIDYLCHOLINES; MEMBRANES;
MIXTURES; MONOLAYERS; VESICLES; DELIVERY
AB We describe a novel class of light-triggerable liposomes prepared from a photo-polymerizable phospholipid DC(8,9)PC (1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine) and DPPC (1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine). Exposure to UV (254 nm) radiation for 0-45 min at 25 A degrees C resulted in photo-polymerization of DC(8,9)PC in these liposomes and the release of an encapsulated fluorescent dye (calcein). Kinetics and extents of calcein release correlated with mol% of DC(8,9)PC in the liposomes. Photopolymerization and calcein release occurred only from DPPC/DC(8,9)PC but not from Egg PC/DC(8,9)PC liposomes. Our data indicate that phase separation and packing of polymerizable lipids in the liposome bilayer are major determinants of photo-activation and triggered contents release.
C1 [Yavlovich, Amichai; Blumenthal, Robert; Puri, Anu] NCI, Membrane Struct & Funct Sect, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA.
[Singh, Alok] USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA.
[Tarasov, Sergey] NCI, Struct Biophys Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Capala, Jacek] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Puri, A (reprint author), NCI, Membrane Struct & Funct Sect, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA.
EM apuri@helix.nih.gov
FU NIH; National Cancer Institute; Center for Cancer Research; NCI Alliance
for Nanotechnology
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research and NCI
Alliance for Nanotechnology (Piotr Grodzinski). We would like to thank
Dr. Julie M. Belanger for critical reading of the manuscript.
NR 25
TC 39
Z9 39
U1 0
U2 22
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1388-6150
J9 J THERM ANAL CALORIM
JI J. Therm. Anal. Calorim.
PD OCT
PY 2009
VL 98
IS 1
BP 97
EP 104
DI 10.1007/s10973-009-0228-8
PG 8
WC Thermodynamics; Chemistry, Analytical; Chemistry, Physical
SC Thermodynamics; Chemistry
GA 512WI
UT WOS:000271282000013
PM 20160877
ER
PT J
AU Giaccone, G
Rajan, A
Ruijter, R
Smit, E
van Groeningen, C
Hogendoorn, PCW
AF Giaccone, Giuseppe
Rajan, Arun
Ruijter, Rita
Smit, Egbert
van Groeningen, Cees
Hogendoorn, Pancras C. W.
TI Imatinib Mesylate in Patients with WHO B3 Thymomas and Thymic Carcinomas
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Imatinib; KIT; Thymoma
ID GASTROINTESTINAL STROMAL TUMORS; GENE-MUTATIONS; KIT; TRIAL
AB Thymic malignancies are rare tumors of the mediastinum. c-KIT is highly expressed in thymic carcinomas (TC) but infrequently in thymomas. Anecdotal experience suggests activity of imatinib mesylate in TC. Patients with unresectable World Health Organization B3 thymomas or TC, performance status 0 to 2, good organ function, and measurable disease were enrolled in this study. Imatinib was administered at 600 rug PO daily. Seven patients were recruited at one institution: two World Health Organization 133 thymomas and five TC. Imatinib treatment was generally well tolerated. Two patients had stable disease and five progressed. Median survival was 4 months, and median time to progression was 2 months. c-KIT expression was found in one of four samples by immunohistochemistry. No mutations were detected in the c-KIT or PDGFRA genes in three samples analyzed. Imatinib has no major activity in this rare tumor. Given the small number of patients treated in this study, selection based on presence of c-KIT mutations might be warranted.
C1 [Giaccone, Giuseppe; Rajan, Arun] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Giaccone, Giuseppe; Ruijter, Rita; van Groeningen, Cees] Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, Amsterdam, Netherlands.
[Smit, Egbert] Vrije Univ Amsterdam Med Ctr, Dept Pulmonol, Amsterdam, Netherlands.
[Hogendoorn, Pancras C. W.] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017; Hogendoorn, Pancras/H-5859-2015
OI Giaccone, Giuseppe/0000-0002-5023-7562; Hogendoorn,
Pancras/0000-0002-1513-8104
NR 16
TC 42
Z9 45
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1556-0864
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD OCT
PY 2009
VL 4
IS 10
BP 1270
EP 1273
PG 4
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 504FP
UT WOS:000270601600015
PM 20197733
ER
PT J
AU Povsic, TJ
Adams, SD
Zavodni, KL
Kelly, F
Melton, LG
Rao, SV
Najjar, SS
Harrington, RA
Peterson, ED
AF Povsic, Thomas J.
Adams, Stacie D.
Zavodni, Katherine L.
Kelly, Francine
Melton, Laura G.
Rao, Sunil V.
Najjar, Samer S.
Harrington, Robert A.
Peterson, Eric D.
TI Aldehyde dehydrogenase activity allows reliable EPC enumeration in
stored peripheral blood samples
SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS
LA English
DT Article
DE Stem cell; Endothelial progenitor cell; Atherosclerosis; Clinical
trials; Cell surface marker analysis; Aldehyde dehydrogenase
ID ENDOTHELIAL PROGENITOR CELLS; THERAPY; NUMBER; RISK
AB Background Interest in the biology of endogenous progenitor cells (EPCs) continues to grow as evidence of their role in vascular repair mounts. EPC enumeration requires specialized laboratory techniques and is performed immediately after sample acquisition, limiting the clinical contexts in which EPC enumeration can be performed and the ability to increase sample sizes through multi-center participation. Methods We compared the numbers of EPCs enumerated in samples processed immediately after acquisition (n = 36) with EPCs enumerated in specimens stored for 24 hours or after cryopreservation of mononuclear cells (MNC) using two EPC identification strategies: cell surface marker expression (CD133/CD34) and aldehyde dehydrogenase activity (ALDH(br) cells). Results EPCs assessed in fresh samples correlated with EPCs enumerated after whole blood storage (r = 0.699 for CD133(+)CD34(+) cells, r = 0.880 for ALDH(br) cells, P < 0.005 and P < 0.0001, respectively) or mononuclear cryopreservation (r = 0.590 for CD133(+)CD34(+) cells, r = 0.894 for ALDH(br) cells, P < 0.0001 for each); however, correlation based on assessment of ALDH(br) cells was higher (P < 0.0003 for comparison of correlation coefficients). Initial results from a multi-site clinical trial suggest that EPC enumeration after mononuclear cell cryopreservation is feasible. Conclusion EPC analysis based on ALDH activity is reproducible, even after extended whole blood storage or MNC cryopreservation.
C1 [Povsic, Thomas J.; Adams, Stacie D.; Zavodni, Katherine L.; Kelly, Francine] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA.
[Melton, Laura G.; Rao, Sunil V.; Harrington, Robert A.; Peterson, Eric D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA.
[Najjar, Samer S.] NIA, Baltimore, MD 21224 USA.
RP Povsic, TJ (reprint author), Duke Univ, Med Ctr, Div Cardiol, Box 3126, Durham, NC 27710 USA.
EM povsi001@mc.duke.edu
FU National Heart, Lung, and Blood Institute [K-18 HL081419-01A1]; Society
of Geriatric Cardiology Merck Geriatric Cardiology Research Award (TJP);
the Duke Clinical Research Institute (TJP)
FX This study was funded in part by National Heart, Lung, and Blood
Institute grant K-18 HL081419-01A1 (TJP), a Society of Geriatric
Cardiology Merck Geriatric Cardiology Research Award (TJP), and a grant
from the Duke Clinical Research Institute (TJP).
NR 13
TC 9
Z9 9
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0929-5305
J9 J THROMB THROMBOLYS
JI J. Thromb. Thrombolysis
PD OCT
PY 2009
VL 28
IS 3
BP 259
EP 265
DI 10.1007/s11239-009-0306-6
PG 7
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 495AD
UT WOS:000269860600002
PM 19184616
ER
PT J
AU Koenen, KC
Amstadter, AB
Nugent, NR
AF Koenen, Karestan C.
Amstadter, Ananda B.
Nugent, Nicole R.
TI Gene-Environment Interaction in Posttraumatic Stress Disorder: An Update
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article; Proceedings Paper
CT 24th Annual Meeting of the
International-Society-for-Traumatic-Stress-Studies
CY NOV, 2008
CL Chicago, IL
SP Int Soc Traumat Stress Studies
ID SEROTONIN TRANSPORTER GENOTYPE; TRAUMA EXPOSURE; ANXIETY DISORDERS;
RISK-FACTORS; VIETNAM-WAR; ADULTS; POLYMORPHISMS; ASSOCIATION; SYMPTOMS;
TWIN
AB The authors provide a detailed review of the extant gene-environment interaction (GxE) research in the etiology of posttraumatic stress disorder (PTSD). They begin with a discussion of why PTSD is uniquely fitting for the innovative framework of GxE methodology, followed by a review of the heritability and main effect molecular genetics studies of PTSD. Next, they discuss the six GxE investigations to date on PTSD. They end with a discussion of future directions and significance of this research, with an emphasis on the expansion of psychosocial factors that may befitting environmental variables for inclusion in this new research area. The authors posit that GxE research is vital to elucidating risk and resilience following exposure to a potentially traumatic event.
C1 [Koenen, Karestan C.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
[Koenen, Karestan C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Amstadter, Ananda B.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA.
[Amstadter, Ananda B.] Med Univ S Carolina, Dept Behav Sci, Charleston, SC 29425 USA.
[Nugent, Nicole R.] Brown Med Sch, NIMH Inst Res Training Program, Providence, RI USA.
RP Koenen, KC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave,Kresge 613, Boston, MA 02115 USA.
EM kkoenen@hsph.harvard.edu
RI Koenen, Karestan/K-5402-2014
OI Koenen, Karestan/0000-0003-3293-4281
FU NIMH NIH HHS [F32 MH083469, F32 MH083469-01, K01 MH087240, K08 MH070627,
K08 MH070627-06, L40 MH084279, L40 MH084279-01, MH078928, R01 MH078928,
R01 MH078928-02, T32 MH078788]; PHS HHS [083469]
NR 46
TC 56
Z9 58
U1 8
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
EI 1573-6598
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD OCT
PY 2009
VL 22
IS 5
BP 416
EP 426
DI 10.1002/jts.20435
PG 11
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 515SK
UT WOS:000271493000010
PM 19743189
ER
PT J
AU Hamill, N
Romero, R
Hassan, SS
Lee, W
Myers, SA
Mittal, P
Kusanovic, JP
Chaiworapongsa, T
Vaisbuch, E
Espinoza, J
Gotsch, F
Carletti, A
Goncalves, LF
Yeo, L
AF Hamill, Neil
Romero, Roberto
Hassan, Sonia S.
Lee, Wesley
Myers, Stephen A.
Mittal, Pooja
Kusanovic, Juan Pedro
Chaiworapongsa, Tinnakorn
Vaisbuch, Edi
Espinoza, Jimmy
Gotsch, Francesca
Carletti, Angela
Goncalves, Luis F.
Yeo, Lami
TI Repeatability and Reproducibility of Fetal Cardiac Ventricular Volume
Calculations Using Spatiotemporal Image Correlation and Virtual Organ
Computer-Aided Analysis
SO JOURNAL OF ULTRASOUND IN MEDICINE
LA English
DT Article
DE cardiac function; Contour Finder; fetal echocardiography; fetus;
4-dimensional ultrasonography; inversion mode; 3-dimensional
echocardiography; ultrasonography; ventricular volume
ID NORMAL HUMAN-FETUS; 4-DIMENSIONAL ULTRASOUND; BLOOD-FLOW; 3-DIMENSIONAL
ULTRASOUND; INTRAUTERINE GROWTH; GESTATIONAL-AGE; STROKE VOLUME;
ECHOCARDIOGRAPHY; HEART; OUTPUT
AB Objective. The objective of this study was to quantify the repeatability and reproducibility of fetal cardiac ventricular volumes obtained using spatiotemporal image correlation (STIC) and Virtual Organ Computer-Aided Analysis (VOCAL; GE Healthcare, Kretztechnik, Zipf, Austria). Methods. A technique was developed to compute ventricular volumes using the subfeature Contour Finder: Trace. Twenty-five normal pregnancies were evaluated for the following: (1) to compare the coefficient of variation (CV) of ventricular volumes obtained using 15 degrees and 30 degrees rotation; (2) to compare the CV between 3 methods of quantifying ventricular volumes: (a) Manual Trace, (b) Inversion Mode, and (c) Contour Finder: Trace; and (3) to determine repeatability by calculating agreement and reliability of ventricular volumes when each STIC was measured twice by 3 observers. Reproducibility was assessed by obtaining 2 STICs from each of 44 normal pregnancies. For each STIC, 2 ventricular volume calculations were performed, and agreement and reliability were evaluated. Additionally, measurement error was examined. Results. (1) Agreement was better with 151 rotation than 30 degrees (15 degrees: 3.6%; 95% confidence interval [CI], 3.0%-4.2%; versus 30 degrees: 7.1%; 95% Cl, 5.8%-8.6%; P < .001); (2) ventricular volumes obtained with Contour Finder: Trace had better agreement than those obtained using either Inversion Mode (Contour Finder: Trace: 3.6%; 95% Cl, 3.0%-4.2%; versus Inversion Mode: 6.0%; 95% Cl, 4.9%-7.2%; P < .001) or Manual Trace (10.5%; 95% Cl, 8.7%-12.5%; P < .001); (3) ventricular volumes were repeatable with good agreement and excellent reliability for both intraobserver and interobserver measurements; and (4) ventricular volumes were reproducible with negligible differences in agreement and good reliability. In addition, bias between STIC acquisitions was minimal (<1%; mean percent difference, -0.4%; 95% limits of agreement, -5.4%-5.9%). Conclusions. Fetal echocardiography using STIC and VOCAL allows repeatable and reproducible calculation of ventricular volumes with the subfeature Contour Finder: Trace.
C1 [Hamill, Neil; Romero, Roberto; Hassan, Sonia S.; Mittal, Pooja; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Vaisbuch, Edi; Espinoza, Jimmy; Gotsch, Francesca; Goncalves, Luis F.; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA.
[Hamill, Neil; Romero, Roberto; Hassan, Sonia S.; Mittal, Pooja; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Vaisbuch, Edi; Espinoza, Jimmy; Goncalves, Luis F.; Yeo, Lami] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Lee, Wesley] William Beaumont Hosp, Royal Oak, MI 48072 USA.
[Myers, Stephen A.] Case Metrohlth, Cleveland, OH USA.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM nichdprbchiefstaff@mail.nih.gov
OI Vaisbuch, Edi/0000-0002-8400-9031
FU Perinatology Research Branch; Division of Intramural Research; Eunice
Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health; US Department of Health and Human
Services
FX This research was supported in part by the Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development National Institutes of
Health, US Department of Health and Human Services.
NR 42
TC 18
Z9 22
U1 0
U2 3
PU AMER INST ULTRASOUND MEDICINE
PI LAUREL
PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906
USA
SN 0278-4297
J9 J ULTRAS MED
JI J. Ultrasound Med.
PD OCT
PY 2009
VL 28
IS 10
BP 1301
EP 1311
PG 11
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 503KH
UT WOS:000270532500004
PM 19778875
ER
PT J
AU Espinoza, J
Romero, R
Kusanovic, JP
Gotsch, F
Erez, O
Hassan, S
Yeo, L
AF Espinoza, Jimmy
Romero, Roberto
Kusanovic, Juan Pedro
Gotsch, Francesca
Erez, Offer
Hassan, Sonia
Yeo, Lami
TI Prenatal Diagnosis of Coarctation of the Aorta With the Multiplanar
Display and B-Flow Imaging Using 4-Dimensional Sonography
SO JOURNAL OF ULTRASOUND IN MEDICINE
LA English
DT Article
ID FETAL ECHOCARDIOGRAPHY; ULTRASOUND; ULTRASONOGRAPHY; HEART
AB Coarctation of the aorta is characterized by narrowing of the distal aortic arch. This obstructive lesion may reduce the blood flow in the fetal aortic arch, leading to arch hypoplasia, although in some cases this may only be clinically evident after birth. A sonographic finding described in neonates with coarctation of the aorta is the "contraductal shelf," which has been proposed to represent residual fibrous tissue derived from the ductus arteriosus. B-flow is a display modality in 4-dimensional (4D) sonography that enhances signals from weak blood reflectors from vessels, suppresses strong signals from surrounding tissues, and is angle independent. Here, we report a case of coarctation of the aorta diagnosed in utero in which B-flow imaging provided important insight into the location and nature of this aortic arch anomaly.
C1 [Espinoza, Jimmy; Romero, Roberto; Kusanovic, Juan Pedro; Gotsch, Francesca; Erez, Offer; Hassan, Sonia; Yeo, Lami] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA.
[Espinoza, Jimmy; Kusanovic, Juan Pedro; Erez, Offer; Hassan, Sonia; Yeo, Lami] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health, US Department of Health and Human
Services
FX This research was supported by the Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development National Institutes of
Health, US Department of Health and Human Services.
NR 13
TC 7
Z9 9
U1 0
U2 3
PU AMER INST ULTRASOUND MEDICINE
PI LAUREL
PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906
USA
SN 0278-4297
J9 J ULTRAS MED
JI J. Ultrasound Med.
PD OCT
PY 2009
VL 28
IS 10
BP 1375
EP 1378
PG 4
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 503KH
UT WOS:000270532500014
PM 19778885
ER
PT J
AU Lee, W
Comstock, CH
Kazmierczak, C
Wilson, J
Goncalves, LF
Mody, S
Yeo, L
Romero, R
AF Lee, Wesley
Comstock, Christine H.
Kazmierczak, Chris
Wilson, Jon
Goncalves, Luis F.
Mody, Swati
Yeo, Lami
Romero, Roberto
TI Prenatal Diagnostic Challenges and Pitfalls for Schizencephaly
SO JOURNAL OF ULTRASOUND IN MEDICINE
LA English
DT Article
AB Schizencephaly is a developmental anomaly that causes unilateral or bilateral clefts of the cerebral hemisphere as a result of disordered neuronal migration. The clefts are lined by gray matter that can extend medially from the subarachnoid cerebrospinal fluid space into the lateral ventricle as part of a disease spectrum that includes porencephaly, Closed-lip schizencephaly (type 1) occurs when the gray matter-lined walls are in contact with each other.(1) By contrast, the open-lip variety (type 2) has separated lips with a cleft of cerebrospinal fluid that extends to the ventricles.(2) Barkovich and Kjos(3) reported that the clinical manifestations of affected infants were related to the size and location of the cleft defect. Late prenatal schizencephaly has been described. We now report a well-documented case that shows diagnostic challenges and pitfalls associated with its early diagnosis by 2- and 3-dimensional sonography and magnetic resonance imaging (MRI).
C1 [Lee, Wesley; Comstock, Christine H.] Oakland Univ, William Beaumont Sch Med, Div Fetal Imaging, Dept Obstet & Gynecol, Royal Oak, MI USA.
[Kazmierczak, Chris] Oakland Univ, William Beaumont Sch Med, Dept Diagnost Radiol, Royal Oak, MI USA.
[Wilson, Jon] Oakland Univ, William Beaumont Sch Med, Dept Anat Pathol, Royal Oak, MI USA.
[Lee, Wesley; Comstock, Christine H.; Goncalves, Luis F.; Yeo, Lami; Romero, Roberto] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Mody, Swati] Wayne State Univ, Dept Pediat Imaging, Detroit, MI USA.
[Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
[Lee, Wesley; Goncalves, Luis F.; Yeo, Lami; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA.
RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA.
EM wlee@beaumont.edu
RI Wilson, Jon/H-5148-2012
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health, US Department of Health and Human
Services
FX We thank the following individuals for their input regarding the
potential nature of the small echogenic structure that mimicked a
closed-lip schizencephalic cleft defect: James Barkovich, MD, Catherine
Garel, MD, Jeffrey Golden, MD, Ana Monteagudo, MD, and Daniela Prayer
MD. This research was supported in part by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development National Institutes of
Health, US Department of Health and Human Services.
NR 13
TC 5
Z9 5
U1 0
U2 0
PU AMER INST ULTRASOUND MEDICINE
PI LAUREL
PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906
USA
SN 0278-4297
J9 J ULTRAS MED
JI J. Ultrasound Med.
PD OCT
PY 2009
VL 28
IS 10
BP 1379
EP 1384
PG 6
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 503KH
UT WOS:000270532500015
PM 19778886
ER
PT J
AU Boris, R
Proano, M
Linehan, WM
Pinto, PA
Bratslavsky, G
AF Boris, Ronald
Proano, Miguel
Linehan, W. Marston
Pinto, Peter A.
Bratslavsky, Gennady
TI Initial Experience With Robot Assisted Partial Nephrectomy for Multiple
Renal Masses
SO JOURNAL OF UROLOGY
LA English
DT Article
DE kidney; nephrectomy; robotics; kidney neoplasms; genetic diseases
ID LAPAROSCOPIC PARTIAL NEPHRECTOMY; NEPHRON-SPARING SURGERY; CELL
CARCINOMA; WARM ISCHEMIA; TUMORS; OUTCOMES; KIDNEY; CRYOABLATION;
FEASIBILITY; RECURRENCE
AB Purpose: We evaluated the feasibility of performing robot assisted partial nephrectomy in patients with multiple renal masses and examined the results of our initial experiences.
Materials and Methods: We reviewed the records of 10 patients with multiple renal masses who underwent attempted robot assisted partial nephrectomy within the last 2 years. Demographic information, and intraoperative, perioperative and renal function outcome data on these patients were reviewed.
Results: A total of 24 tumors in 9 patients were removed with robot assistance. There was 1 open conversion with successful completion of partial nephrectomy. Of the patients 70% had a known hereditary renal cancer syndrome and the remainder had multifocal disease with unknown germline genetic alterations. Frozen section from the tumor bed evaluated in 5 of 10 cases was negative. One patient experienced urinary leak postoperatively, which resolved by postoperative day 9 without intervention. Of the 24 robotically resected masses 22 were malignant. Our most recent 3 patients underwent successful partial nephrectomy without hilar clamping, obviating the need for warm ischemia. Overall renal function was unchanged at most recent followup with a minimal decrease in operated kidney differential function.
Conclusions: Robot assisted partial nephrectomy for multiple renal masses was feasible in our early experience. Patient selection is paramount for successful minimally invasive surgery. Robot assisted partial nephrectomy without hilar clamping, especially in the hereditary patient population in which repeat ipsilateral partial nephrectomy may be anticipated, appears promising but requires further evaluation.
C1 [Boris, Ronald; Proano, Miguel; Linehan, W. Marston; Pinto, Peter A.; Bratslavsky, Gennady] NCI, Urol Oncol Branch, CRC, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, CRC, NIH,Dept Hlth & Human Serv, 10 Ctr Dr,MSC 1107,Bldg 10,Room 2W-5942, Bethesda, MD 20892 USA.
EM bratslag@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center
FX Supported by the National Institutes of Health, National Cancer
Institute, Center for Cancer Research Intramural Research Program.
NR 22
TC 32
Z9 35
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD OCT
PY 2009
VL 182
IS 4
BP 1280
EP 1286
DI 10.1016/j.juro.2009.06.036
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 493UP
UT WOS:000269764100011
PM 19683275
ER
PT J
AU Loeb, S
Kettermann, A
Carter, HB
Ferrucci, L
Metter, EJ
Walsh, PC
AF Loeb, Stacy
Kettermann, Anna
Carter, H. Ballentine
Ferrucci, Luigi
Metter, E. Jeffrey
Walsh, Patrick C.
TI Prostate Volume Changes Over Time: Results From the Baltimore
Longitudinal Study of Aging
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostatic hyperplasia; prostate; organ size; atrophy; longitudinal
studies
ID HYPERPLASIA; MEN; ANTIGEN; AGE; FINASTERIDE; THERAPY; RISK; MRI
AB Purpose: According to a 1944 publication by Swyer benign prostatic hyperplasia develops in some men after age 45 with further prostatic growth whereas in other men prostate size remains stable or decreases with advancing age. Although there is an abundance of literature describing prostatic enlargement in association with benign prostatic hyperplasia, less is known about the phenomenon of prostate atrophy.
Materials and Methods: In the Baltimore Longitudinal Study of Aging serial pelvic magnetic resonance imaging was performed in men without prostate cancer beginning in 1993. From this population we retrospectively identified 278 men with 2 or more magnetic resonance imaging determined prostate volume measurements to examine differential growth rates in a cohort of community men over time.
Results: Median age was 58 years and median prostate size was 28 cc at study entry. At a median followup of 4.3 years prostate size increased in 61.9% and remained stable or decreased in 38.1% of men. The median rate of volume change was 0.6 cc per year (range -9.9 to 62.1), corresponding to a median growth rate of 2.5% per year (range -29.2 to 176.4%). During followup 64.6% of men with an initial prostate size less than 40 cc had prostate growth compared to only 50.9% of men with an initial prostate size of 40 cc or greater.
Conclusions: These results suggest that changes in prostate size are highly variable among aging men. Although benign prostatic hyperplasia is common, a considerable proportion of aging men have a stable or decreasing prostate size. Further research is needed to identify the underlying mechanism for such differences in prostate growth.
C1 [Loeb, Stacy; Kettermann, Anna; Carter, H. Ballentine; Walsh, Patrick C.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
[Ferrucci, Luigi; Metter, E. Jeffrey] NIA, NIH, Clin Res Branch, Baltimore, MD 21224 USA.
RP Loeb, S (reprint author), Johns Hopkins Brady Urol Inst, 600 N Wolfe St,Marburg 100, Baltimore, MD 21287 USA.
EM stacyloeb@gmail.com
OI Loeb, Stacy/0000-0003-3933-9207
FU Intramural NIH HHS [Z01 AG000015-49]
NR 16
TC 23
Z9 24
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD OCT
PY 2009
VL 182
IS 4
BP 1458
EP 1462
DI 10.1016/j.juro.2009.06.047
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 493UP
UT WOS:000269764100082
PM 19683305
ER
PT J
AU McClenahan, SD
Bok, K
Neill, JD
Smith, AW
Rhodes, CR
Sosnovtsev, SV
Green, KY
Romero, CH
AF McClenahan, Shasta D.
Bok, Karin
Neill, John D.
Smith, Alvin W.
Rhodes, Crystal R.
Sosnovtsev, Stanislav V.
Green, Kim Y.
Romero, Carlos H.
TI A capsid gene-based real-time reverse transcription polymerase chain
reaction assay for the detection of marine vesiviruses in the
Caliciviridae
SO JOURNAL OF VIROLOGICAL METHODS
LA English
DT Article
DE Vesiviruses; Caliciviridae; Marine mammals; Real-time RT-PCR; Diagnosis
ID SEA-LION-VIRUS; VESICULAR EXANTHEMA; GIRELLA-NIGRICANS; SWINE VIRUS;
GASTROENTERITIS; ANTIBODIES; SEQUENCE; SEROTYPE; CATS; FISH
AB A real-time reverse transcription polymerase chain reaction (rtRT-PCR) assay was developed for the identification of marine vesiviruses. The primers were designed to target a 176-nucleotide fragment within a highly conserved region of the San Miguel sea lion viruses (SMSVs) capsid gene. The assay detected viral RNA from nine marine vesivirus serotypes described previously, including two serotypes (SMSV-8 and -12) not identified with presently available molecular assays, a highly related bovine vesivirus strain (Bos-1), a mink vesivirus strain (MCV), and two novel genotypes isolated recently from Steller sea lions (SSL V810 and V1415). The real-time assay did not amplify sequences from the corresponding genomic regions of feline calicivirus (also in the genus Vesivirus) and representative members of the genus Norovirus. The rtRT-PCR assay described below may prove useful as a diagnostic tool for the detection of currently circulating, emerging and previously described marine vesiviruses in clinical samples, especially when large numbers are screened in surveillance studies of these restricted viruses. (C) 2009 Elsevier B.V. All rights reserved.
C1 [McClenahan, Shasta D.; Romero, Carlos H.] Univ Florida, Dept Infect Dis & Pathol, Coll Vet Med, Gainesville, FL 32610 USA.
[Neill, John D.] USDA, Natl Anim Dis Ctr, Ames, IA 50010 USA.
[Smith, Alvin W.] Oregon State Univ, Lab Calicivirus Studies, Corvallis, OR 97331 USA.
[Bok, Karin; Rhodes, Crystal R.; Sosnovtsev, Stanislav V.; Green, Kim Y.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Romero, CH (reprint author), Univ Florida, Dept Infect Dis & Pathol, Coll Vet Med, 2015 SW 16th Ave,Bldg 1017, Gainesville, FL 32610 USA.
EM romeroc@vetmed.ufl.edu
FU Department of Infectious Diseases and Pathology; Marine Mammal Health
Program of the College of Veterinary Medicine, University of Florida;
NIH; NIAID
FX This research was funded by the Department of Infectious Diseases and
Pathology and the Marine Mammal Health Program of the College of
Veterinary Medicine, University of Florida. This research was also
partially supported by the Intramural Research Program of the NIH,
NIAID.
NR 38
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-0934
J9 J VIROL METHODS
JI J. Virol. Methods
PD OCT
PY 2009
VL 161
IS 1
BP 12
EP 18
DI 10.1016/j.jviromet.2009.04.026
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Virology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Virology
GA 484TL
UT WOS:000269070300003
PM 19410604
ER
PT J
AU Asabe, S
Wieland, SF
Chattopadhyay, PK
Roederer, M
Engle, RE
Purcell, RH
Chisari, FV
AF Asabe, Shinichi
Wieland, Stefan F.
Chattopadhyay, Pratip K.
Roederer, Mario
Engle, Ronald E.
Purcell, Robert H.
Chisari, Francis V.
TI The Size of the Viral Inoculum Contributes to the Outcome of Hepatitis B
Virus Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CD8(+) T-CELLS; LYMPHOCYTE RESPONSIVENESS; CD8-T-CELL MEMORY; RNA
REPLICATION; PD-1 EXPRESSION; CD4-T-CELL HELP; HBV INFECTION;
EXHAUSTION; TOLERANCE; IMMUNITY
AB The impact of virus dose on the outcome of infection is poorly understood. In this study we show that, for hepatitis B virus (HBV), the size of the inoculum contributes to the kinetics of viral spread and immunological priming, which then determine the outcome of infection. Adult chimpanzees were infected with a serially diluted monoclonal HBV inoculum. Unexpectedly, despite vastly different viral kinetics, both high-dose inocula (10(10) genome equivalents [GE] per animal) and low-dose inocula (10(0) GE per animal) primed the CD4 T-cell response after logarithmic spread was detectable, allowing infection of 100% of hepatocytes and requiring prolonged immunopathology before clearance occurred. In contrast, intermediate (10(7) and 10(4) GE) inocula primed the T-cell response before detectable logarithmic spread and were abruptly terminated with minimal immunopathology before 0.1% of hepatocytes were infected. Surprisingly, a dosage of 10(1) GE primed the T-cell response after all hepatocytes were infected and caused either prolonged or persistent infection with severe immunopathology. Finally, CD4 T-cell depletion before inoculation of a normally rapidly controlled inoculum precluded T-cell priming and caused persistent infection with minimal immunopathology. These results suggest that the relationship between the kinetics of viral spread and CD4 T-cell priming determines the outcome of HBV infection.
C1 [Asabe, Shinichi; Wieland, Stefan F.; Chisari, Francis V.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Chattopadhyay, Pratip K.; Roederer, Mario] NIAID, Immuno Technol Sect, Immunol Lab, Vaccine Res Ctr,NIH, Bethesda, MD 20892 USA.
[Engle, Ronald E.; Purcell, Robert H.] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Chisari, FV (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, SBR-10,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM fchisari@scripps.edu
RI Chattopadhyay, Pratip/B-9227-2008; Chisari, Francis/A-3086-2008;
OI Chisari, Francis/0000-0002-4832-1044; Chattopadhyay,
Pratip/0000-0002-5457-9666
FU National Institutes of Health (NIH) [AI20001, CA76403, N01-AI-52705,
N01-AI-45180, N01-CO-56000]; Sam and Rose Stein Charitable Trust
FX This study was supported by grants AI20001 and CA76403 and by contracts
N01-AI-52705, N01-AI-45180 and N01-CO-56000 from the National Institutes
of Health (NIH); by the Intramural Research Program of the National
Institute of Allergy and Infectious Disease, NIH; and by the Sam and
Rose Stein Charitable Trust.
NR 34
TC 103
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U1 2
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2009
VL 83
IS 19
BP 9652
EP 9662
DI 10.1128/JVI.00867-09
PG 11
WC Virology
SC Virology
GA 491WX
UT WOS:000269614300004
PM 19625407
ER
PT J
AU Hyde, JL
Sosnovtsev, SV
Green, KY
Wobus, C
Virgin, HW
Mackenzie, JM
AF Hyde, Jennifer L.
Sosnovtsev, Stanislav V.
Green, Kim Y.
Wobus, Christiane
Virgin, Herbert W.
Mackenzie, Jason M.
TI Mouse Norovirus Replication Is Associated with Virus-Induced Vesicle
Clusters Originating from Membranes Derived from the Secretory Pathway
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MOUTH-DISEASE VIRUS; FLAVIVIRUS-INFECTED CELLS; NORWALK-LIKE VIRUSES;
DOUBLE-STRANDED-RNA; ENDOPLASMIC-RETICULUM; BREFELDIN-A;
SUBCELLULAR-DISTRIBUTION; VIRAL REPLICATION; GOLGI MEMBRANES; IN-VITRO
AB Human noroviruses (family Caliciviridae) are the leading cause of nonbacterial gastroenteritis worldwide. Despite the prevalence of these viruses within the community, the study of human norovirus has largely been hindered due to the inability to cultivate the viruses ex vivo and the lack of a small-animal model. In 2003, the discovery of a novel murine norovirus (MNV-1) and the identification of the tropism of MNV-1 for cells of a mononuclear origin led to the establishment of the first norovirus tissue culture system. Like other positive-sense RNA viruses, MNV-1 replication is associated with host membranes, which undergo significant rearrangement during infection. We characterize here the subcellular localization of the MNV-1 open reading frame 1 proteins and viral double-stranded RNA (dsRNA). Over the course of infection, dsRNA and the MNV-1 RNA-dependent RNA polymerase (NS7) were observed to proliferate from punctate foci located in the perinuclear region. All of the MNV-1 open reading frame 1 proteins were observed to colocalize with dsRNA during the course of infection. The MNV-1 replication complex was immunolocalized to virus-induced vesicle clusters formed in the cytoplasm of infected cells. Both dsRNA and MNV-1 NS7 were observed to localize to the limiting membrane of the individual clusters by cryo-immunoelectron microscopy. We show that the MNV-1 replication complex initially associates with membranes derived from the endoplasmic reticulum, trans-Golgi apparatus, and endosomes. In addition, we show that MNV-1 replication is insensitive to the fungal metabolite brefeldin A and consistently does not appear to recruit coatomer protein complex I (COPI) or COPII component proteins during replication. These data provide preliminary insights into key aspects of replication of MNV-1, which will potentially further our understanding of the pathogenesis of noroviruses and aid in the identification of potential targets for drug development.
C1 [Hyde, Jennifer L.; Mackenzie, Jason M.] La Trobe Univ, Dept Microbiol, Melbourne, Vic 3086, Australia.
[Hyde, Jennifer L.] Univ Queensland, Sch Mol & Microbial Sci, Brisbane, Qld 4072, Australia.
[Sosnovtsev, Stanislav V.; Green, Kim Y.] NIAID, Norovirus Gastroenteritis Unit, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Wobus, Christiane] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
[Virgin, Herbert W.] Washington Univ, Sch Med, St Louis, MO 63110 USA.
RP Mackenzie, JM (reprint author), La Trobe Univ, Dept Microbiol, Thomas Cherry Bldg,Kingsbury Dr, Melbourne, Vic 3086, Australia.
EM j.mackenzie@latrobe.edu.au
OI Mackenzie, Jason/0000-0001-6613-8350
FU National Health and Medical Research Council of Australia; National
Institutes of Health [AI054483, AI065982]
FX This research was supported by research grants to J. M. M. from the
National Health and Medical Research Council of Australia and to J. M.
M. and H. W. V. from the National Institutes of Health (grants AI054483
and AI065982). This research was also supported, in part, by the
Intramural Research Program of the NIAID, National Institutes of Health
(K. Y. G. and S. V. S.).
NR 54
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Z9 49
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2009
VL 83
IS 19
BP 9709
EP 9719
DI 10.1128/JVI.00600-09
PG 11
WC Virology
SC Virology
GA 491WX
UT WOS:000269614300009
PM 19587041
ER
PT J
AU Shiu, C
Cunningham, CK
Greenough, T
Muresan, P
Sanchez-Merino, V
Carey, V
Jackson, JB
Ziemniak, C
Fox, L
Belzer, M
Ray, SC
Luzuriaga, K
Persaud, D
AF Shiu, Carlum
Cunningham, Coleen K.
Greenough, Thomas
Muresan, Petronella
Sanchez-Merino, Victor
Carey, Vincent
Jackson, J. Brooks
Ziemniak, Carrie
Fox, Lawrence
Belzer, Marvin
Ray, Stuart C.
Luzuriaga, Katherine
Persaud, Deborah
CA Pediat AIDS Clinical Trials Grp P1
TI Identification of Ongoing Human Immunodeficiency Virus Type 1 (HIV-1)
Replication in Residual Viremia during Recombinant HIV-1 Poxvirus
Immunizations in Patients with Clinically Undetectable Viral Loads on
Durable Suppressive Highly Active Antiretroviral Therapy
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CD4(+) T-CELLS; LOW-LEVEL VIREMIA; DRUG-RESISTANCE;
REVERSE-TRANSCRIPTASE; COMBINATION THERAPY; LYMPHOCYTE RESPONSE;
RANDOMIZED-TRIAL; EVOLUTION; ADULTS; RNA
AB In most human immunodeficiency virus type 1 (HIV-1)-infected individuals who achieve viral loads of <50 copies/ml during highly active antiretroviral therapy (HAART), low levels of plasma virus remain detectable for years by ultrasensitive methods. The relative contributions of ongoing virus replication and virus production from HIV-1 reservoirs to persistent low-level viremia during HAART remain controversial. HIV-1 vaccination of HAART-treated individuals provides a model for examining low-level viremia, as immunizations may facilitate virus replication and sequence evolution. In a phase 1 trial of modified vaccinia virus Ankara/fowlpox virus-based HIV-1 vaccines in 20 HIV-infected young adults receiving HAART, we assessed the prevalence of low-level viremia and sequence evolution, using ultrasensitive viral load (<6.5 copies/ml) and genotyping (five-copy sensitivity) assays. Viral evolution, consisting of new drug resistance mutations and novel amino acid changes within a relevant HLA-restricted allele (e. g., methionine, isoleucine, glutamine, or arginine for leucine at position 205 of RT), was found in 1 and 3 of 20 subjects, respectively. Sequence evolution was significantly correlated with levels of viremia of between 6.5 and <50 copies/ml (P = 0.03) and was more likely to occur within epitopes presented by relevant HLA alleles (P < 0.001). These findings suggest that ongoing virus replication contributes to low-level viremia in patients on HAART and that this ongoing replication is subject to CD8(+) T-cell selective pressures.
C1 [Persaud, Deborah] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA.
[Cunningham, Coleen K.] Duke Univ, Med Ctr, Durham, NC USA.
[Greenough, Thomas; Sanchez-Merino, Victor; Luzuriaga, Katherine] Univ Massachusetts, Worcester, MA 01605 USA.
[Muresan, Petronella; Carey, Vincent] Stat & Data Anal Ctr, Boston, MA USA.
[Fox, Lawrence] NIAID, NIH, Bethesda, MD 20892 USA.
[Belzer, Marvin] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
RP Persaud, D (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat, 200 N Wolfe St,Room 3151, Baltimore, MD 21287 USA.
EM dpers@jhmi.edu
RI Ray, Stuart/B-7527-2008
OI Ray, Stuart/0000-0002-1051-7260
FU National Institute of Allergy and Infectious Diseases (NIAID) [U01
A1068632]; National Center for Research Resources; National Institute of
Child Health and Human Development [N01-HD-3-3345]; Pediatric AIDS
Clinical Trials Group (PACTG); NIAID [R01 A155312, R01 A1062446, RO1
32391]
FX We also acknowledge Linda Lambrecht from the University of
Massachusetts, who performed the IFN-gamma ELISPOT assays; Roxann
Ashworth from the Institute of Genetics, Johns Hopkins School of
Medicine, for her independent analyses of the HIV-1 RT sequence
chromatograms; and Estelle Piwowar-Manning for her contributions to the
ultrasensitive viral load quantitation. We also express great
appreciation to the clinical trial sites and the young adults who
participated in this trial.
NR 49
TC 35
Z9 35
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2009
VL 83
IS 19
BP 9731
EP 9742
DI 10.1128/JVI.00570-09
PG 12
WC Virology
SC Virology
GA 491WX
UT WOS:000269614300011
PM 19605490
ER
PT J
AU Uchida, N
Washington, KN
Hayakawa, J
Hsieh, MM
Bonifacino, AC
Krouse, AE
Metzger, ME
Donahue, RE
Tisdale, JF
AF Uchida, Naoya
Washington, Kareem N.
Hayakawa, Jun
Hsieh, Matthew M.
Bonifacino, Aylin C.
Krouse, Allen E.
Metzger, Mark E.
Donahue, Robert E.
Tisdale, John F.
TI Development of a Human Immunodeficiency Virus Type 1-Based Lentiviral
Vector That Allows Efficient Transduction of both Human and Rhesus Blood
Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESTRICTS HIV-1 INFECTION; HEMATOPOIETIC STEM-CELLS; GENE-THERAPY;
PERIPHERAL-BLOOD; CD34(+) CELLS; NONHUMAN-PRIMATES; SIMIAN CELLS;
BONE-MARROW; BETA-GLOBIN; IN-VIVO
AB Human immunodeficiency virus type 1 (HIV-1) vectors transduce rhesus blood cells poorly due to a species-specific block by TRIM5 alpha and APOBEC3G, which target HIV-1 capsid and viral infectivity factor (Vif), respectively. We sought to develop a lentiviral vector capable of transducing both human and rhesus blood cells by combining components of both HIV-1 and simian immunodeficiency virus (SIV), including SIV capsid (sCA) and SIV Vif. A chimeric HIV-1 vector including sCA (chi HIV) was superior to the conventional SIV in transducing a human blood cell line and superior to the conventional HIV-1 vector in transducing a rhesus blood cell line. Among human CD34(+) hematopoietic stem cells (HSCs), the chi HIV and HIV-1 vectors showed similar transduction efficiencies; in rhesus CD34(+) HSCs, the chi HIV vector yielded superior transduction rates. In in vivo competitive repopulation experiments with two rhesus macaques, the chi HIV vector demonstrated superior marking levels over the conventional HIV-1 vector in all blood lineages (first rhesus, 15 to 30% versus 1 to 5%; second rhesus, 7 to 15% versus 0.5 to 2%, respectively) 3 to 7 months postinfusion. In summary, we have developed an HIV-1-based lentiviral vector system that should allow comprehensive preclinical testing of HIV-1-based therapeutic vectors in the rhesus macaque model with eventual clinical application.
C1 [Uchida, Naoya; Washington, Kareem N.; Hayakawa, Jun; Hsieh, Matthew M.; Tisdale, John F.] NHLBI, Mol & Clin Hematol Branch, NIDDK, NIH, Bethesda, MD 20892 USA.
[Uchida, Naoya] Nippon Med Sch, Div Hematol, Dept Internal Med, Tokyo 113, Japan.
[Bonifacino, Aylin C.; Krouse, Allen E.; Metzger, Mark E.; Donahue, Robert E.] NHLBI, Hematol Branch, NIH, Rockville, MD USA.
RP Tisdale, JF (reprint author), NHLBI, Mol & Clin Hematol Branch, NIDDK, NIH, 9000 Rockville Pike,Bldg 10 9N116, Bethesda, MD 20892 USA.
EM johntis@nhlbi.nih.gov
FU National Institute of Diabetes, Digestive, and Kidney Diseases; National
Heart, Lung, and Blood Institute of the National Institutes of Health
FX We thank Keyvan Keyvanfar and Martha Kirby for their assistance in flow
cytometric analyses and the staff at 5 Research Court for their
excellent care and handling of the rhesus macaques.
NR 41
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U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2009
VL 83
IS 19
BP 9854
EP 9862
DI 10.1128/JVI.00357-09
PG 9
WC Virology
SC Virology
GA 491WX
UT WOS:000269614300021
PM 19625395
ER
PT J
AU Quinn, K
Brindley, MA
Weller, ML
Kaludov, N
Kondratowicz, A
Hunt, CL
Sinn, PL
McCray, PB
Stein, CS
Davidson, BL
Flick, R
Mandell, R
Staplin, W
Maury, W
Chiorini, JA
AF Quinn, Kathrina
Brindley, Melinda A.
Weller, Melodie L.
Kaludov, Nikola
Kondratowicz, Andrew
Hunt, Catherine L.
Sinn, Patrick L.
McCray, Paul B., Jr.
Stein, Colleen S.
Davidson, Beverly L.
Flick, Ramon
Mandell, Robert
Staplin, William
Maury, Wendy
Chiorini, John A.
TI Rho GTPases Modulate Entry of Ebola Virus and Vesicular Stomatitis Virus
Pseudotyped Vectors
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID DIFFICILE TOXIN-B; FOLATE RECEPTOR-ALPHA; ENVELOPE GLYCOPROTEINS;
CELLULAR ENTRY; HOST-CELLS; PROTEINS; ENDOCYTOSIS; INHIBITION; BINDING;
INFECTION
AB To explore mechanisms of entry for Ebola virus (EBOV) glycoprotein (GP) pseudotyped virions, we used comparative gene analysis to identify genes whose expression correlated with viral transduction. Candidate genes were identified by using EBOV GP pseudotyped virions to transduce human tumor cell lines that had previously been characterized by cDNA microarray. Transduction profiles for each of these cell lines were generated, and a significant positive correlation was observed between RhoC expression and permissivity for EBOV vector transduction. This correlation was not specific for EBOV vector alone as RhoC also correlated highly with transduction of vesicular stomatitis virus GP (VSVG) pseudotyped vector. Levels of RhoC protein in EBOV and VSV permissive and nonpermissive cells were consistent with the cDNA gene array findings. Additionally, vector transduction was elevated in cells that expressed high levels of endogenous RhoC but not RhoA. RhoB and RhoC overexpression significantly increased EBOV GP and VSVG pseudotyped vector transduction but had minimal effect on human immunodeficiency virus (HIV) GP pseudotyped HIV or adeno-associated virus 2 vector entry, indicating that not all virus uptake was enhanced by expression of these molecules. RhoB and RhoC overexpression also significantly enhanced VSV infection. Similarly, overexpression of RhoC led to a significant increase in fusion of EBOV virus-like particles. Finally, ectopic expression of RhoC resulted in increased nonspecific endocytosis of fluorescent dextran and in formation of increased actin stress fibers compared to RhoA-transfected cells, suggesting that RhoC is enhancing macropinocytosis. In total, our studies implicate RhoB and RhoC in enhanced productive entry of some pseudovirions and suggest the involvement of actin-mediated macropinocytosis as a mechanism of uptake of EBOV GP and VSVG pseudotyped viral particles.
C1 [Quinn, Kathrina; Weller, Melodie L.; Kaludov, Nikola; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Brindley, Melinda A.; Kondratowicz, Andrew; Hunt, Catherine L.; McCray, Paul B., Jr.; Maury, Wendy] Univ Iowa, Dept Microbiol, Carver Coll Med, Iowa City, IA 52242 USA.
[Sinn, Patrick L.; McCray, Paul B., Jr.] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA.
[Stein, Colleen S.; Davidson, Beverly L.] Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA.
[Davidson, Beverly L.] Univ Iowa, Coll Med, Dept Neurol, Iowa City, IA 52242 USA.
[Davidson, Beverly L.] Univ Iowa, Coll Med, Dept Physiol & Biophys, Iowa City, IA 52242 USA.
[Flick, Ramon; Mandell, Robert; Staplin, William] BioProtect Syst, Ames, IA 50011 USA.
RP Chiorini, JA (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1421, Bethesda, MD 20892 USA.
EM Jchiorini@dir.nidcr.nih.gov
FU NIAID [064526]
FX This work was supported by an Intramural NIAID biofense grant to J. A.
Chiorini and an NIAID grant (064526) to Wendy Maury.
NR 49
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Z9 38
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD OCT
PY 2009
VL 83
IS 19
BP 10176
EP 10186
DI 10.1128/JVI.00422-09
PG 11
WC Virology
SC Virology
GA 491WX
UT WOS:000269614300049
PM 19625394
ER
PT J
AU Pinn, VW
AF Pinn, Vivian W.
TI Sixth Annual Interdisciplinary Women's Health Research Symposium
November 17, 2009 Introduction
SO JOURNAL OF WOMENS HEALTH
LA English
DT Editorial Material
C1 NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA.
RP Pinn, VW (reprint author), NIH, Off Res Womens Hlth, 6707 Democracy Blvd,Suite 400, Bethesda, MD 20892 USA.
EM ORWH-Research@od.nih.gov
NR 0
TC 2
Z9 2
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD OCT
PY 2009
VL 18
IS 10
BP 1487
EP 1488
DI 10.1089/jwh.2009.Ab04
PG 2
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 512FJ
UT WOS:000271231200001
PM 19857090
ER
PT J
AU Shardell, MD
Alley, DE
El-Kamary, SS
Hicks, GE
Miller, RR
Magaziner, J
Langenberg, P
Hochberg, MC
Ferrucci, L
AF Shardell, Michelle D.
Alley, Dawn E.
El-Kamary, Samer S.
Hicks, Gregory E.
Miller, Ram R.
Magaziner, Jay
Langenberg, Patricia
Hochberg, Marc C.
Ferrucci, Luigi
TI Sex Differences in the Relationship of Serum Carotenoid Levels with
Mortality Risk among Older US Adults: The Third National Health and
Nutrition Examination Survey (NHANES III)
SO JOURNAL OF WOMENS HEALTH
LA English
DT Meeting Abstract
C1 [Shardell, Michelle D.; Alley, Dawn E.; El-Kamary, Samer S.; Miller, Ram R.; Magaziner, Jay; Langenberg, Patricia] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Hicks, Gregory E.; Hochberg, Marc C.] Univ Delaware, Dept Phys Therapy, Newark, DE 19716 USA.
[Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
EI 1931-843X
J9 J WOMENS HEALTH
JI J. Womens Health
PD OCT
PY 2009
VL 18
IS 10
BP 1492
EP 1492
PG 1
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 512FJ
UT WOS:000271231200012
ER
PT J
AU Hessol, NA
Weber, KM
Holman, S
Robison, E
Goparaju, L
Alden, CB
Kono, N
Watts, DH
Ameli, N
AF Hessol, Nancy A.
Weber, Kathleen M.
Holman, Susan
Robison, Esther
Goparaju, Lakshmi
Alden, Christine B.
Kono, Naoko
Watts, D. Heather
Ameli, Niloufar
TI Retention and Attendance of Women Enrolled in a Large Prospective Study
of HIV-1 in the United States
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID AFRICAN-AMERICAN WOMEN; CLINICAL-TRIALS; INTERAGENCY HIV; COHORT;
PARTICIPATION; INFECTION
AB Objective: The objective was to assess study retention and attendance for two recruitment waves of participants in the Women's Interagency HIV Study (WIHS).
Methods: The WIHS, a prospective study at six clinical centers in the United States, has experienced two phases of participant recruitment. In phase one, women were screened and enrolled at the same time, and in phase two, women were screened and enrolled at separate visits. Compliance with study follow-up was evaluated by examining semiannual study retention and visit attendance.
Results: After 10 study visits, the retention rate in the original recruits (enrolled in 1994-1995) was 83% for the HIV-infected women and 69% for the HIV-uninfected women compared with 86% and 86%, respectively, in the new recruits (enrolled in 2001-2002). In logistic regression analysis of the HIV-infected women, factors associated with early (visits 2 and 3) nonattendance were temporary housing, moderate alcohol consumption, use of crack/cocaine/heroin, having a primary care provider, WIHS site of enrollment, lower CD4 cell count, and higher viral load. Among HIV-uninfected women, the factors associated with early nonattendance were recruitment into the original cohort, household income >=$12,000 per year, temporary housing, unemployment, use of crack/cocaine/heroin, and WIHS site of enrollment. Factors associated with nonattendance at later visits (7-10) among HIV-infected participants were younger age, white race, not having a primary care provider, not having health insurance, WIHS site of enrollment, higher viral load, and nonattendance at a previous visit. In HIV-uninfected participants, younger age, white race, WIHS site of enrollment, and nonattendance at a previous visit were significantly associated with nonattendance at later visits.
Conclusions: Preventing early loss to follow-up resulted in better study retention early, but late loss to follow-up may require different retention strategies.
C1 [Hessol, Nancy A.; Ameli, Niloufar] Univ Calif San Francisco, San Francisco, CA 94122 USA.
[Weber, Kathleen M.] John H Stroger Jr Hosp Cook Cty, Core Ctr, Chicago, IL USA.
[Holman, Susan] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Robison, Esther] Montefiore Med Ctr, Bronx, NY 10467 USA.
[Goparaju, Lakshmi] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Alden, Christine B.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Kono, Naoko] Univ So Calif, Med Ctr, Los Angeles, CA USA.
[Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Hessol, NA (reprint author), Univ Calif San Francisco, 405 Irving St,2nd Floor, San Francisco, CA 94122 USA.
EM Nancy.Hessol@ucsf.edu
FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004,
UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590];
National Institute of Child Health and Human Development [UO1-HD-32632];
National Cancer Institute; National Institute on Drug Abuse; National
Institute on Deafness and Other Communication Disorders; National Center
for Research Resources [UL1 RR024131]
FX We are also grateful to Dr. Peter Bacchetti for his statistical guidance
of the analyses, and we thank Michael Schneider for assistance in
preparing the data and for programming and Heneliaka Jones for help with
manuscript preparation.
NR 20
TC 22
Z9 22
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD OCT
PY 2009
VL 18
IS 10
BP 1627
EP 1637
DI 10.1089/jwh.2008.1337
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 512FJ
UT WOS:000271231200103
PM 19788344
ER
PT J
AU Fried, LP
Xue, QL
Cappola, AR
Ferrucci, L
Chaves, P
Varadhan, R
Guralnik, JM
Leng, SX
Semba, RD
Walston, JD
Blaum, CS
Bandeen-Roche, K
AF Fried, Linda P.
Xue, Qian-Li
Cappola, Anne R.
Ferrucci, Luigi
Chaves, Paulo
Varadhan, Ravi
Guralnik, Jack M.
Leng, Sean X.
Semba, Richard D.
Walston, Jeremy D.
Blaum, Caroline S.
Bandeen-Roche, Karen
TI Nonlinear Multisystem Physiological Dysregulation Associated With
Frailty in Older Women: Implications for Etiology and Treatment
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Frailty etiology; Aging
ID GROWTH-FACTOR-I; CARDIOVASCULAR HEALTH; MUSCLE STRENGTH; SERUM-LEVELS;
IGF-I; INTERLEUKIN-6; COMPLEXITY; MORTALITY; COMMUNITY; SYSTEMS
AB Frailty in older adults, defined as a constellation of signs and symptoms, is associated with abnormal levels in individual physiological systems. We tested the hypothesis that it is the critical mass of physiological systems abnormal that is associated with frailty, over and above the status of each individual system, and that the relationship is nonlinear.
Using data on women aged 70-79 years from the Women's Health and Aging Studies I and II, multiple analytic approaches assessed the cross-sectional association of frailty with eight physiological measures.
Abnormality in each system (anemia, inflammation, insulin-like growth factor-1, dehydroepiandrosterone-sulfate, hemoglobin A1c, micronutrients, adiposity, and fine motor speed) was significantly associated with frailty status. However, adjusting for the level of each system measure, the mean number of systems impaired significantly and nonlinearly predicted frailty. Those with three or more systems impaired were most likely to be frail, with odds of frailty increasing with number of systems at abnormal level, from odds ratios (ORs) of 4.8 to 11 to 26 for those with one to two, three to four, and five or more systems abnormal (p < .05 for all). Finally, two subgroups were identified, one with isolated or no systems abnormal and a second (in 30%) with multiple systems abnormal. The latter group was independently associated with being frail (OR = 2.6, p < .05), adjusting for confounders and chronic diseases and then controlling for individual systems.
Overall, these findings indicate that the likelihood of frailty increases nonlinearly in relationship to the number of physiological systems abnormal, and the number of abnormal systems is more predictive than the individual abnormal system. These findings support theories that aggregate loss of complexity, with aging, in physiological systems is an important cause of frailty. Implications are that a threshold loss of complexity, as indicated by number of systems abnormal, may undermine homeostatic adaptive capacity, leading to the development of frailty and its associated risk for subsequent adverse outcomes. It further suggests that replacement of any one deficient system may not be sufficient to prevent or ameliorate frailty.
C1 [Fried, Linda P.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Xue, Qian-Li; Chaves, Paulo; Varadhan, Ravi; Leng, Sean X.; Semba, Richard D.; Walston, Jeremy D.; Bandeen-Roche, Karen] Johns Hopkins Univ, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD USA.
[Xue, Qian-Li; Chaves, Paulo; Varadhan, Ravi; Walston, Jeremy D.; Bandeen-Roche, Karen] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA.
[Xue, Qian-Li; Varadhan, Ravi] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Cappola, Anne R.] Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
[Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Blaum, Caroline S.] Univ Michigan, Dept Internal Med, Div Geriatr Med, Ann Arbor, MI 48109 USA.
[Blaum, Caroline S.] Vet Adm Hlth Ctr, Educ & Clin Ctr, Ann Arbor, MI USA.
RP Fried, LP (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St,14th Floor, New York, NY 10032 USA.
EM lpfried@columbia.edu
FU National Institute on Aging (NIA); Older Americans Independence Center
[P30 AG021334]; National Institutes of Health/NIA [R37 AG019905]
FX This research was supported by the National Institute on Aging (NIA),
Older Americans Independence Center, grant P30 AG021334 and National
Institutes of Health/NIA grant R37 AG019905.
NR 41
TC 136
Z9 137
U1 3
U2 14
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 OCT
PY 2009
VL 64
IS 10
BP 1049
EP 1057
DI 10.1093/gerona/glp076
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 491VV
UT WOS:000269610600005
PM 19567825
ER
PT J
AU Kutner, NG
Muntner, P
Huang, YJ
Zhang, R
Cohen, AJ
Anderson, AH
Eggers, PW
AF Kutner, Nancy G.
Muntner, Paul
Huang, Yijian
Zhang, Rebecca
Cohen, Andrew J.
Anderson, Amanda H.
Eggers, Paul W.
TI Effect of Hurricane Katrina on the mortality of dialysis patients
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE dialysis; disaster; mortality; USRDS
ID RELIEF TASK-FORCE; HEMODIALYSIS-PATIENTS; STRESS-DISORDER; HEALTH-CARE;
DISASTER; EARTHQUAKE; ORGANIZATION; LESSONS; MARMARA
AB To investigate whether Hurricane Katrina's landfall in August 2005 resulted in excess mortality, we conducted a cohort study of patients who started dialysis between January 2003 and late August 2005 and who received treatment at 94 Katrina-affected clinics in the area. Survival, regardless of patient location after the storm, was followed through February 2006. In adjusted Cox proportional hazards models, Hurricane Katrina (time-varying indicator) was not significantly associated with mortality risk for patients from regions of the Gulf Coast affected by Katrina or those from a subset of 40 New Orleans clinics. Subgroup analyses indicated no significant increased mortality risk by race, income status, or dialysis modality. Sensitivity analyses indicated no significant increased mortality risk for patients from clinics closed for 10 days or longer, patients in their first 90 days of dialysis, or patients not evacuated from the affected areas. Patients remaining in the New Orleans area may have been more vulnerable due to age and comorbidities; however, the change in their mortality risk in the month following the storm was not statistically significant. We suggest that disaster-related education for patients must be ongoing, and that each disaster may present a different set of circumstances and challenges that will require unanticipated response efforts. Kidney International ( 2009) 76, 760-766; doi: 10.1038/ki.2009.268; published online 5 August 2009
C1 [Kutner, Nancy G.] Emory Univ, Sch Med, Dept Rehabil Med, US Renal Data Syst Rehab Qual Life Special Studie, Atlanta, GA 30322 USA.
[Muntner, Paul] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA.
[Cohen, Andrew J.] Brown Univ, Warren Alpert Med Sch, Providence VA Med Ctr, Providence, RI 02912 USA.
[Anderson, Amanda H.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Eggers, Paul W.] NIDDK, NIH, Bethesda, MD USA.
RP Kutner, NG (reprint author), Emory Univ, Sch Med, Dept Rehabil Med, US Renal Data Syst Rehab Qual Life Special Studie, CRM-1441 Clifton Rd NE, Atlanta, GA 30322 USA.
EM nkutner@emory.edu
FU National Institutes of Health [HHSN267200715004C]
FX This study was supported by the National Institutes of Health contract
HHSN267200715004C, ADB no. N01-DK-7-5004. The interpretation and
reporting of the data presented here are the responsibility of the
authors and in no way should be seen as an official policy or
interpretation of the US government. The authors acknowledge the many
helpful insights and recommendations received from manuscript reviewers
and editors. A preliminary report based on a more limited data set
available before 2008 was presented at the American Society of
Nephrology, 4 November 2007, San Francisco, CA, USA.
NR 23
TC 17
Z9 17
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD OCT
PY 2009
VL 76
IS 7
BP 760
EP 766
DI 10.1038/ki.2009.268
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 494NC
UT WOS:000269819100011
PM 19657326
ER
PT J
AU Fishbein, D
Sheppard, M
Hyde, C
Hubal, R
Newlin, D
Serin, R
Chrousos, G
Alesci, S
AF Fishbein, Diana
Sheppard, Monica
Hyde, Christopher
Hubal, Robert
Newlin, David
Serin, Ralph
Chrousos, George
Alesci, Salvatore
TI Deficits in Behavioral Inhibition Predict Treatment Engagement in Prison
Inmates
SO LAW AND HUMAN BEHAVIOR
LA English
DT Review
DE Correctional treatment; Inmates; Neurocognition; Emotional regulation;
Responsivity
ID ANTERIOR CINGULATE CORTEX; SUBSTANCE USE DISORDERS; ABSTINENT
DRUG-ABUSERS; EARLY TRAUMA INVENTORY; AGGRESSIVE-BEHAVIOR; SALIVARY
CORTISOL; PREVENTIVE INTERVENTION; PSYCHOMETRIC PROPERTIES; PROACTIVE
AGGRESSION; PERSONALITY-DISORDER
AB Many inmates do not respond favorably to standard treatments routinely offered in prison. Executive cognitive functioning and emotional regulation may play a key role in treatment responsivity. During intake into treatment, inmates (N = 224) were evaluated for executive functioning, emotional perception, stress reactivity (salivary cortisol), IQ, psychological and behavioral traits, prior drug use, child and family background, and criminal histories and institutional behavior. Outcome measures included program completion, treatment readiness, responsivity and gain, and the Novaco Reaction to Provocation Questionnaire. Relative deficits in behavioral inhibition significantly predicted treatment outcomes, more so than background, psychological, or behavioral variables, and other neurocognitive and emotional regulatory measures. Future replications of these results have potential to improve assessment and treatment of offenders who are otherwise intractable.
C1 [Fishbein, Diana; Sheppard, Monica; Hubal, Robert; Newlin, David] RTI Int, Baltimore, MD 21224 USA.
[Hyde, Christopher] Bioassessments Inc, Elkton, MD 21921 USA.
[Serin, Ralph] Carleton Univ, Ottawa, ON K1S 5B6, Canada.
[Chrousos, George] Natl Inst Child Hlth & Dev, NIH, Bethesda, MD 20892 USA.
[Alesci, Salvatore] NIMH, Bethesda, MD 20892 USA.
RP Fishbein, D (reprint author), RTI Int, 6801 Eastern Ave,Suite 203, Baltimore, MD 21224 USA.
EM dfishbein@rti.org
NR 120
TC 17
Z9 17
U1 6
U2 9
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0147-7307
J9 LAW HUMAN BEHAV
JI Law Hum. Behav.
PD OCT
PY 2009
VL 33
IS 5
BP 419
EP 435
DI 10.1007/s10979-008-9163-7
PG 17
WC Law; Psychology, Social
SC Government & Law; Psychology
GA 503OT
UT WOS:000270547700006
PM 19139980
ER
PT J
AU Landgren, O
Weiss, BM
AF Landgren, O.
Weiss, B. M.
TI Patterns of monoclonal gammopathy of undetermined significance and
multiple myeloma in various ethnic/racial groups: support for genetic
factors in pathogenesis
SO LEUKEMIA
LA English
DT Review
DE MGUS; susceptibility; racial disparity; genetic; African American;
immune related
ID UNITED-STATES; AFRICAN-AMERICAN; FAMILIAL MYELOMA; INTERGROUPE
FRANCOPHONE; SIGNIFICANCE MGUS; ADULT-POPULATION; PREVALENCE; CANCER;
RISK; HISTORY
AB Monoclonal gammopathy of undetermined significance (MGUS) is one of the most common premalignant disorders in Western countries. Recent studies show that almost every multiple myeloma (MM) case is preceded by an MGUS stage. Interestingly, prevalence and incidence patterns for MGUS and MM show striking disparity patterns across ethnic/racial groups, most notably the two-to threefold increase in both these disorders in African Americans compared with Caucasians. In contrast, studies on Asian patients show lower prevalence/incidence for MGUS/MM compared with Caucasians. Familial aggregation for both MGUS and MM has been observed; the risk for MGUS or MM in family members with these disorders is increased about two-to three fold compared with the general population. Although underlying mechanisms remain unclear, there is evidence of heterogeneity among MGUS patients from different ethnic/racial groups. For example, compared with Caucasians, African- American and African MGUS patients have reportedly lower rates of immunoglobulin M (IgM) MGUS (versus IgG/IgA MGUS) and higher rates of unquantifiable immunoglobulins (Igs). This review focuses on racial disparity and familial aggregation patterns for MGUS and MM and discusses how these observations provide novel clues with regard to pathogenesis. Leukemia (2009) 23, 1691-1697; doi: 10.1038/leu. 2009.134; published online 9 July 2009
C1 [Landgren, O.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Weiss, B. M.] Walter Reed Army Med Ctr, Dept Med, Hematol Oncol Serv, Washington, DC 20307 USA.
RP Landgren, O (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,Room 13N240, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
FU National Cancer Institute (NCI); National Institutes of Health (NIH),
Bethesda, Maryland
FX This research was supported by the Intramural Research Program of the
National Cancer Institute (NCI), National Institutes of Health (NIH),
Bethesda, Maryland. The study sponsors did not have any role in the
design of the study, interpretation of the data, the writing of the
paper or the decision to submit the paper for publication. We thank Dr
William F Anderson, NCI/NIH for help in creating Figure 1.
NR 61
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U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD OCT
PY 2009
VL 23
IS 10
BP 1691
EP 1697
DI 10.1038/leu.2009.134
PG 7
WC Oncology; Hematology
SC Oncology; Hematology
GA 506YX
UT WOS:000270816300002
PM 19587704
ER
PT J
AU O'Riain, C
O'Shea, DM
Yang, Y
Le Dieu, R
Gribben, JG
Summers, K
Yeboah-Afari, J
Bhaw-Rosun, L
Fleischmann, C
Mein, CA
Crook, T
Smith, P
Kelly, G
Rosenwald, A
Ott, G
Campo, E
Rimsza, LM
Smeland, EB
Chan, WC
Johnson, N
Gascoyne, RD
Reimer, S
Braziel, RM
Wright, GW
Staudt, LM
Lister, TA
Fitzgibbon, J
AF O'Riain, C.
O'Shea, D. M.
Yang, Y.
Le Dieu, R.
Gribben, J. G.
Summers, K.
Yeboah-Afari, J.
Bhaw-Rosun, L.
Fleischmann, C.
Mein, C. A.
Crook, T.
Smith, P.
Kelly, G.
Rosenwald, A.
Ott, G.
Campo, E.
Rimsza, L. M.
Smeland, E. B.
Chan, W. C.
Johnson, N.
Gascoyne, R. D.
Reimer, S.
Braziel, R. M.
Wright, G. W.
Staudt, L. M.
Lister, T. A.
Fitzgibbon, J.
TI Array-based DNA methylation profiling in follicular lymphoma
SO LEUKEMIA
LA English
DT Article
DE methylation; follicular lymphoma; gene expression; polycomb;
transformation
ID B-CELL LYMPHOMA; NON-HODGKINS LYMPHOMAS; EMBRYONIC STEM-CELLS;
COLORECTAL-CANCER; PROMOTER HYPERMETHYLATION; INSTRUCTIVE MECHANISM;
UNIPARENTAL DISOMY; GENE-EXPRESSION; TRANSFORMATION; POLYCOMB
AB Quantitative methylation profiling was performed using the Illumina GoldenGate Assay in untreated follicular lymphoma (FL) (164), paired pre- and post-transformation FL (20), benign haematopoietic (24) samples and purified B and T cells from two FL cases. Methylation values allowed separation of untreated FL samples from controls with one exception, based primarily on tumour-specific gains of methylation typically occurring within CpG islands. Genes that are targets for epigenetic repression in stem cells by Polycomb Repressor Complex 2 were significantly over-represented among hypermethylated genes. Methylation profiles were conserved in sequential FL and t-FL biopsies, suggesting that widespread methylation represents an early event in lymphomagenesis and may not contribute substantially to transformation. A significant (P<0.05) correlation between FL methylation values and reduced gene expression was shown for up to 28% of loci. Methylation changes occurred predominantly in B cells with variability in the amount of non-malignant tissue between samples preventing conclusive correlation with survival. This represents an important caveat in attributing prognostic relevance to methylation and future studies in cancer will optimally require purified tumour populations to address the impact of methylation on clinical outcome. Leukemia (2009) 23, 1858-1866; doi: 10.1038/leu.2009.114; published online 9 July 2009
C1 [O'Riain, C.; O'Shea, D. M.; Yang, Y.; Le Dieu, R.; Gribben, J. G.; Summers, K.; Lister, T. A.; Fitzgibbon, J.] Barts & London Queen Marys Sch Med & Dent, Ctr Med Oncol, Inst Canc, London EC1M 6BQ, England.
[Yeboah-Afari, J.; Bhaw-Rosun, L.; Fleischmann, C.; Mein, C. A.] Barts & London Queen Marys Sch Med & Dent, Genome Ctr, London, England.
[Crook, T.; Smith, P.] Inst Canc Res, London SW3 6JB, England.
[Kelly, G.] Lincolns Inn Fields, Macrophage Lab, Lincolns Inn Fields, Canc Res UK, London WC2A 3PX, England.
[Rosenwald, A.; Ott, G.] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany.
[Ott, G.] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany.
[Campo, E.] Univ Barcelona, Dept Pathol, Hosp Clin, Barcelona, Spain.
[Rimsza, L. M.] Univ Arizona, Ctr Canc, Dept Pathol, Tucson, AZ USA.
[Smeland, E. B.] Univ Hosp, Rikshosp, Inst Canc Res, Dept Immunol, Oslo, Norway.
[Smeland, E. B.] Univ Oslo, Norwegian Radium Hosp, Ctr Canc Biomed, Fac Div, Oslo, Norway.
[Chan, W. C.] Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE USA.
[Johnson, N.; Gascoyne, R. D.] British Columbia Canc Res Ctr, Dept Pathol, Vancouver, BC V5Z 1L3, Canada.
[Reimer, S.; Braziel, R. M.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA.
[Wright, G. W.; Staudt, L. M.] NCI, Metab Branch, Bethesda, MD 20892 USA.
RP O'Riain, C (reprint author), Barts & London Queen Marys Sch Med & Dent, Ctr Med Oncol, Inst Canc, 3rd Floor,John Vane Sci Bldg,Charterhouse Sq, London EC1M 6BQ, England.
EM c.l.oriain@qmul.ac.uk
OI Campo, elias/0000-0001-9850-9793
FU Cancer Research UK [MONG1E9R]; Medical Research Council Clinical
Research Fellowships; Cancer Research UK; NHS [ONAG1G5R]; National
Institute of Health Strategic Partnering for Evaluation of Cancer
Signatures Program (SPECS) [5 U01 CA114778]
FX We are grateful for the assistance of Sameena Iqbal, Andrew Davies
(Institute of Cancer, London) and Susan Oliver (Oregon Health and
Sciences University), for the critical review of manuscript by Emanuela
Carlotti and Carolyn Owen (Institute of Cancer, London) and for helpful
discussion with Attilla Lorincz (Wolfson Institute, London), Gerd
Pfeifer (City of Hope, California) and Allen Yang (University of
Southern California). We also thank Christy Waterfall and Mark Gibbs at
Illumina UK and Illumina Technical Support staff for their assistance.
CO is a Barts Cambridge Molecular Pathology Clinical Research Fellow
funded by grant support from Cancer Research UK (MONG1E9R). DO and RL
are in receipt of Medical Research Council Clinical Research
Fellowships. This work was also supported by funding from Cancer
Research UK (programme grant to Centre for Medical London NHS Trust
(ONAG1G5R) and by a National Institute of Health Strategic Partnering
for Evaluation of Cancer Signatures Program (SPECS) grant (5 U01
CA114778).
NR 48
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U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD OCT
PY 2009
VL 23
IS 10
BP 1858
EP 1866
DI 10.1038/leu.2009.114
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA 506YX
UT WOS:000270816300019
PM 19587707
ER
PT J
AU Gasperini, P
Tosato, G
AF Gasperini, P.
Tosato, G.
TI Targeting the mammalian target of Rapamycin to inhibit VEGF and
cytokines for the treatment of primary effusion lymphoma
SO LEUKEMIA
LA English
DT Article
DE PEL; rapamycin; IL-10; KSHV; drug-resistance
ID ENDOTHELIAL GROWTH-FACTOR; SARCOMA-ASSOCIATED HERPESVIRUS; NITRIC-OXIDE
SYNTHASE; SIGNAL-TRANSDUCTION PATHWAY; RENAL-TRANSPLANT RECIPIENTS;
B-CELL LYMPHOMAS; KAPOSIS-SARCOMA; VASCULAR-PERMEABILITY; IN-VIVO;
INDUCED ANGIOGENESIS
AB Primary effusion lymphoma (PEL) is a fatal malignancy, which typically presents as a lymphomatous effusion that later disseminates. Rapamycin (Rapa), which targets mTOR (mammalian target of Rapa), is currently evaluated as a treatment for PEL, but the recent development of PEL in Rapa-treated post-transplant recipients questions the drug's use in PEL. Here, we used a murine model of PEL effusion that mimics the human disease to investigate the anti-PEL activity of Rapa. We found that Rapa reduces ascites accumulation and extends mouse survival. Initially, Rapa reduced PEL load compared with control mice, but most mice rapidly showed PEL progression. Levels of VEGF, which promotes vascular permeability contributing to effusion formation, were significantly reduced in ascites of Rapa-treated mice compared with controls. Expression of IL-10, the principal autocrine growth factor for PEL, was initially reduced in PEL from Rapa-treated mice but rapidly increased despite treatment. We found that the hypoxic environment of ascites and Rapa cooperate in stimulating IL-10 expression in PEL, which likely contributes to the emergence of drug resistance. These results identify Rapa an effective drug to reduce PEL effusions but illustrate the rapid development of drug resistance, which likely limits the efficacy of Rapa in PEL. Leukemia (2009) 23, 1867-1874; doi: 10.1038/leu.2009.117; published online 25 June 2009
C1 [Gasperini, P.; Tosato, G.] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gasperini, P (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, 37 Convent Dr 37-4, Bethesda, MD 20892 USA.
EM gasperinip@mail.nih.gov
FU NIH; National Cancer Institute; Center for Cancer Research; FIRC
(Italian Foundation; Associazione Italiana per la Ricerca sul Cancro
FX Supported by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research. PG supported in part by FIRC
(Italian Foundation for Cancer Research). We thank Drs S Steinberg, K
Ueda, R Yarchoan, S Pittaluga, D Whitby, S Sakakibara, M Segarra and P
McCormick for help on aspects of this work.
NR 31
TC 12
Z9 14
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD OCT
PY 2009
VL 23
IS 10
BP 1867
EP 1874
DI 10.1038/leu.2009.117
PG 8
WC Oncology; Hematology
SC Oncology; Hematology
GA 506YX
UT WOS:000270816300020
PM 19554030
ER
PT J
AU Kreitman, RJ
Fitzgerald, DJP
Pastan, I
AF Kreitman, Robert J.
Fitzgerald, David J. P.
Pastan, Ira
TI Approach to the patient after relapse of hairy cell leukemia
SO LEUKEMIA & LYMPHOMA
LA English
DT Article
DE Recombinant immunotoxin; monoclonal antibody; Fv; BL22; LMB-2; HA22
ID MINIMAL RESIDUAL DISEASE; TERM-FOLLOW-UP; IMMUNOTOXIN RFB4(DSFV)-PE38
BL22; CHRONIC LYMPHOCYTIC-LEUKEMIA; NATIONAL-CANCER-INSTITUTE;
RECOMBINANT IMMUNOTOXIN; ANTI-CD22 IMMUNOTOXIN; PSEUDOMONAS EXOTOXIN;
CYTOTOXIC ACTIVITY; DIPHTHERIA-TOXIN
AB The current hairy cell leukemia (HCL) treatment is excellent, but evidence of cure with purine analogs cladribine and pentostatin, is lacking. Significant long-term immune suppression, particularly to CD4+ T-cells, and declining complete remission rates with each course, make the identification of new therapies an important goal. The anti-CD20 monoclonal antibody (Mab) rituximab displays significant activity, and, while causing prolonged normal B-cell depletion, spares T-cells. Recombinant immunotoxins, containing an Fv fragment of a Mab fused to truncated Pseudomonas exotoxin, have shown efficacy in HCL resistant to both purine analogs and rituximab. LMB-2 targets CD25 and can induce remission providing the HCL cells are CD25+. All HCL cells display CD22. Recombinant anti-CD22 immunotoxin BL22, targeting CD22, has shown significant efficacy in phase I and II testing, and avoids prolonged suppression of both normal B- and T-cells. An improved high-affinity version of BL22, termed HA22, is currently undergoing phase I testing.
C1 [Kreitman, Robert J.; Fitzgerald, David J. P.; Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Kreitman, RJ (reprint author), 37-5124B,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kreitmar@mail.nih.gov
FU NCI; NIH; MedImmune, LLC [BL22, HA22]
FX This work is supported in part by the Intramural Research Program of the
NCI, NIH, and work on BL22 and HA22 is supported in part by MedImmune,
LLC.
NR 66
TC 9
Z9 11
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1042-8194
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD OCT
PY 2009
VL 50
IS 1
SU 1
BP 32
EP 37
DI 10.3109/10428190903142216
PG 6
WC Oncology; Hematology
SC Oncology; Hematology
GA 516LL
UT WOS:000271543600008
PM 19814696
ER
PT J
AU Bianciardi, M
Fukunaga, M
van Gelderen, P
Horovitz, SG
de Zwart, JA
Shmueli, K
Duyn, JH
AF Bianciardi, Marta
Fukunaga, Masaki
van Gelderen, Peter
Horovitz, Silvina G.
de Zwart, Jacco A.
Shmueli, Karin
Duyn, Jeff H.
TI Sources of functional magnetic resonance imaging signal fluctuations in
the human brain at rest: a 7 T study
SO MAGNETIC RESONANCE IMAGING
LA English
DT Article; Proceedings Paper
CT International School on Magnetic Resonance and Brain Function
CY MAY 18-25, 2008
CL Erice, ITALY
DE Nonthermal noise; Spontaneous activity; Physiological noise; 7-T BOLD
fMRI; Resting state
ID BOLD SIGNAL; PHYSIOLOGICAL NOISE; FMRI; STATE; CONNECTIVITY;
RESPIRATION; HYPERCAPNIA; DYNAMICS; CORTEX; SLEEP
AB Signal fluctuations in functional magnetic resonance imaging (fMRI) call result from a number of sources that may have a neuronal., physiologic or instrumental origin. To determine the relative contribution of these Sources, we recorded physiological (respiration and cardiac) signals Simultaneously with fMRI in human Volunteers at rest with their eyes closed. State-of the-arty technology was used including high inagnetic field (7 T), a niultichannel detector array and high-resolution (3 mm(3)) echo-planar imaging. We investigated the relative contribution of thermal noise and other sources of variance to the observed fMRI signal fluctuations both ill the Visual cortex and in the whole brain gray matter. The following Sources of variance were evaluated separately: low-frequency drifts due to scanner instability, effects correlated with respiratory and cardiac cycles, effects clue to variability in the respiratory flow rate and cardiac rate, and other sources, tentatively attributed to spontaneous neuronal activity. We found that low-frequency drifts are the most significant source of fMRI signal fluctuations (3.0% signal change in the Visual cortex, TE=32 ills), followed by spontaneous neuronal activity (2.9%), thermal noise (2.1%), effects due to variability in physiological rates (respiration 0.9%, heartbeat 0.9%), and correlated with physiological cycles (0.6%). We Suggest the selection and use of four lagged physiological noise regressors as all effective model to explain the variance related to fluctuations in the rates of respiration volume change and cardiac pulsation. Our results also indicate that, compared to the whole brain gray matter, the visual cortex has higher sensitivity to changes in both the rate of respiration and the spontaneous resting-state activity. Under the conditions of this Study, spontaneous neuronal activity is one of the major contributors to the measured fMRI signal fluctions ions, increasing almost twofold relative to earlier experiments under similar conditions at 3 T. Published by Elsevier Inc.
C1 [Bianciardi, Marta; Fukunaga, Masaki; van Gelderen, Peter; Horovitz, Silvina G.; de Zwart, Jacco A.; Shmueli, Karin; Duyn, Jeff H.] NINDS, Adv MRI Sect, LFMI, NIH, Bethesda, MD 20892 USA.
RP Bianciardi, M (reprint author), NINDS, Adv MRI Sect, LFMI, NIH, Bethesda, MD 20892 USA.
EM bianciardim@mail.nih.gov
RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013; Shmueli,
Karin/B-9432-2017
OI Fukunaga, Masaki/0000-0003-1010-2644;
FU Intramural NIH HHS [Z01 NS002990-08]
NR 27
TC 90
Z9 90
U1 0
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0730-725X
J9 MAGN RESON IMAGING
JI Magn. Reson. Imaging
PD OCT
PY 2009
VL 27
IS 8
BP 1019
EP 1029
DI 10.1016/j.mri.2009.02.004
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 500UA
UT WOS:000270329800003
PM 19375260
ER
PT J
AU Barnett, A
AF Barnett, Alan
TI Theory of Q-ball Imaging Redux: Implications for Fiber Tracking
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE q-ball imaging; fiber tracking; ODF; HARDI
ID DIFFUSION TENSOR; SPIN-ECHO; FIELD-GRADIENT; HUMAN BRAIN; RESTRICTED
DIFFUSION; ANGULAR RESOLUTION; MRI DATA; NMR; TISSUE; ARCHITECTURE
AB Q-ball imaging is widely used to determine fiber directions for fiber tracking. In cl-ball imaging the directional dependence of water diffusion in tissue is described by Tuch's orientation distribution function (ODF); a different function, the cl-ball orientation distribution function, is measured using high angular resolution magnetic resonance diffusion imaging (HARDI). Tuch's ODF is assumed to be well approximated by the cl-ball ODF. In this study it is shown that 1) the cl-ball ODF is not a good approximation to Tuch's ODF; 2) the properties of the q-ball ODF depend strongly on q, the area of the diffusion sensitization gradients; and 3) the cl-ball ODF for a composite system is the weighted average of the cl-ball ODFs for each subsystem, but the weighting factor is the product of the percent composition and a renormalization factor. In addition, a derivation is presented of the cl-ball ODF for a system described by a Gaussian distribution and expressions are derived for both the dependence of the angular resolution on q and for the relation between the angular resolution and the signal loss. These findings might be useful in the design and interpretation of fiber-tracking experiments. Magn Reson Med 62.910-923, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Barnett, Alan] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA.
RP Barnett, A (reprint author), NIH, Magnuson Clin Ctr, Bldg 10,3C213,10 Ctr Dr, Bethesda, MD 20892 USA.
EM asb@nih.gov
FU Intramural NIH HHS
NR 30
TC 22
Z9 22
U1 0
U2 4
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD OCT
PY 2009
VL 62
IS 4
BP 910
EP 923
DI 10.1002/mrm.22073
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 503SA
UT WOS:000270558700010
PM 19672943
ER
PT J
AU Qin, L
van Gelderen, P
Derbyshire, JA
Jin, FH
Lee, J
de Zwart, JA
Tao, Y
Duyn, JH
AF Qin, Lei
van Gelderen, Peter
Derbyshire, John Andrew
Jin, Fenghua
Lee, Jongho
de Zwart, Jacco A.
Tao, Yang
Duyn, Jeff H.
TI Prospective Head-Movement Correction for High-Resolution MRI Using an
In-Bore Optical Tracking System
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE prospective motion correction; optical tracking; MR-compatible camera;
real-time MRI; high-resolution MRI
ID MOTION CORRECTION; NAVIGATOR ECHOES; FMRI; ROTATION
AB In MRI of the human brain, subject motion is a major cause of magnetic resonance image quality degradation. To compensate for the effects of head motion during data acquisition, an in-bore optical motion tracking system is proposed. The system comprises two MR-compatible infrared cameras that are fixed on a holder right above and in front of the head coil. The resulting close proximity of the cameras to the object allows precise tracking of its movement. During image acquisition, the MRI scanner uses this tracking information to prospectively compensate for head motion by adjusting the gradient field direction and radio frequency (RF) phases and frequencies. Experiments performed on subjects demonstrate robust system performance with translation and rotation accuracies of 0.1 mm and 0.15 degrees, respectively. Magn Reson Med 62:924-934, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Qin, Lei; van Gelderen, Peter; Lee, Jongho; de Zwart, Jacco A.; Duyn, Jeff H.] Natl Inst Neurol Disorders & Stroke, Adv MRI, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Qin, Lei; Jin, Fenghua; Tao, Yang] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA.
[Derbyshire, John Andrew] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Duyn, JH (reprint author), Natl Inst Neurol Disorders & Stroke, Adv MRI, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,Bldg 10,Rm B1D-723, Bethesda, MD 20892 USA.
EM jhd@helix.nih.gov
RI Duyn, Jozef/F-2483-2010
FU Intramural NIH HHS [Z01 NS002990-08]
NR 33
TC 59
Z9 59
U1 1
U2 4
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 OCT
PY 2009
VL 62
IS 4
BP 924
EP 934
DI 10.1002/mrm.22076
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 503SA
UT WOS:000270558700011
PM 19526503
ER
PT J
AU Zhang, Y
Li, SZ
Shen, J
AF Zhang, Yan
Li, Shizhe
Shen, Jun
TI Automatic High-Order Shimming Using Parallel Columns Mapping (PACMAP)
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE high-order shimming; spherical harmonics; parallel columns; oblique
plane; field map
ID MAGNETIC-FIELD; ACQUISITION; BRAIN
AB This work presents a new automatic high-order shimming method that maps the B(0) field using a group of parallel columns. We found that a pair of four columns in two separate slices could determine an optimal correction field comprising the spherical harmonic terms up to the third-order. The technique of multiple stimulated echoes was incorporated into the method, allowing the use of at least eight shots to accomplish field mapping. The shim currents were first determined in the logic frame by assuming that the slices were in axial planes, and then uniquely converted into the physical frame where the slices could be at any oblique angle, by using a spherical harmonics rotation transformation. This method thus works regardless of slice orientation. It was demonstrated on a 3T scanner equipped with a complete set of second-order harmonic shim coils. Both phantom and in vivo experiments showed that this newly introduced high-order shimming method is an effective and efficient way to reduce field inhomogeneity for a region of imaging slices. Magn Reson Med 62:1073-1079, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Shen, Jun] NIMH, Mol Imaging Branch, Spect Core Facil, NIH, Bethesda, MD 20892 USA.
RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Spect Core Facil, NIH, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shenj@mail.nih.gov
FU Intramural NIH HHS [Z01 MH002894-01]
NR 19
TC 4
Z9 4
U1 1
U2 4
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD OCT
PY 2009
VL 62
IS 4
BP 1073
EP 1079
DI 10.1002/mrm.22077
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 503SA
UT WOS:000270558700029
PM 19645006
ER
PT J
AU Bennett, GG
Wolin, KY
Puleo, EM
Masse, LC
Atienza, AA
AF Bennett, Gary G.
Wolin, Kathleen Y.
Puleo, Elaine M.
Masse, Louise C.
Atienza, Audie A.
TI Awareness of National Physical Activity Recommendations for Health
Promotion among US Adults
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE HINTS; EXERCISE; DIET; PHYSICAL INACTIVITY
ID AMERICAN-HEART-ASSOCIATION; OF-SPORTS-MEDICINE; PERCEIVED RISK;
CANCER-SOCIETY; PUBLIC-HEALTH; UNITED-STATES; DISEASE; PREVENTION;
KNOWLEDGE; AGENDA
AB BENNETT, G. G., K. Y. WOLIN. E. M. PULEO, L. C. MASSE, and A. A. ATIENZA. Awareness of National Physical Activity Recommendations for Health Promotion among US Adults. Med. Sci. Sports Exerc., Vol. 41, No. 10, pp. 1849-1855, 2009. Purpose: To examine whether knowledge of the 1995 Centers for Disease Control and Prevention (CDC) and the American College of Sports Medicine (ACSM) national physical activity recommendations varies by sociodemographic, behavioral, and communication-related factors. Methods: Cross-sectional analyses of 2381 participants in the 2005 Health Information National Trends Survey, a national probability sample of the US population contacted via random-digit dial. Results: Only a third of respondents were accurately knowledgeable of the CDC/ACSM physical activity recommendations. Recommendation knowledge was higher among women (OR 1.70; 95% confidence interval (CI) = 1.35-2.14) than men, the employed compared with those not currently working (OR = 0.73 95% CI = 0.55-0.95), foreign-born individuals (OR = 1.62; 95% CI = 1.15-2.30) compared with the US-born, and those meeting CDC/ACSM recommendations vs those who do not (OR = 0.74: 95% CI = 0.58-0.96). Conclusions: There is riot widespread knowledge of the consensus national physical activity recommendations. These findings highlight the need for more effective campaigns to promote physical activity among the American public.
C1 [Bennett, Gary G.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Bennett, Gary G.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wolin, Kathleen Y.] Washington Univ, Sch Med, St Louis, MO USA.
[Puleo, Elaine M.] Univ Massachusetts Amherst, Amherst, MA USA.
[Masse, Louise C.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Atienza, Audie A.] NCI, Bethesda, MD 20892 USA.
RP Bennett, GG (reprint author), Duke Univ, Box 90086,9 Flowers Dr, Durham, NC 27708 USA.
EM gary.bennett@duke.edu
RI Wolin, Kathleen/I-2154-2014
OI Wolin, Kathleen/0000-0001-7950-9042
FU Dana-Farber/ Harvard Cancer Center; NCI [1K22CA126992]; US NCI
FX Present address for Gary G. Bennett is Duke University, Durham, NC.
NR 46
TC 30
Z9 30
U1 2
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD OCT
PY 2009
VL 41
IS 10
BP 1849
EP 1855
DI 10.1249/MSS.0b013e3181a52100
PG 7
WC Sport Sciences
SC Sport Sciences
GA 499FI
UT WOS:000270202700003
PM 19727030
ER
PT J
AU Mathias, RA
Deepa, M
Deepa, R
Wilson, AF
Mohan, V
AF Mathias, Rasika A.
Deepa, Mohan
Deepa, Raj
Wilson, Alexander F.
Mohan, Vishwanathan
TI Heritability of quantitative traits associated with type 2 diabetes
mellitus in large multiplex families from South India
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
ID METABOLIC SYNDROME; INSULIN-RESISTANCE; CARDIOVASCULAR RISK; GENE
POLYMORPHISMS; GLUCOSE-TOLERANCE; LINKAGE ANALYSIS; ASIAN INDIANS;
OBESITY; POPULATION; PREVALENCE
AB India is a major contributor to the global public health burden of diabetes. We have undertaken a family Study of large multiplex families from Chennai, South India, and report on the familial aggregation of quantitative traits associated with type 2 diabetes mellitus in these pedigrees. Five hundred twenty-four individuals older than 19 years from 26 large multiplex pedigrees were ascertained. Detailed questionnaires and phenotype data were obtained on all participating individuals including fasting blood glucose, fasting insulin, lipid profiles, height, weight, and other anthropometric and clinical measures. Heritability estimates were calculated for all quantitative traits at the univariate level, and bivariate analyses were done to determine the correlation in genetic and environmental control across these quantitative traits. Heritability estimates ranged from 0.21 to 0.72. The heritability estimates for traits most directly related to type 2 diabetes mellitus were 0.24 +/- 0.08 for fasting blood glucose and 0.41 +/- 0.09 for fasting insulin. In addition, there was evidence for common genetic control for many pairs of these traits. These bivariate analyses suggested common genes for Casting insulin and central obesity measures (body mass index, waist, and hip), with complete genetic correlation between fasting insulin and waist. Quantitative traits associated with type 2 diabetes mellitus have heritabilities suggestive of sonic familial or genetic effect. The evidence for pleiotropic control of insulin and central obesity-related traits supports the presence of an insulin resistance syndrome in South Asians with a tendency for central obesity. Published by Elsevier Inc.
C1 [Mathias, Rasika A.; Wilson, Alexander F.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA.
[Deepa, Mohan; Deepa, Raj; Mohan, Vishwanathan] WHO Collaborating Ctr Noncommunicable Dis Prevent, Madras Diabet Res Fdn, Madras 600086, Tamil Nadu, India.
[Deepa, Mohan; Deepa, Raj; Mohan, Vishwanathan] WHO Collaborating Ctr Noncommunicable Dis Prevent, Dr Mohans Diabet Specialties Ctr, Madras 600086, Tamil Nadu, India.
RP Mathias, RA (reprint author), NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA.
EM rmathias1@mail.nih.gov
RI Wilson, Alexander/C-2320-2009
FU National Human Genome Research Institute, National Institutes of Health
FX The authors would like to thank the clinical coordinators Uma Shankari
G, Rajeshwari K, Maria Margret Susan, and Suresh T and the laboratory
technicians Ganga Kalyani E, Anitha D, Sridevi K, Sasikala K, Sathish
Raj S, and Ms Nazeera R for their help in subject recruitment and sample
processing. The authors thank Dr Linda Kao for her help and advice in
the preparation of this manuscript. This research was supported in part
by the Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health.
NR 37
TC 20
Z9 20
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
J9 METABOLISM
JI Metab.-Clin. Exp.
PD OCT
PY 2009
VL 58
IS 10
BP 1439
EP 1445
DI 10.1016/j.metabol.2009.04.041
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 500TF
UT WOS:000270327100011
PM 19570552
ER
PT J
AU Scott, I
AF Scott, Iain
TI Degradation of RIG-I following cytomegalovirus infection is independent
of apoptosis
SO MICROBES AND INFECTION
LA English
DT Article
DE RIG-I; MAVS; IPS-1; Cardif; vMIA; UL37x1; Cleavage; Apoptosis;
Cytomegalovirus
ID ANTIVIRAL SIGNALING PROTEIN; HEPATITIS-C VIRUS; ADAPTER PROTEIN; INNATE
IMMUNITY; MITOCHONDRIA; MAVS; ACTIVATION; INHIBITOR; CLEAVAGE; PATHWAY
AB Many viruses have evolved strategies to either evade or hijack host cell immune programs, as a means of promoting their own reproduction. For example, the human cytomegalovirus (HCMV) immediate-early protein vMIA/UL37ex1 inhibits host cell apoptosis, and its expression during infection aids virus replication. Here it is shown that stable expression of vMIA/UL37ex1 reduces cleavage of the innate immune response-proteins MAVS and RIG-1 by caspases during apoptosis. Unexpectedly, it is demonstrated that RIG-1, but not MAVS, is degraded during HCMV infection. This process occurs in a non-apoptotic manner, and provides new evidence that HCMV may have evolved a unique strategy to evade RIG-1-mediated immune responses. Published by Elsevier Masson SAS.
C1 [Scott, Iain] NINDS, Biochem Sect, Surg Neurol Branch, Bethesda, MD 20892 USA.
RP Scott, I (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10-CRC,Room 5-3216,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM scotti@mail.nih.gov
FU National Institute of Neurological Disorders and Stroke; National
Institutes of Health
FX The author thanks Richard Youle for support and equipment, Chad
Williamson for help and advice with viral experiments, Wade Gibson for
helpful discussions and both Victor Goldmacher and Kui Li for materials.
This research was supported by the intramural research program of the
National Institute of Neurological Disorders and Stroke, National
Institutes of Health.
NR 23
TC 12
Z9 13
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
J9 MICROBES INFECT
JI Microbes Infect.
PD OCT
PY 2009
VL 11
IS 12
BP 973
EP 979
DI 10.1016/j.micinf.2009.07.001
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 504QI
UT WOS:000270631700009
PM 19591957
ER
PT J
AU Rayavara, K
Rajapandi, T
Wollenberg, K
Kabat, J
Fischer, ER
Desai, SA
AF Rayavara, Kempaiah
Rajapandi, Thavamani
Wollenberg, Kurt
Kabat, Juraj
Fischer, Elizabeth R.
Desai, Sanjay A.
TI A complex of three related membrane proteins is conserved on malarial
merozoites
SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY
LA English
DT Article
DE Apicomplexa; Plasmodium; Merozoite; Transmembrane proteins; Heterologous
expression
ID PLASMODIUM-FALCIPARUM; ERYTHROCYTE INVASION; SURFACE; CELLS; EXPRESSION;
PARASITE; BACULOVIRUS; ANTIGENS; VECTORS; INSECT
AB Invasion of human red blood cells by the malaria parasite Plasmodium falciparum is a coordinated, multi-step process. Here, we describe three novel integral membrane proteins that colocalize on the inner membrane complex immediately beneath the merozoite plasma membrane. Each has six predicted transmembrane domains and is conserved in diverse apicomplexan parasites. Immunoprecipitation studies using specific antibodies reveal that these proteins assemble into a heteromeric complex. Each protein was also expressed on insect cells using the baculovirus vector system with a truncated SUMO tag that facilitates maximal expression and protein purification while permitting cleavage with SUMO protease to release unmodified parasite protein. The expressed proteins were successfully reconstituted into artificial liposomes, but were not recognized by human immune sera. Because all three genes are highly conserved in apicomplexan parasites, the complex formed by their encoded proteins likely serves an essential role for invasive merozoites. Published by Elsevier B.V.
C1 [Rayavara, Kempaiah; Rajapandi, Thavamani; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Wollenberg, Kurt] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Kabat, Juraj; Fischer, Elizabeth R.] NIAID, RTB, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sdesai@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX We thank Jose Riberio for help with bioinformatics, Sanjay Singh and
Rick Fairhurst for providing antibodies and human immune sera, and Owen
Schwartz and Meggan Czapiga for help with confocal microscopy and
deconvolution of images. This research was supported by the Intramural
Research Program of the National Institutes of Health, National
Institute of Allergy and Infectious Diseases.
NR 27
TC 9
Z9 9
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-6851
J9 MOL BIOCHEM PARASIT
JI Mol. Biochem. Parasitol.
PD OCT
PY 2009
VL 167
IS 2
BP 135
EP 143
DI 10.1016/j.molbiopara.2009.05.006
PG 9
WC Biochemistry & Molecular Biology; Parasitology
SC Biochemistry & Molecular Biology; Parasitology
GA 475NM
UT WOS:000268366600006
PM 19465059
ER
PT J
AU Perez-Victoria, FJ
Bonifacino, JS
AF Perez-Victoria, F. Javier
Bonifacino, Juan S.
TI Dual Roles of the Mammalian GARP Complex in Tethering and SNARE Complex
Assembly at the trans-Golgi Network
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID PROTEIN COMPLEX; ORGANELLE IDENTITY; MEMBRANE-FUSION; EARLY ENDOSOME;
BINDING-SITES; TLG1P; RAB5; HOPS; IDENTIFICATION; PURIFICATION
AB Tethering factors and SNAREs control the last two steps of vesicular trafficking: the initial interaction and the fusion, respectively, of transport vesicles with target membranes. The Golgi-associated retrograde protein (GARP) complex regulates retrograde transport from endosomes to the trans-Golgi network (TGN). Although GARP has been proposed to function as a tethering factor at the TGN, direct evidence for such a role is still lacking. Herein we report novel and specific interactions of the mammalian GARP complex with SNAREs that participate in endosome-to-TGN transport, namely, syntaxin 6, syntaxin 16, and Vamp4. These interactions depend on the N-terminal regions of Vps53 and Vps54 and the SNARE motif of the SNAREs. We show that GARP functions upstream of the SNAREs, regulating their localization and assembly into SNARE complexes. However, interactions of GARP with SNAREs are insufficient to promote retrograde transport, because deletion of the C-terminal region of Vps53 precludes GARP function without affecting GARP-SNARE interactions. Finally, we present in vitro data consistent with a tethering role for GARP, which is disrupted by deletion of the Vps53 C-terminal region. These findings indicate that GARP orchestrates retrograde transport from endosomes to the TGN by promoting vesicle tethering and assembly of SNARE complexes in consecutive, independent steps.
C1 [Bonifacino, Juan S.] NICHD, Cell Biol & Metab Program, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Bonifacino, JS (reprint author), NICHD, Cell Biol & Metab Program, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bldg 18T,Room 101, Bethesda, MD 20892 USA.
EM juan@helix.nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370
FU NIH; Ministerio de Educacion y Ciencia of Spain
FX This work was funded by the Intramural Program of NICHD of the NIH.
F.J.P.-V. was the recipient of a postdoctoral fellowship from the
Ministerio de Educacion y Ciencia of Spain.
NR 47
TC 60
Z9 62
U1 0
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD OCT
PY 2009
VL 29
IS 19
BP 5251
EP 5263
DI 10.1128/MCB.00495-09
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 493AT
UT WOS:000269706000005
PM 19620288
ER
PT J
AU Ueda, T
Furusawa, T
Kurahashi, T
Tessarollo, L
Bustin, M
AF Ueda, Tetsuya
Furusawa, Takashi
Kurahashi, Toshihiro
Tessarollo, Lino
Bustin, Michael
TI The Nucleosome Binding Protein HMGN3 Modulates the Transcription Profile
of Pancreatic beta Cells and Affects Insulin Secretion
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID TISSUE-SPECIFIC EXPRESSION; CHROMOSOMAL-PROTEINS; DIABETES-MELLITUS;
GLUT2 GENE; CHROMATIN; ACTIVATION; MUTATIONS; TRANSPORT; CHANNELS;
ISOFORMS
AB Improper glucose-stimulated insulin secretion from pancreatic beta cells is a major factor in the onset of type 2 diabetes. We now report that HMGN3, a nuclear protein that binds to nucleosomes and affects chromatin function, is highly expressed in beta cells and that in mice, loss of HMGN3 impairs glucose-stimulated insulin secretion and leads to a diabetic phenotype. In pancreatic beta cells, loss of HMGN3 affects the transcription of several genes involved in glucose-stimulated insulin secretion, including that of the Glut2 glucose transporter. Chromatin immunoprecipitation reveals that HMGN3 and the transcription factor PDX1 mutually reinforce their specific binding to the chromatin in the promoter of the Glut2 gene, thereby regulating GLUT2 protein levels in pancreatic islets and in beta cells. Our results identify a new regulator of glucose homeostasis and demonstrate a link between the activity of a nucleosome binding structural protein and the regulation of insulin secretion.
C1 [Ueda, Tetsuya; Furusawa, Takashi; Kurahashi, Toshihiro; Bustin, Michael] NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Tessarollo, Lino] NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Bustin, M (reprint author), NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
EM bustin@helix.nih.gov
RI Bustin, Michael/G-6155-2015
FU NCI, NIH
FX This research was supported by the Center for Cancer Research,
intramural program of the NCI, NIH.
NR 44
TC 22
Z9 23
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD OCT
PY 2009
VL 29
IS 19
BP 5264
EP 5276
DI 10.1128/MCB.00526-09
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 493AT
UT WOS:000269706000006
PM 19651901
ER
PT J
AU Storbeck, CJ
Wagner, S
O'Reilly, P
McKay, M
Parks, RJ
Westphal, H
Sabourin, LA
AF Storbeck, Chris J.
Wagner, Simona
O'Reilly, Paul
McKay, Marlene
Parks, Robin J.
Westphal, Heiner
Sabourin, Luc A.
TI The Ldb1 and Ldb2 Transcriptional Cofactors Interact with the Ste20-like
Kinase SLK and Regulate Cell Migration
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID STE20-RELATED KINASE; HOMEODOMAIN PROTEINS; LIM; DOMAIN; ADHESION;
BINDING; ACTIVATION; MICROTUBULE; EXPRESSION; DLDB/CHIP
AB Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses, and tissue repair. Here, we show that the microtubule-associated Ste20 kinase SLK, required for cell migration, interacts with the LIM domain binding transcriptional cofactor proteins Ldb1/CLIM2 and Ldb2/CLIM1/NLI. We demonstrate that Ldb1 and 2 bind directly to the SLK carboxy-terminal AT1-46 homology domain in vitro and in vivo. We find that Ldb1 and -2 colocalize with SLK in migrating cells and that both knockdown and overexpression of either factor results in increased motility. Supporting this, knockdown of Ldb1 increases focal adhesion turnover and enhances migration in fibroblasts. We propose that Ldb1/2 function to maintain SLK in an inactive state before its activation. These findings highlight a novel function for Ldb1 and -2 and expand their role to include the control of cell migration.
C1 [Storbeck, Chris J.; Wagner, Simona; O'Reilly, Paul; Sabourin, Luc A.] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada.
[McKay, Marlene; Parks, Robin J.; Sabourin, Luc A.] Ottawa Hosp, Res Inst, Ottawa, ON K1Y 4E9, Canada.
[Westphal, Heiner] NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA.
RP Sabourin, LA (reprint author), Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada.
EM lsabourin@ohri.ca
FU Canadian Institute for Health Research; MDAUSA; Canadian Breast Cancer
Foundation; Premier's Research for Excellence Award; Canadian Heart and
Stroke Foundation; Ontario Graduate Scholarships in Science and
Technology; Natural Sciences and Engineering Research Council
FX We thank Kim Wong and Doris Parolin for valuable help with confocal
microscopy and live imaging. This work was supported by the Canadian
Institute for Health Research, MDAUSA, the Canadian Breast Cancer
Foundation, and a Premier's Research for Excellence Award. C. J. S. is
the recipient of a Canadian Heart and Stroke Foundation Fellowship. L.
A. S. is the recipient of a Canadian Institutes of Health Research
scholar award. P. O. and S. W. are the recipients of Ontario Graduate
Scholarships in Science and Technology and Natural Sciences and
Engineering Research Council studentships, respectively.
NR 21
TC 18
Z9 21
U1 0
U2 1
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD OCT
PY 2009
VL 20
IS 19
BP 4174
EP 4182
DI 10.1091/mbc.E08-07-0707
PG 9
WC Cell Biology
SC Cell Biology
GA 501BF
UT WOS:000270352400005
PM 19675209
ER
PT J
AU Cardinale, S
Bergmann, JH
Kelly, D
Nakano, M
Valdivia, MM
Kimura, H
Masumoto, H
Larionov, V
Earnshaw, WC
AF Cardinale, Stefano
Bergmann, Jan H.
Kelly, David
Nakano, Megumi
Valdivia, Manuel M.
Kimura, Hiroshi
Masumoto, Hiroshi
Larionov, Vladimir
Earnshaw, William C.
TI Hierarchical Inactivation of a Synthetic Human Kinetochore by a
Chromatin Modifier
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID ZINC-FINGER PROTEINS; HISTONE H3; CENP-A; CENTROMERE FUNCTION;
VERTEBRATE CELLS; DNA-BINDING; HETEROCHROMATIN; COMPLEX; DOMAIN; KAP-1
AB We previously used a human artificial chromosome ( HAC) with a synthetic kinetochore that could be targeted with chromatin modifiers fused to tetracycline repressor to show that targeting of the transcriptional repressor tTS within kinetochore chromatin disrupts kinetochore structure and function. Here we show that the transcriptional corepressor KAP1, a downstream effector of the tTS, can also inactivate the kinetochore. The disruption of kinetochore structure by KAP1 subdomains does not simply result from loss of centromeric CENP-A nucleosomes. Instead it reflects a hierarchical disruption of the outer kinetochore, with CENP-C levels falling before CENP-A levels and, in certain instances, CENP-H being lost more readily than CENP-C. These results suggest that this novel approach to kinetochore dissection may reveal new patterns of protein interactions within the kinetochore.
C1 [Cardinale, Stefano; Bergmann, Jan H.; Kelly, David; Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
[Nakano, Megumi; Larionov, Vladimir] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
[Valdivia, Manuel M.] Univ Cadiz, Dept Bioquim & Biol Mol, Fac Ciencias, Cadiz 11510, Spain.
[Kimura, Hiroshi] Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan.
[Nakano, Megumi; Masumoto, Hiroshi] Kazusa DNA Res Inst, Dept Human Genome Res, Lab Cell Engn, Chiba 2920818, Japan.
RP Earnshaw, WC (reprint author), Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland.
EM bill.earnshaw@ed.ac.uk
RI Cardinale, Stefano/F-4024-2014;
OI Martinez Valdivia, Manuel Jesus/0000-0002-2888-849X; Cardinale,
Stefano/0000-0003-4357-9246
FU Darwin Trust of Edinburgh; Wellcome Trust; National Institutes of
Health; National Cancer Institute; Center for Cancer Research; Ministry
of Education, Science, Sports and Culture of Japan; Ministerio de
Ciencia y Tecnologia [SAF2007-61863]; MEXT of Japan
FX We thank David Schultz (Wistar Institute, Philadelphia, PA) for the gift
of KAP1 wild-type and mutant clones. S. C. and J. H. B. were funded by
Ph. D. studentships from The Darwin Trust of Edinburgh and The Wellcome
Trust, respectively. This research was supported by the intramural
research program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research (V. L.); a grant-in-aid from the
Ministry of Education, Science, Sports and Culture of Japan (H. M.); the
Ministerio de Ciencia y Tecnologia (SAF2007-61863; M. M. V.); and the
Genome Network project and Grants-in-aid from the MEXT of Japan (H. K.).
Work in the W. C. E. lab is funded by The Wellcome Trust, of which he is
a Principal Research Fellow.
NR 49
TC 40
Z9 40
U1 1
U2 1
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD OCT
PY 2009
VL 20
IS 19
BP 4194
EP 4204
DI 10.1091/mbc.E09-06-0489
PG 11
WC Cell Biology
SC Cell Biology
GA 501BF
UT WOS:000270352400007
PM 19656847
ER
PT J
AU To, KKW
Robey, RW
Knutsen, T
Zhan, ZR
Ried, T
Bates, SE
AF To, Kenneth K. W.
Robey, Robert W.
Knutsen, Turid
Zhan, Zhirong
Ried, Thomas
Bates, Susan E.
TI Escape from hsa-miR-519c enables drug-resistant cells to maintain high
expression of ABCG2
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID BINDING CASSETTE TRANSPORTER; BREAST-CANCER CELLS; MULTIDRUG-RESISTANCE;
MESSENGER-RNA; METHOTREXATE RESISTANCE; UNTRANSLATED REGION; CARCINOMA
CELLS; OVARIAN-CANCER; STEM-CELLS; MICRORNAS
AB Overexpression of ABCG2 has been reported in cell lines selected for drug resistance and it is widely believed to be important in the clinical pharmacology of anticancer drugs. We and others have previously identified and validated two microRNAs (miRNA; hsa-miR-519c and hsa-miR-520h) targeting ABCG2. In this study, the shortening of the ABCG2 3' untranslated region (3'UTR) was found to be a common phenomenon in several ABCG2-overexpressing resistant cell lines, which as a result removes the hsa-miR-519c binding site and its repressive effects on mRNA stability and translation blockade, thereby contributing to drug resistance. On the other hand, reduced expression of hsa-miR-520h, previously thought to have allowed ABCG2 overexpression, was found to be caused by the sequestering of the miRNA by the highly expressed ABCG2. In drug-sensitive cells, inhibitors against hsa-miR-519c and hsa-miR-520h could augment the cytotoxic effect of mitoxantrone, suggesting a substantial role for both miRNAs in controlling ABCG2 level and thereby anticancer drug response. However, in drug-resistant cells, altering the levels of the two miRNAs did not have any effect on sensitivity to mitoxantrone. Taken together, these studies suggest that in ABCG2-overexpressing drug-resistant cells, hsa-miR-519c is unable to affect ABCG2 expression because the mRNA lacks its binding site, whereas hsa-miR-520h is sequestered and unable to limit ABCG2 expression. Given the recent observation that a truncated 3'UTR is also observed in ABCG2-overexpressing human embryonic stem cells, our results in drug-resistant cell lines suggest that 3'UTR truncation is a relatively common mechanism of ABCG2 regulation. [Mol Cancer Ther 2009;8(10):2959-68]
C1 [To, Kenneth K. W.] Chinese Univ Hong Kong, Sch Pharm, Hong Kong, Hong Kong, Peoples R China.
[To, Kenneth K. W.; Robey, Robert W.; Zhan, Zhirong; Bates, Susan E.] NCI, Mol Therapeut Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Knutsen, Turid; Ried, Thomas] NCI, Sect Canc Genom, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP To, KKW (reprint author), Chinese Univ Hong Kong, Sch Pharm, Hong Kong, Hong Kong, Peoples R China.
EM kennethto@cuhk.edu.hk
RI To, Kenneth /M-4500-2013
OI To, Kenneth /0000-0003-2755-0283
FU NIH; National Cancer Institute; Center for Cancer Research, Medical
Oncology Branch
FX Grant support: Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research, Medical Oncology Branch.
NR 46
TC 61
Z9 69
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD OCT
PY 2009
VL 8
IS 10
BP 2959
EP 2968
DI 10.1158/1535-7163.MCT-09-0292
PG 10
WC Oncology
SC Oncology
GA 507IJ
UT WOS:000270845500019
PM 19825807
ER
PT J
AU Foreman, JE
Sorg, JM
McGinnis, KS
Rigas, B
Williams, JL
Clapper, ML
Gonzalez, FJ
Peters, JM
AF Foreman, Jennifer E.
Sorg, Joseph M.
McGinnis, Kathleen S.
Rigas, Basil
Williams, Jennie L.
Clapper, Margie L.
Gonzalez, Frank J.
Peters, Jeffrey M.
TI Regulation of Peroxisome Proliferator-Activated Receptor-beta/delta by
the APC/beta-CATENIN Pathway and Nonsteroidal Antiinflammatory Drugs
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE colon cancer; PPAR beta/delta; gene expression; NSAIDs
ID COLORECTAL-CANCER CELLS; PPAR-DELTA; COLON CARCINOGENESIS; LIGAND
ACTIVATION; APC(MIN/+) MICE; TARGET GENES; BETA-CATENIN; EXPRESSION;
METABOLISM; GAMMA
AB Studies indicate that peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) can either attenuate or potentiate colon cancer. One hypothesis suggests that PPAR beta/delta is upregulated by the adenomatous polyposis coli (APC)/beta-CATENIN pathway and a related hypothesis suggests that PPAR beta/delta is downregulated by nonsteroidal antiinflammatory drugs (NSAIDs). The present study examined these possibilities using in vivo and in vitro models. While APC/beta-CATENIN-dependent expression of CYCLIN D1 was observed in vivo and in vitro, expression of PPAR beta/delta was not different in colon or intestinal polyps from wild-type or Apc(min) heterozygous mice or in human colon cancer cell lines with mutations in APC and/or beta-CATENIN. No difference in the level of PPAR beta/delta was found in colon from wild-type or Apc(min) heterozygous mice following treatment with NO-donating aspirin (NO-ASA). NSAIDs inhibited cell growth in RKO (wild-type APC) and DLD1 (mutant APC) human colon cancer cell lines but expression of PPAR beta/delta was not downregulated in these cell lines in response to a broad concentration range of celecoxib, indomethacin, NS-398, or nimesulide. However, indomethacin caused an increase in PPAR beta/delta mRNA and protein that was accompanied with increased expression of a known PPAR beta/delta target gene. Interestingly, expression of PPAR alpha was also increased in the human colon cancer cell lines by several NSAIDs at the highest concentration examined. Results from these studies provide additional evidence indicating that PPAR beta/delta is not upregulated by the APC/beta-CATENIN pathway. Further, these studies suggest that increased PPAR beta/delta and/or PPAR alpha by NSAIDs in human colon cancer cell lines could contribute to the mechanisms underlying the chemopreventive effects of NSAIDs. (C) 2009 Wiley-Liss, Inc.
C1 [Foreman, Jennifer E.; Sorg, Joseph M.; McGinnis, Kathleen S.; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Rigas, Basil; Williams, Jennie L.] SUNY Stony Brook, Canc Prevent Div, Stony Brook, NY 11794 USA.
[Clapper, Margie L.] Fox Chase Canc Ctr, Canc Prevent & Control Program, Philadelphia, PA 19111 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
RI Peters, Jeffrey/D-8847-2011
FU [CA129467]; [CA97999]; [CA124533]; [CA92423]
FX We gratefully acknowledge Drs. Andrew Billin and Timothy Willson for
providing GW0742. This work was Supported in part by CA129467 (M.L.C.),
CA97999, CA124533 U.M.P.), and CA92423 (B.R.).
NR 31
TC 24
Z9 24
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0899-1987
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD OCT
PY 2009
VL 48
IS 10
BP 942
EP 952
DI 10.1002/mc.20546
PG 11
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 503AF
UT WOS:000270502000008
PM 19415698
ER
PT J
AU Tomarev, SI
Nakaya, N
AF Tomarev, Stanislav I.
Nakaya, Naoki
TI Olfactomedin Domain-Containing Proteins: Possible Mechanisms of Action
and Functions in Normal Development and Pathology
SO MOLECULAR NEUROBIOLOGY
LA English
DT Review
DE Olfactomedin; Myocilin; Glaucoma; Eye; Brain; Neurogenesis; Olfactomedin
domain-containing protein; Neural crest
ID TRABECULAR MESHWORK CELLS; OPEN-ANGLE GLAUCOMA; ALPHA-LATROTOXIN
RECEPTOR; GENE-EXPRESSION PROFILE; SEQUENCE TAG ANALYSIS; SECRETED
GLYCOPROTEIN; TRANSCRIPTION FACTOR; AQUEOUS-HUMOR; SEA-URCHIN; IN-VIVO
AB A family of olfactomedin domain-containing proteins consists of at least 13 members in mammals. Although the first protein belonging to this family, olfactomedin, was isolated and partially characterized from frog olfactory neuroepithelim almost 20 years ago, the functions of many family members remain elusive. Most of the olfactomedin domain-containing proteins, similar to frog olfactomedin, are secreted glycoproteins that demonstrate specific expression patterns. Other family members are membrane-bound proteins that may serve as receptors. More than half of the olfactomedin domain-containing genes are expressed in neural tissues. Data obtained over the last several years demonstrate that olfactomedin domain-containing proteins play important roles in neurogenesis, neural crest formation, dorsal ventral patterning, cell-cell adhesion, cell cycle regulation, and tumorigenesis and may serve as modulators of critical signaling pathways (Wnt, bone morphogenic protein). Mutations in two genes encoding myocilin and olfactomedin 2 were implicated in glaucoma, and a growing number of evidence indicate that other genes belonging to the family of olfactomedin domain-containing proteins may contribute to different human disorders including psychiatric disorders. In this review, we summarize recent advances in understanding the possible roles of these proteins with special emphasis on the proteins that are preferentially expressed and function in neural tissues.
C1 [Tomarev, Stanislav I.; Nakaya, Naoki] NEI, Sect Mol Mech Glaucoma, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Tomarev, SI (reprint author), NEI, Sect Mol Mech Glaucoma, Mol & Dev Biol Lab, NIH, 5635 Fishers Lane,Room 1124, Bethesda, MD 20892 USA.
EM tomarevs@nei.nih.gov
FU Intramural NIH HHS [Z01 EY000318-10]
NR 124
TC 68
Z9 68
U1 0
U2 5
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0893-7648
J9 MOL NEUROBIOL
JI Mol. Neurobiol.
PD OCT
PY 2009
VL 40
IS 2
BP 122
EP 138
DI 10.1007/s12035-009-8076-x
PG 17
WC Neurosciences
SC Neurosciences & Neurology
GA 490VC
UT WOS:000269534500003
PM 19554483
ER
PT J
AU Huang, XP
Setola, V
Yadav, PN
Allen, JA
Rogan, SC
Hanson, BJ
Revankar, C
Robers, M
Doucette, C
Roth, BL
AF Huang, Xi-Ping
Setola, Vincent
Yadav, Prem N.
Allen, John A.
Rogan, Sarah C.
Hanson, Bonnie J.
Revankar, Chetana
Robers, Matt
Doucette, Chris
Roth, Bryan L.
TI Parallel Functional Activity Profiling Reveals Valvulopathogens Are
Potent 5-Hydroxytryptamine(2B) Receptor Agonists: Implications for Drug
Safety Assessment
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID VALVULAR HEART-DISEASE; SPRAGUE-DAWLEY RATS; DOPAMINE AGONISTS; 5-HT2B
RECEPTORS; IN-VITRO; FENFLURAMINE; SEROTONIN; VALVES
AB Drug-induced valvular heart disease (VHD) is a serious side effect of a few medications, including some that are on the market. Pharmacological studies of VHD-associated medications (e.g., fenfluramine, pergolide, methysergide, and cabergoline) have revealed that they and/or their metabolites are potent 5-hydroxytryptamine(2B) (5-HT2B) receptor agonists. We have shown that activation of 5-HT2B receptors on human heart valve interstitial cells in vitro induces a proliferative response reminiscent of the fibrosis that typifies VHD. To identify current or future drugs that might induce VHD, we screened approximately 2200 U.S. Food and Drug Administration (FDA)-approved or investigational medications to identify 5-HT2B receptor agonists, using calcium-based high-throughput screening. Of these 2200 compounds, 27 were 5-HT2B receptor agonists (hits); 14 of these had previously been identified as 5-HT2B receptor agonists, including seven bona fide valvulopathogens. Six of the hits (guanfacine, quinidine, xylometazoline, oxymetazoline, fenoldopam, and ropinirole) are approved medications. Twenty-three of the hits were then "functionally profiled" (i.e., assayed in parallel for 5-HT2B receptor agonism using multiple readouts to test for functional selectivity). In these assays, the known valvulopathogens were efficacious at concentrations as low as 30 nM, whereas the other compounds were less so. Hierarchical clustering analysis of the pEC(50) data revealed that ropinirole (which is not associated with valvulopathy) was clearly segregated from known valvulopathogens. Taken together, our data demonstrate that patterns of 5-HT2B receptor functional selectivity might be useful for identifying compounds likely to induce valvular heart disease.
C1 [Huang, Xi-Ping; Setola, Vincent; Yadav, Prem N.; Allen, John A.; Rogan, Sarah C.; Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27514 USA.
[Roth, Bryan L.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27514 USA.
[Roth, Bryan L.] Univ N Carolina, Sch Med, Program Neurosci, Chapel Hill, NC 27514 USA.
[Roth, Bryan L.] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA.
[Roth, Bryan L.] Univ N Carolina, Sch Med, Carolina Integrated Chem Biol & Drug Discovery Ct, Chapel Hill, NC 27514 USA.
[Allen, John A.; Roth, Bryan L.] Univ N Carolina, Sch Med, Ctr Neurodev Disorders, Chapel Hill, NC 27514 USA.
[Roth, Bryan L.] Univ N Carolina, Sch Med, Sch Pharm, Dept Med Chem & Nat Prod, Chapel Hill, NC 27514 USA.
[Huang, Xi-Ping; Setola, Vincent; Roth, Bryan L.] NIMH, Psychoact Drug Screening Program, Bethesda, MD USA.
[Hanson, Bonnie J.; Revankar, Chetana; Robers, Matt; Doucette, Chris] Invitrogen Corp, Madison, WI USA.
RP Roth, BL (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, 120 Mason Farm Rd, Chapel Hill, NC 27514 USA.
EM bryan_roth@med.unc.edu
RI Roth, Bryan/F-3928-2010; Allen, John/D-6141-2011
FU National Institutes of Health National Institute of Mental Health
[R01-MH61887, U19-MH82441, HHSN-271-2008-00025]; National Institutes of
Health National Institute of Child Health & Human Development
[T32-HD040127]; University of North Carolina Neurodevelopmental
Disorders Research Center; University of North Carolina Medical
Scientist Training Program
FX This work was supported in part by the National Institutes of Health
National Institute of Mental Health [Grants R01-MH61887, U19-MH82441,
HHSN-271-2008-00025]; National Institutes of Health National Institute
of Child Health & Human Development [Grant T32-HD040127]; the University
of North Carolina Neurodevelopmental Disorders Research Center; and the
University of North Carolina Medical Scientist Training Program.
NR 23
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U1 1
U2 4
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD OCT
PY 2009
VL 76
IS 4
BP 710
EP 722
DI 10.1124/mol.109.058057
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 497AZ
UT WOS:000270027000004
PM 19570945
ER
PT J
AU Kessl, JJ
Eidahl, JO
Shkriabai, N
Zhao, ZJ
Mckee, CJ
Hess, S
Burke, TR
Kvaratskhelia, M
AF Kessl, Jacques J.
Eidahl, Jocelyn O.
Shkriabai, Nikolozi
Zhao, Zhuojun
McKee, Christopher J.
Hess, Sonja
Burke, Terrence R., Jr.
Kvaratskhelia, Mamuka
TI An Allosteric Mechanism for Inhibiting HIV-1 Integrase with a Small
Molecule
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID VIRAL-DNA BINDING; L-CHICORIC ACID; CRYSTAL-STRUCTURE;
COMPLEX-FORMATION; CATALYTIC DOMAIN; COACTIVATOR P75; HUMAN-CELLS;
IN-VITRO; LEDGF/P75; IDENTIFICATION
AB HIV-1 integrase (IN) is a validated target for developing antiretroviral inhibitors. Using affinity acetylation and mass spectrometric (MS) analysis, we previously identified a tetra-acetylated inhibitor (2E)-3-[3,4-bis(acetoxy)phenyl]-2-propenoate-N-[(2E)3-[3,4-bis(acetyloxy) phenyl]-1-oxo-2-propenyl]-L-serine methyl ester; compound 1] that selectively modified Lys173 at the IN dimer interface. Here we extend our efforts to dissect the mechanism of inhibition and structural features that are important for the selective binding of compound 1. Using a subunit exchange assay, we found that the inhibitor strongly modulates dynamic interactions between IN subunits. Restricting such interactions does not directly interfere with IN binding to DNA substrates or cellular cofactor lens epithelium-derived growth factor, but it compromises the formation of the fully functional nucleoprotein complex. Studies comparing compound 1 with a structurally related IN inhibitor, the tetra-acetylated-chicoric acid derivative (2R, 3R)-2,3-bis[[(2E)-3-[3,4-bis(acetyloxy)phenyl]1-oxo-2-propen-1-yl] oxy]-butanedioic acid (compound 2), indicated striking mechanistic differences between these agents. The structures of the two inhibitors differ only in their central linker regions, with compounds 1 and 2 containing a single methyl ester group and two carboxylic acids, respectively. MS experiments highlighted the importance of these structural differences for selective binding of compound 1 to the IN dimer interface. Moreover, molecular modeling of compound 1 complexed to IN identified a potential inhibitor binding cavity and provided structural clues regarding a possible role of the central methyl ester group in establishing an extensive hydrogen bonding network with both interacting subunits. The proposed mechanism of action and binding site for the small-molecule inhibitor identified in the present study provide an attractive venue for developing allosteric inhibitors of HIV-1 IN.
C1 [Kessl, Jacques J.; Eidahl, Jocelyn O.; Shkriabai, Nikolozi; Zhao, Zhuojun; McKee, Christopher J.; Kvaratskhelia, Mamuka] Ohio State Univ, Coll Pharm, Ctr Retrovirus Res, Columbus, OH 43210 USA.
[Kessl, Jacques J.; Eidahl, Jocelyn O.; Shkriabai, Nikolozi; Zhao, Zhuojun; McKee, Christopher J.; Kvaratskhelia, Mamuka] Ohio State Univ, Coll Pharm, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Hess, Sonja] CALTECH, Beckman Inst, Proteome Explorat Lab, Pasadena, CA 91125 USA.
[Burke, Terrence R., Jr.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA.
RP Kvaratskhelia, M (reprint author), Ohio State Univ, Coll Pharm, Ctr Retrovirus Res, 500 W 12th Ave,Room 238,LM Pk Hall, Columbus, OH 43210 USA.
EM kvaratskhelia.1@osu.edu
RI Hess, Sonja/K-4842-2013; Burke, Terrence/N-2601-2014; Kessl,
Jacques/J-6073-2015
OI Hess, Sonja/0000-0002-5904-9816;
FU National Institutes of Health National Institute of Allergy and
Infectious Diseases [AI062520, AI077341]; Intramural Research Programs
of the National Institutes of Health Center for Cancer Research;
National Institutes of Health National Cancer Institute; National
Institutes of Health National Institute of Diabetes and Digestive and
Kidney Diseases
FX This work was supported by National Institutes of Health National
Institute of Allergy and Infectious Diseases [Grants AI062520,
AI077341]; and by the Intramural Research Programs of the National
Institutes of Health Center for Cancer Research, the National Institutes
of Health National Cancer Institute, and the National Institutes of
Health National Institute of Diabetes and Digestive and Kidney Diseases.
NR 39
TC 37
Z9 37
U1 0
U2 1
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD OCT
PY 2009
VL 76
IS 4
BP 824
EP 832
DI 10.1124/mol.109.058883
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 497AZ
UT WOS:000270027000014
PM 19638533
ER
PT J
AU Federhen, S
Hotton, C
Mizrachi, I
AF Federhen, Scott
Hotton, Carol
Mizrachi, Ilene
TI Comments on the paper by Pleijel et al. (2008): Vouching for GenBank
SO MOLECULAR PHYLOGENETICS AND EVOLUTION
LA English
DT Letter
C1 [Federhen, Scott; Hotton, Carol; Mizrachi, Ilene] Natl Lib Med, NCBI, NIH, Bethesda, MD USA.
RP Federhen, S (reprint author), Natl Lib Med, NCBI, NIH, 8600 Rockville Pike, Bethesda, MD USA.
EM federhen@ncbi.nlm.nih.gov
FU Intramural NIH HHS [Z99 LM999999]
NR 0
TC 4
Z9 4
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1055-7903
J9 MOL PHYLOGENET EVOL
JI Mol. Phylogenet. Evol.
PD OCT
PY 2009
VL 53
IS 1
BP 357
EP 358
DI 10.1016/j.ympev.2009.04.016
PG 2
WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics &
Heredity
GA 484SN
UT WOS:000269067900035
PM 19410006
ER
PT J
AU Meyer-Lindenberg, A
Kolachana, B
Gold, B
Olsh, A
Nicodemus, KK
Mattay, V
Dean, M
Weinberger, DR
AF Meyer-Lindenberg, A.
Kolachana, B.
Gold, B.
Olsh, A.
Nicodemus, K. K.
Mattay, V.
Dean, M.
Weinberger, D. R.
TI Genetic variants in AVPR1A linked to autism predict amygdala activation
and personality traits in healthy humans
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE vasopressin; AVPR1A; fMRI; neuroimaging; autism
ID ANXIETY-RELATED BEHAVIOR; INDIVIDUAL-DIFFERENCES; SOCIAL COMMUNICATION;
SUSCEPTIBILITY GENE; NEURAL CIRCUITRY; GAZE-FIXATION; HUMAN BRAIN;
VASOPRESSIN; OXYTOCIN; ASSOCIATION
AB In mammals, the neuropeptide vasopressin is a key molecule for complex emotional and social behaviours. Two microsatellite polymorphisms, RS1 and RS3, near the promoter of AVPR1A, encoding the receptor subtype most heavily implicated in behaviour regulation, have been linked to autism and behavioural traits. However, the impact of these variants on human brain function is unknown. Here we show that human amygdala function is strongly associated with genetic variation in AVPR1A. Using an imaging genetics approach in a sample of 121 volunteers studied with an emotional face-matching paradigm, we found that differential activation of amygdala is observed in carriers of risk alleles for RS3 and RS1. Alleles in RS1 previously reported to be significantly over- and undertransmitted to autistic probands showed opposing effects on amygdala activation. Furthermore, we show functional difference in human brain between short and long repeat lengths that mirror findings recently obtained in a corresponding variant in voles. Our results indicate a neural mechanism mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder. Molecular Psychiatry (2009) 14, 968-975; doi:10.1038/mp.2008.54; published online 20 May 2008
C1 [Weinberger, D. R.] NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH,DHHS, Bethesda, MD 20892 USA.
[Meyer-Lindenberg, A.] NIMH, Unit Syst Neurosci Psychiat, NIH, DHHS, Bethesda, MD 20892 USA.
[Meyer-Lindenberg, A.; Mattay, V.] NIMH, Neuroimaging Core Facil, NIH, DHHS, Bethesda, MD 20892 USA.
[Meyer-Lindenberg, A.] Cent Inst Mental Hlth, D-6800 Mannheim, Germany.
[Gold, B.; Olsh, A.; Dean, M.] NCI Frederick, Human Genet Sect, Lab Genom Divers, Ctr Canc Res, Frederick, MD USA.
RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Intramural Res Program,NIH,DHHS, Room 4S-235,MSC1379,10 Ctr Dr, Bethesda, MD 20892 USA.
EM weinberd@intra.nimh.nih.gov
RI Dean, Michael/G-8172-2012;
OI Dean, Michael/0000-0003-2234-0631; Meyer-Lindenberg,
Andreas/0000-0001-5619-1123
FU NIH; NIMH; NCI
FX This work was supported by the Intramural Research Program of the NIH,
NIMH and NCI. We thank Dr Andrew Singleton for his technical advice
resolving the microsatellites.
NR 52
TC 86
Z9 88
U1 2
U2 17
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD OCT
PY 2009
VL 14
IS 10
BP 968
EP 975
DI 10.1038/mp.2008.54
PG 8
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 500UM
UT WOS:000270331000007
PM 18490926
ER
PT J
AU Thomas, JD
Majumdar, S
Sloan, KB
AF Thomas, Joshua Denver
Majumdar, Susruta
Sloan, Kenneth Berry
TI Soft Alkyl Ether Prodrugs of a Model Phenolic Drug: The Effect of
Incorporation of Ethyleneoxy Groups on Transdermal Delivery
SO MOLECULES
LA English
DT Article
DE topical delivery; Roberts-Sloan equation; water solubility; lipid
solubility; prodrugs
ID IN-VITRO EVALUATION; TOPICAL DELIVERY; HUMAN SKIN; WATER SOLUBILITY;
DERMAL PRODRUGS; ACETAMINOPHEN; 6-MERCAPTOPURINE; NALTREXONE; DIFFUSION;
ESTERS
AB Two different types of soft alkyl ether prodrugs incorporating ethyleneoxy groups into the promoiety have been synthesized for a model phenol (acetaminophen, APAP): alkyloxycarbonyloxymethyl type (AOCOM) and N-alkyl-N-alkyloxycarbonyl-aminomethyl type (NANAOCAM). The solubilities in isopropyl myristate, S(IPM), and water, S(AQ), partition coefficients between IPM and pH 4.0 buffer, K(IPM:4.0), and the delivery of total species containing APAP through hairless mouse skin from IPM, J(MMIPM), have been measured for the prodrugs. The J(MMIPM) values were accurately predicted by the Roberts-Sloan (RS) equation. Only modest increases in J(MMIPM) were realized (about 1.4 times) by each type. The only prodrug that was more water soluble and more lipid soluble than APAP did not improve J(MMIPM) of APAP. This result may be due to the strong association of water molecules with the ethyleneoxy groups, and especially the triethyleneoxy derivative, which dramatically increases the molecular weight and depresses J(MMIPM).
C1 [Sloan, Kenneth Berry] Univ Florida, Dept Med Chem, Gainesville, FL 32610 USA.
[Majumdar, Susruta] Mem Sloan Kettering Canc Ctr, Lab Mol Pharmacol & Chem, New York, NY 10021 USA.
[Thomas, Joshua Denver] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA.
RP Sloan, KB (reprint author), Univ Florida, Dept Med Chem, POB 100485, Gainesville, FL 32610 USA.
EM sloan@cop.ufl.edu
FU NCI NIH HHS [P30 CA008748]
NR 27
TC 9
Z9 9
U1 0
U2 9
PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI
PI BASEL
PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND
SN 1420-3049
J9 MOLECULES
JI Molecules
PD OCT
PY 2009
VL 14
IS 10
BP 4231
EP 4245
DI 10.3390/molecules14104231
PG 15
WC Chemistry, Organic
SC Chemistry
GA 512QP
UT WOS:000271265300029
PM 19924060
ER
PT J
AU Bielekova, B
Richert, N
Howard, T
Packer, AN
Blevins, G
Ohayon, J
McFarland, HF
Sturzebecher, CS
Martin, R
AF Bielekova, Bibiana
Richert, Nancy
Howard, Thomas
Packer, Amy N.
Blevins, Gregg
Ohayon, Joan
McFarland, Henry F.
Stuerzebecher, Claus-Steffen
Martin, Roland
TI Treatment with the phosphodiesterase type-4 inhibitor rolipram fails to
inhibit blood-brain barrier disruption in multiple sclerosis
SO MULTIPLE SCLEROSIS
LA English
DT Article
DE multiple sclerosis; blood-brain barrier; rolipram; phosphodiesterase-4;
autoimmunity; clinical trial
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN;
REGULATORY T-CELLS; INTERFERON-BETA; INDUCED ARTHRITIS; OUTCOME MEASURE;
CLINICAL-TRIAL; LEWIS RATS; IV; DISEASE
AB Rolipram, a prototypic phosphodiesterase-4 inhibitor, is highly effective in suppressing Th1 autoimmunity in multiple animal models, including experimental autoimmune encephalomyelitis. In addition, rolipram has been extensively studied as a potential neuroprotective agent. Based on its anti-inflammatory activity, we tested the efficacy of rolipram in suppressing inflammatory disease activity in multiple sclerosis in a proof-of-principle phase I/II open-label clinical trial. Enrolled MS patients were evaluated by monthly MRI and clinical examinations during 3 months (four MRIs) of pretreatment baseline and 8 months of rolipram therapy. The primary outcome was a change in contrast-enhanced lesions between baseline and the last 4 months of rolipram therapy. Previously defined biomarkers of rolipram-mediated immunomodulation were evaluated during the study. The trial was stopped prematurely because the drug was poorly tolerated and because of safety concerns: we observed an increase, rather than decrease, in the brain inflammatory activity measured by contrast-enhanced lesions on brain MRI. At the administered doses rolipram was active in vivo as documented by immunological assays. We conclude that the reasons underlying the discrepancy between the therapeutic efficacy of rolipram in experimental autoimmune encephalomyelitis versus multiple sclerosis are at present not clear.
C1 [Martin, Roland] Univ Clin Eppendorf, Inst Neuroimmunol & Clin MS Res, Ctr Mol Neurobiol Hamburg, Univ Med Ctr Eppendorf, D-20251 Hamburg, Germany.
[Blevins, Gregg] Univ Alberta, Div Neurol, Edmonton, AB T6G 2G3, Canada.
[Stuerzebecher, Claus-Steffen] Grunenthal, D-52078 Aachen, Germany.
[Bielekova, Bibiana; Richert, Nancy; Howard, Thomas; Packer, Amy N.; Blevins, Gregg; Ohayon, Joan; McFarland, Henry F.; Martin, Roland] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
RP Martin, R (reprint author), Univ Clin Eppendorf, Inst Neuroimmunol & Clin MS Res, Ctr Mol Neurobiol Hamburg, Univ Med Ctr Eppendorf, Falkenried 94, D-20251 Hamburg, Germany.
EM roland.martin@zmnh.uni-hamburg.de
FU NINDS/NIH
FX Our thanks go to Helen Griffith and Angela Kokkinis for expert nursing
support and to Azita Kashani for help with processing of apheresis
samples. The clinical trial was supported by the Intramural research
program of the NINDS/NIH, in part through a Bench-to-Bedside intramural
research grant to R Martin. Rolipram raw material was provided to the
NINDS investigators by Schering AG, Germany, under Collaborative
Research and Development Agreement (CRADA).
NR 38
TC 17
Z9 17
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
J9 MULT SCLER
JI Mult. Scler.
PD OCT
PY 2009
VL 15
IS 10
BP 1206
EP 1214
DI 10.1177/1352458509345903
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 508AV
UT WOS:000270900100009
PM 19776093
ER
PT J
AU Dwivedi, D
Johri, BN
Ineichen, K
Wray, V
Wiemken, A
AF Dwivedi, Deepti
Johri, Bhavdish N.
Ineichen, Kurt
Wray, Victor
Wiemken, Andres
TI Impact of antifungals producing rhizobacteria on the performance of
Vigna radiata in the presence of arbuscular mycorrhizal fungi
SO MYCORRHIZA
LA English
DT Article
DE Antifungal-producing bacteria; PGPR; Mycorrhiza helper bacteria; AMF
ID PSEUDOMONAS-FLUORESCENS CHA0; BIOLOGICAL-CONTROL; PLANT-GROWTH;
METABOLITE 2,4-DIACETYLPHLOROGLUCINOL; ANTIBIOTIC PRODUCTION; ROCK
PHOSPHATE; MAIZE PLANTS; SOIL; RHIZOSPHERE; BACTERIA
AB Plant growth-promoting rhizobacteria (PGPR) that produce antifungal metabolites are potential threats for the arbuscular mycorrhizal (AM) fungi known for their beneficial symbiosis with plants that is crucially important for low-input sustainable agriculture. To address this issue, we used a compartmented container system where test plants, Vigna radiata, could only reach a separate nutrient-rich compartment indirectly via the hyphae of AM fungi associated with their roots. In this system, where plants depended on nutrient uptake via AM symbiosis, we explored the impact of various PGPR. Plants were inoculated with or without a consortium of four species of AM fungi (Glomus coronatum, Glomus etunicatum, Glomus constrictum, and Glomus intraradices), and one or more of the following PGPR strains: phenazine producing (P(+)) and phenazine-less mutant (P(-)), diacetylphloroglucinol (DAPG) producing (G(+)) and DAPG-less mutant (G(-)) strains of Pseudomonas fluorescens, and an unknown antifungal metabolite-producing Alcaligenes faecalis strain, SLHRE425 (D). PGPR exerted only a small if any effect on the performance of AM symbiosis. G(+) enhanced AM root colonization and had positive effects on shoot growth and nitrogen content when added alone, but not in combination with P(+). D negatively influenced AM root colonization, but did not affect nutrient acquisition. Principal component analysis of all treatments indicated correlation between root weight, shoot weight, and nutrient uptake by AM fungus. The results indicate that antifungal metabolites producing PGPR do not necessarily interfere with AM symbiosis and may even promote it thus carefully chosen combinations of such bioinoculants could lead to better plant growth.
C1 [Dwivedi, Deepti; Johri, Bhavdish N.] GB Pant Univ Agr & Technol, Dept Microbiol, Pantnagar 263145, Uttar Pradesh, India.
[Dwivedi, Deepti] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
[Dwivedi, Deepti; Ineichen, Kurt; Wiemken, Andres] Univ Basel, Dept Bot, CH-4056 Basel, Switzerland.
[Wray, Victor] Helmholtz Ctr Infect Res, Dept Biol Struct, D-38124 Braunschweig, Germany.
RP Dwivedi, D (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
EM dwivedid@niehs.nih.gov
FU Indo-Swiss Collaboration in Biotechnology (ISCB)
FX The authors would like to thank Alok Adholeya for providing some
mycorrhizal inocula; Genevieve Defago and Linda Thomashow for providing
the Pseudomonas cultures; and David Roesti, Feng He, and Bharani Kumar
for statistical analysis and interpretation. We thank Roel M. Schaaper,
Rajesh Kasiviswanathan, and Greg Stuart for critical comments on the
manuscript. This work was funded by Indo-Swiss Collaboration in
Biotechnology (ISCB).
NR 66
TC 8
Z9 8
U1 3
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0940-6360
J9 MYCORRHIZA
JI Mycorrhiza
PD OCT
PY 2009
VL 19
IS 8
BP 559
EP 570
DI 10.1007/s00572-009-0253-2
PG 12
WC Mycology
SC Mycology
GA 495TX
UT WOS:000269919000005
PM 19458967
ER
PT J
AU Bhirde, AA
Sousa, AA
Patel, V
Azari, AA
Gutkind, JS
Leapman, RD
Rusling, JF
AF Bhirde, Ashwin A.
Sousa, Alioscka A.
Patel, Vyomesh
Azari, Afrouz A.
Gutkind, J. Silvio
Leapman, Richard D.
Rusling, James F.
TI Imaging the distribution of individual platinum-based anticancer drug
molecules attached to single-wall carbon nanotubes
SO NANOMEDICINE
LA English
DT Article
DE cisplatin; drug delivery; EGF; squamous cell carcinoma; scanning
transmission electron microscopic tomography; scanning transmission
electron microscopy; single-wall carbon nanotube
ID TRANSMISSION ELECTRON-MICROSCOPE; THERAPEUTIC APPLICATIONS;
CANCER-THERAPY; DELIVERY; NANOPARTICLES; STEM; TRANSPORTERS; TOMOGRAPHY;
SYSTEM; CELLS
AB Aims: To image the distribution of drug molecules attached to single-wall carbon nanotubes (SWNTs). Materials & methods: Herein we report the use of scanning transmission electron microscopy (STEM) for atomic scale visualization and cluantitation of single platinum-based drug molecules attached to SWNTs designed for targeted drug delivery. Fourier transform infrared spectroscopy and energy-dispersive x-ray spectroscopy were used for characterization of the SWNT drug conjugates. Results: Z-contrast STEM imaging enabled visualization of the first-line anticancer drug cisplatin on the nanotubes at single molecule level. The identity and presence of cisplatin on the nanotubes was confirmed using energy-dispersive x-ray spectroscopy and Fourier transform infrared spectroscopy. STEM tomography was also used to provide additional insights concerning the nanotube conjugates. Finally, our observations provide a rationale for exploring the use of SWNT bioconjugates to selectively target and kill squamous cancer cells. Conclusion: Z-contrast STEM imaging provides a means for direct visualization of heavy metal containing molecules (i.e., cisplatin) attached to surfaces of carbon SWNTs along with distribution and quantitation.
C1 [Sousa, Alioscka A.; Azari, Afrouz A.; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA.
[Bhirde, Ashwin A.; Rusling, James F.] Univ Connecticut, Storrs, CT 06269 USA.
[Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Rusling, James F.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06032 USA.
RP Leapman, RD (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, 13 South Dr,Bldg 13,Room 3N17, Bethesda, MD 20892 USA.
EM leapmanr@mail.nih.gov
RI Gutkind, J. Silvio/A-1053-2009
FU National Institute of Dental and Craniofacial Research; National
Institute of Biomedical Imaging and Bioengineering; NIH; NIEHS/NIH
[ES013557]
FX This research was supported by the Intramural Programs of the National
Institute of Dental and Craniofacial Research, the National Institute of
Biomedical Imaging and Bioengineering, NIH and in part by PHS grant
ES013557 from NIEHS/NIH to University CT The authors have no other
relevant affiliations or financial involvement with any organization or
entity with a financial interest in or financial conflict with the
subject matter or materials discussed in the manuscript apart from those
disclosed.
NR 39
TC 10
Z9 10
U1 2
U2 8
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1743-5889
J9 NANOMEDICINE-UK
JI Nanomedicine
PD OCT
PY 2009
VL 4
IS 7
BP 763
EP 772
DI 10.2217/NNM.09.56
PG 10
WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology
SC Biotechnology & Applied Microbiology; Science & Technology - Other
Topics
GA 516MZ
UT WOS:000271547900012
PM 19839812
ER
PT J
AU Klamt, F
Zdanov, S
Levine, RL
Pariser, A
Zhang, YQ
Zhang, BL
Yu, LR
Veenstra, TD
Shacter, E
AF Klamt, Fabio
Zdanov, Stephanie
Levine, Rodney L.
Pariser, Ashley
Zhang, Yaqin
Zhang, Baolin
Yu, Li-Rong
Veenstra, Timothy D.
Shacter, Emily
TI Oxidant-induced apoptosis is mediated by oxidation of the
actin-regulatory protein cofilin
SO NATURE CELL BIOLOGY
LA English
DT Article
ID HYPOCHLOROUS ACID; CELL-DEATH; PERMEABILITY TRANSITION;
HYDROGEN-PEROXIDE; MITOCHONDRIAL PERMEABILITY; LYMPHOMA-CELLS; STRESS;
CYSTEINE; CANCER; CHLORAMINES
AB Physiological oxidants that are generated by activated phagocytes comprise the main source of oxidative stress during inflammation(1,2). Oxidants such as taurine chloramine (TnCl) and hydrogen peroxide (H(2)O(2)) can damage proteins and induce apoptosis, but the role of specific protein oxidation in this process has not been defined. We found that the actin-binding protein cofilin is a key target of oxidation. When oxidation of this single regulatory protein is prevented, oxidant-induced apoptosis is inhibited. Oxidation of cofilin causes it to lose its affinity for actin and to translocate to the mitochondria, where it induces swelling and cytochrome c release by mediating opening of the permeability transition pore (PTP). This occurs independently of Bax activation and requires both oxidation of cofilin Cys residues and dephosphorylation at Ser 3. Knockdown of endogenous cofilin using targeted siRNA inhibits oxidant-induced apoptosis, which is restored by re-expression of wild-type cofilin but not by cofilin containing Cys to Ala mutations. Exposure of cofilin to TnCl results in intramolecular disulphide bonding and oxidation of Met residues to Met sulphoxide, but only Cys oxidation causes cofilin to induce mitochondrial damage.
C1 [Klamt, Fabio; Zdanov, Stephanie; Pariser, Ashley; Zhang, Yaqin; Zhang, Baolin; Shacter, Emily] US FDA, Biochem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
[Klamt, Fabio] Univ Fed Rio Grande do Sul, Ctr Oxidat Stress Res, Dept Biochem, ICBS, BR-90035003 Porto Alegre, RS, Brazil.
[Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
[Yu, Li-Rong] US FDA, Ctr Prote, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Yu, Li-Rong; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Shacter, E (reprint author), US FDA, Biochem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
EM emily.shacter@fda.hhs.gov
RI Zdanov, Stephanie/G-2524-2012; Levine, Rodney/D-9885-2011
FU Intramural NIH HHS [Z01 HL000225-31]; NCI NIH HHS [N01-CO-12400,
N01CO12400]
NR 38
TC 114
Z9 115
U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD OCT
PY 2009
VL 11
IS 10
BP 1241
EP U193
DI 10.1038/ncb1968
PG 18
WC Cell Biology
SC Cell Biology
GA 501KZ
UT WOS:000270382000014
PM 19734890
ER
PT J
AU Pegoraro, G
Kubben, N
Wickert, U
Gohler, H
Hoffmann, K
Misteli, T
AF Pegoraro, Gianluca
Kubben, Nard
Wickert, Ute
Goehler, Heike
Hoffmann, Katrin
Misteli, Tom
TI Ageing-related chromatin defects through loss of the NURD complex
SO NATURE CELL BIOLOGY
LA English
DT Article
ID HUTCHINSON-GILFORD-PROGERIA; PROTEIN-INTERACTION NETWORK; HUMAN-CELLS;
S-PHASE; METHYLATION; TRANSCRIPTION; STABILITY; ENHANCER; DISEASE;
GENOME
AB Physiological and premature ageing are characterized by multiple defects in chromatin structure and accumulation of persistent DNA damage. Here we identify the NURD chromatin remodelling complex as a key modulator of these ageing-associated chromatin defects. We demonstrate loss of several NURD components during premature and normal ageing and we find an ageing-associated reduction in HDAC1 activity. Silencing of individual NURD subunits recapitulated chromatin defects associated with ageing and we provide evidence that structural chromatin defects precede DNA damage accumulation. These results outline a molecular mechanism for chromatin defects during ageing.
C1 [Pegoraro, Gianluca; Kubben, Nard; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Kubben, Nard] Maastricht Univ, Dept Expt & Mol Cardiol, Cardiovasc Res Inst Maastricht, Maastricht, Netherlands.
[Wickert, Ute] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany.
[Goehler, Heike] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
[Hoffmann, Katrin] Humboldt Univ, Inst Med Genet, Charite Berlin, D-13353 Berlin, Germany.
[Hoffmann, Katrin] Max Planck Inst Mol Genet Dev & Dis, D-14195 Berlin, Germany.
RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
OI Pegoraro, Gianluca/0000-0003-2843-9464
FU Telethon Italy Foundation; Italian Association for Cancer Research
(AIRC); Deutsche Forschungsgemeinschaft (DFG) [A4, Z2]; NIH; NCI; Center
for Cancer Research
FX We thank P. Scaffidi and A. Marcello for critical reading of the
manuscript, and P. Scaffidi for sharing data and providing numerous
suggestions during the course of the experiments. Fluorescence imaging
was performed with the assistance of T. Karpova at the NCI Fluorescence
Imaging Microscopy Facility. FACS cell cycle acquisition and analysis
was performed with the help of K. McKinnon at the NCI FACS facility. We
also thank T. Jenuwein, B. Stillman and T. Dittmer for providing
reagents. We thank H. Herrmann and E. Wanker for their support with the
Y2H screening and subsequent confirmation studies. G. P. was partly
supported by postdoctoral fellowships from the Telethon Italy Foundation
and the Italian Association for Cancer Research (AIRC). K. H. and H. G.
were supported by The Deutsche Forschungsgemeinschaft (DFG, SFB 577,
projects A4 and Z2). This work was supported by an Intramural Research
Program of the NIH, NCI, Center for Cancer Research.
NR 26
TC 131
Z9 134
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD OCT
PY 2009
VL 11
IS 10
BP 1261
EP U251
DI 10.1038/ncb1971
PG 18
WC Cell Biology
SC Cell Biology
GA 501KZ
UT WOS:000270382000017
PM 19734887
ER
PT J
AU Yuan, J
Johnson, RL
Huang, RL
Wichterman, J
Jiang, HY
Hayton, K
Fidock, DA
Wellems, TE
Inglese, J
Austin, CP
Su, XZ
AF Yuan, Jing
Johnson, Ronald L.
Huang, Ruili
Wichterman, Jennifer
Jiang, Hongying
Hayton, Karen
Fidock, David A.
Wellems, Thomas E.
Inglese, James
Austin, Christopher P.
Su, Xin-zhuan
TI Genetic mapping of targets mediating differential chemical phenotypes in
Plasmodium falciparum
SO NATURE CHEMICAL BIOLOGY
LA English
DT Article
ID CHLOROQUINE RESISTANCE; MALARIA PARASITES; DRUG-RESISTANCE; FOLIC-ACID;
GENOME; IDENTIFICATION; TRIAMTERENE; ANTIMALARIALS; PYRIMETHAMINE;
SENSITIVITY
AB Studies of gene function and molecular mechanisms in Plasmodium falciparum are hampered by difficulties in characterizing and measuring phenotypic differences between individual parasites. We screened seven parasite lines for differences in responses to 1,279 bioactive chemicals. Hundreds of compounds were active in inhibiting parasite growth; 607 differential chemical phenotypes, defined as pairwise IC(50) differences of fivefold or more between parasite lines, were cataloged. We mapped major determinants for three differential chemical phenotypes between the parents of a genetic cross, and we identified target genes by fine mapping and testing the responses of parasites in which candidate genes were genetically replaced with mutant alleles. Differential sensitivity to dihydroergotamine methanesulfonate (1), a serotonin receptor antagonist, was mapped to a gene encoding the homolog of human P-glycoprotein (PfPgh-1). This study identifies new leads for antimalarial drugs and demonstrates the utility of a high-throughput chemical genomic strategy for studying malaria traits.
C1 [Yuan, Jing; Jiang, Hongying; Hayton, Karen; Wellems, Thomas E.; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Johnson, Ronald L.; Huang, Ruili; Wichterman, Jennifer; Inglese, James; Austin, Christopher P.] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Fidock, David A.] Columbia Univ, Dept Microbiol & Immunol, New York, NY USA.
RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM xsu@niaid.nih.gov
OI Fidock, David/0000-0001-6753-8938; Su, Xinzhuan/0000-0003-3246-3248
FU Divisions of Intramural Research at the National Institute of Allergy
and Infectious Diseases; National Human Genome Research Institute; NIH
FX This work was supported by the Divisions of Intramural Research at the
National Institute of Allergy and Infectious Diseases, and by the
National Human Genome Research Institute and the NIH Roadmap for Medical
Research, all at the US National Institutes of Health. We thank J. Sa,
J. Mu, L. Jiang, D. Raj and M. J. Lopez Barragan for help in drug
assays; P. Shinn and D. VanLeer for compound management; D. Leja for
assistance in artworks and NIAID intramural editor B. R. Marshall for
assistance.
NR 45
TC 39
Z9 39
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD OCT
PY 2009
VL 5
IS 10
BP 765
EP 771
DI 10.1038/nchembio.215
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 497EV
UT WOS:000270039900015
PM 19734910
ER
PT J
AU O'Brien, TR
AF O'Brien, Thomas R.
TI Interferon-alfa, interferon-lambda and hepatitis C
SO NATURE GENETICS
LA English
DT Editorial Material
ID VIRUS-REPLICATION; INFECTION; PEGINTERFERON; RIBAVIRIN; IL-29
AB Three new studies report genetic variants near IL28B, which encodes interferon-lambda 3 (interleukin 28B), are associated with response to treatment of chronic hepatitis C virus infection with interferon-alfa/ribavirin combination therapy. This renews interest in how interferons suppress viremia and could lead to improved clinical decisions for chronic HCV infection treatment based on individual genotype.
C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP O'Brien, TR (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM obrient@mail.nih.gov
NR 15
TC 53
Z9 54
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD OCT
PY 2009
VL 41
IS 10
BP 1048
EP 1050
DI 10.1038/ng.453
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 500UG
UT WOS:000270330400003
PM 19749756
ER
PT J
AU Yeager, M
Chatterjee, N
Ciampa, J
Jacobs, KB
Gonzalez-Bosquet, J
Hayes, RB
Kraft, P
Wacholder, S
Orr, N
Berndt, S
Yu, K
Hutchinson, A
Wang, ZM
Amundadottir, L
Feigelson, HS
Thun, MJ
Diver, WR
Albanes, D
Virtamo, J
Weinstein, S
Schumacher, FR
Cancel-Tassin, G
Cussenot, O
Valeri, A
Andriole, GL
Crawford, ED
Haiman, CA
Henderson, B
Kolonel, L
Le Marchand, L
Siddiq, A
Riboli, E
Key, TJ
Kaaks, R
Isaacs, W
Isaacs, S
Wiley, KE
Gronberg, H
Wiklund, F
Stattin, P
Xu, JF
Zheng, SL
Sun, JL
Vatten, LJ
Hveem, K
Kumle, M
Tucker, M
Gerhard, DS
Hoover, RN
Fraumeni, JF
Hunter, DJ
Thomas, G
Chanock, SJ
AF Yeager, Meredith
Chatterjee, Nilanjan
Ciampa, Julia
Jacobs, Kevin B.
Gonzalez-Bosquet, Jesus
Hayes, Richard B.
Kraft, Peter
Wacholder, Sholom
Orr, Nick
Berndt, Sonja
Yu, Kai
Hutchinson, Amy
Wang, Zhaoming
Amundadottir, Laufey
Feigelson, Heather Spencer
Thun, Michael J.
Diver, W. Ryan
Albanes, Demetrius
Virtamo, Jarmo
Weinstein, Stephanie
Schumacher, Fredrick R.
Cancel-Tassin, Geraldine
Cussenot, Olivier
Valeri, Antoine
Andriole, Gerald L.
Crawford, E. David
Haiman, Christopher A.
Henderson, Brian
Kolonel, Laurence
Le Marchand, Loic
Siddiq, Afshan
Riboli, Elio
Key, Timothy J.
Kaaks, Rudolf
Isaacs, William
Isaacs, Sarah
Wiley, Kathleen E.
Gronberg, Henrik
Wiklund, Fredrik
Stattin, Par
Xu, Jianfeng
Zheng, S. Lilly
Sun, Jielin
Vatten, Lars J.
Hveem, Kristian
Kumle, Merethe
Tucker, Margaret
Gerhard, Daniela S.
Hoover, Robert N.
Fraumeni, Joseph F., Jr.
Hunter, David J.
Thomas, Gilles
Chanock, Stephen J.
TI Identification of a new prostate cancer susceptibility locus on
chromosome 8q24
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; COLORECTAL-CANCER; MULTIPLE LOCI; RISK;
VARIANT; RANGE; SCAN
AB We report a genome-wide association study in 10,286 cases and 9,135 controls of European ancestry in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. We identify a new association with prostate cancer risk on chromosome 8q24 (rs620861, P = 1.3 x 10(-10), heterozygote OR = 1.17, 95% CI 1.10-1.24; homozygote OR = 1.33, 95% CI 1.21-1.45). This defines a new locus associated with prostate cancer susceptibility on 8q24.
C1 [Yeager, Meredith; Hutchinson, Amy; Wang, Zhaoming] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Yeager, Meredith; Chatterjee, Nilanjan; Ciampa, Julia; Gonzalez-Bosquet, Jesus; Hayes, Richard B.; Wacholder, Sholom; Orr, Nick; Berndt, Sonja; Yu, Kai; Hutchinson, Amy; Wang, Zhaoming; Amundadottir, Laufey; Albanes, Demetrius; Weinstein, Stephanie; Tucker, Margaret; Hoover, Robert N.; Fraumeni, Joseph F., Jr.; Thomas, Gilles; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD USA.
[Kraft, Peter; Schumacher, Fredrick R.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Feigelson, Heather Spencer; Thun, Michael J.; Diver, W. Ryan] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Schumacher, Fredrick R.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Cancel-Tassin, Geraldine; Cussenot, Olivier; Valeri, Antoine] Hop Tenon, CeRePP, AP HP, F-75970 Paris, France.
[Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Crawford, E. David] Univ Colorado Denver & Hlth Sci Ctr, Dept Surg, Denver, CO USA.
[Haiman, Christopher A.; Henderson, Brian] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90033 USA.
[Kolonel, Laurence; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA.
[Siddiq, Afshan; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England.
[Key, Timothy J.] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Kaaks, Rudolf] German Canc Res Ctr, Div Clin Epidemiol, DKFZ, D-6900 Heidelberg, Germany.
[Isaacs, William; Isaacs, Sarah; Wiley, Kathleen E.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Gronberg, Henrik; Wiklund, Fredrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Stattin, Par] Umea Univ, Dept Surg Preoperat Sci Urol & Androl, Umea, Sweden.
[Xu, Jianfeng; Zheng, S. Lilly; Sun, Jielin] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA.
[Vatten, Lars J.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, N-7034 Trondheim, Norway.
[Kumle, Merethe] Univ Tromso, Inst Community Med, Tromso, Norway.
[Gerhard, Daniela S.] NCI, Off Canc Genom, NIH, DHHS, Bethesda, MD 20892 USA.
[Hunter, David J.] Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med, Boston, MA 02115 USA.
RP Yeager, M (reprint author), NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA.
EM yeagerm@mail.nih.gov
RI Tucker, Margaret/B-4297-2015; Albanes, Demetrius/B-9749-2015;
Amundadottir, Laufey/L-7656-2016;
OI Amundadottir, Laufey/0000-0003-1859-8971; Hayes,
Richard/0000-0002-0918-661X; Cancel-Tassin,
Geraldine/0000-0002-9583-6382
FU NCI; National Institutes of Health (NIH) [HHSN261200800001E];
[CA129684]; [CA131338]
FX This project was funded in part using grants CA129684 to J.X. and
CA131338 to S.L.Z. This project was funded in whole or in part with
federal funds from the NCI, National Institutes of Health (NIH), under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services (DHHS), nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government.
NR 15
TC 153
Z9 156
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD OCT
PY 2009
VL 41
IS 10
BP 1055
EP 1057
DI 10.1038/ng.444
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 500UG
UT WOS:000270330400005
PM 19767755
ER
PT J
AU Harold, D
Abraham, R
Hollingworth, P
Sims, R
Gerrish, A
Hamshere, ML
Pahwa, JS
Moskvina, V
Dowzell, K
Williams, A
Jones, N
Thomas, C
Stretton, A
Morgan, AR
Lovestone, S
Powell, J
Proitsi, P
Lupton, MK
Brayne, C
Rubinsztein, DC
Gill, M
Lawlor, B
Lynch, A
Morgan, K
Brown, KS
Passmore, PA
Craig, D
McGuinness, B
Todd, S
Holmes, C
Mann, D
Smith, AD
Love, S
Kehoe, PG
Hardy, J
Mead, S
Fox, N
Rossor, M
Collinge, J
Maier, W
Jessen, F
Schurmann, B
van den Bussche, H
Heuser, I
Kornhuber, J
Wiltfang, J
Dichgans, M
Frolich, L
Hampel, H
Hull, M
Rujescu, D
Goate, AM
Kauwe, JSK
Cruchaga, C
Nowotny, P
Morris, JC
Mayo, K
Sleegers, K
Bettens, K
Engelborghs, S
De Deyn, PP
Van Broeckhoven, C
Livingston, G
Bass, NJ
Gurling, H
McQuillin, A
Gwilliam, R
Deloukas, P
Al-Chalabi, A
Shaw, CE
Tsolaki, M
Singleton, AB
Guerreiro, R
Muhleisen, TW
Nothen, MM
Moebus, S
Jockel, KH
Klopp, N
Wichmann, HE
Carrasquillo, MM
Pankratz, VS
Younkin, SG
Holmans, PA
O'Donovan, M
Owen, MJ
Williams, J
AF Harold, Denise
Abraham, Richard
Hollingworth, Paul
Sims, Rebecca
Gerrish, Amy
Hamshere, Marian L.
Pahwa, Jaspreet Singh
Moskvina, Valentina
Dowzell, Kimberley
Williams, Amy
Jones, Nicola
Thomas, Charlene
Stretton, Alexandra
Morgan, Angharad R.
Lovestone, Simon
Powell, John
Proitsi, Petroula
Lupton, Michelle K.
Brayne, Carol
Rubinsztein, David C.
Gill, Michael
Lawlor, Brian
Lynch, Aoibhinn
Morgan, Kevin
Brown, Kristelle S.
Passmore, Peter A.
Craig, David
McGuinness, Bernadette
Todd, Stephen
Holmes, Clive
Mann, David
Smith, A. David
Love, Seth
Kehoe, Patrick G.
Hardy, John
Mead, Simon
Fox, Nick
Rossor, Martin
Collinge, John
Maier, Wolfgang
Jessen, Frank
Schuermann, Britta
van den Bussche, Hendrik
Heuser, Isabella
Kornhuber, Johannes
Wiltfang, Jens
Dichgans, Martin
Froelich, Lutz
Hampel, Harald
Huell, Michael
Rujescu, Dan
Goate, Alison M.
Kauwe, John S. K.
Cruchaga, Carlos
Nowotny, Petra
Morris, John C.
Mayo, Kevin
Sleegers, Kristel
Bettens, Karolien
Engelborghs, Sebastiaan
De Deyn, Peter P.
Van Broeckhoven, Christine
Livingston, Gill
Bass, Nicholas J.
Gurling, Hugh
McQuillin, Andrew
Gwilliam, Rhian
Deloukas, Panagiotis
Al-Chalabi, Ammar
Shaw, Christopher E.
Tsolaki, Magda
Singleton, Andrew B.
Guerreiro, Rita
Muehleisen, Thomas W.
Noethen, Markus M.
Moebus, Susanne
Joeckel, Karl-Heinz
Klopp, Norman
Wichmann, H-Erich
Carrasquillo, Minerva M.
Pankratz, V. Shane
Younkin, Steven G.
Holmans, Peter A.
O'Donovan, Michael
Owen, Michael J.
Williams, Julie
TI Genome-wide association study identifies variants at CLU and PICALM
associated with Alzheimer's disease
SO NATURE GENETICS
LA English
DT Article
ID AMYLOID-PRECURSOR-PROTEIN; SINGLE-NUCLEOTIDE POLYMORPHISMS;
APOLIPOPROTEIN-J; CEREBROSPINAL-FLUID; BETA-PROTEIN; LARGE-SCALE;
SUSCEPTIBILITY LOCI; MOUSE MODEL; IN-VITRO; CLUSTERIN
AB We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 x 10(-157)) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 x 10(-9)) and 5. to the PICALM gene (rs3851179, P = 1.9 x 10(-8)). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 x 10(-10), odds ratio = 0.86; rs3851179, P = 1.3 x 10(-9), odds ratio = 0.86).
C1 [Harold, Denise; Abraham, Richard; Hollingworth, Paul; Sims, Rebecca; Gerrish, Amy; Hamshere, Marian L.; Pahwa, Jaspreet Singh; Moskvina, Valentina; Dowzell, Kimberley; Williams, Amy; Jones, Nicola; Thomas, Charlene; Stretton, Alexandra; Morgan, Angharad R.; Holmans, Peter A.; O'Donovan, Michael; Owen, Michael J.; Williams, Julie] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol,Sch Med, Cardiff, S Glam, Wales.
[Lovestone, Simon] Kings Coll London, Natl Inst Hlth Res, Biomed Res Ctr Mental Hlth, S London & Maudsley Natl Hlth Serv Fdn Trust, London WC2R 2LS, England.
[Powell, John; Proitsi, Petroula; Lupton, Michelle K.] Kings Coll London, Inst Psychiat, Dept Neurosci, London WC2R 2LS, England.
[Brayne, Carol] Univ Cambridge, Inst Publ Hlth, Cambridge, England.
[Rubinsztein, David C.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England.
[Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn] St James Hosp, Mercers Inst Res Aging, Dublin 8, Ireland.
[Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn] Trinity Coll Dublin, Dublin, Ireland.
[Morgan, Kevin; Brown, Kristelle S.] Univ Nottingham, Queens Med Ctr, Inst Genet, Nottingham NG7 2RD, England.
[Passmore, Peter A.; Craig, David; McGuinness, Bernadette; Todd, Stephen] Queens Univ Belfast, Ageing Grp, Ctr Publ Hlth, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland.
[Holmes, Clive] Univ Southampton, Div Clin Neurosci, Sch Med, Southampton, Hants, England.
[Mann, David] Univ Manchester, Clin Neurosci Res Grp, Greater Manchester Neurosci Ctr, Salford, Lancs, England.
[Smith, A. David] Univ Oxford, John Radcliffe Hosp, Oxford Project Investigate Memory & Ageing, Oxford OX3 9DU, England.
[Love, Seth; Kehoe, Patrick G.] Univ Bristol, Dementia Res Grp, Inst Clin Neurosci, Frenchay Hosp, Bristol, Avon, England.
[Hardy, John] Inst Neurol, Dept Mol Neurosci Ctr, London WC1N 3BG, England.
[Hardy, John] Inst Neurol, Reta Lilla Weston Labs, London WC1N 3BG, England.
[Mead, Simon; Collinge, John] UCL Inst Neurol, MRC, Prion Unit, London, England.
[Fox, Nick; Rossor, Martin] UCL Inst Neurol, Dementia Res Ctr, Dept Neurodegenerat Dis, London, England.
[Maier, Wolfgang; Jessen, Frank; Schuermann, Britta] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany.
[van den Bussche, Hendrik] Univ Med Ctr Hamburg Eppendorf, Inst Primary Med Care, Hamburg, Germany.
[Heuser, Isabella] Charite, Dept Psychiat, Berlin, Germany.
[Kornhuber, Johannes] Univ Erlangen Nurnberg, Dept Psychiat & Psychotherapy, Erlangen, Germany.
[Wiltfang, Jens] Univ Duisburg Essen, Dept Psychiat & Psychotherapy, Landschaftsverband Rheinland Hosp Essen, Essen, Germany.
[Dichgans, Martin] Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.
[Dichgans, Martin] Klinikum Univ Munchen, Dept Neurol, Munich, Germany.
[Froelich, Lutz] Univ Heidelberg, Dept Geriatr Psychiat, Cent Inst Mental Hlth, Med Fac Mannheim, D-6800 Mannheim, Germany.
[Hampel, Harald] Univ Dublin Trinity Coll, Discipline Psychiat, Sch Med, Dublin 2, Ireland.
[Hampel, Harald] Univ Dublin Trinity Coll, Inst Neurosci, Lab Neuroimaging & Biomarker Res, Dublin 2, Ireland.
[Hampel, Harald; Rujescu, Dan] Univ Munich, Dept Psychiat, Alzheimer Mem Ctr, D-8000 Munich, Germany.
[Hampel, Harald; Rujescu, Dan] Univ Munich, Dept Psychiat, Geriatr Psychiat Branch, D-8000 Munich, Germany.
[Huell, Michael] Univ Freiburg, Ctr Geriatr Med, Sch Med, Freiburg, Germany.
[Huell, Michael] Univ Freiburg, Sect Gerontopsychiat & Neuropsychol, Sch Med, Freiburg, Germany.
[Goate, Alison M.; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Mayo, Kevin] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Goate, Alison M.; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Mayo, Kevin] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Goate, Alison M.; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Mayo, Kevin] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Kauwe, John S. K.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA.
[Sleegers, Kristel; Bettens, Karolien; Van Broeckhoven, Christine] VIB, Neurodegenerat Brain Dis Grp, Dept Mol Genet, Antwerp, Belgium.
[Sleegers, Kristel; Bettens, Karolien; Engelborghs, Sebastiaan; De Deyn, Peter P.; Van Broeckhoven, Christine] Inst Born Bunge, Antwerp, Belgium.
[Sleegers, Kristel; Bettens, Karolien; Engelborghs, Sebastiaan; De Deyn, Peter P.; Van Broeckhoven, Christine] Univ Antwerp, B-2020 Antwerp, Belgium.
[Engelborghs, Sebastiaan; De Deyn, Peter P.] Ziekenhuis Netwerk Antwerpen Middelheim, Memory Clin, Antwerp, Belgium.
[Engelborghs, Sebastiaan; De Deyn, Peter P.] Ziekenhuis Netwerk Antwerpen Middelheim, Dept Neurol, Antwerp, Belgium.
[Livingston, Gill; Bass, Nicholas J.; Gurling, Hugh; McQuillin, Andrew] UCL, Dept Mental Hlth Sci, London, England.
[Gwilliam, Rhian; Deloukas, Panagiotis] Wellcome Trust Sanger Inst, Cambridge, England.
[Al-Chalabi, Ammar; Shaw, Christopher E.] Kings Coll London, MRC, Ctr Neurodegenerat Res, Dept Clin Neurosci,Inst Psychiat, London WC2R 2LS, England.
[Tsolaki, Magda] Aristotle Univ Thessaloniki, Dept Neurol 3, GR-54006 Thessaloniki, Greece.
[Singleton, Andrew B.; Guerreiro, Rita] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany.
[Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany.
[Moebus, Susanne; Joeckel, Karl-Heinz] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany.
[Klopp, Norman; Wichmann, H-Erich] German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Carrasquillo, Minerva M.; Younkin, Steven G.] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA.
[Pankratz, V. Shane] Mayo Clin & Mayo Fdn, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
RP Williams, J (reprint author), Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol,Sch Med, Cardiff, S Glam, Wales.
EM owenmj@cardiff.ac.uk; williamsj@cardiff.ac.uk
RI Rubinsztein, David/C-3472-2011; Singleton, Andrew/C-3010-2009; Mead,
Simon/E-9414-2011; Powell, John/G-4412-2011; Kauwe, John/B-2034-2009;
Morris, John/A-1686-2012; Hardy, John/C-2451-2009; passmore,
anthony/C-9824-2009; Lovestone, Simon/E-8725-2010; Todd,
Stephen/A-4299-2009; Livingston, Gill/C-7081-2008; Al-Chalabi,
Ammar/E-5361-2010; McGuinness, Bernadette/A-4056-2010; Love,
Seth/E-6545-2012; Jessen, Frank/E-7655-2012; Hull, Michael/F-2618-2012;
Guerreiro, Rita/A-1327-2011; Deloukas, Panos/B-2922-2013; Gurling,
Hugh/A-5029-2010; Goldsmith, Seraphina/M-7829-2013; Kornhuber,
Johannes/B-9613-2014; Fox, Nick/B-1319-2009; Holmans, Peter/F-4518-2015;
Smith, Anthony/A-4233-2010; McQuillin, Andrew/C-1623-2008;
OI Mead, Simon/0000-0002-4326-1468; Powell, John/0000-0001-6124-439X;
Kauwe, John/0000-0001-8641-2468; Al-Chalabi, Ammar/0000-0002-4924-7712;
O'Donovan, Michael/0000-0001-7073-2379; Gill,
Michael/0000-0003-0206-5337; Harold, Denise/0000-0001-5195-0143;
Cruchaga, Carlos/0000-0002-0276-2899; Escott-Price,
Valentina/0000-0003-1784-5483; Nothen, Markus/0000-0002-8770-2464; Todd,
Stephen/0000-0002-2312-9195; Deloukas, Panos/0000-0001-9251-070X;
Goldsmith, Seraphina/0000-0003-4379-988X; Kornhuber,
Johannes/0000-0002-8096-3987; Fox, Nick/0000-0002-6660-657X; Holmans,
Peter/0000-0003-0870-9412; Smith, Anthony/0000-0002-1095-6722;
McQuillin, Andrew/0000-0003-1567-2240; Wiltfang,
Jens/0000-0003-1492-5330
FU Wellcome Trust; Medical Research Council (MRC, UK); Alzheimer's Research
Trust (ART); Welsh Assembly Government; Mercer's Institute for Research
on Ageing; South West Dementia Brain Bank; Charles Wolfson Charitable
Trust; Motor Neurone Disease Association; US National Institutes of
Health (NIH); Barnes Jewish Foundation; Charles and Joanne Knight
Alzheimer's Research Initiative; Robert and Clarice Smith and Abigail
Van Buren AD Research Program; UCL Hospital/UCL Biomedical Centre;
Lundbeck; German Federal Ministry of Education and Research (BMBF);
Competence Network Dementia and Competence Network Degenerative
Dementia; Alfried Krupp von Bohlen und Halbach-Stiftung; Helmholtz
Zentrum Munchen; German National Genome Research Network; Munich Center
of Health Sciences; Heinz Nixdorf Foundation; US National Institute of
Neurological Disorders and Stroke; National Institute on Aging (NIA);
IRP; Department of Health and Human Services [Z01 AG000950-06]; National
Institute of Allergy and Infectious Diseases; National Human Genome
Research Institute; National Institute of Child Health and Human
Development; Juvenile Diabetes Research Foundation International; VIB
Genetic Service Facility; Biobank of the Institute Born-Bunge; Special
Research Fund of the University of Antwerp; Fund for Scientific
Research-Flanders; Foundation for Alzheimer Research; Belgian Federal
Science Policy Office
FX Warden, D Lehmann, N. Leigh, J. Uphill, J. Beck, T. Campbell, S. Klier,
G. Adamson, J. Wyatt, M. L. Perez, T. Meitinger, P. Lichtner, G.
Eckstein, N. Graff-Radford, R. Petersen, D. Dickson, G. Fischer, H.
Bickel, H. Jahn, H. Kaduszkiewicz, C. Luckhaus, S. Riedel-Heller, S.
Wolf, S. Weyerer, the Helmholtz Zentrum Munchen genotyping staff, E.
Reiman, TGEN and the NIMH AD Genetics Initiative. We thank Advanced
Research Computing @ Cardiff (ARCCA), which facilitated data analysis.
NR 59
TC 1200
Z9 1229
U1 11
U2 174
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD OCT
PY 2009
VL 41
IS 10
BP 1088
EP U61
DI 10.1038/ng.440
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 500UG
UT WOS:000270330400011
PM 19734902
ER
PT J
AU Eeles, RA
Kote-Jarai, Z
Al Olama, AA
Giles, GG
Guy, M
Severi, G
Muir, K
Hopper, JL
Henderson, BE
Haiman, CA
Schleutker, J
Hamdy, FC
Neal, DE
Donovan, JL
Stanford, JL
Ostrander, EA
Ingles, SA
John, EM
Thibodeau, SN
Schaid, D
Park, JY
Spurdle, A
Clements, J
Dickinson, JL
Maier, C
Vogel, W
Dork, T
Rebbeck, TR
Cooney, KA
Cannon-Albright, L
Chappuis, PO
Hutter, P
Zeegers, M
Kaneva, R
Zhang, HW
Lu, YJ
Foulkes, WD
English, DR
Leongamornlert, DA
Tymrakiewicz, M
Morrison, J
Ardern-Jones, AT
Hall, AL
O'Brien, LT
Wilkinson, RA
Saunders, EJ
Page, EC
Sawyer, EJ
Edwards, SM
Dearnaley, DP
Horwich, A
Huddart, RA
Khoo, VS
Parker, CC
Van As, N
Woodhouse, CJ
Thompson, A
Christmas, T
Ogden, C
Cooper, CS
Southey, MC
Lophatananon, A
Liu, JF
Kolonel, LN
Le Marchand, L
Wahlfors, T
Tammela, TL
Auvinen, A
Lewis, SJ
Cox, A
FitzGerald, LM
Koopmeiners, JS
Karyadi, DM
Kwon, EM
Stern, MC
Corral, R
Joshi, AD
Shahabi, A
McDonnell, SK
Sellers, TA
Pow-Sang, J
Chambers, S
Aitken, J
Gardiner, RA
Batra, J
Kedda, MA
Lose, F
Polanowski, A
Patterson, B
Serth, J
Meyer, A
Luedeke, M
Stefflova, K
Ray, AM
Lange, EM
Farnham, J
Khan, H
Slavov, C
Mitkova, A
Cao, GW
Easton, DF
AF Eeles, Rosalind A.
Kote-Jarai, Zsofia
Al Olama, Ali Amin
Giles, Graham G.
Guy, Michelle
Severi, Gianluca
Muir, Kenneth
Hopper, John L.
Henderson, Brian E.
Haiman, Christopher A.
Schleutker, Johanna
Hamdy, Freddie C.
Neal, David E.
Donovan, Jenny L.
Stanford, Janet L.
Ostrander, Elaine A.
Ingles, Sue A.
John, Esther M.
Thibodeau, Stephen N.
Schaid, Daniel
Park, Jong Y.
Spurdle, Amanda
Clements, Judith
Dickinson, Joanne L.
Maier, Christiane
Vogel, Walther
Doerk, Thilo
Rebbeck, Timothy R.
Cooney, Kathleen A.
Cannon-Albright, Lisa
Chappuis, Pierre O.
Hutter, Pierre
Zeegers, Maurice
Kaneva, Radka
Zhang, Hong-Wei
Lu, Yong-Jie
Foulkes, William D.
English, Dallas R.
Leongamornlert, Daniel A.
Tymrakiewicz, Malgorzata
Morrison, Jonathan
Ardern-Jones, Audrey T.
Hall, Amanda L.
O'Brien, Lynne T.
Wilkinson, Rosemary A.
Saunders, Edward J.
Page, Elizabeth C.
Sawyer, Emma J.
Edwards, Stephen M.
Dearnaley, David P.
Horwich, Alan
Huddart, Robert A.
Khoo, Vincent S.
Parker, Christopher C.
Van As, Nicholas
Woodhouse, Christopher J.
Thompson, Alan
Christmas, Tim
Ogden, Chris
Cooper, Colin S.
Southey, Melissa C.
Lophatananon, Artitaya
Liu, Jo-Fen
Kolonel, Laurence N.
Le Marchand, Loic
Wahlfors, Tiina
Tammela, Teuvo L.
Auvinen, Anssi
Lewis, Sarah J.
Cox, Angela
FitzGerald, Liesel M.
Koopmeiners, Joseph S.
Karyadi, Danielle M.
Kwon, Erika M.
Stern, Mariana C.
Corral, Roman
Joshi, Amit D.
Shahabi, Ahva
McDonnell, Shannon K.
Sellers, Thomas A.
Pow-Sang, Julio
Chambers, Suzanne
Aitken, Joanne
Gardiner, R. A. (Frank)
Batra, Jyotsna
Kedda, Mary Anne
Lose, Felicity
Polanowski, Andrea
Patterson, Briony
Serth, Juergen
Meyer, Andreas
Luedeke, Manuel
Stefflova, Klara
Ray, Anna M.
Lange, Ethan M.
Farnham, Jim
Khan, Humera
Slavov, Chavdar
Mitkova, Atanaska
Cao, Guangwen
Easton, Douglas F.
CA British Assoc Urological Surg
UK ProtecT Study Collaborators
PRACTICAL Consortium
TI Identification of seven new prostate cancer susceptibility loci through
a genome-wide association study
SO NATURE GENETICS
LA English
DT Article
ID AUSTRALIAN CASE-CONTROL; MULTIPLE; RISK; VARIANTS; ANTIGEN
AB Prostate cancer (PrCa) is the most frequently diagnosed cancer in males in developed countries. To identify common PrCa susceptibility alleles, we previously conducted a genome-wide association study in which 541,129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and in 1,894 controls. We have now extended the study to evaluate promising associations in a second stage in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls and in a third stage involving an additional 16,229 cases and 14,821 controls from 21 studies. In addition to replicating previous associations, we identified seven new prostate cancer susceptibility loci on chromosomes 2, 4, 8, 11 and 22 (with P = 1.6 x 10(-8) to P = 2.7 x 10(-33)).
C1 [Eeles, Rosalind A.; Kote-Jarai, Zsofia; Guy, Michelle; Leongamornlert, Daniel A.; Tymrakiewicz, Malgorzata; Hall, Amanda L.; O'Brien, Lynne T.; Wilkinson, Rosemary A.; Saunders, Edward J.; Page, Elizabeth C.; Sawyer, Emma J.; Edwards, Stephen M.; Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Cooper, Colin S.] Inst Canc Res, Surrey, England.
[Eeles, Rosalind A.; Ardern-Jones, Audrey T.; Hall, Amanda L.; Page, Elizabeth C.; Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Van As, Nicholas; Woodhouse, Christopher J.; Thompson, Alan; Christmas, Tim; Ogden, Chris] Royal Marsden Natl Hlth Serv Fdn Trust, Surrey, England.
[Eeles, Rosalind A.; Ardern-Jones, Audrey T.; Hall, Amanda L.; Page, Elizabeth C.; Dearnaley, David P.; Horwich, Alan; Huddart, Robert A.; Khoo, Vincent S.; Parker, Christopher C.; Van As, Nicholas; Woodhouse, Christopher J.; Thompson, Alan; Christmas, Tim; Ogden, Chris] Royal Marsden Natl Hlth Serv Fdn Trust, London, England.
[Al Olama, Ali Amin; Morrison, Jonathan; Easton, Douglas F.] Univ Cambridge, Canc Res UK Genet Epidemiol Unit, Dept Publ Hlth & Primary Care, Strangeways Lab, Cambridge, England.
[Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia.
[Giles, Graham G.; Severi, Gianluca; Hopper, John L.; English, Dallas R.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Carlton, Vic 3053, Australia.
[Muir, Kenneth; Lophatananon, Artitaya; Liu, Jo-Fen] Univ Nottingham, Sch Med, Queens Med Ctr, Nottingham, England.
[Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Schleutker, Johanna; Wahlfors, Tiina] Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland.
[Hamdy, Freddie C.] Univ Oxford, Nuffield Dept Surg, Oxford, England.
[Neal, David E.] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge, England.
[Donovan, Jenny L.; Lewis, Sarah J.] Univ Bristol, Dept Social Med, Bristol, Avon, England.
[Stanford, Janet L.; FitzGerald, Liesel M.; Koopmeiners, Joseph S.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Stanford, Janet L.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA.
[Ostrander, Elaine A.; Karyadi, Danielle M.; Kwon, Erika M.] NHGRI, NIH, Bethesda, MD 20892 USA.
[John, Esther M.] No Calif Canc Ctr, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Thibodeau, Stephen N.; Schaid, Daniel; McDonnell, Shannon K.] Mayo Clin, Rochester, MN USA.
[Park, Jong Y.; Sellers, Thomas A.; Pow-Sang, Julio] Univ S Florida, H Lee Moffitt Canc Ctr, Div Canc Prevent & Control, Tampa, FL 33682 USA.
[Spurdle, Amanda; Lose, Felicity] Queensland Inst Med Res, Mol Canc Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Clements, Judith; Batra, Jyotsna; Kedda, Mary Anne; Lose, Felicity] Queensland Univ Technol, Australian Prostate Canc Res Ctr Queensland, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia.
[Clements, Judith; Batra, Jyotsna; Kedda, Mary Anne; Lose, Felicity] Queensland Univ Technol, Sch Life Sci, Brisbane, Qld 4001, Australia.
[Clements, Judith; Batra, Jyotsna; Kedda, Mary Anne; Lose, Felicity] Queensland Univ Technol, Sch Publ Hlth, Brisbane, Qld 4001, Australia.
[Dickinson, Joanne L.; Polanowski, Andrea; Patterson, Briony] Univ Tasmania, Menzies Res Inst, Hobart, Tas, Australia.
[Maier, Christiane; Vogel, Walther; Luedeke, Manuel] Inst Human Genet & Anthropol, Ulm, Germany.
[Doerk, Thilo] Hannover Med Sch, Clin Obstet, D-3000 Hannover, Germany.
[Doerk, Thilo] Hannover Med Sch, Clin Gynaecol, D-3000 Hannover, Germany.
[Rebbeck, Timothy R.; Stefflova, Klara] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.; Stefflova, Klara] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Cooney, Kathleen A.; Ray, Anna M.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Cooney, Kathleen A.; Ray, Anna M.] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI USA.
[Cannon-Albright, Lisa; Farnham, Jim] Univ Utah, Sch Med, Dept Biomed Informat, Salt Lake City, UT USA.
[Chappuis, Pierre O.] Univ Hosp Geneva, Div Med Genet, Geneva, Switzerland.
[Chappuis, Pierre O.] Univ Hosp Geneva, Div Oncol, Geneva, Switzerland.
[Hutter, Pierre] Inst Cent Hop Valaisans, Div Med Genet, Sion, Switzerland.
[Zeegers, Maurice; Khan, Humera] Univ Birmingham, Unit Genet Epidemiol, Dept Publ Hlth Epidemiol & Biostat, Sch Med, Birmingham B15 2TT, W Midlands, England.
[Zeegers, Maurice] Maastricht Univ, Dept Complex Genet, Cluster Genet & Cell Biol, Nutr & Toxicol Res Inst,Med Ctr, Maastricht, Netherlands.
[Kaneva, Radka; Mitkova, Atanaska] Med Univ Sofia, Mol Med Ctr, Sofia, Bulgaria.
[Kaneva, Radka; Mitkova, Atanaska] Med Univ Sofia, Dept Chem & Biochem, Sofia, Bulgaria.
[Zhang, Hong-Wei; Cao, Guangwen] Second Mil Med Univ, Dept Epidemiol, Shanghai, Peoples R China.
[Lu, Yong-Jie] Univ London, Inst Canc, Barts & London Sch Med & Dent, London, England.
[Foulkes, William D.] McGill Univ, Program Canc Genet, Montreal, PQ, Canada.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia.
[Lophatananon, Artitaya] Chulabhorn Canc Res Ctr, Bangkok, Thailand.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA.
[Tammela, Teuvo L.] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Tammela, Teuvo L.] Tampere Univ Hosp, Dept Urol, Tampere, Finland.
[Auvinen, Anssi] Univ Tampere, Tampere Sch Publ Hlth, FIN-33101 Tampere, Finland.
[Cox, Angela] Univ Sheffield, Inst Canc Studies, Sheffield, S Yorkshire, England.
[Koopmeiners, Joseph S.] Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA.
[Chambers, Suzanne; Aitken, Joanne] Canc Council Queensland, Viertel Ctr Res Canc Control, Brisbane, Qld, Australia.
[Aitken, Joanne] Univ Queensland, Sch Populat Hlth, Brisbane, Qld, Australia.
[Gardiner, R. A. (Frank)] Univ Queensland, Dept Surg, Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia.
[Serth, Juergen] Hannover Med Sch, Urol Clin, D-3000 Hannover, Germany.
[Serth, Juergen] Hannover Med Sch, Clin Urol Oncol, D-3000 Hannover, Germany.
[Meyer, Andreas] Hannover Med Sch, Dept Radiat Oncol, D-3000 Hannover, Germany.
[Lange, Ethan M.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Slavov, Chavdar] Med Univ Sofia, Dept Urol, Alexandrovska Univ Hosp, Sofia, Bulgaria.
RP Eeles, RA (reprint author), Inst Canc Res, Surrey, England.
EM rosalind.eeles@icr.ac.uk
RI Gardiner, Robert/G-2096-2010; Spurdle, Amanda/A-4978-2011; Batra,
Jyotsna/B-4130-2011; Thomson, Russell/H-5653-2012; Dickinson,
Joanne/J-7728-2014; Chambers, Suzanne/H-5957-2012; Dork,
Thilo/J-8620-2012; O'Mara, Tracy/M-7508-2016;
OI Clements, Judith/0000-0001-6026-1964; English,
Dallas/0000-0001-7828-8188; Ostrander, Elaine/0000-0001-6075-9738;
Evans, Gareth/0000-0002-8482-5784; Saunders, Ed/0000-0003-4343-3570;
Farnham, James/0000-0002-8213-949X; Lewis, Sarah/0000-0003-4311-6890;
Auvinen, Anssi/0000-0003-1125-4818; Neal, David/0000-0002-6033-5086;
Leongamornlert, Daniel/0000-0002-3486-3168; Graham,
John/0000-0003-3381-9787; albright, lisa/0000-0003-2602-3668; foulkes,
william/0000-0001-7427-4651; Cox, Angela/0000-0002-5138-1099; Giles,
Graham/0000-0003-4946-9099; Spurdle, Amanda/0000-0003-1337-7897;
Thomson, Russell/0000-0003-4949-4120; O'Mara, Tracy/0000-0002-5436-3232;
van As, Nicholas/0000-0001-6829-8788; Clarke, Noel/0000-0001-7776-8059;
Lose, Felicity/0000-0001-8337-3547; Eeles, Rosalind/0000-0002-3698-6241
FU Cancer Research UK [10118, 10588, C1287/A10118, C16913/A6135,
C16913/A6835, C5047/A10692, C5047/A3354, C5047/A7357, C522/A8649];
Department of Health; Intramural NIH HHS; Medical Research Council
[G0500966, G0501019]; NCI NIH HHS [P50 CA097186-08, CA54281, CA56678,
CA63464, CA92579, CA97186, N01 PC035141, N01-PC-35141, P50 CA069568, P50
CA069568-12, P50 CA097186, P50 CA105641, P50 CA105641-05, R01 CA056678,
R01 CA056678-05, R01 CA063464, R01 CA063464-10, R01 CA072818, R01
CA072818-09, R01 CA084979, R01 CA084979-05, R01 CA092579, R01
CA092579-05, R01 CA128813, R01 CA128813-02, R01CA128813, R01CA84979, R37
CA054281, R37 CA054281-17, U01 CA089600, U01 CA089600-04]; NCRR NIH HHS
[M01 RR000064-41, M01 RR00064]
NR 17
TC 264
Z9 274
U1 2
U2 34
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 OCT
PY 2009
VL 41
IS 10
BP 1116
EP U97
DI 10.1038/ng.450
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 500UG
UT WOS:000270330400016
PM 19767753
ER
PT J
AU Prickett, TD
Agrawal, NS
Wei, XM
Yates, KE
Lin, JC
Wunderlich, JR
Cronin, JC
Cruz, P
Rosenberg, SA
Samuels, Y
AF Prickett, Todd D.
Agrawal, Neena S.
Wei, Xiaomu
Yates, Kristin E.
Lin, Jimmy C.
Wunderlich, John R.
Cronin, Julia C.
Cruz, Pedro
Rosenberg, Steven A.
Samuels, Yardena
CA NISC Comparative Sequencing Progra
TI Analysis of the tyrosine kinome in melanoma reveals recurrent mutations
in ERBB4
SO NATURE GENETICS
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; SOMATIC MUTATIONS; BREAST-CANCER; KINASE DOMAIN;
INHIBITOR; CELLS; ACTIVATION; RESISTANCE; LAPATINIB; PATHWAYS
AB Tyrosine phosphorylation is important in signaling pathways underlying tumorigenesis. We performed a mutational analysis of the protein tyrosine kinase (PTK) gene family in cutaneous metastatic melanoma. We identified 30 somatic mutations affecting the kinase domains of 19 PTKs and subsequently evaluated the entire coding regions of the genes encoding these 19 PTKs for somatic mutations in 79 melanoma samples. We found ERBB4 mutations in 19% of individuals with melanoma and found mutations in two other kinases (FLT1 and PTK2B) in 10% of individuals with melanomas. We examined seven missense mutations in the most commonly altered PTK gene, ERBB4, and found that they resulted in increased kinase activity and transformation ability. Melanoma cells expressing mutant ERBB4 had reduced cell growth after shRNA-mediated knockdown of ERBB4 or treatment with the ERBB inhibitor lapatinib. These studies could lead to personalized therapeutics specifically targeting the kinases that are mutationally altered in individual melanomas.
C1 [Prickett, Todd D.; Agrawal, Neena S.; Wei, Xiaomu; Yates, Kristin E.; Cronin, Julia C.; Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Lin, Jimmy C.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD USA.
[Wunderlich, John R.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Cruz, Pedro] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[NISC Comparative Sequencing Progra] NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA.
RP Samuels, Y (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
EM samuelsy@mail.nih.gov
FU National Human Genome Research Institute; National Cancer Institute;
National Institutes of Health, USA
FX We thank B. Vogelstein, T. Waldman, D. Bell, P. Meltzer, L. Brody, G.
Merlino, S. Gutkind and I. Cardenas-Navia for their helpful comments on
the manuscript; members of the NISC Comparative Sequencing Program for
generating the sequence data analyzed here; and S. Anderson and M. Kirby
for assistance with FACS analysis. This work supported by the Intramural
Research Programs of the National Human Genome Research Institute and
National Cancer Institute, National Institutes of Health, USA.
NR 30
TC 192
Z9 195
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD OCT
PY 2009
VL 41
IS 10
BP 1127
EP U112
DI 10.1038/ng.438
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 500UG
UT WOS:000270330400018
PM 19718025
ER
PT J
AU Urban, TJ
Weintrob, AC
Fellay, J
Colombo, S
Shianna, KV
Gumbs, C
Rotger, M
Pelak, K
Dang, KK
Detels, R
Martinson, JJ
O'Brien, SJ
Letvin, NL
McMichael, AJ
Haynes, BF
Carrington, M
Telenti, A
Michael, NL
Goldstein, DB
AF Urban, Thomas J.
Weintrob, Amy C.
Fellay, Jacques
Colombo, Sara
Shianna, Kevin V.
Gumbs, Curtis
Rotger, Margalida
Pelak, Kimberly
Dang, Kristen K.
Detels, Roger
Martinson, Jeremy J.
O'Brien, Stephen J.
Letvin, Norman L.
McMichael, Andrew J.
Haynes, Barton F.
Carrington, Mary
Telenti, Amalio
Michael, Nelson L.
Goldstein, David B.
TI CCL3L1 and HIV/AIDS susceptibility
SO NATURE MEDICINE
LA English
DT Letter
ID GENE COPY NUMBER; HIV-1-INFECTED INDIVIDUALS; HIV-1 INFECTION;
CHEMOKINE; ASSOCIATION; MIP-1-ALPHA; ACCURATE
C1 [Urban, Thomas J.; Fellay, Jacques; Gumbs, Curtis; Pelak, Kimberly; Dang, Kristen K.; Goldstein, David B.] Duke Univ, Duke Inst Genome Sci & Policy, Ctr Human Genome Variat, Durham, NC 27706 USA.
[Weintrob, Amy C.] Walter Reed Army Med Ctr, Infect Dis Clin Res Program, Washington, DC 20307 USA.
[Colombo, Sara; Rotger, Margalida; Telenti, Amalio] Univ Hosp Ctr, Inst Microbiol, Lausanne, Switzerland.
[Colombo, Sara; Rotger, Margalida; Telenti, Amalio] Univ Lausanne, Lausanne, Switzerland.
[Detels, Roger] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Martinson, Jeremy J.] Univ Pittsburgh, Dept Infect Dis & Microbiol, Pittsburgh, PA USA.
[O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
[Letvin, Norman L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA USA.
[McMichael, Andrew J.] John Radcliffe Hosp, Weatherall Inst Mol Med, Human Immunol Unit, MRC, Oxford OX3 9DU, England.
[Haynes, Barton F.] Duke Univ, Duke Human Vaccine Inst, Durham, NC USA.
[Carrington, Mary] NCI, SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA.
[Michael, Nelson L.] US Mil HIV Res Program, Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD USA.
RP Urban, TJ (reprint author), Duke Univ, Duke Inst Genome Sci & Policy, Ctr Human Genome Variat, Durham, NC 27706 USA.
EM d.goldstein@duke.edu
RI SHCS, all/G-4072-2011; SHCS, int. coll. A/G-4083-2011; Fellay,
Jacques/A-6681-2009;
OI Fellay, Jacques/0000-0002-8240-939X; Martinson,
Jeremy/0000-0003-4673-7238
FU Medical Research Council [MC_U137884177]; NCI NIH HHS [N01-CO-12400,
N01CO12400]; NIAID NIH HHS [U19 AI067854-05, U19 AI067854]
NR 13
TC 44
Z9 44
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD OCT
PY 2009
VL 15
IS 10
BP 1110
EP 1112
DI 10.1038/nm1009-1110
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 504EC
UT WOS:000270596400012
PM 19812560
ER
PT J
AU Plum, L
Lin, HV
Dutia, R
Tanaka, J
Aizawa, KS
Matsumoto, M
Kim, AJ
Cawley, NX
Paik, JH
Loh, YP
DePinho, RA
Wardlaw, SL
Accili, D
AF Plum, Leona
Lin, Hua V.
Dutia, Roxanne
Tanaka, Jun
Aizawa, Kumiko S.
Matsumoto, Michihiro
Kim, Andrea J.
Cawley, Niamh X.
Paik, Ji-Hye
Loh, Y. Peng
DePinho, Ronald A.
Wardlaw, Sharon L.
Accili, Domenico
TI The obesity susceptibility gene Cpe links FoxO1 signaling in
hypothalamic pro-opiomelanocortin neurons with regulation of food intake
SO NATURE MEDICINE
LA English
DT Article
ID PROTHYROTROPIN-RELEASING HORMONE; PROHORMONE CONVERTASES;
BETA-ENDORPHIN; BODY-WEIGHT; CPE(FAT)/CPE(FAT) MICE; STIMULATING
HORMONE; ENERGY HOMEOSTASIS; LEPTIN; PEPTIDE; INSULIN
AB Reduced food intake brings about an adaptive decrease in energy expenditure that contributes to the recidivism of obesity after weight loss. Insulin and leptin inhibit food intake through actions in the central nervous system that are partly mediated by the transcription factor FoxO1. We show that FoxO1 ablation in pro-opiomelanocortin (Pomc)-expressing neurons in mice (here called Pomc-Foxo1(-/-) mice) increases Carboxypeptidase E (Cpe) expression, resulting in selective increases of alpha-melanocyt-estimulating hormone (alpha-Msh) and carboxy-cleaved beta-endorphin, the products of Cpe-dependent processing of Pomc. This neuropeptide profile is associated with decreased food intake and normal energy expenditure in Pomc-Foxo1(-/-) mice. We show that Cpe expression is downregulated by diet-induced obesity and that FoxO1 deletion offsets the decrease, protecting against weight gain. Moreover, moderate Cpe overexpression in the arcuate nucleus phenocopies features of the FoxO1 mutation. The dissociation of food intake from energy expenditure in Pomc-Foxo1(-/-) mice represents a model for therapeutic intervention in obesity and raises the possibility of targeting Cpe to develop weight loss medications.
C1 [Plum, Leona; Lin, Hua V.; Dutia, Roxanne; Tanaka, Jun; Aizawa, Kumiko S.; Matsumoto, Michihiro; Kim, Andrea J.; Wardlaw, Sharon L.; Accili, Domenico] Columbia Univ, Naomi Berrie Diabet Ctr, New York, NY 10027 USA.
[Plum, Leona; Lin, Hua V.; Dutia, Roxanne; Tanaka, Jun; Aizawa, Kumiko S.; Matsumoto, Michihiro; Kim, Andrea J.; Wardlaw, Sharon L.; Accili, Domenico] Columbia Univ, Dept Med, New York, NY USA.
[Matsumoto, Michihiro] Int Med Ctr Japan, Dept Clin Pharmacol, Tokyo, Japan.
[Cawley, Niamh X.; Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurosci, Cellular Neurobiol Sect, Bethesda, MD USA.
[Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA.
[Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
[Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA.
RP Accili, D (reprint author), Columbia Univ, Naomi Berrie Diabet Ctr, New York, NY 10027 USA.
EM da230@columbia.edu
FU Deutsche Forschungsgemeinschaft [PL542/1-1]; US National Institutes of
Health [DK57539, DK58282, DK80003, DK63608]; Robert A. and Renee E.
Belfer Family Institute for Innovative Cancer Science
FX Supported by Deutsche Forschungsgemeinschaft PL542/1-1 (L.P.), US
National Institutes of Health DK57539 and DK58282 (D.A.), DK80003
(S.L.W.) and DK63608 (Columbia Diabetes and Endocrinology Research
Center). We thank R. Leibel for insightful discussions, L. Zeltser and
S. Padilla for help with in situ hybridization, N. Seidah (Clinical
Research Institute of Montreal) and D. Good (University of
Massachusetts) for plasmids encoding pCsk1, A. White (University of
Manchester) for neuropeptide antisera, and M. Low (Oregon Health
Sciences University) for Pomc-Gfp transgenic mice, Y. Liu for technical
assistance and members of the Accili and Wardlaw laboratories for
stimulating discussions. R.A.D. is an American Cancer Society Research
Professor and an Ellison Medical Foundation Senior Scholar and is
supported by the Robert A. and Renee E. Belfer Family Institute for
Innovative Cancer Science.
NR 55
TC 78
Z9 80
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD OCT
PY 2009
VL 15
IS 10
BP 1195
EP U125
DI 10.1038/nm.2026
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 504EC
UT WOS:000270596400032
PM 19767734
ER
PT J
AU Hohmann-Marriott, MF
Sousa, AA
Azari, AA
Glushakova, S
Zhang, GF
Zimmerberg, J
Leapman, RD
AF Hohmann-Marriott, Martin F.
Sousa, Alioscka A.
Azari, Afrouz A.
Glushakova, Svetlana
Zhang, Guofeng
Zimmerberg, Joshua
Leapman, Richard D.
TI Nanoscale 3D cellular imaging by axial scanning transmission electron
tomography
SO NATURE METHODS
LA English
DT Article
ID PLASMODIUM-FALCIPARUM; BIOLOGICAL SPECIMENS; STEM TOMOGRAPHY;
RESOLUTION; ULTRASTRUCTURE; ORGANIZATION; ARCHITECTURE; MICROSCOPY
AB Electron tomography provides three-dimensional structural information about supramolecular assemblies and organelles in a cellular context, but image degradation, caused by scattering of transmitted electrons, limits applicability in specimens thicker than 300 nm. We found that scanning transmission electron tomography of 1,000-nm-thick samples using axial detection provided resolution comparable to that of conventional electron tomography. We demonstrated the method by reconstructing a human erythrocyte infected with the malaria parasite Plasmodium falciparum.
C1 [Hohmann-Marriott, Martin F.; Sousa, Alioscka A.; Azari, Afrouz A.; Zhang, Guofeng; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
[Glushakova, Svetlana; Zimmerberg, Joshua] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
RP Leapman, RD (reprint author), Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
EM sousaali@mail.nih.gov; leapmanr@mail.nih.gov
FU National Institute of Biomedical Imaging and Bioengineering; Eunice
Kennedy Shriver National Institute; Child Health and Human Development
of the National Institutes of Health; US National Research Council
FX This work was supported by the Intramural Research Programs of the
National Institute of Biomedical Imaging and Bioengineering, and the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the National Institutes of Health. We thank T. Reese for
help with the freeze-substitution technique. M. F. H.-M. acknowledges
support through the Joint National Institute of Standards and
Technology-National Institute of Biomedical Imaging and Bioengineering
Postdoctoral Associateship program of the US National Research Council.
NR 21
TC 60
Z9 60
U1 2
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD OCT
PY 2009
VL 6
IS 10
BP 729
EP 732
DI 10.1038/NMETH.1367
PG 4
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 501BX
UT WOS:000270355200016
PM 19718033
ER
PT J
AU Oesch, N
Diamond, J
AF Oesch, Nicholas
Diamond, Jeffrey
TI A night vision neuron gets a day job
SO NATURE NEUROSCIENCE
LA English
DT Editorial Material
ID INNER PLEXIFORM LAYER; AII AMACRINE CELLS; MOUSE RETINA; GANGLION-CELLS;
RABBIT RETINA; DEPOLARIZING BIPOLAR; CAT RETINA; ROD; RESPONSES; PATHWAY
AB During the day, certain retinal ganglion cells respond specifically to dark, approaching stimuli. A study finds that the retinal circuit that gives rise to this response makes use of an amacrine cell that was previously known for its role in night vision circuitry, demonstrating that some neurons lead double lives.
C1 [Oesch, Nicholas; Diamond, Jeffrey] US Natl Inst Neurol Disorders & Stroke, US Natl Inst Hlth, Bethesda, MD USA.
RP Oesch, N (reprint author), US Natl Inst Neurol Disorders & Stroke, US Natl Inst Hlth, Bethesda, MD USA.
EM diamondj@ninds.nih.gov
NR 14
TC 4
Z9 4
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD OCT
PY 2009
VL 12
IS 10
BP 1209
EP 1211
DI 10.1038/nn1009-1209
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 498US
UT WOS:000270170200002
PM 19783975
ER
PT J
AU Menendez, D
Inga, A
Resnick, MA
AF Menendez, Daniel
Inga, Alberto
Resnick, Michael A.
TI The expanding universe of p53 targets
SO NATURE REVIEWS CANCER
LA English
DT Review
ID TUMOR-SUPPRESSOR P53; WILD-TYPE P53; CELL-CYCLE ARREST; NF-KAPPA-B;
FACTOR-BINDING-SITES; SINGLE-NUCLEOTIDE POLYMORPHISM; MASTER REGULATORY
NETWORK; ESTROGEN-RECEPTOR-ALPHA; C-TERMINAL DOMAIN; PROTEIN-KINASE-C
AB The p53 tumour suppressor is modified through mutation or changes in expression in most cancers, leading to the altered regulation of hundreds of genes that are directly influenced by this sequence-specific transcription factor. Central to the p53 master regulatory network are the target response element (RE) sequences. The extent of p53 transactivation and transcriptional repression is influenced by many factors, including p53 levels, cofactors and the specific RE sequences, all of which contribute to the role that p53 has in the aetiology of cancer. This Review describes the identification and functionality of REs and highlights the inclusion of non-canonical REs that expand the universe of genes and regulation mechanisms in the p53 tumour suppressor network.
C1 [Menendez, Daniel; Resnick, Michael A.] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
[Inga, Alberto] IST, Natl Inst Canc Res, Unit Mol Mutagenesis & DNA Repair, I-16132 Genoa, Italy.
RP Resnick, MA (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
EM resnick@niehs.nih.gov
RI Xie, Huangming/B-2260-2012
FU National Institute of Environmental Health Sciences [1 Z01 ES065079];
Italian Association for Cancer Research
FX This work was supported by intramural research funds from the National
Institute of Environmental Health Sciences project 1 Z01 ES065079 (to
D.M. and M.A.R.) and partially supported by the Italian Association for
Cancer Research (to A.I.).
NR 203
TC 285
Z9 292
U1 3
U2 35
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD OCT
PY 2009
VL 9
IS 10
BP 724
EP 737
DI 10.1038/nrc2730
PG 14
WC Oncology
SC Oncology
GA 497YZ
UT WOS:000270102800010
PM 19776742
ER
PT J
AU Ivy, SP
Wick, JY
Kaufman, BM
AF Ivy, S. Percy
Wick, Jeannette Y.
Kaufman, Bennett M.
TI An overview of small-molecule inhibitors of VEGFR signaling
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Review
ID ENDOTHELIAL-GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; ADVANCED SOLID
TUMORS; VASCULAR-PERMEABILITY FACTOR; ORALLY-ACTIVE INHIBITOR; FOCAL
ADHESION KINASE; HIPPEL-LINDAU-DISEASE; I DOSE-ESCALATION; PHASE-I;
ANTITUMOR-ACTIVITY
AB VEGFR inhibitors are in broad use for the treatment of metastatic renal-cell carcinoma, gastrointestinal stromal tumors and hepatocellular carcinoma and in development in a number of other oncology indications, including colorectal cancer, non-small-cell lung cancer, pancreatic cancer, thyroid malignancies, ovarian cancer, breast cancer and sarcomas. This Review outlines the structure-activity relationships of the 44 VEGFR inhibitors currently in development. An overview of the pharmacokinetic profile of each molecule and its stage in development is provided. Phase III clinical trials being conducted for licensing of these agents for specific indications and phase III developmental efficacy trials are described in detailed tables that include the disease studied, trial design including combination therapy, study end points, and projected or final accrual. The relative frequency of on-target and off-target adverse events observed in 3,060 patients is described for a subset of agents in development in clinical trials sponsored by the National Cancer Institute. No interagent comparisons were undertaken and no data from pharmaceutical pharmacovigilance databases were used. The on-target effects seem to be mechanistically based and predicted by VEGFR inhibition. Small-molecule inhibitors of angiogenesis are active in a wide variety of malignancies and fill a unique niche for cancer therapeutics.
C1 [Ivy, S. Percy] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA.
[Wick, Jeannette Y.] NCI, Pharmaceut Management Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA.
[Kaufman, Bennett M.] PSI Int Inc, Fairfax, VA USA.
RP Ivy, SP (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, 6130 Execut Blvd,Suite 7131, Rockville, MD 20852 USA.
EM ivyp@ctep.nci.nih.gov
NR 98
TC 174
Z9 178
U1 2
U2 44
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD OCT
PY 2009
VL 6
IS 10
BP 569
EP 579
DI 10.1038/nrclinonc.2009.130
PG 11
WC Oncology
SC Oncology
GA 498SP
UT WOS:000270163800008
PM 19736552
ER
PT J
AU Milescu, M
Bosmans, F
Lee, S
Alabi, AA
Il Kim, J
Swartz, KJ
AF Milescu, Mirela
Bosmans, Frank
Lee, Seungkyu
Alabi, AbdulRasheed A.
Il Kim, Jae
Swartz, Kenton J.
TI Interactions between lipids and voltage sensor paddles detected with
tarantula toxins
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID DEPENDENT K+ CHANNEL; POTASSIUM CHANNEL; PROTEIN INTERACTIONS; SENSING
DOMAINS; GATING MODIFIER; SODIUM-CHANNELS; MUTANT CYCLES; MEMBRANE;
HANATOXIN; ACTIVATION
AB Voltage-activated ion channels open and close in response to changes in voltage, a property that is essential for generating nerve impulses. Studies on voltage-activated potassium (Kv) channels show that voltage-sensor activation is sensitive to the composition of lipids in the surrounding membrane. Here we explore the interaction of lipids with S1-S4 voltage-sensing domains and find that the conversion of the membrane lipid sphingomyelin to ceramide-1-phosphate alters voltage-sensor activation in an S1-S4 voltage-sensing protein lacking an associated pore domain, and that the S3b-S4 paddle motif determines the effects of lipid modification on Kv channels. Using tarantula toxins that bind to paddle motifs within the membrane, we identify mutations in the paddle motif that weaken toxin binding by disrupting lipid-paddle interactions. Our results suggest that lipids bind to voltage-sensing domains and demonstrate that the pharmacological sensitivities of voltage-activated ion channels are influenced by the surrounding lipid membrane.
C1 [Milescu, Mirela; Bosmans, Frank; Alabi, AbdulRasheed A.; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Bosmans, Frank] Katholieke Univ Leuven, Toxicol Lab, Leuven, Belgium.
[Lee, Seungkyu; Il Kim, Jae] Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju, South Korea.
RP Milescu, M (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM Mirela.Milescu@nih.gov; Kenton.Swartz@nih.gov
RI Bosmans, Frank/A-9660-2013
OI Bosmans, Frank/0000-0002-6476-235X
FU Intramural Research Program of the NINDS; National Insitutes of Health
(NIH); NIH-FWO
FX We thank M. Holmgren, J. Kumar, M. Mayer, J. Mindell, S. Silberberg and
members of the Swartz laboratory for helpful discussions and the US
National Institute of Neurological Disorders and Stroke (NINDS) DNA
sequencing facility for DNA sequencing. We thank Y. Okamura ( Okazaki
Center for Integrative Biosciences) for providing Ci-VSP complementary
DNA, Y. Xu and Z. Lu ( University of Pennsylvania) for supplying
recombinant SMaseD and W. Schmalhofer and M. Garcia ( Merck Research
Labs) for supplying 125I-GxTx-1E. This work was supported by
the Intramural Research Program of the NINDS, National Insitutes of
Health (NIH) ( to K. J. S.) and by an NIH-FWO postdoctoral fellowship (
to F. B.).
NR 45
TC 80
Z9 81
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD OCT
PY 2009
VL 16
IS 10
BP 1080
EP U102
DI 10.1038/nsmb.1679
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 503EA
UT WOS:000270514200016
PM 19783984
ER
PT J
AU Li, GZ
Meng, HH
Yang, MQ
Yang, JY
AF Li, Guo-Zheng
Meng, Hao-Hua
Yang, Mary Qu
Yang, Jack Y.
TI Combining support vector regression with feature selection for
multivariate calibration
SO NEURAL COMPUTING & APPLICATIONS
LA English
DT Article
DE Multivariate calibration; Feature selection; Support vector regression;
Artificial neural networks; Partial least square
ID MACHINES
AB Multivariate calibration is a classic problem in the analytical chemistry field and frequently solved by partial least squares (PLS) and artificial neural networks (ANNs) in the previous works. The spaciality of multivariate calibration is high dimensionality with small sample. Here, we apply support vector regression (SVR) as well as ANNs, and PLS to the multivariate calibration problem in the determination of the three aromatic amino acids (phenylalanine, tyrosine and tryptophan) in their mixtures by fluorescence spectroscopy. The results of the leave-one-out method show that SVR performs better than other methods, and appear to be one good method for this task. Furthermore, feature selection is performed for SVR to remove redundant features and a novel algorithm named Prediction RIsk based FEature selection for support vector Regression (PRIFER) is proposed. Results on the above multivariate calibration data set show that PRIFER is a powerful tool for solving the multivariate calibration problems.
C1 [Li, Guo-Zheng] Tongji Univ, Dept Control Sci & Engn, Shanghai 201804, Peoples R China.
[Meng, Hao-Hua] Shanghai Univ, Sch Comp Engn & Sci, Shanghai 200072, Peoples R China.
[Yang, Mary Qu] US Dept HHS, Natl Human Genome Res Inst, NIH, Rockville, MD 20852 USA.
[Yang, Jack Y.] Harvard Univ, Sch Med, Cambridge, MA 02140 USA.
RP Li, GZ (reprint author), Tongji Univ, Dept Control Sci & Engn, Shanghai 201804, Peoples R China.
EM drgzli@gmail.com
RI Li, Guo-Zheng /D-5744-2011
OI Li, Guo-Zheng /0000-0001-5568-0347
FU Nature Science Foundation of China [20503015, 60873129]; Shanghai
Rising-Star Program [08QA14032]; Institute of Systems Biology of
Shanghai University
FX Thanks to the late professor Nian-Yi Chen for his advices to this paper.
This work was supported in part by the Nature Science Foundation of
China under grant no. 20503015 and 60873129, the Shanghai Rising-Star
Program under grant no. 08QA14032 and open funding by Institute of
Systems Biology of Shanghai University.
NR 28
TC 16
Z9 19
U1 1
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-0643
J9 NEURAL COMPUT APPL
JI Neural Comput. Appl.
PD OCT
PY 2009
VL 18
IS 7
BP 813
EP 820
DI 10.1007/s00521-008-0202-6
PG 8
WC Computer Science, Artificial Intelligence
SC Computer Science
GA 495SC
UT WOS:000269914300015
ER
PT J
AU Kinney, JW
Sanchez-Alavez, M
Barr, AM
Criado, JR
Crawley, JN
Behrens, MM
Henriksen, SJ
Bartfai, T
AF Kinney, Jefferson W.
Sanchez-Alavez, Manuel
Barr, Alasdair M.
Criado, Jose R.
Crawley, Jacqueline N.
Behrens, M. Margarita
Henriksen, Steven J.
Bartfai, Tamas
TI Impairment of memory consolidation by galanin correlates with in vivo
inhibition of both LTP and CREB phosphorylation
SO NEUROBIOLOGY OF LEARNING AND MEMORY
LA English
DT Article
DE Galanin; pCREB; Morris water maze; LTP; In vivo; Learning and memory
ID LONG-TERM POTENTIATION; RAT VENTRAL HIPPOCAMPUS; SYNAPTIC PLASTICITY;
ADENYLATE-CYCLASE; DENTATE GYRUS; PHOSPHOINOSITIDE TURNOVER;
ACETYLCHOLINE-RELEASE; RECEPTOR SUBTYPES; PROTEIN; TRANSMISSION
AB Changes in the state of CREB phosphorylation and in LTP in the hippocampus have been associated with learning and memory. Here we show that galanin, the neuropeptide released in the hippocampal formation from cholinergic and noradrenergic fibers, that has been shown to produce impairments in memory consolidation in the Morris water maze task inhibits both LTP and CREB phosphorylation in the rat hippocampus in vivo. While there are many transmitters regulating CREB phosphorylation none has been shown to suppress behaviorally-induced hippocampal CREB phosphorylation as potently as galanin. The in vivo inhibition of dentate gyrus-LTP and of CREB phosphorylation by the agonist occupancy of GalR1 and GalR2-type galanin receptors provides strong in vivo cellular and molecular correlates to galanin-induced learning deficits and designates galanin as a major regulator of the memory consolidation process. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Kinney, Jefferson W.] Univ Nevada, Dept Psychol, Las Vegas, NV 89154 USA.
[Sanchez-Alavez, Manuel; Barr, Alasdair M.; Behrens, M. Margarita; Bartfai, Tamas] Scripps Res Inst, Dept Neuropharmacol, Harold Dorris Neurol Res Ctr, La Jolla, CA 92037 USA.
[Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA.
RP Kinney, JW (reprint author), 4505 Maryland Pkwy,POB 455030, Las Vegas, NV 89154 USA.
EM Jefferson.kinney@unlv.edu
RI yu, yan/C-2322-2012; Behrens, M. Margarita/K-2576-2014
FU Intramural NIH HHS [Z01 MH002179-22]; NIMH NIH HHS [R01 MH074055, R01
MH074055-02]
NR 55
TC 16
Z9 19
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1074-7427
EI 1095-9564
J9 NEUROBIOL LEARN MEM
JI Neurobiol. Learn. Mem.
PD OCT
PY 2009
VL 92
IS 3
BP 429
EP 438
DI 10.1016/j.nlm.2009.06.005
PG 10
WC Behavioral Sciences; Neurosciences; Psychology; Psychology,
Multidisciplinary
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 594JC
UT WOS:000277532500018
PM 19531380
ER
PT J
AU Traore, M
Landoure, G
Motley, W
Sangare, M
Meilleur, K
Coulibaly, S
Traore, S
Niare, B
Mochel, F
La Pean, A
Vortmeyer, A
Mani, H
Fischbeck, KH
AF Traore, M.
Landoure, G.
Motley, W.
Sangare, M.
Meilleur, K.
Coulibaly, S.
Traore, S.
Niare, B.
Mochel, F.
La Pean, A.
Vortmeyer, A.
Mani, H.
Fischbeck, K. H.
TI Novel mutation in the NHLRC1 gene in a Malian family with a severe
phenotype of Lafora disease
SO NEUROGENETICS
LA English
DT Article
DE Clinical neurology; Epilepsy/seizures; Myoclonus; Dementia; Genetics
ID PROGRESSIVE MYOCLONUS EPILEPSY; DIAGNOSTIC PITFALLS; SKIN BIOPSY;
LATE-ONSET; DEGRADATION; PROTEINS; COMPLEX
AB We studied a Malian family with parental consanguinity and two of eight siblings affected with late-childhood-onset progressive myoclonus epilepsy and cognitive decline, consistent with the diagnosis of Lafora disease. Genetic analysis showed a novel homozygous single-nucleotide variant in the NHLRC1 gene, c.560A > C, producing the missense change H187P. The changed amino acid is highly conserved, and the mutation impairs malin's ability to degrade laforin in vitro. Pathological evaluation showed manifestations of Lafora disease in the entire brain, with particularly severe involvement of the pallidum, thalamus, and cerebellum. Our findings document Lafora disease with severe manifestations in the West African population.
C1 [Landoure, G.] UCL, Royal Free Hosp, London NW3 2PF, England.
[Traore, M.; Landoure, G.; Sangare, M.; Coulibaly, S.; Traore, S.; Niare, B.] Univ Bamako, Dept Neurosci, Bamako, Mali.
[Landoure, G.; Motley, W.; Sangare, M.; Meilleur, K.; Mochel, F.; La Pean, A.; Vortmeyer, A.; Fischbeck, K. H.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Meilleur, K.] NINR, NIH, Bethesda, MD 20892 USA.
[Meilleur, K.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA.
[Mochel, F.] Hop La Pitie Salpetriere, INSERM, U679, Paris, France.
[Mani, H.] NCI, NIH, Bethesda, MD 20892 USA.
RP Landoure, G (reprint author), UCL, Royal Free Hosp, Rowland Hill St,1st Floor,Room 1-7012, London NW3 2PF, England.
EM g.landoure@ucl.ac.uk
FU National Institute of Neurological Disorders and Stroke; Teaching
Hospital and Medical School of Point G of the University of Bamako
FX This work was supported by the intramural program of the National
Institute of Neurological Disorders and Stroke at NIH and the Teaching
Hospital and Medical School of Point G of the University of Bamako. We
are grateful to the patients and their families for participating in
this study. We thank Drs. Aldiouma Guindo and Seidina Diakite for the
use of their lab in Mali (Malaria Pathogenesis and Protection Unit) and
Drs. Matthew Gentry and Jack Dixon for providing the reagents and advice
for the functional assays. We declare that experiments comply with the
current laws of Mali and the United States of America.
NR 28
TC 9
Z9 9
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1364-6745
J9 NEUROGENETICS
JI Neurogenetics
PD OCT
PY 2009
VL 10
IS 4
BP 319
EP 323
DI 10.1007/s10048-009-0190-4
PG 5
WC Genetics & Heredity; Clinical Neurology
SC Genetics & Heredity; Neurosciences & Neurology
GA 501MM
UT WOS:000270386000006
PM 19322595
ER
PT J
AU Sarlls, JE
Pierpaoli, C
AF Sarlls, Joelle E.
Pierpaoli, Carlo
TI In vivo diffusion tensor imaging of the human optic chiasm at
sub-millimeter resolution
SO NEUROIMAGE
LA English
DT Article
ID FAST SPIN-ECHO; WHITE-MATTER; WEIGHTED MRI; HUMAN BRAIN; NERVE;
ARCHITECTURE; ORIENTATION; ANISOTROPY; FRAMEWORK; TRACKING
AB In this work we report findings from an in vivo diffusion tensor imaging (DTI) study of the human optic chiasm at sub-millimeter voxel resolution. Data were collected at 3 T using a diffusion-weighted radial-FSE sequence, which provides images free from typical magnetic susceptibility artifacts. The general DTI features observed in the optic chiasm region were consistent across subjects. They included a central area with high anisotropy and highest diffusivity in a predominately right/left direction corresponding to the decussation of nasal hemiretinae fibers, surrounded by a band of low anisotropy reflecting heterogeneous orientation of fibers within the voxel, and a lateral area with high anisotropy and highest diffusivity in a predominately anterior/posterior direction corresponding to temporal hemiretinae fibers that do not cross. Animal studies indicate that there is a significant dorsal-ventral reorganization of the retinotopic distribution of fibers along the optic pathways. We found that diffusion ellipsoids in the central portion of the optic chiasm show considerable planar anisotropy in the coronal plane indicating fiber crossings in the superior/inferior direction, rather than strictly right/left. This architectural feature of the chiasm suggests that dorso-ventral reorganization of fibers in the optic pathways also occurs in humans. We have shown that by collecting sub-millimeter resolution data, DTI can be used to investigate fine details of small and complex white matter structures, in vivo, with a clinical scanner. High spatial resolution, however, is necessary in the slice direction as well as in-plane to reduce the CSF contribution to the signal and to increase fiber coherence within voxels. Published by Elsevier Inc.
C1 [Sarlls, Joelle E.; Pierpaoli, Carlo] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Sarlls, JE (reprint author), NICHHD, NIH, Bldg 13,Room 3W16,13 South Dr, Bethesda, MD 20892 USA.
EM sarllsjo@mail.nih.gov
RI Pierpaoli, Carlo/E-1672-2011
FU NIMH [00M0085]
FX The authors would like to thank Dr. Cheng Guan Koay for his assistance
in implementing the calculation of dispersion measures for the averaged
eigenvectors in an ROI. We Would like to thank Dr. Peter Basser for his
comments and suggestions and Dr. Stefano Marenco for his essential
contributions. We would also like to thank Christie Rebsch for her time
and efforts put toward this work. The authors thank Liz Salak for
editing the manuscript. This study was partly funded by NIMH through
protocol 00M0085, V.S. Mattay principal investigator.
NR 36
TC 8
Z9 9
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD OCT 1
PY 2009
VL 47
IS 4
BP 1244
EP 1251
DI 10.1016/j.neuroimage.2009.05.098
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 484HN
UT WOS:000269035100014
PM 19520170
ER
PT J
AU Luo, QF
Lu, H
Lu, HB
Senseman, D
Worsley, K
Yang, YH
Gao, JH
AF Luo, Qingfei
Lu, Huo
Lu, Hanbing
Senseman, David
Worsley, Keith
Yang, Yihong
Gao, Jia-Hong
TI Physiologically evoked neuronal current MRI in a bloodless turtle brain:
Detectable or not?
SO NEUROIMAGE
LA English
DT Article
ID HUMAN OPTIC-NERVE; MAGNETIC-FIELDS; VISUAL-CORTEX; ELECTRICAL-ACTIVITY;
SIGNAL MODULATION; PYRAMIDAL NEURONS; SNAIL GANGLIA; RESONANCE;
STIMULATION; FMRI
AB Contradictory reports regarding the detection of neuronal currents have left the feasibility of neuronal Current MRI (ncMRI) an open question. Most previous ncMRI studies in human subjects are suspect due to their inability to separate or eliminate hemodynamic effects. In this study, we used a bloodless turtle brain preparation that eliminates hemodynamic effects, to explore the feasibility of detecting visually-evoked ncMRI signals at 9.4 T Intact turtle brains, with eyes attached, were dissected from the cranium and placed in artificial cerebral spinal fluid. Light flashes were delivered to the eyes to evoke neuronal activity. Local field potential (LFP) and MRI signals were measured in an interleaved fashion. Robust visually-evoked LFP signals were observed in turtle brains, but no significant signal changes synchronized with neuronal currents were found in the ncMRI images. In this study, detection thresholds of 0.1% and 0.1 degrees were set for MRI magnitude and phase signal changes, respectively. The absence of significant signal changes in the MRI images suggests that visually-evoked ncMRI signals in the turtle brain are below these detectable levels. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Luo, Qingfei; Gao, Jia-Hong] Univ Chicago, Brain Res Imaging Ctr, Chicago, IL 60637 USA.
[Luo, Qingfei; Gao, Jia-Hong] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA.
[Lu, Huo] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, San Antonio, TX 78229 USA.
[Lu, Hanbing; Yang, Yihong] NIDA, NIH, Baltimore, MD 21224 USA.
[Senseman, David] Univ Texas San Antonio, Dept Biol, San Antonio, TX 78249 USA.
[Worsley, Keith] Univ Chicago, Dept Stat, Chicago, IL 60637 USA.
[Gao, Jia-Hong] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
RP Gao, JH (reprint author), Univ Chicago, Brain Res Imaging Ctr, 5841 S Maryland Ave,MC 2026, Chicago, IL 60637 USA.
EM jgao@uchicago.edu
OI Luo, Qingfei/0000-0002-1078-799X
FU NIH [RO1 EB004753]; NIH/NIDA
FX This work was supported by a NIH grant (RO1 EB004753 to JHG) and the
Intramural Research Program of the NIH/NIDA.
NR 47
TC 20
Z9 20
U1 1
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD OCT 1
PY 2009
VL 47
IS 4
BP 1268
EP 1276
DI 10.1016/j.neuroimage.2009.06.017
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 484HN
UT WOS:000269035100017
PM 19539040
ER
PT J
AU Geng, XJ
Christensen, GE
Gu, H
Ross, TJ
Yang, YH
AF Geng, Xiujuan
Christensen, Gary E.
Gu, Hong
Ross, Thomas J.
Yang, Yihong
TI Implicit reference-based group-wise image registration and its
application to structural and functional MRI
SO NEUROIMAGE
LA English
DT Article
ID BRAIN ANATOMY; AUTOMATIC CONSTRUCTION; SPATIAL NORMALIZATION; NONRIGID
REGISTRATION; SHAPE MODELS; ATLAS; VISUALIZATION; POPULATION; VALIDATION
AB In this study, an implicit reference group-wise (IRG) registration with a small deformation, linear elastic model was used to jointly estimate correspondences between a set of MRI images. The performance of pair-wise and group-wise registration algorithms was evaluated for spatial normalization of structural and functional MRI data. Traditional spatial normalization is accomplished by group-to-reference (G2R) registration in which a group of images are registered pair-wise to a reference image. G2R registration is limited due to bias associated with selecting a reference image. In contrast, implicit reference group-wise (IRG) registration estimates correspondences between a group of images by jointly registering the images to ail implicit reference corresponding to the group average. The implicit reference is estimated during IRG registration eliminating the bias associated with selecting a specific reference image. Registration performance was evaluated using segmented T1-weighted magnetic resonance images from the Nonrigid Image Registration Evaluation Project (NIREP), DTI and fMRI images. Implicit reference pair-wise (IRP) registration-a special case of IRG registration for two images-is shown to produce better relative overlap than IRG for pair-wise registration using the same small deformation, linear elastic registration model. However, IRP-G2R registration is shown to have significant transitivity error, i.e., significant inconsistencies between correspondences defined by different pair-wise transformations. In contrast, IRG registration produces consistent correspondence between images in a group at the cost of slightly reduced pair-wise RO accuracy compared to IRP-G2R. IRG spatial normalization of the fractional anisotropy (FA) maps of DTI is shown to have smaller FA variance compared with G2R methods using the same elastic registration model. Analyses of fMRI data sets with sensorimotor and visual tasks show that IRG registration, on average, increases the statistical detectability of brain activation compared to G2R registration. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Geng, Xiujuan; Gu, Hong; Ross, Thomas J.; Yang, Yihong] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD USA.
[Christensen, Gary E.] Univ Iowa, Dept Elect & Comp Engn, Iowa City, IA 52242 USA.
RP Geng, XJ (reprint author), NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD USA.
EM gengx@nida.nih.gov
RI Ross, Thomas/B-7469-2008; Geng, Xiujuan/I-3852-2012
OI Ross, Thomas/0000-0002-7745-3572;
FU National Institute on Drug Abuse (NIDA); National Institute of Health
(NIH) [EB004126]
FX This work was supported in part by the intramural Research Program of
the National Institute on Drug Abuse (NIDA), National Institute of
Health (NIH) and NIH grant EB004126.
NR 39
TC 31
Z9 31
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD OCT 1
PY 2009
VL 47
IS 4
BP 1341
EP 1351
DI 10.1016/j.neuroimage.2009.04.024
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 484HN
UT WOS:000269035100024
PM 19371788
ER
PT J
AU Deuker, L
Bullmore, ET
Smith, M
Christensen, S
Nathan, PJ
Rockstroh, B
Bassett, DS
AF Deuker, Lorena
Bullmore, Edward T.
Smith, Marie
Christensen, Soren
Nathan, Pradeep J.
Rockstroh, Brigitte
Bassett, Danielle S.
TI Reproducibility of graph metrics of human brain functional networks
SO NEUROIMAGE
LA English
DT Article
ID SMALL-WORLD NETWORKS; WORKING-MEMORY; THEORETICAL ANALYSIS;
CONNECTIVITY; SCHIZOPHRENIA; EEG; SYNCHRONIZATION; METAANALYSIS
AB Graph theory provides many metrics of complex network organization that can be applied to analysis of brain networks derived from neuroimaging data. Here we investigated the test-retest reliability of graph metrics of functional networks derived from magnetoencephalography (MEG) data recorded in two sessions from 16 healthy volunteers who were studied at rest and during performance of the n-back working memory task in each session. For each subject's data at each session, we used a wavelet filter to estimate the mutual information (MI) between each pair of MEG sensors in each of the classical frequency intervals from gamma to low 6 in the overall range 1-60 Hz. Undirected binary graphs were generated by thresholding the MI matrix and 8 global network metrics were estimated: the clustering coefficient, path length, small-worldness, efficiency, cost-efficiency, assortativity, hierarchy, and synchronizability. Reliability of each graph metric was assessed using the intraclass correlation (ICC). Good reliability was demonstrated for most metrics applied to the n-back data (mean ICC=0.62). Reliability was greater for metrics in lower frequency networks. Higher frequency gamma and beta-band networks were less reliable at a global level but demonstrated high reliability of nodal metrics in frontal and parietal regions. Performance of the n-back task was associated with greater reliability than measurements on resting state data. Task practice was also associated with greater reliability. Collectively these results suggest that graph metrics are sufficiently reliable to be considered for future longitudinal studies of functional brain network changes. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Deuker, Lorena; Bullmore, Edward T.; Nathan, Pradeep J.; Bassett, Danielle S.] Univ Cambridge, Addenbrookes Hosp, Brain Mapping Unit, Dept Psychiat,Behav & Clin Neurosci Inst, Cambridge CB2 2QQ, England.
[Deuker, Lorena; Rockstroh, Brigitte] Univ Constance, Dept Psychol, D-7750 Constance, Germany.
[Bullmore, Edward T.; Christensen, Soren; Nathan, Pradeep J.] Addenbrookes Hosp, GSK Clin Unit Cambridge, Cambridge, England.
[Smith, Marie] MRC Cognit, Cambridge, England.
[Smith, Marie] Brain Sci Unit, Cambridge, England.
[Bassett, Danielle S.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Bassett, Danielle S.] Univ Cambridge, Dept Phys, Biol Soft Syst Sector, Cambridge CB2 2QQ, England.
RP Bullmore, ET (reprint author), Univ Cambridge, Addenbrookes Hosp, Brain Mapping Unit, Dept Psychiat,Behav & Clin Neurosci Inst, Cambridge CB2 2QQ, England.
EM etb23@cam.ac.uk; dp317@cam.ac.uk
RI Smith, Marie/N-8491-2013; Bullmore, Edward/C-1706-2012
OI Bullmore, Edward/0000-0002-8955-8283
FU GlaxoSmithKline; Brain Sciences Unit; Wellcome Trust; MRC; German
Academic Exchange Service (DAAD); National Institutes of Health Graduate
Partnerships Program
FX This experiment was sponsored by GlaxoSmithKline and conducted at the
MRC Cognition and Brain Sciences Unit and the Wellcome Trust and
MRC-funded Behavioural and Clinical Neurosciences Institute, Cambridge
UK. Software development was Supported by a Human Brain Project grant
from the National Institute of Biomedical Imaging and Bioengineering and
the National Institute of Mental Health. LD was supported by a
scholarship from the German Academic Exchange Service (DAAD). DSB was
supported by the National Institutes of Health Graduate Partnerships
Program.
NR 32
TC 96
Z9 96
U1 0
U2 19
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD OCT 1
PY 2009
VL 47
IS 4
BP 1460
EP 1468
DI 10.1016/j.neuroimage.2009.05.035
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 484HN
UT WOS:000269035100035
PM 19463959
ER
PT J
AU de Zwart, JA
van Gelderen, P
Jansma, JM
Fukunaga, M
Bianciardi, M
Duyn, JH
AF de Zwart, Jacco A.
van Gelderen, Peter
Jansma, J. Martijn
Fukunaga, Masaki
Bianciardi, Marta
Duyn, Jeff H.
TI Hemodynamic nonlinearities affect BOLD fMRI response timing and
amplitude
SO NEUROIMAGE
LA English
DT Article
ID CEREBRAL-BLOOD-FLOW; IMPULSE-RESPONSE; FUNCTIONAL MRI; SOMATOSENSORY
CORTEX; HUMAN BRAIN; STIMULUS; EVENT; RAT; DYNAMICS; SYSTEM
AB The interpretation of functional magnetic resonance imaging (fMRI) studies based on blood oxygen-level dependent (BOLD) contrast generally relies on the assumption of a linear relationship between evoked neuronal activity and fMRI response. While nonlinearities in this relationship have been suggested by a number of studies, it remains unclear to what extent they relate to the neurovascular response and are therefore inherent to BOLD fMRI Full characterization of potential vascular nonlinearities is required for accurate inferences about the neuronal system under study. To investigate the extent of vascular nonlinearities, evoked activity was studied in. humans with BOLD fMRI (n = 28) and magneto-encephalography (MEG) (n = 5). Brief (600-800 ms) rapidly repeated (1 Hz) visual stimuli were delivered using a Stimulation paradigm that minimized neuronal nonlinearities. Nevertheless, BOLD fMRI experiments showed substantial remaining nonlinearities. The smallest stimulus separation (200-400 ms) resulted in significant response broadening (15-20% amplitude decrease; 10-12% latency increase: 6-14% duration increase) with respect to a linear prediction. The substantial slowing and widening of the response in the presence of preceding stimuli suggest a vascular rather than neuronal origin to the observed nonlinearity. This was confirmed by the MEG data, which showed no significant neuro-electric nonlinear interactions between stimuli as little as 200 ms apart. The presence of substantial vascular nonlinearities has important implications for rapid event-related studies by fMRI and other imaging modalities that infer neuronal activity from hemodynamic parameters. Published by Elsevier Inc.
C1 [de Zwart, Jacco A.; van Gelderen, Peter; Jansma, J. Martijn; Fukunaga, Masaki; Bianciardi, Marta; Duyn, Jeff H.] NINDS, Adv MRI Sect, LFMI, NIH, Bethesda, MD 20892 USA.
RP de Zwart, JA (reprint author), NINDS, Adv MRI Sect, LFMI, NIH, Bldg 10,Rm B1D-728,9000 Rockville Pk-MSC 1065, Bethesda, MD 20892 USA.
EM jacco.deZwart@nih.gov
RI Duyn, Jozef/F-2483-2010; Fukunaga, Masaki/F-6441-2013
OI Fukunaga, Masaki/0000-0003-1010-2644
FU Intramural NIH HHS [Z99 NS999999]
NR 44
TC 20
Z9 20
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD OCT 1
PY 2009
VL 47
IS 4
BP 1649
EP 1658
DI 10.1016/j.neuroimage.2009.06.001
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 484HN
UT WOS:000269035100053
PM 19520175
ER
PT J
AU Stroth, N
Eiden, LE
AF Stroth, N.
Eiden, L. E.
TI PACAP REGULATES NEUROPEPTIDE EXPRESSION AT THE SYMPATHOADRENAL SYNAPSE
DURING METABOLIC STRESS
SO NEUROPEPTIDES
LA English
DT Meeting Abstract
CT Joint Meeting of the European-Neuropeptides-Club/Summer Neuropeptides
Conference
CY JUL 20-23, 2009
CL Salzburg, AUSTRIA
SP European Neuropeptides Club
C1 [Stroth, N.; Eiden, L. E.] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0143-4179
J9 NEUROPEPTIDES
JI Neuropeptides
PD OCT
PY 2009
VL 43
IS 5
BP 411
EP 411
PG 1
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 521AH
UT WOS:000271890700013
ER
PT J
AU Eiden, LE
AF Eiden, L. E.
TI Neuropeptide signaling and the stress transcriptome
SO NEUROPEPTIDES
LA English
DT Meeting Abstract
CT Joint Meeting of the European-Neuropeptides-Club/Summer Neuropeptides
Conference
CY JUL 20-23, 2009
CL Salzburg, AUSTRIA
SP European Neuropeptides Club
C1 [Eiden, L. E.] NIMH, Mol Neurosci Sect, Intramural Res Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0143-4179
J9 NEUROPEPTIDES
JI Neuropeptides
PD OCT
PY 2009
VL 43
IS 5
BP 440
EP 441
PG 2
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 521AH
UT WOS:000271890700107
ER
PT J
AU Moody, TW
Berna, M
Mantey, S
Jensen, RT
AF Moody, T. W.
Berna, M.
Mantey, S.
Jensen, R. T.
TI NMB causes transactivation of EGF receptors in lung cancer cells
SO NEUROPEPTIDES
LA English
DT Meeting Abstract
CT Joint Meeting of the European-Neuropeptides-Club/Summer Neuropeptides
Conference
CY JUL 20-23, 2009
CL Salzburg, AUSTRIA
SP European Neuropeptides Club
C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
NIDDK, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0143-4179
J9 NEUROPEPTIDES
JI Neuropeptides
PD OCT
PY 2009
VL 43
IS 5
BP 444
EP 444
PG 1
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 521AH
UT WOS:000271890700121
ER
PT J
AU Cservenak, M
Palkovits, M
Usdin, TB
Dobolyi, A
AF Cservenak, M.
Palkovits, M.
Usdin, T. B.
Dobolyi, A.
TI Activation of posterior thalamic TIP39 neurons in mother rats
SO NEUROPEPTIDES
LA English
DT Meeting Abstract
CT Joint Meeting of the European-Neuropeptides-Club/Summer Neuropeptides
Conference
CY JUL 20-23, 2009
CL Salzburg, AUSTRIA
SP European Neuropeptides Club
C1 [Cservenak, M.; Palkovits, M.; Dobolyi, A.] Hungarian Acad Sci, Dept Anat Histol & Embryol, Neuromorphol & Neuroendocrine Res Lab, Budapest, Hungary.
[Cservenak, M.; Palkovits, M.; Dobolyi, A.] Semmelweis Univ, H-1085 Budapest, Hungary.
[Usdin, T. B.] NIMH, Sect Fundamental Neurosci, Bethesda, MD 20892 USA.
RI Palkovits, Miklos/F-2707-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0143-4179
J9 NEUROPEPTIDES
JI Neuropeptides
PD OCT
PY 2009
VL 43
IS 5
BP 449
EP 450
PG 2
WC Endocrinology & Metabolism; Neurosciences
SC Endocrinology & Metabolism; Neurosciences & Neurology
GA 521AH
UT WOS:000271890700139
ER
PT J
AU Krasnova, IN
Hodges, AB
Ladenheim, B
Rhoades, R
Phillip, CG
Cesena, A
Ivanova, E
Hohmann, CF
Cadet, JL
AF Krasnova, Irina N.
Hodges, Amber B.
Ladenheim, Bruce
Rhoades, Raina
Phillip, Crystal G.
Cesena, Angela
Ivanova, Ekaterina
Hohmann, Christine F.
Cadet, Jean Lud
TI Methamphetamine treatment causes delayed decrease in novelty-induced
locomotor activity in mice
SO NEUROSCIENCE RESEARCH
LA English
DT Article
DE Methamphetamine; Dopamine; Neurotoxicity; Striatum; Cortex;
Novelty-induced locomotor activity
ID INDUCED NEURONAL APOPTOSIS; INDUCED NEUROTOXICITY; RECOGNITION MEMORY;
DOPAMINE TRANSPORTERS; PSYCHIATRIC-SYMPTOMS; PARKINSONS-DISEASE;
NONHUMAN-PRIMATES; BASAL GANGLIA; MOTOR; RATS
AB Methamphetamine (METH) is a psychostimulant that causes damage to dopamine (DA) axons and to non-monoaminergic neurons in the brain. The aim of the present study was to investigate short- and long-term effects of neurotoxic METH treatment on novelty-induced locomotor activity in mice. Male BALB/c mice, 12-14 weeks old, were injected with saline or METH (i.p., 7.5 mg/kg x 4 times, every 2 h). Behavior and neurotoxic effects were assessed at 10 days, 3 and 5 months following drug treatment. METH administration caused marked decreases in DA levels in the mouse striatum and cortex at 10 days post-drug. However, METH did not induce any changes in novelty-induced locomotor activity. At 3 and 5 months after treatment METH-exposed mice showed significant recovery of DA levels in the striatum and cortex. In contrast, these animals demonstrated significant decreases in locomotor activity at 5 months in comparison to aged-matched control mice. Further assessment of METH toxicity using TUNEL staining showed that the drug induced increased cell death in the striatum and cortex at 3 days after administration. Taken together, these data suggest that delayed deficits in novelty-induced locomotor activity observed in METH-exposed animals are not due to neurodegeneration of DA terminals but to combined effects of METH and age-dependent dysfunction of non-DA intrinsic striatal and/or corticostriatal neurons. Published by Elsevier Ireland Ltd and the Japan Neuroscience Society.
C1 [Krasnova, Irina N.; Ladenheim, Bruce; Cesena, Angela; Ivanova, Ekaterina; Cadet, Jean Lud] Natl Inst Drug Abuse, Mol Neuropsychiat Res Branch, NIH, DHHS, Baltimore, MD 21224 USA.
[Hodges, Amber B.; Rhoades, Raina; Phillip, Crystal G.; Hohmann, Christine F.] Morgan State Univ, Dept Biol, Baltimore, MD 21224 USA.
RP Cadet, JL (reprint author), Natl Inst Drug Abuse, Mol Neuropsychiat Res Branch, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM jcadet@intra.nida.nih.gov
FU NIH/DHHS [3SO6 GM051971, U54 MH066417, R25 CM058904]
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse of the NIH/DHHS (to I.N.K., B.L., A-C.,
E.I. and J.LC.), and by grants 3SO6 GM051971 and U54 MH066417 (to
C.F.H.) and R25 CM058904 (to R.R. and C.G.P.).
NR 62
TC 12
Z9 12
U1 2
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0168-0102
J9 NEUROSCI RES
JI Neurosci. Res.
PD OCT
PY 2009
VL 65
IS 2
BP 160
EP 165
DI 10.1016/j.neures.2009.06.007
PG 6
WC Neurosciences
SC Neurosciences & Neurology
GA 498SJ
UT WOS:000270163100006
PM 19559060
ER
PT J
AU Machado-Vieira, R
Manji, HK
Zarate, CA
AF Machado-Vieira, Rodrigo
Manji, Husseini K.
Zarate, Carlos A.
TI The Role of the Tripartite Glutamatergic Synapse in the Pathophysiology
and Therapeutics of Mood Disorders
SO NEUROSCIENTIST
LA English
DT Review
DE glutamate; tripartite; bipolar disorder; ketamine; riluzole
ID METHYL-D-ASPARTATE; MAJOR DEPRESSIVE DISORDER; OPEN-LABEL TRIAL;
MAGNETIC-RESONANCE SPECTROSCOPY; SEROTONIN REUPTAKE INHIBITORS;
OBSESSIVE-COMPULSIVE DISORDER; ANTERIOR CINGULATE ACTIVITY; BIPOLAR
AFFECTIVE-DISORDER; MGLU5 RECEPTOR ANTAGONIST; GAMMA-AMINOBUTYRIC-ACID
AB Bipolar disorder and major depressive disorder are common, chronic, and recurrent mood disorders that affect the lives of millions of individuals worldwide. Growing evidence suggests that glutamatergic system dysfunction is directly involved in mood disorders. This article describes the role of the "tripartite glutamatergic synapse," comprising presynaptic and post-synaptic neurons and glial cells, in the pathophysiology and therapeutics of mood disorders. Glutamatergic neurons and glia directly control synaptic and extrasynaptic glutamate levels/release through integrative effects that target glutamate excitatory amino acid transporters, postsynaptic density proteins, ionotropic receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [AMPA], N-methyl-D-aspartate [NAIDA], and kainate) and metabotropic receptors. This article also explores the glutamatergic modulators riluzole and ketamine, which are considered valuable proof-of-concept agents for developing the next generation of antidepressants and mood stabilizers. In therapeutically relevant paradigms ketamine preferentially targets postsynaptic AMPA/NMDA receptors, and riluzole preferentially targets presynaptic voltage-operated channels and glia.
C1 [Machado-Vieira, Rodrigo; Zarate, Carlos A.] NIMH, Expt Therapeut Mood & Anxiety Disorders Res Progr, NIH, Bethesda, MD 20892 USA.
[Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
RP Zarate, CA (reprint author), NIMH, Expt Therapeut Mood & Anxiety Disorders Program, Mark O Hatfield Clin Res Ctr, 10 Ctr Dr,CRC,Unit 4 SE,Room 7-3445, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190
FU Intramural NIH HHS [Z01 MH002828-05, Z01 MH002857-03]
NR 149
TC 89
Z9 95
U1 7
U2 15
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1073-8584
EI 1089-4098
J9 NEUROSCIENTIST
JI Neuroscientist
PD OCT
PY 2009
VL 15
IS 5
BP 525
EP 539
DI 10.1177/1073858409336093
PG 15
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 500LP
UT WOS:000270303800018
PM 19471044
ER
PT J
AU Koenigs, M
Grafman, J
AF Koenigs, Michael
Grafman, Jordan
TI Posttraumatic Stress Disorder: The Role of Medial Prefrontal Cortex and
Amygdala
SO NEUROSCIENTIST
LA English
DT Review
DE posttraumatic stress disorder; prefrontal cortex; amygdala; emotion
ID CONDITIONED FEAR; ORBITOFRONTAL CORTEX; MAJOR DEPRESSION; COMBAT
VETERANS; EXTINCTION; BRAIN; PTSD; HUMANS; ACTIVATION; VIETNAM
AB Posttraumatic stress disorder (PTSD) is characterized by recurrent distressing memories of an emotionally traumatic event. In this review, the authors present neuroscientific data highlighting the function of two brain areas-the amygdala and ventromedial prefrontal cortex (vmPFC)-in PTSD and related emotional processes. A convergent body of human and nonhuman Studies suggests that the amygdala mediates the acquisition and expression of conditioned fear and the enhancement of emotional memory, whereas the vmPFC mediates the extinction of conditioned fear and the volitional regulation of negative emotion. It has been theorized that the vmPFC exerts inhibition on the amygdala, and that a defect in this inhibition could account for the symptoms of PTSD. This theory is supported by functional imaging studies of PTSD patients, who exhibit hypoactivity in the vmPFC but hyperactivity in the amygdala. A recent study of brain-injured and trauma-exposed combat veterans confirms that amygdala damage reduces the likelihood of developing PTSD. But contrary to the prediction of the top-down inhibition model, vmPFC damage also reduces the likelihood of developing PTSD. The putative roles of the amygdala and the vmPFC in the pathophysiology of PTSD, as well as implications for potential treatments, are discussed in light of these results.
C1 [Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Koenigs, Michael] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA.
RP Grafman, J (reprint author), Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, 10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA.
EM grafmanj@ninds.nih.gov
OI Grafman, Jordan H./0000-0001-8645-4457; Koenigs,
Michael/0000-0002-5799-4881
FU National Institute of Neurological Disorders and Stroke intramural
research [DAMD17-01-1-0675]
FX This work was Supported in part by the National Institute of
Neurological Disorders and Stroke intramural research program,
DAMD17-01-1-0675 (J.G.)
NR 59
TC 93
Z9 98
U1 9
U2 31
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1073-8584
J9 NEUROSCIENTIST
JI Neuroscientist
PD OCT
PY 2009
VL 15
IS 5
BP 540
EP 548
DI 10.1177/1073858409333072
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 500LP
UT WOS:000270303800019
PM 19359671
ER
PT J
AU Yamada, S
Lonser, RR
Colohan, ART
Yamada, SM
Won, DJ
AF Yamada, Shokei
Lonser, Russell R.
Colohan, Austin R. T.
Yamada, Shoko M.
Won, Daniel J.
TI BYPASS COAPTATION FOR CERVICAL ROOT AVULSION: INDICATIONS FOR OPTIMAL
OUTCOME
SO NEUROSURGERY
LA English
DT Article
DE Bypass coaptation; Cervical root avulsion; Nerve regeneration
ID BRACHIAL-PLEXUS INJURY; CONFIGURATION; NEUROTIZATION
AB OBJECTIVE: Previously, we reported bypass coaptation of the C3 and C4 anterior rami to the upper trunk of the brachial plexus for restoration of the muscles denervated as a result of C5 and C6 nerve root avulsion. This procedure is thought to be superior to the transfer of individual peripheral nerve fibers to the brachial plexus branches. Therefore, the benefits of the bypass coaptation procedures in the treatment of various root avulsions are presented.
METHODS: Twenty-six patients were selected as suitable candidates for bypass coaptation procedures. They were divided into 3 groups: 1) Erb-Duchenne palsy due to C5 and C6 root avulsion, 2) Klumpke palsy due to C8 and T1 root avulsion, and 3) the flail arm (or flail upper limb) due to C5 through T1 root avulsion. The surgical techniques are described in detail.
RESULTS: The coaptation procedures for the first group resulted in excellent recovery of all the denervated muscles. The patients in the second group showed reinnervation of the finger muscles and finger sensory distributions in infants within the first year after surgery. The flail arm group regained satisfactory proximal muscle function but only mild distal muscle function. One exception was a child who showed significant recovery in proximal and distal motor and sensory function.
CONCLUSION: We recommend the bypass coaptation as a useful procedure for the following categories: Erb-Duchenne palsy due to C5 and C6 root avulsion in all ages, Klumpke palsy due to the C8 and T1 avulsion, and the flail arm due to C5 through T1 avulsion in young children. However, bypass procedures for the flail limb in adults require additional innovative methods to facilitate the growth rate of regenerating nerves.
C1 [Yamada, Shokei; Colohan, Austin R. T.] Loma Linda Univ, Dept Neurosurg, Loma Linda, CA 92543 USA.
[Lonser, Russell R.] NIH, Dept Neurol Surg, Bethesda, MD 20892 USA.
[Yamada, Shoko M.] Teikyo Univ, Ichihara Med Ctr, Dept Neurosurg, Chiba, Japan.
[Won, Daniel J.] Kaiser Permanente Med Ctr, Div Pediat, Dept Neurosurg, Fontana, CA USA.
RP Yamada, S (reprint author), Loma Linda Univ, Dept Neurosurg, 11234 Anderson St, Loma Linda, CA 92543 USA.
EM yamada1000@gmail.com
NR 20
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-396X
J9 NEUROSURGERY
JI Neurosurgery
PD OCT
PY 2009
VL 65
IS 4
BP A203
EP A211
DI 10.1227/01.NEU.0000358615.92344.D1
PG 9
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 502XB
UT WOS:000270492600031
PM 28180833
ER
PT J
AU Wine, RN
McPherson, CA
Harry, GJ
AF Wine, Robert N.
McPherson, Christopher A.
Harry, G. Jean
TI IGF-1 and pAKT Signaling Promote Hippocampal CA1 Neuronal Survival
Following Injury to Dentate Granule Cells
SO NEUROTOXICITY RESEARCH
LA English
DT Article
DE Microglia; Hippocampus; Pyramidal neurons; Trimethyltin; IGF-1; pAkt;
Seizure
ID GROWTH-FACTOR-I; TUMOR-NECROSIS-FACTOR; PROTEIN-KINASE B/AKT; L
CALCIUM-CHANNELS; PHOSPHATIDYLINOSITOL 3-KINASE; NERVOUS-SYSTEM; AKT
ACTIVATION; MESSENGER-RNA; TNF-ALPHA; CULTURED HIPPOCAMPAL
AB Insulin-like growth factor-1 (IGF-1) protects neurons from apoptosis and in vivo offers neuroprotective support to hippocampal CA1 pyramidal neurons following ischemia or seizure. IGF-1 signals through IGF-1 receptors activating phosphytidylinositol 3-kinase (PI3K)/Akt or pMAPK pathways. IGF-1 can be induced with injury and microglia and astrocytes may serve as a source of this neurotrophic factor to promote neuronal survival. An acute systemic injection of trimethyltin (TMT; 2 mg/kg, ip) to mice induces apoptosis of dentate granule neurons within 24 h and a differential response of microglia with ramified microglia present in the CA-1 region. Using this model, we studied the role of IGF-1 in the survival of CA-1 pyramidal neurons under conditions of altered synaptic input due to changes in the dentate gyrus. Within 24 h of injection, IGF-1 mRNA levels were elevated in the hippocampus and IGF-1 protein detected in both astrocytes and microglia. IGF-1 was redistributed within the CA-1 neurons corresponding with an increase in cytoplasmic pAkt, elevated PKB alpha/Akt protein levels, and a decrease in the antagonist, Rho. pMAPK was not detected in CA-1 neurons and ERK2 showed a transient decrease followed by a significant increase, suggesting a lack of recruitment of the pMAPK signaling pathway for neuronal survival. In mice deficient for IGF-1, a similar level of apoptosis was observed in dentate granule neurons as compared to wildtype; however, TMT induced a significant level CA-1 neuronal death, further supporting a role for IGF-1 in the survival of CA-1 neurons.
C1 [Wine, Robert N.; McPherson, Christopher A.; Harry, G. Jean] NIEHS, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Harry, GJ (reprint author), NIEHS, Mol Toxicol Lab, NIH, POB 12233,MD C1-04, Res Triangle Pk, NC 27709 USA.
EM harry@niehs.nih.gov
FU Division of Intramural Research, National Institute of Environmental
Health Sciences, National Institutes of Health
FX This research was funded by the Division of Intramural Research,
National Institute of Environmental Health Sciences, National Institutes
of Health.
NR 90
TC 20
Z9 21
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1029-8428
J9 NEUROTOX RES
JI Neurotox. Res.
PD OCT
PY 2009
VL 16
IS 3
BP 280
EP 292
DI 10.1007/s12640-009-9060-y
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 484AG
UT WOS:000269014400010
PM 19526277
ER
PT J
AU Landon, MB
Spong, CY
Thom, E
Carpenter, MW
Ramin, SM
Casey, B
Wapner, RJ
Varner, MW
Rouse, DJ
Thorp, JM
Sciscione, A
Catalano, P
Harper, M
Saade, G
Lain, KY
Sorokin, Y
Peaceman, AM
Tolosa, JE
Anderson, GB
AF Landon, Mark B.
Spong, Catherine Y.
Thom, Elizabeth
Carpenter, Marshall W.
Ramin, Susan M.
Casey, Brian
Wapner, Ronald J.
Varner, Michael W.
Rouse, Dwight J.
Thorp, John M., Jr.
Sciscione, Anthony
Catalano, Patrick
Harper, Margaret
Saade, George
Lain, Kristine Y.
Sorokin, Yoram
Peaceman, Alan M.
Tolosa, Jorge E.
Anderson, Garland B.
CA Eunice Kennedy Shriver NICHHD Mate
TI A Multicenter, Randomized Trial of Treatment for Mild Gestational
Diabetes.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID IMPAIRED GLUCOSE-TOLERANCE; ADVERSE PREGNANCY OUTCOMES; SERVICES
TASK-FORCE; CLINICAL-TRIALS; MELLITUS; MANAGEMENT; HYPERGLYCEMIA;
RECOMMENDATIONS; DELIVERY
AB Background: It is uncertain whether treatment of mild gestational diabetes mellitus improves pregnancy outcomes.
Methods: Women who were in the 24th to 31st week of gestation and who met the criteria for mild gestational diabetes mellitus (i.e., an abnormal result on an oral glucose-tolerance test but a fasting glucose level below 95 mg per deciliter [5.3 mmol per liter]) were randomly assigned to usual prenatal care (control group) or dietary intervention, self-monitoring of blood glucose, and insulin therapy, if necessary (treatment group). The primary outcome was a composite of stillbirth or perinatal death and neonatal complications, including hyperbilirubinemia, hypoglycemia, hyperinsulinemia, and birth trauma.
Results: A total of 958 women were randomly assigned to a study group -- 485 to the treatment group and 473 to the control group. We observed no significant difference between groups in the frequency of the composite outcome (32.4% and 37.0% in the treatment and control groups, respectively; P=0.14). There were no perinatal deaths. However, there were significant reductions with treatment as compared with usual care in several prespecified secondary outcomes, including mean birth weight (3302 vs. 3408 g), neonatal fat mass (427 vs. 464 g), the frequency of large-for-gestational-age infants (7.1% vs. 14.5%), birth weight greater than 4000 g (5.9% vs. 14.3%), shoulder dystocia (1.5% vs. 4.0%), and cesarean delivery (26.9% vs. 33.8%). Treatment of gestational diabetes mellitus, as compared with usual care, was also associated with reduced rates of preeclampsia and gestational hypertension (combined rates for the two conditions, 8.6% vs. 13.6%; P=0.01).
Conclusions: Although treatment of mild gestational diabetes mellitus did not significantly reduce the frequency of a composite outcome that included stillbirth or perinatal death and several neonatal complications, it did reduce the risks of fetal overgrowth, shoulder dystocia, cesarean delivery, and hypertensive disorders. (ClinicalTrials.gov number, NCT00069576.)
N Engl J Med 2009;361:1339-48.
C1 [Landon, Mark B.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver NICHHD, Bethesda, MD USA.
[Thom, Elizabeth] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Carpenter, Marshall W.] Brown Univ, Dept Obstet, Providence, RI 02912 USA.
[Carpenter, Marshall W.] Brown Univ, Dept Gynecol, Providence, RI 02912 USA.
[Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Casey, Brian] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Wapner, Ronald J.] Columbia Univ, New York, NY USA.
[Varner, Michael W.] Univ Utah, Salt Lake City, UT USA.
[Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA.
[Thorp, John M., Jr.] Univ N Carolina, Chapel Hill, NC USA.
[Sciscione, Anthony] Drexel Univ, Philadelphia, PA 19104 USA.
[Catalano, Patrick] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Saade, George; Anderson, Garland B.] Univ Texas Med Branch, Galveston, TX USA.
[Lain, Kristine Y.] Univ Pittsburgh, Pittsburgh, PA USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA.
[Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
RP Landon, MB (reprint author), Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
EM mark.landon@osumc.edu
RI Varner, Michael/K-9890-2013;
OI Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD27915, HD34116, HD40485, HD34208, HD27869, HD40500,
HD40560, HD34136, HD40544, HD27860, HD40545, HD53097, HD21410, HD27917,
HD40512, HD53118, HD36801]; General Clinical Research Centers
[M01-RR00034]; National Center for Research Resources [UL1-RR024989,
M01-RR00080, UL1-RR025764, C06-RR11234]
FX Supported by grants from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development ( HD27915, HD34116, HD40485,
HD34208, HD27869, HD40500, HD40560, HD34136, HD40544, HD27860, HD40545,
HD53097, HD21410, HD27917, HD40512, HD53118, HD36801), the General
Clinical Research Centers (M01-RR00034), and the National Center for
Research Resources (UL1-RR024989, M01-RR00080, UL1-RR025764,
C06-RR11234).
NR 32
TC 642
Z9 677
U1 10
U2 57
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 1
PY 2009
VL 361
IS 14
BP 1339
EP 1348
DI 10.1056/NEJMoa0902430
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 500KZ
UT WOS:000270300000008
PM 19797280
ER
PT J
AU Hopkins, JF
Panja, S
McNeil, SAN
Woodson, SA
AF Hopkins, Julia F.
Panja, Subrata
McNeil, Stephanie A. N.
Woodson, Sarah A.
TI Effect of salt and RNA structure on annealing and strand displacement by
Hfq
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID SM-LIKE PROTEIN; HELIX-COIL TRANSITION; ESCHERICHIA-COLI HFQ; SMALL
REGULATORY RNA; DSRA RNA; SECONDARY STRUCTURE; CHAPERONE ACTIVITY;
MOLECULAR BEACONS; BINDING; RPOS
AB The Sm-like protein Hfq promotes the association of small antisense RNAs (sRNAs) with their mRNA targets, but the mechanism of Hfq's RNA chaperone activity is unknown. To investigate RNA annealing and strand displacement by Hfq, we used oligonucleotides that mimic functional sequences within DsrA sRNA and the complementary rpoS mRNA. Hfq accelerated at least 100-fold the annealing of a fluorescently labeled molecular beacon to a 16-nt RNA. The rate of strand exchange between the oligonucleotides increased 80-fold. Therefore, Hfq is very active in both helix formation and exchange. However, high concentrations of Hfq destabilize the duplex by preferentially binding the single-stranded RNA. RNA binding and annealing were completely inhibited by 0.5M salt. The target site in DsrA sRNA was 1000-fold less accessible to the molecular beacon than an unstructured oligonucleotide, and Hfq accelerated annealing with DsrA only 2-fold. These and other results are consistent with recycling of Hfq during the annealing reaction, and suggest that the net reaction depends on the relative interaction of Hfq with the products and substrates.
C1 [Panja, Subrata; Woodson, Sarah A.] Johns Hopkins Univ, TC Jenkins Dept Biophys, Baltimore, MD 21218 USA.
[McNeil, Stephanie A. N.] Johns Hopkins Univ, NIH, Grad Partnership Program, Baltimore, MD 21218 USA.
[Hopkins, Julia F.] Johns Hopkins Univ, Program Cellular Mol & Dev Biol & Biophys, Baltimore, MD 21218 USA.
RP Woodson, SA (reprint author), Johns Hopkins Univ, TC Jenkins Dept Biophys, 3400 N Charles St, Baltimore, MD 21218 USA.
EM swoodson@jhu.edu
OI Woodson, Sarah/0000-0003-0170-1987
FU National Institutes of Health [R01 GM46686]
FX The National Institutes of Health (R01 GM46686).
NR 45
TC 23
Z9 23
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD OCT
PY 2009
VL 37
IS 18
BP 6205
EP 6213
DI 10.1093/nar/gkp646
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 510RR
UT WOS:000271109300030
PM 19671524
ER
PT J
AU Entezam, A
Usdin, K
AF Entezam, Ali
Usdin, Karen
TI ATM and ATR protect the genome against two different types of tandem
repeat instability in Fragile X premutation mice
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID HUNTINGTONS-DISEASE GENE; CGG REPEAT; TRANSGENIC MICE; CAG REPEAT;
IN-VITRO; REPLICATION; EXPRESSION; INACTIVATION; POPULATION; EXPANSIONS
AB Expansion of a tandem repeat tract is responsible for the Repeat Expansion diseases, a group of more than 20 human genetic disorders that includes those like Fragile X (FX) syndrome that result from repeat expansion in the FMR1 gene. We have previously shown that the ATM and Rad3-related (ATR) checkpoint kinase protects the genome against one type of repeat expansion in a FX premutation mouse model. By crossing the FX premutation mice to Ataxia Telangiectasia-Mutated (Atm) mutant mice, we show here that ATM also prevents repeat expansion. However, our data suggest that the ATM-sensitive mechanism is different from the ATR-sensitive one. Specifically, the effect of the ATM deficiency is more marked when the premutation allele is paternally transmitted and expansions occur more frequently in male offspring regardless of the Atm genotype of the offspring. The gender effect is most consistent with a repair event occurring in the early embryo that is more efficient in females, perhaps as a result of the action of an X-linked DNA repair gene. Our data thus support the hypothesis that two different mechanisms of FX repeat expansion exist, an ATR-sensitive mechanism seen on maternal transmission and an ATM-sensitive mechanism that shows a male expansion bias.
C1 [Entezam, Ali; Usdin, Karen] NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA.
[Entezam, Ali] Univ Exeter, Peninsula Coll Med & Dent, Inst Biomed & Clin Sci, Exeter EX1 2LU, Devon, England.
RP Usdin, K (reprint author), NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA.
EM ku@helix.nih.gov
FU NIDDK (National Institutes of Health)
FX The Intramural Program of the NIDDK (National Institutes of Health).
Funding for open access charge: The Intramural program of NIDDK,
National Institutes of Health.
NR 37
TC 24
Z9 24
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD OCT
PY 2009
VL 37
IS 19
BP 6371
EP 6377
DI 10.1093/nar/gkp666
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 514JH
UT WOS:000271389900007
PM 19710035
ER
PT J
AU Rosa, ID
Goffart, S
Wurm, M
Wiek, C
Essmann, F
Sobek, S
Schroeder, P
Zhang, HL
Krutmann, J
Hanenberg, H
Schulze-Osthoff, K
Mielke, C
Pommier, Y
Boege, F
Christensen, MO
AF Rosa, Ilaria Dalla
Goffart, Steffi
Wurm, Melanie
Wiek, Constanze
Essmann, Frank
Sobek, Stefan
Schroeder, Peter
Zhang, Hongliang
Krutmann, Jean
Hanenberg, Helmut
Schulze-Osthoff, Klaus
Mielke, Christian
Pommier, Yves
Boege, Fritz
Christensen, Morten O.
TI Adaptation of topoisomerase I paralogs to nuclear and mitochondrial DNA
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID CULTURED HUMAN-CELLS; N-TERMINAL DOMAIN; MAMMALIAN MITOCHONDRIA;
SACCHAROMYCES-CEREVISIAE; LIVING CELLS; HELA-CELLS; III-ALPHA;
TRANSCRIPTION; VIVO; MTDNA
AB Topoisomerase I is essential for DNA metabolism in nuclei and mitochondria. In yeast, a single topoisomerase I gene provides for both organelles. In vertebrates, topoisomerase I is divided into nuclear and mitochondrial paralogs (Top1 and Top1mt). To assess the meaning of this gene duplication, we targeted Top1 to mitochondria or Top1mt to nuclei. Overexpression in the fitting organelle served as control. Targeting of Top1 to mitochondria blocked transcription and depleted mitochondrial DNA. This was also seen with catalytically inactive Top1 mutants, but not with Top1mt overexpressed in mitochondria. Targeting of Top1mt to the nucleus revealed that it was much less able to interact with mitotic chromosomes than Top1 overexpressed in the nucleus. Similar experiments with Top1/Top1mt hybrids assigned these functional differences to structural divergences in the DNA-binding core domains. We propose that adaptation of this domain to different chromatin environments in nuclei and mitochondria has driven evolutional development and conservation of organelle-restricted topoisomerase I paralogs in vertebrates.
C1 [Rosa, Ilaria Dalla; Sobek, Stefan; Mielke, Christian; Boege, Fritz; Christensen, Morten O.] Univ Dusseldorf, Sch Med, Inst Clin Chem, D-40225 Dusseldorf, Germany.
[Rosa, Ilaria Dalla; Sobek, Stefan; Mielke, Christian; Boege, Fritz; Christensen, Morten O.] Univ Dusseldorf, Sch Med, Diagnost Lab, D-40225 Dusseldorf, Germany.
[Goffart, Steffi] Inst Med Technol, Tampere, Finland.
[Wurm, Melanie; Wiek, Constanze; Hanenberg, Helmut] Univ Dusseldorf, Childrens Hosp, Dept Pediat Oncol Hematol & Immunol, Sch Med, D-40225 Dusseldorf, Germany.
[Essmann, Frank; Schulze-Osthoff, Klaus] Univ Tubingen, Interfac Inst Biochem, D-72076 Tubingen, Germany.
[Schroeder, Peter; Krutmann, Jean] Univ Dusseldorf, Environm Hlth Res Inst, D-40225 Dusseldorf, Germany.
[Zhang, Hongliang; Pommier, Yves] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
RP Boege, F (reprint author), Univ Dusseldorf, Sch Med, Inst Clin Chem, D-40225 Dusseldorf, Germany.
EM boege@med.uni-duesseldorf.de; christensen@med.uni-duesseldorf.de
RI Schulze-Osthoff, Klaus/N-9025-2013; Goffart, Steffi/N-3597-2015
OI Schulze-Osthoff, Klaus/0000-0003-1443-2720; Goffart,
Steffi/0000-0001-8491-1458
FU Deutsche Forschungsgemeinschaft [CH 713/1-1, HA2322/2-1, SFB 728, GRK
1033]; National Cancer Institute, National Institute of Health
FX Deutsche Forschungsgemeinschaft (grants CH 713/1-1, HA2322/2-1, SFB 728
and GRK 1033); Intramural Program of the Center for Cancer Research,
National Cancer Institute, National Institute of Health. Funding for
open access charge: Deutsche Forschungsgemeinschaft (SFB 728 and GRK
1033).
NR 50
TC 3
Z9 3
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD OCT
PY 2009
VL 37
IS 19
BP 6414
EP 6428
DI 10.1093/nar/gkp708
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 514JH
UT WOS:000271389900011
ER
PT J
AU Yeung, ML
Bennasser, Y
Watashi, K
Le, SY
Houzet, L
Jeang, KT
AF Yeung, Man Lung
Bennasser, Yamina
Watashi, Koichi
Le, Shu-Yun
Houzet, Laurent
Jeang, Kuan-Teh
TI Pyrosequencing of small non-coding RNAs in HIV-1 infected cells:
evidence for the processing of a viral-cellular double-stranded RNA
hybrid
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SMALL INTERFERING RNAS; EMBRYONIC
STEM-CELLS; PRIMER-BINDING-SITE; HIV-1 TAR ELEMENT; HEPATITIS-C VIRUS;
REVERSE TRANSCRIPTION; MICRORNA EXPRESSION; CAENORHABDITIS-ELEGANS;
TYPE-1 REPLICATION
AB Small non-coding RNAs of 18-25 nt in length can regulate gene expression through the RNA interference (RNAi) pathway. To characterize small RNAs in HIV-1-infected cells, we performed linker-ligated cloning followed by high-throughput pyrosequencing. Here, we report the composition of small RNAs in HIV-1 productively infected MT4 T-cells. We identified several HIV-1 small RNA clones and a highly abundant small 18-nt RNA that is antisense to the HIV-1 primer-binding site (PBS). This 18-nt RNA apparently originated from the dsRNA hybrid formed by the HIV-1 PBS and the 30 end of the human cellular tRNAlys3. It was found to associate with the Ago2 protein, suggesting its possible function in the cellular RNAi machinery for targeting HIV-1.
C1 [Yeung, Man Lung; Bennasser, Yamina; Watashi, Koichi; Houzet, Laurent; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Le, Shu-Yun] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM kj7c@nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU NIAID; NCI; IATAP
FX NIAID; NCI; IATAP program from the office of the director, National
Institutes of Health. Funding for open access charge: National
Institutes of Health intramural funds.
NR 68
TC 80
Z9 84
U1 3
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD OCT
PY 2009
VL 37
IS 19
BP 6575
EP 6586
DI 10.1093/nar/gkp707
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 514JH
UT WOS:000271389900024
PM 19729508
ER
PT J
AU Dorjsuren, D
Wilson, DM
Beard, WA
McDonald, JP
Austin, CP
Woodgate, R
Wilson, SH
Simeonov, A
AF Dorjsuren, Dorjbal
Wilson, David M., III
Beard, William A.
McDonald, John P.
Austin, Christopher P.
Woodgate, Roger
Wilson, Samuel H.
Simeonov, Anton
TI A real-time fluorescence method for enzymatic characterization of
specialized human DNA polymerases
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PRONE LESION BYPASS; AURINTRICARBOXYLIC ACID; XERODERMA-PIGMENTOSUM;
Y-FAMILY; POL-IOTA; IN-VITRO; REVERSE-TRANSCRIPTASE; TRANSLESION
SYNTHESIS; MOLECULAR BEACON; MAMMALIAN-CELLS
AB Specialized DNA polymerases are involved in DNA synthesis during base-excision repair and translesion synthesis across a wide range of chemically modified DNA templates. Notable features of these enzymes include low catalytic efficiency, low processivity and low fidelity. Traditionally, in vitro studies of these enzymes have utilized radiolabeled substrates and gel electrophoretic separation of products. We have developed a simple homogeneous fluorescence-based method to study the enzymology of specialized DNA polymerases in real time. The method is based on fluorescent reporter strand displacement from a tripartite substrate containing a quencher-labeled template strand, an unlabeled primer and a fluorophore-labeled reporter. With this method, we could follow the activity of human DNA polymerases beta, eta, iota and kappa under different reaction conditions, and we investigated incorporation of the aberrant nucleotide, 8-oxodGTP, as well as bypass of an abasic site or 8-oxoG DNA template lesion in different configurations. Lastly, we demonstrate that the method can be used for small molecule inhibitor discovery and characterization in highly miniaturized settings, and we report the first nanomolar inhibitors of Y-family DNA polymerases i and g. The fluorogenic method presented here should facilitate mechanistic and inhibitor investigations of these polymerases and is also applicable to the study of highly processive replicative polymerases.
C1 [Dorjsuren, Dorjbal; Austin, Christopher P.; Simeonov, Anton] NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Wilson, David M., III] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Beard, William A.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[McDonald, John P.; Woodgate, Roger] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Genom Integr, NIH, Bethesda, MD 20892 USA.
RP Simeonov, A (reprint author), NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
EM asimeono@mail.nih.gov
FU National Institutes of Health Roadmap for Medical Research; NIA; NIEHS
[Z01-ES050158, Z01-ES050161]; NICHD; NHGRI; NIH [1U19CA105010]
FX Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research; Intramural Research Program of NIA, NIEHS,
(Z01-ES050158 and Z01-ES050161), NICHD and NHGRI, NIH, and in
association with NIH Grant 1U19CA105010. Funding for open access charge:
Molecular Libraries Initiative of the NIH Roadmap for Medical Research.
NR 64
TC 29
Z9 29
U1 1
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD OCT
PY 2009
VL 37
IS 19
AR e128
DI 10.1093/nar/gkp641
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 514JH
UT WOS:000271389900032
PM 19684079
ER
PT J
AU Scuteri, A
Najjar, SS
Orru', M
Albai, G
Strait, J
Tarasov, KV
Piras, MG
Cao, A
Schlessinger, D
Uda, M
Lakatta, EG
AF Scuteri, A.
Najjar, S. S.
Orru', M.
Albai, G.
Strait, J.
Tarasov, K. V.
Piras, M. G.
Cao, A.
Schlessinger, D.
Uda, M.
Lakatta, E. G.
TI Age- and gender-specific awareness, treatment, and control of
cardiovascular risk factors and subclinical vascular lesions in a
founder population: The SardiNIA Study
SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
LA English
DT Article
DE Hypertension; Diabetes; Hypercholesterolemia; Subclinical vascular
disease; Treatment; Control; Population
ID NUTRITION EXAMINATION SURVEY; CORONARY-ARTERY-DISEASE; BLOOD-PRESSURE
CONTROL; UNITED-STATES; DIABETES-MELLITUS; MYOCARDIAL-INFARCTION;
NATIONAL-HEALTH; HYPERTENSION TREATMENT; INDEPENDENT PREDICTOR;
METABOLIC SYNDROME
AB Aim: We investigated the gender-specific control of cardiovascular (CV) risk factors and subclinical vascular lesions in a founder population in Italy.
Methods and Results: 6148 subjects were enrolled (aged 14-102 years) from four towns. Hypertension (HT), diabetes mellitus (DM) and dyslipidemia (LIP) were defined in accordance with guidelines. A self-reported diagnosis defined awareness of these conditions, and the current use of specific medications as treatment.
Prevalence was HT 29.2%, DM 4.8%, LIP 44.1% and was higher in men than in women. Disease prevalence increased with age for every CV risk factor. Men were less likely than women to take anti-HT drugs and to reach BP control (9.9% vs. 16%). Only 17.6% of HT >65 years had a BP <= 140/90 mmHg, though 48.5% were treated. The use of statins was very tow (<1/3 of eligible subjects >65 years, those with the highest treatment rate). The ratio of control-to-treated HT was tower in subjects with, than in those without, thicker carotid arteries (31.5% vs. 38.8%, p < 0.05) or stiffer aortas (26.0% vs. 40.0%, p < 0.05) or carotid plaques (26.3% vs. 41.1%, p < 0.05).
Conclusion: A large number of subjects at high CV risk are not treated and the management of subclinical vascular lesions is far from optimal. (C) 2008 Elsevier B.V. All rights reserved.
C1 [Scuteri, A.] IRCCS, INRCA, UO Geriatria, I-00189 Rome, Italy.
[Orru', M.; Albai, G.; Piras, M. G.; Cao, A.; Uda, M.] CNR, INN, Cagliari, Italy.
[Najjar, S. S.; Strait, J.; Tarasov, K. V.; Lakatta, E. G.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Schlessinger, D.] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Scuteri, A (reprint author), IRCCS, INRCA, UO Geriatria, Via Cassia 1167, I-00189 Rome, Italy.
EM angeloelefante@interfree.it
OI Tarasov, Kirill/0000-0001-7799-4670; piras, maria
grazia/0000-0001-9004-0900
FU National Institute on Aging (NIA) [N01-AG-1-2109]; National Institutes
of Health (NIH)
FX This work was supported by the Intramural Research Program of the
National Institute on Aging (NIA), National Institutes of Health (NIH).
The SardiNIA ("ProgeNIA") team was supported by Contract N01-AG-1-2109
from the NIA.
NR 53
TC 27
Z9 27
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0939-4753
J9 NUTR METAB CARDIOVAS
JI Nutr. Metab. Carbiovasc. Dis.
PD OCT
PY 2009
VL 19
IS 8
BP 532
EP 541
DI 10.1016/j.numecd.2008.11.004
PG 10
WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition
& Dietetics
SC Cardiovascular System & Cardiology; Endocrinology & Metabolism;
Nutrition & Dietetics
GA 547ZV
UT WOS:000273929500003
PM 19321325
ER
PT J
AU Monteiro, JP
Freimanis-Hance, L
Faria, LB
Mussi-Pinhata, MM
Korelitz, J
Vannucchi, H
Queiroz, W
Succi, RCM
Hazra, R
AF Monteiro, Jacqueline P.
Freimanis-Hance, Laura
Faria, Lidiane B.
Mussi-Pinhata, Marisa M.
Korelitz, James
Vannucchi, Helio
Queiroz, Wladimir
Succi, Regina C. M.
Hazra, Rohan
TI Both human immunodeficiency virus-infected and human immunodeficiency
virus-exposed, uninfected children living in Brazil, Argentina, and
Mexico have similar rates of low concentrations of retinol,
beta-carotene, and vitamin E
SO NUTRITION RESEARCH
LA English
DT Article
DE beta-carotene; Children; HIV; Retinol; Vitamin E
ID ACUTE-PHASE RESPONSE; ALPHA-TOCOPHEROL; A-DEFICIENCY; FILIPINO
SCHOOLCHILDREN; NUTRITIONAL ASSESSMENT; MICRONUTRIENT LEVELS;
HIV-INFECTION; SERUM; SUPPLEMENTATION; COHORT
AB Our objective was to describe the prevalence of low concentrations of retinol, beta-carotene, and vitamin E in a group of human immunodeficiency virus (HIV)-infected Latin American children and a comparison group of HIV-exposed, uninfected children. Our hypothesis was that the rates of low concentrations of these micronutrients would be higher in the HIV-infected group than those in the HIV-exposed, uninfected group. This was a cross-sectional substudy of a larger cohort study at clinical pediatric HIV centers in Latin America. Serum levels of micronutrients were measured in the first stored sample obtained after each child's first birthday by high-performance liquid chromatography. Low concentrations of retinol, beta-carotene, and vitamin E were defined as serum levels below 0.70, 0.35, and 18.0 mu mol/L, respectively. The Population for this analysis was 336 children (124 HIV-infected, 212 HIV-exposed, uninfected) aged I year or older to younger than 4 years. Rates of low concentrations were 74% for retinol, 27% for beta-carotene, and 89% for vitamin E. These rates were not affected by HIV status. Among the HIV-infected children, those treated with anti retrovirals were less likely to have retinol deficiency, but no other HIV-related factors correlated with micronutrient low serum levels. Low concentrations of retinol, beta-carotene, and vitamin E are very common in children exposed to HIV living in Brazil, Argentina, and Mexico, regardless of HIV-infection status. Published by Elsevier Inc.
C1 [Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA.
[Monteiro, Jacqueline P.; Faria, Lidiane B.; Mussi-Pinhata, Marisa M.; Vannucchi, Helio] Univ Sao Paulo, BR-14049 Ribeirao Preto, SP, Brazil.
[Freimanis-Hance, Laura; Korelitz, James] WESTAT Corp, Rockville, MD 20850 USA.
[Queiroz, Wladimir] Inst Infectol Emilio Ribas, Sao Paulo, Brazil.
[Succi, Regina C. M.] Univ Fed Sao Paulo, Sao Paulo, Brazil.
RP Hazra, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA.
EM hazrar@mail.nih.gov
RI Mussi-Pinhata, Marisa/G-6568-2012; Vannucchi, Helio/B-8060-2013;
Monteiro, Jacqueline/F-6987-2012
OI Vannucchi, Helio/0000-0003-4161-3228;
FU NICHD [N01-HD-3-3345, N01-DK-8-0001]
FX Source of Financial Support: NICHD Contracts #N01-HD-3-3345 and
#N01-DK-8-0001.
NR 48
TC 12
Z9 13
U1 1
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0271-5317
J9 NUTR RES
JI Nutr. Res.
PD OCT
PY 2009
VL 29
IS 10
BP 716
EP 722
DI 10.1016/j.nutres.2009.10.001
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 528GW
UT WOS:000272432000005
PM 19917451
ER
PT J
AU Dinsmoor, MJ
Gilbert, S
Landon, MB
Rouse, DJ
Spong, CY
Varner, MW
Caritis, SN
Wapner, RJ
Sorokin, Y
Midovnik, M
O'Sullivan, MJ
Sibai, BM
Langer, O
AF Dinsmoor, Mara J.
Gilbert, Sharon
Landon, Mark B.
Rouse, Dwight J.
Spong, Catherine Y.
Varner, Michael W.
Caritis, Steve N.
Wapner, Ronald J.
Sorokin, Yoram
Midovnik, Menachem
O'Sullivan, Mary J.
Sibai, Baha M.
Langer, Oded
CA Eunice Kennedy Shriver Natl Inst C
TI Perioperative Antibiotic Prophylaxis for Nonlaboring Cesarean Delivery
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT 54th Annual Meeting of the Society-for-Gynecologic-Investigation
CY MAR 14-17, 2007
CL Reno, NV
SP Soc Gynecol Invest
ID INTACT MEMBRANES; INFECTION; SECTION
AB OBJECTIVE: To estimate the efficacy of antibiotic prophylaxis at the time of nonlaboring cesarean delivery in reducing postpartum infection-related complications.
METHODS: We performed a secondary analysis of an observational study of cesarean deliveries performed at 13 centers from 1999-2000. Patients were included if they had cesarean delivery before labor, did not have intrapartum infection, and were not given antibiotics at delivery for reasons other than prophylaxis. The occurrence of postpartum endometritis, wound infection, and other, less common infection-related complications was compared between those who did and did not receive antibiotic prophylaxis. Results were adjusted for smoking, payer status, gestational age and body mass index at delivery, race, diabetes, antepartum infections, presence of anemia, operative time, type of cesarean delivery (primary or repeat), and center.
RESULTS: Of the 9,432 women who met study criteria, the 6,006 (64%) who received antibiotic prophylaxis were younger, heavier at delivery, and were more likely to be African American, receive public insurance, and have diabetes. Patients who received antibiotic prophylaxis were less likely to develop postpartum endometritis (121 [2.0%] compared with 88 [2.6%], adjusted odds ratio [OR] 0.40, 95% confidence interval [CI] 0.28-0.59) or wound infection (31 [0.52%] compared with 33 [0.96%], adjusted OR 0.49, 95% CI 0.28-0.86).
CONCLUSION: Antibiotic prophylaxis at the time of nonlaboring cesarean delivery significantly reduces the risks of postpartum endometritis and wound infection. (Obstet Gynecol 2009;114:752-6)
C1 Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
Ohio State Univ, Columbus, OH 43210 USA.
Univ Alabama, Birmingham, AL USA.
Univ Utah, Salt Lake City, UT USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
Wayne State Univ, Detroit, MI USA.
Univ Cincinnati, Cincinnati, OH USA.
Univ Miami, Miami, FL USA.
Univ Tennessee, Memphis, TN USA.
Univ Texas San Antonio, San Antonio, TX USA.
George Washington Univ, Ctr Biostat, Washington, DC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Dinsmoor, MJ (reprint author), Northwestern Univ, Dept Obstet & Gynecol, Feinberg Sch Med, NorthShore Univ HealthSyst, 2650 Ridge Ave,Walgreen Bldg,Suite 1507, Evanston, IL 60201 USA.
EM mdinsmoor@northshore.org
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973
FU NICHD NIH HHS [U10 HD021410, HD21410, HD21414, HD27860, HD27861,
HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD34210, HD36801,
U01 HD036801, U01 HD036801-02, U10 HD021410-14, U10 HD021414-14, U10
HD027860, U10 HD027860-12, U10 HD027861-09, U10 HD027869, U10
HD027869-11, U10 HD027905, U10 HD027905-09, U10 HD027915, U10
HD027915-08, U10 HD027917, U10 HD027917-09, U10 HD034116, U10
HD034116-04, U10 HD034122, U10 HD034122-04, U10 HD034136, U10
HD034136-04, U10 HD034208, U10 HD034208-04, U10 HD036801, U10 HD040485,
U10 HD040500, U10 HD040512, U10 HD040512-01, UG1 HD027869, UG1 HD027915,
UG1 HD034116, UG1 HD034208]
NR 11
TC 21
Z9 26
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD OCT
PY 2009
VL 114
IS 4
BP 752
EP 756
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 503WY
UT WOS:000270573800007
PM 19888031
ER
PT J
AU Hasan, R
Baird, DD
Herring, AH
Olshan, AF
Funk, MLJ
Hartmann, KE
AF Hasan, Reem
Baird, Donna D.
Herring, Amy H.
Olshan, Andrew F.
Funk, Michele L. Jonsson
Hartmann, Katherine E.
TI Association Between First-Trimester Vaginal Bleeding and Miscarriage
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID THREATENED-ABORTION; EARLY-PREGNANCY; PREDICTION; ULTRASOUND; OUTCOMES;
BIRTH
AB OBJECTIVE: To estimate the strength of association between first-trimester bleeding and miscarriage, setting aside bleeding at time of loss.
METHODS: Women enrolled in a community-based pregnancy cohort study before or during early pregnancy. Detailed first-trimester bleeding data were collected by telephone interview. Bleeding episodes proximal to miscarriage (within 4 days) were excluded. We used discrete-time hazard models to evaluate the association between bleeding and miscarriage. Models were adjusted for maternal age, prior miscarriage, and smoking. Exploratory regression tree analysis was used to evaluate the relative importance of other bleeding characteristics (duration, associated pain, color, timing).
RESULTS: Of the 4,510 participants, 1,204 (27%) reported some first-trimester vaginal bleeding or spotting, and 517 miscarriages were observed. Eight percent of those with bleeding reported heavy bleeding episodes. When we evaluated any bleeding, including episodes of only spotting, the unadjusted relative odds ratio (OR) of miscarriage for women with bleeding (n=1,204) was 1.1 (95% confidence interval [CI] 0.9-1.3). However, women who reported heavy bleeding (n=97) had nearly three times the risk of miscarriage compared with women without bleeding during the first trimester (OR 3.0, 95% Cl 1.9-4.6). Adjustment for covariates had little effect on estimates. Further analyses suggested that women with heavy bleeding accompanied by pain were the group accounting for most of the elevated risk.
CONCLUSION: Heavy bleeding in the first trimester, particularly when accompanied by pain, is associated with higher risk of miscarriage. Spotting and light episodes are not, especially if lasting only 1-2 days. (Obstet Gynecol 2009;114:860-7)
C1 [Hasan, Reem] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.
Vanderbilt Univ, Med Ctr, Inst Med & Publ Hlth, Nashville, TN USA.
Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Nashville, TN USA.
RP Hasan, R (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, MD A3-05, Res Triangle Pk, NC 27709 USA.
EM reem_hasan@med.unc.edu
RI Jonsson Funk, Michele/F-6885-2011; Baird, Donna/D-5214-2017
OI Jonsson Funk, Michele/0000-0002-3756-7540; Baird,
Donna/0000-0002-5544-2653
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [5R01HD043883, 5R01HD049675]; American Water Works
Association Research Foundation [2579]; National Institute of
Environmental Health Sciences [P30ES10126]
FX The field research was supported in part by grants from the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(5R01HD043883 and 5R01HD049675) and the American Water Works Association
Research Foundation (2579). Additional funds were provided by the
National Institute of Environmental Health Sciences (Intramural Research
Program and P30ES10126).
NR 21
TC 27
Z9 27
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD OCT
PY 2009
VL 114
IS 4
BP 860
EP 867
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 503WY
UT WOS:000270573800022
PM 19888046
ER
PT J
AU Minig, L
Trimble, EL
Sarsotti, C
Sebastiani, MM
Spong, CY
AF Minig, Lucas
Trimble, Edward L.
Sarsotti, Carlos
Sebastiani, Mario M.
Spong, Catherine Y.
TI Building the Evidence Base for Postoperative and Postpartum Advice
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID ACTIVITY RESTRICTIONS; PHYSICAL-ACTIVITY; WEIGHT RETENTION; WOUND
DEHISCENCE; HERNIA REPAIR; WORK; HYSTERECTOMY; SURGERY; RETURN;
QUESTIONNAIRE
AB Recommendations for activity after obstetric and gynecologic procedures remain based on tradition and anecdote. After reviewing the current evidence base, guidelines, and practice for postdischarge instructions related to physical activity after the most common obstetric and gynecologic surgical procedures, we conclude that the available data do not support many of the recommendations currently provided. Restrictions on lifting and climbing stairs should likely be abandoned. Guidance on driving should focus on the concern regarding cognitive function and analgesics rather than concerns of wound separation/dehiscence. Given the impact of these recommendations on daily life events, consistent, evidence-based advice on when and how women can safely resume exercise, driving, working, and sexual intercourse is critical. The evidence base informing advice for most of these issues is minimal; we need prospective, well-designed studies to help guide us and our patients. (Obstet Gynecol 2009;114:892-900)
C1 [Minig, Lucas] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
Grp Estudio Disfunc & Rehabil Piso Pelvico, Buenos Aires, DF, Argentina.
Hosp Italiano Buenos Aires, Dept Obstet, Buenos Aires, DF, Argentina.
NICHHD, Pregnancy & Perinatol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Minig, L (reprint author), NCI, Div Canc Treatment & Diag, NIH, Bldg 10 B3B406, Bethesda, MD 20892 USA.
EM lucasminig@yahoo.com
NR 66
TC 12
Z9 12
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD OCT
PY 2009
VL 114
IS 4
BP 892
EP 900
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 503WY
UT WOS:000270573800026
PM 19888050
ER
PT J
AU Reddy, UM
Goldenberg, R
Silver, R
Smith, GCS
Pauli, RM
Wapner, RJ
Gardosi, J
Pinar, H
Grafe, M
Kupferminc, M
Varli, IH
Erwich, JJHM
Fretts, RC
Willinger, M
AF Reddy, Uma M.
Goldenberg, Robert
Silver, Robert
Smith, Gordon C. S.
Pauli, Richard M.
Wapner, Ronald J.
Gardosi, Jason
Pinar, Halit
Grafe, Marjorie
Kupferminc, Michael
Varli, Ingela Hulthen
Erwich, Jan Jaap H. M.
Fretts, Ruth C.
Willinger, Marian
TI Stillbirth Classification-Developing an International Consensus for
Research Executive Summary of a National Institute of Child Health and
Human Development Workshop
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID UMBILICAL-CORD LENGTH; FETAL-DEATH; FETOMATERNAL HEMORRHAGE;
REPRODUCTIVE-PERFORMANCE; CLINICAL-SIGNIFICANCE; PERINATAL-MORTALITY;
SERVICE PROGRAM; GESTATIONAL-AGE; BIRTH-WEIGHT; PREGNANCY
AB Stillbirth is a major obstetric complication, with 3.2 million stillbirths worldwide and 26,000 stillbirths in the United States every year. The Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop from October 22-24, 2007, to review the pathophysiology of conditions underlying stillbirth to define causes of death. The optimal classification system would identify the pathophysiologic entity initiating the chain of events that irreversibly led to death. Because the integrity of the classification is based on available pathologic, clinical, and diagnostic data, experts emphasized that a complete stillbirth workup should be performed. Experts developed evidence-based characteristics of maternal, fetal, and placental conditions to attribute a condition as a cause of stillbirth. These conditions include infection, maternal medical conditions, antiphospholipid syndrome, heritable thrombophilias, red cell alloimmunization, platelet alloimmunization, congenital malformations, chromosomal abnormalities including confined placental mosaicism, fetomaternal hemorrhage, placental and umbilical cord abnormalities including vasa previa and placental abruption, complications of multifetal gestation, and uterine complications. In all cases, owing to lack of sufficient knowledge about disease states and normal development, there will be a degree of uncertainty regarding whether a specific condition was indeed the cause of death. (Obstet Gynecol 2009,114:901-14)
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
Drexel Univ, Philadelphia, PA 19104 USA.
Univ Utah, Salt Lake City, UT USA.
Univ Cambridge, Cambridge, England.
Univ Wisconsin, Madison, WI USA.
Columbia Univ, New York, NY USA.
W Midlands Perinatal Inst, Birmingham, W Midlands, England.
Brown Univ, Providence, RI 02912 USA.
Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, IL-69978 Tel Aviv, Israel.
Karolinska Univ Hosp, Stockholm, Sweden.
Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
Harvard Vanguard Med Assoc, Boston, MA USA.
RP Reddy, UM (reprint author), 6700 Execut Blvd,Rm 4B03F, Bethesda, MD 20892 USA.
EM reddyu@mail.nih.gov
RI Smith, Gordon/A-8070-2008
OI Smith, Gordon/0000-0003-2124-0997
FU Intramural NIH HHS [Z99 HD999999]
NR 72
TC 56
Z9 57
U1 1
U2 6
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 OCT
PY 2009
VL 114
IS 4
BP 901
EP 914
PG 14
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 503WY
UT WOS:000270573800027
PM 19888051
ER
PT J
AU Pronk, A
Coble, J
Ji, BT
Shu, XO
Rothman, N
Yang, G
Gao, YT
Zheng, W
Chow, WH
AF Pronk, A.
Coble, J.
Ji, B-T
Shu, X-O
Rothman, N.
Yang, G.
Gao, Y-T
Zheng, W.
Chow, W-H
TI Occupational risk of lung cancer among lifetime non-smoking women in
Shanghai, China
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID GERMANY; EPIDEMIOLOGY; MEN
AB Objectives: Occupational lung carcinogens have been primarily studied in men. The aim of this study was to investigate occupational lung cancer risk in a cohort of Chinese non-smoking women.
Methods: In 1996-2000, 71 067 non-smoking women who had held a job outside the home were interviewed for the prospective Shanghai Women's Health Study in China. Exposure to lung carcinogens was assessed by matching occupation and industry titles from lifetime occupational histories with lists of jobs identified by the International Agency for Research on Cancer to have potential exposure to: (1) known (A-list); or (2) suspected (B-list) carcinogens. In addition, similar occupational titles were grouped independent of the a priori defined lists. Relative risks (RRs) were calculated using Cox proportional hazards regression.
Results: During follow-up through 2005, 219 incident lung cancer cases were diagnosed. Jobs on the A-list and B-list were held by 0.8-6.7% and 2.7-9.4% of the cohort, respectively. Overall, ever holding any job on the A-list or B-list was not associated with lung cancer incidence. Indications of excess risk were found for two subgroups: painters (A-list) and rubber workers (B-list) (RR = 2.0 and 1.7, respectively, p <= 0.1). An exploratory analysis of 35 occupational categories independent of the lists showed significantly increased risks for leather products/shoes, wood/paper products and miscellaneous production/transportation. The former two of these categories were similar to subgroups of the B-list, but broader than the specific a priori defined jobs.
Conclusions: Significantly elevated lung cancer risk was associated with employment in some broad occupational categories that also included jobs with potential exposure to suspected carcinogens (B-list). The results suggest that although similar exposures to those described on the B-list may play a role in this cohort of Chinese women, carcinogenic exposure may not be restricted only to the jobs on the B-list.
C1 [Pronk, A.; Coble, J.; Ji, B-T; Rothman, N.; Chow, W-H] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Shu, X-O; Yang, G.; Zheng, W.] Vanderbilt Univ, Sch Med, Dept Med,Vanderbilt Ingram Canc Ctr, Div Epidemiol,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA.
[Gao, Y-T] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
RP Pronk, A (reprint author), 6120 Execut Blvd,EPS 8111,MSC 7240, Bethesda, MD 20892 USA.
EM pronka@mail.nih.gov
FU National Institute of Health (NIH) [R01 CA70867]; Intramural Research
Program [N02 CP1101066]
FX This research was supported by National Institute of Health (NIH)
research grant R01 CA70867 and by the Intramural Research Program
contract N02 CP1101066.
NR 21
TC 15
Z9 15
U1 1
U2 5
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD OCT
PY 2009
VL 66
IS 10
BP 672
EP 678
DI 10.1136/oem.2008.043695
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 497BB
UT WOS:000270027400007
PM 19625285
ER
PT J
AU Chong, DY
Johnson, MW
Shen, D
Chan, CC
Callanan, DG
AF Chong, Deborah Y.
Johnson, Mark W.
Shen, Defen
Chan, Chi-Chao
Callanan, David G.
TI Vitreous Metastases of Primary Cutaneous B-Cell Lymphoma
SO OCULAR IMMUNOLOGY AND INFLAMMATION
LA English
DT Article
DE primary cutaneous B-cell lymphoma; metastases; vitritis
AB Purpose: To describe two cases of vitreous metastases of primary cutaneous B-cell lymphoma (PCBCL).
Methods: Observational case series.
Results: A 73-year-old man and an 81-year-old woman, both with a history of PCBCL, diffuse large cell type, presented with decreased visual acuity due to vitritis. Both patients underwent vitreous biopsy that demonstrated B-cell lymphoma, large cell type, and confirmed metastases of cutaneous B-cell lymphoma to the vitreous.
Conclusion: PCBCL, diffuse large cell type, is a rare form of non-Hodgkin lymphoma that can metastasize to the vitreous without visible chorioretinal involvement.
C1 [Chong, Deborah Y.; Callanan, David G.] Texas Retina Associates, Arlington, TX USA.
[Johnson, Mark W.] Univ Michigan, WK Kellogg Eye Ctr, Ann Arbor, MI 48109 USA.
[Shen, Defen; Chan, Chi-Chao] NIH, Immunol Lab, Bethesda, MD 20892 USA.
RP Callanan, DG (reprint author), Vandergriff Profess Bldg,1001 N Waldrop Dr,Suite, Arlington, TX 76012 USA.
EM dcallanan@texasretina.com
FU Intramural NIH HHS [Z01 EY000222-23]
NR 5
TC 3
Z9 3
U1 1
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 0927-3948
J9 OCUL IMMUNOL INFLAMM
JI Ocul. Immunol. Inflamm.
PD OCT
PY 2009
VL 17
IS 5
BP 342
EP 344
DI 10.3109/09273940903144705
PG 3
WC Ophthalmology
SC Ophthalmology
GA 520HF
UT WOS:000271832700012
PM 19831568
ER
PT J
AU Switzer, CH
Ridnour, LA
Cheng, RYS
Sparatore, A
Del Soldato, P
Moody, TW
Vitek, MP
Roberts, DD
Wink, DA
AF Switzer, C. H.
Ridnour, L. A.
Cheng, R. Y. S.
Sparatore, A.
Del Soldato, P.
Moody, T. W.
Vitek, M. P.
Roberts, D. D.
Wink, D. A.
TI Dithiolethione compounds inhibit Akt signaling in human breast and lung
cancer cells by increasing PP2A activity
SO ONCOGENE
LA English
DT Article
DE dithiolethione; PP2A; Akt; cancer; breast; lung
ID PROTEIN PHOSPHATASE 2A; NONSTEROIDAL ANTIINFLAMMATORY DRUGS;
TUMOR-SUPPRESSOR; HEME OXYGENASE-1; KINASE-B; TYROSINE PHOSPHORYLATION;
REGULATORY SUBUNITS; 3T3-L1 ADIPOCYTES; C-MYC; PATHWAY
AB The chemopreventative effects of dithiolethione compounds are attributed to their activation of antioxidant response elements (AREs) by reacting with the Nrf2/Keap1 protein complex. In this study, we show anti-proliferative effects of the dithiolethione compound ACS1 in human cancer cell lines (A549 and MDA-MB-231) by increasing the activity of the tumor suppressor protein phoshatase 2A (PP2A). ACS-1 inhibited epidermal growth factor (EGF)-induced cellular proliferation in a concentration-and time-dependent manner. Akt activation, as determined by serine-473 phosphorylation, was inhibited by ACS-1 in cells stimulated with either EGF or fibronectin. Furthermore, ACS-1 inhibited mammalian target of rapamycin signaling and decreased c-myc protein levels. ACS-1 did not proximally alter EGF receptor or integrin signaling, but caused a concentration-dependent increase in PP2A activity. The effect of ACS-1 on Akt activation was not observed in the presence of the PP2A inhibitor okadaic acid. ACS-1 effects on PP2A activity were independent of ARE activation and cAMP formation. In addition to ACS-1, other dithiolethione compounds showed similar effects in reducing Akt activation, suggesting that this class of compounds may have other effects beyond chemoprevention. Oncogene (2009) 28, 3837-3846; doi:10.1038/onc.2009.244; published online 24 August 2009
C1 [Switzer, C. H.; Ridnour, L. A.; Cheng, R. Y. S.; Wink, D. A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
[Sparatore, A.] Univ Milan, Dipartimento Sci Farmaceut Pietro Pratesi, Milan, Italy.
[Del Soldato, P.] Sulfidris, Milan, Italy.
[Vitek, M. P.] Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA.
[Roberts, D. D.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Wink, DA (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3-B35, Bethesda, MD 20892 USA.
EM wink@mail.nih.gov
RI Roberts, David/A-9699-2008; Switzer, Christopher/D-9203-2013; Sparatore,
Anna/J-8634-2015;
OI Roberts, David/0000-0002-2481-2981; Sparatore, Anna/0000-0003-2135-2649;
Cheng, Robert/0000-0003-0287-6439
FU Intramural NIH HHS [Z01 BC010899-01]
NR 49
TC 26
Z9 26
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT
PY 2009
VL 28
IS 43
BP 3837
EP 3846
DI 10.1038/onc.2009.244
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 512KT
UT WOS:000271248400007
PM 19701246
ER
PT J
AU Shamir, L
Ling, SM
Scott, W
Hochberg, M
Ferrucci, L
Goldberg, IG
AF Shamir, L.
Ling, S. M.
Scott, W.
Hochberg, M.
Ferrucci, L.
Goldberg, I. G.
TI Early detection of radiographic knee osteoarthritis using computer-aided
analysis
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Article
DE Image analysis; Osteoarthritis detection; Early detection
ID ARTICULAR-CARTILAGE; IMAGE-ANALYSIS; JOINT SPACE; BONE; SELECTION;
SEVERITY; TEXTURE; HIP
AB Objective: To determine whether computer-based analysis can detect features predictive of osteoarthritis (OA) development in radiographically normal knees.
Method: A systematic computer-aided image analysis method weighted neighbor distances using a compound hierarchy of algorithms representing morphology (WND-CHARM) was used to analyze pairs of weight-bearing knee X-rays. Initial X-rays were all scored as normal Kellgren-Lawrence (KL) grade 0, and on follow-up approximately 20 years later either developed OA (defined as KL grade = 2) or remained normal.
Results: The computer-aided method predicted whether a knee would change from KL grade 0 to grade 3 with 72% accuracy (P < 0.00001), and to grade 2 with 62% accuracy (P < 0.01). Although a large part of the predictive signal comes from the image tiles that contained the joint, the region adjacent to the tibial spines provided the strongest predictive signal.
Conclusion: Radiographic features detectable using a computer-aided image analysis method can predict the future development of radiographic knee OA. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
C1 [Shamir, L.; Goldberg, I. G.] NIA, Image Informat & Computat Biol Unit, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Ling, S. M.; Ferrucci, L.] NIA, Clin Res Branch, NIH, Baltimore, MD 21225 USA.
[Scott, W.] Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD 21287 USA.
[Hochberg, M.] Univ Maryland, Med Ctr, Dept Med, Baltimore, MD 21201 USA.
RP Shamir, L (reprint author), NIA, Image Informat & Computat Biol Unit, Genet Lab, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM shamirl@mail.nih.gov
RI Goldberg, Ilya/H-5307-2011
OI Goldberg, Ilya/0000-0001-8514-6110
FU NIH; National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging.
NR 33
TC 24
Z9 25
U1 1
U2 5
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 1063-4584
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD OCT
PY 2009
VL 17
IS 10
BP 1307
EP 1312
DI 10.1016/j.joca.2009.04.010
PG 6
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 513OR
UT WOS:000271332900009
PM 19426848
ER
PT J
AU Merchant, MS
AF Merchant, Melinda S.
TI Long-Term Impact of Cancer Care on Activities of Daily Living: Are We
Causing Our Sarcoma Survivors to Grow Up Too Quickly?
SO PEDIATRIC BLOOD & CANCER
LA English
DT Editorial Material
ID PEDIATRIC SARCOMA; CHILDHOOD-CANCER; HEALTH; LIFE
C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Merchant, MS (reprint author), NCI, Pediat Oncol Branch, NIH, 10 Ctr Dr Bldg 10 CRC,Room 1W-3952, Bethesda, MD 20892 USA.
EM merchanm@mail.nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD OCT
PY 2009
VL 53
IS 4
BP 531
EP 532
DI 10.1002/pbc.22166
PG 2
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 487SJ
UT WOS:000269295500004
PM 19588522
ER
PT J
AU Gorlick, R
Kolb, EA
Houghton, PJ
Morton, CL
Phelps, D
Schaiquevich, P
Stewart, C
Keir, ST
Lock, R
Carol, H
Reynolds, CP
Maris, JM
Wu, JR
Smith, MA
AF Gorlick, Richard
Kolb, E. Anders
Houghton, Peter J.
Morton, Christopher L.
Phelps, Doris
Schaiquevich, Paula
Stewart, Clinton
Keir, Stephen T.
Lock, Richard
Carol, Hernan
Reynolds, C. Patrick
Maris, John M.
Wu, Jianrong
Smith, Malcolm A.
TI Initial Testing (Stage 1) of Lapatinib by the Pediatric Preclinical
Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; lapatinib; preclinical testing
ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL-LINES; IN-VIVO;
CANCER MODELS; EXPRESSION; CHILDHOOD; OSTEOSARCOMA; GW572016; ERBB2
AB Background. Lapatinib is a small molecule reversible tyrosine kinase inhibitor of EGFR and ErbB2 that shows in vitro and in vivo activity against a range of EGFR and ErbB2-dependent adult cancer cell lines and that has clinical efficacy against ErbB2-overexpressing breast cancer. Methods. Lapatinib was tested against the cell lines of the PPTP in vitro panel at concentrations ranging from 1.0 nM to 10.0 mu M. Lapatinib was tested against the xenografts of the PPTP in vivo panels using a twice-daily oral administration schedule for 6 weeks (5 days on, 2 days off) at a dose of 160 mg/kg (320 mg/kg/ day). Lapatinib pharmacokinetic parameters were determined in scid(-/-) mice. Results. The median IC(50) value for lapatinib against the entire PPTP cell line panel was 6.84 mu M (range, 2.08 to >10.0 mu M). Lapatinib was well tolerated in vivo, with toxicity in only 1.5% of the treated animals. Lapatinib induced significant differences in EFS distribution compared to controls in 1 of 41 xenografts tested. No objective responses were observed in any of the solid tumor panels or in the ALL panel. Lapatinib systemic exposure was consistent with previously observed values. Conclusions. Lapatinib has little activity against the xenografts of the PPTP's in vivo panel, and its in vitro activity occurs at concentrations above those associated with specific EGFR/ErbB2 inhibition. These results likely reflect lack of ErbB2 overexpression in the models studied and suggest that adult and pediatric cancers may fundamentally differ in the applicability of EGFR family members as therapeutic targets. Pediatr Blood Cancer 2009;53: 594-598. (C) 2009 Wiley-Liss, Inc.
C1 [Gorlick, Richard] Yeshiva Univ, Albert Einstein Coll Med, Childrens Hosp Montefiore, Bronx, NY 10467 USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Houghton, Peter J.; Morton, Christopher L.; Phelps, Doris; Schaiquevich, Paula; Stewart, Clinton; Wu, Jianrong] St Jude Childrens Hosp, Memphis, TN 38105 USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Lock, Richard; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia.
[Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Gorlick, R (reprint author), Yeshiva Univ, Albert Einstein Coll Med, Childrens Hosp Montefiore, 3415 Bainbridge Ave,Rosenthal Rm 300, Bronx, NY 10467 USA.
EM rgorlick@montefiore.org
RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock,
Richard/G-4253-2013;
OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C.
Patrick/0000-0002-2827-8536
FU National Cancer Institute [NOI-CM-42216, CA21765, CA 108786]
FX Grant sponsor: National Cancer Institute; Grant numbers: NOI-CM-42216,
CA21765, CA 108786.
NR 24
TC 21
Z9 21
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD OCT
PY 2009
VL 53
IS 4
BP 594
EP 598
DI 10.1002/pbc.21989
PG 5
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 487SJ
UT WOS:000269295500015
PM 19554571
ER
PT J
AU Parks, R
Rasch, EK
Mansky, PJ
Oakley, F
AF Parks, Rebecca
Rasch, Elizabeth K.
Mansky, Patrick J.
Oakley, Frances
TI Differences in Activities of Daily Living Performance Between Long-Term
Pediatric Sarcoma Survivors and a Matched Comparison Group on
Standardized Testing
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE ADL; late effects; pediatric sarcoma; pediatric sarcoma survivors
ID QUALITY-OF-LIFE; CHILDHOOD-CANCER; ADULT SURVIVORS; PROCESS SKILLS;
FOLLOW-UP; THERAPY; CARE; OUTCOMES; EDUCATION; CHILDREN
AB Background. in a cross-sectional study examining late effects of pediatric sarcoma therapy, long-term Survivors were evaluated on their activities of daily living (ADL) performance. Procedure. Thirty-two persons with Ewing sarcoma family of tumors, rhabdomyosarcoma, and non-rhabdomysarcoma-soft tissue sarcoma enrolled an average of 17 years after treatment. Participants were evaluated using the Assessment of Motor and Process Skills (AMPS) [1], a standardized observational evaluation of ADL task performance. Means and 95% confidence intervals for ADL motor and ADL process ability measures were calculated for four groups: (1) sarcoma survivors, (2) "well" adults matched for age and gender, (3) "well" adults matched for gender that were 10 years older, and (4) "well" adults matched for gender that were 20 years older. Results. ADL motor ability was significantly lower for sarcoma survivors than for the age-and gender-matched comparison group (P<0.05). There was no significant difference between ADL motor ability of sarcoma survivors and the comparison group 10 years older, but sarcoma survivors had significantly better ADL motor ability (P<0.05) than the oldest comparison group (20 years older). Sarcoma survivors had significantly worse ADL process ability than the age-matched group (P< 0.05). There was no difference in ADL process ability between the sarcoma survivors and comparison groups that were 10 and 20 years older. Conclusions. This first report of a clinical evaluation of ADL limitation in pediatric sarcoma survivors treated with intensive multimodal cancer therapy suggests that influences on performance of daily life activities are more common than previously reported. Pediatr Blood Cancer 2009;53: 622-628. Published 2009 Wiley-Liss, Inc.
C1 [Parks, Rebecca; Rasch, Elizabeth K.; Oakley, Frances] NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Mansky, Patrick J.] NIH, Div Intramural Res, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
RP Parks, R (reprint author), Bldg 10-CRC,Room I-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA.
EM rparks@nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute
FX Grant sponsor: Intramural Research Program of the National Institutes of
Health; Grant sponsor: National Cancer Institute.
NR 60
TC 6
Z9 6
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD OCT
PY 2009
VL 53
IS 4
BP 622
EP 628
DI 10.1002/pbc.22101
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 487SJ
UT WOS:000269295500020
PM 19533662
ER
PT J
AU Uzzaman, A
Maric, I
Noel, P
Kettelhut, BV
Metcalfe, DD
Carter, MC
AF Uzzaman, Ashraf
Maric, Irina
Noel, Pierre
Kettelhut, Brett V.
Metcalfe, Dean D.
Carter, Melody C.
TI Pediatric-Onset Mastocytosis: A Long Term Clinical Follow-Up and
Correlation With Bone Marrow Histopathology
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE bone marrow; cutaneous mastocytosis; KIT; pediatric mastocytosis; serum
tryptase; urticaria pigmentosa
ID CUTANEOUS MASTOCYTOSIS; SYSTEMIC MASTOCYTOSIS; URTICARIA-PIGMENTOSA;
CATALYTIC DOMAIN; TRYPTASE LEVELS; C-KIT; ANAPHYLAXIS; MUTATION;
DISEASE; BLOOD
AB Background. Pediatric onset mastocytosis Usually presents as Urticaria pigmentosa; and less often as diffuse cutaneous mastocytosis. While the literature indicates that disease often resolves, there has been a move to more aggressive therapy for mastocytosis early in life. We addressed the long term prognosis of pediatric-onset disease by examining 17 children with mastocytosis which we had reported oil in 1989 [1]. Procedure. We successfully contacted 15 of these patients and data was collected regarding their clinical status. Original bone marrow specimens were re-stained, reexamined, and correlated with disease Outcome using consensus criteria. Three of five patients with persistent disease underwent repeat bone marrow biopsies. Results. There was complete regression of disease as defined by cutaneous findings and symptoms (clinical disease severity) in 10 of 15 patients (67%). Three patients had major (20%) and two had partial regression of disease (13%). Repeat marrow examinations on three patients with persistent disease documented systemic mastocytosis based on marrow findings in one patient who had partial regression of disease and was the only patient with initial morphologic evidence of systemic disease. Of the remaining two patients, one demonstrated partial regression and the other major regression of disease; and neither had evidence of systemic mastocytosis. Conclusion. This study demonstrates that initial bone marrow biopsies were prognostic in that those without evidence of systemic disease experienced disease regression; and that the long term prognosis for children managed symptomatically with mastocytosis is highly encouraging. Pediatr Blood Cancer 2009;53: 629-634. (C) 2009 Wiley-Liss, Inc.
C1 [Uzzaman, Ashraf; Metcalfe, Dean D.; Carter, Melody C.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Maric, Irina; Noel, Pierre] NIH, Hematol Sect, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Kettelhut, Brett V.] Univ Nebraska Med Ctr, Dept Pediat, Omaha, NE USA.
RP Carter, MC (reprint author), Bldg 10,Room 1 1C213,10 Ctr Dr MSC1881, Bethesda, MD 20892 USA.
EM mcarter@niaid.nih.gov
FU NIH
FX Grant sponsor: NIH.
NR 20
TC 35
Z9 35
U1 1
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD OCT
PY 2009
VL 53
IS 4
BP 629
EP 634
DI 10.1002/pbc.22125
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 487SJ
UT WOS:000269295500021
PM 19526526
ER
PT J
AU Wolters, PL
Gropman, AL
Martin, SC
Smith, MR
Hildenbrand, HL
Brewer, CC
Smith, ACM
AF Wolters, Pamela L.
Gropman, Andrea L.
Martin, Staci C.
Smith, Michaele R.
Hildenbrand, Hanna L.
Brewer, Carmen C.
Smith, Ann C. M.
TI Neurodevelopment of Children Under 3 Years of Age With Smith-Magenis
Syndrome
SO PEDIATRIC NEUROLOGY
LA English
DT Article
ID SYNDROME DEL 17P11.2; BEHAVIORAL-PHENOTYPE; DOWN-SYNDROME; MALADAPTIVE
BEHAVIOR; LANGUAGE-DEVELOPMENT; CIRCADIAN-RHYTHM; YOUNG-CHILDREN;
ORAL-MOTOR; DELETION; DISORDERS
AB Systematic data regarding early neurodevelopmental functioning in Smith-Magenis syndrome are limited. Eleven children with Smith-Magenis syndrome less than 3 years of age (mean, 19 months; range, 5-34 months) received prospective multidisciplinary assessments using standardized measures. The total sample scored in the moderately to severely delayed range in cognitive functioning, expressive language, and motor skills and exhibited generalized hypotonia, oral-motor abnormalities, and middle ear dysfunction. Socialization skills were average, and significantly higher than daily living, communication, and motor abilities, which were below average. Mean behavior ratings were in the nonautistic range. According to exploratory analyses, the toddler subgroup scored significantly lower than the infant subgroup in cognition, expressive language, and adaptive behavior, suggesting that the toddlers were more delayed than the infants relative to their respective peers. Infants aged approximately 1 year or younger exhibited cognitive, language, and motor skills that ranged from average to delayed, but with age-appropriate social skills and minimal maladaptive behaviors. At ages 2 to 3 years, the toddlers consistently exhibited cognitive, expressive language, adaptive behavior, and motor delays and mildly to moderately autistic behaviors. Combining age groups in studies may mask developmental and behavioral differences. Increased knowledge of these early neurodevelopmental characteristics should facilitate diagnosis and appropriate intervention. (C) 2009 Published by Elsevier Inc.
C1 [Wolters, Pamela L.; Martin, Staci C.] Med Illness Counseling Ctr, Chevy Chase, MD USA.
[Gropman, Andrea L.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA.
[Smith, Ann C. M.] Kelly Govt Solut, Rockville, MD USA.
[Wolters, Pamela L.; Martin, Staci C.] NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
[Smith, Michaele R.; Hildenbrand, Hanna L.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
[Brewer, Carmen C.] Natl Inst Deafness & Other Commun Disorders, NIH, Otolaryngol Branch, Bethesda, MD USA.
[Gropman, Andrea L.; Smith, Ann C. M.] NHGRI, NIH, Off Clin Director, Bethesda, MD 20892 USA.
RP Wolters, PL (reprint author), 9030 Old Georgetown Rd,Bldg 82,Room 109, Bethesda, MD 20892 USA.
EM woltersp@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH);
National Human Genome Research Institute (NIH-NHGRI); National Cancer
Institute; NHGRI; NCI [71004-09, N01-SC-07006, HHSN261200477004C];
National Institute oil Deafness and Other Communication Disorders
(NIH-NIDCD) [Z01-DC-000064-05]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (NIH). National Human Genome
Research Institute (NIH-NHGRI). and the National Cancer Institute
(NIH-NCI) Center for Cancer Research, through a Bench-to-Bedside award
from the NIH Clinical Center to the Medical Genetics Branch of the
NHGRI, and by NCI contracts 71004-09. N01-SC-07006, and
HHSN261200477004C with the Medical Illness Counseling Center (MICC).
Additional support was obtained through the intramural research fund
Z01-DC-000064-05 of the National Institute oil Deafness and Other
Communication Disorders (NIH-NIDCD). The authors express their sincere
appreciation to the families who participated in this research, and also
extend their gratitude to the other members of the Smith-Magenis
syndrome research team. especially Donna M. Krasnewich. MD, Suzan
Parada, RN, Mary Anne-Toledo-Tamula. NIA. Joanne E. Flanagan, MS. OT,
and Rebecca Morse. MA.
NR 50
TC 13
Z9 13
U1 2
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD OCT
PY 2009
VL 41
IS 4
BP 250
EP 258
DI 10.1016/j.pediatrneuro1.2009.04.015
PG 9
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 501IY
UT WOS:000270376400003
PM 19748044
ER
PT J
AU McGowan, EC
Kostadinov, S
McLean, K
Gotsch, F
Venturini, D
Romero, R
Laptook, AR
Sharma, S
AF McGowan, Elisabeth C.
Kostadinov, Stefan
McLean, Kathryn
Gotsch, Francesca
Venturini, Deborah
Romero, Roberto
Laptook, Abbot R.
Sharma, Surendra
TI Placental IL-10 Dysregulation and Association With Bronchopulmonary
Dysplasia Risk
SO PEDIATRIC RESEARCH
LA English
DT Article
ID LOW-BIRTH-WEIGHT; NECROSIS-FACTOR-ALPHA; CHRONIC LUNG-DISEASE;
HYALINE-MEMBRANE DISEASE; INSTITUTES-OF-HEALTH; PRETERM INFANTS;
AMNIOTIC-FLUID; CYTOKINE EXPRESSION; PREMATURE-INFANTS; GENE PROMOTER
AB Cytokine profiles in amniotic fluid, cord serum, and tracheal aspirate of premature infants suggest a shift toward a proinflammatory state. Cytokines also contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). We hypothesize that the initiating events for BPD are reflected in the placenta and propose that placental expression of cytokines provide a blueprint of events leading to BPD. This is I retrospective, case-controlled study of, placental cytokines of premature infants with (n = 49) and without (n = 49) BPD, matched for gender, birth weight, and year of birth at Women and Infants Hospital between 2003 and 2005. Cytokine expression, including IL-6 and IL-10, was determined by immunohistochemistry in membrane rolls, umbilical cords, and placentas. IL-6 was similarly expressed in all tissues of infants with and without BPD. In contrast, anti-inflammatory cytokine IL-10 was less prominent in the placenta of patients with BPD compared with those without BPD. IL-10 expression in the villous trophoblast layer was associated with a reduced odds ratio of developing BPD (adjusted OR 0.08, 95% CI 0.01-0.70, p = 0.02). These results suggest that a placental balance between inflammatory and anti-inflammatory cytokines is crucial to normal lung organogenesis. Importantly, IL-10 seems to be protective against the development of BPD. (Pediatr Res 66: 455-460, 2009)
C1 [McGowan, Elisabeth C.; McLean, Kathryn; Venturini, Deborah; Laptook, Abbot R.; Sharma, Surendra] Brown Univ, Warren Alpert Med Sch, Women & Infants Hosp, Dept Pediat, Providence, RI 02915 USA.
[Kostadinov, Stefan] Brown Univ, Warren Alpert Med Sch, Women & Infants Hosp, Dept Pathol, Providence, RI 02915 USA.
[Gotsch, Francesca; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48210 USA.
RP Sharma, S (reprint author), Women & Infants Hosp Rhode Isl, Dept Pediat, 101 Dudley St, Providence, RI 02905 USA.
EM ssharma@wihri.org
FU NIH NCRR [P20RR018728]; Eunice Kennedy Shriver National Institute of
Child Health and Human Development, NIH, DHHS [WSU05056]; NICHD
[N01-HD-2-3342]
FX Supported in part by the grant front NIH NCRR (P20RR018728), the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, NIH, DHHS, and a subcontract WSU05056 under NICHD contract
N01-HD-2-3342.
NR 37
TC 14
Z9 14
U1 0
U2 0
PU INT PEDIATRIC RESEARCH FOUNDATION, INC
PI BALTIMORE
PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA
SN 0031-3998
J9 PEDIATR RES
JI Pediatr. Res.
PD OCT
PY 2009
VL 66
IS 4
BP 455
EP 460
PG 6
WC Pediatrics
SC Pediatrics
GA 500FZ
UT WOS:000270285400018
PM 19581835
ER
PT J
AU Bocchini, JA
Bernstein, HH
Bradley, JS
Brady, MT
Byington, CL
Fisher, MC
Glode, MP
Jackson, MA
Keyserling, HL
Kimberlin, DW
Orenstein, WA
Schutze, GE
Willoughby, RE
Dennehy, PH
Frenck, RW
Rubin, LG
Bell, B
Bortolussi, R
Clover, RD
Fischer, MA
Gellin, B
Gorman, RL
Pratt, RD
Lee, L
Read, JS
Starke, JR
Swanson, J
Baker, CJ
Long, SS
Pickering, LK
Ledbetter, EO
Meissner, HC
O'Dell, JD
Weinberg, ST
Frantz, J
AF Bocchini, Joseph A., Jr.
Bernstein, Henry H.
Bradley, John S.
Brady, Michael T.
Byington, Carrie L.
Fisher, Margaret C.
Glode, Mary P.
Jackson, Mary Anne
Keyserling, Harry L.
Kimberlin, David W.
Orenstein, Walter A.
Schutze, Gordon E.
Willoughby, Rodney E.
Dennehy, Penelope H.
Frenck, Robert W., Jr.
Rubin, Lorry G.
Bell, Beth
Bortolussi, Robert
Clover, Richard D.
Fischer, Marc A.
Gellin, Bruce
Gorman, Richard L.
Pratt, R. Douglas
Lee, Lucia
Read, Jennifer S.
Starke, Jeffrey R.
Swanson, Jack
Baker, Carol J.
Long, Sarah S.
Pickering, Larry K.
Ledbetter, Edgar O.
Meissner, H. Cody
O'Dell, J. Dennis
Weinberg, Stuart T.
Frantz, Jennifer
CA Comm Infect Dis
TI Policy Statement-Recommendations for the Prevention and Treatment of
Influenza in Children, 2009-2010
SO PEDIATRICS
LA English
DT Article
DE influenza; novel influenza A (H1N1) virus; immunization; live-attenuated
influenza vaccine; trivalent inactivated influenza vaccine; vaccine;
children; pediatrics
ID INFECTIOUS-DISEASES
AB The purpose of this statement is to update current recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. Pediatrics 2009; 124: 1216-1226
C1 [Bell, Beth; Fischer, Marc A.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
[Bortolussi, Robert] Canadian Paediat Soc, Ottawa, ON, Canada.
[Clover, Richard D.] Amer Acad Family Phys, Leawood, KS USA.
[Gorman, Richard L.; Read, Jennifer S.] NIH, Bethesda, MD USA.
[Pratt, R. Douglas; Lee, Lucia] US FDA, Rockville, MD 20857 USA.
EM jfrantz@aap.org
OI Dennehy, Penelope/0000-0002-2259-5370; Byington,
Carrie/0000-0002-7350-9495
NR 5
TC 24
Z9 24
U1 0
U2 0
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD OCT
PY 2009
VL 124
IS 4
BP 1216
EP 1226
DI 10.1542/peds.2009-1806
PG 11
WC Pediatrics
SC Pediatrics
GA 500CI
UT WOS:000270274300028
ER
PT J
AU El-Mohandes, AAE
Kiely, M
Gantz, MG
Blake, SM
El-Khorazaty, MN
AF El-Mohandes, Ayman A. E.
Kiely, Michele
Gantz, Marie G.
Blake, Susan M.
El-Khorazaty, M. Nabil
TI Prediction of Birth Weight By Cotinine Levels During Pregnancy in a
Population of Black Smokers
SO PEDIATRICS
LA English
DT Article
DE birth weight; pregnancy; smoking
ID MATERNAL CIGARETTE-SMOKING; GESTATIONAL-AGE; CARBON-MONOXIDE;
META-EVALUATION; FETAL-GROWTH; RISK-FACTORS; WOMEN; INTERVENTION;
REDUCTION; CESSATION
AB OBJECTIVE: The goal was to investigate the association between maternal salivary cotinine levels (SCLs) and pregnancy outcomes among black smokers.
METHODS: In a randomized, controlled trial conducted in 2001-2004 in Washington, DC, 714 women (126 active smokers [18%]) were tested for SCLs at the time of recruitment and later in pregnancy. Sociodemographic health risks and pregnancy outcomes were recorded.
RESULTS: Birth weights were significantly lower for infants born to mothers with baseline SCLs of >= 20 ng/mL in comparison with <20 ng/mL (P = .024), >= 50 ng/mL in comparison with <50 ng/mL (P = .002), and >= 100 ng/mL in comparison with <100 ng/mL (P = .002), in bivariate analyses. In linear regression analyses adjusting for sociodemographic and medical factors, SCLs of >= 20 ng/mL were associated with a reduction in birth weight of 88 g when SCLs were measured at baseline (P = .042) and 205 g when SCLs were measured immediately before delivery (P < .001). Corresponding results were 129 g (P = .006) and 202 g (P < .001) for >= 50 ng/mL and 139 g (P = .007) and 205 g (P = 0.001) for >= 100 ng/mL. Gestational age was not affected significantly at any SCL, regardless of when SCLs were measured.
CONCLUSIONS: Elevated SCLs early in pregnancy or before delivery were associated with reductions in birth weight. At any cutoff level, birth weight reduction was more significant for the same SCL measured in late pregnancy. Maintaining lower levels of smoking for women who are unable to quit may be beneficial. Pediatrics 2009; 124: e671-e680
C1 [El-Mohandes, Ayman A. E.] George Washington Univ, Dept Prevent & Community Hlth, Sch Publ Hlth & Hlth Serv, Med Ctr, Washington, DC 20037 USA.
[Kiely, Michele] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Gantz, Marie G.; El-Khorazaty, M. Nabil] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
RP El-Mohandes, AAE (reprint author), George Washington Univ, Dept Prevent & Community Hlth, Sch Publ Hlth & Hlth Serv, Med Ctr, 2175 K St NW,Suite 700, Washington, DC 20037 USA.
EM sphaxe@gwumc.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [3U18HD030445, 3U18HD030447, 5U18HD31206, 3U18HD03919,
5U18HD036104]; National Center on Minority Health and Health Disparities
FX This study was supported by grants 3U18HD030445, 3U18HD030447,
5U18HD31206, 3U18HD03919, and 5U18HD036104 from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development and by
the National Center on Minority Health and Health Disparities.
NR 33
TC 3
Z9 3
U1 1
U2 1
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD OCT
PY 2009
VL 124
IS 4
BP E671
EP E680
DI 10.1542/peds.2008-3784
PG 10
WC Pediatrics
SC Pediatrics
GA 500CI
UT WOS:000270274300049
PM 19786427
ER
PT J
AU Traupman, EK
Smith, TW
Uchino, BN
Berg, CA
Trobst, KK
Costa, PT
AF Traupman, Emily K.
Smith, Timothy W.
Uchino, Bert N.
Berg, Cynthia A.
Trobst, Krista K.
Costa, Paul T., Jr.
TI Interpersonal circumplex octant, control, and affiliation scales for the
NEO-PI-R
SO PERSONALITY AND INDIVIDUAL DIFFERENCES
LA English
DT Article
DE Interpersonal circumplex; NEO-PI-R; Control; Dominance; Affiliation
ID PERSONALITY; HOSTILITY; TAXONOMY; DISEASE; HEALTH
AB The Five Factor Model (FFM) traits of agreeableness and extraversion are rotational equivalents of the interpersonal circumplex (IPC) dimensions of affiliation and control. Given that the NEO-PI-R is a widely used measure of the FFM, availability of IPC dimension scales within this inventory could facilitate integration of FFM and interpersonal perspectives. In a study of 301 married couples, we evaluated an IPC scoring system for the NEO-PI-R (Wiggins & Trobst, 1998) comprising 6-item octant scales and composites representing control and affiliation. The octant scales demonstrated expected circular structure. Octant and dimension scales demonstrated convergent and discriminant validity, in analyses of self-report and spouse-rating versions of this IPC measure and the Impact Message Inventory. Further, extraversion corresponded to friendly dominance in the IPC and agreeableness to submissive friendliness. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Traupman, Emily K.; Smith, Timothy W.; Uchino, Bert N.; Berg, Cynthia A.] Univ Utah, Dept Psychol, Salt Lake City, UT 84112 USA.
[Trobst, Krista K.] York Univ, Dept Psychol, N York, ON M3J 1P3, Canada.
[Costa, Paul T., Jr.] NIA, Lab Personal & Cognit, IRP, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Smith, TW (reprint author), Univ Utah, Dept Psychol, 380 South 1530 East Room 502,Behav Sci Bldg, Salt Lake City, UT 84112 USA.
EM tim.smith@psych.utah.edu
OI Costa, Paul/0000-0003-4375-1712
FU NIA NIH HHS [R01 AG018903]
NR 21
TC 18
Z9 18
U1 2
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0191-8869
J9 PERS INDIV DIFFER
JI Pers. Individ. Differ.
PD OCT
PY 2009
VL 47
IS 5
BP 457
EP 463
DI 10.1016/j.paid.2009.04.018
PG 7
WC Psychology, Social
SC Psychology
GA 468SU
UT WOS:000267842200013
PM 27840466
ER
PT J
AU Gill, JM
Saligan, L
Woods, S
Page, G
AF Gill, Jessica M.
Saligan, Leo
Woods, Stephanie
Page, Gayle
TI PTSD is Associated With an Excess of Inflammatory Immune Activities
SO PERSPECTIVES IN PSYCHIATRIC CARE
LA English
DT Article
DE Cortisol; immune; inflammatory; PTSD; trauma
ID POSTTRAUMATIC-STRESS-DISORDER; C-REACTIVE PROTEIN; COMBAT VETERANS;
CYTOKINE PRODUCTION; PARTNER VIOLENCE; INNATE IMMUNITY; RECEPTOR;
CORTISOL; WOMEN; INTERLEUKIN-6
AB PURPOSE.
Post-traumatic stress disorder (PTSD) is associated with inflammatory-related medical conditions. This review examines studies of immune function in individuals with PTSD to determine if excessive inflammation is associated with PTSD.
CONCLUSIONS.
Current studies suggest an excess of inflammatory actions of the immune system in individuals with chronic PTSD. High levels of inflammatory cytokines have also been linked to PTSD vulnerability in traumatized individuals. There is also evidence that excessive inflammation is in part due to insufficient regulation by cortisol.
PRACTICE IMPLICATIONS.
An excess of inflammatory immune activity may contribute to health declines in individuals with PTSD, and treating PTSD symptoms may reduce these risks.
C1 [Gill, Jessica M.] NINR, NIH, Bethesda, MD 20892 USA.
[Woods, Stephanie] Univ Akron, Sch Nursing, Akron, OH 44325 USA.
[Page, Gayle] Johns Hopkins Univ, Sch Nursing, Bethesda, MD USA.
RP Gill, JM (reprint author), NINR, NIH, Bethesda, MD 20892 USA.
EM gillj@mail.nih.gov
NR 84
TC 87
Z9 89
U1 4
U2 10
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0031-5990
J9 PERSPECT PSYCHIATR C
JI Perspect. Psychiatr. Care
PD OCT
PY 2009
VL 45
IS 4
BP 262
EP 277
PG 16
WC Nursing; Psychiatry
SC Nursing; Psychiatry
GA 498YL
UT WOS:000270182400004
PM 19780999
ER
PT J
AU Boudreau, RM
Hanlon, JT
Roumani, YF
Studenski, SA
Ruby, CM
Wright, RM
Hilmer, SN
Shorr, RI
Bauer, DC
Simonsick, EM
Newman, AB
AF Boudreau, Robert M.
Hanlon, Joseph T.
Roumani, Yazan F.
Studenski, Stephanie A.
Ruby, Christine M.
Wright, Rollin M.
Hilmer, Sarah N.
Shorr, Ronald I.
Bauer, Douglas C.
Simonsick, Eleanor M.
Newman, Anne B.
TI Central nervous system medication use and incident mobility limitation
in community elders: the health, aging, and body composition study
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Article
DE aged; mobility; central nervous system drugs
ID LOWER-EXTREMITY FUNCTION; BENZODIAZEPINE USE; OLDER-ADULTS; PHYSICAL
PERFORMANCE; DISABILITY; ASSOCIATION; MORTALITY; PEOPLE; DRUGS; WOMEN
AB Purpose To evaluate whether CNS medication use in older adults was associated with a higher risk of future incident mobility limitation.
Methods This 5-year longitudinal cohort study included 3055 participants from the health, aging and body composition (Health ABC) study who were well-functioning at baseline. CNS medication use (benzodiazepine and opioid receptor agonists, antipsychotics, and antidepressants) was determined yearly (except year 4) during in-home or in-clinic interviews. Summated standardized daily doses (low, medium, and high) and duration of CNS drug use were computed. Incident mobility limitation was operationalized as two consecutive self-reports of having any difficulty walking 1/4 mile or climbing 10 steps without resting every 6 months after baseline. Multivariable Cox proportional hazard analyses were conducted adjusting for demographics, health behaviors, health status, and common indications for CNS medications.
Results Each year at least 13.9% of participants used a CNS medication. By year 6, overall 49% had developed incident mobility limitation. In multivariable models, CNS medication users compared to never users showed a higher risk for incident mobility limitation (adjusted hazard ratio (Adj. HR) 1.28; 95% confidence interval (CI) 1.12-1.47). Similar findings of increased risk were seen in analyses examining dose- and duration-response relationships.
Conclusions CNS medication use is independently associated with an increased risk of future incident mobility limitation in community dwelling elderly. Further studies are needed to determine the impact of reducing CNS medication exposure on mobility problems. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Hanlon, Joseph T.; Roumani, Yazan F.; Studenski, Stephanie A.; Ruby, Christine M.; Wright, Rollin M.; Newman, Anne B.] Univ Pittsburgh, Dept Geriatr Med, Sch Med, Pittsburgh, PA 15213 USA.
[Boudreau, Robert M.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Hanlon, Joseph T.; Ruby, Christine M.] Univ Pittsburgh, Dept Pharm & Therapeut, Sch Pharm, Pittsburgh, PA 15213 USA.
[Hanlon, Joseph T.; Studenski, Stephanie A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res, Pittsburgh, PA USA.
[Hanlon, Joseph T.; Studenski, Stephanie A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA.
[Hilmer, Sarah N.] Univ Sydney, Sydney, NSW 2006, Australia.
[Hilmer, Sarah N.] Royal N Shore Hosp, Sydney, NSW, Australia.
[Shorr, Ronald I.] N Florida S Georgia Vet Hlth Syst Geriatr Res Edu, Gainesville, FL USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Geriatr Med, Sch Med, Kaufman Med Bldg Suite 514,3471 5th Ave, Pittsburgh, PA 15213 USA.
EM hanlonj@dom.pitt.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Hilmer, Sarah/0000-0002-5970-1501;
Boudreau, Robert/0000-0003-0162-5187
FU NIH, National Institute of Aging [R01AG027017, P30AG024827,
N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]
FX This study was primarily supported by National Institute of Aging grants
and contracts (R01AG027017; P30AG024827, N01-AG-6-2101, N01-AG-6-2103,
and N01-AG-6-2106). This research was also supported in part by the
Intramural Research program of the NIH, National Institute on Aging. Dr
Hanlon and Dr Boudreau have full access to all the data in the study and
take responsibility for the integrity of the data and the accuracy of
the data analysis. Study concept and design was done by Bauer, Hanlon,
Boudreau, Newman, Shorr, Simonsick, and Studenski. Data were accumulated
by Hanlon, Boudreau, and Newman. Analysis and interpretation of the data
were done by Hanlon, Boudreau, Newman, Shorr, Simonsick, Bauer, Ruby,
Roumani, Studenski, Wright, and Hilmer. The manuscript was drafted by
Hanlon, Boudreau, Roumani, Hilmer, Studenski, Wright, and Simonsick.
Critical revision of the manuscript for important intellectual content
was done by Hanlon, Boudreau, Newman, Roumani, Hilmer, Shorr, Bauer,
Studenski, Ruby, Wright, and Simonsick. Statistical analysis was done by
Boudreau, Roumani. Funding was obtained by Hanlon and Newman. The study
was supervised by Hanlon and Newman.
NR 28
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PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD OCT
PY 2009
VL 18
IS 10
BP 916
EP 922
DI 10.1002/pds.1797
PG 7
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 510GN
UT WOS:000271076200006
PM 19585466
ER
PT J
AU Schindler, CW
Panlilio, LV
Thorndike, EB
AF Schindler, Charles W.
Panlilio, Leigh V.
Thorndike, Eric B.
TI Effect of rate of delivery of intravenous cocaine on self-administration
in rats
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE Cocaine; Self-administration; Infusion duration; Choice; Rat
ID INJECTION SPEED; REINFORCING STRENGTH; SEEKING BEHAVIOR; RHESUS-MONKEYS;
HUMANS; INFUSION; CHOICE; AMPHETAMINE; ADDICTION; SCHEDULE
AB Many studies of drug self-administration in primates have shown that faster infusions of a drug are more reinforcing than slower infusions. Similar effects have not been shown in rats. We assessed the influence of delivery rate by allowing rats to choose between the same doses of intravenous cocaine delivered over two different infusion speeds. Rats were trained in chambers containing two nose-poke response devices. in Experiment 1, responses in one nose-poke delivered 0.3 mg/kg/injection of cocaine over 10 s, and responses in the other delivered the same dose over 100 s. In Experiment 2, the same procedure was used, but with 1.0 mg/kg/injection dose delivered over 1.7 versus 100 s. During acquisition, most rats preferred the faster infusion. When the delivery rates associated with the nose pokes were reversed, rats trained with 0.3 mg/kg/injection failed to switch nose-poke preference, but half the rats trained with 1.0 mg/kg/injection did switch. In Experiment 3, the choice was between I mg/kg cocaine delivered over 1.7 s and no reinforcement. Here, rats quickly learned to respond in the nose-poke associated with cocaine and quickly switched their choice during reversal. In Experiment 4, two groups of rats were allowed to choose between food delivered with a delay of I versus 5 s or I versus 10 s, respectively. Rats preferred the shorter delay during initial training. In reversal, some rats in the I vs 5 s group failed to reverse, while all the rats in the I vs 10 s group reversed. These results show that faster infusions of cocaine are clearly more reinforcing during acquisition, but delivery rate may not be as important to the maintenance of self-administration once it has been established. The results with food Suggest that these findings represent general principles of behavior and are not unique to drug self-administration. Published by Elsevier Inc.
C1 [Schindler, Charles W.; Panlilio, Leigh V.; Thorndike, Eric B.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, DHHS,NIH,Intramural Res Program, Baltimore, MD 21224 USA.
RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, DHHS,NIH,Intramural Res Program, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM cschindl@helix.nih.gov
FU NIH; NIDA
FX This research was supported by the Intramural Research Program of the
NIH, NIDA. The authors would like to thank Kevin Thornton, Peter Riley
and Reeva Morton for their assistance in conducting the experiments.
NR 31
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U1 2
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD OCT
PY 2009
VL 93
IS 4
BP 375
EP 381
DI 10.1016/j.pbb.2009.05.008
PG 7
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 491NW
UT WOS:000269586800003
PM 19464316
ER
PT J
AU Davis, CM
Rice, KC
Riley, AL
AF Davis, Catherine M.
Rice, Kenner C.
Riley, Anthony L.
TI Opiate-agonist induced taste aversion learning in the Fischer 344 and
Lewis inbred rat strains: Evidence for differential mu opioid receptor
activation
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE F344; LEW; Morphine; CTA; Heroin; SNC80; (-)-U50,488H; Opioid
ID MORPHINE-TOLERANCE; KNOCKOUT MICE; INDUCED ANTINOCICEPTION;
LOCOMOTOR-ACTIVITY; LITHIUM-CHLORIDE; PLACE PREFERENCE; CXBK MICE;
DELTA; COCAINE; ANALGESIA
AB The Fischer 344 (F344) and Lewis (LEW) inbred rat strains react differently to morphine in a number of behavioral and physiological preparations, including the acquisition of aversions induced by this compound. The present experiment tested the ability of various compounds with relative selectivity at kappa, delta and mu receptor subtypes to assess the relative roles of these subtypes in mediating the differential aversive effects of morphine in the two strains. In the assessment of the role of the kappa receptor in morphine-induced aversions, animals in both strains were given access to saccharin followed by varying doses of the kappa agonist (-)-U50,488H (0.0. 0.28. 0.90 and 1.60 mg/kg). Although (-)-U50.488H induced aversions in both strains, no strain differences emerged. A separate subset of subjects was trained with the selective delta opioid agonist, SNC80 (0.0. 5.6, 10.0 and 18.0 mg/kg), and again although SNC80 induced aversions, there were no strain differences. Finally, a third subset of subjects was trained with heroin (0.0. 3.2, 5.6 and 10.0 mg/kg), a compound with activity at all three opiate receptor subtypes. Although heroin induced aversions in both strains, the aversions were significantly greater in the F344 strain, suggesting that differential activation of the mu opioid receptor likely mediates the reported strain differences in morphine-induced aversion learning. These data were discussed in terms of strain differences in opioid system functioning and the implications of such differences for other morphine-induced behavioral effects reported in F344 and LEW rats. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Davis, Catherine M.] American Univ, Psychopharmacol Lab, Dept Psychol, Washington, DC 20016 USA.
[Rice, Kenner C.] Natl Inst Drug Abuse, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20852 USA.
[Rice, Kenner C.] NIAAA, Bethesda, MD 20852 USA.
RP Davis, CM (reprint author), American Univ, Psychopharmacol Lab, Dept Psychol, 4400 Massachusetts Ave NW, Washington, DC 20016 USA.
EM cd2994a@american.edu
OI Davis-Takacs, Catherine/0000-0002-2591-6352
FU Mellon Foundation; National Institute on Drug Abuse; National Institute
on Alcohol Abuse and Alcoholism
FX This work was supported by a grant from the Mellon Foundation to Anthony
L Riley, and a portion of this work was supported by the intramural
research programs of the National Institute on Drug Abuse and the
National Institute on Alcohol Abuse and Alcoholism.
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U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD OCT
PY 2009
VL 93
IS 4
BP 397
EP 405
DI 10.1016/j.pbb.2009.06.001
PG 9
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 491NW
UT WOS:000269586800006
PM 19508878
ER
PT J
AU Siber, A
Rajter, RF
French, RH
Ching, WY
Parsegian, VA
Podgornik, R
AF Siber, A.
Rajter, R. F.
French, R. H.
Ching, W. Y.
Parsegian, V. A.
Podgornik, R.
TI Dispersion interactions between optically anisotropic cylinders at all
separations: Retardation effects for insulating and semiconducting
single-wall carbon nanotubes
SO PHYSICAL REVIEW B
LA English
DT Article
ID VANDERWAALS FORCES; RODS
AB We derive the complete form of the van der Waals dispersion interaction between two infinitely long anisotropic semiconducting/insulating thin cylinders at all separations. The derivation is based on the general theory of dispersion interactions between anisotropic media as formulated in Munday et al. [Phys. Rev. A 71, 042102 (2005)]. This formulation is then used to calculate the dispersion interactions between a pair of single-walled carbon nanotubes at all separations and all angles. Nonretarded and retarded forms of the interactions are developed separately. The possibility of repulsive dispersion interactions and nonmonotonic dispersion interactions is discussed within the framework of the formulation.
C1 [Siber, A.] Univ Zagreb, Inst Phys, Zagreb 10001, Croatia.
[Rajter, R. F.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA.
[French, R. H.] DuPont Co Inc, Cent Res, Wilmington, DE 19880 USA.
[Ching, W. Y.] Univ Missouri, Dept Phys, Kansas City, MO 64110 USA.
[Parsegian, V. A.] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
[Podgornik, R.] NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA.
[Podgornik, R.] Univ Ljubljana, Fac Math & Phys, Dept Phys, SI-1000 Ljubljana, Slovenia.
[Podgornik, R.] Univ Ljubljana, Sch Med, Inst Biophys, SI-1000 Ljubljana, Slovenia.
[Podgornik, R.] Jozef Stefan Inst, Dept Theoret Phys, SI-1000 Ljubljana, Slovenia.
RP Siber, A (reprint author), Univ Zagreb, Inst Phys, Bijenicka Cesta 46,POB 304, Zagreb 10001, Croatia.
RI Ching, Wai-Yim/B-4686-2009; Siber, Antonio/B-8881-2008; French,
Roger/E-1986-2011; Podgornik, Rudolf/C-6209-2008
OI Ching, Wai-Yim/0000-0001-7738-8822; Siber, Antonio/0000-0003-1665-6541;
French, Roger/0000-0002-6162-0532; Podgornik, Rudolf/0000-0002-3855-4637
FU European Commission [NMP3-CT-2005-013862]; Slovenian Research Agency
[J1-0908]; Croatian Ministry of Science [035-0352828-2837]; NSF
[CMS-0609050]; Dupont-MIT Alliance; DOE [DE-FG02-84DR45170]; Intramural
Research Program of the NIH; Eunice Kennedy Shriver National Institute
of Child Health and Human Development
FX A. S. and R. P. would like to acknowledge partial financial support for
this work by the European Commission under Contract No.
NMP3-CT-2005-013862 (INCEMS) and by the Slovenian Research Agency under
Contract No. J1-0908 Active Media Nanoactuators with Dispersion Forces).
A. S. also acknowledges support by the Croatian Ministry of Science
(Project No. 035-0352828-2837). R. R. would like to acknowledge
financial support for this work by the NSF under Contract No.
CMS-0609050 (NIRT) and the Dupont-MIT Alliance (DMA). W. Y. C. is
supported by the DOE under Grant No. DE-FG02-84DR45170. This study was
supported by the Intramural Research Program of the NIH, Eunice Kennedy
Shriver National Institute of Child Health and Human Development.
NR 25
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U1 0
U2 4
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 1098-0121
J9 PHYS REV B
JI Phys. Rev. B
PD OCT
PY 2009
VL 80
IS 16
AR 165414
DI 10.1103/PhysRevB.80.165414
PG 10
WC Physics, Condensed Matter
SC Physics
GA 513VL
UT WOS:000271352100123
ER
PT J
AU Agarwala, SS
Becker, JC
Eggermont, AM
Flaherty, KT
Garbe, C
Goldstein, AM
Halpern, A
Kashani-Sabet, M
Hauschild, A
Kirkwood, JM
Leachman, S
Lorigan, P
McMahon, M
Messina, J
Ribas, A
Samlowski, WE
Schadendorf, D
Sondak, VK
AF Agarwala, Sanjiv S.
Becker, Jurgen C.
Eggermont, Alexander M.
Flaherty, Keith T.
Garbe, Claus
Goldstein, Alisa M.
Halpern, Allan
Kashani-Sabet, Mohammed
Hauschild, Axel
Kirkwood, John M.
Leachman, Sancy
Lorigan, Paul
McMahon, Martin
Messina, Jane
Ribas, Antoni
Samlowski, Wolfram E.
Schadendorf, Dirk
Sondak, Vernon K.
TI Meeting report: consensus from the first and second Global Workshops in
Melanoma November 19-20, 2008
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Editorial Material
ID STAGE-IV MELANOMA; ADJUVANT THERAPY; PHASE-III; INTERFERON-ALPHA-2B;
TRIAL
AB This overview of the current state of melanoma research and treatment and directions for moving forward represents the consensus of discussions between expert panelists at the First and Second Global Workshops on Melanoma held in Fajardo, Peurto Rico on November 30-December 1, 2007 and Clearwater Beach, Florida on November 19-20, 2008.
C1 [Agarwala, Sanjiv S.] St Lukes Canc Ctr, Bethlehem, PA USA.
[Flaherty, Keith T.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Becker, Jurgen C.] Univ Wurzburg, Dept Dermatol Venerol & Allergol, Wurzburg, Germany.
[Becker, Jurgen C.] Univ Wurzburg, Dept Dermatol, D-8700 Wurzburg, Germany.
[Eggermont, Alexander M.] Erasumus Univ, Med Ctr, Dept Surg Oncol, Rotterdam, Netherlands.
[Garbe, Claus] Univ Med Ctr Tubingen, Dept Dermatol, Div Dermatooncol, Tubingen, Germany.
[Goldstein, Alisa M.] NCI, Bethesda, MD 20892 USA.
[Halpern, Allan] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Kashani-Sabet, Mohammed] Univ Calif San Francisco, Melanoma Ctr, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Hauschild, Axel] Univ Kiel, Dept Dermatol, D-2300 Kiel, Germany.
[Kirkwood, John M.] Univ Pittsburgh, Sch Med, Clin Res Dept Med, Pittsburgh, PA USA.
[Kirkwood, John M.] Univ Pittsburgh, Sch Med, Inst Canc, Melanoma & Skin Canc Program, Pittsburgh, PA USA.
[Leachman, Sancy] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Melanoma & Cutaneous Oncol Program, Salt Lake City, UT USA.
[Lorigan, Paul] Christie Hosp Fdn Trust, Manchester, Lancs, England.
[McMahon, Martin] UCSF Comprehens Canc Ctr, Canc Res Inst, San Francisco, CA USA.
[Messina, Jane; Sondak, Vernon K.] Univ S Florida, Cutaneous Oncol Program, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Ribas, Antoni] Univ Calif Los Angeles, Div Hematol & Oncol, Los Angeles, CA USA.
[Samlowski, Wolfram E.] Nevada Canc Inst, Sect Melanoma Renal Canc & Immunotherapy, Las Vegas, NV USA.
[Schadendorf, Dirk] Univ Essen Gesamthsch, Clin Dermatol & Venerol, Essen, Germany.
[Sondak, Vernon K.] Univ S Florida, Coll Med, Dept Oncol Sci, Tampa, FL USA.
[Sondak, Vernon K.] Univ S Florida, Coll Med, Dept Surg, Tampa, FL 33612 USA.
RP Agarwala, SS (reprint author), St Lukes Canc Ctr, Bethlehem, PA USA.
EM AgarwaS@slhn.org
RI Hauschild, Axel/B-3185-2010; McMahon, Martin/L-3303-2013; Lorigan,
Paul/J-6898-2015;
OI McMahon, Martin/0000-0003-2812-1042; Lorigan, Paul/0000-0002-8875-2164;
Samlowski, Wolfram/0000-0002-0713-914X
NR 8
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD OCT
PY 2009
VL 22
IS 5
BP 532
EP 543
DI 10.1111/j.1755-148X.2009.00602.x
PG 12
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 489AD
UT WOS:000269390800009
PM 19659612
ER
PT J
AU Horvath, A
Stratakis, CA
AF Horvath, Anelia
Stratakis, Constantine A.
TI Carney complex and lentiginosis
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Review
DE Carney complex; lentiginosis; skin pigmentation
ID PEUTZ-JEGHERS-SYNDROME; NODULAR ADRENOCORTICAL DISEASE; DEPENDENT
PROTEIN-KINASE; EPITHELIOID BLUE NEVUS; GERMLINE MUTATIONS; ENDOCRINE
OVERACTIVITY; ADRENAL-HYPERPLASIA; SPOTTY PIGMENTATION; MELANOCORTIN
RECEPTORS; GENETIC-HETEROGENEITY
AB P>Initially described as the 'complex of myxomas, spotty skin pigmentation and endocrine overactivity,' Carney complex (CNC) is known as an autosomal dominant multiple neoplasia syndrome involving skin and cardiac myxomas, pigmented skin lesions and endocrine tumors. Pigmented cutaneous manifestations in CNC are important diagnostically because they can be used for the early detection of the disease and, thus, the prevention of life-threatening complications of CNC related to heart myxomas and endocrine abnormalities. Specific for the disease skin lesions are present in more than half of the CNC patients. A major challenge is to distinguish pigmented skin lesions associated with CNC from other skin pathology, and thus accurately estimate the risk of cancer in affected patients; curiously, patients with CNC do not appear to have predisposition to skin cancers whereas this is not the case with other genetic syndromes associated with melanotic and other cutaneous lesions. In this paper, we review the current knowledge on cutaneous pathology associated with CNC and the most recent data on the molecular basis of the disease.
C1 [Horvath, Anelia; Stratakis, Constantine A.] NICHHD, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), NICHHD, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development (NICHD); NIH [Z01-HD-000642-04]
FX Studies on CNC and related syndromes have been supported by the Eunice
Kennedy Shriver National Institute of Child Health & Human Development
(NICHD), NIH, intramural project Z01-HD-000642-04 (to Dr. C. A.
Stratakis).
NR 61
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U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD OCT
PY 2009
VL 22
IS 5
BP 580
EP 587
DI 10.1111/j.1755-148X.2009.00613.x
PG 8
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 489AD
UT WOS:000269390800012
PM 19650827
ER
PT J
AU Loftus, SK
Baxter, LL
Buac, K
Watkins-Chow, DE
Larson, DM
Pavan, WJ
AF Loftus, Stacie K.
Baxter, Laura L.
Buac, Kristina
Watkins-Chow, Dawn E.
Larson, Denise M.
Pavan, William J.
TI Comparison of melanoblast expression patterns identifies distinct
classes of genes
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE melanoblast; retinal pigmented epithelium; in situ hybridization; MITF;
SOX10
ID MELANOCYTE-SPECIFIC EXPRESSION; TRANSCRIPTION FACTOR SOX10;
CREST-DERIVED MELANOCYTES; RECEPTOR TYROSINE KINASE; C-KIT RECEPTOR;
WAARDENBURG-SYNDROME; NEURAL CREST; DOPACHROME-TAUTOMERASE;
HIRSCHSPRUNG-DISEASE; SPOTTED MICE
AB P>A full understanding of transcriptional regulation requires integration of information obtained from multiple experimental datasets. These include datasets annotating gene expression within the context of an entire organism under normal and genetically perturbed conditions. Here we describe an expression dataset annotating pigment cell-expressed genes of the developing melanocyte and retinal pigmented epithelium lineages. Expression images are annotated and available at http://research.nhgri.nih.gov/manuscripts/Loftus/March2009/. Data are also summarized in a standardized manner using a universal melanoblast scoring scale that accounts for the embryonic location of cells and regional cell density. This approach allowed us to classify 14 pigment genes into four groupings classified by cell lineage expression, temporal-spatial context, and differential alteration in response to altered MITF and SOX10 status. Significant differences in regional populations were also observed across inbred strain backgrounds, highlighting the value of this approach to identify modifier allele influences on melanoblast number and distributions. This analysis revealed novel features of in vivo expression patterns that are not measurable by in vitro-based assays, providing data that in combination with genomic analyses will allow modeling of pigment cell gene expression in development and disease.
C1 [Loftus, Stacie K.; Baxter, Laura L.; Buac, Kristina; Watkins-Chow, Dawn E.; Larson, Denise M.; Pavan, William J.] NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA.
RP Loftus, SK (reprint author), NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA.
EM sloftus@mail.nih.gov
OI Watkins-Chow, Dawn/0000-0002-4355-0868
FU NIH; NHGRI
FX This work was funded through the NIH intramural program, NHGRI.
Experiments were performed in accordance with the NHGRI animal care and
use protocol G-94-7. We would like to thank Dr. Lidia Kos for Erbb3
cDNA, Lowell Umayam and Anh-Dao Nguyen (NHGRI Bioinfomatics core) for
database design and support, and Darryl Leja (NHGRI) for graphics
assistance.
NR 58
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PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD OCT
PY 2009
VL 22
IS 5
BP 611
EP 622
DI 10.1111/j.1755-148X.2009.00584.x
PG 12
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 489AD
UT WOS:000269390800015
PM 19493314
ER
PT J
AU Hearing, VJ
AF Hearing, Vincent J.
TI Antibodies specific to melanocyte-specific proteins available from the
Hearing Laboratory
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
ID MONOCLONAL-ANTIBODIES; MAMMALIAN TYROSINASE; LOCUS; IDENTIFICATION;
BIOSYNTHESIS; EXPRESSION; PATTERNS; SKIN
C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 2132, Bethesda, MD 20892 USA.
EM hearingv@nih.gov
NR 15
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD OCT
PY 2009
VL 22
IS 5
BP 651
EP 651
DI 10.1111/j.1755-148X.2009.00601.x
PG 1
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 489AD
UT WOS:000269390800021
ER
PT J
AU Xi, L
Moscou, MJ
Meng, Y
Xu, WH
Caldo, RA
Shaver, M
Nettleton, D
Wise, RP
AF Xi, Liu
Moscou, Matthew J.
Meng, Yan
Xu, Weihui
Caldo, Rico A.
Shaver, Miranda
Nettleton, Dan
Wise, Roger P.
TI Transcript-Based Cloning of RRP46, a Regulator of rRNA Processing and R
Gene-Independent Cell Death in Barley-Powdery Mildew Interactions
SO PLANT CELL
LA English
DT Article
ID F-SP HORDEI; ML-A LOCUS; DISEASE RESISTANCE; HYPERSENSITIVE RESPONSE;
ARABIDOPSIS-THALIANA; LEAF SENESCENCE; DEFENSE RESPONSE; PLANT DEFENSE;
BASAL DEFENSE; MOSAIC-VIRUS
AB Programmed cell death (PCD) plays a pivotal role in plant development and defense. To investigate the interaction between PCD and R gene-mediated defense, we used the 22K Barley1 GeneChip to compare and contrast time-course expression profiles of Blumeria graminis f. sp hordei (Bgh) challenged barley (Hordeum vulgare) cultivar C. I. 16151 (harboring the Mla6 powdery mildew resistance allele) and its fast neutron-derived Bgh-induced tip cell death1 mutant, bcd1. Mixed linear model analysis identified genes associated with the cell death phenotype as opposed to R gene-mediated resistance. One-hundred fifty genes were found at the threshold P value < 0.0001 and a false discovery rate < 0.6%. Of these, 124 were constitutively overexpressed in the bcd1 mutant. Gene Ontology and rice (Oryza sativa) alignment-based annotation indicated that 68 of the 124 overexpressed genes encode ribosomal proteins. A deletion harboring six genes on chromosome 5H cosegregates with bcd1-specified cell death and is associated with misprocessing of rRNAs but segregates independent of R gene-mediated resistance. Barley stripe mosaic virus-induced gene silencing of one of the six deleted genes, RRP46 (rRNA-processing protein 46), phenocopied bcd1-mediated tip cell death. These findings suggest that RRP46, a critical component of the exosome core, mediates RNA processing and degradation involved in cell death initiation as a result of attempted penetration by Bgh during the barley-powdery mildew interaction but is independent of gene-for-gene resistance.
C1 [Xi, Liu; Moscou, Matthew J.; Meng, Yan; Xu, Weihui; Caldo, Rico A.; Wise, Roger P.] Iowa State Univ, Dept Plant Pathol, Ames, IA 50011 USA.
[Xi, Liu; Moscou, Matthew J.; Meng, Yan; Xu, Weihui; Caldo, Rico A.; Wise, Roger P.] Iowa State Univ, Ctr Plant Responses Environm Stresses, Ames, IA 50011 USA.
[Shaver, Miranda; Wise, Roger P.] NIH, Natl Sci Fdn, Bioinformat & Computat Syst Biol Summer Inst, Ames, IA 50011 USA.
[Nettleton, Dan] Iowa State Univ, Dept Stat, Ames, IA 50011 USA.
[Wise, Roger P.] Iowa State Univ, USDA ARS, Ames, IA 50011 USA.
RP Wise, RP (reprint author), Iowa State Univ, Dept Plant Pathol, Ames, IA 50011 USA.
EM rpwise@iastate.edu
RI Moscou, Matthew/D-5266-2011
OI Moscou, Matthew/0000-0003-2098-6818
FU USDA Initiative for Future Agriculture and Food Systems
[2001-52100-11346]; NIH-NSF Bioinformatics and Computational Systems
Biology Summer Institute [06-08769]; National Science Foundation Plant
Genome [05-00461]
FX The authors thank Liz Miller for technical assistance during the mutant
isolation, and Greg Fuerst for excellent technical assistance throughout
the project. This research was supported by the USDA Initiative for
Future Agriculture and Food Systems Grant 2001-52100-11346, NIH-NSF
Bioinformatics and Computational Systems Biology Summer Institute grant
06-08769, and National Science Foundation Plant Genome grant 05-00461.
This article is a joint contribution of the Iowa Agriculture and Home
Economics Experiment Station and the Corn Insects and Crop Genetics
Research Unit, USDA-Agricultural Research Service. Mention of trade
names or commercial products in this publication is solely for the
purpose of providing specific information and does not imply
recommendation or endorsement by the U. S. Department of Agriculture.
NR 66
TC 18
Z9 20
U1 0
U2 9
PU AMER SOC PLANT BIOLOGISTS
PI ROCKVILLE
PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA
SN 1040-4651
J9 PLANT CELL
JI Plant Cell
PD OCT
PY 2009
VL 21
IS 10
BP 3280
EP 3295
DI 10.1105/tpc.109.066167
PG 16
WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology
SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology
GA 525XW
UT WOS:000272252100023
PM 19861556
ER
PT J
AU Holmes, EC
Grenfell, BT
AF Holmes, Edward C.
Grenfell, Bryan T.
TI Discovering the Phylodynamics of RNA Viruses
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID INFLUENZA-A VIRUS; POPULATION-DYNAMICS; MEASLES EPIDEMICS; H3N2 VIRUSES;
EVOLUTION; TRANSMISSION; HUMANS; PHYLOGEOGRAPHY; DIVERSITY; EMERGENCE
C1 [Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA.
[Holmes, Edward C.; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolut Biol, Princeton, NJ 08544 USA.
[Grenfell, Bryan T.] Princeton Univ, Woodrow Wilson Sch, Princeton, NJ 08544 USA.
RP Holmes, EC (reprint author), Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, Mueller Lab, University Pk, PA 16802 USA.
EM ech15@psu.edu
OI Holmes, Edward/0000-0001-9596-3552
FU NIGMS NIH HHS [GM080533, R01 GM080533]
NR 43
TC 57
Z9 57
U1 1
U2 21
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-734X
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD OCT
PY 2009
VL 5
IS 10
AR e1000505
DI 10.1371/journal.pcbi.1000505
PG 6
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 522XI
UT WOS:000272033100002
PM 19855824
ER
PT J
AU Liu, J
Nussinov, R
AF Liu, Jin
Nussinov, Ruth
TI The Mechanism of Ubiquitination in the Cullin-RING E3 Ligase Machinery:
Conformational Control of Substrate Orientation
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID TUMOR-SUPPRESSOR PROTEIN; STRUCTURAL BASIS; FOLDING FUNNELS; BINDING
CASCADES; COMPLEX; INSIGHTS; RECOGNITION; DYNAMICS; ACTIVATION;
ALLOSTERY
AB In cullin-RING E3 ubiquitin ligases, substrate binding proteins, such as VHL-box, SOCS-box or the F-box proteins, recruit substrates for ubiquitination, accurately positioning and orienting the substrates for ubiquitin transfer. Yet, how the E3 machinery precisely positions the substrate is unknown. Here, we simulated nine substrate binding proteins: Skp2, Fbw7, beta-TrCP1, Cdc4, Fbs1, TIR1, pVHL, SOCS2, and SOCS4, in the unbound form and bound to Skp1, ASK1 or Elongin C. All nine proteins have two domains: one binds to the substrate; the other to E3 ligase modules Skp1/ASK1/Elongin C. We discovered that in all cases the flexible inter-domain linker serves as a hinge, rotating the substrate binding domain, optimally and accurately positioning it for ubiquitin transfer. We observed a conserved proline in the linker of all nine proteins. In all cases, the prolines pucker substantially and the pucker is associated with the backbone rotation toward the E2/ubiquitin. We further observed that the linker flexibility could be regulated allosterically by binding events associated with either domain. We conclude that the flexible linker in the substrate binding proteins orients the substrate for the ubiquitin transfer. Our findings provide a mechanism for ubiquitination and polyubiquitination, illustrating that these processes are under conformational control.
C1 [Liu, Jin; Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Liu, J (reprint author), NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
EM ruthnu@helix.nih.gov
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
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 number N01-CO-12400. This research was supported (in part) by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 43
TC 34
Z9 34
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-734X
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD OCT
PY 2009
VL 5
IS 10
AR e1000527
DI 10.1371/journal.pcbi.1000527
PG 10
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 522XI
UT WOS:000272033100007
PM 19798438
ER
PT J
AU Averdam, A
Petersen, B
Rosner, C
Neff, J
Roos, C
Eberle, M
Aujard, F
Munich, C
Schempp, W
Carrington, M
Shiina, T
Inoko, H
Knaust, F
Coggill, P
Sehra, H
Beck, S
Abi-Rached, L
Reinhardt, R
Walter, L
AF Averdam, Anne
Petersen, Beatrix
Rosner, Cornelia
Neff, Jennifer
Roos, Christian
Eberle, Manfred
Aujard, Fabienne
Muenich, Claudia
Schempp, Werner
Carrington, Mary
Shiina, Takashi
Inoko, Hidetoshi
Knaust, Florian
Coggill, Penny
Sehra, Harminder
Beck, Stephan
Abi-Rached, Laurent
Reinhardt, Richard
Walter, Lutz
TI A Novel System of Polymorphic and Diverse NK Cell Receptors in Primates
SO PLOS GENETICS
LA English
DT Article
ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES;
NATURAL-KILLER-CELLS; HLA-E BINDS; MAXIMUM-LIKELIHOOD;
MICROCEBUS-MURINUS; SEQUENCE ALIGNMENT; GENE-COMPLEX; MIXED MODELS;
EVOLUTION
AB There are two main classes of natural killer (NK) cell receptors in mammals, the killer cell immunoglobulin-like receptors (KIR) and the structurally unrelated killer cell lectin-like receptors (KLR). While KIR represent the most diverse group of NK receptors in all primates studied to date, including humans, apes, and Old and New World monkeys, KLR represent the functional equivalent in rodents. Here, we report a first digression from this rule in lemurs, where the KLR (CD94/NKG2) rather than KIR constitute the most diverse group of NK cell receptors. We demonstrate that natural selection contributed to such diversification in lemurs and particularly targeted KLR residues interacting with the peptide presented by MHC class I ligands. We further show that lemurs lack a strict ortholog or functional equivalent of MHC-E, the ligands of nonpolymorphic KLR in "higher" primates. Our data support the existence of a hitherto unknown system of polymorphic and diverse NK cell receptors in primates and of combinatorial diversity as a novel mechanism to increase NK cell receptor repertoire.
C1 [Averdam, Anne; Petersen, Beatrix; Rosner, Cornelia; Neff, Jennifer; Roos, Christian; Walter, Lutz] German Primate Ctr, Dept Primate Genet, Gottingen, Germany.
[Roos, Christian; Walter, Lutz] German Primate Ctr, Gene Bank Primates, Gottingen, Germany.
[Eberle, Manfred] German Primate Ctr, Dept Behav Ecol & Sociobiol, Gottingen, Germany.
[Aujard, Fabienne] CNRS, UMR MNHN 7179, Brunoy, France.
[Muenich, Claudia; Schempp, Werner] Univ Freiburg, Inst Human Genet, Freiburg, Germany.
[Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Shiina, Takashi; Inoko, Hidetoshi] Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan.
[Knaust, Florian; Reinhardt, Richard] Max Planck Inst Mol Genet, Berlin, Germany.
[Coggill, Penny; Sehra, Harminder] Wellcome Trust Sanger Inst, Hinxton, England.
[Beck, Stephan] UCL, Inst Canc, London, England.
[Abi-Rached, Laurent] Stanford Univ, Dept Biol Struct, Sch Med, Stanford, CA 94305 USA.
RP Averdam, A (reprint author), German Primate Ctr, Dept Primate Genet, Gottingen, Germany.
EM lwalter@gwdg.de
RI Abi-Rached, Laurent/H-7236-2012;
OI Walter, Lutz/0000-0001-9408-3131
FU Deutsche Forschungsgemeinschaft [GRK 289]; Nationales
Genomforschungsnetz (NGFN); European Commission [28594]; National Cancer
Institute, National Institutes of Health [HHSN261200800001E]; Intramural
Research Program of the NIH; National Cancer Institute; Center for
Cancer Research; National Institutes of Health [AI 31168]
FX This study was supported by grants from the Deutsche
Forschungsgemeinschaft (GRK 289) to JN and LW and by the Nationales
Genomforschungsnetz (NGFN) to RR. AA was in part supported by the
European Commission (contract 28594). PC, HS, and SB were supported by
the Wellcome Trust. The contribution of MC was funded whole or in part
with federal funds from the National Cancer Institute, National
Institutes of Health, under Contract No. HHSN261200800001E. The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does mention of
trade names, commercial products, or organizations imply endorsement by
the U. S. Government. This research was supported in part by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. LAR was supported by National Institutes of
Health Grant AI 31168 to Peter Parham. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 45
TC 35
Z9 35
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD OCT
PY 2009
VL 5
IS 10
AR e1000688
DI 10.1371/journal.pgen.1000688
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 522WZ
UT WOS:000272032100026
PM 19834558
ER
PT J
AU Braun, R
Rowe, W
Schaefer, C
Zhang, JH
Buetow, K
AF Braun, Rosemary
Rowe, William
Schaefer, Carl
Zhang, Jinghui
Buetow, Kenneth
TI Needles in the Haystack: Identifying Individuals Present in Pooled
Genomic Data
SO PLOS GENETICS
LA English
DT Article
AB Recent publications have described and applied a novel metric that quantifies the genetic distance of an individual with respect to two population samples, and have suggested that the metric makes it possible to infer the presence of an individual of known genotype in a sample for which only the marginal allele frequencies are known. However, the assumptions, limitations, and utility of this metric remained incompletely characterized. Here we present empirical tests of the method using publicly accessible genotypes, as well as analytical investigations of the method's strengths and limitations. The results reveal that the null distribution is sensitive to the underlying assumptions, making it difficult to accurately calibrate thresholds for classifying an individual as a member of the population samples. As a result, the false-positive rates obtained in practice are considerably higher than previously believed. However, despite the metric's inadequacies for identifying the presence of an individual in a sample, our results suggest potential avenues for future research on tuning this method to problems of ancestry inference or disease prediction. By revealing both the strengths and limitations of the proposed method, we hope to elucidate situations in which this distance metric may be used in an appropriate manner. We also discuss the implications of our findings in forensics applications and in the protection of GWAS participant privacy.
C1 [Braun, Rosemary; Rowe, William; Zhang, Jinghui; Buetow, Kenneth] NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA.
[Schaefer, Carl; Buetow, Kenneth] NCI, Ctr Biomed Informat & Informat Technol, NIH, Bethesda, MD 20892 USA.
RP Braun, R (reprint author), NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA.
EM braunr@mail.nih.gov
OI Braun, Rosemary/0000-0001-9668-9866
FU National Cancer Institute, National Institutes of Health, Bethesda, MD
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health, Bethesda, MD.
RB was supported by the Cancer Prevention Fellowship Program, National
Cancer Institute, National Institutes of Health, Bethesda, MD. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 4
TC 24
Z9 25
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD OCT
PY 2009
VL 5
IS 10
AR e1000668
DI 10.1371/journal.pgen.1000668
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 522WZ
UT WOS:000272032100006
PM 19798441
ER
PT J
AU Wheeler, HE
Metter, EJ
Tanaka, T
Absher, D
Higgins, J
Zahn, JM
Wilhelmy, J
Davis, RW
Singleton, A
Myers, RM
Ferrucci, L
Kim, SK
AF Wheeler, Heather E.
Metter, E. Jeffrey
Tanaka, Toshiko
Absher, Devin
Higgins, John
Zahn, Jacob M.
Wilhelmy, Julie
Davis, Ronald W.
Singleton, Andrew
Myers, Richard M.
Ferrucci, Luigi
Kim, Stuart K.
TI Sequential Use of Transcriptional Profiling, Expression Quantitative
Trait Mapping, and Gene Association Implicates MMP20 in Human Kidney
Aging
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CANDIDATE GENES; PARKINSON-DISEASE;
ALZHEIMER-DISEASE; ALLELIC VARIATION; HUMAN LONGEVITY; RENAL-FUNCTION;
HUMAN HOMOLOG; HUMAN BRAIN; AGE
AB Kidneys age at different rates, such that some people show little or no effects of aging whereas others show rapid functional decline. We sequentially used transcriptional profiling and expression quantitative trait loci (eQTL) mapping to narrow down which genes to test for association with kidney aging. We first performed whole-genome transcriptional profiling to find 630 genes that change expression with age in the kidney. Using two methods to detect eQTLs, we found 101 of these age-regulated genes contain expression-associated SNPs. We tested the eQTLs for association with kidney aging, measured by glomerular filtration rate (GFR) using combined data from the Baltimore Longitudinal Study of Aging (BLSA) and the InCHIANTI study. We found a SNP association (rs1711437 in MMP20) with kidney aging (uncorrected p = 3.6 x 10(-5), empirical p = 0.01) that explains 1%-2% of the variance in GFR among individuals. The results of this sequential analysis may provide the first evidence for a gene association with kidney aging in humans.
C1 [Wheeler, Heather E.; Kim, Stuart K.] Stanford Univ, Med Ctr, Dept Genet, Stanford, CA 94305 USA.
[Metter, E. Jeffrey; Tanaka, Toshiko; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
[Metter, E. Jeffrey; Tanaka, Toshiko; Ferrucci, Luigi] Medstar Res Inst, Baltimore, MD USA.
[Absher, Devin; Myers, Richard M.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA.
[Higgins, John] Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA.
[Zahn, Jacob M.; Wilhelmy, Julie; Davis, Ronald W.] Stanford Genome Technol Ctr, Palo Alto, CA USA.
[Singleton, Andrew] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Kim, Stuart K.] Stanford Univ, Med Ctr, Dept Dev Biol, Stanford, CA 94305 USA.
RP Wheeler, HE (reprint author), Stanford Univ, Med Ctr, Dept Genet, Stanford, CA 94305 USA.
EM kim@cmgm.stanford.edu
RI Singleton, Andrew/C-3010-2009;
OI Wheeler, Heather/0000-0003-1365-9667
FU National Institutes of Health [R01 AG025941-01A2]; Ellison Medical
Foundation; NIH, National Institute on Aging; Italian Ministry of Health
[ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263
MD 821336]
FX This work was supported by the National Institutes of Health (R01
AG025941-01A2) and the Ellison Medical Foundation. The BLSA was
supported in part by the Intramural Research Program of the NIH,
National Institute on Aging. A portion of that support was through an
R&D contract with MedStar Research Institute. The InCHIANTI study
baseline (1998-2000) was supported as a "targeted project"
(ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the
U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD
821336). HEW was funded by a NIH grant to the Stanford Genetics and
Developmental Biology Training Program. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 62
TC 37
Z9 37
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD OCT
PY 2009
VL 5
IS 10
AR e1000685
DI 10.1371/journal.pgen.1000685
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 522WZ
UT WOS:000272032100023
PM 19834535
ER
PT J
AU Gordon, I
Paoloni, M
Mazcko, C
Khanna, C
AF Gordon, Ira
Paoloni, Melissa
Mazcko, Christina
Khanna, Chand
TI The Comparative Oncology Trials Consortium: Using Spontaneously
Occurring Cancers in Dogs to Inform the Cancer Drug Development Pathway
SO PLOS MEDICINE
LA English
DT Editorial Material
ID TYROSINE KINASE INHIBITOR; CANINE OSTEOSARCOMA; MURAMYL TRIPEPTIDE;
COMPANION ANIMALS; CLINICAL-TRIALS; CISPLATIN; HUMANS; HYPERTHERMIA;
MALIGNANCIES; TRANSLATION
C1 [Gordon, Ira] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Paoloni, Melissa; Mazcko, Christina; Khanna, Chand] NCI, Comparat Oncol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Gordon, I (reprint author), NCI, Radiat Oncol Branch, Bldg 10, Bethesda, MD 20892 USA.
EM khannac@mail.nih.gov
NR 30
TC 56
Z9 56
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1549-1277
J9 PLOS MED
JI PLos Med.
PD OCT
PY 2009
VL 6
IS 10
AR e1000161
DI 10.1371/journal.pmed.1000161
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 522XB
UT WOS:000272032300005
PM 19823573
ER
PT J
AU Schwarz, A
Helling, S
Collin, N
Teixeira, CR
Medrano-Mercado, N
Hume, JCC
Assumpcao, TC
Marcus, K
Stephan, C
Meyer, HE
Ribeiro, JMC
Billingsley, PF
Valenzuela, JG
Sternberg, JM
Schaub, GA
AF Schwarz, Alexandra
Helling, Stefan
Collin, Nicolas
Teixeira, Clarissa R.
Medrano-Mercado, Nora
Hume, Jen C. C.
Assumpcao, Teresa C.
Marcus, Katrin
Stephan, Christian
Meyer, Helmut E.
Ribeiro, Jose M. C.
Billingsley, Peter F.
Valenzuela, Jesus G.
Sternberg, Jeremy M.
Schaub, Guenter A.
TI Immunogenic Salivary Proteins of Triatoma infestans: Development of a
Recombinant Antigen for the Detection of Low-Level Infestation of
Triatomines
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID RURAL NORTHWESTERN ARGENTINA; MOSQUITO ANOPHELES-GAMBIAE;
RHODNIUS-PROLIXUS STAL; CHAGAS-DISEASE CONTROL; ANTIBODY-RESPONSE;
BLOODSUCKING BUG; LUTZOMYIA-LONGIPALPIS; 2-DIMENSIONAL ELECTROPHORESIS;
TRYPANOSOMA-CRUZI; ARTHROPOD SALIVA
AB Background: Triatomines are vectors of Trypanosoma cruzi, the etiological agent of Chagas disease in Latin America. The most effective vector, Triatoma infestans, has been controlled successfully in much of Latin America using insecticide spraying. Though rarely undertaken, surveillance programs are necessary in order to identify new infestations and estimate the intensity of triatomine bug infestations in domestic and peridomestic habitats. Since hosts exposed to triatomines develop immune responses to salivary antigens, these responses can be evaluated for their usefulness as epidemiological markers to detect infestations of T. infestans.
Methodology/Principal Findings: T. infestans salivary proteins were separated by 2D-gel electrophoresis and tested for their immunogenicity by Western blotting using sera from chickens and guinea pigs experimentally exposed to T. infestans. From five highly immunogenic protein spots, eight salivary proteins were identified by nano liquid chromatography-electrospray ionization-tandem mass spectrometry (nanoLC-ESI-MS/MS) and comparison to the protein sequences of the National Center for Biotechnology Information (NCBI) database and expressed sequence tags of a unidirectionally cloned salivary gland cDNA library from T. infestans combined with the NCBI yeast protein sub-database. The 14.6 kDa salivary protein [gi vertical bar 149689094] was produced as recombinant protein (rTiSP14.6) in a mammalian cell expression system and recognized by all animal sera. The specificity of rTiSP14.6 was confirmed by the lack of reactivity to anti-mosquito and anti-sand fly saliva antibodies. However, rTiSP14.6 was recognized by sera from chickens exposed to four other triatomine species, Triatoma brasiliensis, T. sordida, Rhodnius prolixus, and Panstrongylus megistus and by sera of chickens from an endemic area of T. infestans and Chagas disease in Bolivia.
Conclusions/Significance: The recombinant rTiSP14.6 is a suitable and promising epidemiological marker for detecting the presence of small numbers of different species of triatomines and could be developed for use as a new tool in surveillance programs, especially to corroborate vector elimination in Chagas disease vector control campaigns.
C1 [Schwarz, Alexandra; Billingsley, Peter F.; Sternberg, Jeremy M.] Univ Aberdeen, Sch Biol Sci, Aberdeen, Scotland.
[Schwarz, Alexandra; Schaub, Guenter A.] Ruhr Univ Bochum, Grp Zool Parasitol, Bochum, Germany.
[Helling, Stefan; Marcus, Katrin; Stephan, Christian; Meyer, Helmut E.] Ruhr Univ Bochum, Med Proteom Ctr, Bochum, Germany.
[Collin, Nicolas; Teixeira, Clarissa R.; Ribeiro, Jose M. C.; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Medrano-Mercado, Nora] Univ Mayor San Simon, Dept Biol, Fac Ciencias & Tecnol, Lab Chagas Dis & Immunoparasitol, Cochabamba, Bolivia.
[Hume, Jen C. C.] NIAID, Int Studies & Entomol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Assumpcao, Teresa C.] Univ Brasilia, Lab Host Parasite Interface, Brasilia, DF, Brazil.
[Billingsley, Peter F.] Sanaria, Rockville, MD USA.
RP Schwarz, A (reprint author), Univ Aberdeen, Sch Biol Sci, Zool Bldg, Aberdeen, Scotland.
EM alexandraschwarz@arcor.de
OI Sternberg, Jeremy/0000-0002-1596-3622; Ribeiro, Jose/0000-0002-9107-0818
FU German Academic Exchange Service (DAAD), Bonn, Germany; the Boehringer
Ingelheim Fonds (BIF); Deutsche Forschungsgemeinschaft [Scha 339/ 13-
1]; Humboldt Foundation; University of Aberdeen, Scotland
FX This work was supported by grants from the German Academic Exchange
Service (DAAD), Bonn, Germany (short- term scholarship), the Boehringer
Ingelheim Fonds (BIF), Heidesheim, Germany (travel award), and the `
Deutsche Forschungsgemeinschaft' (project Scha 339/ 13- 1). The support
by the Humboldt Foundation to NMM is gratefully acknowledged, and AS was
funded by the University of Aberdeen, Scotland (Sixth Century
Scholarship). This work was also in part supported by the Intramural
Research Program of the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 78
TC 20
Z9 21
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD OCT
PY 2009
VL 3
IS 10
AR e532
DI 10.1371/journal.pntd.0000532
PG 13
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 522XF
UT WOS:000272032800009
PM 19841746
ER
PT J
AU Bossart, KN
Zhu, ZY
Middleton, D
Klippel, J
Crameri, G
Bingham, J
McEachern, JA
Green, D
Hancock, TJ
Chan, YP
Hickey, AC
Dimitrov, DS
Wang, LF
Broder, CC
AF Bossart, Katharine N.
Zhu, Zhongyu
Middleton, Deborah
Klippel, Jessica
Crameri, Gary
Bingham, John
McEachern, Jennifer A.
Green, Diane
Hancock, Timothy J.
Chan, Yee-Peng
Hickey, Andrew C.
Dimitrov, Dimiter S.
Wang, Lin-Fa
Broder, Christopher C.
TI A Neutralizing Human Monoclonal Antibody Protects against Lethal Disease
in a New Ferret Model of Acute Nipah Virus Infection
SO PLOS PATHOGENS
LA English
DT Article
ID HENDRA VIRUS; SUBUNIT VACCINE; HAMSTER MODEL; TRANSMISSION;
GLYCOPROTEIN; BANGLADESH; RECEPTOR; CATS; BATS; MORBILLIVIRUS
AB Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID(50) within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody.
C1 [Bossart, Katharine N.; Middleton, Deborah; Klippel, Jessica; Crameri, Gary; Bingham, John; McEachern, Jennifer A.; Green, Diane; Hancock, Timothy J.; Wang, Lin-Fa] Australian Anim Hlth Lab, CSIRO Livestock Ind, Geelong, Vic, Australia.
[Zhu, Zhongyu; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21701 USA.
[Zhu, Zhongyu] NCI, BRP, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Chan, Yee-Peng; Hickey, Andrew C.; Broder, Christopher C.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
RP Bossart, KN (reprint author), Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
EM kbossart@bu.edu; cbroder@usuhs.mil
RI Crameri, Gary/H-8441-2013; Barr, Jennifer/H-9254-2013; Bingham,
John/H-8591-2013;
OI Bossart, Katharine/0000-0001-6886-6896
FU Jack Brockhoff Foundation; NIH [AI056423, AI054715, AI077995]
FX This study was supported by a Jack Brockhoff Foundation grant to KNB and
NIH grants AI056423, AI054715 and AI077995 to CCB. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 37
TC 101
Z9 102
U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD OCT
PY 2009
VL 5
IS 10
AR e1000642
DI 10.1371/journal.ppat.1000642
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 522XK
UT WOS:000272033300046
PM 19888339
ER
PT J
AU Casazza, JP
Brenchley, JM
Hill, BJ
Ayana, R
Ambrozak, D
Roederer, M
Douek, DC
Betts, MR
Koup, RA
AF Casazza, Joseph P.
Brenchley, Jason M.
Hill, Brenna J.
Ayana, Ribka
Ambrozak, David
Roederer, Mario
Douek, Daniel C.
Betts, Michael R.
Koup, Richard A.
TI Autocrine Production of beta-Chemokines Protects CMV-Specific CD4(+) T
Cells from HIV Infection
SO PLOS PATHOGENS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MACROPHAGE INFLAMMATORY PROTEIN-1;
CYTOMEGALOVIRUS RETINITIS; HIV-1-INFECTED SUBJECTS; ANTIRETROVIRAL
THERAPY; RESPONSES REVEALS; NONHUMAN-PRIMATES; RECEPTOR CCR5; IN-VIVO;
IDENTIFICATION
AB Induction of a functional subset of HIV-specific CD4(+) T cells that is resistant to HIV infection could enhance immune protection and decrease the rate of HIV disease progression. CMV-specific CD4(+) T cells, which are less frequently infected than HIV-specific CD4(+) T cells, are a model for such an effect. To determine the mechanism of this protection, we compared the functional response of HIV gag-specific and CMV pp65-specific CD4(+) T cells in individuals co-infected with CMV and HIV. We found that CMV-specific CD4(+) T cells rapidly up-regulated production of MIP-1 alpha and MIP-1 beta mRNA, resulting in a rapid increase in production of MIP-1 alpha and MIP-1 beta after cognate antigen stimulation. Production of beta-chemokines was associated with maturational phenotype and was rarely seen in HIV-specific CD4(+) T cells. To test whether production of beta-chemokines by CD4(+) T cells lowers their susceptibility to HIV infection, we measured cell-associated Gag DNA to assess the in vivo infection history of CMV-specific CD4(+) T cells. We found that CMV-specific CD4(+) T cells which produced MIP-1 beta contained 10 times less Gag DNA than did those which failed to produce MIP-1 beta. These data suggest that CD4(+) T cells which produce MIP-1 alpha and MIP-1 beta bind these chemokines in an autocrine fashion which decreases the risk of in vivo HIV infection.
C1 [Casazza, Joseph P.; Ayana, Ribka; Ambrozak, David; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Brenchley, Jason M.; Hill, Brenna J.] NIAID, Immunopathogenesis Unit, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Betts, Michael R.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
RP Casazza, JP (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM jcasazza@mail.nih.gov
FU Intramural NIH/NIAID funding
FX This work was supported by Intramural NIH/NIAID funding. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 42
TC 38
Z9 38
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD OCT
PY 2009
VL 5
IS 10
AR e1000646
DI 10.1371/journal.ppat.1000646
PG 13
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 522XK
UT WOS:000272033300050
PM 19876388
ER
PT J
AU McDonald, SM
Matthijnssens, J
McAllen, JK
Hine, E
Overton, L
Wang, SL
Lemey, P
Zeller, M
Van Ranst, M
Spiro, DJ
Patton, JT
AF McDonald, Sarah M.
Matthijnssens, Jelle
McAllen, John K.
Hine, Erin
Overton, Larry
Wang, Shiliang
Lemey, Philippe
Zeller, Mark
Van Ranst, Marc
Spiro, David J.
Patton, John T.
TI Evolutionary Dynamics of Human Rotaviruses: Balancing Reassortment with
Preferred Genome Constellations
SO PLOS PATHOGENS
LA English
DT Article
ID GROUP-A ROTAVIRUS; LINKED-IMMUNOSORBENT-ASSAY; G-GENOTYPE; STRAINS;
VACCINE; GASTROENTERITIS; VIRUS; SEROTYPES; CHILDREN; PROTEIN
AB Group A human rotaviruses (RVs) are a major cause of severe gastroenteritis in infants and young children. Yet, aside from the genes encoding serotype antigens (VP7; G-type and VP4; P-type), little is known about the genetic make-up of emerging and endemic human RV strains. To gain insight into the diversity and evolution of RVs circulating at a single location over a period of time, we sequenced the eleven-segmented, double-stranded RNA genomes of fifty-one G3P[8] strains collected from 1974 to 1991 at Children's Hospital National Medical Center, Washington, D. C. During this period, G1P[8] strains typically dominated, comprising on average 56% of RV infections each year in hospitalized children. A notable exception was in the 1976 and 1991 winter seasons when the incidence of G1P[8] infections decreased dramatically, a trend that correlated with a significant increase in G3P[8] infections. Our sequence analysis indicates that the 1976 season was characterized by the presence of several genetically distinct, co-circulating clades of G3P[8] viruses, which contained minor but significant differences in their encoded proteins. These 1976 lineages did not readily exchange gene segments with each other, but instead remained stable over the course of the season. In contrast, the 1991 season contained a single major clade, whose genome constellation was similar to one of the 1976 clades. The 1991 clade may have gained a fitness advantage after reassorting with as of yet unidentified RV strain(s). This study reveals for the first time that genetically distinct RV clades of the same G/P-type can co-circulate and cause disease. The findings from this study also suggest that, although gene segment exchange occurs, most reassortant strains are replaced over time by lineages with preferred genome constellations. Elucidation of the selective pressures that favor maintenance of RVs with certain sets of genes may be necessary to anticipate future vaccine needs.
C1 [McDonald, Sarah M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Matthijnssens, Jelle; Lemey, Philippe; Zeller, Mark; Van Ranst, Marc] Katholieke Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, Lab Clin & Epidemiol Virol, Louvain, Belgium.
[McAllen, John K.; Hine, Erin; Overton, Larry; Wang, Shiliang; Spiro, David J.] J Craig Venter Inst, Rockville, MD USA.
RP McDonald, SM (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM jpatton@niaid.nih.gov
RI Patton, John/P-1390-2014; Matthijnssens, Jelle/A-6770-2015;
Matthijnssens, Jelle/B-8634-2016;
OI Van Ranst, Marc/0000-0002-1674-4157
FU Intramural Research Program of the NIH; National Institute of Allergy
and Infectious Diseases; Research Fund K.U. Leuven
FX SMM and JTP are supported by the Intramural Research Program of the NIH,
National Institute of Allergy and Infectious Diseases. JM is supported
by a postdoctoral fellowship of the Research Fund K.U. Leuven. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 43
TC 82
Z9 83
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD OCT
PY 2009
VL 5
IS 10
AR e1000634
DI 10.1371/journal.ppat.1000634
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 522XK
UT WOS:000272033300038
PM 19851457
ER
PT J
AU Moore, MD
Nikolaitchik, OA
Chen, JB
Hammarskjold, ML
Rekosh, D
Hu, WS
AF Moore, Michael D.
Nikolaitchik, Olga A.
Chen, Jianbo
Hammarskjoeld, Marie-Louise
Rekosh, David
Hu, Wei-Shau
TI Probing the HIV-1 Genomic RNA Trafficking Pathway and Dimerization by
Genetic Recombination and Single Virion Analyses
SO PLOS PATHOGENS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; NUCLEAR EXPORT;
MESSENGER-RNA; VIRAL REPLICATION; CELLS; DISTANCE; RATES; EXPRESSION;
MUTATIONS
AB Once transcribed, the nascent full-length RNA of HIV-1 must travel to the appropriate host cell sites to be translated or to find a partner RNA for copackaging to form newly generated viruses. In this report, we sought to delineate the location where HIV-1 RNA initiates dimerization and the influence of the RNA transport pathway used by the virus on downstream events essential to viral replication. Using a cell-fusion-dependent recombination assay, we demonstrate that the two RNAs destined for copackaging into the same virion select each other mostly within the cytoplasm. Moreover, by manipulating the RNA export element in the viral genome, we show that the export pathway taken is important for the ability of RNA molecules derived from two viruses to interact and be copackaged. These results further illustrate that at the point of dimerization the two main cellular export pathways are partially distinct. Lastly, by providing Gag in trans, we have demonstrated that Gag is able to package RNA from either export pathway, irrespective of the transport pathway used by the gag mRNA. These findings provide unique insights into the process of RNA export in general, and more specifically, of HIV-1 genomic RNA trafficking.
C1 [Moore, Michael D.; Nikolaitchik, Olga A.; Chen, Jianbo; Hu, Wei-Shau] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Hammarskjoeld, Marie-Louise; Rekosh, David] Univ Virginia, Myles H Thaler Ctr AIDS Res, Charlottesville, VA USA.
RP Moore, MD (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
EM whu@ncifcrf.gov
RI Chen, Jianbo/N-3737-2014
OI Chen, Jianbo/0000-0001-6491-6577
FU Intramural Research Program of the National Institutes of Health (NIH);
National Cancer Institute, Center for Cancer Research; NIH [AI068501,
CA097095]
FX This work is supported in part by the Intramural Research Program of the
National Institutes of Health (NIH, www.nih.gov), National Cancer
Institute, Center for Cancer Research (MDM, OAR, and WSH), and in part
by NIH grants AI068501 (to DR), CA097095 (to MLH) and AI068501 (to MLH).
Partial salary support for DR and MLH was provided by the Myles H.
Thaler and Charles H. Ross Jr. professorships at UVA (www.virginia.edu).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 37
TC 53
Z9 53
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD OCT
PY 2009
VL 5
IS 10
AR e1000627
DI 10.1371/journal.ppat.1000627
PG 10
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 522XK
UT WOS:000272033300031
PM 19834549
ER
PT J
AU Wearing, HJ
Rohani, P
AF Wearing, Helen J.
Rohani, Pejman
TI Estimating the Duration of Pertussis Immunity Using Epidemiological
Signatures
SO PLOS PATHOGENS
LA English
DT Article
ID BORDETELLA-PERTUSSIS; STOCHASTIC SIMULATION; HOUSEHOLD EXPOSURE; WANING
IMMUNITY; VACCINATION; TRANSMISSION; DISEASE; IMMUNIZATION; INFECTION;
ENGLAND
AB Case notifications of pertussis have shown an increase in a number of countries with high rates of routine pediatric immunization. This has led to significant public health concerns over a possible pertussis re-emergence. A leading proposed explanation for the observed increase in incidence is the loss of immunity to pertussis, which is known to occur after both natural infection and vaccination. Little is known, however, about the typical duration of immunity and its epidemiological implications. Here, we analyze a simple mathematical model, exploring specifically the inter-epidemic period and fade-out frequency. These predictions are then contrasted with detailed incidence data for England and Wales. We find model output to be most sensitive to assumptions concerning naturally acquired immunity, which allows us to estimate the average duration of immunity. Our results support a period of natural immunity that is, on average, long-lasting (at least 30 years) but inherently variable.
C1 [Wearing, Helen J.] Univ New Mexico, Dept Biol, Albuquerque, NM 87131 USA.
[Wearing, Helen J.] Univ New Mexico, Dept Math & Stat, Albuquerque, NM 87131 USA.
[Rohani, Pejman] Univ Georgia, Ctr Trop & Emerging Global Dis, Athens, GA 30602 USA.
[Rohani, Pejman] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA.
[Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Wearing, HJ (reprint author), Univ New Mexico, Dept Biol, Albuquerque, NM 87131 USA.
EM hwearing@unm.edu
FU National Institutes of Health [R01 GM69111]; National Science Foundation
[DEB 0343176]; Ellison Medical Foundation; University of New Mexico
FX This work was supported by the National Institutes of Health (R01
GM69111), the National Science Foundation (DEB 0343176) and a New
Scholar Award in Global Infectious Disease from the Ellison Medical
Foundation to PR. HJW was supported, in part, by start-up funds from the
University of New Mexico. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 42
TC 57
Z9 58
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7366
J9 PLOS PATHOG
JI PLoS Pathog.
PD OCT
PY 2009
VL 5
IS 10
AR e1000647
DI 10.1371/journal.ppat.1000647
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 522XK
UT WOS:000272033300051
PM 19876392
ER
PT J
AU Xu, S
Shen, J
AF Xu, Su
Shen, Jun
TI Studying enzymes by in vivo C-13 magnetic resonance spectroscopy
SO PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
LA English
DT Review
DE Fast chemical exchange; Enzyme-catalyzed reactions; Enzyme kinetics; In
vivo C-13 magnetization transfer effect; Magnetic resonance spectroscopy
ID CREATINE-KINASE REACTION; RAT SKELETAL-MUSCLE; LACTATE-DEHYDROGENASE
ISOENZYMES; KETOGLUTARATE GLUTAMATE EXCHANGE; TRANSFER KINETIC
MEASUREMENTS; CHLORALOSE-ANESTHETIZED RATS; TRICARBOXYLIC-ACID CYCLE;
ANHYDRASE-II DEFICIENCY; RENAL TUBULAR-ACIDOSIS; CARBONIC-ANHYDRASE
C1 [Xu, Su; Shen, Jun] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Shen, J (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shenj@intra.nimh.nih.gov
FU NIMH; NIH
FX This work was supported by the Intramural Research Program of the NIMH,
NIH. The authors thank Ms. Ioline Henter for help with manuscript
preparation.
NR 166
TC 4
Z9 4
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0079-6565
J9 PROG NUCL MAG RES SP
JI Prog. Nucl. Magn. Reson. Spectrosc.
PD OCT
PY 2009
VL 55
IS 3
BP 266
EP 283
DI 10.1016/j.pnmrs.2009.06.002
PG 18
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Spectroscopy
SC Chemistry; Physics; Spectroscopy
GA 489EM
UT WOS:000269402800005
PM 20161496
ER
PT J
AU Xu, JF
Sun, JEL
Kader, AK
Lindstrom, S
Wiklund, F
Hsu, FC
Johansson, JE
Zheng, SL
Thomas, G
Hayes, RB
Kraft, P
Hunter, DJ
Chanock, SJ
Isaacs, WB
Gronberg, H
AF Xu, Jianfeng
Sun, Jielin
Kader, A. Karim
Lindstrom, Sara
Wiklund, Fredrik
Hsu, Fang-Chi
Johansson, Jan-Erik
Zheng, S. Lilly
Thomas, Gilles
Hayes, Richard B.
Kraft, Peter
Hunter, David J.
Chanock, Stephen J.
Isaacs, William B.
Gronberg, Henrik
TI Estimation of Absolute Risk for Prostate Cancer Using Genetic Markers
and Family History
SO PROSTATE
LA English
DT Article
DE SNPs; association; early detection; chemoprevention
ID GENOME-WIDE ASSOCIATION; SEQUENCE VARIANTS; MULTIPLE; POPULATIONS; LOCI;
SUSCEPTIBILITY; FINASTERIDE; PREDICTION
AB BACKGROUND. Multiple DNA sequence variants in the form of single-nucleotide polymorphisms (SNPs) have been found to be reproducibly associated with prostate cancer (PCa) risk.
METHODS. Absolute risk for PCa among men with various numbers of inherited risk alleles and family history of PCa was estimated in a population-based case-control study in Sweden (2,893 cases and 1,781 controls), and a nested case-control study from the Prostate, Lung, Colon and Ovarian (PLCO) Cancer Screening Trial in the U.S. (1,172 cases and 1,157 controls).
RESULTS. Increased number of risk alleles and positive family history were independently associated with PCa risk. Considering men with 11 risk alleles (mode) and negative family history as having baseline risk, men who had >= 14 risk alleles and positive family history had an odds ratio (OR) of 4.92 [95% confidence interval (CI): 3.64-6.64] in the Swedish study. These associations were confirmed in the U.S. population. Once a man's SNP genotypes and family history are known, his absolute risk for PCa can be readily calculated and easily interpreted. For example, 55-year-old men with a family history and >= 14 risk alleles have a 52% and 41% risk of being diagnosed with PCa in the next 20 years in the Swedish and U.S. populations, respectively. In comparison, without knowledge of genotype and family history, these men had an average population absolute risk of 13%.
CONCLUSION. This risk prediction model may be used to identify men at considerably elevated PCa risk who may be selected for chemoprevention. Prostate 69: 1565-1572, 2009. (C) 2009 Wiley-Liss, Inc.
C1 [Xu, Jianfeng; Sun, Jielin; Kader, A. Karim; Hsu, Fang-Chi; Zheng, S. Lilly] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC 27157 USA.
[Xu, Jianfeng; Sun, Jielin; Hsu, Fang-Chi; Zheng, S. Lilly] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC 27157 USA.
[Kader, A. Karim] Wake Forest Univ, Bowman Gray Sch Med, Dept Urol, Winston Salem, NC 27157 USA.
[Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Hsu, Fang-Chi] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Johansson, Jan-Erik] Orebro Univ Hosp, Dept Urol, Orebro, Sweden.
[Thomas, Gilles; Hayes, Richard B.; Kraft, Peter; Hunter, David J.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Isaacs, William B.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
RP Xu, JF (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM jxu@wfubmc.edu; wisaacs@jhmi.edu
OI Hayes, Richard/0000-0002-0918-661X
FU National Cancer Institute [CA105055, CA106523, CA95052]; Department of
Defense [PC051264]; Swedish Cancer Society (Cancerfonden); Swedish
Academy of Sciences (Vetenskapsradet)
FX Grant sponsor: National Cancer Institute; Grant numbers: CA105055,
CA106523, CA95052; Grant sponsor: Department of Defense; Grant number:
PC051264; Grant sponsor: Swedish Cancer Society (Cancerfonden); Grant
sponsor: Swedish Academy of Sciences (Vetenskapsradet).
NR 29
TC 53
Z9 55
U1 1
U2 3
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-4137
J9 PROSTATE
JI Prostate
PD OCT 1
PY 2009
VL 69
IS 14
BP 1565
EP 1572
DI 10.1002/pros.21002
PG 8
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 497OV
UT WOS:000270070300009
PM 19562736
ER
PT J
AU Remmert, K
Uruno, T
Hammer, JA
AF Remmert, Kirsten
Uruno, Takehito
Hammer, John A., III
TI Purification of capping protein using the capping protein binding site
of CARMIL as an affinity matrix
SO PROTEIN EXPRESSION AND PURIFICATION
LA English
DT Article
DE Capping protein; CARMIL; Affinity matrix; CAH3 domain
ID ACTIN-BASED MOTILITY; ARP2/3 COMPLEX; BARBED END; MYOSIN-I; FILAMENT;
POLYMERIZATION; IDENTIFICATION; DICTYOSTELIUM; MECHANISM; INSIGHTS
AB Capping protein (CP) is a ubiquitously expressed, heterodimeric actin binding protein that is essential for normal actin dynamics in cells. The existing methods for purifying native CP from tissues and recombinant CP from bacteria are time-consuming processes that involve numerous conventional chromatographic steps and functional assays to achieve a homogeneous preparation of the protein. Here, we report the rapid purification of Acanthamoeba CP from amoeba extracts and recombinant mouse CP from E. coli extracts using as an affinity matrix GST-fusion proteins containing the CP binding site from Acanthamoeba CARMIL and mouse CARMIL-1, respectively. This improved method for CP purification should facilitate the in vitro analysis of CP structure, function, and regulation. Published by Elsevier Inc.
C1 [Remmert, Kirsten; Uruno, Takehito; Hammer, John A., III] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Hammer, JA (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Room 2523,9000 Rockville Pike, Rockville, MD USA.
EM hammerj@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 20
TC 3
Z9 3
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-5928
J9 PROTEIN EXPRES PURIF
JI Protein Expr. Purif.
PD OCT
PY 2009
VL 67
IS 2
BP 113
EP 119
DI 10.1016/j.pep.2009.05.002
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 541LJ
UT WOS:000273416900008
PM 19427903
ER
PT J
AU Post, RM
AF Post, Robert M.
TI Bipolar Disorder, with a Focus on Childhood-onset Bipolar Disorder
SO PSYCHIATRIC ANNALS
LA English
DT Editorial Material
ID ADOLESCENTS; CHILDREN
C1 [Post, Robert M.] George Washington Univ, Washington, DC 20052 USA.
[Post, Robert M.] Bipolar Collaborat Network, Bethesda, MD USA.
[Post, Robert M.] NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA.
RP Post, RM (reprint author), George Washington Univ, Washington, DC 20052 USA.
NR 10
TC 0
Z9 0
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0048-5713
J9 PSYCHIAT ANN
JI Psychiatr. Ann.
PD OCT
PY 2009
VL 39
IS 10
BP 874
EP +
DI 10.3928/00485718-20090924-04
PG 2
WC Psychiatry
SC Psychiatry
GA 507IY
UT WOS:000270847300002
ER
PT J
AU Gillum, RF
Santibanez, S
Bennett, G
Donahue, M
AF Gillum, R. F.
Santibanez, Scott
Bennett, Glen
Donahue, Michael
TI ASSOCIATIONS OF PRAYER, MIND-BODY THERAPY, AND SMOKING CESSATION IN A
NATIONAL SURVEY
SO PSYCHOLOGICAL REPORTS
LA English
DT Article
ID CIGARETTE-SMOKING; AFRICAN-AMERICANS; INTERVENTIONS; RELAXATION;
PROGRAM; ADULTS; HEART; SOUL
AB Smoking is the leading preventable cause of death. Many people use mind-body therapies and/or prayer to assist them in smoking cessation, but more information on their effectiveness is needed. In the 2002 National Health Interview Survey, 5,864 persons aged 18 or older reported smoking in the prior 12 mo.; among these, users of any of 10 mind-body therapies or prayer were compared to nonusers to assess smoking cessation attempts and smoking cessation over a 1-yr. period. Weighted logistic regression showed that the adjusted odds of reporting quit attempts during the year prior to interview or of reporting no longer smoking at interview were significantly higher in those using prayer alone, ally mind-body therapy alone, or both, compared with those who used neither. In the Subset of 2,839 persons who reported smoking 12 mo. prior to interview and attempting to quit during the year prior to interview, the odds of reporting no longer smoking at interview were no greater for those who used prayer, any mind-body therapy, or both, than in those using neither.
C1 [Gillum, R. F.] Howard Univ, Sch Divin, Washington, DC 20017 USA.
[Gillum, R. F.] Howard Univ, Coll Med, Washington, DC 20017 USA.
[Santibanez, Scott] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
[Bennett, Glen] Natl Inst Hlth, Bethesda, MD 20892 USA.
[Donahue, Michael] Inst Psychol Sci, Alexandria, VA USA.
RP Gillum, RF (reprint author), Howard Univ, Sch Divin, Washington, DC 20017 USA.
EM frank.gillum@gmail.com
NR 26
TC 2
Z9 2
U1 1
U2 5
PU AMMONS SCIENTIFIC, LTD
PI MISSOULA
PA PO BOX 9229, MISSOULA, MT 59807-9229 USA
SN 0033-2941
J9 PSYCHOL REP
JI Psychol. Rep.
PD OCT
PY 2009
VL 105
IS 2
BP 593
EP 604
DI 10.2466/PR0.105.2.593-604
PG 12
WC Psychology, Multidisciplinary
SC Psychology
GA 508TM
UT WOS:000270959200029
PM 19928621
ER
PT J
AU Fortune-Greeley, AK
Flynn, KE
Jeffery, DD
Williams, MS
Keefe, FJ
Reeve, BB
Willis, GB
Weinfurt, KP
AF Fortune-Greeley, Alice K.
Flynn, Kathryn E.
Jeffery, Diana D.
Williams, Megan S.
Keefe, Francis J.
Reeve, Bryce B.
Willis, Gordon B.
Weinfurt, Kevin P.
TI Using cognitive interviews to evaluate items for measuring sexual
functioning across cancer populations: improvements and remaining
challenges
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Clinical trials as topic; Neoplasms; Patient satisfaction;
Psychometrics; Quality indicators; Quality of life; Sexuality; Treatment
outcome
ID QUALITY-OF-LIFE; INFORMATION-SYSTEM PROMIS; INTIMACY; INDEX
AB One goal of the Patient-Reported Outcomes Measurement Information System (TM) (PROMIS (TM)) is to develop a measure of sexual functioning that broadens the definition of sexual activity and incorporates items that reflect constructs identified as important by patients with cancer. We describe how cognitive interviews improved the quality of the items and discuss remaining challenges to assessing sexual functioning in research with cancer populations.
We conducted 39 cognitive interviews of patients with cancer and survivors on the topic of sexual experience. Each of the 83 candidate items was seen by 5-24 participants. Participants included both men and women and varied by cancer type, treatment trajectory, race, and literacy level. Significantly revised items were retested in subsequent interviews.
Cognitive interviews provided useful feedback about the relevance, sensitivity, appropriateness, and clarity of the items. Participants identified broad terms (e.g., "sex life") to assess sexual experience and exposed the challenges of measuring sexual functioning consistently, considering both adjusted and unadjusted sexual experiences.
Cognitive interviews were critical for item refinement in the development of the PROMIS measure of sexual function. Efforts are underway to validate the measure in larger cancer populations.
C1 [Fortune-Greeley, Alice K.; Flynn, Kathryn E.; Weinfurt, Kevin P.] Duke Clin Res Inst, Ctr Clin & Genet Econ, Durham, NC 27715 USA.
[Flynn, Kathryn E.; Keefe, Francis J.; Weinfurt, Kevin P.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC USA.
[Williams, Megan S.] Duke Univ, Sch Nursing, Durham, NC USA.
[Jeffery, Diana D.; Reeve, Bryce B.; Willis, Gordon B.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Weinfurt, KP (reprint author), Duke Clin Res Inst, Ctr Clin & Genet Econ, POB 17969, Durham, NC 27715 USA.
EM kevin.weinfurt@duke.edu
RI Flynn, Kathryn/M-5346-2013;
OI Flynn, Kathryn/0000-0002-4427-3583; Fortune-Greeley,
Alice/0000-0001-9004-571X
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
[U01AR052186]; National Cancer Institute
FX Funding/Support: This work was funded by grant U01AR052186 from the
National Institute of Arthritis and Musculoskeletal and Skin Diseases,
with additional support from the National Cancer Institute. Disclaimer:
The content of this paper is solely the responsibility of the authors
and does not necessarily represent the official views of the National
Institute of Arthritis and Musculoskeletal and Skin Diseases, the
National Cancer Institute, or the National Institutes of Health. PROMIS
Sexual Function Domain Committee: Maria R. Fawzy, Kathryn E. Flynn,
Tracey L. Krupski, Laura S. Porter, Rebecca Shelby, and Kevin P.
Weinfurt (Duke University); Elizabeth A. Hahn (Northwestern University);
and Diana D. Jeffery and Bryce B. Reeve (National Cancer Institute).
Additional Contributions: We thank Elizabeth Clipp of Duke University
and Wendy Demark-Wahnefried of MD Anderson Cancer Center for assistance
with PROMIS grant development; Denise Snyder of Duke University for
assistance with data collection; Justin Levens and Chantelle Hardy of
Duke University for conducting the cognitive interviews; Janice Tzeng of
Duke University for research assistance; and Damon Seils of Duke
University for editorial assistance and manuscript preparation.
NR 21
TC 20
Z9 20
U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
J9 QUAL LIFE RES
JI Qual. Life Res.
PD OCT
PY 2009
VL 18
IS 8
BP 1085
EP 1093
DI 10.1007/s11136-009-9523-x
PG 9
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 495IU
UT WOS:000269885400014
PM 19672697
ER
PT J
AU Lushchak, OV
Bayliak, MM
Korobova, OV
Levine, RL
Lushchak, VI
AF Lushchak, Oleh V.
Bayliak, Maria M.
Korobova, Olha V.
Levine, Rodney L.
Lushchak, Volodymyr I.
TI Buffer modulation of menadione-induced oxidative stress in Saccharomyces
cerevisiae
SO REDOX REPORT
LA English
DT Article
DE aconitase; antioxidant enzymes; glutathione; protein carbonyls; reactive
oxygen species; Saccharomyces cerevisiae
ID REDOX-DEPENDENT MODULATION; CARBONATE RADICAL-ANION; AMINO-ACID
OXIDATION; CU,ZN-SUPEROXIDE DISMUTASE; HYDROGEN-PEROXIDE;
SUPEROXIDE-DISMUTASE; MITOCHONDRIAL ACONITASE; BICARBONATE BUFFER;
CHEMISTRY; PROTEINS
AB The objective of this study was to compare, in vivo, the effects of bicarbonate and phosphate buffers on survival and menadione-induced oxidative stress in yeast cells. The latter were treated with different concentrations of menadione in the presence of these two buffers. At 25 mM concentration of buffers, menadione only slightly reduced yeast surviving; at up mM concentration, cell killing by menadione was much more pronounced in bicarbonate than in phosphate buffer. Although the content of protein carbonyl groups did not show development of oxidative stress under menadione-induced stress, inactivation of aconitase and decrease in glutathione level mirrored its induction. However, cellular glutathione and aconitase activity decrease did not correlate with yeast survival. In vitro, aconitase was more quickly inactivated in up mM carbonate, than in up mM phosphate buffer. The possible involvement of the carbonate radical in these processes is discussed.
C1 [Lushchak, Oleh V.; Bayliak, Maria M.; Korobova, Olha V.; Lushchak, Volodymyr I.] Vassyl Stefanyk Precarpathian Natl Univ, Dept Biochem, UA-76025 Ivano Frankivsk, Ukraine.
[Levine, Rodney L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
RP Lushchak, VI (reprint author), Vassyl Stefanyk Precarpathian Natl Univ, Dept Biochem, 57 Shevchenko Str, UA-76025 Ivano Frankivsk, Ukraine.
EM lushchak@pu.if.ua
RI Lushchak, Oleh/A-8772-2015; Bayliak, Maria/P-8950-2015; Levine,
Rodney/D-9885-2011
OI Lushchak, Oleh/0000-0002-4627-1987; Bayliak, Maria/0000-0001-6268-8910;
FU Intramural NIH HHS [ZIA HL000225-32]
NR 40
TC 7
Z9 7
U1 0
U2 3
PU MANEY PUBLISHING
PI LEEDS
PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND
SN 1351-0002
J9 REDOX REP
JI Redox Rep.
PD OCT
PY 2009
VL 14
IS 5
BP 214
EP 220
DI 10.1179/135100009X12525712409454
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 517OL
UT WOS:000271625100004
PM 19843376
ER
PT J
AU Prause, AS
Stoffel, MH
Portier, CJ
Mevissen, M
AF Prause, Andrea S.
Stoffel, Michael H.
Portier, Christopher J.
Mevissen, Meike
TI Expression and function of 5-HT7 receptors in smooth muscle preparations
from equine duodenum, ileum, and pelvic flexure
SO RESEARCH IN VETERINARY SCIENCE
LA English
DT Article
DE 5-HT7 receptor; Interstitial cells of Cajal; c-Kit; Equine; Intestine;
Motility
ID GUINEA-PIG ILEUM; GASTROINTESTINAL-TRACT; INTERSTITIAL-CELLS;
SMALL-INTESTINE; PHARMACOLOGICAL CHARACTERIZATION;
5-HYDROXYTRYPTAMINE(4) RECEPTOR; MEDIATING CONTRACTION; LONGITUDINAL
MUSCLE; HORSES; SEROTONIN
AB In horses, gastrointestinal (GI) disorders occur frequently and cause a considerable demand for efficient medication. 5-Hydroxytryptamine receptors (5-HT) have been reported to be involved in GI tract motility and thus, are potential targets for treating functional bowel disorders. Our studies extend current knowledge on the 5-HT7 receptor in equine duodenum, ileum and pelvic flexure by studying its expression throughout the intestine and its role in modulating contractility in vitro by immunofluorescence and organ bath experiments, respectively.
5-HT7 immunoreactivity was demonstrated in both smooth muscle layers, particularly in the circular one, and within the myenteric plexus. Interstitial cells of Cajal (ICC), identified by c-Kit labeling, show a staining pattern similar to that of 5-HT7 immunoreactivity.
The selective 5-HT7 receptor antagonist SB-269970 increased the amplitude of contractions in spontaneous contracting specimens of the ileum and in electrical field-stimulated specimens of the pelvic flexure concentration-dependently.
Our in vitro experiments suggest an involvement of the 5-HT7 receptor subtype in contractility of equine intestine. While the 5-HT7 receptor has been established to be constitutively active and inhibits smooth muscle contractility, our experiments demonstrate an increase in contractility by the 5-HT7 receptor ligand SB-269970, suggesting it exerting inverse agonist properties. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Prause, Andrea S.; Mevissen, Meike] Univ Bern, Div Vet Pharmacol & Toxicol, CH-3012 Bern, Switzerland.
[Stoffel, Michael H.] Univ Bern, Div Vet Anat, CH-3012 Bern, Switzerland.
[Portier, Christopher J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
RP Mevissen, M (reprint author), Univ Bern, Div Vet Pharmacol & Toxicol, CH-3012 Bern, Switzerland.
EM meike.mevissen@vpi.unibe.ch
RI Portier, Christopher/A-3160-2010; Stoffel, Michael/I-6939-2015
OI Portier, Christopher/0000-0002-0954-0279; Stoffel,
Michael/0000-0002-4699-5125
FU Vetsuisse and the Berne University Research Foundation; Intramural
Research Program of the NIH; NIEHS
FX This study was funded by Vetsuisse and the Berne University Research
Foundation. This research was supported [in part] by the Intramural
Research Program of the NIH, and NIEHS.
NR 44
TC 7
Z9 9
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0034-5288
J9 RES VET SCI
JI Res. Vet. Sci.
PD OCT
PY 2009
VL 87
IS 2
BP 292
EP 299
DI 10.1016/j.rvsc.2009.03.009
PG 8
WC Veterinary Sciences
SC Veterinary Sciences
GA 482PH
UT WOS:000268900700029
PM 19364615
ER
PT J
AU Ballarino, GJ
Olivier, KN
Claypool, RJ
Holland, SM
Prevots, DR
AF Ballarino, Guillermo J.
Olivier, Kenneth N.
Claypool, Reginald J.
Holland, Steven M.
Prevots, D. Rebecca
TI Pulmonary nontuberculous mycobacterial infections: Antibiotic treatment
and associated costs
SO RESPIRATORY MEDICINE
LA English
DT Article
DE Mycobacteria, atypical; Nontuberculous mycobacteria; Anti mycobacterial.
agents; Health-care costs; Drug toxicity; Mycobacterium avium complex
ID UNITED-STATES; DISEASES; HIV; EPIDEMIOLOGY; SPECIMENS; DIAGNOSIS; CARE
AB Recent studies suggest an increasing prevalence of pulmonary nontuberculous mycobacteria (NTM) disease. In the absence of prevalence and cost data, the public health burden of pulmonary NTM disease is difficult to assess. The goal of this study was to assess costs associated with NTM disease treatment and to identify risk factors associated with increased costs. Records from subjects with pulmonary NTM disease enrolled in a natural history protocol were abstracted for presenting symptoms, comorbidities, microbiology, and treatment histories. Antibiotic frequency, duration, adverse reaction, and costs were noted, the total antibiotic burden and cost were calculated, and risk factors associated with high costs were analyzed. From Jan 2004 to Dec 2005, 33 subjects were enrolled; 27 met disease criteria and had sufficient data to assess antibiotic use. Mycobacterium avium complex was present in 89% and Mycobacterium abscessus was present in 21% of subjects. Subjects received a median of 5 (1-10) antibiotics. Adverse effects were common seen in up to 50% with common antibiotics and up to 100% with uncommonly used antibiotics. Median burden of treatment was 2638 (84-7689) drug-days and the median total cost per patient was $19,876 ($398-70,917). Subjects with high treatment costs had an adjusted 9.5 fold (95% CI 1.5-97.2) likelihood of having M. abscessus and a 4.2 fold (95% CI 0.6-59.3) increased likelihood of having more extensive disease. Pulmonary NTM represent an underappreciated disease burden in the US population, with an associated treatment cost comparable to that for other chronic diseases of infectious origin such as HIV/AIDS. Published by Elsevier Ltd.
C1 [Prevots, D. Rebecca] NIAID, Epidemiol Unit, Lab Clin Infect Dis, NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Ballarino, Guillermo J.] George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA.
RP Prevots, DR (reprint author), NIAID, Epidemiol Unit, Lab Clin Infect Dis, NIH,US Dept HHS, Qrtrs 15B-1,8 W Dr,MSC 2665, Bethesda, MD 20892 USA.
EM rprevots@niaid.nih.gov
FU NIAID; NIH
FX This research was supported by the Intramural Research Program of the
NIAID, NIH.
NR 18
TC 25
Z9 28
U1 0
U2 1
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0954-6111
J9 RESP MED
JI Respir. Med.
PD OCT
PY 2009
VL 103
IS 10
BP 1448
EP 1455
DI 10.1016/j.rmed.2009.04.026
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System
SC Cardiovascular System & Cardiology; Respiratory System
GA 497IT
UT WOS:000270053200009
PM 19467851
ER
PT J
AU Shah, V
Pohida, T
Turkbey, B
Mani, H
Merino, M
Pinto, PA
Choyke, P
Bernardo, M
AF Shah, Vijay
Pohida, Thomas
Turkbey, Baris
Mani, Haresh
Merino, Maria
Pinto, Peter A.
Choyke, Peter
Bernardo, Marcelino
TI A method for correlating in vivo prostate magnetic resonance imaging and
histopathology using individualized magnetic resonance -based molds
SO REVIEW OF SCIENTIFIC INSTRUMENTS
LA English
DT Article
ID DIFFUSION-WEIGHTED MRI; CONTRAST-ENHANCED MRI; TISSUE-SHRINKAGE; CANCER;
LOCALIZATION; SPECIMENS; 3-T
AB A method for the design and rapid manufacture of a patient specific tissue slicing device based on in vivo images in order to facilitate the process of correlating the images with histopathology is presented. The method is applied to radical prostatectomy specimens where the customized mold is designed using magnetic resonance (MR) images of each patient obtained prior to surgery. In this case, the mold holds the prostate in place while a knife with a single blade or multiple blades is inserted in slots which are positioned to obtain tissue blocks corresponding to the slices in the MR images. The resulting histological specimens demonstrate good anatomical correlation with the MR images. (C) 2009 American Institute of Physics. [doi:10.1063/1.3242697]
C1 [Shah, Vijay; Bernardo, Marcelino] NCI, SAIC Frederick Inc, Frederick, MD 20892 USA.
[Shah, Vijay; Turkbey, Baris; Choyke, Peter; Bernardo, Marcelino] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
[Pohida, Thomas] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Mani, Haresh; Merino, Maria] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Pinto, Peter A.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Bernardo, M (reprint author), NCI, SAIC Frederick Inc, Frederick, MD 20892 USA.
EM bernardom@mail.nih.gov
RI Shah, Vijay/D-4083-2014
OI Shah, Vijay/0000-0003-3856-156X
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project was funded in part with federal funds from the National
Cancer Institute, National Institutes of Health, under Contract No.
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U. S. Government. This research
was supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 22
TC 35
Z9 35
U1 1
U2 1
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0034-6748
J9 REV SCI INSTRUM
JI Rev. Sci. Instrum.
PD OCT
PY 2009
VL 80
IS 10
AR 104301
DI 10.1063/1.3242697
PG 6
WC Instruments & Instrumentation; Physics, Applied
SC Instruments & Instrumentation; Physics
GA 513YE
UT WOS:000271359300030
PM 19895076
ER
PT J
AU Calvo, F
AF Calvo, Fabien
TI 10(th) anniversary of the French-language Thoracic Oncology Intergroup
Meetings Paris, the 18(th) and 19(th) of June 2009 Introduction
SO REVUE DE PNEUMOLOGIE CLINIQUE
LA French
DT Editorial Material
C1 Natl Canc Inst, Bethesda, MD 20892 USA.
RP Calvo, F (reprint author), Natl Canc Inst, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER
PI BRIDGEWATER
PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA
SN 0761-8417
J9 REV PNEUMOL CLIN
JI Rev. Pneumol. Clin.
PD OCT
PY 2009
VL 65
BP S2
EP S2
PG 1
WC Respiratory System
SC Respiratory System
GA 527OS
UT WOS:000272377000002
ER
PT J
AU Patterson, GH
AF Patterson, George H.
TI Fluorescence microscopy below the diffraction limit
SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
LA English
DT Review
DE STED; SPIM; DLSM; SIM; PALM; STORM; Photoactivation; Photoswitching
ID STRUCTURED-ILLUMINATION MICROSCOPY; PHOTOACTIVATED LOCALIZATION
MICROSCOPY; OPTICAL RECONSTRUCTION MICROSCOPY; FIELD LIGHT-MICROSCOPY;
PLASMA-MEMBRANE; SUPERRESOLUTION MICROSCOPY; 3-DIMENSIONAL RESOLUTION;
STIMULATED-EMISSION; ELECTRON-MICROSCOPY; AXIAL RESOLUTION
AB Fluorescence imaging with conventional microscopy has experienced numerous advances in almost every limiting factor from sensitivity to speed. But improved resolution beyond the fundamental limitation of light diffraction has been elusive until recent years. Now, techniques are available that surpass this barrier and improve resolution up to 10 times over that of conventional microscopy. This chapter provides an overview of these new "super-resolution" imaging methods. Published by Elsevier Ltd.
C1 Natl Inst Biomed Imaging & Bioengn, Biophoton Sect, NIH, Bethesda, MD USA.
RP Patterson, GH (reprint author), Natl Inst Biomed Imaging & Bioengn, Biophoton Sect, NIH, Bethesda, MD USA.
EM pattersg@mail.nih.gov
FU Intramural NIH HHS [Z99 EB999999]
NR 69
TC 19
Z9 19
U1 4
U2 37
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1084-9521
J9 SEMIN CELL DEV BIOL
JI Semin. Cell Dev. Biol.
PD OCT
PY 2009
VL 20
IS 8
BP 886
EP 893
DI 10.1016/j.semcdb.2009.08.006
PG 8
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 552OA
UT WOS:000274300800002
PM 19698798
ER
PT J
AU Lynch, JK
AF Lynch, John Kylan
TI Epidemiology and classification of perinatal stroke
SO SEMINARS IN FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Epidemiology; Ischemic stroke; Outcome; Perinatal stroke; Risk factors
ID ARTERIAL ISCHEMIC-STROKE; NEONATAL CEREBRAL INFARCTION; FACTOR-V-LEIDEN;
SINOVENOUS THROMBOSIS; CARDIAC-SURGERY; PRETERM INFANT; RISK-FACTORS;
SCHOOL-AGE; FOLLOW-UP; CHILDREN
AB Stroke is an important cause of mortality and chronic morbidity in infants and children. Case definitions for perinatal stroke have varied among studies by clinical and laboratory criteria. A recent US National Institutes of Health workshop on perinatal stroke provided consensus recommendations on the definition and classification of perinatal stroke. The incidence of perinatal stroke has been estimated at 1 in 1600 to 5000 births. The clinical presentation of perinatal stroke depends on the time of diagnosis, acute or delayed, but most will present with seizures. Risk factors for perinatal stroke have not been well studied. Several maternal and neonatal disorders have been reported in infants with perinatal stroke. Children who suffer perinatal stroke typically develop long-term disabilities including motor deficits, cognitive and behavioral disorders, and epilepsy. More than half will develop long-term motor or cognitive problems and the recurrence rate after perinatal stroke is very low. (c) 2009 Published by Elsevier Ltd.
C1 Natl Inst Neurol Disorders & Stroke, Div Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA.
RP Lynch, JK (reprint author), Natl Inst Neurol Disorders & Stroke, Div Stroke Diagnost & Therapeut, 10 Ctr Dr,MSC 1447, Bethesda, MD 20892 USA.
EM lynchj@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke at the National
Institutes of Health
FX Dr. Lynch is supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke at the National
Institutes of Health.
NR 48
TC 43
Z9 48
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1744-165X
J9 SEMIN FETAL NEONAT M
JI Semin. Fetal Neonatal Med.
PD OCT
PY 2009
VL 14
IS 5
BP 245
EP 249
DI 10.1016/j.siny.2009.07.001
PG 5
WC Pediatrics
SC Pediatrics
GA 504UF
UT WOS:000270642500002
PM 19664976
ER
PT J
AU Zebrack, B
Hamilton, R
Smith, AW
AF Zebrack, Brad
Hamilton, Rachel
Smith, Ashley Wilder
TI Psychosocial Outcomes and Service Use Among Young Adults With Cancer
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID QUALITY-OF-LIFE; LONG-TERM SURVIVORS; SUPPORT GROUP PARTICIPATION;
SOCIAL-WORK SERVICES; BREAST-CANCER; SELF-EFFICACY; TESTICULAR CANCER;
CHILDHOOD-CANCER; HEALTH-CARE; PSYCHOLOGICAL DISTRESS
C1 [Zebrack, Brad; Hamilton, Rachel] Univ Michigan, Sch Social Work, Ann Arbor, MI 48109 USA.
[Smith, Ashley Wilder] NCI, Outcomes Res Branch, Bethesda, MD 20892 USA.
RP Zebrack, B (reprint author), 1080 S Univ, Ann Arbor, MI 48109 USA.
NR 143
TC 32
Z9 32
U1 4
U2 16
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD OCT
PY 2009
VL 36
IS 5
BP 468
EP 477
DI 10.1053/j.seminoncol.2009.07.003
PG 10
WC Oncology
SC Oncology
GA 510KF
UT WOS:000271086700010
PM 19835742
ER
PT J
AU Gaydos, C
Maldeis, NE
Hardick, A
Hardick, J
Quinn, TC
AF Gaydos, Charlotte
Maldeis, Nancy E.
Hardick, Andrew
Hardick, Justin
Quinn, Thomas C.
TI Mycoplasma genitalium as a Contributor to the Multiple Etiologies of
Cervicitis in Women Attending Sexually Transmitted Disease Clinics
SO SEXUALLY TRANSMITTED DISEASES
LA English
DT Article
ID REAL-TIME PCR; PELVIC-INFLAMMATORY-DISEASE; TRANSCRIPTION-MEDIATED
AMPLIFICATION; CHLAMYDIA-TRACHOMATIS INFECTION; ROCHE LIGHTCYCLER
INSTRUMENT; POLYMERASE-CHAIN-REACTION; VAGINAL SWAB SAMPLES;
TRICHOMONAS-VAGINALIS; MUCOPURULENT CERVICITIS; NEISSERIA-GONORRHOEAE
AB Objectives: The purpose of this study was to investigate the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium, in women attending a sexually transmitted disease (STD) clinic, as well as the frequency of coinfections, and relationship of each organism to cervicitis.
Methods: In this cross-sectional study of 324 women attending Baltimore City STD Clinics, C. trachomatis, N. gonorrhoeae, T vaginalis, and M. genitalium were detected using nucleic acid amplification tests. Demographic characteristics and risk factors were ascertained.
Results: Overall prevalence of infection with C. trachomatis, N. gonorrhoeae, T. vaginalis, and M. genitalium was found to be 11.1%, 4.6%, 15.3%, and 19.2%, respectively. Prevalence in women with cervicitis was 15.8%, 6%, 18.9%, and 28.6% for C. trachomatis, N. gonorrhoeae, T. vaginalis, and M. genitalium, respectively. Percentages of coinfections were high. C. trachomatis and M. genitalium were significantly associated with cervicitis in univariate analysis, but only M. genitalium was significantly associated with cervicitis (AOR: 2.5) in multiple logistic regression models.
Conclusion: Knowledge of the statistical association of M. genitalium with cervicitis in this study increases the need for further confirmation of the etiologic significance of this organism with cervicitis in more diverse populations. The high prevalence merits more study and may have implications for diagnosis and treatment of cervicitis.
C1 [Gaydos, Charlotte; Hardick, Andrew; Hardick, Justin; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA.
[Maldeis, Nancy E.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Quinn, Thomas C.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Gaydos, C (reprint author), 530 Rangos Bldg,855 N Wolfe St, Baltimore, MD 21205 USA.
EM cgaydos@jhmi.edu
RI Gaydos, Charlotte/E-9937-2010
FU The HIV Prevention Trials Network (HPTN); NIAID; National Institutes of
Child Health and Human Development (NICH/HD); National Institute on Drug
Abuse; National Institute of Mental Health; Office of AIDS Research;
NIH; DHHS [U01-AI-068613]; Division of Intramural Research; National
Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD
FX The tests per-formed for Transcription Mediated Amplifications Tests
were conducted using APTIMA reagents provided by GenProbe, Inc, San
Diego, CA, and supported in part by The HIV Prevention Trials Network
(HPTN) sponsored by the NIAID, National Institutes of Child Health and
Human Development (NICH/HD), National Institute on Drug Abuse, National
Institute of Mental Health, and Office of AIDS Research, of the NIH,
DHHS (U01-AI-068613), and by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, NIH, Bethesda,
MD.
NR 45
TC 49
Z9 53
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-5717
J9 SEX TRANSM DIS
JI Sex. Transm. Dis.
PD OCT
PY 2009
VL 36
IS 10
BP 598
EP 606
DI 10.1097/OLQ.0b013e3181b01948
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA 500GN
UT WOS:000270286900001
PM 19704398
ER
PT J
AU Gaydos, C
Maldeis, NE
Hardick, A
Hardick, J
Quinn, TC
AF Gaydos, C.
Maldeis, N. E.
Hardick, A.
Hardick, J.
Quinn, T. C.
TI Mycoplasma genitalium compared to chlamydia, gonorrhoea and trichomonas
as an aetiological agent of urethritis in men attending STD clinics
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Article
ID REAL-TIME PCR; SEXUALLY-TRANSMITTED-DISEASES; NONGONOCOCCAL URETHRITIS;
ASYMPTOMATIC MEN; URINE; AMPLIFICATION; TRANSMISSION; ASSOCIATION;
PERFORMANCE; PREVALENCE
AB Objectives: To investigate prevalence of Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis in men, frequency of co-infections, and association of organisms with urethritis in men.
Methods: This was a cross-sectional study of 290 men (age range 19-34 years) attending Baltimore City STD clinics. M genitalium, C trachomatis, N gonorrhoeae and T vaginalis, during 2004 were detected using nucleic acid amplification tests (NAATs) (153 with urethritis and 137 without urethritis). Demographic characteristics and risk factors were ascertained.
Results: The overall prevalences of infection with C trachomatis, N gonorrhoeae, T vaginalis and M genitalium were 20.3%, 12.8%, 3.4% and 15.2%, respectively. Prevalences in men with urethritis were 32.7%, 24.2%, 5.2% and 22.2% for C trachomatis, N gonorrhoeae, T vaginalis and M genitalium, respectively. Percentages of co- infections were high. All men with N gonorrhoeae had urethritis. C trachomatis and M genitalium were found to be significantly associated with urethritis in univariate analysis and in multiple logistic regression analysis.
Conclusion: The association of M genitalium with urethritis in this study provides confirmation of the importance of screening men for M genitalium as a cause of non-gonococcal urethritis and supports treatment considerations for urethritis for agents other than gonococci and chlamydia.
C1 [Gaydos, C.; Hardick, A.; Hardick, J.; Quinn, T. C.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA.
[Maldeis, N. E.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Quinn, T. C.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Gaydos, C (reprint author), 530 Rangos Bldg,855 N Wolfe St, Baltimore, MD 21205 USA.
EM cgaydos@jhmi.edu
RI Gaydos, Charlotte/E-9937-2010
FU GenProbe, InC; NIAID; National Institutes of Child Health and Human
Development (NICH/HD); National Institute on Drug Abuse; National
Institute of Mental Health; Office of AIDS Research, of the NIH, DHHS
[U01-AI-068613]; Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, NIH, Bethesda, MD
FX This work was conducted using Aptima reagents provided by GenProbe, InC
and supported in part by the HIV Prevention Trials Network (HPTN)
sponsored by the NIAID, National Institutes of Child Health and Human
Development (NICH/HD), National Institute on Drug Abuse, National
Institute of Mental Health, and Office of AIDS Research, of the NIH,
DHHS (U01-AI-068613), and by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, NIH, Bethesda,
MD.
NR 15
TC 29
Z9 34
U1 0
U2 2
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD OCT
PY 2009
VL 85
IS 6
BP 438
EP 440
DI 10.1136/sti.2008.035477
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA 505VA
UT WOS:000270725200009
PM 19383597
ER
PT J
AU Yuan, M
Yang, YN
Zheng, G
AF Yuan, Min
Yang, Yaning
Zheng, Gang
TI TWO-STAGE GENOME-WIDE ASSOCIATION STUDIES WITH DNA POOLING AND GENETIC
MODEL SELECTION
SO STATISTICA SINICA
LA English
DT Article
DE Cost-effective design; DNA pooling; genetic model selection; joint
analysis; robustness; trend tests; two-stage
ID HARDY-WEINBERG EQUILIBRIUM; LARGE-SCALE ASSOCIATION; SAMPLE-SIZE;
DISEASE ASSOCIATION; TREND TESTS; DESIGNS; DISEQUILIBRIUM; EFFICIENT;
SCANS; POWER
AB The two-stage design is a common cost-effective approach for genome-wide association studies. The first stage serves as a screening to identify a subset of single-nucleotide polymorphisms (SNPs) from 100,000 to 500,000 SNPs using a fraction of case-control samples. In the second stage, only the selected SNPs are genotyped using the remaining case-control samples. On the other hand, DNA pooling is another common strategy to save genotyping cost. In this article, we propose a method using DNA pooling in the first stage and genotype-based analysis in the second stage. A joint analysis to combine both stages is applied to a two-stage design with DNA pooling when the underlying genetic model is known. When the genetic model is unknown, we use a robust procedure in the joint analysis by applying genetic model selection in the second stage based on the difference of Hardy-Weinberg disequilibrium coefficients between cases and controls. Performance of our method and comparison with other approaches are investigated by simulation studies.
C1 [Yuan, Min; Yang, Yaning] Univ Sci & Technol China, Dept Stat & Finance, Hefei, Anhui, Peoples R China.
[Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
RP Yuan, M (reprint author), Univ Sci & Technol China, Dept Stat & Finance, Hefei, Anhui, Peoples R China.
EM myuan@mail.ustc.edu.cn; ynyang@ustc.edu.cn; zhengg@nhlbi.nih.gov
FU Chinese Council of Scholarship; China NSF; Chinese Academy of Science
FX The work of Yuan was completed while she was visiting Department of
Statistics, Columbia University, partially supported by the Chinese
Council of Scholarship. She also thanks Dr. Zhiliang Ying for his
encouragement and support during her visit. The work of Yuan and Yang
was also partially supported by a China NSF Grant and a grant from the
Chinese Academy of Science. We would like to thank two reviewers for
their insightful suggestions and comments which have greatly improved
our presentation.
NR 32
TC 0
Z9 1
U1 0
U2 3
PU STATISTICA SINICA
PI TAIPEI
PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115,
TAIWAN
SN 1017-0405
EI 1996-8507
J9 STAT SINICA
JI Stat. Sin.
PD OCT
PY 2009
VL 19
IS 4
BP 1769
EP 1786
PG 18
WC Statistics & Probability
SC Mathematics
GA 521ZT
UT WOS:000271966500027
ER
PT J
AU Nasonkin, I
Mahairaki, V
Xu, LY
Hatfield, G
Cummings, BJ
Eberhart, C
Ryugo, DK
Maric, D
Bar, E
Koliatsos, VE
AF Nasonkin, Igor
Mahairaki, Vasiliki
Xu, Leyan
Hatfield, Glen
Cummings, Brian J.
Eberhart, Charles
Ryugo, David K.
Maric, Dragan
Bar, Eli
Koliatsos, Vassilis E.
TI Long-Term, Stable Differentiation of Human Embryonic Stem Cell-Derived
Neural Precursors Grafted into the Adult Mammalian Neostriatum
SO STEM CELLS
LA English
DT Article
DE Cellular therapy; Embryonic stem cells; Neural differentiation; Neural
induction; Neural stem cells; Pluripotent stem cells; Stem cell
plasticity; Stem cell transplantation
ID CENTRAL-NERVOUS-SYSTEM; LATERAL GANGLIONIC EMINENCE; IN-VITRO
DIFFERENTIATION; DOUBLECORTIN-LIKE-KINASE; SPINAL-CORD; RAT-BRAIN;
STRIATAL PROGENITORS; DOPAMINERGIC-NEURONS; ADHERENT CULTURE; PRONEURAL
BHLH
AB Stem cell grafts have been advocated as experimental treatments for neurological diseases by virtue of their ability to offer trophic support for injured neurons and, theoretically, to replace dead neurons. Human embryonic stem cells (HESCs) are a rich source of neural precursors (NPs) for grafting, but have been questioned for their tendency to form tumors. Here we studied the ability of HESC-derived NP grafts optimized for cell number and differentiation stage prior to transplantation, to survive and stably differentiate and integrate in the basal forebrain (neostriatum) of young adult nude rats over long periods of time (6 months). NPs were derived from adherent monolayer cultures of HESCs exposed to noggin. After transplantation, NPs showed a drastic reduction in mitotic activity and an avid differentiation into neurons that projected via major white matter tracts to a variety of forebrain targets. A third of NP-derived neurons expressed the basal forebrain-neostriatal marker dopamine-regulated and cyclic AMP-regulated phosphoprotein. Graft-derived neurons formed mature synapses with host postsynaptic structures, including dendrite shafts and spines. NPs inoculated in white matter tracts showed a tendency toward glial (primarily astrocytic) differentiation, whereas NPs inoculated in the ventricular epithelium persisted as nestin(+) precursors. Our findings demonstrate the long-term ability of noggin-derived human NPs to structurally integrate tumor-free into the mature mammalian forebrain, while maintaining some cell fate plasticity that is strongly influenced by particular central nervous system (CNS) niches. STEM CELLS 2009;27:2414-2426
C1 [Nasonkin, Igor; Mahairaki, Vasiliki; Xu, Leyan; Hatfield, Glen; Bar, Eli; Koliatsos, Vassilis E.] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA.
[Koliatsos, Vassilis E.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Koliatsos, Vassilis E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Cummings, Brian J.] Univ Calif Irvine, Reeve Irvine Res Ctr, Irvine, CA USA.
[Eberhart, Charles] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Eberhart, Charles] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Ryugo, David K.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol, Baltimore, MD 21205 USA.
Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Maric, Dragan] Natl Inst Neurol Disorders & Stroke, Flow Cytometry Core Facil, NIH, Bethesda, MD USA.
RP Nasonkin, I (reprint author), NEI, NIH, Neurobiol Neurodegenerat & Repair Lab, 9000 Rockville Pike,Bldg 6,Rm 341, Bethesda, MD 20892 USA.
EM nasonkini@mail.nih.gov; koliat@jhmi.edu
RI Cummings, Brian/C-9180-2012; Ryugo, David/G-1940-2012
OI Cummings, Brian/0000-0003-3628-5290; Ryugo, David/0000-0002-5250-7503
FU National Institutes of Health [NS45140-03, NIDCD DC000232, NIDCD P30
DC005211, EY01765]; Robert Packard Center; Muscular Dystrophy
Association
FX We thank Alex Kecojevic, Annie Welsh, Tan Pongstaporn, and Christa Baker
for their technical help and StemCells Inc. and Dr. Christopher Walsh
for their generous gifts of the SC121 and DCAMKL1 antibodies,
respectively. This work was supported by the National Institutes of
Health grants NS45140-03, NIDCD DC000232, NIDCD P30 DC005211, and
EY01765, the Robert Packard Center for ALS Research at Johns Hopkins,
and the Muscular Dystrophy Association.
NR 58
TC 32
Z9 32
U1 0
U2 8
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 OCT
PY 2009
VL 27
IS 10
BP 2414
EP 2426
DI 10.1002/stem.177
PG 13
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 520GP
UT WOS:000271830200005
PM 19609935
ER
PT J
AU Wendell, CR
Zonderman, AB
Metter, EJ
Najjar, SS
Waldstein, SR
AF Wendell, Carrington Rice
Zonderman, Alan B.
Metter, E. Jeffrey
Najjar, Samer S.
Waldstein, Shari R.
TI Carotid Intimal Medial Thickness Predicts Cognitive Decline Among Adults
Without Clinical Vascular Disease
SO STROKE
LA English
DT Article
DE carotid intimal medial thickness; subclinical vascular disease;
atherosclerosis; cognitive function; neuropsychology
ID CARDIOVASCULAR RISK-FACTORS; CEREBROVASCULAR-DISEASE;
ALZHEIMERS-DISEASE; IMPAIRMENT; ATHEROSCLEROSIS; ASSOCIATIONS;
PERFORMANCE; DEMENTIA; LESIONS; HEALTH
AB Background and Purpose-Though clinical cardiovascular and cerebrovascular diseases are established risk factors for cognitive decline and dementia, less is known about the relations between vascular health and cognition among individuals without these diseases. Carotid intimal medial thickness (IMT), a measure of subclinical vascular disease, is associated with concurrent decrements in cognitive function, but relatively little research has examined longitudinal relations between carotid IMT and prospective cognitive decline.
Methods-We examined relations of carotid IMT to prospective trajectories of cognitive function among 538 (aged 20 to 93, 39% male, 66% white) participants in the Baltimore Longitudinal Study of Aging (BLSA) free of known cardiovascular, cerebrovascular, and neurological disease. Participants underwent initial carotid ultrasonography and repeat neuropsychological testing on up to 8 occasions over up to 11 years of follow-up. Mixed-effects regression analyses were adjusted for age, gender, race, education, mean arterial pressure, body mass index, total cholesterol, smoking, depressive symptoms, and cardiovascular medication use.
Results-Individuals with greater carotid IMT displayed accelerated decline in performance over time on multiple tests of verbal and nonverbal memory, as well as a test of semantic association fluency and executive function.
Conclusions-Carotid IMT predicts accelerated cognitive decline, particularly in the domain of memory, among community-dwelling individuals free of vascular and neurological disease. (Stroke. 2009;40:3180-3185.)
C1 [Wendell, Carrington Rice; Waldstein, Shari R.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21250 USA.
[Wendell, Carrington Rice; Zonderman, Alan B.; Metter, E. Jeffrey; Najjar, Samer S.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Waldstein, Shari R.] Univ Maryland, Sch Med, Div Gerontol, Dept Med, Baltimore, MD 21201 USA.
Baltimore VA Med Center, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA.
RP Wendell, CR (reprint author), Univ Maryland Baltimore Cty, Dept Psychol, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
EM rice3@umbc.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institutes of Health; National Institute on Aging.
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging.
NR 35
TC 72
Z9 72
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD OCT
PY 2009
VL 40
IS 10
BP 3180
EP 3185
DI 10.1161/STROKEAHA.109.557280
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 499NV
UT WOS:000270229800004
PM 19644063
ER
PT J
AU Mathur, A
Gorden, P
Libutti, SK
AF Mathur, Aarti
Gorden, Philip
Libutti, Steven K.
TI Insulinoma
SO SURGICAL CLINICS OF NORTH AMERICA
LA English
DT Article
DE Insulinoma; Pancreatic neuroendocrine tumor; Metastatic insulinoma;
Management; Surgery
ID ISOLATED HEPATIC PERFUSION; ENDOCRINE GASTROENTEROPANCREATIC TUMORS;
GASTROINTESTINAL NEUROENDOCRINE TUMORS; INTRAARTERIAL CALCIUM
STIMULATION; ISLET-CELL CARCINOMA; NEOPLASIA TYPE-I; LIVER METASTASES;
SURGICAL-MANAGEMENT; 25-YEAR EXPERIENCE; PHASE-I
AB Insulinoma is a rare neuroendocrine tumor with an incidence of 4 per 1 million persons per year, which may occur as a unifocal sporadic event in patients without an inherited syndrome or as a part of multiple endocrine neoplasia type 1. Key neuroglycopenic and hypoglycemic symptoms in conjunction with biochemical proof establish the diagnosis. Once the diagnosis is established, the insulinoma is preoperatively localized within the pancreas with the goal of surgical excision for cure. This review discusses the historical background, diagnosis, and management of sporadic insulinoma.
C1 [Libutti, Steven K.] Montefiore Einstein Ctr Canc Care, Bronx, NY 10467 USA.
[Mathur, Aarti] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Gorden, Philip] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
[Libutti, Steven K.] Albert Einstein Canc Ctr, Bronx, NY 10467 USA.
[Libutti, Steven K.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Surg, Bronx, NY 10467 USA.
RP Libutti, SK (reprint author), Montefiore Einstein Ctr Canc Care, 3400 Bainbridge Ave, Bronx, NY 10467 USA.
EM slibutti@montefiore.org
FU Intramural NIH HHS [Z99 DK999999]
NR 68
TC 27
Z9 29
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0039-6109
EI 1558-3171
J9 SURG CLIN N AM
JI Surg. Clin.-North Am.
PD OCT
PY 2009
VL 89
IS 5
BP 1105
EP +
DI 10.1016/j.suc.2009.06.009
PG 18
WC Surgery
SC Surgery
GA 519QN
UT WOS:000271782300006
PM 19836487
ER
PT J
AU Siegenthaler, MP
Beyersdorf, F
AF Siegenthaler, Michael P.
Beyersdorf, Friedhelm
TI Endovascular Repair of Thoracoabdominal Aortic Aneurysms
SO TEXAS HEART INSTITUTE JOURNAL
LA English
DT Article
DE Aortic aneurysm, abdominal/surgery; aortic aneurysm, thoracic/surgery;
blood vessel prosthesis implantation/methods; mortality/trends;
paraplegia/etiology; stents; surgical procedures, minimally
invasive/methods; tomography, X-ray computed; treatment outcome
ID MORTALITY
AB Results of conventional open surgery for thoracoabdominal aortic aneurysm (TAAA) have shown 10% to 20% mortality rates in real-life series, such as R state registries,(1) but a few specialized centers report better data.(2) The role of endovascular repair in patients with TAAAs is uncertain. In endovascular TAAA cases, in which complete covering of the visceral and renal aortic segment is necessary, a branched or a fenestrated endograft(3)-or a hybrid open surgical revascularization followed by stent-graft repair-is required.(4) Branched grafts are available only for elective cases, because the Current grafts have to be custom-made.
This presentation focuses on our experience between 2000 and 2008 with endovascular treatment of TAAA, with selective open Surgical visceral and renal bypasses performed only if necessary, followed by immediate endovascular stent-graft therapy of the aneurysm.(5) Our surgical technique IS illustrated, and the pitfalls associated with this method discussed.
C1 [Siegenthaler, Michael P.; Beyersdorf, Friedhelm] Univ Freiburg, Dept Cardiovasc Surg, D-79106 Freiburg, Germany.
RP Siegenthaler, MP (reprint author), Suburban Hosp, NIH Heart Ctr, 8600 Old Georgetown Rd, Bethesda, MD 20814 USA.
EM siegenthalermp@nhlbi.nih.gov
NR 6
TC 1
Z9 1
U1 1
U2 1
PU TEXAS HEART INST
PI HOUSTON
PA PO BOX 20345, HOUSTON, TX 77225-0345 USA
SN 0730-2347
J9 TEX HEART I J
JI Tex. Heart Inst. J.
PD OCT
PY 2009
VL 36
IS 5
BP 446
EP 448
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 505JD
UT WOS:000270688600018
PM 19876425
ER
PT J
AU McCrae, RR
AF McCrae, Robert R.
TI The Physics and Chemistry of Personality
SO THEORY & PSYCHOLOGY
LA English
DT Article
DE Five-Factor Model; philosophy of science; processes; social-cognitive
approaches; traits
ID 5-FACTOR MODEL; INDIVIDUAL-DIFFERENCES; TRAIT; PSYCHOLOGY; SELF; AGE;
CONSISTENCY; MOTIVATION; UNIVERSAL; CRITERIA
AB Physics and chemistry, two basic natural sciences, are today seamlessly integrated, but for much of their history they were separate enterprises with distinct methods and goals. Physicists have consistently sought simplicity and mathematical rigor, whereas chemists seem to have been fascinated by the challenges of complexity. Parallels between these two sciences and the two major branches of contemporary personality psychology are described in an attempt to put in perspective the daunting enterprise of constructing a unified science of human nature.
C1 [McCrae, Robert R.] NIA, NIH, DHHS, Bethesda, MD 20892 USA.
RP McCrae, RR (reprint author), 809 Evesham Ave, Baltimore, MD 21212 USA.
EM RRMcCrae@gmail.com
NR 67
TC 10
Z9 10
U1 3
U2 5
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0959-3543
J9 THEOR PSYCHOL
JI Theory Psychol.
PD OCT
PY 2009
VL 19
IS 5
BP 670
EP 687
DI 10.1177/0959354309341928
PG 18
WC Psychology, Multidisciplinary
SC Psychology
GA 507BQ
UT WOS:000270825400005
ER
PT J
AU Karschner, EL
Schwope, DM
Schwilke, EW
Gorelick, DA
Goodwin, RS
Lowe, RH
Kelly, DL
Huestis, MA
AF Karschner, Erin L.
Schwope, David M.
Schwilke, Eugene W.
Gorelick, David A.
Goodwin, Robert S.
Lowe, Ross H.
Kelly, Deanna L.
Huestis, Marilyn A.
TI Whole Blood/Plasma Ratios in Ten Chronic Cannabis Users after Frequent
Oral THC Administration
SO THERAPEUTIC DRUG MONITORING
LA English
DT Meeting Abstract
CT 11th International Congress of Therapeutic Drug Monitoring and Clinical
Toxicology
CY OCT 03-08, 2009
CL Montreal, CANADA
C1 [Gorelick, David A.] Natl Inst Drug Abuse, Off Sci Director, Intramural Res Program, NIH, Baltimore, MD USA.
[Kelly, Deanna L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0163-4356
J9 THER DRUG MONIT
JI Ther. Drug Monit.
PD OCT
PY 2009
VL 31
IS 5
MA 8
BP 606
EP 606
PG 1
WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
GA 502UB
UT WOS:000270484600021
ER
PT J
AU Concheiro, M
Jones, HE
Johnson, RE
Shakleya, DM
Huestis, MA
AF Concheiro, Marta
Jones, Hendree E.
Johnson, Rolley E.
Shakleya, Diaa M.
Huestis, Marilyn A.
TI Placenta for Monitoring in utero Drug Exposure to Buprenorphine and
Correlation with Neonatal Outcomes
SO THERAPEUTIC DRUG MONITORING
LA English
DT Meeting Abstract
CT 11th International Congress of Therapeutic Drug Monitoring and Clinical
Toxicology
CY OCT 03-08, 2009
CL Montreal, CANADA
C1 [Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA.
[Jones, Hendree E.; Johnson, Rolley E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 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 0163-4356
J9 THER DRUG MONIT
JI Ther. Drug Monit.
PD OCT
PY 2009
VL 31
IS 5
MA 11
BP 607
EP 607
PG 1
WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
GA 502UB
UT WOS:000270484600024
ER
PT J
AU Schwope, DM
Schwilke, EW
Karschner, EL
Gorelick, DA
Goodwin, RS
Lowe, RH
Kelly, DL
Huestis, MA
AF Schwope, David M.
Schwilke, Eugene W.
Karschner, Erin L.
Gorelick, David A.
Goodwin, Robert S.
Lowe, Ross H.
Kelly, Deanna L.
Huestis, Marilyn A.
TI Whole Blood Total Cannabinoids during Multiple Daily Oral THC Dosing
SO THERAPEUTIC DRUG MONITORING
LA English
DT Meeting Abstract
CT 11th International Congress of Therapeutic Drug Monitoring and Clinical
Toxicology
CY OCT 03-08, 2009
CL Montreal, CANADA
C1 [Gorelick, David A.] Natl Inst Drug Abuse, Off Sci Director, IRP, NIH, Baltimore, MD USA.
[Kelly, Deanna L.] Univ Maryland, Maryland Psychiat Res Ctr, Catonsville, MD 21228 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 0163-4356
J9 THER DRUG MONIT
JI Ther. Drug Monit.
PD OCT
PY 2009
VL 31
IS 5
MA 40
BP 615
EP 615
PG 1
WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology
GA 502UB
UT WOS:000270484600053
ER
PT J
AU Ross, DS
Litofsky, D
Ain, KB
Bigos, T
Brierley, JD
Cooper, DS
Haugen, BR
Jonklaas, J
Ladenson, PW
Magner, J
Robbins, J
Skarulis, MC
Steward, DL
Maxon, HR
Sherman, SI
AF Ross, Douglas S.
Litofsky, Danielle
Ain, Kenneth B.
Bigos, Thomas
Brierley, James D.
Cooper, David S.
Haugen, Bryan R.
Jonklaas, Jacqueline
Ladenson, Paul W.
Magner, James
Robbins, Jacob
Skarulis, Monica C.
Steward, David L.
Maxon, Harry R.
Sherman, Steven I.
TI Recurrence After Treatment of Micropapillary Thyroid Cancer
SO THYROID
LA English
DT Article
ID LYMPH-NODE METASTASIS; PAPILLARY; CARCINOMA; MICROCARCINOMA; DISEASE;
EXPERIENCE; MANAGEMENT; INSTITUTE
AB Background: Despite very low mortality associated with micropapillary thyroid cancer, locoregional recurrence is common and controversy exists regarding optimal surgical treatment and the role of adjunctive radioiodine.
Methods: The National Thyroid Cancer Treatment Cooperative Study Group Registry was analyzed for recurrences in patients with unifocal versus multifocalmicropapillary cancer, with or without nodal disease, depending upon the extent of surgery and the use of adjunctive radioiodine. Six hundred eleven patients considered disease-free after initial therapy were followed for 2572 person-years.
Results: Thirty patients (6.2%) had recurrences detected at a mean 2.8 years after primary treatment. Recurrences did not differ between patients with unifocal and multifocal disease overall; however, among patients who received less than a near-total thyroidectomy (NTT), those with multifocal disease had more recurrences than those with unifocal disease (18% vs. 4%, p = 0.01). Patients with multifocal disease who had a total (T) or NTT trended toward fewer recurrences than those undergoing less than an NTT (6% vs. 18%, p = 0.058). In patients who did not receive radioiodine therapy, recurrence was more common in patients with multifocal disease versus unifocal disease (7% vs. 2%, p - 0.02). However, radioiodine did not reduce recurrences in patients with multifocal disease or patients with positive nodes. Patients with positive nodes had more recurrences than node-negative patients regardless of surgical extent or use of radioiodine.
Conclusions: Patients with micropapillary multifocal disease have a reduced risk of recurrence after a T/NTT compared with less surgery. A randomized, controlled trial is necessary and feasible to determine if radioiodine ablation of thyroid remnants is advantageous in patients with intrathyroidal micropapillary cancer.
C1 [Ross, Douglas S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Litofsky, Danielle; Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Ain, Kenneth B.] Univ Kentucky, Med Ctr, VA Med Ctr, Lexington, KY USA.
[Bigos, Thomas] Maine Med Ctr, Portland, ME 04102 USA.
[Brierley, James D.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Cooper, David S.; Ladenson, Paul W.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Haugen, Bryan R.] Univ Colorado Denver, Aurora, CO USA.
[Haugen, Bryan R.] Hlth Sci Ctr, Aurora, CO USA.
[Jonklaas, Jacqueline] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Magner, James] Genzyme Corp, Cambridge, MA USA.
[Robbins, Jacob; Skarulis, Monica C.] NIH, Bethesda, MD 20892 USA.
[Steward, David L.; Maxon, Harry R.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA.
RP Ross, DS (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM dross@partners.org
RI Jonklaas, Jacqueline/G-2807-2010;
OI Jonklaas, Jacqueline/0000-0002-2238-2666; Ain,
Kenneth/0000-0002-2668-934X; Sherman, Steven/0000-0002-3079-5153
NR 21
TC 82
Z9 88
U1 0
U2 3
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD OCT
PY 2009
VL 19
IS 10
BP 1043
EP U3
DI 10.1089/thy.2008.0407
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 512VR
UT WOS:000271279900004
PM 19772419
ER
PT J
AU Djouad, F
Rackwitz, L
Song, YJ
Janjanin, S
Tuan, RS
AF Djouad, Farida
Rackwitz, Lars
Song, Yingjie
Janjanin, Sasa
Tuan, Rocky S.
TI ERK1/2 Activation Induced by Inflammatory Cytokines Compromises
Effective Host Tissue Integration of Engineered Cartilage
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID NF-KAPPA-B; MESENCHYMAL STEM-CELLS; NECROSIS-FACTOR-ALPHA;
GROWTH-FACTOR-BETA; ARTICULAR-CARTILAGE; TNF-ALPHA; GENE-EXPRESSION;
MESSENGER-RNA; MATRIX; CHONDROCYTES
AB Objective: Proinflammatory cytokines are known to provoke degradative signaling cascades that promote extracellular matrix disintegration in articular cartilage. Because integration of the repair tissue into the surrounding native cartilage to produce a mechanically stable interface has a profound impact on the viability and functionality of the restored joint surface, this study examined the effects of proinflammatory cytokines on the properties of tissue-engineered cartilage in the context of integration. Methods: Using an established in vitro cartilage defect model, we examined the integration of chondrocyte-laden agarose constructs into native articular cartilage and the biochemical and biomechanical alterations of these implants upon treatment with interleukin 1-beta (IL1-beta) and tumor necrosis factor-alpha (TNF-alpha). Additionally, we probed extracellular regulated kinase (ERK) signaling involvement in response to proinflammatory cytokines. Results: The time-dependent accumulation of extracellular matrix and concomitant increase in Young's modulus observed in the absence of cytokines was significantly decreased upon IL1-beta and TNF-alpha treatment. Push-out test showed the highest interface strength in hybrid cultures maintained without cytokines, which was significantly lowered with IL1-beta and TNF-alpha treatment. Histological characteristics of the interface region are consistent with the biochemical findings. Treatment with an inhibitor of ERK pathway antagonized the deleterious effects caused by both cytokines. Conclusion: This study is the first to show the functional catastrophic effects of IL1-beta and TNF-alpha on the biochemical, structural, and integrative properties of tissue-engineered cartilage and their significant counteraction by the blockade of ERK signaling pathway. With the discovery of new potential chemical entities, ERK inhibitor may emerge as a new therapeutic approach for functional integration and mechanical integrity of an engineered cartilage to the host tissue and, therefore, enhance long-term viability and functionality of the restored joint surface.
C1 [Djouad, Farida; Rackwitz, Lars; Song, Yingjie; Janjanin, Sasa; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, 50 South Dr,Room 1140,MSC 8022, Bethesda, MD 20892 USA.
EM tuanr@mail.nih.gov
OI Djouad, Farida/0000-0001-8248-6822
FU Intramural NIH HHS
NR 32
TC 14
Z9 14
U1 1
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD OCT
PY 2009
VL 15
IS 10
BP 2825
EP 2835
DI 10.1089/ten.tea.2008.0663
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 503QG
UT WOS:000270553200007
PM 19243242
ER
PT J
AU Hallett, M
Benecke, R
Blitzer, A
Comella, CL
AF Hallett, Mark
Benecke, Reiner
Blitzer, Andrew
Comella, Cynthia L.
TI Treatment of focal dystonias with botulinum neurotoxin
SO TOXICON
LA English
DT Article; Proceedings Paper
CT 6th International Conference on Basic and Therapeutic Aspects of
Botulinum and Tetanus Toxins
CY JUN 12-15, 2008
CL Baveno, ITALY
DE Botulinum toxin; Focal dystonia; Cranial dystonia; Cervical dystonia;
Spasmodic dysphonia; Focal hand dystonia
ID TRANSCRANIAL MAGNETIC STIMULATION; ADDUCTOR SPASMODIC DYSPHONIA;
LARYNGEAL NERVE-SECTION; 1-YEAR FOLLOW-UP; WRITERS CRAMP; HAND DYSTONIA;
CERVICAL DYSTONIA; DOUBLE-BLIND; SPASTIC DYSPHONIA; TOXIN MANAGEMENT
AB This is a review on the use of injections of botulinum toxin for the treatment of focal dystonias. Disorders covered include cranial dystonia, cervical dystonia, spasmodic dysphonia, and focal hand dystonia. Considered are clinical aspects, alternative treatment strategies and principles of use of botulinum toxin injections. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Benecke, Reiner] Univ Rostock, Dept Neurol, Rostock, Germany.
[Blitzer, Andrew] Columbia Univ Coll Phys & Surg, Dept Otolaryngol, Ctr Voice & Swallowing Disorders, New York, NY 10032 USA.
[Comella, Cynthia L.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 7D37,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
FU Intramural NIH HHS [ZIA NS003032-05]
NR 31
TC 26
Z9 27
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0041-0101
J9 TOXICON
JI Toxicon
PD OCT
PY 2009
VL 54
IS 5
BP 628
EP 633
DI 10.1016/j.toxicon.2008.12.008
PG 6
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 496IW
UT WOS:000269965400013
PM 19103214
ER
PT J
AU Seltsam, A
Grueger, D
Blasczyk, R
Flegel, WA
AF Seltsam, Axel
Grueger, Daniela
Blasczyk, Rainer
Flegel, Willy A.
TI Easy identification of antibodies to high-prevalence Scianna antigens
and detection of admixed alloantibodies using soluble recombinant
Scianna protein
SO TRANSFUSION
LA English
DT Article
ID BLOOD-GROUP ANTIGEN; PARTICLE GEL IMMUNOASSAY; RAPID DETECTION; GROUP
SYSTEM; HUMAN ERMAP; SUBSTANCE; SEMA7A; DUFFY
AB BACKGROUND:
Identification of antibodies against high-prevalence Scianna (Sc; ERMAP) antigens, like Sc1 and Sc5, is difficult and may incur delays in blood procurement and costs. The detection of additional clinically significant alloantibodies is hampered in the presence of anti-Scianna. Soluble recombinant Scianna protein is demonstrated to facilitate antibody diagnostics in both cases.
STUDY DESIGN AND METHODS:
Soluble recombinant Scianna protein (Sc:1,-2,3,-4,5,6,7) was produced comprising the antigenic extracellular domain fused to a V5-His tag. The protein was isolated from eukaryotic cell culture supernatants of stably transfected HEK293 cells. Seven serum samples with anti-Sc1, anti-Sc2, and anti-Sc5 and 30 serum samples with antibodies to other blood group antigens were evaluated in hemagglutination inhibition assays. Antisera with mixed antibody specificities and autoantibodies were also tested.
RESULTS:
Soluble Scianna protein inhibited specifically antibodies to the high-prevalence Scianna antigens Sc1 and Sc5. No antibodies were neutralized that were directed to the low-prevalence Sc2 antigen or to a large representative set of antigens from other blood group systems. Clinically relevant antibodies could be identified despite being masked by anti-Sc1 and anti-Sc5. A mixture of Scianna and JMH proteins allowed detecting a common antibody despite the presence of antibodies to high-prevalence antigens of the Scianna or JMH blood group systems.
CONCLUSION:
Antibody detection systems comprising soluble recombinant Scianna protein provide an easy single-step method for detection and identification of antibodies to high-prevalence Scianna antigens. Reagents with Scianna and other recombinant blood group proteins and mixtures of such proteins would be useful routine reagents in immunohematology.
C1 Inst Springe, German Red Cross Blood Donor Serv NSTOB, Springe, Germany.
Hannover Med Sch, Inst Transfus Med, D-3000 Hannover, Germany.
Inst Ulm, German Red Cross Blood Donor Serv Baden Wurttembe, Ulm, Germany.
Univ Hosp Ulm, Inst Transfus Med, Ulm, Germany.
RP Flegel, WA (reprint author), Natl Inst Hlth, Lab Serv Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
EM flegelwa@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 26
TC 2
Z9 4
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD OCT
PY 2009
VL 49
IS 10
BP 2090
EP 2096
DI 10.1111/j.1537-2995.2009.02255.x
PG 7
WC Hematology
SC Hematology
GA 502BW
UT WOS:000270430100015
PM 19555420
ER
PT J
AU Klein, HG
AF Klein, Harvey G.
TI In Memoriam-Robert M. Winslow (1941-2009) OBITUARY
SO TRANSFUSION
LA English
DT Biographical-Item
C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Klein, HG (reprint author), NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
EM hklein@dtm.cc.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD OCT
PY 2009
VL 49
IS 10
BP 2243
EP 2244
PG 2
WC Hematology
SC Hematology
GA 502BW
UT WOS:000270430100036
ER
PT J
AU Tounkara, A
Diakite, M
Noumsi, GT
Sarro, YDS
Siddiqui, S
Parta, M
AF Tounkara, A.
Diakite, M.
Noumsi, G. T.
Sarro, Y. D. S.
Siddiqui, S.
Parta, M.
TI Retrospective surveillance of HIV prevalence in blood donors can help in
the selection of the best social group for blood donation in Mali
SO TRANSFUSION MEDICINE
LA English
DT Article
DE blood donors; HIV; Mali; West Africa
ID ESTIMATING HIV/AIDS; RISK; INFECTION; TRANSFUSION; AFRICA
AB The National Centre for Blood Transfusion, Bamako, Mali has collected data that characterizes trend in HIV prevalence over 10 years by gender, age, occupation, marital status and donor category. These data help to describe national HIV prevalence and assist in formulating blood donation policies. Donations from 1993 to 2002 were categorized by donor age (decade), occupation (student, military and other), marital status (single, married and other), gender and donor status (volunteer, occasional and family). Comparisons were made using conservative estimates of donation frequency/donor category. Donations increased by more than 400%. By 1999, increased HIV prevalence in donations from women was consistently present. Donations from the age group of 30-39 years showed an increased prevalence beginning in 2000, which by 2002 was almost 10 times greater than in the low-prevalence (< 20 years) group (5.9 vs. 0.6%). By 2000, both categories - students and military were less likely to be HIV positive than those from other occupational categories, and donations from married persons were less likely to be HIV positive by 1997. The highest prevalence was observed in the 'occasional' donor category, which increased to > 14% by 2001; volunteer donation HIV positive peaked at 2.3% in 1999. HIV prevalence in blood donations in Bamako, Mali, demonstrates important trends from 1993 to 2002. The prevalence of > 14% in donations from occasional donors and significant trends by decade, gender, marital status and occupation argue for increased analysis of the blood donor population to improve blood safety and to understand the demographics of HIV infection in Mali.
C1 [Tounkara, A.; Sarro, Y. D. S.; Siddiqui, S.] Univ Bamako, FMPOS NIAID HIV TB Res Initiat, Bamako, Mali.
[Tounkara, A.; Sarro, Y. D. S.; Siddiqui, S.; Parta, M.] Ctr Natl Transfus Sanguine, Bamako, Mali.
[Diakite, M.] Mali NIH Int Ctr Excellence Res MRTC ICER, Fac Med Pharm & Odontostomatol, Bamako, Mali.
[Noumsi, G. T.; Parta, M.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Tounkara, A (reprint author), Univ Bamako, FMPOS NIAID HIV TB Res Initiat, BP 1805, Bamako, Mali.
EM anatol@mrtcbko.org
FU National Blood Bank of Mali; Government of Mali
FX We thank the blood donor groups, colleagues at the National Blood Bank
of Mali for their support and participation and the Government of Mali
for financial support. We thank two anonymous reviewers for a critical
review and helpful suggestions.
NR 16
TC 3
Z9 3
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0958-7578
J9 TRANSFUSION MED
JI Transfus. Med.
PD OCT
PY 2009
VL 19
IS 5
BP 252
EP 259
DI 10.1111/j.1365-3148.2009.00950.x
PG 8
WC Hematology
SC Hematology
GA 491OU
UT WOS:000269589400005
PM 19747288
ER
PT J
AU Berger, VW
AF Berger, Vance W.
TI The (lack of) quality in assessing the quality of transplantation trials
SO TRANSPLANT INTERNATIONAL
LA English
DT Letter
C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA.
EM vb78c@nih.gov
NR 5
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0934-0874
EI 1432-2277
J9 TRANSPL INT
JI Transpl. Int.
PD OCT
PY 2009
VL 22
IS 10
BP 1029
EP 1029
DI 10.1111/j.1432-2277.2009.00899.x
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 490YG
UT WOS:000269543400014
PM 19497066
ER
PT J
AU Helming, L
Gordon, S
AF Helming, Laura
Gordon, Siamon
TI Molecular mediators of macrophage fusion
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
ID GIANT-CELL FORMATION; TETRASPANINS CD9; APOPTOTIC CELLS; DC-STAMP;
IN-VIVO; ALTERNATIVE ACTIVATION; CUTTING EDGE; OSTEOCLAST; CD81;
PHAGOCYTOSIS
AB Fusion of macrophages leads to the formation of osteoclasts in bone and of multinucleated giant cells in granulomas. The precise function of granuloma-associated multinucleates giant cells is not clear but substantial progress has recently been made in identifying the molecular machinery involved in macrophage fusion. Signaling processes mediated by DAP12 and STAT6 induce a fusion-competent status. Chemotaxis through CCL2, cell-cell adhesion mediated by E-cadherin, exposure of phosphatidylserine, lipid recognition by CD36 and cytoskeletal rearrangements depending on RAC1 are prerequisites for successful macrophage fusion. We review current knowledge on the molecular mediators of giant cell formation, compare giant cells with osteoclasts and highlight key target areas for future research and medical relevance.
C1 [Helming, Laura] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, Munich, Germany.
[Gordon, Siamon] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
[Gordon, Siamon] NCI, NIH, Frederick, MD 21701 USA.
RP Helming, L (reprint author), Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, Munich, Germany.
EM laura.helming@lrz.tum.de
FU Medical Research Council [G0600727]
NR 54
TC 119
Z9 121
U1 0
U2 18
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD OCT
PY 2009
VL 19
IS 10
BP 514
EP 522
DI 10.1016/j.tcb.2009.07.005
PG 9
WC Cell Biology
SC Cell Biology
GA 511EU
UT WOS:000271147500004
PM 19733078
ER
PT J
AU Cizza, G
Primma, S
Csako, G
AF Cizza, Giovanni
Primma, Svetlana
Csako, Gyorgy
TI Depression as a risk factor for osteoporosis
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
ID BONE-MINERAL DENSITY; SEROTONIN REUPTAKE INHIBITORS; BODY-MASS INDEX;
PREMENOPAUSAL WOMEN; MAJOR DEPRESSION; POSTMENOPAUSAL WOMEN; HIP
FRACTURE; OLDER WOMEN; ANOREXIA-NERVOSA; MENTAL DISTRESS
AB Osteoporosis is a major public health threat. Multiple studies have reported an association between depression and low bone mineral density, but a causal link between these two conditions is disputed. Here we review the endocrine and immune alterations secondary to depression that might affect bone mass. We also discuss the possible role of poor lifestyle in the etiology of osteoporosis in subjects with depression and the potential effect of antidepressants on bone loss. We propose that depression induces bone loss and osteoporotic fractures, primarily via specific immune and endocrine mechanisms, while poor lifestyle habits and use of specific antidepressants are potential contributory factors.
C1 [Cizza, Giovanni; Primma, Svetlana] NIDDK, Clin Endocrine Sect, Clin Endocrinol Branch, NIH,DHHS, Bethesda, MD 20892 USA.
[Csako, Gyorgy] NIH, Dept Lab Med, Ctr Clin, DHHS, Bethesda, MD 20892 USA.
RP Cizza, G (reprint author), NIDDK, Clin Endocrine Sect, Clin Endocrinol Branch, NIH,DHHS, Bethesda, MD 20892 USA.
EM cizzag@intra.niddk.nih.gov
FU National Institute of Diabetes, Digestive and Kidney Diseases; Clinical
Center, NIH
FX This research was supported by the Intramural Research Programs of the
National Institute of Diabetes, Digestive and Kidney Diseases and the
Clinical Center, NIH.
NR 60
TC 45
Z9 50
U1 0
U2 8
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1043-2760
J9 TRENDS ENDOCRIN MET
JI Trends Endocrinol. Metab.
PD OCT
PY 2009
VL 20
IS 8
BP 367
EP 373
DI 10.1016/j.tem.2009.05.003
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 506GX
UT WOS:000270764200001
PM 19747841
ER
PT J
AU Krsmanovic, LZ
Hu, L
Leung, PK
Feng, H
Catt, KJ
AF Krsmanovic, Lazar Z.
Hu, Lian
Leung, Po-Ki
Feng, Hao
Catt, Kevin J.
TI The hypothalamic GnRH pulse generator: multiple regulatory mechanisms
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
ID GONADOTROPIN-RELEASING-HORMONE; ESTROGEN-RECEPTOR-ALPHA; HUMAN
CHORIONIC-GONADOTROPIN; MESSENGER RIBONUCLEIC-ACIDS;
PROTEIN-COUPLED-RECEPTOR; RAT ANTERIOR-PITUITARY; GENE-EXPRESSION;
RHESUS-MONKEY; IN-VITRO; NEUROPEPTIDE RELEASE
AB Pulsatile secretion of gonadotropin-releasing hormone (GnRH) release is an intrinsic property of hypothalamic GnRH neurons. Pulse generation has been attributed to multiple specific mechanisms, including spontaneous electrical activity of GnRH neurons, calcium and cAMP signaling, a GnRH receptor autocrine regulatory component, a GnRH concentration-dependent switch in GnRH receptor (GnRH-R) coupling to specific G proteins, the expression of G protein-coupled receptors (GPCRs) and steroid receptors, and homologous and heterologous interactions between cell membrane receptors expressed in GnRH neurons. The coexistence of multiple regulatory mechanisms for pulsatile GnRH secretion provides a high degree of redundancy in maintaining this crucial component of the mammalian reproductive process. These studies provide insights into the basic cellular and molecular mechanisms involved in GnRH neuronal function.
C1 [Krsmanovic, Lazar Z.; Hu, Lian; Leung, Po-Ki; Feng, Hao; Catt, Kevin J.] NICHHD, Sect Hormonal Regulat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Catt, KJ (reprint author), NICHHD, Sect Hormonal Regulat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
EM kcatt@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 67
TC 27
Z9 28
U1 0
U2 8
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1043-2760
J9 TRENDS ENDOCRIN MET
JI Trends Endocrinol. Metab.
PD OCT
PY 2009
VL 20
IS 8
BP 402
EP 408
DI 10.1016/j.tem.2009.05.002
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 506GX
UT WOS:000270764200006
PM 19740674
ER
PT J
AU Wise, RA
AF Wise, Roy A.
TI Roles for nigrostriatal-not just mesocorticolimbic-dopamine in reward
and addiction
SO TRENDS IN NEUROSCIENCES
LA English
DT Review
ID VENTRAL TEGMENTAL AREA; LONG-TERM POTENTIATION; BRAIN-STIMULATION
REWARD; NUCLEUS-ACCUMBENS DOPAMINE; SYNAPTIC PLASTICITY;
COCAINE-SEEKING; SELF-STIMULATION; SUBSTANTIA-NIGRA; CAUDATE-NUCLEUS;
DORSAL STRIATUM
AB Forebrain dopamine circuitry has traditionally been studied by two largely independent specialist groups: students of Parkinson's disease who study the nigrostriatal dopamine system that originates in the substantial nigra (SN) and students of motivation and addiction who study the role of the mesolimbic and mesocortical dopamine systems that originate in the ventral tegmental area (VTA). The anatomical evidence for independent nigrostriatal and mesolimbic dopamine systems has, however, long been obsolete. There is now compelling evidence that both nominal "systems" participate in reward function and addiction. Electrical stimulation of both SN and VTA is rewarding, blockade of glutamatergic or cholinergic input to either SN or VTA attenuates the habit-forming effects of intravenous cocaine, and dopamine in both nigrostriatal and mesocorticolimbic terminal fields participates in the defining property of rewarding events: the reinforcement of memory consolidation. Thus, the similarities between nigrostriatal and mesolimbic dopamine systems can be as important as their differences.
C1 Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD USA.
RP Wise, RA (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD USA.
EM rwise@intra.nida.nih.gov
RI Wise, Roy/A-6465-2012
FU Intramural Research Program; National Institute on Drug Abuse; National
Institutes of Health; Department of Health and Human Services
FX Supported by funding from the Intramural Research Program, National
Institute on Drug Abuse, National Institutes of Health, Department of
Health and Human Services. I thank Yavin Shabam, Stefanie Geisler and
Maria Flavia Barbano for constructive comments on an earlier draft of
the paper.
NR 94
TC 182
Z9 188
U1 3
U2 32
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0166-2236
J9 TRENDS NEUROSCI
JI Trends Neurosci.
PD OCT
PY 2009
VL 32
IS 10
BP 517
EP 524
DI 10.1016/j.tins.2009.06.004
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 509GQ
UT WOS:000271003400001
PM 19758714
ER
PT J
AU Hall, MD
Handley, MD
Gottesman, MM
AF Hall, Matthew D.
Handley, Misty D.
Gottesman, Michael M.
TI Is resistance useless? Multidrug resistance and collateral sensitivity
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID HAMSTER OVARY CELLS; BREAST-CANCER-CELLS; MAGNETIC-RESONANCE
SPECTROSCOPY; MDR1 GENE-EXPRESSION; K562 LEUKEMIC-CELLS; P-GLYCOPROTEIN;
CROSS-RESISTANCE; DRUG-RESISTANCE; TUMOR-CELLS; IRON CHELATORS
AB When cancer cells develop resistance to chemotherapeutics, it is frequently conferred by the ATP-dependent efflux pump P-glycoprotein (MDR1, P-gp, ABCB1). P-gp can efflux a wide range of cancer drugs; its expression confers cross-resistance, termed "multidrug resistance" (MDR), to a wide range of drugs. Strategies to overcome this resistance have been actively sought for more than 30 years, yet clinical solutions do not exist. A less understood aspect of MDR is the hypersensitivity of resistant cancer cells to other drugs, a phenomenon known as "collateral sensitivity" (CS). This review highlights the extent of this effect for the first time, and discusses hypotheses (e.g. generation of reactive oxygen species) to account for the underlying generality of this phenomenon, and proposes exploitation of CS as a strategy to improve response to chemotherapy.
C1 [Hall, Matthew D.; Handley, Misty D.; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM gottesmm@mail.nih.gov
RI Hall, Matthew/B-2132-2010
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute. The authors
would like to acknowledge Dr. Gergely Szakaes, who began the work on CS
in our laboratory, and Dr. Elias Georges, who has worked extensively on
verapamil CS and first reported the ROS hypothesis for CS. We thank
members of the Laboratory of Cell Biology for helpful discussions, and
George Leiman and Kyle R. Brimacombe for editorial assistance. The
authors also acknowledge the contributions from the referees, whose
critical comments enhanced this review.
NR 127
TC 115
Z9 121
U1 1
U2 15
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD OCT
PY 2009
VL 30
IS 10
BP 546
EP 556
DI 10.1016/j.tips.2009.07.003
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 509XZ
UT WOS:000271053900005
PM 19762091
ER
PT J
AU Kimani, JW
Yoshiura, K
Shi, M
Jugessur, A
Moretti-Ferreira, D
Christensen, K
Murray, JC
AF Kimani, Jane W.
Yoshiura, Koh-ichiro
Shi, Min
Jugessur, Astanand
Moretti-Ferreira, Danilo
Christensen, Kaare
Murray, Jeffrey C.
TI Search for Genomic Alterations in Monozygotic Twins Discordant for Cleft
Lip and/or Palate
SO TWIN RESEARCH AND HUMAN GENETICS
LA English
DT Article
DE monozygotic twins; discordant; cleft lip and palate; genome-wide
ID FEMALE; HYBRIDIZATION; CONCORDANT; FREQUENCY; MUTATION; GENES
AB Phenotypically discordant monozygotic twins offer the possibility of gene discovery through delineation of molecular abnormalities in one member of the twin pair. One proposed mechanism of discordance is postzygotically occurring genomic alterations resulting from mitotic recombination and other somatic changes. Detection of altered genomic fragments can reveal candidate gene loci that can be verified through additional analyses. We investigated this hypothesis using array comparative genomic hybridization; the 50K and 250K Affymetrix GeneChip (R) SNP arrays and an Illumina custom array consisting of 1,536 SNPs, to scan for genomic alterations in a sample of monozygotic twin pairs with discordant cleft lip and/or palate phenotypes. Paired analysis for deletions, amplifications and loss of heterozygosity, along with sequence verification of SNPs with discordant genotype calls did not reveal any genomic discordance between twin pairs in lymphocyte DNA samples. Our results demonstrate that postzygotic genomic alterations are not a common cause of monozygotic twin discordance for isolated cleft lip and/or palate. However, rare or balanced genomic alterations, tissue-specific events and small aberrations beyond the detection level of our experimental approach cannot be ruled out. The stability of genomes we observed in our study samples also suggests that detection of discordant events in other monozygotic twin pairs would be remarkable and of potential disease significance.
C1 [Kimani, Jane W.; Murray, Jeffrey C.] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Yoshiura, Koh-ichiro] Nagasaki Univ, Grad Sch Biomed Sci, Dept Human Genet, Nagasaki 852, Japan.
[Shi, Min] NIEHS, Biostat Branch, Bethesda, MD USA.
[Jugessur, Astanand] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
[Moretti-Ferreira, Danilo] Genet Univ Estadual Paulista, Serv Aconselhamento, Botucatu, SP, Brazil.
[Christensen, Kaare] Univ So Denmark, Inst Publ Hlth, Dept Epidemiol, Odense, Denmark.
RP Murray, JC (reprint author), Univ Iowa, Dept Pediat, S Grand Ave,2182 ML, Iowa City, IA 52242 USA.
EM jeff-murray@uiowa.edu
RI Christensen, Kaare/C-2360-2009; Moretti-Ferreira, Danilo/F-9565-2012
OI Christensen, Kaare/0000-0002-5429-5292;
FU NIH; National Institute of Environmental Health Sciences
[Z01ES04007-12]; [R37DE008S59]; [P50DE016215]; [R01DE015197]
FX We would like to thank the patients and families who contributed samples
and information for this study. We are also grateful to Maria Johnson
for technical assistance. This study was supported by the following
grants: R37DE008S59, P50DE016215, R01DE015197, and by the Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences (Z01ES04007-12).
NR 29
TC 12
Z9 12
U1 0
U2 1
PU AUSTRALIAN ACAD PRESS
PI BOWEN HILLS
PA 32 JEAYS ST, BOWEN HILLS, QLD 4006, AUSTRALIA
SN 1832-4274
J9 TWIN RES HUM GENET
JI Twin Res. Hum. Genet.
PD OCT
PY 2009
VL 12
IS 5
BP 462
EP 468
PG 7
WC Genetics & Heredity; Obstetrics & Gynecology
SC Genetics & Heredity; Obstetrics & Gynecology
GA 507NW
UT WOS:000270862300007
PM 19803774
ER
PT J
AU Hancock, HA
Smith, LH
Cuesta, J
Durrani, AK
Angstadt, M
Palmeri, ML
Kimmel, E
Frenkel, V
AF Hancock, Hilary A.
Smith, Lauren H.
Cuesta, Julian
Durrani, Amir K.
Angstadt, Mary
Palmeri, Mark L.
Kimmel, Eitan
Frenkel, Victor
TI INVESTIGATIONS INTO PULSED HIGH-INTENSITY FOCUSED ULTRASOUND-ENHANCED
DELIVERY: PRELIMINARY EVIDENCE FOR A NOVEL MECHANISM
SO ULTRASOUND IN MEDICINE AND BIOLOGY
LA English
DT Article
DE Pulsed high-intensity focused ultrasound; Muscle; Extravasation;
Interstitial transport; Radiation force displacements; Shear strain
ID ACOUSTIC RADIATION FORCE; STRETCH-SHORTENING CYCLES; BRAIN-BARRIER
DISRUPTION; ECCENTRIC EXERCISE; IN-VITRO; MONOCLONAL-ANTIBODY;
SKELETAL-MUSCLE; DRUG-DELIVERY; SOLID TUMORS; FISH SKIN
AB Pulsed high-intensity focused ultrasound (HIFU) exposures without ultrasound contrast agents have been used for noninvasively enhancing the delivery of various agents to improve their therapeutic efficacy in a variety of tissue models in a nondestructive manner. Despite the versatility of these exposures, little is known about the mechanisms by which their effects are produced. In this study, pulsed-HIFU exposures were given in the calf muscle of mice, followed by the administration of a variety of fluorophores, both soluble and particulate, by local or systemic injection. In vivo imaging (whole animal and microscopic) was used to quantify observations of increased extravasation and interstitial transport of the fluorophores as a result of the exposures. Histological analysis indicated that the exposures caused some structural alterations such as enlarged gaps between muscle fiber bundles. These effects were consistent with increasing the permeability of the tissues; however, they were found to be transient and reversed themselves gradually within 72 h. Simulations of radiation force-induced displacements and the resulting local shear strain they produced were carried out to potentially explain the manner by which these effects occurred. A better understanding of the mechanisms involved with pulsed HIFU exposures for noninvasively enhancing delivery will facilitate the process for optimizing their use. (E-mail: vfrenkel@cc.nih.gov) Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology.
C1 [Hancock, Hilary A.; Smith, Lauren H.; Cuesta, Julian; Durrani, Amir K.; Angstadt, Mary; Frenkel, Victor] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Palmeri, Mark L.] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
[Kimmel, Eitan] Technion Israel Inst Technol, Dept Biomed Engn, IL-32000 Haifa, Israel.
RP Frenkel, V (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10,Room 1N306A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM vfrenkel@cc.nih.gov
RI Palmeri, Mark/B-7167-2015
OI Palmeri, Mark/0000-0001-8995-0050
FU NIH, National Institutes of Health [CA114075]
FX The authors would like to thank Dr. Stuart J. Warden and Dr. Matthew R.
Dreher for their thoughtful consultations and discussions. This research
was supported in part by NIH R01 grant number CA114075 and the
intramural research program of the Clinical Center, National Institutes
of Health.
NR 53
TC 68
Z9 71
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-5629
J9 ULTRASOUND MED BIOL
JI Ultrasound Med. Biol.
PD OCT
PY 2009
VL 35
IS 10
BP 1722
EP 1736
DI 10.1016/j.ultrasmedbio.2009.04.020
PG 15
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 600TN
UT WOS:000278011900016
PM 19616368
ER
PT J
AU Ramsey, SD
McDermott, CL
Zeliadt, SB
Blough, DK
Fedorenko, CR
Arora, NK
Penson, DF
Oakley-Girvan, I
Hamilton, AS
Van den Eeden, SK
Potosky, AL
AF Ramsey, S. D.
McDermott, C. L.
Zeliadt, S. B.
Blough, D. K.
Fedorenko, C. R.
Arora, N. K.
Penson, D. F.
Oakley-Girvan, I
Hamilton, A. S.
Van den Eeden, S. K.
Potosky, A. L.
TI COMPLEMENTARY AND ALTERNATIVE MEDICINE (CAM) USE AMONG LOCAL STAGE
PROSTATE CANCER PATIENTS: TYPES, FACTORS ASSOCIATED WITH USE AND
PERCEIVED BENEFITS
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Ramsey, S. D.; McDermott, C. L.; Fedorenko, C. R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Zeliadt, S. B.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Blough, D. K.] Univ Washington, Seattle, WA 98195 USA.
[Arora, N. K.] NCI, Bethesda, MD 20892 USA.
[Penson, D. F.] Univ So Calif, Norris Canc Ctr, Los Angeles, CA USA.
[Oakley-Girvan, I] No Calif Canc Ctr, Fremont, CA USA.
[Hamilton, A. S.] USC, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA USA.
[Van den Eeden, S. K.] Kaiser Permanente, Oakland, CA USA.
[Potosky, A. L.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1098-3015
J9 VALUE HEALTH
JI Value Health
PD OCT
PY 2009
VL 12
IS 7
BP A283
EP A283
DI 10.1016/S1098-3015(10)74386-2
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 495GH
UT WOS:000269878100311
ER
PT J
AU Reed, SD
Whellan, DJ
Li, Y
Friedman, JY
Pina, IL
Settles, SJ
Davidson-Ray, L
Johnson, J
Cooper, LS
O'Connor, CM
Schulman, KA
AF Reed, S. D.
Whellan, D. J.
Li, Y.
Friedman, J. Y.
Pina, I. L.
Settles, S. J.
Davidson-Ray, L.
Johnson, J.
Cooper, L. S.
O'Connor, C. M.
Schulman, K. A.
TI COST OF EXERCISE TRAINING AND ITS IMPACT ON MEDICAL RESOURCE USE AND
COSTS: RESULTS OF HF-ACTION TRIAL
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Reed, S. D.; Li, Y.; Friedman, J. Y.; Settles, S. J.; Johnson, J.; O'Connor, C. M.; Schulman, K. A.] Duke Clin Res Inst, Durham, NC USA.
[Whellan, D. J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Pina, I. L.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Davidson-Ray, L.] Duke Univ, Durham, NC USA.
[Cooper, L. S.] NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1098-3015
J9 VALUE HEALTH
JI Value Health
PD OCT
PY 2009
VL 12
IS 7
BP A323
EP A323
DI 10.1016/S1098-3015(10)74588-5
PG 1
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 495GH
UT WOS:000269878100513
ER
PT J
AU Xiao, S
Paldurai, A
Nayak, B
Subbiah, M
Collins, PL
Samal, SK
AF Xiao, Sa
Paldurai, Anandan
Nayak, Baibaswata
Subbiah, Madhuri
Collins, Peter L.
Samal, Siba K.
TI Complete genome sequence of avian paramyxovirus type 7 (strain
Tennessee) and comparison with other paramyxoviruses
SO VIRUS RESEARCH
LA English
DT Article
DE Avian paramyxovirus; Genome sequence; APMV-7; Strain Tennessee
ID NEWCASTLE-DISEASE-VIRUS; HEMAGGLUTININ-NEURAMINIDASE GLYCOPROTEIN;
COMPLETE NUCLEOTIDE-SEQUENCE; FUSION PROTEIN; RNA VIRUSES; UNTRANSLATED
REGIONS; MATRIX PROTEIN; AMINO-ACID; REPLICATION; CLEAVAGE
AB The complete genome sequence of avian paramyxovirus serotype 7 (APMV-7) prototype strain dove/Tennessee/4/75 was determined. The genome size is 15,480 nucleotides (nt) long and follows the "rule of six". The genome contains six non-overlapping genes in the order of 3'-N-P/V/W-M-F-HN-L-5'. The T-leader and 5'-trailer sequences of the genome are 55 and 127 nt long, respectively. The first 12 nt of the leader and trailer sequences are complementary to each other. The viral genes are flanked by highly conserved gene-start (GS) and gene-end (GE) transcription signals, and in addition the T-leader sequence contains a sequence ((35)AAUUAUUUUUU(45)) that is identical to the GE signal present at two of the genes. The genes are separated by intergenic sequences (IGS) ranging between 11 and 70 nt. The phosphoprotein (P) gene contains a conserved RNA editing site (3'-UUUUUCCC-5') presumed to be involved in the production of V and W proteins. The viral fusion (F) protein has a single basic amino acid at the putative cleavage site ((101)TLPSS (R) under bar down arrow F(107)); however, the virus did not require exogenous protease for in vitro replication. The virus grew in only a few established cell lines, indicating a restricted host range. Sequence alignment and phylogenetic analysis of the predicted amino acid sequence of APMV-7 proteins with the cognate proteins of the viruses of all five genera of the family Paramyxoviridue showed that APMV-7 is more closely related to APMV-2, -6, -8 than to APMV-1, -3, -4 and -9. The mean death time in embryonated chicken eggs was found to be more than 144 h, indicating APMV-7 to be avirulent for chickens. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.
C1 [Xiao, Sa; Paldurai, Anandan; Nayak, Baibaswata; Subbiah, Madhuri; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
RI Nayak, Baibaswata/L-6156-2016
FU MAID [NOIA060009]; NIH; U.S. Government
FX We thank Sachin Kumar for helpful suggestions in the present complete
genome sequencing experiment. We thank Dianel Rockemann, Flavia Dias and
all our laboratory members for their excellent technical assistance and
help. We also thank Ireen Dryburgh-Barry for proofreading the
manuscript. "This research was supported by MAID contract no. NOIA060009
(85% support) and MAID, NIH Intramural Research Program (15% support).
The views expressed herein do not necessarily reflect the official
policies of the Department of Health and Human Services; nor does
mention of trade names, commercial practices, or organizations imply
endorsement by the U.S. Government."
NR 53
TC 32
Z9 32
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD OCT
PY 2009
VL 145
IS 1
BP 80
EP 91
DI 10.1016/j.virusres.2009.06.003
PG 12
WC Virology
SC Virology
GA 503JY
UT WOS:000270531600011
PM 19540277
ER
PT J
AU Chattopadhyay, MK
Chen, WP
Poy, G
Cam, M
Stiles, D
Tabor, H
AF Chattopadhyay, Manas K.
Chen, Weiping
Poy, George
Cam, Margaret
Stiles, David
Tabor, Herbert
TI Microarray studies on the genes responsive to the addition of spermidine
or spermine to a Saccharomyces cerevisiae spermidine synthase mutant
SO YEAST
LA English
DT Article
DE microarray; polyamines; spermidine; spermine; yeast
ID AMINO-ACID-METABOLISM; TRANSCRIPTIONAL REGULATION; POLYAMINE MODULON;
NEUROSPORA-CRASSA; SPE2-DELTA MUTANT; CELL-GROWTH; YEAST-CELLS;
EXPRESSION; BIOSYNTHESIS; HYPUSINE
AB The naturally occurring polyamines putrescine, spermidine or spermine are ubiquitous in all cells. Although polyamines have prominent regulatory roles in cell division and growth, precise molecular and cellular functions are not well-established in vivo. In this work we have performed microarray experiments with a spermidine synthase, spermine oxidase mutant (Delta spe3 Delta fms1) strain to investigate the responsiveness of yeast genes to supplementation with spermidine or spermine. Expression analysis identified genes responsive to the addition of either excess spermidine (10(-5) (M)) or spermine (10-5 m) compared to a control culture containing 10(-8) (M) spermidine. 247 genes were upregulated > two-fold and 11 genes were upregulated > 10-fold after spermidine addition. Functional categorization of the genes showed induction of transport-related genes and genes involved in methionine, arginine, lysine, NAD and biotin biosynthesis. 268 genes were downregulated more than two-fold, and six genes were downregulated > eight-fold after spermidine addition. A majority of the downregulated genes are involved in nucleic acid metabolism and various stress responses. In contrast, only a few genes (18) were significantly responsive to spermine. Thus, results from global gene expression profiling demonstrate a more major role for spermidine in modulating gene expression in yeast than spermine. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Chattopadhyay, Manas K.; Tabor, Herbert] NIDDK, NIH, Lab Biochem & Genet, Bethesda, MD 20892 USA.
[Chen, Weiping; Poy, George; Cam, Margaret; Stiles, David] NIDDK, NIH, Microarray Core Facil, Bethesda, MD 20892 USA.
RP Chattopadhyay, MK (reprint author), NIDDK, NIH, Lab Biochem & Genet, 8 Ctr Dr,Bldg 8,Room 219, Bethesda, MD 20892 USA.
EM manasc@intra.niddk.nih.gov
FU NIH (National Institute of Diabetes, Digestive and Kidney Diseases).
FX This research was supported by the Intramural Research Programme of the
NIH (National Institute of Diabetes, Digestive and Kidney Diseases).
NR 39
TC 15
Z9 15
U1 1
U2 6
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0749-503X
J9 YEAST
JI Yeast
PD OCT
PY 2009
VL 26
IS 10
BP 531
EP 544
DI 10.1002/yea.1703
PG 14
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Microbiology; Mycology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Microbiology; Mycology
GA 507MY
UT WOS:000270859500001
PM 19688718
ER
PT J
AU Nagata, S
Pastan, I
AF Nagata, Satoshi
Pastan, Ira
TI Removal of B cell epitopes as a practical approach for reducing the
immunogenicity of foreign protein-based therapeutics
SO ADVANCED DRUG DELIVERY REVIEWS
LA English
DT Review
DE Deimmunization; Mutagenesis; Antigen; Antigenicity; Antibody;
Biopharmaceutical
ID RECOMBINANT STAPHYLOKINASE VARIANTS; BOTULINUM NEUROTOXIN-A;
IMMUNE-RESPONSES; HUMAN-ANTIBODY; T-CELL; ANTIGENIC DETERMINANTS;
MONOCLONAL-ANTIBODIES; CYTOCHROME-C; IMMUNOTOXIN; PREDICTION
AB Immunogenicity of non-human proteins with useful therapeutic properties has prevented their development for use in the therapy of disease. However, this class of proteins could be very useful, if their immunogenicity could be markedly reduced so that many treatment cycles could be administered. One approach to reduce the immunogenicity of foreign proteins is to identify B cell epitopes on the protein and eliminate them by mutagenesis. In this article, theoretical aspects and experimental evidence for the feasibility of B cell epitope removal is reviewed. A special focus is given to our results with deimmunization of recombinant immunotoxins in which Fvs are fused to a 38 kDa portion of the bacterial protein, Pseudomonas exotoxin A (PE38). Immunotoxins targeting CD22 and CD25 have produced complete remissions in many patients with drug resistant Hairy Cell Leukemia and are being evaluated in other malignancies. Experimental data summarized in this review indicates that removal of B cell epitopes is a practical approach for making less immunogenic protein therapeutics from non-human functional proteins. This approach requires grouping of the epitopes to identify targets for deimmunization followed by quantitative analysis of the decrease in affinity produced by the mutations in B cell epitopes. Published by Elsevier B.V.
C1 [Nagata, Satoshi] Sanford Res USD, Canc Biol Res Ctr, Sioux Falls, SD 57105 USA.
[Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Nagata, S (reprint author), Sanford Res USD, Canc Biol Res Ctr, 1400 W 22nd St, Sioux Falls, SD 57105 USA.
EM nagatas@sanfordhealth.org; pastani@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research.
NR 101
TC 34
Z9 36
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0169-409X
EI 1872-8294
J9 ADV DRUG DELIVER REV
JI Adv. Drug Deliv. Rev.
PD SEP 30
PY 2009
VL 61
IS 11
BP 977
EP 985
DI 10.1016/j.addr.2009.07.014
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 511BC
UT WOS:000271137600009
PM 19679153
ER
PT J
AU Lee, JY
Yang, ST
Kim, HJ
Lee, SK
Jung, HH
Shin, SY
Kim, JI
AF Lee, Ju Yeon
Yang, Sung-Tae
Kim, Hyo Jeong
Lee, Seung Kyu
Jung, Hyun Ho
Shin, Song Yub
Kim, Jae Il
TI Different modes of antibiotic action of homodimeric and monomeric
bactenecin, a cathelicidin-derived antibacterial peptide
SO BMB REPORTS
LA English
DT Article
DE Antibacterial activity; Homodimeric bactenecin; Model membrane;
Monomeric bactenecin; Oligomerization
ID ANTIMICROBIAL CATIONIC PEPTIDE; CELL-PENETRATING PEPTIDE; CYTOPLASMIC
MEMBRANE; BACTERICIDAL ACTION; BOVINE NEUTROPHILS; FLUORESCENCE;
PURIFICATION; LIPOSOMES; MECHANISM; RICH
AB The bactenecin is an antibacterial peptide with an intramolecular disulfide bond. We recently found that homodimeric bactenecin exhibits more potent antibacterial activity than the monomeric form and retains its activity at physiological conditions. Here we assess the difference in the modes of antibiotic action of homodimeric and monomeric bactenecins. Both monomeric and dimeric bactenecins almost completely killed both Staphylococcus aureus and E. coli within 10-30 min at concentrations of 8-16 mu M. However, exposure to liposomes elicited an increase in the fluorescence quantum yield from a tryptophan-containing monomeric analog, while the homodimeric analog showed a significant reduction in fluorescence intensity. Moreover, unlike the monomer, the homodimer displayed apparent membrane-lytic activity enabling release of various sized dyes from liposomes, and rapidly and fully depolarized the S. aureus membrane. Together, our results suggest that homodimeric bactenecin forms pores in the bacterial membrane, while monomeric one penetrates through the membrane to target intracellular molecules/organelles. [BMB reports 2009; 42(9): 586-592]
C1 [Lee, Ju Yeon; Yang, Sung-Tae; Kim, Hyo Jeong; Lee, Seung Kyu; Jung, Hyun Ho; Kim, Jae Il] Gwangju Inst Sci & Technol, Dept Life Sci, Res Ctr Bioimaging, Kwangju 500712, South Korea.
[Yang, Sung-Tae] NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Shin, Song Yub] Chosun Univ, Sch Med, Dept Cellular & Mol Med, Kwangju 501759, South Korea.
[Shin, Song Yub] Chosun Univ, Grad Sch, Dept Biomat, Kwangju 501759, South Korea.
[Kim, Jae Il] AnyGen Co Ltd, Kwangju 500712, South Korea.
RP Kim, JI (reprint author), Gwangju Inst Sci & Technol, Dept Life Sci, Res Ctr Bioimaging, Kwangju 500712, South Korea.
EM jikim@gist.ac.kr
NR 26
TC 10
Z9 11
U1 2
U2 6
PU KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
PI SEOUL
PA KOREA SCIENCE & TECHNOLOGY CENTER, # 801, 635-4 , YEOKSAM-DONG,
KANGNAM-KU, SEOUL, 135-703, SOUTH KOREA
SN 1976-6696
J9 BMB REP
JI BMB Rep.
PD SEP 30
PY 2009
VL 42
IS 9
BP 586
EP 592
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 505QH
UT WOS:000270708900007
PM 19788860
ER
PT J
AU Morris, JC
Waldmann, TA
AF Morris, John C.
Waldmann, Thomas A.
TI Antibody-based therapy of leukaemia
SO EXPERT REVIEWS IN MOLECULAR MEDICINE
LA English
DT Review
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ANTI-CD20
MONOCLONAL-ANTIBODY; NON-HODGKINS-LYMPHOMA; T-CELL LEUKEMIA; ACUTE
LYMPHOBLASTIC-LEUKEMIA; PHASE-II TRIAL; PREVIOUSLY UNTREATED PATIENTS;
DOSE-ESCALATION TRIAL; HUMAN CD52 ANTIBODY
AB Over the past decade, monoclonal antibodies have dramatically impacted the treatment of haematological malignancies, as evidenced by the effect of rituximab on the response rate and survival of patients with follicular and diffuse large B cell non-Hodgkin's lymphoma. Currently, only two monoclonal antibodies - the anti-CD33 immunotoxin gemtuzumab ozogamicin and the CD52-directed antibody alemtuzumab - are approved for treatment of relapsed acute myeloid leukaemia in older patients and B cell chronic lymphocytic leukaemia, respectively. Although not approved for such treatment, alemtuzumab is also active against T cell prolymphocytic leukaemia, cutaneous T cell lymphoma and Sezary syndrome, and adult T cell leukaemia and lymphoma. In addition, rituximab has demonstrated activity against B cell chronic lymphocytic and hairy cell leukaemia. Monoclonal antibodies targeting CD4, CD19, CD20, CD22, CD23, CD25, CD45, CD66 and CD122 are now being studied in the clinic for the treatment of leukaemia. Here, we discuss how these new antibodies have been engineered to reduce immunogenicity and improve antibody targeting and binding. Improved interactions with Fc receptors on immune effector cells can enhance destruction of target cells through antibody-dependent cellular cytotoxicity and complement-mediated cell lysis. The antibodies can also be armed with cellular toxins or radionuclides to enhance the destruction of leukaemia cells.
C1 [Morris, John C.] NCI, Metab Branch, Ctr Canc Res, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
RP Morris, JC (reprint author), NCI, Metab Branch, Ctr Canc Res, Mark O Hatfield Clin Res Ctr, Room 4-5330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jmorris@mail.nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute,
Center for Cancer Research
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. The authors wish
to thank the reviewers for their thoughtful and helpful comments on this
article.
NR 195
TC 19
Z9 20
U1 0
U2 9
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1462-3994
J9 EXPERT REV MOL MED
JI Expert Rev. Mol. Med.
PD SEP 30
PY 2009
VL 11
AR e29
DI 10.1017/S1462399409001215
PG 25
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 577UO
UT WOS:000276249700001
PM 19788782
ER
PT J
AU Matveev, V
Bertram, R
Sherman, A
AF Matveev, Victor
Bertram, Richard
Sherman, Arthur
TI Ca2+ Current versus Ca2+ Channel Cooperativity of Exocytosis
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID FAST CNS SYNAPSE; TRANSMITTER RELEASE; CALCIUM-CHANNEL; NEUROTRANSMITTER
RELEASE; NEUROMUSCULAR-JUNCTION; PRESYNAPTIC CALCIUM; MONTE-CARLO; RAT
CALYX; VESICLE; DEPENDENCE
AB Recently there has been significant interest and progress in the study of spatiotemporal dynamics of Ca2+ that triggers exocytosis at a fast chemical synapse, which requires understanding the contribution of individual calcium channels to the release of a single vesicle. Experimental protocols provide insight into this question by probing the sensitivity of exocytosis to Ca2+ influx. While varying extracellular or intracellular Ca2+ concentration assesses the intrinsic biochemical Ca2+ cooperativity of neurotransmitter release, varying the number of open Ca2+ channels using pharmacological channel block or the tail current titration probes the cooperativity between individual Ca2+ channels in triggering exocytosis. Despite the wide use of these Ca2+ sensitivity measurements, their interpretation often relies on heuristic arguments. Here we provide a detailed analysis of the Ca2+ sensitivity measures probed by these experimental protocols, present simple expressions for special cases, and demonstrate the distinction between the Ca2+ current cooperativity, defined by the relationship between exocytosis rate and the whole-terminal Ca2+ current magnitude, and the underlying Ca2+ channel cooperativity, defined as the average number of channels involved in the release of a single vesicle. We find simple algebraic expressions that show that the two are different but linearly related. Further, we use three-dimensional computational modeling of buffered Ca2+ diffusion to analyze these distinct Ca2+ cooperativity measures, and demonstrate the role of endogenous Ca2+ buffers on such measures. We show that buffers can either increase or decrease the Ca2+ current cooperativity of exocytosis, depending on their concentration and the single-channel Ca2+ current.
C1 [Matveev, Victor] New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA.
[Bertram, Richard] Florida State Univ, Dept Math, Tallahassee, FL 32306 USA.
[Bertram, Richard] Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA.
[Bertram, Richard] Florida State Univ, Program Mol Biophys, Tallahassee, FL 32306 USA.
[Sherman, Arthur] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Matveev, V (reprint author), New Jersey Inst Technol, Dept Math Sci, Newark, NJ 07102 USA.
EM matveev@njit.edu
FU National Science Foundation [DMS-0817703, DMS-0613179]; Intramural
Research Program of the National Institutes of Health-National Institute
of Diabetes and Digestive and Kidney Diseases
FX This work was supported by National Science Foundation Grants
DMS-0817703 (to V.M.) and DMS-0613179 (to R.B.) and by the Intramural
Research Program of the National Institutes of Health-National Institute
of Diabetes and Digestive and Kidney Diseases (A.S.).
NR 36
TC 15
Z9 16
U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 30
PY 2009
VL 29
IS 39
BP 12196
EP 12209
DI 10.1523/JNEUROSCI.0263-09.2009
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 501EV
UT WOS:000270363300019
PM 19793978
ER
PT J
AU Vullhorst, D
Neddens, J
Karavanova, I
Tricoire, L
Petralia, RS
McBain, CJ
Buonanno, A
AF Vullhorst, Detlef
Neddens, Joerg
Karavanova, Irina
Tricoire, Ludovic
Petralia, Ronald S.
McBain, Chris J.
Buonanno, Andres
TI Selective Expression of ErbB4 in Interneurons, But Not Pyramidal Cells,
of the Rodent Hippocampus
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; NEUREGULIN RECEPTOR ERBB4; LONG-TERM
POTENTIATION; TYROSINE KINASE; DEVELOPMENTAL PROFILE; NEURAL
DEVELOPMENT; CEREBRAL-CORTEX; ADULT-RAT; SYNAPSES; NEURONS
AB NRG1 and ERBB4 have emerged as some of the most reproducible schizophrenia risk genes. Moreover, the Neuregulin (NRG)/ErbB4 signaling pathway has been implicated in dendritic spine morphogenesis, glutamatergic synaptic plasticity, and neural network control. However, despite much attention this pathway and its effects on pyramidal cells have received recently, the presence of ErbB4 in these cells is still controversial. As knowledge of the precise locus of receptor expression is crucial to delineating the mechanisms by which NRG signaling elicits its diverse physiological effects, we have undertaken a thorough analysis of ErbB4 distribution in the CA1 area of the rodent hippocampus using newly generated rabbit monoclonal antibodies and ErbB4-mutant mice as negative controls. We detected ErbB4 immunoreactivity in GABAergic interneurons but not in pyramidal neurons, a finding that was further corroborated by the lack of ErbB4 mRNA in electrophysiologically identified pyramidal neurons as determined by single-cell reverse transcription-PCR. Contrary to some previous reports, we also did not detect processed ErbB4 fragments or nuclear ErbB4 immunoreactivity. Ultrastructural analysis in CA1 interneurons using immunoelectron microscopy revealed abundant ErbB4 expression in the somatodendritic compartment in which it accumulates at, and adjacent to, glutamatergic postsynaptic sites. In contrast, we found no evidence for presynaptic expression in cultured GAD67-positive hippocampal interneurons and in CA1 basket cell terminals. Our findings identify ErbB4-expressing interneurons, but not pyramidal neurons, as a primary target of NRG signaling in the hippocampus and, furthermore, implicate ErbB4 as a selective marker for glutamatergic synapses on inhibitory interneurons.
C1 [Buonanno, Andres] NIDCD, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Tricoire, Ludovic; McBain, Chris J.] NIDCD, Lab Cellular & Mol Neurophysiol, Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Petralia, Ronald S.] NIDCD, Neurochem Lab, Bethesda, MD 20892 USA.
RP Buonanno, A (reprint author), NIDCD, Mol Neurobiol Sect, NIH, Bldg 35,Room 2C-1000,35 Lincoln Dr, Bethesda, MD 20892 USA.
EM buonanno@mail.nih.gov
FU National Institute of Child Health and Human Development (NICHD);
National Institute on Deafness and Other Communication Disorders
intramural program
FX This work was supported by the National Institute of Child Health and
Human Development (NICHD) intramural program (D.V., J.N., I.K., L.T.,
C.J.M., A.B.) and the National Institute on Deafness and Other
Communication Disorders intramural program (R.S.P.). We thank Dr.
Ya-Xian Wang for help with immunoelectron microscopy, Dr. Z. Sheng for
the SNPH Delta MT-GFP construct, and V. Schram and C. Smith from the
NICHD and National Institute of Neurological Disorders and Stroke
microscopy core facilities for expert assistance.
NR 45
TC 98
Z9 99
U1 0
U2 3
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 30
PY 2009
VL 29
IS 39
BP 12255
EP 12264
DI 10.1523/JNEUROSCI.2454-09.2009
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 501EV
UT WOS:000270363300025
PM 19793984
ER
PT J
AU Coddou, C
Codocedo, JF
Li, S
Lillo, JG
Acuna-Castillo, C
Bull, P
Stojilkovic, SS
Huidobro-Toro, JP
AF Coddou, Claudio
Codocedo, Juan F.
Li, Shuo
Lillo, Juan G.
Acuna-Castillo, Claudio
Bull, Paulina
Stojilkovic, Stanko S.
Huidobro-Toro, J. Pablo
TI Reactive Oxygen Species Potentiate the P2X(2) Receptor Activity through
Intracellular Cys(430)
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID GROWING ESCHERICHIA-COLI; SMOOTH-MUSCLE CELLS; HYDROGEN-PEROXIDE;
HISTIDINE-RESIDUES; RESPIRATORY-CHAIN; RAT HEPATOCYTES; HEAVY-METALS;
MODULATION; CHANNELS; MERCURY
AB P2X receptor channels (P2XRs) are allosterically modulated by several compounds, mainly acting at the ectodomain of the receptor. Like copper, mercury, a metal that induces oxidative stress in cells, also stimulates the activity of P2X(2)R and inhibits the activity of P2X(4)R. However, the mercury modulation is not related to the extracellular residues critical for copper modulation. To identify the site(s) for mercury action, we generated two chimeras using the full size P2X(2) subunit, termed P2X(2a), and a splice variant lacking a 69 residue segment in the C terminal, termed P2X(2b), as the donors for intracellular and transmembrane segments and the P2X(4) subunit as the donor for ectodomain segment of chimeras. The potentiating effect of mercury on ATP-induced current was preserved in Xenopus oocytes expressing P2X(4/2a) chimera but was absent in oocytes expressing P2X(4/2b) chimera. Site-directed mutagenesis experiments revealed that the Cys(430) residue mediates effects of mercury on the P2X(2a)R activity. Because mercury could act as an oxidative stress inducer, we also tested whether hydrogen peroxide (H2O2) and mitochondrial stress inducers myxothiazol and rotenone mimicked mercury effects. These experiments, done in both oocytes and human embryonic kidney HEK293 cells, revealed that these compounds potentiated the ATP-evoked P2X(2a)R and P2X(4/2a)R currents but not P2X(2b)R and P2X(2a)-C430A and P2X(2a)-C430S mutant currents, whereas antioxidants dithiothreitrol and N-acetylcysteine prevented the H2O2 potentiation. Alkylation of Cys(430) residue with methylmethane-thiosulfonate also abolished the mercury and H2O2 potentiation. Altogether, these results are consistent with the hypothesis that the Cys(430) residue is an intracellular P2X(2a)R redox sensor.
C1 [Coddou, Claudio; Codocedo, Juan F.; Lillo, Juan G.; Bull, Paulina; Huidobro-Toro, J. Pablo] Pontificia Univ Catolica Chile, Dept Fisiol, Fac Ciencias Biol,Inst Milenio Biol Fundamental &, Ctr Regulac Celular & Patol Prof JV Luco, Santiago, Chile.
[Coddou, Claudio; Codocedo, Juan F.; Lillo, Juan G.; Bull, Paulina; Huidobro-Toro, J. Pablo] Pontificia Univ Catolica Chile, Dept Fisiol, Dept Mol Genet & Microbiol, Santiago, Chile.
[Coddou, Claudio; Li, Shuo; Stojilkovic, Stanko S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Acuna-Castillo, Claudio] Univ Santiago Chile, Fac Quim & Biol, Dept Biol, Santiago, Chile.
RP Huidobro-Toro, JP (reprint author), Pontificia Univ Catolica Chile, Dept Fisiol, Fac Ciencias Biol,Inst Milenio Biol Fundamental &, Ctr Regulac Celular & Patol Prof JV Luco, Alameda 340,Casilla 114-D,PC 6513677, Santiago, Chile.
EM jphuid@bio.puc.cl
OI Codocedo Henriquez, Juan Francisco/0000-0002-9683-2156
FU Fondo de Investigacion Avanzada en Areas Prioritarias [13980001];
National Institute of Child Health and Human Development/National
Institutes of Health
FX This research was funded by Fondo de Investigacion Avanzada en Areas
Prioritarias Grant 13980001 and by the Intramural Research Program of
the National Institute of Child Health and Human Development/National
Institutes of Health. The Millennium Institute for Fundamental and
Applied Biology and Programa de Financiamento Basal Grant 12/2007 also
contributed with funds.
NR 35
TC 17
Z9 17
U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 30
PY 2009
VL 29
IS 39
BP 12284
EP 12291
DI 10.1523/JNEUROSCI.2096-09.2009
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 501EV
UT WOS:000270363300028
PM 19793987
ER
PT J
AU Prokunina-Olsson, L
Kaplan, LM
Schadt, EE
Collins, FS
AF Prokunina-Olsson, Ludmila
Kaplan, Lee M.
Schadt, Eric E.
Collins, Francis S.
TI Alternative Splicing of TCF7L2 Gene in Omental and Subcutaneous Adipose
Tissue and Risk of Type 2 Diabetes
SO PLOS ONE
LA English
DT Article
AB Background: Single nucleotide polymorphisms (SNPs) rs7903146 and rs12255372 located within TCF7L2 gene have been identified as the strongest common genetic risk factors for development of type 2 diabetes (T2D). We hypothesized that these genetic variants might increase the risk of T2D through regulation of alternative splicing or expression level of TCF7L2 in human adipose tissue.
Methodology/Principal Findings: Expression of 13 assays detecting alternatively spliced forms of TCF7L2 was measured by quantitative reverse-transcriptase PCR (qRT-PCR) in paired biopsies of omental and subcutaneous adipose tissue from 159 obese individuals (BMI 54.6+/212.2 kg/m(2)). TCF7L2 expression in both types of adipose tissue was not associated with SNPs rs7903146 and rs12255372, T2D status and blood levels of glucose or glycosylated hemoglobin (HbA1c). Expression of assays "ex12-13", "ex12-14" and "ex13-13a" detecting C-terminal alternative exons of TCF7L2 was higher in subcutaneous compared to omental adipose tissue by 1.46 fold (p=6.5x10(-15)), 1.41 fold (p=1.4x10(-9)) and 1.26 fold (p=4.7x10(-6)) in the control group and by 1.86 fold (p=1.7x10(-4)), 1.77 fold (p=7.3x10(-4)) and 1.58 fold (p=6.1x10(-4)) in the T2D group. A pathway enrichment analysis on transcripts significantly co-expressed with TCF7L2 in a microarray set combined with individual expression assays, suggested tissue-specific roles of TCF7L2 splicing forms in regulation of transcription, signal transduction and cell adhesion.
Conclusions: Expression of TCF7L2 alternatively spliced forms may have different functional roles in omental and subcutaneous adipose tissue but is not associated with SNPs rs7903146 and rs12255372 or T2D status.
RP Prokunina-Olsson, L (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM prokuninal@mail.nih.gov
OI Prokunina-Olsson, Ludmila/0000-0002-9622-2091
FU Intramural NIH HHS; NIDDK NIH HHS [P30 DK040561, P30 DK040561-14]
NR 26
TC 22
Z9 22
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 30
PY 2009
VL 4
IS 9
AR e7231
DI 10.1371/journal.pone.0007231
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 501BO
UT WOS:000270354100005
PM 19789636
ER
PT J
AU Hyun, S
Sun, YQ
Sundaram, R
AF Hyun, Seunggeun
Sun, Yanqing
Sundaram, Rajeshwari
TI Assessing cumulative incidence functions under the semiparametric
additive risk model
SO STATISTICS IN MEDICINE
LA English
DT Article
DE competing risks; survival analysis; cumulative incidence function;
confidence interval; semiparametric model
AB In analyzing competing risks data, a quantity of considerable interest is the cumulative incidence function. Often, the effect of covariates on the cumulative incidence function is modeled via the proportional hazards model for the cause-specific hazard function. As the proportionality assumption may be too restrictive in practice, we consider an alternative more flexible semiparametric additive hazards model of (Biometrika 1994; 81:501-514) for the cause-specific hazard. This model specifies the effect of covariates on the cause-specific hazard to be additive as well as allows the effect of some covariates to be fixed and that of others to be time varying. We present an approach for constructing confidence intervals as well as confidence bands for the cause-specific cumulative incidence function of subjects with given values of the covariates. Furthermore, we also present an approach for constructing confidence intervals and confidence bands for comparing two cumulative incidence functions given values of the covariates. The finite sample property of the proposed estimators is investigated through simulations. We conclude our paper with an analysis of the well-known malignant melanoma data using our method. Published in 2009 by John Wiley & Sons, Ltd.
C1 [Sundaram, Rajeshwari] NICHHD, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA.
[Hyun, Seunggeun] Univ S Carolina Upstate, Div Math & Comp Sci, Spartanburg, SC 29303 USA.
[Sun, Yanqing] Univ N Carolina, Dept Math & Stat, Charlotte, NC 28223 USA.
RP Sundaram, R (reprint author), NICHHD, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM sundaramr2@mail.nih.gov
OI Sundaram, Rajeshwari/0000-0002-6918-5002
FU NSF [DMS-0304922, DMS-0604576]; NIH [2 RO1 A1054165-04]; Intramural
research program of Eunice Kennedy Shriver National Institute of Child
Health and Human Development
FX Contract/grant sponsor: NSF; contract/grant numbers: DMS-0304922,
DMS-0604576 Contract/grant sponsor: NIH; contract/grant number: 2 RO1
A1054165-04 Contract/grant sponsor: Intramural research program of
Eunice Kennedy Shriver National Institute of Child Health and Human
Development
NR 12
TC 2
Z9 2
U1 0
U2 3
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD SEP 30
PY 2009
VL 28
IS 22
BP 2748
EP 2768
DI 10.1002/sim.3640
PG 21
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA 498YS
UT WOS:000270183400002
PM 19585462
ER
PT J
AU Jia, L
Kropachev, K
Ding, SA
Van Houten, B
Geacintov, NE
Broyde, S
AF Jia, Lei
Kropachev, Konstantin
Ding, Shuang
Van Houten, Bennett
Geacintov, Nicholas E.
Broyde, Suse
TI Exploring Damage Recognition Models in Prokaryotic Nucleotide Excision
Repair with a Benzo[a]pyrene-Derived Lesion in UvrB
SO BIOCHEMISTRY
LA English
DT Article
ID ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; DNA-DAMAGE; SOLUTION CONFORMATION;
STRUCTURAL BASIS; QUALITY-CONTROL; ATPASE ACTIVITY; DIOL EPOXIDES;
BINDING; PROTEIN
AB The UvrB protein is a central unit for damage recognition in the prokaryotic nucleotide excision repair system, which excises bulky DNA lesions. We have utilized molecular modeling and MD simulations based on crystal structures, mutagenesis, and fluorescence data, to model the 10R-(+)-cis-anti-B[a]P-N(2)-dG lesion, derived from the tumorigenic (+)-anti-B[a]PDE metabolite of benzo[a]pyrene, at different locations on the inner and outer strand in UvrB. Our results suggest that this lesion is accommodated on the inner strand where it might translocate through the tunnel created by the beta-hairpin and UvrB domain 1B and ultimately could be housed in the pocket behind the beta-hairpin prior to excision by UvrC. Lesions that vary in size and shape may be stopped at the gate to the tunnel, within the tunnel, or in the pocket when UvrC initiates excision. Common features of beta-hairpin intrusion between the two DNA strands and nucleotide flipping manifested in structures of prokaryotic and eukaryotic NER lesion recognition proteins are consistent with common recognition mechanisms, based on lesion-induced local thermodynamic distortion/destabilization and nucleotide flipping.
C1 [Jia, Lei; Ding, Shuang; Broyde, Suse] NYU, Dept Biol, New York, NY 10003 USA.
[Kropachev, Konstantin; Geacintov, Nicholas E.; Broyde, Suse] NYU, Dept Chem, New York, NY 10003 USA.
[Van Houten, Bennett] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Broyde, S (reprint author), NYU, Dept Biol, 100 Washington Sq E,Room 1009, New York, NY 10003 USA.
EM broyde@nyu.edu
FU National Institutes of Health; National Cancer Institute [CA28038,
CA099194]; NIEHS; Intramural Research Program; National Science
Foundation Partnerships for Advanced Computational Infrastructure;
[CA75449]
FX This work was supported by the National Institutes of Health, National
Cancer Institute Grants CA28038 to S.B. and CA099194 to N.E.G., and the
NIEHS, NIH, Intramural Research Program to B.V.H.. Partial support for
computational infrastructure and systems management was also provided by
Grant CA75449 to S.B. Computational support was provided in part by the
National Science Foundation Partnerships for Advanced Computational
Infrastructure.
NR 61
TC 13
Z9 13
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD SEP 29
PY 2009
VL 48
IS 38
BP 8948
EP 8957
DI 10.1021/bi9010072
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 495LE
UT WOS:000269892000004
PM 19681599
ER
PT J
AU Koonin, EV
Wolf, YI
AF Koonin, Eugene V.
Wolf, Yuri I.
TI The fundamental units, processes and patterns of evolution, and the Tree
of Life conundrum
SO BIOLOGY DIRECT
LA English
DT Editorial Material
ID HORIZONTAL GENE-TRANSFER; EUKARYOTIC EVOLUTION; SELFISH OPERONS; ORIGIN;
VIRUSES; CELLS; SEQUENCE; REPLICATORS; HYPOTHESIS; GENOMICS
AB Background: The elucidation of the dominant role of horizontal gene transfer (HGT) in the evolution of prokaryotes led to a severe crisis of the Tree of Life (TOL) concept and intense debates on this subject.
Concept: Prompted by the crisis of the TOL, we attempt to define the primary units and the fundamental patterns and processes of evolution. We posit that replication of the genetic material is the singular fundamental biological process and that replication with an error rate below a certain threshold both enables and necessitates evolution by drift and selection. Starting from this proposition, we outline a general concept of evolution that consists of three major precepts.
1. The primary agency of evolution consists of Fundamental Units of Evolution (FUEs), that is, units of genetic material that possess a substantial degree of evolutionary independence. The FUEs include both bona fide selfish elements such as viruses, viroids, transposons, and plasmids, which encode some of the information required for their own replication, and regular genes that possess quasi-independence owing to their distinct selective value that provides for their transfer between ensembles of FUEs (genomes) and preferential replication along with the rest of the recipient genome.
2. The history of replication of a genetic element without recombination is isomorphously represented by a directed tree graph (an arborescence, in the graph theory language). Recombination within a FUE is common between very closely related sequences where homologous recombination is feasible but becomes negligible for longer evolutionary distances. In contrast, shuffling of FUEs occurs at all evolutionary distances. Thus, a tree is a natural representation of the evolution of an individual FUE on the macro scale, but not of an ensemble of FUEs such as a genome.
3. The history of life is properly represented by the "forest" of evolutionary trees for individual FUEs (Forest of Life, or FOL). Search for trends and patterns in the FOL is a productive direction of study that leads to the delineation of ensembles of FUEs that evolve coherently for a certain time span owing to a shared history of vertical inheritance or horizontal gene transfer; these ensembles are commonly known as genomes, taxa, or clades, depending on the level of analysis. A small set of genes (the universal genetic core of life) might show a (mostly) coherent evolutionary trend that transcends the entire history of cellular life forms. However, it might not be useful to denote this trend "the tree of life", or organismal, or species tree because neither organisms nor species are fundamental units of life.
Conclusion: A logical analysis of the units and processes of biological evolution suggests that the natural fundamental unit of evolution is a FUE, that is, a genetic element with an independent evolutionary history. Evolution of a FUE on the macro scale is naturally represented by a tree. Only the full compendium of trees for individual FUEs (the FOL) is an adequate depiction of the evolution of life. Coherent evolution of FUEs over extended evolutionary intervals is a crucial aspect of the history of life but a "species" or "organismal" tree is not a fundamental concept.
Reviewers: This articles was reviewed by Valerian Dolja, W. Ford Doolittle, Nicholas Galtier, and William Martin
C1 [Koonin, Eugene V.; Wolf, Yuri I.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov; wolf@ncbi.nlm.nih.gov
FU Intramural NIH HHS
NR 73
TC 37
Z9 38
U1 0
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD SEP 29
PY 2009
VL 4
AR 33
DI 10.1186/1745-6150-4-33
PG 13
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 510AW
UT WOS:000271061400001
PM 19788730
ER
PT J
AU Joshi, A
Nagashima, K
Freed, EO
AF Joshi, Anjali
Nagashima, Kunio
Freed, Eric O.
TI Defects in cellular sorting and retroviral assembly induced by GGA
overexpression
SO BMC CELL BIOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; INFECTIOUS-ANEMIA VIRUS; TRANS-GOLGI
NETWORK; FACTOR-BINDING PROTEINS; GAG-MEMBRANE-BINDING; HIV-1 GAG;
INTRACELLULAR TRAFFICKING; LATE DOMAIN; UBIQUITIN BINDING;
INCLUSION-BODIES
AB Background: We previously demonstrated that overexpression of Golgi-localized, gamma-ear containing, Arf-binding (GGA) proteins inhibits retrovirus assembly and release by disrupting the function of endogenous ADP ribosylation factors (Arfs). GGA overexpression led to the formation of large, swollen vacuolar compartments, which in the case of GGA1 sequestered HIV-1 Gag.
Results: In the current study, we extend our previous findings to characterize in depth the GGA-induced compartments and the determinants for retroviral Gag sequestration in these structures. We find that GGA-induced structures are derived from the Golgi and contain aggresome markers. GGA overexpression leads to defects in trafficking of transferrin receptor and recycling of cation-dependent mannose 6-phosphate receptor. Additionally, we find that compartments induced by GGA overexpression sequester Tsg101, poly-ubiquitin, and, in the case of GGA3, Hrs. Interestingly, brefeldin A treatment, which leads to the dissociation of endogenous GGAs from membranes, does not dissociate the GGA-induced compartments. GGA mutants that are defective in Arf binding and hence association with membranes also induce the formation of GGA-induced structures. Overexpression of ubiquitin reverses the formation of GGA-induced structures and partially rescues HIV-1 particle production. We found that in addition to HIV-1 Gag, equine infectious anemia virus Gag is also sequestered in GGA1-induced structures. The determinants in Gag responsible for sequestration map to the matrix domain, and recruitment to these structures is dependent on Gag membrane binding.
Conclusion: These data provide insights into the composition of structures induced by GGA overexpression and their ability to disrupt endosomal sorting and retroviral particle production.
C1 [Joshi, Anjali; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Nagashima, Kunio] NCI, Image Anal Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21701 USA.
[Joshi, Anjali] Texas Tech Univ, Hlth Sci Ctr, Dept Biomed Sci, Paul L Foster Sch Med,Ctr Excellence Infect Dis, El Paso, TX 79905 USA.
RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
EM ajoshi145@yahoo.com; nagashim@ncifcrf.gov; efreed@nih.gov
FU Center for Cancer Research, National Cancer Institute, NIH; National
Cancer Institute, NIH [N01-CO-12400]
FX We thank F. Soheilian and S. Ablan for expert technical assistance and
members of the Freed lab for helpful discussion and critical review of
the manuscript. We thank J. Bonifacino for kindly providing GGA
expression vectors, E. Sztul for the GFP-250 construct, A. Ono for the
Fyn10deltaMA and Fyn10fullMA Gag chimeras, R. Kopito for the ubiquitin
expression vector pCW7, R. Kahn for the GGA1 antibody, and P. Woodman
for the GFP-tagged Vps4EQ expression vector. The HIV-Ig and TZM-bl cells
were obtained from the NIH AIDS Research and Reference Reagent Program,
EIAV anti-p26 antibody was kindly provided by R. Montelaro and MLV
anti-p30 was a gift from A. Rein. This research was supported by the
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, NIH, and by the Intramural AIDS Targeted Antiviral
Program. This project was funded in part with federal funds from the
National Cancer Institute, NIH, under contract N01-CO-12400. The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does mention of
trade names, commercial products, or organizations imply endorsement by
the U. S. Government.
NR 80
TC 10
Z9 10
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2121
J9 BMC CELL BIOL
JI BMC Cell Biol.
PD SEP 29
PY 2009
VL 10
AR 72
DI 10.1186/1471-2121-10-72
PG 14
WC Cell Biology
SC Cell Biology
GA 511XC
UT WOS:000271204000001
PM 19788741
ER
PT J
AU Vasan, RS
Demissie, S
Kimura, M
Cupples, LA
White, C
Gardner, JP
Cao, XG
Levy, D
Benjamin, EJ
Aviv, A
AF Vasan, Ramachandran S.
Demissie, Serkalem
Kimura, Masayuki
Cupples, L. Adrienne
White, Charles
Gardner, Jeffrey P.
Cao, Xiaogian
Levy, Daniel
Benjamin, Emelia J.
Aviv, Abraham
TI Association of Leukocyte Telomere Length With Echocardiographic Left
Ventricular Mass The Framingham Heart Study
SO CIRCULATION
LA English
DT Article
DE telomere; echocardiography; hypertension; epidemiology; hypertrophy
ID GROWTH-FACTOR-I; ANGIOTENSIN-ALDOSTERONE SYSTEM; CARDIOVASCULAR
RISK-FACTORS; DIABETES-MELLITUS; OXIDATIVE STRESS; INSULIN-RESISTANCE;
BLOOD-PRESSURE; HYPERTENSIVE SUBJECTS; GENERAL-POPULATION;
PHYSICAL-ACTIVITY
AB Background-Leukocyte telomere length (LTL) decreases over the adult life course owing to the cumulative burden of oxidative stress, inflammation, and exposure to vascular risk factors. Left ventricular (LV) mass is a biomarker of long-standing exposure to cardiovascular disease risk factors. We hypothesized that LTL is related inversely to LV mass.
Methods and Results-We related LTL (measured by Southern blot analysis) to echocardiographic LV mass and its components (LV diastolic dimension and LV wall thickness) in 850 Framingham Heart Study participants (mean age 58 years, 58% women) using multivariable linear regression with adjustment for age, sex, height, weight, systolic blood pressure, hypertension treatment, and smoking. Overall, multivariable-adjusted LTL was positively related to LV mass (beta-coefficient per SD increase 0.072; P=0.001), LV wall thickness (beta=0.053; P=0.01), and LV diastolic dimension (beta=0.035; P=0.09). We observed effect modification by hypertension status (P for interaction=0.02 for LV mass); LTL was more strongly associated with LV mass and LV wall thickness in individuals with hypertension (beta-coefficient per SD increment of 0.10 and 0.08, respectively; P<0.01 for both). Participants with hypertension who were in the top quartile of LV mass had LTL that was 250 base pairs longer than those in the lowest quartile (P for trend across quartiles=0.009).
Conclusions-In contrast to our expectation, in the present community-based sample, LTL was positively associated with LV mass and wall thickness, especially so in participants with hypertension. These data are consistent with the hypothesis that longer LTL may be a marker of propensity to LV hypertrophy. (Circulation. 2009; 120: 1195-1202.)
C1 [Vasan, Ramachandran S.; Demissie, Serkalem; Cupples, L. Adrienne; Levy, Daniel; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Prevent Med, Evans Dept Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Evans Dept Med, Boston, MA 02118 USA.
Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Demissie, Serkalem; Cupples, L. Adrienne; White, Charles] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Kimura, Masayuki; Gardner, Jeffrey P.; Cao, Xiaogian; Aviv, Abraham] Univ Med & Dent New Jersey, Ctr Human Dev & Aging, Newark, NJ 07103 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA.
RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM vasan@bu.edu
OI Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195, 2 K24 HL04334, RO1HL080124, 6R01-NS 17950, R01AG021593]
FX This work was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (contract No. N01-HC-25195), 2 K24
HL04334, RO1HL080124 (Dr Vasan), 6R01-NS 17950; and R01AG021593 (Dr
Aviv).
NR 63
TC 31
Z9 33
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD SEP 29
PY 2009
VL 120
IS 13
BP 1195
EP 1202
DI 10.1161/CIRCULATIONAHA.109.853895
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 500AU
UT WOS:000270270200006
PM 19752323
ER
PT J
AU Merz, CNB
Alberts, MJ
Balady, GJ
Ballantyne, CM
Berra, K
Black, HR
Blumenthal, RS
Davidson, MH
Fazio, SB
Ferdinand, KC
Fine, LJ
Fonseca, V
Franklin, BA
McBride, PE
Mensah, GA
Merli, GJ
O'Gara, PT
Thompson, PD
Underberg, JA
AF Merz, C. Noel Bairey
Alberts, Mark J.
Balady, Gary J.
Ballantyne, Christie M.
Berra, Kathy
Black, Henry R.
Blumenthal, Roger S.
Davidson, Michael H.
Fazio, Sara B.
Ferdinand, Keith C.
Fine, Lawrence J.
Fonseca, Vivian
Franklin, Barry A.
McBride, Patrick E.
Mensah, George A.
Merli, Geno J.
O'Gara, Patrick T.
Thompson, Paul D.
Underberg, James A.
CA ACCF AHA ACP
TI ACCF/AHA/ACP 2009 Competence and Training Statement: A Curriculum on
Prevention of Cardiovascular Disease A Report of the American College of
Cardiology Foundation/American Heart Association/American College of
Physicians Task Force on Competence and Training (Writing Committee to
Develop a Competence and Training Statement on Prevention of
Cardiovascular Disease)
SO CIRCULATION
LA English
DT Editorial Material
DE ACCF/AHA Competence and Training Statements; competency; prevention;
cardiovascular; training; vascular; cardiac; cardiac rehabilitation
ID CORONARY-ARTERY-DISEASE; ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE
PROFESSIONALS; RANDOMIZED CONTROLLED-TRIAL; LIPID-LOWERING THERAPY;
HIGH-BLOOD-PRESSURE; INTERDISCIPLINARY WORKING GROUP;
STROKE-STATISTICS-SUBCOMMITTEE; 64-SLICE COMPUTED-TOMOGRAPHY;
SUSTAINED-RELEASE BUPROPION
C1 [Merz, C. Noel Bairey; Ballantyne, Christie M.; Blumenthal, Roger S.; McBride, Patrick E.] Amer Coll, Cardiol Fdn, Bryn Mawr, PA 19010 USA.
[Alberts, Mark J.] Amer Acad Neurol, St Paul, MN USA.
[Black, Henry R.] Amer Soc Hypertens, New York, NY 10016 USA.
[Fazio, Sara B.; Merli, Geno J.] Amer Coll Physicians, Philadelphia, PA 19106 USA.
[Ferdinand, Keith C.] Assoc Black Cardiologists, Atlanta, GA 30308 USA.
[Fine, Lawrence J.] NHLBI, Bethesda, MD USA.
[Fonseca, Vivian] Amer Diabet Assoc, Alexandria, VA USA.
[Franklin, Barry A.; O'Gara, Patrick T.] Amer Heart Assoc, Dallas, TX USA.
[Fine, Lawrence J.; Mensah, George A.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Thompson, Paul D.] Amer Coll Sports Med, Indianapolis, IN USA.
[Underberg, James A.] Amer Coll Prevent Med, Washington, DC USA.
[Fine, Lawrence J.; Mensah, George A.] NIH, Bethesda, MD USA.
RP Merz, CNB (reprint author), Amer Coll, Cardiol Fdn, Bryn Mawr, PA 19010 USA.
NR 223
TC 17
Z9 19
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD SEP 29
PY 2009
VL 120
IS 13
BP E100
EP E126
DI 10.1161/CIRCULATIONAHA.109.192640
PG 27
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 500AU
UT WOS:000270270200021
ER
PT J
AU McCroskery, S
Bailey, A
Lin, L
Daniels, MP
AF McCroskery, S.
Bailey, A.
Lin, L.
Daniels, M. P.
TI TRANSMEMBRANE AGRIN REGULATES DENDRITIC FILOPODIA AND SYNAPSE FORMATION
IN MATURE HIPPOCAMPAL NEURON CULTURES
SO NEUROSCIENCE
LA English
DT Article
DE synapse formation; lenti-virus; shRNA; agrin; filopodia; dendrite
ID HEPARAN-SULFATE PROTEOGLYCAN; CENTRAL-NERVOUS-SYSTEM; RAT HIPPOCAMPAL;
DEFICIENT MICE; NEURITE OUTGROWTH; RECOMBINANT AGRIN; CORTICAL-NEURONS;
SPINE FORMATION; IN-VIVO; RECEPTOR
AB The transmembrane isoform of agrin (Tm-agrin) is the predominant form expressed in the brain but its putative roles in brain development are not well understood. Recent reports have implicated Tm-agrin in the formation and stabilization of filopodia on neurites of immature central and peripheral neurons in culture. In maturing central neurons, dendritic filopodia are believed to facilitate synapse formation. In the present study we have investigated the role of Tm-agrin in regulation of dendritic filopodia and synaptogenesis in maturing cultures of rat hippocampal neurons. We did this by infecting the neurons with an RNAi lentivirus to deplete endogenous agrin during the developmental period when filopodia density on the dendritic arbor was high, and synapse formation was rapid. We found that dendritic filopodia density was markedly reduced, as was synapse density along dendrites. Moreover, synapse formation was more sharply reduced on dendrites of infected neurons contacted by uninfected axons than on uninfected dendrites contacted by infected axons. The results are consistent with a physiological role for Tm-agrin in the maturation of hippocampal neurons involving positive regulation of dendritic filopodia and consequent promotion of synaptogenesis, but also suggest a role for axonal agrin in synaptogenesis. Published by Elsevier Ltd on behalf of IBRO.
C1 [McCroskery, S.; Bailey, A.; Lin, L.; Daniels, M. P.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[McCroskery, S.] ERMA New Zealand, New Organisms Grp, Wellington, New Zealand.
[Lin, L.] NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA.
[Daniels, M. P.] NHLBI, Electron Microscopy Core Facil, NIH, Bethesda, MD 20892 USA.
RP Daniels, MP (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM danielsm2@mail.nih.gov
FU National Heart, Lung and Blood Institute, NIH
FX This research was supported by the Intramural Research Program of the
National Heart, Lung and Blood Institute, NIH.
NR 57
TC 21
Z9 23
U1 3
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD SEP 29
PY 2009
VL 163
IS 1
BP 168
EP 179
DI 10.1016/j.neuroscience.2009.06.012
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 489FD
UT WOS:000269404600015
PM 19524020
ER
PT J
AU Leker, RR
Toth, ZE
Shahar, T
Cassiani-Ingoni, R
Szalayova, I
Key, S
Bratincsak, A
Mezey, E
AF Leker, R. R.
Toth, Z. E.
Shahar, T.
Cassiani-Ingoni, R.
Szalayova, I.
Key, S.
Bratincsak, A.
Mezey, E.
TI TRANSFORMING GROWTH FACTOR alpha INDUCES ANGIOGENESIS AND NEUROGENESIS
FOLLOWING STROKE
SO NEUROSCIENCE
LA English
DT Article
DE stroke; transforming growth factor alpha; neurogenesis; angiogenesis
ID ADULT HIPPOCAMPAL NEUROGENESIS; TYRAMIDE SIGNAL AMPLIFICATION;
CEREBRAL-ARTERY OCCLUSION; REDUCES INFARCT VOLUME; BONE-MARROW; FACTOR
RECEPTOR; PERIPHERAL-BLOOD; STEM-CELLS; IN-VIVO; G-CSF
AB The cytokine transforming growth factor alpha (TGF alpha) has proangiogenic and proneurogenic effects and can potentially reduce infarct volumes. Therefore, we administered TGF alpha or vehicle directly into the area surrounding the infarct in female mice that received gender-mismatched bone marrow transplants from green fluorescent protein (GFP)-expressing males prior to undergoing permanent middle cerebral artery occlusion. Newborn cells were tracked with bromodeoxyuridine (BrdU) labeling and immunohistochemistry at 90 days after stroke onset. We also studied the ingress of bone marrow-derived cells into the ischemic brain to determine whether such cells contribute to angiogenesis or neurogenesis. Infarct volumes were measured at 90 days poststroke. The results show that TGF alpha led to significant increments in the number of newborn neurons and glia in the ischemic hemisphere. TGF alpha also led to significant increments in the number of bone marrow-derived cells entering into the ischemic hemisphere. Most of these cells did not label with BrdU and represented endothelial cells that incorporated into blood vessels in the infarct border zone. Our results also show that infarct size was significantly reduced in animals treated with TGF alpha compared with controls. These results suggest that TGF alpha can induce angiogenesis, neurogenesis and neuroprotection after stroke. At least part of the pro-angiogenic effect appears to be secondary to the incorporation of bone marrow-derived endothelial cells into blood vessels in the infarct border zone. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
C1 [Leker, R. R.] Hebrew Univ Jerusalem, Hadassah Med Ctr, Stroke Serv, Dept Neurol,Peritz & Chantal Scheinberg Cerebrova, IL-91120 Jerusalem, Israel.
[Leker, R. R.; Toth, Z. E.; Shahar, T.; Cassiani-Ingoni, R.; Szalayova, I.; Key, S.; Bratincsak, A.; Mezey, E.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Toth, Z. E.] Semmelweis Univ, Dept Anat Histol & Embryol, Neuromorphol & Neuroendocrine Res Lab, H-1085 Budapest, Hungary.
[Toth, Z. E.] Hungarian Acad Sci, Budapest, Hungary.
RP Leker, RR (reprint author), Hebrew Univ Jerusalem, Hadassah Med Ctr, Stroke Serv, Dept Neurol,Peritz & Chantal Scheinberg Cerebrova, Hadassah Kerem POB 12000, IL-91120 Jerusalem, Israel.
EM leker@cc.huji.ac.il
FU Chantel and Peritz Scheinberg Cerebrovascular Research Fund; Sol Irwin
Juni Trust Fund; NIDCR intramural research program
FX Dr. Leker was supported in part by the Chantel and Peritz Scheinberg
Cerebrovascular Research Fund and by the Sol Irwin Juni Trust Fund. This
study was supported by the NIDCR intramural research program.
NR 44
TC 24
Z9 24
U1 1
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD SEP 29
PY 2009
VL 163
IS 1
BP 233
EP 243
DI 10.1016/j.neuroscience.2009.05.050
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 489FD
UT WOS:000269404600021
PM 19481589
ER
PT J
AU Fritsch, B
Qashu, F
Figueiredo, TH
Aroniadou-Anderjaska, V
Rogawski, MA
Braga, MFM
AF Fritsch, B.
Qashu, F.
Figueiredo, T. H.
Aroniadou-Anderjaska, V.
Rogawski, M. A.
Braga, M. F. M.
TI PATHOLOGICAL ALTERATIONS IN GABAERGIC INTERNEURONS AND REDUCED TONIC
INHIBITION IN THE BASOLATERAL AMYGDALA DURING EPILEPTOGENESIS
SO NEUROSCIENCE
LA English
DT Review
DE basolateral amygdala; interneurons; epileptogenesis; status epilepticus;
kainate receptors; inhibitory synaptic transmission
ID TEMPORAL-LOBE EPILEPSY; GLUTAMIC-ACID DECARBOXYLASE; INDUCED STATUS
EPILEPTICUS; BENZODIAZEPINE-RECEPTOR BINDING; LIMBIC STATUS EPILEPTICUS;
MESSENGER-RNA EXPRESSION; DENTATE GRANULE CELLS; RAT HIPPOCAMPUS;
GABA(A) RECEPTOR; KAINATE RECEPTORS
AB An acute brain insult such as traumatic head/brain injury, stroke, or an episode of status epilepticus can trigger epileptogenesis, which, after a latent, seizure-free period, leads to epilepsy. The discovery of effective pharmacological interventions that can prevent the development of epilepsy requires knowledge of the alterations that occur during epileptogenesis in brain regions that play a central role in the induction and expression of epilepsy. In the present study, we investigated pathological alterations in GABAergic inter-neurons in the rat basolateral amygdala (BLA), and the functional impact of these alterations on inhibitory synaptic transmission, on days 7 to 10 after status epilepticus induced by kainic acid. Using design-based stereology combined with glutamic acid decarboxylase (GAD) 67 immunohistochemistry, we found a more extensive loss of GABAergic interneurons compared to the loss of principal cells. Fluoro-Jade C staining showed that neuronal degeneration was still ongoing. These alterations were accompanied by an increase in the levels of GAD and the alpha 1 subunit of the GABA(A) receptor, and a reduction in the GluK1 (previously known as GluR5) subunit, as determined by Western blots. Whole-cell recordings from BLA pyramidal neurons showed a significant reduction in the frequency and amplitude of action potential-dependent spontaneous inhibitory postsynaptic currents (IPSCs), a reduced frequency but not amplitude of miniature IPSCs, and impairment in the modulation of IPSCs via GluK1-containing kainate receptors (GluK1Rs). Thus, in the BLA, GABAergic interneurons are more vulnerable to seizure-induced damage than principal cells. Surviving interneurons increase their expression of GAD and the alpha 1 GABA(A) receptor subunit, but this does not compensate for the interneuronal loss; the result is a dramatic reduction of tonic inhibition in the BLA circuitry. As activation of GluK1Rs by ambient levels of glutamate facilitates GABA release, the reduced level and function of these receptors may contribute to the reduction of tonic inhibitory activity. These alterations at a relatively early stage of epileptogenesis may facilitate the progress towards the development of epilepsy. Published by Elsevier Ltd on behalf of IBRO.
C1 [Figueiredo, T. H.; Aroniadou-Anderjaska, V.; Braga, M. F. M.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, F Edward Hebert Sch Med, Bethesda, MD 20814 USA.
[Fritsch, B.; Rogawski, M. A.] NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA.
[Qashu, F.; Aroniadou-Anderjaska, V.; Braga, M. F. M.] Uniformed Serv Univ Hlth Sci, Neurosci Program, F Edward Hebert Sch Med, Bethesda, MD 20814 USA.
[Rogawski, M. A.] Univ Calif Davis, Sch Med, Dept Neurol, Sacramento, CA 95817 USA.
RP Braga, MFM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, F Edward Hebert Sch Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM mbraga@usuhs.mil
RI Rogawski, Michael/B-6353-2009;
OI Rogawski, Michael/0000-0002-3296-8193; Fritsch,
Brita/0000-0003-4884-9049
FU National Institutes of Health CounterACT Program [U01 NS058162-01];
Defense Threat Reduction Agency-Joint Science and Technology Office
[1.E0021_07-US-C]; NINDS Intramural Research Program
FX This work was supported by the National Institutes of Health CounterACT
Program (NINDS award U01 NS058162-01 to M.F.M.B.), the Defense Threat
Reduction Agency-Joint Science and Technology Office, Medical S&T
Division (grant 1.E0021_07-US-C to M.F.M.B.), and the NINDS Intramural
Research Program (M.A.R.).
NR 101
TC 27
Z9 29
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
J9 NEUROSCIENCE
JI Neuroscience
PD SEP 29
PY 2009
VL 163
IS 1
BP 415
EP 429
DI 10.1016/j.neuroscience.2009.06.034
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 489FD
UT WOS:000269404600037
PM 19540312
ER
PT J
AU Sung, MH
Salvatore, L
De Lorenzi, R
Indrawan, A
Pasparakis, M
Hager, GL
Bianchi, ME
Agresti, A
AF Sung, Myong-Hee
Salvatore, Luigi
De Lorenzi, Rossana
Indrawan, Anindya
Pasparakis, Manolis
Hager, Gordon L.
Bianchi, Marco E.
Agresti, Alessandra
TI Sustained Oscillations of NF-kappa B Produce Distinct Genome Scanning
and Gene Expression Profiles
SO PLOS ONE
LA English
DT Article
AB NF-kappa B is a prototypic stress-responsive transcription factor that acts within a complex regulatory network. The signaling dynamics of endogenous NF-kappa B in single cells remain poorly understood. To examine real time dynamics in living cells, we monitored NF-kappa B activities at multiple timescales using GFP-p65 knock-in mouse embryonic fibroblasts. Oscillations in NFkB were sustained in most cells, with several cycles of transient nuclear translocation after TNF-alpha stimulation. Mathematical modeling suggests that NF-kappa B oscillations are selected over other non-oscillatory dynamics by fine-tuning the relative strengths of feedback loops like I kappa B alpha. The ability of NF-kappa B to scan and interact with the genome in vivo remained remarkably constant from early to late cycles, as observed by fluorescence recovery after photobleaching (FRAP). Perturbation of long-term NF-kappa B oscillations interfered with its short-term interaction with chromatin and balanced transcriptional output, as predicted by the mathematical model. We propose that negative feedback loops do not simply terminate signaling, but rather promote oscillations of NF-kappa B in the nucleus, and these oscillations are functionally advantageous.
RP Sung, MH (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
EM sungm@mail.nih.gov; agresti.alessandra@hsr.it
RI Agresti, Alessandra/K-5228-2016;
OI Agresti, Alessandra/0000-0001-5006-9506; Pasparakis,
Manolis/0000-0002-9870-0966
FU Intramural NIH HHS; Associazione Italiana per la Ricerca sul Cancro
NR 30
TC 56
Z9 56
U1 1
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 29
PY 2009
VL 4
IS 9
AR e7163
DI 10.1371/journal.pone.0007163
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500HR
UT WOS:000270290100005
PM 19787057
ER
PT J
AU Skoko, D
Li, M
Huang, Y
Mizuuchi, M
Cai, ML
Bradley, CM
Pease, PJ
Xiao, BT
Marko, JF
Craigie, R
Mizuuchi, K
AF Skoko, Dunja
Li, Min
Huang, Ying
Mizuuchi, Michiyo
Cai, Mengli
Bradley, Christina M.
Pease, Paul J.
Xiao, Botao
Marko, John F.
Craigie, Robert
Mizuuchi, Kiyoshi
TI Barrier-to-autointegration factor (BAF) condenses DNA by looping
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE autointegration; BAF (Banf1); DNA condensation; DNA looping; retrovirus
ID LEM-DOMAIN PROTEINS; NUCLEAR-ENVELOPE; STRUCTURAL BASIS; RETROVIRAL DNA;
CELLULAR FACTOR; BINDING; COMPLEX; EMERIN; LAP2-ALPHA; ROLES
AB Barrier-to-autointegration factor (BAF) is a protein that has been proposed to compact retroviral DNA, making it inaccessible as a target for self-destructive integration into itself (autointegration). BAF also plays an important role in nuclear organization. We studied the mechanism of DNA condensation by BAF using total internal reflection fluorescence microscopy. We found that BAF compacts DNA by a looping mechanism. Dissociation of BAF from DNA occurs with multiphasic kinetics; an initial fast phase is followed by a much slower dissociation phase. The mechanistic basis of the broad timescale of dissociation is discussed. This behavior mimics the dissociation of BAF from retroviral DNA within preintegration complexes as monitored by functional assays. Thus the DNA binding properties of BAF may alone be sufficient to account for its association with the preintegration complex.
C1 [Skoko, Dunja; Li, Min; Huang, Ying; Mizuuchi, Michiyo; Bradley, Christina M.; Craigie, Robert; Mizuuchi, Kiyoshi] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Cai, Mengli] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Pease, Paul J.] Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 94720 USA.
[Xiao, Botao; Marko, John F.] Northwestern Univ, Dept Phys & Astron, Evanston, IL 60208 USA.
[Marko, John F.] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA.
RP Mizuuchi, K (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM kmizu@helix.nih.gov
FU National Science Foundation [DMR-0715099, PHY-0852130]; Chicago
Biomedical Consortium
FX We are grateful to Vassili Ivanov for the help with the microscope
system. This work was supported by the National Institute of Diabetes
and Digestive and Kidney Diseases intramural program and by the NIH
Intramural Aids Targeted Antiviral Program, National Institutes of
Health, Department of Health and Human Services, US Government. The work
of B. X. and J. F. M. was supported by National Science Foundation
Grants DMR-0715099, PHY-0852130 and by a Catalyst Award from the Chicago
Biomedical Consortium.
NR 31
TC 34
Z9 34
U1 0
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 29
PY 2009
VL 106
IS 39
BP 16610
EP 16615
DI 10.1073/pnas.0909077106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500MH
UT WOS:000270305800015
PM 19805345
ER
PT J
AU Kim, HW
Chang, YC
Chen, M
Rapoport, SI
Rao, JS
AF Kim, Hyung-Wook
Chang, Yunyoung C.
Chen, Mei
Rapoport, Stanley I.
Rao, Jagadeesh S.
TI Chronic NMDA administration to rats increases brain pro-apoptotic
factors while decreasing anti-Apoptotic factors and causes cell death
SO BMC NEUROSCIENCE
LA English
DT Article
ID SPINAL-CORD NEURONS; CYTOSOLIC PHOSPHOLIPASE A(2); D-ASPARTATE RECEPTOR;
ARACHIDONIC-ACID; ALZHEIMERS-DISEASE; FRONTAL-CORTEX; UNANESTHETIZED
RATS; MOOD STABILIZERS; BIPOLAR DISORDER; PROTEIN
AB Background: Chronic N-Methyl-d-aspartate (NMDA) administration to rats is reported to increase arachidonic acid signaling and upregulate neuroinflammatory markers in rat brain. These changes may damage brain cells. In this study, we determined if chronic NMDA administration (25 mg/kg i.p., 21 days) to rats would alter expression of pro-and anti-apoptotic factors in frontal cortex, compared with vehicle control.
Results: Using real time RT-PCR and Western blotting, chronic NMDA administration was shown to decrease mRNA and protein levels of anti-apoptotic markers Bcl-2 and BDNF, and of their transcription factor phospho-CREB in the cortex. Expression of pro-apoptotic Bax, Bad, and 14-3-3 zeta was increased, as well as Fluoro-Jade B (FJB) staining, a marker of neuronal loss.
Conclusion: This alteration in the balance between pro-and anti-apoptotic factors by chronic NMDA receptor activation in this animal model may contribute to neuronal loss, and further suggests that the model can be used to examine multiple processes involved in excitotoxicity.
C1 [Kim, Hyung-Wook; Chang, Yunyoung C.; Chen, Mei; Rapoport, Stanley I.; Rao, Jagadeesh S.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
EM kimhyung@mail.nih.gov; yunyoung.chang@gmail.com; chenmei@mail.nih.gov;
sir@helix.nih.gov; jrao@mail.nih.gov
FU National Institute on Aging, National Institutes of Health
FX This work was entirely supported by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health. We thank
Dr Sang-Ho Choi for assistance with florescence microscopy. We thank
Kathy Benjamin for critically reading the manuscript.
NR 54
TC 7
Z9 7
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2202
J9 BMC NEUROSCI
JI BMC Neurosci.
PD SEP 28
PY 2009
VL 10
AR 123
DI 10.1186/1471-2202-10-123
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 513LK
UT WOS:000271323600001
PM 19785755
ER
PT J
AU Maizels, RM
Pearce, EJ
Artis, D
Yazdanbakhsh, M
Wynn, TA
AF Maizels, Rick M.
Pearce, Edward J.
Artis, David
Yazdanbakhsh, Maria
Wynn, Thomas A.
TI Regulation of pathogenesis and immunity in helminth infections
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Review
ID EGG-INDUCED IMMUNOPATHOLOGY; FOLLICULAR HELPER-CELLS; CD4(+) T-CELLS;
SCHISTOSOMA-MANSONI; MOLECULAR-MECHANISMS; FILARIAL INFECTION; TH2
RESPONSES; MOUSE MODELS; EXPRESSION; INFLAMMATION
AB Helminths are multicellular eukaryotic parasites that infect over one quarter of the world's population. Through coevolution with the human immune system, these organisms have learned to exploit immunoregulatory pathways, resulting in asymptomatic tolerance of infections in many individuals. When infections and the resulting immune responses become dysregulated, however, acute and chronic pathologies often develop. A recent international meeting focused on how these parasites modulate host immunity and how control of parasitic and immunopathological disease might be achieved.
C1 [Maizels, Rick M.] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland.
[Maizels, Rick M.] Univ Edinburgh, Inst Immunol & Infect Res, Edinburgh, Midlothian, Scotland.
[Pearce, Edward J.] Trudeau Inst, Saranac Lake, NY 12983 USA.
[Artis, David] Univ Penn, Dept Pathobiol, Sch Vet Med, Philadelphia, PA 19104 USA.
[Yazdanbakhsh, Maria] Leiden Univ, Dept Parasitol, Med Ctr, Leiden, Netherlands.
[Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Maizels, RM (reprint author), Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland.
EM rick.maizels@ed.ac.uk
RI Wynn, Thomas/C-2797-2011
FU Wellcome Trust
NR 44
TC 120
Z9 124
U1 0
U2 36
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD SEP 28
PY 2009
VL 206
IS 10
BP 2059
EP 2066
DI 10.1084/jem.20091903
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 500AM
UT WOS:000270269300002
PM 19770272
ER
PT J
AU Nolting, J
Daniel, C
Reuter, S
Stuelten, C
Li, P
Sucov, H
Kim, BG
Letterio, JJ
Kretschmer, K
Kim, HJ
von Boehmer, H
AF Nolting, Jens
Daniel, Carolin
Reuter, Sabine
Stuelten, Christina
Li, Peng
Sucov, Henry
Kim, Byung-Gyu
Letterio, John J.
Kretschmer, Karsten
Kim, Hye-Jung
von Boehmer, Harald
TI Retinoic acid can enhance conversion of naive into regulatory T cells
independently of secreted cytokines
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID TRANSCRIPTION FACTOR FOXP3; ORAL TOLERANCE; RECEPTOR; INDUCTION; GROWTH;
PROMOTER; GENE; DIFFERENTIATION; BINDING; MICE
AB It has been reported that retinoic acid (RA) enhances regulatory T (T reg) cell conversion by inhibiting the secretion of cytokines that interfere with conversion. This report shows that these conclusions provide a partial explanation at best. First, RA not only interfered with cytokine secretion but also with the ability of these cytokines to inhibit T reg cell conversion of naive T cells. Furthermore, RA enhanced conversion even in the absence of inhibitory cytokines. The latter effect depended on the RA receptor alpha (RAR alpha) but did not require Smad3, despite the fact that RA enhanced Smad3 expression. The RAR alpha 1 isoform was not essential for RA-dependent enhancement of transforming growth factor beta-driven conversion, suggesting that conversion can also be mediated by RAR alpha 2. Interleukin (IL)-6 strongly reduced RAR alpha expression levels such that a deficiency of the predominant RAR alpha 1 isoform leaves too little RAR alpha 2 for RA to inhibit the generation of Th17 cells in the presence of IL-6.
C1 [Nolting, Jens; Daniel, Carolin; Reuter, Sabine; Kretschmer, Karsten; Kim, Hye-Jung; von Boehmer, Harald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Stuelten, Christina] NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA.
[Li, Peng; Sucov, Henry] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA.
[Kim, Byung-Gyu; Letterio, John J.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Dept Pediat, Cleveland, OH 44106 USA.
RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
EM harald_von_boehmer@dfci.harvard.edu
RI Kretschmer, Karsten/E-8174-2010; Daniel, Carolin/M-4624-2014
OI Daniel, Carolin/0000-0003-4698-7069
FU National Institutes of Health [NIH-AI53102]; Leopoldina research
fellowship [BMBF-LPD 9901/8-184]; LOEWE (LiFF) program of the federal
state of Hessen, Germany
FX This report was supported by the National Institutes of Health (grant
NIH-AI53102 to H. von Boehmer), and C. Daniel was supported by a
Leopoldina research fellowship (BMBF-LPD 9901/8-184) and the LOEWE
(LiFF) program of the federal state of Hessen, Germany.
NR 29
TC 78
Z9 80
U1 0
U2 5
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD SEP 28
PY 2009
VL 206
IS 10
BP 2131
EP 2139
DI 10.1084/jem.20090639
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 500AM
UT WOS:000270269300009
PM 19737861
ER
PT J
AU Kapogiannis, D
Barbey, AK
Su, M
Krueger, F
Grafman, J
AF Kapogiannis, Dimitrios
Barbey, Aron K.
Su, Michael
Krueger, Frank
Grafman, Jordan
TI Neuroanatomical Variability of Religiosity
SO PLOS ONE
LA English
DT Article
ID VOXEL-BASED MORPHOMETRY; CORTICAL THICKNESS; ENVIRONMENTAL MEDIATION;
ANTISOCIAL-BEHAVIOR; MEMORY PERFORMANCE; TAXI DRIVERS; NEURAL BASIS;
LIFE-SPAN; CORTEX; MATTER
AB We hypothesized that religiosity, a set of traits variably expressed in the population, is modulated by neuroanatomical variability. We tested this idea by determining whether aspects of religiosity were predicted by variability in regional cortical volume. We performed structural magnetic resonance imaging of the brain in 40 healthy adult participants who reported different degrees and patterns of religiosity on a survey. We identified four Principal Components of religiosity by Factor Analysis of the survey items and associated them with regional cortical volumes measured by voxel-based morphometry. Experiencing an intimate relationship with God and engaging in religious behavior was associated with increased volume of R middle temporal cortex, BA 21. Experiencing fear of God was associated with decreased volume of L precuneus and L orbitofrontal cortex BA 11. A cluster of traits related with pragmatism and doubting God's existence was associated with increased volume of the R precuneus. Variability in religiosity of upbringing was not associated with variability in cortical volume of any region. Therefore, key aspects of religiosity are associated with cortical volume differences. This conclusion complements our prior functional neuroimaging findings in elucidating the proximate causes of religion in the brain.
RP Kapogiannis, D (reprint author), NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
EM grafmanj@ninds.nih.gov
RI Barbey, Aron/L-7312-2015;
OI Barbey, Aron/0000-0002-6092-0912; Grafman, Jordan
H./0000-0001-8645-4457; Lauwereyns, Jan/0000-0003-0551-2550
FU Intramural NIH HHS [Z99 AG999999, ZIA AG000966-03]
NR 75
TC 17
Z9 18
U1 0
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 28
PY 2009
VL 4
IS 9
AR e7180
DI 10.1371/journal.pone.0007180
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 500HQ
UT WOS:000270290000005
PM 19784372
ER
PT J
AU Clauser, SB
Johnson, MR
O'Brien, DM
Beveridge, JM
Fennell, ML
Kaluzny, AD
AF Clauser, Steven B.
Johnson, Maureen R.
O'Brien, Donna M.
Beveridge, Joy M.
Fennell, Mary L.
Kaluzny, Arnold D.
TI Improving clinical research and cancer care delivery in community
settings: evaluating the NCI community cancer centers program
SO IMPLEMENTATION SCIENCE
LA English
DT Article
ID NETWORKS; TRIALS
AB Background: In this article, we describe the National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) pilot and the evaluation designed to assess its role, function, and relevance to the NCI's research mission. In doing so, we describe the evolution of and rationale for the NCCCP concept, participating sites' characteristics, its multi-faceted aims to enhance clinical research and quality of care in community settings, and the role of strategic partnerships, both within and outside of the NCCCP network, in achieving program objectives.
Discussion: The evaluation of the NCCCP is conceptualized as a mixed method multi-layered assessment of organizational innovation and performance which includes mapping the evolution of site development as a means of understanding the inter-and intra-organizational change in the pilot, and the application of specific evaluation metrics for assessing the implementation, operations, and performance of the NCCCP pilot. The assessment of the cost of the pilot as an additional means of informing the longer-term feasibility and sustainability of the program is also discussed.
Summary: The NCCCP is a major systems-level set of organizational innovations to enhance clinical research and care delivery in diverse communities across the United States. Assessment of the extent to which the program achieves its aims will depend on a full understanding of how individual, organizational, and environmental factors align (or fail to align) to achieve these improvements, and at what cost.
C1 [Clauser, Steven B.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Johnson, Maureen R.] NCI, Off Director, Bethesda, MD 20892 USA.
[O'Brien, Donna M.] Community Healthcare Strategies LLC, New York, NY USA.
[Beveridge, Joy M.] SAIC Frederick Inc, Clin Res Program Directorate, Frederick, MD USA.
[Fennell, Mary L.] Brown Univ, Dept Sociol, Providence, RI 02912 USA.
[Fennell, Mary L.] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA.
[Kaluzny, Arnold D.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
RP Clauser, SB (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM clausers@mail.nih.gov; johnsonm@mail.nih.gov; donnamobrien@aol.com;
jbeveridge@saic.org; Mary_Fennell@brown.edu; kaluzny@email.unc.edu
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
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 No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US government.
NR 28
TC 14
Z9 14
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1748-5908
J9 IMPLEMENT SCI
JI Implement. Sci.
PD SEP 26
PY 2009
VL 4
AR 63
DI 10.1186/1748-5908-4-63
PG 11
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 515FP
UT WOS:000271453500001
PM 19781094
ER
PT J
AU Lindstrom, KM
Guyer, AE
Mogg, K
Bradley, BP
Fox, NA
Ernst, M
Nelson, EE
Leibenluft, E
Britton, JC
Monk, CS
Pine, DS
Bar-Haim, Y
AF Lindstrom, Kara M.
Guyer, Amanda E.
Mogg, Karin
Bradley, Brendan P.
Fox, Nathan A.
Ernst, Monique
Nelson, Eric E.
Leibenluft, Ellen
Britton, Jennifer C.
Monk, Christopher S.
Pine, Daniel S.
Bar-Haim, Yair
TI Normative data on development of neural and behavioral mechanisms
underlying attention orienting toward social-emotional stimuli: An
exploratory study
SO BRAIN RESEARCH
LA English
DT Article
DE Face; Emotion; Attention; Development; fMRI; Affect
ID GENERALIZED ANXIETY DISORDER; THREATENING FACIAL EXPRESSIONS; PREFRONTAL
CORTEX ACTIVATION; ANGRY FACES; VENTRAL STRIATUM; COGNITIVE BIAS; INPUTS
DEFINE; CHILDREN; ADOLESCENTS; AMYGDALA
AB The ability of positive and negative facial signals to influence attention orienting is crucial to social functioning. Given the dramatic developmental change in neural architecture supporting social function, positive and negative facial cues may influence attention orienting differently in relatively young or old individuals. However, virtually no research examines such age-related differences in the neural circuitry supporting attention orienting to emotional faces. we examined age-related correlations in attention-orienting biases to positive and negative face emotions in a healthy sample (N=37; 9-40 years old) using functional magnetic resonance imaging and a dot-probe task. The dot-probe task in an fMRI setting yields both behavioral and neural indices of attention biases towards or away from an emotional cue (happy or angry face). In the full sample, angry-face attention bias scores did not correlate with age, and age did not correlate with brain activation to angry faces. However, age did positively correlate with attention bias towards happy faces; age also negatively correlated with left cuneus and left caudate activation to a happy bias fMRI contrast. Secondary analyses suggested age-related changes in attention bias to happy faces. The tendency in younger children to direct attention away from happy faces (relative to neutral faces) was diminished in the older age groups, in tandem with increasing neural deactivation. Implications for future work on developmental changes in attention-emotion processing are discussed. Published by Elsevier B.V.
C1 [Lindstrom, Kara M.; Guyer, Amanda E.; Ernst, Monique; Nelson, Eric E.; Leibenluft, Ellen; Britton, Jennifer C.; Pine, Daniel S.] NIMH, MAP, NIH, Bethesda, MD 20892 USA.
[Lindstrom, Kara M.] Karolinska Inst, Dept Clin Neurosci, S-10401 Stockholm, Sweden.
[Lindstrom, Kara M.] Stockholm Brain Inst, Stockholm, Sweden.
[Mogg, Karin; Bradley, Brendan P.] Univ Southampton, Dept Psychol, Southampton SO9 5NH, Hants, England.
[Fox, Nathan A.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA.
[Monk, Christopher S.] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA.
[Bar-Haim, Yair] Tel Aviv Univ, Dept Psychol, Adler Ctr Res Child Dev & Psychopathol, Tel Aviv, Israel.
RP Lindstrom, KM (reprint author), NIMH, MAP, NIH, 15K N Dr,Room 108,MSC 2670, Bethesda, MD 20892 USA.
EM lindstrk@mail.nih.gov
RI Mogg, Karin/C-1181-2008; Bradley, Brendan/B-9724-2008; Nelson,
Eric/B-8980-2008; Britton, Jennifer/J-4501-2013; Monk,
Christopher/J-1805-2014;
OI Mogg, Karin/0000-0002-2738-7378; Nelson, Eric/0000-0002-3376-2453;
Bradley, Brendan/0000-0003-2801-4271
FU National Institute of Mental Health, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health.
NR 55
TC 15
Z9 15
U1 8
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD SEP 25
PY 2009
VL 1292
BP 61
EP 70
DI 10.1016/j.brainres.2009.07.045
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 502TK
UT WOS:000270482900006
PM 19631626
ER
PT J
AU Park, JY
Wang, PY
Matsumoto, T
Sung, HJ
Ma, WZ
Choi, JW
Anderson, SA
Leary, SC
Balaban, RS
Kang, JG
Hwang, PM
AF Park, Joon-Young
Wang, Ping-yuan
Matsumoto, Takumi
Sung, Ho Joong
Ma, Wenzhe
Choi, Jeong W.
Anderson, Stasia A.
Leary, Scot C.
Balaban, Robert S.
Kang, Ju-Gyeong
Hwang, Paul M.
TI p53 Improves Aerobic Exercise Capacity and Augments Skeletal Muscle
Mitochondrial DNA Content
SO CIRCULATION RESEARCH
LA English
DT Article
DE aerobic; exercise; mitochondrial DNA; p53; TFAM
ID TRANSCRIPTION FACTOR-A; RIBONUCLEOTIDE REDUCTASE; PHYSICAL-FITNESS;
BIOGENESIS; MICE; ACTIVATION; EXPRESSION; MORTALITY; APOPTOSIS; DISEASE
AB Rationale: Exercise capacity is a physiological characteristic associated with protection from both cardiovascular and all-cause mortality. p53 regulates mitochondrial function and its deletion markedly diminishes exercise capacity, but the underlying genetic mechanism orchestrating this is unclear. Understanding the biology of how p53 improves exercise capacity may provide useful insights for improving both cardiovascular as well as general health.
Objective: The purpose of this study was to understand the genetic mechanism by which p53 regulates aerobic exercise capacity.
Methods and Results: Using a variety of physiological, metabolic, and molecular techniques, we further characterized maximum exercise capacity and the effects of training, measured various nonmitochondrial and mitochondrial determinants of exercise capacity, and examined putative regulators of mitochondrial biogenesis. As p53 did not affect baseline cardiac function or inotropic reserve, we focused on the involvement of skeletal muscle and now report a wider role for p53 in modulating skeletal muscle mitochondrial function. p53 interacts with Mitochondrial Transcription Factor A (TFAM), a nuclear-encoded gene important for mitochondrial DNA ( mtDNA) transcription and maintenance, and regulates mtDNA content. The increased mtDNA in p53(+/+) compared to p53(-/-) mice was more marked in aerobic versus glycolytic skeletal muscle groups with no significant changes in cardiac tissue. These in vivo observations were further supported by in vitro studies showing overexpression of p53 in mouse myoblasts increases both TFAM and mtDNA levels whereas depletion of TFAM by shRNA decreases mtDNA content.
Conclusions: Our current findings indicate that p53 promotes aerobic metabolism and exercise capacity by using different mitochondrial genes and mechanisms in a tissue-specific manner. (Circ Res. 2009; 105: 705-712.)
C1 [Park, Joon-Young; Wang, Ping-yuan; Matsumoto, Takumi; Sung, Ho Joong; Ma, Wenzhe; Choi, Jeong W.; Anderson, Stasia A.; Balaban, Robert S.; Kang, Ju-Gyeong; Hwang, Paul M.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Park, Joon-Young] Temple Univ, Philadelphia, PA 19122 USA.
[Leary, Scot C.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
[Leary, Scot C.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
RP Hwang, PM (reprint author), NHLBI, Translat Med Branch, NIH, 10CRC-5-5330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hwangp@mail.nih.gov
RI Leary, Scot/B-3036-2012
FU Division of Intramural Research; National Heart, Lung, and Blood
Institute; National Institutes of Health; Japan Society for the
Promotion of Science
FX This research was supported by the Division of Intramural Research,
National Heart, Lung, and Blood Institute, National Institutes of
Health, and a postdoctoral fellowship to T. M. from the Japan Society
for the Promotion of Science.
NR 51
TC 79
Z9 81
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD SEP 25
PY 2009
VL 105
IS 7
BP 705
EP U110
DI 10.1161/CIRCRESAHA.109.205310
PG 19
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 498OJ
UT WOS:000270150800013
PM 19696408
ER
PT J
AU Deschamps, A
Sun, JH
Murphy, E
AF Deschamps, Anne
Sun, Junhui
Murphy, Elizabeth
TI Increased S-Nitrosylation in Rat Hearts Treated with a G-Protein Coupled
Estrogen Receptor Agonist
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT Basic Cardiovascular Sciences Conference 2009
CY JUL 20-23, 2009
CL Lake Las Vegas, Henderson, NV
SP Amer Heart Assoc
HO Lake Las Vegas
C1 [Deschamps, Anne; Sun, Junhui; Murphy, Elizabeth] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD SEP 25
PY 2009
VL 105
IS 7
MA P216
BP E51
EP E51
PG 1
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 498OJ
UT WOS:000270150800221
ER
PT J
AU Elrod, JW
Wong, R
Karch, JM
York, AJ
Murphy, E
Molkentin, JD
AF Elrod, John W.
Wong, Renee
Karch, Jason M.
York, Allen J.
Murphy, Elizabeth
Molkentin, Jeffery D.
TI Cyclophilin-D Null Mice Display Progressive Cardiac Hypertrophy and
Failure in Response to Both Pathological and Physiological Myocardial
Stress
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT Basic Cardiovascular Sciences Conference 2009
CY JUL 20-23, 2009
CL Lake Las Vegas, Henderson, NV
SP Amer Heart Assoc
HO Lake Las Vegas
C1 [Elrod, John W.; Karch, Jason M.; York, Allen J.; Molkentin, Jeffery D.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Wong, Renee; Murphy, Elizabeth] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD SEP 25
PY 2009
VL 105
IS 7
MA P177
BP E44
EP E44
PG 1
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 498OJ
UT WOS:000270150800184
ER
PT J
AU Lagranha, C
Aponte, A
Steenbergen, C
Murphy, E
AF Lagranha, Claudia
Aponte, Angel
Steenbergen, Charles
Murphy, Elizabeth
TI Posttranslational Modification of alpha-Ketoglutarate Dehydrogenase
Results in Decrease of ROS Production
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT Basic Cardiovascular Sciences Conference 2009
CY JUL 20-23, 2009
CL Lake Las Vegas, Henderson, NV
SP Amer Heart Assoc
HO Lake Las Vegas
C1 [Lagranha, Claudia; Aponte, Angel; Murphy, Elizabeth] NHLBI, NIH, Bethesda, MD 20892 USA.
[Steenbergen, Charles] Johns Hopkins Univ, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD SEP 25
PY 2009
VL 105
IS 7
MA P131
BP E35
EP E35
PG 1
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 498OJ
UT WOS:000270150800141
ER
PT J
AU Li, Y
Sirenko, S
Lukyanenko, Y
Lyashkov, AE
Vinogradova, TM
Lakatta, EG
AF Li, Yue
Sirenko, Syevda
Lukyanenko, Yevgeniya
Lyashkov, Alexey E.
Vinogradova, Tatiana M.
Lakatta, Edward G.
TI High Basal Phosphorylation of Phospholamban at Ca2+/Calmodulin Kinase
II-Dependent Site Modulates Spontaneous Subsarcolemmal Local Ca2+
Releases that Drive Normal Automaticity of Sinoatrial Nodal Cells
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT Basic Cardiovascular Sciences Conference 2009
CY JUL 20-23, 2009
CL Lake Las Vegas, Henderson, NV
SP Amer Heart Assoc
HO Lake Las Vegas
C1 [Li, Yue; Sirenko, Syevda; Lukyanenko, Yevgeniya; Lyashkov, Alexey E.; Vinogradova, Tatiana M.; Lakatta, Edward G.] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD SEP 25
PY 2009
VL 105
IS 7
MA P17
BP E14
EP E14
PG 1
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 498OJ
UT WOS:000270150800032
ER
PT J
AU Sun, JH
Murphy, E
AF Sun, Junhui
Murphy, Elizebeth
TI Changes of Caveolar Proteome in Ischemic Preconditioned Mouse Hearts
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT Basic Cardiovascular Sciences Conference 2009
CY JUL 20-23, 2009
CL Lake Las Vegas, Henderson, NV
SP Amer Heart Assoc
HO Lake Las Vegas
C1 [Sun, Junhui; Murphy, Elizebeth] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD SEP 25
PY 2009
VL 105
IS 7
MA P135
BP E36
EP E36
PG 1
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 498OJ
UT WOS:000270150800145
ER
PT J
AU Teng, RF
Calvert, JW
Piknova, B
Schechter, AN
Lefer, DJ
Noguchi, CT
AF Teng, Ruifeng
Calvert, John W.
Piknova, Barbora
Schechter, Alan N.
Lefer, David J.
Noguchi, Constance T.
TI Exogenous Erythropoietin Cardioprotection in a Mouse
Ischemia/Reperfusion Injury Model Requires Nitric Oxide Synthase and
Endothelial Cell Response
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT Basic Cardiovascular Sciences Conference 2009
CY JUL 20-23, 2009
CL Lake Las Vegas, Henderson, NV
SP Amer Heart Assoc
HO Lake Las Vegas
C1 [Teng, Ruifeng; Piknova, Barbora; Schechter, Alan N.; Noguchi, Constance T.] NIH, Rockville, MD USA.
[Calvert, John W.; Lefer, David J.] Emory Univ, Sch Med, Carlyle Fraser Heart Ctr, Atlanta, GA USA.
RI Sun, Junhui/C-3499-2011; Calvert, John/F-4497-2014
OI Calvert, John/0000-0001-6858-6042
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD SEP 25
PY 2009
VL 105
IS 7
MA P222
BP E52
EP E52
PG 1
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 498OJ
UT WOS:000270150800227
ER
PT J
AU Wong, R
Elrod, J
Gabel, S
Steenbergen, C
Molkentin, J
Murphy, E
AF Wong, Renee
Elrod, John
Gabel, Scott
Steenbergen, Charles
Molkentin, Jeff
Murphy, Elizabeth
TI Oxidative Metabolism Is Elevated in Cyclophilin D-Knockout Mice
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT Basic Cardiovascular Sciences Conference 2009
CY JUL 20-23, 2009
CL Lake Las Vegas, Henderson, NV
SP Amer Heart Assoc
HO Lake Las Vegas
C1 [Wong, Renee; Murphy, Elizabeth] NHLBI, NIH, Bethesda, MD 20892 USA.
[Elrod, John; Molkentin, Jeff] Univ Cincinnati, Childrens Med Cntr, Cincinnati, OH USA.
[Gabel, Scott] Natl Inst Environm Hlth Sci, NIH, Rsch Triangle Pk, NC USA.
[Steenbergen, Charles] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD SEP 25
PY 2009
VL 105
IS 7
MA P60
BP E22
EP E22
PG 1
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 498OJ
UT WOS:000270150800073
ER
PT J
AU Zhou, YF
Wang, SN
Yu, ZX
Hoyt, RF
Hunter, T
Horvath, KA
AF Zhou, Yifu
Wang, Suna
Yu, Zuxi
Hoyt, Robert F., Jr.
Hunter, Timothy
Horvath, Keith A.
TI Vascular Endothelial Growth Factor Promotes Adipogenesis of Bone
Marrow-Derived Mesenchymal Stem Cells
SO CIRCULATION RESEARCH
LA English
DT Meeting Abstract
CT Basic Cardiovascular Sciences Conference 2009
CY JUL 20-23, 2009
CL Lake Las Vegas, Henderson, NV
SP Amer Heart Assoc
HO Lake Las Vegas
C1 [Zhou, Yifu; Wang, Suna; Yu, Zuxi; Hoyt, Robert F., Jr.; Hunter, Timothy; Horvath, Keith A.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7330
J9 CIRC RES
JI Circ.Res.
PD SEP 25
PY 2009
VL 105
IS 7
MA P158
BP E40
EP E41
PG 2
WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Hematology
GA 498OJ
UT WOS:000270150800167
ER
PT J
AU Cook, KM
Hilton, ST
Mecinovic, J
Motherwell, WB
Figg, WD
Schofield, CJ
AF Cook, Kristina M.
Hilton, Stephen T.
Mecinovic, Jasmin
Motherwell, William B.
Figg, William D.
Schofield, Christopher J.
TI Epidithiodiketopiperazines Block the Interaction between
Hypoxia-inducible Factor-1 alpha (HIF-1 alpha) and p300 by a Zinc
Ejection Mechanism
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID IONIZATION MASS-SPECTROMETRY; STRUCTURAL BASIS; METAL-COMPLEXES;
IN-VIVO; GLIOTOXIN; TRANSCRIPTION; SPORIDESMIN; CELLS; INHIBITOR;
PATHWAY
AB The hypoxic response in humans is regulated by the hypoxia-inducible transcription factor system; inhibition of hypoxia-inducible factor (HIF) activity has potential for the treatment of cancer. Chetomin, a member of the epidithiodiketopiperazine (ETP) family of natural products, inhibits the interaction between HIF-alpha and the transcriptional coactivator p300. Structure-activity studies employing both natural and synthetic ETP derivatives reveal that only the structurally unique ETP core is required and sufficient to block the interaction of HIF-1 alpha and p300. In support of both cell-based and animal work showing that the cytotoxic effect of ETPs is reduced by the addition of Zn2+ through an unknown mechanism, our mechanistic studies reveal that ETPs react with p300, causing zinc ion ejection. Cell studies with both natural and synthetic ETPs demonstrated a decrease in vascular endothelial growth factor and antiproliferative effects that were abrogated by zinc supplementation. The results have implications for the design of selective ETPs and for the interaction of ETPs with other zinc ion-binding protein targets involved in gene expression.
C1 [Cook, Kristina M.; Figg, William D.] NCI, NIH, Bethesda, MD 20814 USA.
[Cook, Kristina M.; Mecinovic, Jasmin; Schofield, Christopher J.] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England.
[Cook, Kristina M.; Mecinovic, Jasmin; Schofield, Christopher J.] Univ Oxford, Oxford Ctr Integrat Syst Biol, Oxford OX1 3TA, England.
[Hilton, Stephen T.] Univ London, Sch Pharm, Dept Pharmaceut & Biol Chem, London WC1N 1AX, England.
[Motherwell, William B.] UCL, Dept Chem, London WC1H 0AJ, England.
RP Figg, WD (reprint author), 10 Ctr Dr,9000 Rockville Pike,Bldg 10,Rm 5A01, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Hilton, Stephen/C-2699-2008; Cook, Kristina/B-8012-2008; Mecinovic,
Jasmin/F-9694-2015; Figg Sr, William/M-2411-2016;
OI Hilton, Stephen/0000-0001-8782-4499; Cook, Kristina/0000-0002-0503-7166;
Mecinovic, Jasmin/0000-0002-5559-3822; Schofield,
Christopher/0000-0002-0290-6565
FU National Institutes of Health [Z01SC 006538]; Cancer Research UK; The
Wellcome Trust; Biochemical and Biotechnology Research Council
FX This work was supported, in whole or in part, by the National Institutes
of Health Grant Z01SC 006538. This work was also supported by grants
from Cancer Research UK, The Wellcome Trust, and the Biochemical and
Biotechnology Research Council.
NR 40
TC 79
Z9 83
U1 4
U2 17
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 25
PY 2009
VL 284
IS 39
BP 26831
EP 26838
DI 10.1074/jbc.M109.009498
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 496KC
UT WOS:000269969600064
PM 19589782
ER
PT J
AU Plassmeyer, ML
Reiter, K
Shimp, RL
Kotova, S
Smith, PD
Hurt, DE
House, B
Zou, XY
Zhang, YL
Hickman, M
Uchime, O
Herrera, R
Nguyen, V
Glen, J
Lebowitz, J
Jin, AJ
Miller, LH
MacDonald, NJ
Wu, YM
Narum, DL
AF Plassmeyer, Matthew L.
Reiter, Karine
Shimp, Richard L., Jr.
Kotova, Svetlana
Smith, Paul D.
Hurt, Darrell E.
House, Brent
Zou, Xiaoyan
Zhang, Yanling
Hickman, Merrit
Uchime, Onyinyechukwu
Herrera, Raul
Nguyen, Vu
Glen, Jacqueline
Lebowitz, Jacob
Jin, Albert J.
Miller, Louis H.
MacDonald, Nicholas J.
Wu, Yimin
Narum, David L.
TI Structure of the Plasmodium falciparum Circumsporozoite Protein, a
Leading Malaria Vaccine Candidate
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SECONDARY STRUCTURE ANALYSES; NPNA-REPEAT MOTIF; CD8+ T-CELLS; STRUCTURE
PREDICTION; IMMUNOLOGICAL CHARACTERIZATION; INFECTED HEPATOCYTES;
BERGHEI SPOROZOITES; PROTECTIVE ANTIGEN; CRYSTAL-STRUCTURE;
HEPARAN-SULFATE
AB The Plasmodium falciparum circumsporozoite protein (CSP) is critical for sporozoite function and invasion of hepatocytes. Given its critical nature, a phase III human CSP malaria vaccine trial is ongoing. The CSP is composed of three regions as follows: an N terminus that binds heparin sulfate proteoglycans, a four amino acid repeat region (NANP), and a C terminus that contains a thrombospondin-like type I repeat (TSR) domain. Despite the importance of CSP, little is known about its structure. Therefore, recombinant forms of CSP were produced by expression in both Escherichia coli (Ec) and then refolded (EcCSP) or in the methylotrophic yeast Pichia pastoris (PpCSP) for structural analyses. To analyze the TSR domain of recombinant CSP, conformation-dependent monoclonal antibodies that recognized unfixed P. falciparum sporozoites and inhibited sporozoite invasion of HepG2 cells in vitro were identified. These monoclonal antibodies recognized all recombinant CSPs, indicating the recombinant CSPs contain a properly folded TSR domain structure. Characterization of both EcCSP and PpCSP by dynamic light scattering and velocity sedimentation demonstrated that both forms of CSP appeared as highly extended proteins (R(h) 4.2 and 4.58 nm, respectively). Furthermore, high resolution atomic force microscopy revealed flexible, rod-like structures with a ribbon-like appearance. Using this information, we modeled the NANP repeat and TSR domain of CSP. Consistent with the biochemical and biophysical results, the repeat region formed a rod-like structure about 21-25 nm in length and 1.5 nm in width. Thus native CSP appears as a glycosylphosphatidylinositol-anchored, flexible rod-like protein on the sporozoite surface.
C1 [Plassmeyer, Matthew L.; Reiter, Karine; Shimp, Richard L., Jr.; Zhang, Yanling; Hickman, Merrit; Uchime, Onyinyechukwu; Herrera, Raul; Nguyen, Vu; Glen, Jacqueline; Miller, Louis H.; MacDonald, Nicholas J.; Wu, Yimin; Narum, David L.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA.
[Kotova, Svetlana; Smith, Paul D.; Lebowitz, Jacob; Jin, Albert J.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
[Hurt, Darrell E.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct Computat Biol, NIH, Bethesda, MD 20892 USA.
[House, Brent; Zou, Xiaoyan] USN, Naval Med Res Ctr, Silver Spring, MD 20910 USA.
RP Narum, DL (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, 5640 Fishers Ln,Twinbrook 1, Rockville, MD 20852 USA.
EM dnarum@niaid.nih.gov
RI Zou, Xiaoyan/E-5564-2010; Hurt, Darrell/B-5076-2013;
OI Hurt, Darrell/0000-0002-9829-8567; Jin, Albert/0000-0003-3826-1081
FU National Institutes of Health
FX This work was supported, in whole or in part, by National Institutes of
Health (Intramural Research Program, including NIAID and National
Institute of Biomedical Imaging and Bioengineering).
NR 67
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U1 2
U2 16
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 25
PY 2009
VL 284
IS 39
BP 26951
EP 26963
DI 10.1074/jbc.M109.013706
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 496KC
UT WOS:000269969600075
PM 19633296
ER
PT J
AU Rokney, A
Shagan, M
Kessel, M
Smith, Y
Rosenshine, I
Oppenheim, AB
AF Rokney, Assaf
Shagan, Merav
Kessel, Martin
Smith, Yoav
Rosenshine, Ilan
Oppenheim, Amos B.
TI E. coli Transports Aggregated Proteins to the Poles by a Specific and
Energy-Dependent Process
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE protein aggregation; protein quality control; bacteria; pole; polar
localization
ID ESCHERICHIA-COLI; BACILLUS-SUBTILIS; QUALITY-CONTROL; CELL;
LOCALIZATION; DNAK; CHAPERONES; PROTEASES; MUTATION; DELETION
AB Aggregation of proteins due to failure of quality control mechanisms is deleterious to both eukaryotes and prokaryotes. We found that in Escherichia coli, protein aggregates are delivered to the pole and form a large polar aggregate (LPA). The formation of LPAs involves two steps: the formation of multiple small aggregates and the delivery of these aggregates to the pole to form an LPA. Formation of randomly distributed aggregates, their delivery to the poles, and LPA formation are all energy-dependent processes. The latter steps require the proton motive force, activities of the DnaK and DnaJ chaperones, and MreB. About 90 min after their formation, the LPAs are dissolved in a process that is dependent upon ClpB, DnaK, and energy. Our results confirm and substantiate the notion that the formation of LPAs allows asymmetric inheritance of the aggregated proteins to a small number of daughter cells, enabling their rapid elimination from most of the bacterial population. Moreover, the results show that the processing of aggregated proteins by the protein quality control system is a multi-step process with distinct spatial and temporal controls. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Rokney, Assaf; Shagan, Merav; Rosenshine, Ilan; Oppenheim, Amos B.] Hebrew Univ Jerusalem, Dept Microbiol & Mol Genet, IMRIC, Fac Med, IL-91120 Jerusalem, Israel.
[Kessel, Martin] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Smith, Yoav] Hebrew Univ Jerusalem, Genom Data Anal Unit, Sch Med, IL-91120 Jerusalem, Israel.
RP Rokney, A (reprint author), Hebrew Univ Jerusalem, Dept Microbiol & Mol Genet, IMRIC, Fac Med, POB 12272, IL-91120 Jerusalem, Israel.
EM assaf.rokney@mail.huji.ac.il; ilanr@ekmd.huji.ac.il
FU National Institutes of Health [R21 AI071240-01]; the Israel-United
States Bi-National Foundation; Israel Science Foundation; Israel Academy
of Science and Humanities
FX This work was supported by grants from the National Institutes of Health
(R21 AI071240-01 to Amos Oppenheim and Marcia Goldberg), the
Israel-United States Bi-National Foundation, and the Israel Science
Foundation, which was founded by the Israel Academy of Science and
Humanities. I.R. is an Etta Rosensohn Professor of Bacteriology. We
thank Ariella Oppenheim for her support and insightful comments. We
thank Nathalie Balaban and Sivan Pearl for their help with microscopy.
NR 33
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U1 2
U2 11
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD SEP 25
PY 2009
VL 392
IS 3
BP 589
EP 601
DI 10.1016/j.jmb.2009.07.009
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 500QE
UT WOS:000270317700004
PM 19596340
ER
PT J
AU Dev, K
Santangelo, TJ
Rothenburg, S
Neculai, D
Dey, M
Sicheri, F
Dever, TE
Reeve, JN
Hinnebusch, AG
AF Dev, Kamal
Santangelo, Thomas J.
Rothenburg, Stefan
Neculai, Dante
Dey, Madhusudan
Sicheri, Frank
Dever, Thomas E.
Reeve, John N.
Hinnebusch, Alan G.
TI Archaeal aIF2B Interacts with Eukaryotic Translation Initiation Factors
eIF2 alpha and eIF2B alpha: Implications for aIF2B Function and eIF2B
Regulation
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE aIF2B; eIF2; eIF2B; archaea; S. cerevisiae
ID GUANINE-NUCLEOTIDE-EXCHANGE; GDP-GTP EXCHANGE; PYROCOCCUS-HORIKOSHII
OT3; PROTEIN-KINASE PKR; CRYSTAL-STRUCTURE; THERMOCOCCUS-KODAKARAENSIS;
SACCHAROMYCES-CEREVISIAE; FACTOR-II; IN-VITRO; GCN4
AB Translation initiation is down-regulated in eukaryotes by phosphorylation of the alpha-subunit of eIF2 (eukaryotic initiation factor 2), which inhibits its guanine nucleotide exchange factor, eIF2B. The N-terminal S1 domain of phosphorylated eIF2 alpha interacts with a subcomplex of eIF2B formed by the three regulatory subunits alpha/GCN3, beta/GCD7, and delta/GCD2, blocking the GDP-GTP exchange activity of the catalytic epsilon-subunit of eIF2B. These regulatory subunits have related sequences and have sequences in common with many archaeal proteins, some of which are involved in methionine salvage and CO(2) fixation. Our sequence analyses however predicted that members of one phylogenetically distinct and coherent group of these archaeal proteins [designated aIF2Bs (archaeal initiation factor 2Bs)] are functional homologs of the alpha, beta, and delta subunits of eIF2B. Three of these proteins, from different archaea, have been shown to bind in vitro to the alpha-subunit of the archaeal aIF2 from the cognate archaeon. In one case, the aIF2B protein was shown further to bind to the S1 domain of the alpha-subunit of yeast eIF2 in vitro and to interact with eIF2B alpha/GCN3 in vivo in yeast. The aIF2B-eIF2 alpha interaction was however independent of eIF2 alpha phosphorylation. Mass spectrometry has identified several proteins that co-purify with alpha IF2B from Thermococcus kodakaraensis, and these include aIF2 alpha, a sugar-phosphate nucleotidyltransferase with sequence similarity to eIF2B epsilon, and several large-subunit (50S) ribosomal proteins. Based on this evidence that aIF2B has functions in common with eIF2B, the crystal structure established for an aIF2B was used to construct a model of the eIF2B regulatory subcomplex. In this model, the evolutionarily conserved regions and sites of regulatory mutations in the three eIF2B subunits in yeast are juxtaposed in one continuous binding surface for phosphorylated eIF2 alpha. Published by Elsevier Ltd.
C1 [Dev, Kamal; Rothenburg, Stefan; Dey, Madhusudan; Dever, Thomas E.; Hinnebusch, Alan G.] NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA.
[Santangelo, Thomas J.; Reeve, John N.] Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA.
[Neculai, Dante; Sicheri, Frank] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
RP Hinnebusch, AG (reprint author), NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA.
EM ahinnebusch@nih.gov
RI Rothenburg, Stefan/A-8340-2008; Neculai, Dante/A-9923-2011; Sicheri,
Frank/F-8856-2013; Neculai, Dante/M-2884-2013;
OI Dever, Thomas/0000-0001-7120-9678
FU Intramural Research Program of the National Institutes oNational
Institutes of Health [GM53185]; Canadian Cancer Society
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Institutes of Health grant
GM53185 to J.N.R., and by the Canadian Cancer Society for ES. and D.N.
We thank Ernie Hannig for GCD11 antibodies, Hongfang Qiu and Graham
Pavitt for assistance and advice to K.D., and Loubna Tazi for comments
on the manuscript.
NR 46
TC 14
Z9 15
U1 0
U2 6
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD SEP 25
PY 2009
VL 392
IS 3
BP 701
EP 722
DI 10.1016/j.jmb.2009.07.030
PG 22
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 500QE
UT WOS:000270317700013
PM 19616556
ER
PT J
AU Sauder, CJ
Zhang, CX
Link, MA
Duprex, WP
Carbone, KM
Rubin, SA
AF Sauder, Christian J.
Zhang, Cheryl X.
Link, Malen A.
Duprex, W. Paul
Carbone, Kathryn M.
Rubin, Steven A.
TI Presence of lysine at aa 335 of the hemagglutinin-neuraminidase protein
of mumps virus vaccine strain Urabe AM9 is not a requirement for
neurovirulence
SO VACCINE
LA English
DT Article
DE Mumps virus; Urabe AM9 vaccine; Neurovirulence
ID NUCLEOTIDE-SEQUENCE; POSITION 1081; SAFETY TEST; IN-VITRO; SH GENE;
P-GENE; F-GENE; PARAMYXOVIRUS; TRANSCRIPTION; MUTATIONS
AB The recent global resurgence of mumps has drawn attention to the continued need for robust mumps immunization programs. Unfortunately, some vaccines derived from inadequately attenuated vaccine strains of mumps virus have caused meningitis in vaccinees, leading to withdrawal of certain vaccine strains from the market, public resistance to vaccination, or in some cases, cessation of national mumps vaccination programs. The most widely implicated mumps vaccine in cases of postvaccination meningitis is derived from the Urabe AM9 strain, which remains in use in some countries. The Urabe AM9 vaccine virus has been shown to exhibit a considerable degree of nucleotide and amino acid heterogeneity. Some studies have specifically implicated variants containing a lysine residue at amino acid position 335 in the hemagglutinin-neuraminidase (HN) protein with neurotoxicity, whereas a glutamic acid residue at this position was associated with attenuation. To test this hypothesis we generated two modified Urabe AM9 cDNA clones coding either for a lysine or a glutamic acid at position 335 in the HN gene. The two viruses were rescued by reverse genetics and characterized in vitro and in vivo. Both viruses exhibited similar growth kinetics in neuronal and non-neuronal cell lines and were of similar neurotoxicity when tested in rats, suggesting that amino acid 335 is not a crucial determinant of Urabe AM9 growth or neurovirulence. Published by Elsevier Ltd.
C1 [Sauder, Christian J.; Zhang, Cheryl X.; Link, Malen A.; Rubin, Steven A.] US FDA, DVP, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Duprex, W. Paul] Queens Univ Belfast, Sch Biomed Sci, Belfast BT9 7BL, Antrim, North Ireland.
[Carbone, Kathryn M.] Natl Inst Dent & Craniefacial Res, NIH, Bethesda, MD 20892 USA.
RP Sauder, CJ (reprint author), US FDA, DVP, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, 8800 Rockville Pike,Bldg 29A,HFM 460,Room 2C20, Bethesda, MD 20892 USA.
EM christian.sauder@fda.hhs.gov
OI Duprex, W Paul/0000-0003-1716-6376
NR 42
TC 6
Z9 6
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD SEP 25
PY 2009
VL 27
IS 42
BP 5822
EP 5829
DI 10.1016/j.vaccine.2009.07.051
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 502ON
UT WOS:000270469900017
PM 19660591
ER
PT J
AU Santra, S
Sun, Y
Korioth-Schmitz, B
Fitzgerald, J
Charbonneau, C
Santos, G
Seaman, MS
Ratcliffe, SJ
Monteflori, DC
Nabel, GJ
Ertl, HCJ
Letvin, NL
AF Santra, Sampa
Sun, Yue
Korioth-Schmitz, Birgit
Fitzgerald, Julie
Charbonneau, Cherie
Santos, Giannina
Seaman, Michael S.
Ratcliffe, Sarah J.
Monteflori, David C.
Nabel, Gary J.
Ertl, Hildegund C. J.
Letvin, Norman L.
TI Heterologous prime/boost immunizations of rhesus monkeys using
chimpanzee adenovirus vectors
SO VACCINE
LA English
DT Article
DE Chimpanzee adenovirus; HIV-1 vaccine
ID IMMUNODEFICIENCY-VIRUS TYPE-1; IMMUNE-RESPONSES; NEUTRALIZING
ANTIBODIES; VACCINE CARRIERS; NONHUMAN-PRIMATES; SIV CHALLENGE; HIV-1
VACCINE; VIREMIA; STEP; IMMUNOGENICITY
AB Pre-existing immunity to human adenovirus serotype 5 (AdHu5) has been shown to suppress the immunogenicity of recombinant Ad5 (rAdHu5) vector-based vaccines for human immunodeficiency virus type 1 (HIV-1) in both preclinical studies and clinical trials. As a potential solution to this problem we developed adenovirus vaccine vectors of chimpanzee origin. In the present study we assessed the immunogenicity of various chimpanzee adenovirus vectors in a prime/boost regimen to HIV-1 envelope and SIV Gag-Pol in rhesus monkeys and their ability to protect against pathogenic viral challenge. Although rAdHu5-primed monkeys had higher magnitude T cell responses than rAdC7 or rAdC68 prior to challenge, the rAdC7-rAdC1/C5 and rAdHu5-rAdC1/C5 immunizations resulted in comparable magnitude recall cellular immune responses and comparable level of control of viremia post-challenge. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Letvin, Norman L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis,Dept Med, Boston, MA 02215 USA.
[Fitzgerald, Julie; Ratcliffe, Sarah J.; Ertl, Hildegund C. J.] Univ Penn, Sch Med, Wistar Inst, Philadelphia, PA 19104 USA.
[Monteflori, David C.] Duke Univ, Med Ctr, Dept Surg, Lab AIDS Vaccine Res & Dev, Durham, NC 27710 USA.
[Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Letvin, NL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis,Dept Med, E-CLS-1043,3 Blackfan Circle, Boston, MA 02215 USA.
EM nletvin@bidmc.harvard.edu
RI Korioth-Schmitz, Birgit/M-7816-2015;
OI Korioth-Schmitz, Birgit/0000-0002-5271-9223; Ratcliffe,
Sarah/0000-0002-6644-8284
FU NIH [P01-A152271, Al060354]; Harvard University Center for AIDS Research
(CFAR)
FX This work was supported by NIH grant P01-A152271 and Harvard University
Center for AIDS Research (CFAR) program grant NIH Al060354.
NR 34
TC 31
Z9 31
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD SEP 25
PY 2009
VL 27
IS 42
BP 5837
EP 5845
DI 10.1016/j.vaccine.2009.07.050
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 502ON
UT WOS:000270469900019
PM 19660588
ER
PT J
AU Earl, PL
Cotter, C
Moss, B
VanCott, T
Currier, J
Eller, LA
McCutchan, F
Birx, DL
Michael, NL
Marovich, MA
Robb, M
Earla, PL
AF Earl, Patricia L.
Cotter, Catherine
Moss, Bernard
VanCott, Thomas
Currier, Jeffrey
Eller, Leigh Anne
McCutchan, Francine
Birx, Deborah L.
Michael, Nelson L.
Marovich, Mary A.
Robb, Merlin
Earla, Patricia L.
TI Design and evaluation of multi-gene, multi-clade HIV-1 MVA vaccines
SO VACCINE
LA English
DT Article
DE MVA; HIV vaccine; Immune response
ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VITRO EXPRESSION; TYPE-1 SUBTYPE-C;
T-CELL EPITOPES; ANKARA MVA; ENVELOPE GLYCOPROTEIN; IMMUNE-RESPONSES;
RHESUS-MONKEYS; GAG-POL; PROTECTIVE IMMUNITY
AB Recombinant modified vaccinia virus Ankara (rMVA) expressing HIV-1 genes are promising vaccine candidates. Toward the goal of conducting clinical trials with one or a cocktail of recombinant viruses, four rMVAs expressing env and gag-pol genes from primary HIV-1 isolates representing predominant subtypes from Kenya, Tanzania, Uganda, and Thailand (A, C, D, and CRF01_AE, respectively) were constructed. Efficient expression, processing, and function of Env and Gag were demonstrated. All inserted genes were shown to be genetically stable after repeated passage in cell culture. Strong HIV-specific cellular and humoral immune responses were elicited in mice immunized with each individual vaccine candidate. The MVA/CMDR vaccine candidate expressing CRF01_AE genes has elicited HIV-specific T-cell responses in two independent Phase I clinical trials. Further testing of the other rMVA is warranted. Published by Elsevier Ltd.
C1 [Earl, Patricia L.; Cotter, Catherine; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Cotter, Catherine; VanCott, Thomas; Currier, Jeffrey; Eller, Leigh Anne; McCutchan, Francine; Birx, Deborah L.; Michael, Nelson L.; Marovich, Mary A.; Robb, Merlin; Earla, Patricia L.] Walter Reed Army Inst Res, Mil HIV Res Program, Rockville, MD USA.
RP Earl, PL (reprint author), NIAID, Viral Dis Lab, NIH, 33 North Dr,MSC 3210, Bethesda, MD 20892 USA.
EM pearl@niaid.nih.gov
FU Intramural Research Program; National Institute of Allergy and
Infectious Diseases; U.S. Army Medical Research and Materiel Command
[DAMD17-98-27007]
FX This work was supported in part by the Intramural Research Program,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health and by the U.S. Army Medical Research and Materiel
Command and its Cooperative Agreement (DAMD17-98-27007) with the Henry
M. Jackson Foundation for the Advancement of Military Medicine. The
opinions or assertions contained herein are the private views of the
author, and are not to be construed as official, or as reflecting true
views of the Department of the Army or the Department of Defense.
Research was conducted in compliance with the Animal Welfare Act and
other federal statutes and regulations relating to animals and
experiments involving animals and adheres to principles stated in the
Guidefor the Care and Use of Laboratory Animals, NRC Publication, 1996
edition.
NR 80
TC 34
Z9 36
U1 1
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD SEP 25
PY 2009
VL 27
IS 42
BP 5885
EP 5895
DI 10.1016/j.vaccine.2009.07.039
PG 11
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 502ON
UT WOS:000270469900025
PM 19654066
ER
PT J
AU Hager, GL
McNally, JG
Misteli, T
AF Hager, Gordon L.
McNally, James G.
Misteli, Tom
TI Transcription Dynamics
SO MOLECULAR CELL
LA English
DT Review
ID RNA-POLYMERASE-II; EMBRYONIC STEM-CELLS; ESTROGEN-RECEPTOR-ALPHA;
BETA-GLOBIN LOCUS; TATA-BINDING PROTEIN; INTERACTIONS IN-VIVO;
GLUCOCORTICOID-RECEPTOR; LIVING CELLS; GENE-EXPRESSION; ANDROGEN
RECEPTOR
AB All aspects of transcription and its regulation involve dynamic events. The basal transcription machinery and regulatory components are dynamically recruited to their target genes, and dynamic interactions of transcription factors with chromatin-and with each other-play a key role in RNA polymerase assembly, initiation, and elongation. These short-term binding dynamics of transcription factors are superimposed by long-term cyclical behavior of chromatin opening and transcription factor-binding events. Its dynamic nature is not only a fundamental property of the transcription machinery, but it is emerging as an important modulator of physiological processes, particularly in differentiation and development.
C1 [Hager, Gordon L.; McNally, James G.; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
RP Hager, GL (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM hagerg@mail.nih.gov; mcnallyj@mail.nih.gov; mistelit@mail.nih.gov
FU Intramural NIH HHS [Z01 BC010309-10]
NR 110
TC 259
Z9 261
U1 3
U2 37
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD SEP 24
PY 2009
VL 35
IS 6
BP 741
EP 753
DI 10.1016/j.molcel.2009.09.005
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 503SE
UT WOS:000270559100009
PM 19782025
ER
PT J
AU Volberding, P
Demeter, L
Bosch, RJ
Aga, E
Pettinelli, C
Hirsch, M
Vogler, M
Martinez, A
Little, S
Connick, E
AF Volberding, Paul
Demeter, Lisa
Bosch, Ronald J.
Aga, Evgenia
Pettinelli, Carla
Hirsch, Martin
Vogler, Mary
Martinez, Ana
Little, Susan
Connick, Elizabeth
CA ACTG 371 Team
TI Antiretroviral therapy in acute and recent HIV infection: a prospective
multicenter stratified trial of intentionally interrupted treatment
SO AIDS
LA English
DT Article; Proceedings Paper
CT 15th Conference on Retroviruses and Opportunistic Infections
CY FEB 03-06, 2008
CL Boston, MA
DE acute HIV infection; antiretroviral therapy; primary HIV infection;
recent HIV infection; treatment interruption
ID STRUCTURED TREATMENT INTERRUPTIONS; NATURAL-HISTORY; VIRAL LOAD; IMMUNE
ACTIVATION; LYMPHOID-TISSUE; RNA LEVELS; SET-POINT; T-CELLS; VIRUS; AIDS
AB Background: Antiretroviral therapy in early HIV infection may enhance outcome and viral control may be better in acute versus recent infection 24 weeks after treatment interruption.
Methods: A prospective trial of treatment stratified by acute versus recent HIV-1 infection. If HIV viral load <50 copies/ml after at least 52 weeks, treatment was interrupted. If viremia rebounded, treatment and interruption were repeated. The primary endpoint was maintaining viral load less than 5000 copies/ml for 24 weeks following treatment interruption.
Results: Of the 121 patients enrolled at 15 sites, ninety-five percent were men, median age was 34 years; 69% were white. Median viral load was higher in acute HIV-1 infection (210000 copies/ml) than recent HIV-1 infection (43000 copies/ml). The 73 primary endpoint patients (28 acute HIV-1 infection, 45 recent HIV-1 infection) had significantly higher baseline CD4(+) T-cell Counts (P=0.044) and lower viral load (P=0.016). The primary endpoint was achieved in 29 (40%) of the 73 and in 24% of the 121 enrolled overall. There was no significant outcome difference (P=0.81) between the acute HIV-1 infection [43%, 95% confidence interval (CI) 24-63%] and recent HIV-1 infection (38%, 95% CI 24-53%) groups. Differences after longer follow-up can not be ascertained by this trial. Baseline viral load less than 100000/ml 22/46 (48%) compared with more than 100000/ml, 7/27 (26%) and higher baseline CD4(+) immune activation predicted success.
Conclusion: Forty percent of patients treated during acute HIV-1 infection or recent HIV-1 infection sustained a viral load less than 5000 copies/ml after 24 weeks of treatment interruption. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Volberding, Paul] Univ Calif San Francisco, San Francisco, CA 94121 USA.
[Demeter, Lisa] Univ Rochester, Rochester, NY USA.
[Bosch, Ronald J.; Aga, Evgenia; Hirsch, Martin] Harvard Univ, Boston, MA 02115 USA.
[Pettinelli, Carla; Martinez, Ana] NIAID, Bethesda, MD 20892 USA.
[Vogler, Mary] Cornell Univ, New York, NY 10021 USA.
[Little, Susan] Univ Calif San Diego, San Diego, CA 92103 USA.
[Connick, Elizabeth] Univ Colorado, Denver, CO 80202 USA.
RP Volberding, P (reprint author), Univ Calif San Francisco, 4150 Clement St, San Francisco, CA 94121 USA.
EM Paul.volberding@va.gov
FU NIAID NIH HHS [AI-38858, AI-68634, AI 69450, AI-68636, AI-69432, P30
AI027763, P30 AI027763-19, AI-38855, U01 AI038855, U01 AI038858, U01
AI068636, U01 AI069450, UM1 AI068636, UM1 AI069450]
NR 27
TC 35
Z9 35
U1 0
U2 2
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 SEP 24
PY 2009
VL 23
IS 15
BP 1987
EP 1995
DI 10.1097/QAD.0b013e32832eb285
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 502QP
UT WOS:000270475400007
PM 19696651
ER
PT J
AU Porter, BO
Shen, J
Kovacs, JA
Davey, RT
Rehm, C
Lozier, J
Csako, G
Nghiem, K
Costello, R
Lane, HC
Sereti, I
AF Porter, Brian O.
Shen, Jean
Kovacs, Joseph A.
Davey, Richard T.
Rehm, Catherine
Lozier, Jay
Csako, Gyorgy
Nghiem, Khanh
Costello, Rene
Lane, Henry Clifford
Sereti, Irini
TI Interleukin-2 cycling causes transient increases in high-sensitivity
C-reactive protein and D-dieter that are not associated with plasma
HIV-RNA levels
SO AIDS
LA English
DT Article; Proceedings Paper
CT 16th Conference on Retroviruses and Opportunistic Infections
CY FEB 08-11, 2009
CL Montreal, CANADA
DE C-reactive protein; D-dimer; HIV infections; interleukin-2; randomized
controlled trial
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED INTERNATIONAL TRIAL;
ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; ACUTE-PHASE; IL-2;
ACTIVATION; MARKERS; IMMUNOTHERAPY; INTERRUPTION
AB Objective: To determine the effects of interleukin (IL)-2 treatment on inflammatory and thrombotic biomarkers in chronically HIV-infected adults receiving antiretroviral therapy.
Methods: Cryopreserved plasma was evaluated retrospectively for C-reactive protein (CRP) and D-dieter at baseline, end of an IL-2 cycle, and long-term follow up from two randomized, controlled trials: 57 IL-2-naive adults receiving either three to six cycles of IL-2 as well as antiretroviral therapy (nucleoside analogues) or antiretroviral therapy alone for 12 months, and 40 IL-2-experienced adults on highly active antiretroviral therapy who either interrupted or continued therapy for 6 months after a baseline IL-2 cycle. High-sensitivity CRP (hsCRP) was measured by immunonephelometry (detection limit 0.175 mg/l) and D-dimer by latex agglutination (detection limit 0.20 mg/l). Median within group differences and pre and post-IL-2 changes between groups were assessed via nonparametric Wilcoxon signed-rank and Mann-Whitney U-tests. Spearman's rank test was used to assess correlations between changes in hsCRP, D-dieter, and HIV-RNA viral load.
Results: Significant increases in hsCRP (study 1: 138.6 mg/l; study 2: 58.9 mg/l) and D-dieter (study 1: 3.1 mg/l; study 2: 0.4 mg/l, all P < 0.0001) occurred by the end of the initial IL-2 cycle, returning to baseline by the end of study. No correlations were seen between changes in hsCRP or D-dieter and HIV-RNA, CD4 T-cell count, or proliferation (Ki67 expression). No thrombotic or cardiovascular serious adverse events occurred during these study periods.
Conclusion: IL-2 dosing caused transient increases in plasma hsCRP and D-dieter levels, regardless of HIV-RNA viral load, suggesting the possibility of increased risk for thrombotic events. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Sereti, Irini] NIAID, NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Shen, Jean] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Lozier, Jay; Csako, Gyorgy; Nghiem, Khanh; Costello, Rene] NIH, CC, Dept Lab Med, Bethesda, MD 20892 USA.
RP Sereti, I (reprint author), NIAID, NIH, Ctr Clin, Bldg 10,Room 11B07A,10 Ctr Dr, Bethesda, MD 20892 USA.
EM isereti@niaid.nih.gov
FU Intramural NIH HHS [Z01 AI000585-18]
NR 22
TC 14
Z9 15
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD SEP 24
PY 2009
VL 23
IS 15
BP 2015
EP 2019
DI 10.1097/QAD.0b013e32832d72c6
PG 5
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 502QP
UT WOS:000270475400010
PM 19617815
ER
PT J
AU Pulsipher, MA
Chitphakdithai, P
Logan, BR
Leitman, SF
Anderlini, P
Klein, JP
Horowitz, MM
Miller, JP
King, RJ
Confer, DL
AF Pulsipher, Michael A.
Chitphakdithai, Pintip
Logan, Brent R.
Leitman, Susan F.
Anderlini, Paolo
Klein, John P.
Horowitz, Mary M.
Miller, John P.
King, Roberta J.
Confer, Dennis L.
TI Donor, recipient, and transplant characteristics as risk factors after
unrelated donor PBSC transplantation: beneficial effects of higher
CD34(+) cell dose
SO BLOOD
LA English
DT Article
ID VERSUS-HOST-DISEASE; BLOOD STEM-CELLS; COLONY-STIMULATING FACTOR;
IDENTICAL SIBLING TRANSPLANTATION; ACUTE MYELOCYTIC-LEUKEMIA; CHRONIC
MYELOID-LEUKEMIA; BONE-MARROW TRANSPLANTS; PERIPHERAL-BLOOD; HEMATOLOGIC
MALIGNANCIES; GRAFT-REJECTION
AB We report outcomes of 932 recipients of unrelated donor peripheral blood stem cell hematopoietic cell transplantation (URD-PBSC HCT) for acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome enrolled on a prospective National Marrow Donor Program trial from 1999 through 2003. Preparative regimens included myeloablative (MA; N = 611), reduced-intensity (RI; N = 160), and nonmyeloablative (NMA; N = 161). For MA recipients, CD34(+) counts greater than 3.8 X 10(6)/kg improved neutrophil and platelet engraftment, whereas improved overall survival (OS) and reduced transplant-related mortality (TRM) were seen for all preparative regimens when CD34(+) cell doses exceeded 4.5 X 10(6)/kg. Higher infused doses of CD34(+) cell dose did not result in increased rates of either acute or chronic graft-versus-host disease (GVHD). Three-year OS and disease-free survival (DFS) of recipients of MA, RI, and NMA approaches were similar (33%, 35%, and 32% OS; 33%, 30%, and 29% DFS, respectively). In summary, recipients of URD-PBSC HCT receiving preparative regimens differing in intensity experienced similar survival. Higher CD34(+) cell doses resulted in more rapid engraftment, less TRM, and better 3-year OS (39% versus 25%, MA, P = .004; 38% versus 21% RI/NMA, P = .004) but did not increase the risk of GVHD. This trial was registered at www.clinicaltrials.gov as #NCT00785525. (Blood. 2009; 114: 2606-2616)
C1 [Pulsipher, Michael A.] Univ Utah, Sch Med, Primary Childrens Hosp, Salt Lake City, UT 84132 USA.
[Chitphakdithai, Pintip; King, Roberta J.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Logan, Brent R.; Klein, John P.; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Leitman, Susan F.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Miller, John P.; Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA.
RP Pulsipher, MA (reprint author), Univ Utah, Sch Med, Div Hematol Blood & Marrow Transplant, 30 North,1900 East,Rm 5C402, Salt Lake City, UT 84132 USA.
EM michael.pulsipher@hsc.utah.edu
FU National Marrow Donor Program and the Health Resources and Services
Administration [240-97-0036, 231-02-0007]; National Cancer Institute
[U24-CA76518]; National Institute of Allergy and Infectious Diseases;
National Heart, Lung and Blood Institute; Office of Naval Research;
Health Services Research Administration (DHHS); Abbott Laboratories;
Aetna; American International Group Inc; American Red Cross; Amgen Inc;
AnorMED Inc; Astellas Pharma US Inc; Baxter International Inc; Berlex
Laboratories Inc; Biogen IDEC Inc; BloodCenter of Wisconsin; Blue Cross
and Blue Shield Association; Bristol-Myers Squibb Company; BRT
Laboratories Inc; Cangene Corporation; Celgene Corporation; CellGenix
Inc; Cell Therapeutics Inc; CelMed Biosciences; Cylex Inc; Cytonome Inc;
CytoTherm; DOR BioPharma Inc; Dynal Biotech, an Invitrogen Company;
Enzon Pharmaceuticals Inc; Gambro BCT Inc; Gamida Cell Ltd; Genzyme
Corporation; Gift of Life Bone Marrow Foundation; GlaxoSmithKline Inc;
Histogenetics Inc; HKS Medical Information Systems; Kirin Brewery Co
Ltd; Merck Company; The Medical College of Wisconsin; Millennium
Pharmaceuticals Inc; Miller Pharmacal Group; Milliman USA Inc; Miltenyi
Biotec Inc; MultiPlan Inc; National Marrow Donor Program; Nature
Publishing Group; Novartis Pharmaceuticals Inc; Osiris Therapeutics Inc;
Pall Medical; Pfizer Inc; Pharmion Corporation; PDL BioPharma, Inc;
Roche Laboratories; Sanofi-aventis; Schering Plough Corporation;
StemCyte Inc; StemSoft Software Inc; SuperGen, Inc; Sysmex; The Marrow
Foundation; THERAKOS Inc; University of Colorado Cord Blood Bank;
ViaCell Inc; University of Colorado Cord Blood Bank; ViaCell Inc;
ViraCor Laboratories; Wellpoint Inc; Zelos Therapeutics Inc;
Bundesministerium fur Bildung und Forschung (Kompetenznetz "Akute und
chronische Leukamien" Germany [01GI9981]
FX This work was supported by funding from the National Marrow Donor
Program and the Health Resources and Services Administration (contract
Nos. 240-97-0036 and 231-02-0007) to the National Marrow Donor Program.
The CIBMTR is supported by the National Cancer Institute (Public Health
Service grant U24-CA76518), the National Institute of Allergy and
Infectious Diseases, and the National Heart, Lung and Blood Institute;
Office of Naval Research; Health Services Research Administration
(DHHS); and grants from Abbott Laboratories; Aetna; American
International Group Inc; American Red Cross; Amgen Inc; Anonymous
donation to the Medical College of Wisconsin; AnorMED Inc; Astellas
Pharma US Inc; Baxter International Inc; Berlex Laboratories Inc; Biogen
IDEC Inc; BloodCenter of Wisconsin; Blue Cross and Blue Shield
Association; Bristol-Myers Squibb Company; BRT Laboratories Inc; Cangene
Corporation; Celgene Corporation; CellGenix Inc; Cell Therapeutics Inc;
CelMed Biosciences; Cylex Inc; Cytonome Inc; CytoTherm; DOR BioPharma
Inc; Dynal Biotech, an Invitrogen Company; Enzon Pharmaceuticals Inc;
Gambro BCT Inc; Gamida Cell Ltd; Genzyme Corporation; Gift of Life Bone
Marrow Foundation; GlaxoSmithKline Inc; Histogenetics Inc; HKS Medical
Information Systems; Kirin Brewery Co Ltd; Merck & Company; The Medical
College of Wisconsin; Millennium Pharmaceuticals Inc; Miller Pharmacal
Group; Milliman USA Inc; Miltenyi Biotec Inc; MultiPlan Inc; National
Marrow Donor Program; Nature Publishing Group; Novartis Pharmaceuticals
Inc; Osiris Therapeutics Inc; Pall Medical; Pfizer Inc; Pharmion
Corporation; PDL BioPharma, Inc; Roche Laboratories; Sanofi-aventis;
Schering Plough Corporation; StemCyte Inc; StemSoft Software Inc;
SuperGen, Inc; Sysmex; The Marrow Foundation; THERAKOS Inc; University
of Colorado Cord Blood Bank; ViaCell Inc; ViraCor Laboratories;
Wellpoint Inc; and Zelos Therapeutics Inc. The German AML Intergroup is
supported by the Bundesministerium fur Bildung und Forschung
(Kompetenznetz "Akute und chronische Leukamien"; grant 01GI9981),
Germany.; The views expressed in this article do not reflect the
official policy or position of the Health Resources and Services
Administration, the National Marrow Donor Program, the National
Institute of Health, the Department of the Navy, the Department of
Defense, or any other agency of the US government.
NR 46
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U2 6
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD SEP 24
PY 2009
VL 114
IS 13
BP 2606
EP 2616
DI 10.1182/blood-2009-03-208355
PG 11
WC Hematology
SC Hematology
GA 498KK
UT WOS:000270138600011
PM 19608747
ER
PT J
AU Dyer, KD
Percopo, CM
Fischer, ER
Gabryszewski, SJ
Rosenberg, HF
AF Dyer, Kimberly D.
Percopo, Caroline M.
Fischer, Elizabeth R.
Gabryszewski, Stanislaw J.
Rosenberg, Helene F.
TI Pneumoviruses infect eosinophils and elicit MyD88-dependent release of
chemoattractant cytokines and interleukin-6
SO BLOOD
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; AIRWAY EPITHELIAL-CELLS; INDUCED CHEMOKINE
EXPRESSION; PNEUMONIA VIRUS; INTERFERON-GAMMA; HOST-DEFENSE; PULMONARY
EOSINOPHILIA; MICE PVM; ASTHMA; DEGRANULATION
AB Eosinophils are recruited to the lung in response to infection with pneumovirus pathogens and have been associated with both the pathophysiologic sequelae of infection and, more recently, with accelerated virus clearance. Here, we demonstrate that the pneumovirus pathogens, respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM), can infect human and mouse eosinophils, respectively, and that virus infection of eosinophils elicits the release of disease-related proinflammatory mediators from eosinophils. RSV replication in human eosinophils results in the release of infectious virions and in the release of the proinflammatory mediator, interleukin-6 (IL-6). PVM replication in cultured bone marrow eosinophils (bmEos) likewise results in release of infectious virions and the proinflammatory mediators IL-6, IP-10, CCL2, and CCL3. In contrast to the findings reported in lung tissue of RSV-challenged mice, PVM replication is accelerated in MyD88 gene-deleted bmEos, whereas release of cytokines is diminished. Interestingly, exogenous IL-6 suppresses virus replication in MyD88 gene-deleted bmEos, suggesting a role for a MyD88-dependent cytokine-mediated feedback circuit in modulating this response. Taken together, our findings suggest that eosinophils are targets of virus infection and may have varied and complex contributions to the pathogenesis and resolution of pneumovirus disease. (Blood. 2009; 114: 2649-2656)
C1 [Dyer, Kimberly D.; Percopo, Caroline M.; Gabryszewski, Stanislaw J.; Rosenberg, Helene F.] NIAID, Eosinophil Biol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Fischer, Elizabeth R.] NIAID, Res Technol Branch, Rocky Mt Labs, NIH, Hamilton, MN USA.
RP Dyer, KD (reprint author), 10 Ctr Dr,Bldg 10 Rm 11C216, Bethesda, MD 20892 USA.
EM kdyer@niaid.nih.gov
FU Division Intramural Research (DIR); NIAID
FX This work is supported by Division Intramural Research (DIR) funding
from the NIAID ( H. F. R.).
NR 58
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U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 24
PY 2009
VL 114
IS 13
BP 2649
EP 2656
DI 10.1182/blood-2009-01-199497
PG 8
WC Hematology
SC Hematology
GA 498KK
UT WOS:000270138600017
PM 19652202
ER
PT J
AU Bryceson, YT
Ljunggren, HG
Long, EO
AF Bryceson, Yenan T.
Ljunggren, Hans-Gustaf
Long, Eric O.
TI Minimal requirement for induction of natural cytotoxicity and
intersection of activation signals by inhibitory receptors
SO BLOOD
LA English
DT Article
ID LEUKOCYTE ADHESION DEFICIENCY; RESTING NK CELLS; SEQUENCE-DERIVED
PEPTIDES; MHC CLASS-I; HLA-E BINDS; KILLER-CELLS; TYROSINE
PHOSPHORYLATION; INTEGRIN ACTIVATION; CROSS-LINKING; FC-RECEPTORS
AB Natural killer (NK) cells provide innate control of infected and neoplastic cells. Multiple receptors have been implicated in natural cytotoxicity, but their individual contribution remains unclear. Here, we studied the activation of primary, resting human NK cells by Drosophila cells expressing ligands for receptors NKG2D, DNAM-1, 2B4, CD2, and LFA-1. Each receptor was capable of inducing inside-out signals for LFA-1, promoting adhesion, but none induced degranulation. Rather, release of cytolytic granules required synergistic activation through co-engagement of receptors, shown here for NKG2D and 2B4. Although engagement of NKG2D and 2B4 was not sufficient for strong target cell lysis, collective engagement of LFA-1, NKG2D, and 2B4 defined a minimal requirement for natural cytotoxicity. Remarkably, inside-out signaling induced by each one of these receptors, including LFA-1, was inhibited by receptor CD94/NKG2Abinding to HLA-E. Strong inside-out signals induced by the combination of NKG2D and 2B4 or by CD16 could overcome CD94/NKG2A inhibition. In contrast, degranulation induced by these receptors was still subject to inhibition by CD94/NKG2A. These results reveal multiple layers in the activation pathway for natural cytotoxicity and that steps as distinct as inside-out signaling to LFA-1 and signals for granule release are sensitive to inhibition by CD94/NKG2A. (Blood. 2009; 114: 2657-2666)
C1 [Bryceson, Yenan T.; Ljunggren, Hans-Gustaf] Karolinska Univ, Karolinska Inst, Huddinge Hosp, Ctr Infect Med,Dept Med, S-14186 Huddinge, Sweden.
[Bryceson, Yenan T.; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Bryceson, YT (reprint author), Karolinska Univ, Karolinska Inst, Huddinge Hosp, Ctr Infect Med,Dept Med, S-14186 Huddinge, Sweden.
EM yenan.bryceson@ki.se; elong@nih.gov
RI Long, Eric/G-5475-2011;
OI Long, Eric/0000-0002-7793-3728; Bryceson, Yenan/0000-0002-7783-9934
FU NIH; Mary Beve Foundation; David and Astrid Hagelen Foundation; NIAID;
Swedish Foundation for Strategic Research, Research Council and Cancer
Society
FX Y.T.B. was supported by the NIH-Karolinska Institutet Graduate
Partnership Program, the Mary Beve Foundation, and the David and Astrid
Hagelen Foundation. This research was supported by the Intramural
Research Program of the NIH, NIAID (E.O.L.) and the Swedish Foundation
for Strategic Research, Research Council and Cancer Society (H.-G.L.).
NR 66
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U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 24
PY 2009
VL 114
IS 13
BP 2657
EP 2666
DI 10.1182/blood-2009-01-201632
PG 10
WC Hematology
SC Hematology
GA 498KK
UT WOS:000270138600018
PM 19628705
ER
PT J
AU Purdue, MP
Lan, Q
Martinez-Maza, O
Oken, MM
Hocking, W
Huang, WY
Baris, D
Conde, B
Rothman, N
AF Purdue, Mark P.
Lan, Qing
Martinez-Maza, Otoniel
Oken, Martin M.
Hocking, William
Huang, Wen-Yi
Baris, Dalsu
Conde, Betty
Rothman, Nathaniel
TI A prospective study of serum soluble CD30 concentration and risk of
non-Hodgkin lymphoma
SO BLOOD
LA English
DT Article
ID CELL LYMPHOMA; TYPE-2; PATHOGENESIS; EXPRESSION; CYTOKINES; IMMUNITY
AB Prediagnostic serum concentration of soluble CD30 (sCD30), a marker for chronic B-cell stimulation, has been associated with increased risk of developing AIDS-related non-Hodgkin lymphoma (NHL) in a recent study of HIV(+) patients. To investigate among healthy persons whether serum sCD30 is associated with NHL risk, we carried out a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. There was a strong dose-response relationship between prediagnostic sCD30 concentration and NHL risk among 234 cases and 234 individually matched controls (odds ratio [95% confidence interval] for second, third, and fourth quartiles vs first quartile: 1.4 [0.8-2.6], 2.2 [1.2-4.1], 4.1 [2.2-7.8]; P(trend) < .001), which persisted among cases diagnosed 6 to 10 years after providing a blood sample. Given that a similar relationship has been observed among HIV(+) patients, our findings suggest that chronic B-cell stimulation may be an important mechanism involved in B-cell lymphomagenesis among severely immunocompromised and healthy populations alike. (Blood. 2009; 114: 2730-2732)
C1 [Purdue, Mark P.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol, Los Angeles, CA 90095 USA.
[Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Immunol, Los Angeles, CA 90095 USA.
[Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol Genet, Los Angeles, CA 90095 USA.
[Oken, Martin M.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Hocking, William] Marshfield Clin Fdn Med Res & Educ, Dept Hematol Oncol, Marshfield, WI USA.
[Conde, Betty] SAIC Frederick Inc, Prot Express Lab, Adv Technol Program, NCI, Frederick, MD USA.
RP Purdue, MP (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept Hlth & Human Serv, EPS 8009,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM purduem@mail.nih.gov
RI Martinez-Maza, Otoniel/B-2667-2009; Purdue, Mark/C-9228-2016;
OI Martinez-Maza, Otoniel/0000-0003-1364-0675; Purdue,
Mark/0000-0003-1177-3108; Hocking, William/0000-0002-0690-3759
FU National Cancer Institute; National Institutes of Health
[HHSN261200800001E]
FX This work was supported in whole or in part with federal funds from the
National Cancer Institute, National Institutes of Health (contract
HHSN261200800001E).
NR 14
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U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 24
PY 2009
VL 114
IS 13
BP 2730
EP 2732
DI 10.1182/blood-2009-04-217521
PG 3
WC Hematology
SC Hematology
GA 498KK
UT WOS:000270138600025
PM 19638620
ER
PT J
AU Fiskus, W
Wang, YC
Sreekumar, A
Buckley, KM
Shi, HD
Jillella, A
Ustun, C
Rao, R
Fernandez, P
Chen, JG
Balusu, R
Koul, S
Atadja, P
Marquez, VE
Bhalla, KN
AF Fiskus, Warren
Wang, Yongchao
Sreekumar, Arun
Buckley, Kathleen M.
Shi, Huidong
Jillella, Anand
Ustun, Celalettin
Rao, Rekha
Fernandez, Pravina
Chen, Jianguang
Balusu, Ramesh
Koul, Sanjay
Atadja, Peter
Marquez, Victor E.
Bhalla, Kapil N.
TI Combined epigenetic therapy with the histone methyltransferase EZH2
inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor
panobinostat against human AML cells
SO BLOOD
LA English
DT Article
ID GROUP PROTEIN EZH2; FOXO TRANSCRIPTION FACTORS; ACUTE MYELOID-LEUKEMIA;
DNA METHYLATION; TUMOR SUPPRESSION; POLYCOMB; CANCER; REPRESSION; GENE;
EXPRESSION
AB The polycomb repressive complex (PRC) 2 contains 3 core proteins, EZH2, SUZ12, and EED, in which the SET (suppressor of variegation-enhancer of zeste-trithorax) domain of EZH2 mediates the histone methyltransferase activity. This induces trimethylation of lysine 27 on histone H3, regulates the expression of HOX genes, and promotes proliferation and aggressiveness of neoplastic cells. In this study, we demonstrate that treatment with the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A (DZNep) depletes EZH2 levels, and inhibits trimethylation of lysine 27 on histone H3 in the cultured human acute myeloid leukemia (AML) HL-60 and OCI-AML3 cells and in primary AML cells. DZNep treatment induced p16, p21, p27, and FBXO32 while depleting cyclin E and HOXA9 levels. Similar findings were observed after treatment with small interfering RNA to EZH2. In addition, DZNep treatment induced apoptosis in cultured and primary AML cells. Furthermore, compared with treatment with each agent alone, cotreatment with DZNep and the pan-histone deacetylase inhibitor panobinostat caused more depletion of EZH2, induced more apoptosis of AML, but not normal CD34(+) bone marrow progenitor cells, and significantly improved survival of nonobese diabetic/severe combined immunodeficiency mice with HL-60 leukemia. These findings indicate that the combination of DZNep and panobinostat is effective and relatively selective epigenetic therapy against AML cells. (Blood. 2009;114:2733-2743)
C1 [Bhalla, Kapil N.] Med Coll Georgia, Ctr Canc, Augusta, GA 30912 USA.
[Atadja, Peter] Novartis Inst Biomed Res, Cambridge, MA USA.
[Marquez, Victor E.] NIH, Bethesda, MD 20892 USA.
RP Bhalla, KN (reprint author), Med Coll Georgia, Ctr Canc, 1120 15th St,CN-2101, Augusta, GA 30912 USA.
EM kbhalla@mcg.edu
RI Fernandez, Pravina/H-6279-2011
FU National Institutes of Health/National Cancer Institute [R01 CA116629,
R01 CA123207]; Intramural Research Program of the National Institutes of
Health; National Cancer Institute; Center for Cancer Research
FX This work was supported in part by National Institutes of
Health/National Cancer Institute R01 CA116629 (K.N.B.) and R01 CA123207
(K.N.B.). This research was supported in part by the Intramural Research
Program of the National Institutes of Health, National Cancer Institute,
Center for Cancer Research.
NR 51
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U1 3
U2 16
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 24
PY 2009
VL 114
IS 13
BP 2733
EP 2743
DI 10.1182/blood-2009-03-213496
PG 11
WC Hematology
SC Hematology
GA 498KK
UT WOS:000270138600026
PM 19638619
ER
PT J
AU Fandy, TE
Herman, JG
Kerns, P
Jiemjit, A
Sugar, EA
Choi, SH
Yang, AS
Aucott, T
Dauses, T
Odchimar-Reissig, R
Licht, J
McConnell, MJ
Nasrallah, C
Kim, MKH
Zhang, WJ
Sun, YZ
Murgo, A
Espinoza-Delgado, I
Oteiza, K
Owoeye, I
Silverman, LR
Gore, SD
Carraway, HE
AF Fandy, Tamer E.
Herman, James G.
Kerns, Patrick
Jiemjit, Anchalee
Sugar, Elizabeth A.
Choi, Si-Ho
Yang, Allen S.
Aucott, Timothy
Dauses, Tianna
Odchimar-Reissig, Rosalie
Licht, Jonathan
McConnell, Melanie J.
Nasrallah, Chris
Kim, Marianne K. H.
Zhang, Weijia
Sun, Yezou
Murgo, Anthony
Espinoza-Delgado, Igor
Oteiza, Katharine
Owoeye, Ibitayo
Silverman, Lewis R.
Gore, Steven D.
Carraway, Hetty E.
TI Early epigenetic changes and DNA damage do not predict clinical response
in an overlapping schedule of 5-azacytidine and entinostat in patients
with myeloid malignancies
SO BLOOD
LA English
DT Article
ID HISTONE DEACETYLASE INHIBITION; 5-AZA-2'-DEOXYCYTIDINE DECITABINE
TREATMENT; MYELODYSPLASTIC SYNDROME; VALPROIC ACID; METHYLTRANSFERASE
INHIBITORS; HEMATOPOIETIC MALIGNANCIES; HEMATOLOGIC MALIGNANCIES;
METHYLATION STATUS; HUMAN CANCER; LEUKEMIA
AB Sequential administration of DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors has demonstrated clinical efficacy in patients with hematologic malignancies. However, the mechanism behind their clinical efficacy remains controversial. In this study, the methylation dynamics of 4 TSGs (p15(INK4B), CDH-1, DAPK-1, and SOCS-1) were studied in sequential bone marrow samples from 30 patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who completed a minimum of 4 cycles of therapy with 5-azacytidine and entinostat. Reversal of promoter methylation after therapy was observed in both clinical responders and nonresponders across all genes. There was no association between clinical response and either baseline methylation or methylation reversal in the bone marrow or purified CD34(+) population, nor was there an association with change in gene expression. Transient global hypomethylation was observed in samples after treatment but was not associated with clinical response. Induction of histone H3/H4 acetylation and the DNA damage-associated variant histone gamma-H2AX was observed in peripheral blood samples across all dose cohorts. In conclusion, methylation reversal of candidate TSGs during cycle 1 of therapy was not predictive of clinical response to combination "epigenetic" therapy. This trial is registered with http://www.clinicaltrials.gov under NCT00101179. (Blood. 2009;114:2764-2773)
C1 [Fandy, Tamer E.; Herman, James G.; Kerns, Patrick; Jiemjit, Anchalee; Aucott, Timothy; Dauses, Tianna; Oteiza, Katharine; Owoeye, Ibitayo; Gore, Steven D.; Carraway, Hetty E.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Sugar, Elizabeth A.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Sugar, Elizabeth A.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Choi, Si-Ho; Yang, Allen S.] Univ So Calif, Norris Canc Ctr, Div Hematol, Los Angeles, CA USA.
[Odchimar-Reissig, Rosalie; Silverman, Lewis R.] Mt Sinai Med Ctr, Div Med Oncol, New York, NY 10029 USA.
[Licht, Jonathan; Kim, Marianne K. H.] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, Chicago, IL 60611 USA.
[McConnell, Melanie J.] Malaghan Inst Med Res, Wellington, New Zealand.
[Nasrallah, Chris] Univ Calif Berkeley, Ctr Theoret Evolutionary Genet, Berkeley, CA 94720 USA.
[Zhang, Weijia] Mt Sinai Sch Med, Div Hematol Oncol, New York, NY USA.
[Sun, Yezou] Mt Sinai Sch Med, Personalized Med Res Program, New York, NY USA.
[Murgo, Anthony; Espinoza-Delgado, Igor] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
RP Gore, SD (reprint author), 1650 Orleans St,Canc Res Bldg 1,Rm 288, Baltimore, MD 21231 USA.
EM gorest@jhmi.edu
FU NCI NIH HHS [U01CA70095, U01 CA070095, R01 CA125635, R21 CA110507, K24
CA111717]; Wellcome Trust
NR 44
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U1 1
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 24
PY 2009
VL 114
IS 13
BP 2764
EP 2773
DI 10.1182/blood-2009-02-203547
PG 10
WC Hematology
SC Hematology
GA 498KK
UT WOS:000270138600029
PM 19546476
ER
PT J
AU Fushan, AA
Drayna, DT
AF Fushan, Alexey A.
Drayna, Dennis T.
TI MALS: an efficient strategy for multiple site-directed mutagenesis
employing a combination of DNA amplification, ligation and suppression
PCR
SO BMC BIOTECHNOLOGY
LA English
DT Article
ID GENERATION; SINGLE; OLIGONUCLEOTIDES; POLYMERASES; MUTATIONS; DELETION
AB Background: Multiple approaches for the site-directed mutagenesis (SDM) have been developed. However, only several of them are designed for simultaneous introduction of multiple nucleotide alterations, and these are time consuming. In addition, many of the existing multiple SDM methods have technical limitations associated with type and number of mutations that can be introduced, or are technically demanding and require special chemical reagents.
Results: In this study we developed a quick and efficient strategy for introduction of multiple complex mutations in a target DNA without intermediate subcloning by using a combination of connecting SDM and suppression PCR. The procedure consists of sequential rounds, with each individual round including PCR amplification of target DNA with two non-overlapping pairs of oligonucleotides. The desired mutation is incorporated at the 5' end of one or both internal oligonucleotides. DNA fragments obtained during amplification are mixed and ligated. The resulting DNA mixture is amplified with external oligonucleotides that act as suppression adapters. Suppression PCR limits amplification to DNA molecules representing full length target DNA, while amplification of other types of molecules formed during ligation is suppressed. To create additional mutations, an aliquot of the ligation mixture is then used directly for the next round of mutagenesis employing internal oligonucleotides specific for another region of target DNA.
Conclusion: A wide variety of complex multiple mutations can be generated in a short period of time. The procedure is rapid, highly efficient and does not require special chemical reagents. Thus, MALS represents a powerful alternative to the existing methods for multiple SDM.
C1 [Fushan, Alexey A.; Drayna, Dennis T.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
RP Fushan, AA (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
EM fushana@nidcd.nih.gov; drayna@nidcd.nih.gov
FU NIDCD/NIH [Z01-000046-09]
FX This research was supported by NIDCD/NIH funding Z01-000046-09. We thank
Dr. Thomas Friedman and Dr. Robert Morell (Laboratory of Molecular
Genetics, NIDCD/NIH) for their comments and suggestions on the
manuscript.
NR 19
TC 4
Z9 4
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6750
J9 BMC BIOTECHNOL
JI BMC Biotechnol.
PD SEP 24
PY 2009
VL 9
AR 83
DI 10.1186/1472-6750-9-83
PG 8
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 510BR
UT WOS:000271063500001
PM 19778447
ER
PT J
AU Bernstein, SL
Guo, Y
Peterson, K
Wistow, G
AF Bernstein, Steven L.
Guo, Yan
Peterson, Katherine
Wistow, Graeme
TI Expressed sequence tag analysis of adult human optic nerve for NEIBank:
Identification of cell type and tissue markers
SO BMC NEUROSCIENCE
LA English
DT Article
ID 6000 NONREDUNDANT TRANSCRIPTS; RETINAL GANGLION-CELLS; SENSORY NEURONS;
SPLICE VARIANTS; HUMAN GENOME; ISCHEMIA; PROJECT; TRANSPORT; RECEPTOR;
GENES
AB Background: The optic nerve is a pure white matter central nervous system (CNS) tract with an isolated blood supply, and is widely used in physiological studies of white matter response to various insults. We examined the gene expression profile of human optic nerve (ON) and, through the NEIBANK online resource, to provide a resource of sequenced verified cDNA clones. An unnormalized cDNA library was constructed from pooled human ON tissues and was used in expressed sequence tag (EST) analysis. Location of an abundant oligodendrocyte marker was examined by immunofluorescence. Quantitative real time polymerase chain reaction (qRT-PCR) and Western analysis were used to compare levels of expression for key calcium channel protein genes and protein product in primate and rodent ON.
Results: Our analyses revealed a profile similar in many respects to other white matter related tissues, but significantly different from previously available ON cDNA libraries. The previous libraries were found to include specific markers for other eye tissues, suggesting contamination. Immune/inflammatory markers were abundant in the new ON library. The oligodendrocyte marker QKI was abundant at the EST level. Immunofluorescence revealed that this protein is a useful oligodendrocyte cell-type marker in rodent and primate ONs. L-type calcium channel EST abundance was found to be particularly low. A qRT-PCR-based comparative mammalian species analysis reveals that L-type calcium channel expression levels are significantly lower in primate than in rodent ON, which may help account for the class-specific difference in responsiveness to calcium channel blocking agents. Several known eye disease genes are abundantly expressed in ON. Many genes associated with normal axonal function, mRNAs associated with axonal transport, inflammation and neuroprotection are observed.
Conclusion: We conclude that the new cDNA library is a faithful representation of human ON and EST data provide an initial overview of gene expression patterns in this tissue. The data provide clues for tissue-specific and species-specific properties of human ON that will help in design of therapeutic models.
C1 [Bernstein, Steven L.; Guo, Yan] Univ Maryland, Sch Med, Dept Ophthalmol & Neurobiol, Baltimore, MD 21201 USA.
[Bernstein, Steven L.; Guo, Yan] Univ Maryland, Sch Med, Dept Genet, Baltimore, MD 21201 USA.
[Peterson, Katherine; Wistow, Graeme] NEI, Sect Mol Struct & Funct Genom, NIH, Bethesda, MD 20892 USA.
RP Bernstein, SL (reprint author), Univ Maryland, Sch Med, Dept Ophthalmol & Neurobiol, Baltimore, MD 21201 USA.
EM slbernst@umaryland.edu; yguo004@umaryland.edu; petersonk@nei.nih.gov;
graeme@helix.nih.gov
FU NIH [2RO1EY015304, 1R01EY19529]; Intramural program of the NEI
FX This work was supported by NIH grant 2RO1EY015304 (SLB), NIH grant
1R01EY19529 (SLB) and by the Intramural program of the NEI (GW, KP). We
thank James Gao, Patee Buchoff and Cynthia Jaworski (all NEI) for help
with informatics.
NR 29
TC 3
Z9 3
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2202
J9 BMC NEUROSCI
JI BMC Neurosci.
PD SEP 24
PY 2009
VL 10
AR 121
DI 10.1186/1471-2202-10-121
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 513LF
UT WOS:000271323100001
PM 19778450
ER
PT J
AU Burbelo, PD
Ching, KH
Issa, AT
Loftus, CM
Li, Y
Satoh, M
Reeves, WH
Iadarola, MJ
AF Burbelo, Peter D.
Ching, Kathryn H.
Issa, Alexandra T.
Loftus, Caroline M.
Li, Yi
Satoh, Minoru
Reeves, Westley H.
Iadarola, Michael J.
TI Rapid serological detection of autoantibodies associated with Sjogren's
syndrome
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID LUCIFERASE IMMUNOPRECIPITATION SYSTEMS; 4-ANTIGEN MIXTURE; INFECTION;
DIAGNOSIS; DISEASE; ASSAY; SENSITIVITY; ANTIBODIES; TESTS
AB Background: Sjogren's syndrome (SjS) is a relatively common autoimmune disease characterized by oral and ocular dryness. There is an increasing need for simple, sensitive and rapid technologies for the diagnosis of SjS and other autoimmune diseases. Here we investigated whether a quick version of luciferase immunoprecipitation systems (QLIPS) could be used to produce a rapid, specific and quantitative test to detect autoantibodies associated with SjS.
Methods: Using QLIPS, which requires only ten minutes of incubation, a cohort of control and SjS sera were tested for antibodies to three SjS autoantigens ( La, Ro60 and Ro52). Sensitivity and specificity of the QLIPS tests were compared with LIPS and existing ELISA data. The QLIPS test for Ro52 was then evaluated with a new validation cohort and its diagnostic performance determined.
Results: Using QLIPS, autoantibodies to three SjS antigens, La, Ro60, and Ro52 were detected in 49%, 56% and 70%, respectively, of the SjS patients and none of the controls ( 100% specificity). With antibody titers in the Ro52-seropositive SjS samples approximately 1,000 times higher than the healthy controls, not only was Ro52 the most informative, but detection of anti-Ro52 antibodies under these non-equilibrium conditions was improved compared to the standard 2 hour LIPS format. Validation of the anti-Ro52 QLIPS test in a new, independent cohort of SjS and control serum samples showed 66% sensitivity and 100% specificity.
Conclusion: Together these results suggest that the QLIPS format for Ro52 yields both a more rapid and more discriminating test for detecting Ro52 autoantibodies than existing immunoassays and has the potential to be adapted for point-of-care evaluation of patients with SjS and other rheumatologic diseases.
C1 [Burbelo, Peter D.; Ching, Kathryn H.; Issa, Alexandra T.; Loftus, Caroline M.; Li, Yi; Satoh, Minoru; Reeves, Westley H.; Iadarola, Michael J.] Natl Inst Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA.
[Burbelo, Peter D.; Ching, Kathryn H.; Issa, Alexandra T.; Loftus, Caroline M.; Li, Yi; Satoh, Minoru; Reeves, Westley H.; Iadarola, Michael J.] Univ Florida, Div Rheumatol & Clin Immunol, Gainesville, FL USA.
[Burbelo, Peter D.; Ching, Kathryn H.; Issa, Alexandra T.; Loftus, Caroline M.; Li, Yi; Satoh, Minoru; Reeves, Westley H.; Iadarola, Michael J.] Univ Florida, Ctr Autoimmune Dis, Gainesville, FL USA.
RP Burbelo, PD (reprint author), Natl Inst Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA.
EM burbelop@nidcr.nih.gov; Chingk@mail.nih.gov; alexa.issa@gmail.com;
c.marie.loftus@gmail.com; liyi@medicine.ufl.edu;
minoru.satoh@medicine.ufl.edu; westley.reeves@gmail.com;
miadarola@dir.nidcr.nih.gov
RI Satoh, Minoru/E-2421-2011
FU Division of Intramural Research; National Institute of Dental and
Craniofacial Research; NIH Clinical Research Center [AR44731]
FX This work was supported by the Division of Intramural Research, National
Institute of Dental and Craniofacial Research and, in part, by a Bench
to Bedside award from the NIH Clinical Research Center and by NIH grant
(AR44731). We greatly thank Dr. Gabor Illei and Dr. Nikolay Nikolov for
providing the initial cohort of SjS and control sera samples.
NR 26
TC 13
Z9 13
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD SEP 24
PY 2009
VL 7
AR 83
DI 10.1186/1479-5876-7-83
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 508WN
UT WOS:000270968900002
PM 19778440
ER
PT J
AU Guigon, CJ
Cheng, SY
AF Guigon, Celine J.
Cheng, Sheue-yann
TI Novel non-genomic signaling of thyroid hormone receptors in thyroid
carcinogenesis
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE Thyroid hormone receptor mutants; Thyroid cancer; Non-genomic action;
Phosphatidylinositol 3 kinase; Pituitary tumor transforming gene;
beta-catenin; Mouse model
ID TUMOR-TRANSFORMING GENE; EPITHELIAL-MESENCHYMAL TRANSITION; SECRETING
PITUITARY-TUMOR; BETA-CATENIN DEGRADATION; CLEAR-CELL CARCINOMA;
PROTEIN-KINASE-B; MOUSE MODEL; PHOSPHATIDYLINOSITOL 3-KINASE;
PHOSPHOINOSITIDE 3-KINASE; HEPATOCELLULAR-CARCINOMA
AB The thyroid hormone receptors (TRs) are transcription factors that mediate the pleiotropic activities of the thyroid hormone, T3. Four T3-binding isorforms, TR alpha 1, TR beta 1, TR beta 2, and TR beta 3, are encoded by two genes, THRA and THRB. Mutations and altered expression of TRs have been reported in human cancers. A targeted germ-line mutation of the Thr beta gene in the mouse leads to spontaneous development of follicular thyroid carcinoma (TR beta(PV/PV) mouse). The TR beta PV mutant has lost T3-binding activity and displays potent dominant negative activity. The striking phenotype of thyroid cancer exhibited by TR beta(PV/PV) mice has recently led to the discovery of novel non-genomic actions of TR beta PV that contribute to thyroid carcinogenesis. These actions involve direct physical interaction of TR beta PV with cellular proteins, namely the regulatory subunit of the phosphatidylinositol 3-kinase (p85 alpha), the pituitary tumor transforming gene (MG) and beta-catenin, that are critically involved in cell proliferation, motility, migration, and metastasis. Thus, a TR beta mutant (TR beta PV), via a novel mode of non-genomic action, acts as an oncogene in thyroid carcinogenesis. Published by Elsevier Ireland Ltd.
C1 [Guigon, Celine J.; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
FU Intramural Research Program of Center for Cancer Research; National
Cancer Institute; National Institutes of Health
FX The present research was supported by the Intramural Research Program of
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 77
TC 20
Z9 23
U1 1
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD SEP 24
PY 2009
VL 308
IS 1-2
BP 63
EP 69
DI 10.1016/j.mce.2009.01.007
PG 7
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 472IS
UT WOS:000268124400010
PM 19549593
ER
PT J
AU Fernandes, HB
Catches, JS
Petralia, RS
Copits, BA
Xu, J
Russell, TA
Swanson, GT
Contractor, A
AF Fernandes, Herman B.
Catches, Justin S.
Petralia, Ronald S.
Copits, Bryan A.
Xu, Jian
Russell, Theron A.
Swanson, Geoffrey T.
Contractor, Anis
TI High-Affinity Kainate Receptor Subunits Are Necessary for Ionotropic but
Not Metabotropic Signaling
SO NEURON
LA English
DT Article
ID MOSSY-FIBER SYNAPSES; EXCITATORY SYNAPTIC-TRANSMISSION; SHORT-TERM
PLASTICITY; RAT-BRAIN; HIPPOCAMPUS; MICE; CA3; ACTIVATION; EXPRESSION;
NEURONS
AB Kainate receptors signal through both ionotropic and metabotropic pathways. The high-affinity subunits, GluK4 and GluK5, are unique among the five receptor subunits, as they do not form homomeric receptors but modify the properties of heteromeric assemblies. Disruption of the Grik4 gene locus resulted in a significant reduction in synaptic kainate receptor currents. Moreover, ablation of GluK4 and GluK5 caused complete loss of synaptic ionotropic kainate receptor function. The principal subunits were distributed away from postsynaptic densities and presynaptic active zones. There was also a profound alteration in the activation properties of the remaining kainate receptors. Despite this, kainate receptor-mediated inhibition of the slow afterhyperpolarization current (I(SAHP)) which is dependent on metabotropic pathways, was intact in GluK4/GluK5 knockout mice. These results uncover a previously unknown obligatory role for the high-affinity subunits for ionotropic kainate receptor function and further demonstrate that kainate receptor participation in metabotropic signaling pathways does not require their classic role as ion channels.
C1 [Fernandes, Herman B.; Catches, Justin S.; Xu, Jian; Russell, Theron A.; Contractor, Anis] Northwestern Univ, Sch Med, Dept Physiol, Chicago, IL 60611 USA.
[Petralia, Ronald S.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
[Copits, Bryan A.; Swanson, Geoffrey T.] Northwestern Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Chicago, IL 60611 USA.
RP Contractor, A (reprint author), Northwestern Univ, Sch Med, Dept Physiol, 303 E Chicago Ave, Chicago, IL 60611 USA.
EM a-contractor@northwestern.edu
OI Contractor, Anis/0000-0002-5131-2536
FU National Institute of Health (NINDS) [R01NS044322, R01NS058894]; NIH
intramural support (NIDCD)
FX We gratefully thank Professor Stephen Heinemann in whose laboratory the
floxed GluK4 mice were originally generated. Ashley Westwood provided
technical help with mouse husbandry and genotyping and or Ya-Xian Wang
contributed to the immunogold labeling. This work was supported by
extramural grants from the National Institute of Health (NINDS)
(R01NS044322 to G.T.S. and R01NS058894 to A.C.) and NIH intramural
support (NIDCD) (to R.S.P.). Justin Catches is a John N. Nicholson
Fellow.
NR 44
TC 52
Z9 52
U1 0
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD SEP 24
PY 2009
VL 63
IS 6
BP 818
EP 829
DI 10.1016/j.neuron.2009.08.010
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 503VP
UT WOS:000270569700014
PM 19778510
ER
PT J
AU Wan, X
Kim, SY
Guenther, LM
Mendoza, A
Briggs, J
Yeung, C
Currier, D
Zhang, H
Mackall, C
Li, WJ
Tuan, RS
Deyrup, AT
Khanna, C
Helman, L
AF Wan, X.
Kim, S. Y.
Guenther, L. M.
Mendoza, A.
Briggs, J.
Yeung, C.
Currier, D.
Zhang, H.
Mackall, C.
Li, W-J
Tuan, R. S.
Deyrup, A. T.
Khanna, C.
Helman, L.
TI Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin
SO ONCOGENE
LA English
DT Article
DE beta 4 integrin; osteosarcoma; metastases; ezrin; interaction
ID ALPHA-6-BETA-4 INTEGRIN; CYTOPLASMIC DOMAINS; CELL-MIGRATION; BINDING;
INVASION; KINASE; GROWTH; EXPRESSION; TUMORIGENESIS; TRANSDUCTION
AB The development of pulmonary metastasis is the major cause of death in osteosarcoma, and its molecular basis is poorly understood. In this study, we show that beta 4 integrin is highly expressed in human osteosarcoma cell lines and tumor samples. Furthermore, highly metastatic MNNG-HOS cells have increased levels of beta 4 integrin. Suppression of beta 4 integrin expression by shRNA and disruption of beta 4 integrin function by transfection of dominant-negative beta 4 integrin was sufficient to revert this highly metastatic phenotype in the MNNG-HOS model without significantly affecting primary tumor growth. These findings suggest a role for beta 4 integrin expression in the metastatic phenotype in human osteosarcoma cells. In addition, we identified a previously uncharacterized interaction between beta 4 integrin and ezrin, a membrane-cytoskeletal linker protein that is implicated in the metastatic behavior of osteosarcoma. The beta 4 integrin-ezrin interaction appears to be critical for maintenance of beta 4 integrin expression. These data begin to integrate ezrin and beta 4 integrin expression into a model of action for the mechanism of osteosarcoma metastases. Oncogene (2009) 28, 3401-3411; doi: 10.1038/onc.2009.206; published online 13 July 2009
C1 [Wan, X.] NCI, Mol Oncol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Li, W-J; Tuan, R. S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA.
[Deyrup, A. T.] Emory Univ, Dept Pathol, Atlanta, GA USA.
RP Wan, X (reprint author), NCI, Mol Oncol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bldg 10,Rm CRC-1W-3750, Bethesda, MD 20892 USA.
EM xiaolinw@mail.nih.gov
FU NIH; National Cancer Institute; Center for Cancer Research
FX We thank Dr AM Mercurio for providing empty vector and beta 4 mutant
(Y1494F), Dr L Trusolino for providing control-shRNA and beta 4-shRNA,
Dr M Arpin for providing GST and GST-ezrin-CT, Dr R Nguyen for providing
BSA and ezrinNT. This research was supported by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 39
TC 35
Z9 42
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD SEP 24
PY 2009
VL 28
IS 38
BP 3401
EP 3411
DI 10.1038/onc.2009.206
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 497ZD
UT WOS:000270103300007
PM 19597468
ER
PT J
AU Lea, WA
Xi, J
Jadhav, A
Lu, L
Austin, CP
Simeonov, A
Eckenhoff, RG
AF Lea, Wendy A.
Xi, Jin
Jadhav, Ajit
Lu, Louis
Austin, Christopher P.
Simeonov, Anton
Eckenhoff, Roderic G.
TI A High-Throughput Approach for Identification of Novel General
Anesthetics
SO PLOS ONE
LA English
DT Article
AB Anesthetic development has been a largely empirical process. Recently, we described a GABAergic mimetic model system for anesthetic binding, based on apoferritin and an environment-sensitive fluorescent probe. Here, a competition assay based on 1-aminoanthracene and apoferritin has been taken to a high throughput screening level, and validated using the LOPAC(1280) library of drug-like compounds. A raw hit rate of similar to 15% was reduced through the use of computational filters to yield an overall hit rate of similar to 1%. These hits were validated using isothermal titration calorimetry. The success of this initial screen and computational triage provides feasibility to undergo a large scale campaign to discover novel general anesthetics.
RP Lea, WA (reprint author), NHGRI, NIH Chem Genom Ctr, Bethesda, MD 20892 USA.
EM asimeono@mail.nih.gov; roderic.eckenhoff@uphs.upenn.edu
FU NIGMS NIH HHS [P01 GM055876, NIH P-01 GM55876]; NIMH NIH HHS [R03
MH084836, R-03 MH84836]
NR 12
TC 10
Z9 12
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD SEP 24
PY 2009
VL 4
IS 9
AR e7150
DI 10.1371/journal.pone.0007150
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 498SW
UT WOS:000270164600004
PM 19777064
ER
PT J
AU Plested, AJR
Mayer, ML
AF Plested, Andrew J. R.
Mayer, Mark L.
TI AMPA Receptor Ligand Binding Domain Mobility Revealed by Functional
Cross Linking
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID DISULFIDE BOND FORMATION; GLUTAMATE-RECEPTOR; CONFORMATIONAL-CHANGES;
CRYSTAL-STRUCTURES; SYNAPTIC DEPRESSION; CORE DIMER; DESENSITIZATION;
COMPLEX; ANTAGONISTS; ACTIVATION
AB Glutamate receptors mediate the majority of excitatory synaptic transmission in the CNS. The AMPA-subtype has rapid kinetics, with activation, deactivation and desensitization proceeding on the millisecond timescale or faster. Crystallographic, biochemical, and functional studies suggest that GluR2 Cys mutants which form intermolecular disulfide cross-links between the lower D2 lobes of the ligand binding cores can be trapped in a conformation that represents the desensitized state. We used multi-channel rapid perfusion techniques to examine the state dependence of cross-linking in these mutants. Under reducing conditions, both wild-type GluR2 and the G725C and S729C mutants have normal activation and desensitization kinetics, but the Cys mutants can be efficiently trapped in nonconducting states when oxidized. In contrast the I664C mutant is only partially inactivated under oxidizing conditions. For S729C, disulfide cross-links form rapidly when receptors are desensitized in the presence of glutamate, but receptors also become trapped at rest, in the absence of agonist. We assessed such spontaneous trapping in various conditions, including CNQX, a competitive antagonist; kainate, a weak partial agonist; or when desensitization was blocked by the L483Y mutation that stabilizes the D1 dimer interface. These experiments suggest that trapping in the absence of glutamate is due to two motions: Spontaneous breaking of the D1 dimer interface and hyperextension of the lower lobes of the ligand binding core. These data show that the glutamate binding domains are surprisingly mobile in the absence of ligand, which could influence receptor activity in the brain.
C1 [Plested, Andrew J. R.; Mayer, Mark L.] NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Mayer, ML (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,Dept Hlth & Human Serv, Bldg 35,Room 3B 1002,35 Lincoln Dr, Bethesda, MD 20892 USA.
EM mlm@helix.nih.gov
RI Mayer, Mark/H-5500-2013;
OI Plested, Andrew/0000-0001-6062-0832
FU National Institute of Child Health and Human Development; National
Institutes of Health; Department of Health and Human Services
FX This work was supported by the intramural research program of the
National Institute of Child Health and Human Development, National
Institutes of Health, and Department of Health and Human Services.
A.J.R. P performed experiments and analyzed data; A.J.R. P and M. L. M.
designed experiments and wrote the paper. We thank Carla Glasser for
preparing cDNAs; Drs. James Howe and Wei Zhang ( Yale University) for
advice and the gift of piezo wafers; Dr. J. Diamond [National Institute
of Neurological Disorders and Stroke (NINDS)] for the loan of the EX100
amplifier; and the NINDS DNA sequencing facility and Dr. P. Seeburg for
the gift of wild-type cDNAs.
NR 27
TC 34
Z9 34
U1 0
U2 2
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 23
PY 2009
VL 29
IS 38
BP 11912
EP 11923
DI 10.1523/JNEUROSCI.2971-09.2009
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 497YS
UT WOS:000270102000021
PM 19776277
ER
PT J
AU Zabow, G
Dodd, SJ
Moreland, J
Koretsky, AP
AF Zabow, G.
Dodd, S. J.
Moreland, J.
Koretsky, A. P.
TI The fabrication of uniform cylindrical nanoshells and their use as
spectrally tunable MRI contrast agents
SO NANOTECHNOLOGY
LA English
DT Article
ID SUPERPARAMAGNETIC IRON-OXIDE; POROUS ALUMINA TEMPLATES; STEM-CELLS;
NANOPARTICLES; ARRAYS; METAL; NANOCRYSTALS; REDEPOSITION; PARTICLES;
NANOTUBES
AB A new form of tunable magnetic resonance imaging agent based on precisely dimensioned cylindrical magnetic nanoshells is introduced. Using top-down prepatterned substrates, the nanoshells are fabricated by exploiting what is usually regarded as a detrimental processing side-effect, namely the redeposition of material back-sputtered during ion-milling. The well-resolved nuclear magnetic resonance peaks of the resulting nanostructures attest to the nanoscale fabrication control and the general feasibility of such sputter redeposition for fabrication of a variety of self-supporting, highly monodisperse nanoscale structures.
C1 [Zabow, G.; Dodd, S. J.; Koretsky, A. P.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Zabow, G.; Moreland, J.] Natl Inst Stand & Technol, Electromagnet Div, Boulder, CO USA.
RP Zabow, G (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM zabow@boulder.nist.gov
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
FU NIH NINDS Intramural Research Program
FX This work was supported in part by the NIH NINDS Intramural Research
Program.
NR 39
TC 21
Z9 21
U1 0
U2 11
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0957-4484
EI 1361-6528
J9 NANOTECHNOLOGY
JI Nanotechnology
PD SEP 23
PY 2009
VL 20
IS 38
AR 385301
DI 10.1088/0957-4484/20/38/385301
PG 8
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary;
Physics, Applied
SC Science & Technology - Other Topics; Materials Science; Physics
GA 488NP
UT WOS:000269356900004
PM 19713581
ER
PT J
AU Poulin, KW
Smirnov, AV
Hawkins, ME
Balis, FM
Knutson, JR
AF Poulin, Kristi Wojtuszewski
Smirnov, Aleksandr V.
Hawkins, Mary E.
Balis, Frank M.
Knutson, Jay R.
TI Conformational Heterogeneity and Quasi-Static Self-Quenching in DNA
Containing a Fluorescent Guanine Analogue, 3MI or 6MI
SO BIOCHEMISTRY
LA English
DT Article
ID 2-AMINOPURINE FLUORESCENCE; NUCLEOTIDE INCORPORATION; GUANOSINE ANALOG;
KLENOW FRAGMENT; BASE STACKING; POLYMERASE-I; OLIGONUCLEOTIDES;
DEPENDENCE; DECAY
AB Two different microenvironments in the DNA sequence 5'-act aGa gat ccc tca gac cct ttt agt cag tGt gga-3' (in both single-and double-stranded forms) are explored using two similar fluorescent nucleoside analogues, 3MI and 6MI. Each probe was evaluated in two environments, one strand with the probe flanked by thymines (PTRT) and the other by adenines (PTRA) with positions indicated by G's in the sequence. Both time-resolved anisotropies and lifetimes of the probes depend upon local interactions, and these are altered by duplex formation. Integrals of lifetime curves compared with quantum yields reveal that each probe displays a "dark" component (below detection limits, with a lifetime of < 70 ps). For 6MI in PTRA, this QSSQ "quasi-static self-quenching" or "dark" component represents approximately half the Molecules, whether in single- or double-stranded form. In PTRT, 6MI displays an unusual increase in the quantum yield upon formation of the double strand (from 0.107 to 0.189) apparently the result of escape from QSSQ which simultaneously declines from 66 to 33%. This is also accompanied by doubling of steady-state anisotropy. Only 6MI in the PTRT duplex displays a rotational correlation time of > 7 ns. In other words, the DS 6MI PTRA environment falls to constrain local motion and QSSQ remains the same as in the single strand; in contrast, the flanking T duplex environment restricts local motion and halves QSSQ. We collected both steady-state and time-resolved fluorescence quenching titrations of 3MI and 6MI in Solution with the mononucleotides AMP, CMP, GMP, and TMP. The dynamic quenching rank of the free probes (quenching constant, k(q): T > A > G > C) is totally different from that of incorporated probes. We hypothesize the production of weak 3MI.C or 6MI.C complexes that are somehow rendered less subject to dynamic quenching by collision with subsequent C molecules.
C1 [Hawkins, Mary E.; Balis, Frank M.] NCI, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Poulin, Kristi Wojtuszewski; Smirnov, Aleksandr V.; Knutson, Jay R.] NHLBI, Opt Spect, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Hawkins, ME (reprint author), NCI, Pharmacol & Expt Therapeut Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM mh100x@nih.gov; jk1r@nih.gov
NR 25
TC 14
Z9 14
U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD SEP 22
PY 2009
VL 48
IS 37
BP 8861
EP 8868
DI 10.1021/bi9003414
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 492ZN
UT WOS:000269702200013
ER
PT J
AU McDermott, MM
Ferrucci, L
Guralnik, J
Tian, L
Liu, K
Hoff, F
Liao, YH
Criqui, MH
AF McDermott, Mary McGrae
Ferrucci, Luigi
Guralnik, Jack
Tian, Lu
Liu, Kiang
Hoff, Frederick
Liao, Yihua
Criqui, Michael H.
TI Pathophysiological Changes in Calf Muscle Predict Mobility Loss at
2-Year Follow-Up in Men and Women With Peripheral Arterial Disease
SO CIRCULATION
LA English
DT Article
DE aging; claudication; muscles; peripheral vascular disease; prognosis
ID ANKLE-BRACHIAL INDEX; LOWER-EXTREMITY ISCHEMIA; PHYSICAL-ACTIVITY;
SKELETAL-MUSCLE; FUNCTIONAL DECLINE; DAILY-LIFE; CLASSIFICATION;
OSTEOARTHRITIS; ASSOCIATIONS; CRITERIA
AB Background-Associations of pathophysiological calf muscle characteristics with functional decline in people with lower extremity peripheral arterial disease are unknown.
Methods and Results-Three hundred seventy participants with peripheral arterial disease underwent baseline measurement of calf muscle area, density, and percent fat with the use of computed tomography. Participants were followed up annually for 2 years. The outcome of mobility loss was defined as becoming unable to walk 1/4 mile or walk up and down 1 flight of stairs without assistance among those without baseline mobility limitations. Additional outcomes were >= 20% decline in 6-minute walk distance and becoming unable to walk for 6 minutes continuously among participants who walked continuously for 6 minutes at baseline. With adjustment for age, sex, race, body mass index, the ankle-brachial index, smoking, physical activity, relevant medications, and comorbidities, lower calf muscle density (P for trend <0.001) and lower calf muscle area (P for trend=0.039) were each associated with increased mobility loss rates. Compared with participants in the highest baseline tertiles, participants in the lowest tertile of calf muscle percent fat had a hazard ratio of 0.18 for incident mobility loss (95% confidence interval, 0.06 to 0.55; P = 0.003), and participants in the lowest tertile of muscle density had a 3.50 hazard ratio for incident mobility loss (95% confidence interval, 1.28 to 9.57; P = 0.015). No significant associations of calf muscle characteristics with 6-minute walk outcomes were observed.
Conclusions-Our findings suggest that interventions to prevent mobility loss in peripheral arterial disease should focus on reversing pathophysiological findings in calf muscle. (Circulation. 2009; 120: 1048-1055.)
C1 [McDermott, Mary McGrae; Liu, Kiang; Hoff, Frederick; Liao, Yihua] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Ferrucci, Luigi; Guralnik, Jack] NIA, Bethesda, MD 20892 USA.
[Tian, Lu] Stanford Univ, Stanford, CA 94305 USA.
[Criqui, Michael H.] Univ Calif San Diego, San Diego, CA 92103 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-HL58099, R01-HL64739,
R01-HL071223, R01-HL076298]; National Center for Research Resources
[RR-00048]; National Institutes of Health; Intramural Research Program;
National Institute on Aging
FX This study was supported by grants R01-HL58099, R01-HL64739,
R01-HL071223, and R01-HL076298 from the National Heart, Lung, and Blood
Institute and by grant RR-00048 from the National Center for Research
Resources, National Institutes of Health. This study was also supported
in part by the Intramural Research Program, National Institute on Aging,
National Institutes of Health.
NR 20
TC 26
Z9 26
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD SEP 22
PY 2009
VL 120
IS 12
BP 1048
EP 1055
DI 10.1161/CIRCULATIONAHA.108.842328
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 496YF
UT WOS:000270015600006
PM 19738138
ER
PT J
AU Ma, J
Sun, J
Zhang, H
Zhang, R
Kang, WH
Gao, CG
Liu, HS
Ma, XH
Min, ZX
Zhao, WX
Ning, QL
Wang, SH
Zhang, YC
Guo, TW
Lu, SM
AF Ma, Jie
Sun, Jian
Zhang, Huan
Zhang, Rui
Kang, Wan-Hu
Gao, Cheng-Ge
Liu, Hai-Sheng
Ma, Xue-Hong
Min, Zi-Xin
Zhao, Wen-Xiang
Ning, Qi-Lan
Wang, Shu-Hong
Zhang, Yin-Cang
Guo, Ting-Wei
Lu, She-Min
TI Evidence for transmission disequilibrium at the DAOA gene locus in a
schizophrenia family sample
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Schizophrenia; DAOA; SNP; TDT; Haplotype; Association
ID AMINO-ACID OXIDASE; BIPOLAR-AFFECTIVE-DISORDER; G72/G30 LOCUS; CHINESE
POPULATION; CANDIDATE GENES; NO ASSOCIATION; POLYMORPHISMS;
SUSCEPTIBILITY; G72; LINKAGE
AB Recently, the DAOA gene locus on chromosome 13q32-q34 has been implicated in the etiology of schizophrenia. We genotyped three single-nucleotide polymorphisms (SNPs: rs778294, rs779293 and rs3918342) in this region in 126 Chinese family trios. In this study, we have identified statistically Significant transmission disequilibrium in two markers rs778293 (P=0.01) and rs3918342 (P=0.02), and a highly significant under-transmission between haplotype CAT (P=0.0005) and schizophrenia. The results provide further evidence to support that DAOA gene locus is involved in conferring susceptibility to schizophrenia. (c) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Ma, Jie; Sun, Jian; Zhang, Rui; Min, Zi-Xin; Zhao, Wen-Xiang; Ning, Qi-Lan; Wang, Shu-Hong; Lu, She-Min] Xi An Jiao Tong Univ, Sch Med, Dept Genet & Mol Biol, Xian, Shaanxi, Peoples R China.
[Kang, Wan-Hu; Gao, Cheng-Ge; Ma, Xue-Hong] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 1, Xian, Shaanxi, Peoples R China.
[Zhang, Huan] Xi An Jiao Tong Univ, Sch Med, Affiliated Hosp 2, Xian, Shaanxi, Peoples R China.
[Liu, Hai-Sheng] Xian First Social Welf Hosp, Xian, Shaanxi, Peoples R China.
[Zhang, Yin-Cang] Northwest Univ, Coll Int Cultural Exchanges, Xian, Shaanxi, Peoples R China.
[Guo, Ting-Wei] NIDDK, NIH, Phoenix, AZ USA.
RP Lu, SM (reprint author), Xi An Jiao Tong Univ, Sch Med, Dept Genet & Mol Biol, 76 W Yan Ta Rd, Xian, Shaanxi, Peoples R China.
EM Lushemin@mail.xjtu.edu.cn
OI Lu, Shemin/0000-0001-8250-850X
FU National Natural Science Foundation of China [30800618]; Chinese
Ministry of Education, PRC; Headmaster Foundation of Van Jiaotong
University
FX We are deeply grateful to all of the families who participated in this
study, as well as to the psychiatrists and mental health workers who
helped us with the identification of the families. This work was
supported by grants from the National Natural Science Foundation of
China (No. 30800618), the Chinese Ministry of Education, PRC, and the
Headmaster Foundation of Van Jiaotong University.
NR 38
TC 6
Z9 9
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD SEP 22
PY 2009
VL 462
IS 2
BP 105
EP 108
DI 10.1016/j.neulet.2009.06.070
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA 484SR
UT WOS:000269068300002
PM 19560517
ER
PT J
AU Li, QS
Brass, AL
Ng, A
Hu, ZY
Xavier, RJ
Liang, TJ
Elledge, SJ
AF Li, Qisheng
Brass, Abraham L.
Ng, Aylwin
Hu, Zongyi
Xavier, Ramnik J.
Liang, T. Jake
Elledge, Stephen J.
TI A genome-wide genetic screen for host factors required for hepatitis C
virus propagation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE HCV; RNA interference; viral host factors; functional genomics; viral
lifecycle
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELLULAR COFACTORS; IN-VITRO; REPLICATION;
INFECTION; IDENTIFICATION; CULTURE; PROTEINS
AB Hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and a leading indication for liver transplantation. Current therapy fails in many instances and is associated with significant side effects. HCV encodes only a few proteins and depends heavily on host factors for propagation. Each of these host dependencies is a potential therapeutic target. To find host factors required by HCV, we completed a genome-wide small interfering RNA (siRNA) screen using an infectious HCV cell culture system. We applied a two-part screening protocol to allow identification of host factors involved in the complete viral lifecycle. The candidate genes found included known or previously identified factors, and also implicate many additional host cell proteins in HCV infection. To create a more comprehensive view of HCV and host cell interactions, we performed a bioinformatic meta-analysis that integrates our data with those of previous functional and proteomic studies. The identification of host factors participating in the complete HCV lifecycle will both advance our understanding of HCV pathogenesis and illuminate therapeutic targets.
C1 [Brass, Abraham L.; Elledge, Stephen J.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Brigham & Womens Hosp,Dept Genet,Div Genet, Boston, MA 02115 USA.
[Ng, Aylwin; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Li, Qisheng; Hu, Zongyi; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Brass, Abraham L.] Massachusetts Gen Hosp, Ragon Inst, MIT, Charlestown, MA 02129 USA.
[Brass, Abraham L.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Elledge, SJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Brigham & Womens Hosp,Dept Genet,Div Genet, Boston, MA 02115 USA.
EM jakel@bdg10.niddk.nih.gov; selledge@genetics.med.harvard.edu
RI Li, Qisheng/K-1909-2013
FU Center for the Study of Inflammatory Bowel Disease Genetics and Genomics
Core and National Institutes of Health [DK043351]; Intramural Research
Program of the National Institute of Diabetes and Digestive and Kidney
Diseases; National Institutes of Health [U54 AI057159]; New England
Regional Center of Excellence for Biodefense and Emerging Infectious
Diseases; Howard Hughes Medical Institute
FX We thank the ICCB-Longwood: C. Shamu, S. Chang, S. Rudnicki, S.
Johnston, K. Rudnicki, D. Wrobel, and Z. Cooper. Funding support: A. L.
B. (Harvard Center for AIDS Research), A. N. (Crohns and Colitis
Foundation of America), R. J. X. (Center for the Study of Inflammatory
Bowel Disease Genetics and Genomics Core and National Institutes of
Health Grant DK043351). The ICCB-Longwood is in part supported by a
grant to T. Mitchison (National Cancer Institute). This work was
supported by the Intramural Research Program of the National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes of
Health, and the New England Regional Center of Excellence for Biodefense
and Emerging Infectious Diseases (National Institutes of Health Grant
U54 AI057159 to Dennis Kasper). S. J. E. is an Investigator with the
Howard Hughes Medical Institute.
NR 37
TC 220
Z9 225
U1 1
U2 15
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 22
PY 2009
VL 106
IS 38
BP 16410
EP 16415
DI 10.1073/pnas.0907439106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 497PF
UT WOS:000270071600074
PM 19717417
ER
PT J
AU Szentpetery, Z
Balla, A
Kim, YJ
Lemmon, MA
Balla, T
AF Szentpetery, Zsofia
Balla, Andras
Kim, Yeun Ju
Lemmon, Mark A.
Balla, Tamas
TI Live cell imaging with protein domains capable of recognizing
phosphatidylinositol 4,5-bisphosphate; a comparative study
SO BMC CELL BIOLOGY
LA English
DT Article
ID PLECKSTRIN HOMOLOGY DOMAINS; INOSITOL 1,4,5-TRISPHOSPHATE;
PHOSPHOLIPASE-C; LIVING CELLS; RECEPTOR ACTIVATION; TUBBY PROTEINS; CA2+
RELEASE; PH DOMAINS; BINDING; PHOSPHOINOSITIDES
AB Background: Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P-2] is a critically important regulatory phospholipid found in the plasma membrane of all eukaryotic cells. In addition to being a precursor of important second messengers, PtdIns(4,5)P-2 also regulates ion channels and transporters and serves the endocytic machinery by recruiting clathrin adaptor proteins. Visualization of the localization and dynamic changes in PtdIns(4,5)P-2 levels in living cells is critical to understanding the biology of PtdIns(4,5)P-2. This has been mostly achieved with the use of the pleckstrin homology (PH) domain of PLC delta 1 fused to GFP. Here we report on a comparative analysis of several recently-described yeast PH domains as well as the mammalian Tubby domain to evaluate their usefulness as PtdIns(4,5)P-2 imaging tools.
Results: All of the yeast PH domains that have been previously shown to bind PtdIns(4,5)P-2 showed plasma membrane localization but only a subset responded to manipulations of plasma membrane PtdIns(4,5)P-2. None of these domains showed any advantage over the PLC delta 1PH-GFP reporter and were compromised either in their expression levels, nuclear localization or by causing peculiar membrane structures. In contrast, the Tubby domain showed high membrane localization consistent with PtdIns(4,5)P-2 binding and displayed no affinity for the soluble headgroup, Ins(1,4,5)P-3. Detailed comparison of the Tubby and PLC delta 1PH domains showed that the Tubby domain has a higher affinity for membrane PtdIns(4,5)P-2 and therefore displays a lower sensitivity to report on changes of this lipid during phospholipase C activation.
Conclusion: These results showed that both the PLC delta 1PH-GFP and the GFP-Tubby domain are useful reporters of PtdIns(4,5)P-2 changes in the plasma membrane, with distinct advantages and disadvantages. While the PLC delta 1PH-GFP is a more sensitive reporter, its Ins(1,4,5)P-3 binding may compromise its accuracy to measure PtdIns(4,5)P-2 changes. The Tubby domain is more accurate to report on PtdIns(4,5)P-2 but its higher affinity and lower sensitivity may limit its utility when phospholipase C activation is only moderate. These studies also demonstrated that similar changes in PtdIns(4,5)P-2 levels in the plasma membrane can differentially regulate multiple effectors if they display different affinities to PtdIns(4,5)P-2.
C1 [Szentpetery, Zsofia; Kim, Yeun Ju; Balla, Tamas] NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Balla, Andras] Semmelweis Univ, Sch Med, Dept Physiol, Budapest, Hungary.
[Lemmon, Mark A.] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
RP Balla, T (reprint author), NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
EM szentpeteryzsofia@yahoo.com; aballa@puskin.sote.hu; KimYJ@mail.nih.gov;
mlemmon@mail.med.upenn.edu; ballat@mail.nih.gov
OI Balla, Andras/0000-0002-6450-2793; Balla, Tamas/0000-0002-9077-3335;
Lemmon, Mark/0000-0002-3379-5319
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development of the National
Institutes of Health
FX We are grateful to Dr. Roger Y. Tsien for the monomeric red fluorescent
protein and to Dr Philip W. Majerus for the human type-IV 5-ptase clone.
Confocal imaging was performed at the Microscopy & Imaging Core of the
National Institute of Child Health and Human Development, NIH with the
kind assistance of Drs. Vincent Schram and James T. Russell. This
research was supported in part by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the National Institutes of Health.
NR 38
TC 44
Z9 45
U1 2
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2121
J9 BMC CELL BIOL
JI BMC Cell Biol.
PD SEP 21
PY 2009
VL 10
AR 67
DI 10.1186/1471-2121-10-67
PG 20
WC Cell Biology
SC Cell Biology
GA 511WX
UT WOS:000271203500001
PM 19769794
ER
PT J
AU Sherman, KJ
Cherkin, DC
Ichikawa, L
Avins, AL
Barlow, WE
Khalsa, PS
Deyo, RA
AF Sherman, Karen J.
Cherkin, Daniel C.
Ichikawa, Laura
Avins, Andrew L.
Barlow, William E.
Khalsa, Partap S.
Deyo, Richard A.
TI Characteristics of patients with chronic back pain who benefit from
acupuncture
SO BMC MUSCULOSKELETAL DISORDERS
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE; CLINICAL-PREDICTION;
DIAGNOSIS; EXPENDITURES; EXPECTATIONS; PATTERNS
AB Background: Although many clinicians believe there are clinically important subgroups of persons with "non-specific" low back pain, such subgroups have not yet been clearly identified. As part of a large trial evaluating acupuncture for chronic low back pain, we sought to identify subgroups of participants that were particularly responsive to acupuncture.
Methods: We performed a secondary analysis of data for the 638 participants in our clinical trial comparing different types of acupuncture to usual care to identify baseline characteristics that predicted responses to individualized, standardized, or simulated acupuncture treatments. After identifying factors that predicted improvements in back-related function or symptoms, we determined if these factors were more likely to predict improvement for those receiving the acupuncture treatments than for those receiving usual care. This was accomplished by testing for an interaction between the prognostic factors and treatment group in four models: functional outcomes (measured by the Roland-Morris Disability Scale) at 8 and 52 weeks post-randomization and symptom outcomes (measured with a numerical rating scale) at 8 and 52 weeks.
Results: Overall, the strongest predictors of improvement in back function and symptoms were higher baseline levels of these measures, receipt of an acupuncture treatment, and non-use of narcotic analgesics. Benefit from acupuncture compared to usual care was greater with worse pretreatment levels of back dysfunction (interaction p < 0.004 for the functional outcome, Roland-Morris Disability Scale at 8 weeks). No other consistent interactions were observed.
Conclusion: This secondary analysis found little evidence for the existence of subgroups of patients with chronic back pain that would be especially likely to benefit from acupuncture. However, persons with chronic low back pain who had more severe baseline dysfunction had the most short-term benefit from acupuncture.
C1 [Sherman, Karen J.; Cherkin, Daniel C.; Ichikawa, Laura; Barlow, William E.] Grp Hlth Res Inst, Seattle, WA USA.
[Avins, Andrew L.] No Calif Kaiser Permanente, Div Res, Oakland, CA USA.
[Barlow, William E.] Canc Res & Biostat, Seattle, WA USA.
[Khalsa, Partap S.] Natl Ctr Complementary & Alternat Med, Div Extramural Res & Training, NIH, Bethesda, MD USA.
[Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA.
RP Sherman, KJ (reprint author), Grp Hlth Res Inst, Seattle, WA USA.
EM sherman.k@ghc.org; cherkin.d@ghc.org; ichikawa.l@ghc.org;
andrew.avins@ucsf.edu; williamb@crab.org; khalsap@mail.nih.gov;
deyor@ohsu.edu
FU National Center for Complementary and Alternative Medicine (NCCAM) [U01
AT 001110]
FX We also thank Lhasa OMS, Weymouth Massachusetts, for donating the Seirin
acupuncture needles used in this study. We also thank the original
members of the SPINE study team for their contributions to the conduct
of the trial.
NR 37
TC 18
Z9 20
U1 0
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2474
J9 BMC MUSCULOSKEL DIS
JI BMC Musculoskelet. Disord.
PD SEP 21
PY 2009
VL 10
AR 114
DI 10.1186/1471-2474-10-114
PG 10
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA 503RB
UT WOS:000270555800002
PM 19772583
ER
PT J
AU Giaccone, G
Zatloukal, P
Roubec, J
Floor, K
Musil, J
Kuta, M
van Klaveren, RJ
Chaudhary, S
Gunther, A
Shamsili, S
AF Giaccone, Giuseppe
Zatloukal, Petr
Roubec, Jaromir
Floor, Karijn
Musil, Jaromir
Kuta, Milan
van Klaveren, Rob J.
Chaudhary, Subhash
Gunther, Adrie
Shamsili, Setareh
TI Multicenter Phase II Trial of YM155, a Small-Molecule Suppressor of
Survivin, in Patients With Advanced, Refractory, Non-Small-Cell Lung
Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT International Conference of the
American-Association-for-Cancer-Research/National-Cancer-Institute/Europ
ean-Organisation-for-Research-and-Treatment-of-Cancer
CY OCT 22-26, 2007
CL San Francisco, CA
SP Amer Assoc Canc Res, NCI, European Org Res & Treatment Canc
ID ANTI-APOPTOSIS GENE; ANTIAPOPTOSIS GENE; PROGNOSTIC-FACTORS; EXPRESSION;
CHEMOTHERAPY; DOCETAXEL; CARCINOMA; NEUROBLASTOMA; THERAPY; MARKER
AB Purpose
To evaluate the antitumor activity and safety of YM155, a novel, small-molecule suppressor of survivin, as single-agent therapy in patients with previously treated, advanced non-small-cell lung cancer (NSCLC).
Patients and Methods
Patients with stage IIIb/IV NSCLC who had experienced treatment failure during one or two prior chemotherapy regimens (at least one of which was platinum based) received YM155 as a continuous intravenous infusion (4.8 mg/m(2)/d) over 168 hours followed by observation for 14 days in 21-day treatment cycles. The primary end point was objective tumor response rate (ORR). Secondary end points included duration of stable disease (SD), progression-free survival (PFS), overall survival (OS), safety and pharmacokinetic profiles, and pharmacodynamic evaluations.
Results
Thirty-seven patients received YM155. Two patients achieved a confirmed partial response, with an ORR of 5.4% (95% CI, 0.7% to 18.2%). An additional 14 patients (37.8%) achieved SD resulting in a disease control rate of 43.2% (95% CI, 27.1% to 60.5%). Median duration of PFS was 1.7 months (95% CI, 1.3 to 2.8 months). Median duration of OS was 6.6 months (95% CI, 4 to 12.2 months), with a 1-year survival rate of 35.1%. Treatment with YM155 was well tolerated with the majority of treatment discontinuations not treatment related.
Conclusion
YM155 exhibited modest single-agent activity in patients with refractory, advanced NSCLC. A favorable safety/tolerability profile was reported. Further evaluation of YM155 in combination with chemotherapy and other targeted agents may be warranted. J Clin Oncol 27:4481-4486. (C) 2009 by American Society of Clinical Oncology
C1 Vrije Univ Med Ctr, Amsterdam, Netherlands.
Erasmus MC, Rotterdam, Netherlands.
Astellas Pharma Europe BV, Leiderdorp, Netherlands.
Charles Univ Prague, Fac Med 3, Prague, Czech Republic.
Teaching Hosp Bulovka, Prague, Czech Republic.
Charles Univ Prague, Fac Med 2, Prague, Czech Republic.
Teaching Hosp Motol, Prague, Czech Republic.
Teaching Hosp Ostrava Poruba, Ostrava, Czech Republic.
Nemocnice Chomutov, Chomutov, Czech Republic.
Onkol Ctr JG Mendla, Novy Jicin, Czech Republic.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
NR 35
TC 130
Z9 138
U1 0
U2 6
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2009
VL 27
IS 27
BP 4481
EP 4486
DI 10.1200/JCO.2008.21.1862
PG 6
WC Oncology
SC Oncology
GA 496ZO
UT WOS:000270019900009
PM 19687333
ER
PT J
AU Veytsman, I
Nieman, L
Fojo, T
AF Veytsman, Irina
Nieman, Lynnette
Fojo, Tito
TI Management of Endocrine Manifestations and the Use of Mitotane As a
Chemotherapeutic Agent for Adrenocortical Carcinoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID ADRENAL-CORTICAL CARCINOMA; PHASE-II TRIAL;
POSITRON-EMISSION-TOMOGRAPHY; INDEPENDENT PROSTATE-CANCER;
CLINICAL-PRACTICE GUIDELINE; SOUTHWEST-ONCOLOGY-GROUP; HIGH-DOSE
KETOCONAZOLE; CUSHINGS-SYNDROME; ADJUVANT MITOTANE; PRIMARY
ALDOSTERONISM
AB Adrenal cortical carcinoma (ACC) is a rare malignancy in which patients have poor overall 5-year survival. Patients with ACC can present with symptoms of hormone excess, including Cushing's syndrome, virilization, feminization, or-less frequently-hypertension with hypokalemia. In many patients with ACC, advanced disease at presentation precludes surgery or is followed by local relapse or distant metastatic disease that cannot be managed surgically. In these instances, chemotherapy is often tried, but its limited efficacy all too often leaves the problem of persistent hormonal excess. Physicians who treat patients with ACC and severe hypercortisolism should recognize that uncontrolled hormone production is a malignant disease, which has severe consequences that require aggressive management. Because chemotherapy benefits only a small percentage of patients, steroidogenesis inhibitors, including mitotane, ketoconazole, metyrapone, and etomidate, should be used singly or in combination even as chemotherapy is administered. Diligent management with frequent adjustments is required, especially in patients with chemotherapy-refractory tumors that continue to grow. In the absence of randomized, controlled trials, adjuvant use of mitotane remains controversial, although the authors of a recent case-control study argue for its use. Despite difficulty administering effective doses, most clinicians agree that mitotane should be used if the tumor cannot be removed surgically or should be used as adjuvant therapy if there is a high likelihood of recurrence. The option of long-term monotherapy is restricted to patients who tolerate mitotane and either experience a clinical response or are at high risk for recurrence. Recommendations are provided to help manage patients with this difficult disease and to improve the quality of their lives. J Clin Oncol 27: 4619-4629. (C) 2009 by American Society of Clinical Oncology
C1 [Fojo, Tito] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
Program Reprod & Adult Endocrinol, Bethesda, MD USA.
RP Fojo, T (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tfojo@helix.nih.gov
FU Intramural NIH HHS [ZIE HD008832-03]
NR 121
TC 57
Z9 59
U1 0
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 20
PY 2009
VL 27
IS 27
BP 4619
EP 4629
DI 10.1200/JCO.2008.17.2775
PG 11
WC Oncology
SC Oncology
GA 496ZO
UT WOS:000270019900029
PM 19667279
ER
PT J
AU Bushel, PR
AF Bushel, Pierre R.
TI Delineation of Perturbed Biological Systems that Govern Hepatotoxic
Potential
SO MOLECULAR & CELLULAR TOXICOLOGY
LA English
DT Meeting Abstract
C1 [Bushel, Pierre R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KOREAN SOC TOXICOGENOMICS & TOXICOPROTEOMICS
PI SEOUL
PA KOREA INST SCIENCE & TECHNOLOGY, PO BOX 131 CHEONGRYANG, SEOUL, 130-650,
SOUTH KOREA
SN 1738-642X
J9 MOL CELL TOXICOL
JI Mol. Cell. Toxicol.
PD SEP 20
PY 2009
VL 5
IS 3
BP 40
EP 40
PG 1
WC Biochemistry & Molecular Biology; Toxicology
SC Biochemistry & Molecular Biology; Toxicology
GA 497BG
UT WOS:000270028200002
ER
PT J
AU Bushel, PR
AF Bushel, Pierre R.
TI Cross Tissue Inference: Genomic Indicators of Hepatotoxicity Conferred
through Perturbed Systems in the Blood
SO MOLECULAR & CELLULAR TOXICOLOGY
LA English
DT Meeting Abstract
C1 [Bushel, Pierre R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KOREAN SOC TOXICOGENOMICS & TOXICOPROTEOMICS
PI SEOUL
PA KOREA INST SCIENCE & TECHNOLOGY, PO BOX 131 CHEONGRYANG, SEOUL, 130-650,
SOUTH KOREA
SN 1738-642X
J9 MOL CELL TOXICOL
JI Mol. Cell. Toxicol.
PD SEP 20
PY 2009
VL 5
IS 3
BP 42
EP 42
PG 1
WC Biochemistry & Molecular Biology; Toxicology
SC Biochemistry & Molecular Biology; Toxicology
GA 497BG
UT WOS:000270028200009
ER
PT J
AU Paules, RS
Bushel, PR
Fannin, RD
Cui, YX
Heinloth, AN
Auman, JT
Lobenhofer, EK
Chou, JW
Li, JY
Russo, M
O'Connell, T
Boorman, GA
Jayadev, S
Tennant, RW
Watkins, PB
AF Paules, Richard S.
Bushel, Pierre R.
Fannin, Rickie D.
Cui, Yuxia
Heinloth, Alexandra N.
Auman, J. Todd
Lobenhofer, Edward K.
Chou, Jeff W.
Li, Jianying
Russo, Mark
O'Connell, Thomas
Boorman, Gary A.
Jayadev, Supriya
Tennant, Raymond W.
Watkins, Paul B.
TI An 'Omics' Approach for Identifying Biomarkers of Adverse Effects
SO MOLECULAR & CELLULAR TOXICOLOGY
LA English
DT Meeting Abstract
C1 [Paules, Richard S.; Bushel, Pierre R.; Fannin, Rickie D.; Cui, Yuxia; Heinloth, Alexandra N.; Auman, J. Todd; Chou, Jeff W.; Li, Jianying; Boorman, Gary A.; Tennant, Raymond W.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Lobenhofer, Edward K.] Cogenics, Morrisville, NC 27560 USA.
[Russo, Mark; O'Connell, Thomas; Watkins, Paul B.] Univ N Carolina, Chapel Hill, NC 27599 USA.
[O'Connell, Thomas; Watkins, Paul B.] Hamner Inst, Res Triangle Pk, NC 27709 USA.
[Jayadev, Supriya] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU KOREAN SOC TOXICOGENOMICS & TOXICOPROTEOMICS
PI SEOUL
PA KOREA INST SCIENCE & TECHNOLOGY, PO BOX 131 CHEONGRYANG, SEOUL, 130-650,
SOUTH KOREA
SN 1738-642X
J9 MOL CELL TOXICOL
JI Mol. Cell. Toxicol.
PD SEP 20
PY 2009
VL 5
IS 3
BP 46
EP 46
PG 1
WC Biochemistry & Molecular Biology; Toxicology
SC Biochemistry & Molecular Biology; Toxicology
GA 497BG
UT WOS:000270028200024
ER
PT J
AU Xiao, XD
Feng, Y
Vu, BK
Ishima, R
Dimitrov, DS
AF Xiao, Xiaodong
Feng, Yang
Vu, Bang K.
Ishima, Rieko
Dimitrov, Dimiter S.
TI A large library based on a novel (CH2) scaffold: Identification of HIV-1
inhibitors
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE CH2; Scaffold; Antibody library; HIV; Phage display; Human
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CORECEPTOR-BINDING-SITE; ANTIBODIES;
DOMAINS; RECOGNITION; PROTEINS; RECEPTOR
AB Isolated immunoglobulin CH2 domains were proposed as scaffolds for selection of binders with potential effector functions. We tested the feasibility of this approach by constructing a large (size 5 x 10(10)) library where all amino acids in two loops (BC and FG) were mutated to four residues (Y, A, D, or S). Three binders were selected from this library by panning against a gp120-CD4 complex. The strongest binder, m1a1, recognized specifically a highly conserved CD4i epitope and inhibited to various extents seven out of nine HIV-1 isolates from different clades. The loop BC and the conformational state of the scaffold are critical for its binding. These results provide a proof of concept for the potential of CH2 as a scaffold for construction of libraries containing potentially useful binders. The newly identified HIV-1 inhibitors could be further improved to candidate therapeutics and/or used as research reagents for exploration of conserved gp120 structures. Published by Elsevier Inc.
C1 [Xiao, Xiaodong; Feng, Yang; Vu, Bang K.; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, NIH, Frederick, MD 21702 USA.
[Ishima, Rieko] Univ Pittsburgh, Dept Biol Struct, Sch Med, Pittsburgh, PA 15260 USA.
RP Dimitrov, DS (reprint author), NCI, Prot Interact Grp, CCRNP, NIH, Bldg 469,Rm 150B, Frederick, MD 21702 USA.
EM dimitrov@ncifcrf.gov
FU Intramural AIDS Targeted Antiviral Program (IATAP); National Institutes
of Health (NIH); Intramural Research Program of the NIH; National Cancer
Institute; Center for Cancer Research
FX We thank Christopher Broder, Gerald Quinnan, Dennis Burton and Tim Fouts
for providing reagents, and the members of our group Weizao Chen,
Zhongyu Zhu, Rui Gong, John Owens and Meiyun Zhang for help. This work
was supported by the Intramural AIDS Targeted Antiviral Program (IATAP),
National Institutes of Health (NIH) and by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research.
NR 25
TC 25
Z9 26
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD SEP 18
PY 2009
VL 387
IS 2
BP 387
EP 392
DI 10.1016/j.bbrc.2009.07.044
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 483OX
UT WOS:000268978200031
PM 19615335
ER
PT J
AU Maragkakis, M
Alexiou, P
Papadopoulos, GL
Reczko, M
Dalamagas, T
Giannopoulos, G
Goumas, G
Koukis, E
Kourtis, K
Simossis, VA
Sethupathy, P
Vergoulis, T
Koziris, N
Sellis, T
Tsanakas, P
Hatzigeorgiou, AG
AF Maragkakis, Manolis
Alexiou, Panagiotis
Papadopoulos, Giorgio L.
Reczko, Martin
Dalamagas, Theodore
Giannopoulos, George
Goumas, George
Koukis, Evangelos
Kourtis, Kornilios
Simossis, Victor A.
Sethupathy, Praveen
Vergoulis, Thanasis
Koziris, Nectarios
Sellis, Timos
Tsanakas, Panagiotis
Hatzigeorgiou, Artemis G.
TI Accurate microRNA target prediction correlates with protein repression
levels
SO BMC BIOINFORMATICS
LA English
DT Article
ID CAENORHABDITIS-ELEGANS; SMALL RNAS; IDENTIFICATION; GENOMICS; GENES
AB Background: MicroRNAs are small endogenously expressed non-coding RNA molecules that regulate target gene expression through translation repression or messenger RNA degradation. MicroRNA regulation is performed through pairing of the microRNA to sites in the messenger RNA of protein coding genes. Since experimental identification of miRNA target genes poses difficulties, computational microRNA target prediction is one of the key means in deciphering the role of microRNAs in development and disease.
Results: DIANA-microT 3.0 is an algorithm for microRNA target prediction which is based on several parameters calculated individually for each microRNA and combines conserved and non-conserved microRNA recognition elements into a final prediction score, which correlates with protein production fold change. Specifically, for each predicted interaction the program reports a signal to noise ratio and a precision score which can be used as an indication of the false positive rate of the prediction.
Conclusion: Recently, several computational target prediction programs were benchmarked based on a set of microRNA target genes identified by the pSILAC method. In this assessment DIANA-microT 3.0 was found to achieve the highest precision among the most widely used microRNA target prediction programs reaching approximately 66%. The DIANA-microT 3.0 prediction results are available online in a user friendly web server at http://www.microrna.gr/microT
C1 [Maragkakis, Manolis; Alexiou, Panagiotis; Papadopoulos, Giorgio L.; Reczko, Martin; Simossis, Victor A.; Hatzigeorgiou, Artemis G.] Biomed Sci Res Ctr Alexander Fleming, Inst Mol Oncol, Vari, Greece.
[Maragkakis, Manolis] Univ Halle Wittenberg, Inst Comp Sci, D-06120 Halle, Germany.
[Alexiou, Panagiotis] Aristotle Univ Thessaloniki, Sch Biol, Thessaloniki 54124, Greece.
[Reczko, Martin] Synaptic Ltd, Iraklion, Greece.
[Dalamagas, Theodore; Giannopoulos, George; Vergoulis, Thanasis; Sellis, Timos] Athena Res Ctr, Inst Management Informat Syst, Athens, Greece.
[Giannopoulos, George; Vergoulis, Thanasis; Sellis, Timos] Natl Tech Univ Athens, Dept Comp Sci, Sch Elect & Comp Engn, Knowledge & Database Syst Lab, GR-10682 Athens, Greece.
[Goumas, George; Koukis, Evangelos; Kourtis, Kornilios; Koziris, Nectarios; Tsanakas, Panagiotis] Natl Tech Univ Athens, Dept Comp Sci, Sch Elect & Comp Engn, Comp Syst Lab, GR-10682 Athens, Greece.
[Sethupathy, Praveen] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20876 USA.
[Hatzigeorgiou, Artemis G.] Univ Penn, Dept Comp & Informat Sci, Philadelphia, PA 19104 USA.
RP Maragkakis, M (reprint author), Biomed Sci Res Ctr Alexander Fleming, Inst Mol Oncol, Vari, Greece.
EM maragkakis@fleming.gr; pan.alexiou@fleming.gr; papadopoulos@fleming.gr;
reczko@fleming.gr; dalamag@imis.athenainnovation.gr;
giann@dblab.ece.ntua.gr; goumas@cslab.ece.ntua.gr;
vkoukis@cslab.ece.ntua.gr; kkourt@cslab.ece.ntua.gr;
simossis@fleming.gr; sethupathyp@mail.nih.gov;
bergoulis@dblab.ece.ntua.gr; nkoziris@cslab.ece.ntua.gr;
timos@imis.athena-innovation.gr; tsanakas@admin.grnet.gr;
artemis@fleming.gr
RI Maragkakis, Manolis/F-5427-2010; ALEXIOU, PANAGIOTIS/C-8906-2011;
OI Maragkakis, Manolis/0000-0002-3158-1763; Alexiou,
Panagiotis/0000-0003-3437-7482; Reczko, Martin/0000-0002-0005-8718
NR 26
TC 200
Z9 206
U1 1
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD SEP 18
PY 2009
VL 10
AR 295
DI 10.1186/1471-2105-10-295
PG 10
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 500DD
UT WOS:000270276500001
PM 19765283
ER
PT J
AU Hsieh, SM
Smith, RA
Lintell, NA
Hunter, KW
Griffiths, LR
AF Hsieh, Szu-Min
Smith, Robert A.
Lintell, Nicholas A.
Hunter, Kent W.
Griffiths, Lyn R.
TI Polymorphisms of the SIPA1 gene and sporadic breast cancer
susceptibility
SO BMC CANCER
LA English
DT Article
ID METASTASIS; PROTEIN
AB Background: The novel breast cancer metastasis modulator gene signal-induced proliferation-associated 1 (Sipa1) underlies the breast cancer metastasis efficiency modifier locus Mtes 1 and has been shown to influence mammary tumour metastatic efficiency in the mouse, with an ectopically expressing Sipa1 cell line developing 1.5 to 2 fold more surface pulmonary metastases. Sipa1 encodes a mitogen-inducible GTPase activating (GAP) protein for members of the Ras-related proteins; participates in cell adhesion and modulates mitogen-induced cell cycle progression. Germline SIPA1 SNPs showed association with positive lymph node metastasis and hormonal receptor status in a Caucasian cohort. We hypothesized that SIPA1 may also be correlated to breast carcinoma incidence as well as prognosis. Therefore, this study investigated the potential relationship of SIPA1 and human breast cancer incidence by a germline SNP genotype frequency association study in a case-control Caucasian cohort in Queensland, Australia.
Methods: The SNPs genotyped in this study were identified in a previous study and the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The data were analysed with chisquare method and the Monte Carlo style CLUMP analysis program.
Results: Results indicated significance with SIPA1 SNP rs3741378; the CC genotype was more frequently observed in the breast cancer group compared to the disease-free control group, indicating the variant C allele was associated with increased breast cancer incidence.
Conclusion: This observation indicates SNP rs3741378 as a novel potential sporadic breast cancer predisposition SNP. While it showed association with hormonal receptor status in breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S) to Phe (F)) changes a hydrophilic residue (S) to a hydrophobic residue (F) and may significantly alter the protein functions of SIPA1 in breast tumourgenesis. SIPA1 SNPs rs931127 (5' near gene), and rs746429 (synonymous (Ala (A) to Ala (A)), did not show significant associations with breast cancer incidence, yet were associated with lymph node metastasis in the previous study. This suggests that SIPA1 may be involved in different stages of breast carcinogenesis and since this study replicates a previous study of the associated SNP, it implicates variants of the SIPA1 gene as playing a potential role in breast cancer.
C1 [Hsieh, Szu-Min; Smith, Robert A.; Griffiths, Lyn R.] Griffith Univ, Griffith Inst Hlth & Med Res, Nathan, Qld 4111, Australia.
[Hsieh, Szu-Min; Lintell, Nicholas A.; Hunter, Kent W.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
RP Griffiths, LR (reprint author), Griffith Univ, Griffith Inst Hlth & Med Res, Gold Coast Campus, Nathan, Qld 4111, Australia.
EM hsiehsz@mail.nih.gov; robert.a.smith@griffith.edu.au;
lintelln@mail.nih.gov; hunterk@mail.nih.gov; l.griffiths@griffith.edu.au
OI Griffiths, Lyn/0000-0002-6774-5475
NR 7
TC 8
Z9 9
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD SEP 18
PY 2009
VL 9
AR 331
DI 10.1186/1471-2407-9-331
PG 6
WC Oncology
SC Oncology
GA 500NW
UT WOS:000270310600001
PM 19765277
ER
PT J
AU Iguchi, G
Chrysovergis, K
Lee, SH
Baek, SJ
Langenbach, R
Eling, TE
AF Iguchi, Genzo
Chrysovergis, Kali
Lee, Seong-Ho
Baek, Seung Joon
Langenbach, Robert
Eling, Thomas E.
TI A reciprocal relationship exists between non-steroidal anti-inflammatory
drug-activated gene-1 (NAG-1) and cyclooxygenase-2
SO CANCER LETTERS
LA English
DT Article
DE GDF-15; NAG-1; COX-2; Colorectal cancer
ID CELECOXIB INDUCES APOPTOSIS; BETA SUPERFAMILY MEMBER; GROWTH-FACTOR
RECEPTOR; INTESTINAL NEOPLASIA; CANCER PREVENTION; ADENOMA GROWTH; MIN
MICE; EXPRESSION; INHIBITORS; PATHWAY
AB Non-steroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) and COX-2 are involved in cellular processes such as inflammation, apoptosis, and tumorigenesis. To address the relationship between COX-2 and NAG-1 expression, we investigated the expression of NAG-1 and COX-2 in normal and tumor tissue from human patients, Apc(Min/+) mice, and COX-2(-/-) mice. While COX-2 expression is highly induced in tumor tissue, NAG-1 expression is reduced. Furthermore, PGE2 reduces NAGA while celebrex induces NAGA expression. The results suggest that a possible inverse relationship exists between the expression of NAGA and COX-2 in tumor formation of colon tissue. Published by Elsevier Ltd.
C1 [Iguchi, Genzo; Chrysovergis, Kali; Langenbach, Robert; Eling, Thomas E.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Iguchi, Genzo] Kobe Univ, Dept Biosignal Pathophysiol, Grad Sch Med, Nada Ku, Kobe, Hyogo 6578501, Japan.
[Lee, Seong-Ho; Baek, Seung Joon] Univ Tennessee, Dept Pathobiol, Coll Vet Med, Knoxville, TN 37996 USA.
RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM eling@niehs.nih.gov
OI Baek, Seung/0000-0001-7866-7778
FU National Institute of Environmental Health Sciences; National Institutes
of Health; Intramural program
FX We wish to thank Chris Lee and Colleen Anna for their support. This work
was supported, in part, by the National Institute of Environmental
Health Sciences, National Institutes of Health, Intramural program.
NR 33
TC 20
Z9 20
U1 0
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD SEP 18
PY 2009
VL 282
IS 2
BP 152
EP 158
DI 10.1016/j.canlet.2009.03.006
PG 7
WC Oncology
SC Oncology
GA 483UQ
UT WOS:000268994300004
PM 19375854
ER
PT J
AU Strober, W
AF Strober, Warren
TI The Multifaceted Influence of the Mucosal Microflora on Mucosal
Dendritic Cell Responses
SO IMMUNITY
LA English
DT Review
ID INFLAMMATORY-BOWEL-DISEASE; INTESTINAL EPITHELIAL-CELLS; INVASIVE
ESCHERICHIA-COLI; REGULATORY T-CELLS; ENTERIC BACTERIAL-ANTIGENS;
NEONATAL FC-RECEPTOR; ILEAL CROHNS-DISEASE; TOLL-LIKE RECEPTORS;
IMMUNE-RESPONSES; NEGATIVE REGULATOR
AB Over the last decade, it has become apparent that the complex interactions between components of the mucosal microflora and the mucosal immune system can involve either direct contact with dendritic cells in the lamina propria or, alternatively, contact with epithelial cells lining the mucosa that then influence the function of dendritic cells. Although in some cases these interactions involve signaling specific to particular organisms and in others, to classes of organisms, a common theme is that signaling is invariably channeled through receptors that address many organisms or all organisms such as the pattern-recognition receptors TLR and NLR. Here, I review this information with the intention of identifying how the mucosal microflora influences specific functions of the mucosal immune system such the production of particular cytokines as well as broader functions such as the maintenance of mucosal immune homeostasis and host defense.
C1 NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
EM wstrober@niaid.nih.gov
NR 83
TC 55
Z9 58
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD SEP 18
PY 2009
VL 31
IS 3
BP 377
EP 388
DI 10.1016/j.immuni.2009.09.001
PG 12
WC Immunology
SC Immunology
GA 503IA
UT WOS:000270525900004
PM 19766081
ER
PT J
AU Varma, R
AF Varma, Rajat
TI Diffusion and Signaling Revisited
SO IMMUNITY
LA English
DT Editorial Material
ID MAST-CELLS; RECEPTOR; IGE
AB In this issue of Immunity, Andrews et al. (2009) used single-molecule fluorescence microscopy to demonstrate that the IgE receptor Fc epsilon RI in the plasma membrane can signal in a mobile state.
C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Varma, R (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA.
EM varmarajat@niaid.nih.gov
RI Varma, Rajat/I-1209-2012
OI Varma, Rajat/0000-0001-5131-0402
NR 10
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD SEP 18
PY 2009
VL 31
IS 3
BP 452
EP 454
DI 10.1016/j.immuni.2009.08.018
PG 3
WC Immunology
SC Immunology
GA 503IA
UT WOS:000270525900011
PM 19766088
ER
PT J
AU Sarafova, SD
Van Laethem, F
Adoro, S
Guinter, T
Sharrow, SO
Feigenbaum, L
Singer, A
AF Sarafova, Sophia D.
Van Laethem, Francois
Adoro, Stanley
Guinter, Terry
Sharrow, Susan O.
Feigenbaum, Lionel
Singer, Alfred
TI Upregulation of CD4 Expression during MHC Class II-Specific Positive
Selection Is Essential for Error-free Lineage Choice
SO IMMUNITY
LA English
DT Article
ID T-CELL DEVELOPMENT; GENE-EXPRESSION; TRANSGENIC MICE; THYMOCYTE
DIFFERENTIATION; LYMPHOCYTE DEVELOPMENT; CORECEPTOR EXPRESSION;
TRANSCRIPTION FACTORS; STOCHASTIC MECHANISM; SILENCER ELEMENT; ANTIGEN
RECEPTOR
AB The lineage fate of developing thymocytes is determined by the persistence or cessation of T cell receptor (TCR) signaling during positive selection, with persistent TCR signaling required for CD4 lineage choice. We show here that transcriptional upregulation of CD4 expression is essential for error-free lineage choice during major histocompatibility complex class II (MHC II)-specific positive selection and is critical for error-free lineage choice in TCR-transgenic mice whose thymocytes compete for the identical selecting ligand. CD4 upregulation occurred for endogenously encoded CD4 coreceptors, but CD4 transgenes were downregulated during positive selection, disrupting MHC II-specific TCR signaling and causing lineage errors regardless of the absolute number or signaling strength of transgenic CD4 proteins. Thus, the kinetics of CD4 coreceptor expression during MIHC II-specific positive selection determines the integrity of CD4 lineage choice, revealing an elegant symmetry between coreceptor kinetics and lineage choice.
C1 [Sarafova, Sophia D.; Van Laethem, Francois; Adoro, Stanley; Guinter, Terry; Sharrow, Susan O.; Singer, Alfred] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA.
[Feigenbaum, Lionel] NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA.
[Sarafova, Sophia D.] Davidson Coll, Dept Biol, Davidson, NC 28036 USA.
RP Singer, A (reprint author), NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA.
EM singera@nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute; enter
for Cancer Research
FX We thank N. Taylor, R. Bosselut, H. Park, and R. Hodes for helpful
discussions and critical readings of the manuscript; R. Bosselut for the
original construction of re-engineered CD4hCD2 transgenes; L.
Granger and A. Adams for expert flow cytometry; D. Plugge for data
analysis support; and K. Tsaneva-Atanasova for help with statistical
analyses. This research was supported by the Intramural Research Program
of the NIH, National Cancer Institute, and enter for Cancer Research.
NR 42
TC 10
Z9 10
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD SEP 18
PY 2009
VL 31
IS 3
BP 480
EP 490
DI 10.1016/j.immuni.2009.07.006
PG 11
WC Immunology
SC Immunology
GA 503IA
UT WOS:000270525900015
PM 19747858
ER
PT J
AU Uranishi, H
Zolotukhin, AS
Lindtner, S
Warming, S
Zhang, GM
Bear, J
Copeland, NG
Jenkins, NA
Pavlakis, GN
Felber, BK
AF Uranishi, Hiroaki
Zolotukhin, Andrei S.
Lindtner, Susan
Warming, Soren
Zhang, Gen-Mu
Bear, Jenifer
Copeland, Neal G.
Jenkins, Nancy A.
Pavlakis, George N.
Felber, Barbara K.
TI The RNA-binding Motif Protein 15B (RBM15B/OTT3) Acts as Cofactor of the
Nuclear Export Receptor NXF1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DROSOPHILA EYE DEVELOPMENT; TRANSPORT ELEMENT RTE; HNRNP-LIKE PROTEINS;
MESSENGER-RNA; SPLIT-ENDS; MENTAL-RETARDATION; SIGNALING PATHWAY;
GENETIC SCREEN; FAMILY-MEMBERS; TARGET GENES
AB The human SPEN family proteins SHARP, RBM15/OTT1, and RBM15B/OTT3 share the structural domain architecture but show distinct functional properties. Here, we examined the function of OTT3 and compared it with its paralogues RBM15 and SHARP. We found that OTT3, like RBM15, has post-transcriptional regulatory activity, whereas SHARP does not, supporting a divergent role of RBM15 and OTT3. OTT3 shares with RBM15 the association with the splicing factor compartment and the nuclear envelope as well as the binding to mRNA export factors NXF1 and Aly/REF. Mutational analysis revealed direct interaction of OTT3 and RBM15 with NXF1 via their C-terminal regions. Biochemical and subcellular localization studies showed that OTT3 and RBM15 also interact with each other in vivo, further supporting a shared function. Genetic knockdown of RBM15 in mouse is embryonically lethal, indicating that OTT3 cannot compensate for the RBM15 loss, which supports the notion that these proteins, in addition to sharing similar activities, likely have distinct biological roles.
C1 [Uranishi, Hiroaki; Lindtner, Susan; Pavlakis, George N.] NCI, Human Retrovirus Sect, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Zolotukhin, Andrei S.; Zhang, Gen-Mu; Bear, Jenifer; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Warming, Soren; Copeland, Neal G.; Jenkins, Nancy A.] NCI, Mouse Canc Genet Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Felber, BK (reprint author), POB B,Bldg 535,Rm 209, Frederick, MD 21702 USA.
EM felberb@mail.nih.gov
FU National Institutes of Health Intramural Research Program
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program.
NR 56
TC 24
Z9 24
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD SEP 18
PY 2009
VL 284
IS 38
BP 26106
EP 26116
DI 10.1074/jbc.M109.040113
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 493LK
UT WOS:000269738000066
PM 19586903
ER
PT J
AU Luongo, C
Yang, LJ
Winter, CC
Spann, KM
Murphy, BR
Collins, PL
Buchholz, UJ
AF Luongo, Cindy
Yang, Lijuan
Winter, Christine C.
Spann, Kirsten M.
Murphy, Brian R.
Collins, Peter L.
Buchholz, Ursula J.
TI Codon stabilization analysis of the "248" temperature sensitive mutation
for increased phenotypic stability of respiratory syncytial virus
vaccine candidates
SO VACCINE
LA English
DT Article
DE Pneumovirus; Respiratory syncytial virus vaccine; Temperature sensitive
ID F-GLYCOPROTEIN; RSV VACCINE; L GENE; LIVE; ATTENUATION; CHILDREN;
MUTANT; ADULTS; CHIMPANZEES; IMMUNOGENICITY
AB Human respiratory syncytial virus (RSV) is the most important viral agent of serious pediatric respiratory tract illness worldwide. Presently, the most promising vaccine candidate is a live, attenuated, cDNA-derived virus, RSV rA2cp248/404/1030 Delta SH, whose attenuation phenotype is based in large part on a series of point mutations including a glutamine to leucine (Q to L) substitution at amino acid residue 831 of the polymerase protein 1, a mutation originally called "248". This mutation specifies both a temperature sensitive (ts) and attenuation phenotype. Reversion of this mutation from leucine back to glutamine was detected in some samples in clinical phase 1 trials. To identify the most genetically stable "attenuating" codon at this position to be included in a more stable RSV vaccine, we sought to create and evaluate recombinant RSVs representing all 20 possible amino acid assignments at this position, as well as small insertions and deletions. The recoverable viruses constituted a panel representing 18 different amino acid assignments, and were evaluated for temperature sensitivity in vitro and attenuation in mice. The original leucine mutation was found to be the most attenuating, followed only by phenylalanine. The paucity of highly attenuating assignments limited the possibility of increasing genetic stability. Indeed, it was not possible to find a leucine or phenylalanine codon requiring more than a single nucleotide change to yield a "non-attenuating" codon, as is necessary for the stabilization strategy. Nonetheless, serial passage of the six possible leucine codons in vitro at increasing temperatures revealed differences, with slower reversion to non-attenuated phenotypes for a subset of codons. Thus, it should be possible to modestly increase the phenotypic stability of the rA2cp248/404/1030 Delta SH vaccine virus by codon modification at the locus of the 248 mutation. In addition to characterizing the phenotypes associated with a particular locus in the RSV L protein, this manuscript provides insight into the problem of the instability of point mutations and the limitations of strategies to stabilize them. Published by Elsevier Ltd.
C1 [Luongo, Cindy; Yang, Lijuan; Winter, Christine C.; Murphy, Brian R.; Collins, Peter L.; Buchholz, Ursula J.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
[Spann, Kirsten M.] Univ Queensland, Clin Med Virol Ctr, Sir Albert Sakzewski Virus Res Ctr, Herston, Qld 4029, Australia.
RP Buchholz, UJ (reprint author), Bldg 50,Room 6505,50 South Dr,MSC 8007, Bethesda, MD 20892 USA.
EM ubuchholz@niaid.nih.gov
RI Spann, Kirsten/B-4524-2013
OI Spann, Kirsten/0000-0003-0567-8382
FU MedImmune, Inc., Gaithersburg; NIAID, NIH
FX We thank the staff of the animal facility, Bldg. 50, for care of the
mice used in this study. We thank Jeff Skinner, BCBB/NIAID, for support
with the statistical analyses. This research was supported by a
Cooperative Research and Development Agreement with MedImmune, Inc.,
Gaithersburg, and by the Intramural Research Program of NIAID, NIH.
NR 29
TC 19
Z9 20
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD SEP 18
PY 2009
VL 27
IS 41
BP 5667
EP 5676
DI 10.1016/j.vaccine.2009.07.022
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 497OW
UT WOS:000270070400018
PM 19646406
ER
PT J
AU Bergmann-Leitner, ES
Leitner, WW
Duncan, EH
Savranskaya, T
Angov, E
AF Bergmann-Leitner, Elke S.
Leitner, Wolfgang W.
Duncan, Elizabeth H.
Savranskaya, Tatyana
Angov, Evelina
TI Molecular adjuvants for malaria DNA vaccines based on the modulation of
host-cell apoptosis
SO VACCINE
LA English
DT Article
DE Malaria; DNA vaccine; Molecular adjuvant; Circumsporozoite protein;
Protection
ID CIRCUMSPOROZOITE PROTEIN; PLASMODIUM-BERGHEI; PROTECTIVE IMMUNITY;
T-CELLS; EFFICACY; INFECTION; RESPONSES; ANTIGEN; SPOROZOITES;
ENHANCEMENT
AB Malaria represents a major global health problem but despite extensive efforts, no effective vaccine is available. Various vaccine candidates have been developed that provide protection in animal models, such as a gene gun-delivered DNA vaccine encoding the circumsporozoite protein (CSP) of Plasmodium berghei. A common shortcoming of most malaria vaccines is the requirement for multiple immunizations leaving room for improvement even for established vaccine candidates such as the CSP-DNA vaccine. In this study, we explored whether regulating apoptosis in DNA vaccine transfected host cells could accelerate the onset of protective immunity and provide significant protection after a single immunization. A proapoptotic gene (Bax) was used as a molecular adjuvant in an attempt to mimic the immunostimulatory apoptosis triggered by viral or virus-derived vaccines, while anti-apoptotic genes such as Bcl-XL may increase the life span of transfected cells thus prolonging antigen production. Surprisingly, co-delivery of either Bax or Bcl-XL greatly reduced CSP-DNA vaccine efficacy after a single immunization. Co-delivery of Bax for three immunizations still had a detrimental effect on protective immunity, while repeated co-delivery of Bcl-XL had no negative impact. The fine characterization of humoral and cellular immune response modulated by these two molecular adjuvants revealed a previously unknown effect, i.e., a shift in the Th-profile. These results demonstrate that pro- or anti-apoptotic molecules should not be used as molecular adjuvants without careful evaluation of the resulting immune response. This finding represents yet another example that strategies to enhance vaccine efficacy developed for other model systems such as viral diseases cannot easily be applied to any vaccine. (c) 2009 Elsevier Ltd. All rights reserved.
C1 [Bergmann-Leitner, Elke S.; Duncan, Elizabeth H.; Angov, Evelina] Walter Reed Army Inst Res, US Mil Malaria Vaccine Program, Dept Mol Parasitol, Silver Spring, MD 20910 USA.
[Leitner, Wolfgang W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
[Savranskaya, Tatyana] Walter Reed Army Inst Res, Div Entomol, Silver Spring, MD 20910 USA.
RP Bergmann-Leitner, ES (reprint author), Walter Reed Army Inst Res, US Mil Malaria Vaccine Program, Dept Mol Parasitol, 503 Robert Grant Ave, Silver Spring, MD 20910 USA.
EM Elke.Bergmannleitner@us.army.mil
RI Bergmann-Leitner, Elke/B-3548-2011; Leitner, Wolfgang/F-5741-2011
OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Leitner,
Wolfgang/0000-0003-3125-5922
FU United States Agency for International Development [936-6001,
AAG-P-00-98-00006, AAG-P-0098-00005]; United States Army Medical
Research and Materiel Command
FX The authors would like to thank Dr. Richard joule for the proand
anti-apoptotic plasmids. The work was initiated under the guidance of
Dr. Jeffrey Lyon and supported by the United States Agency for
International Development, Project Number 936-6001, Award Number
AAG-P-00-98-00006, Award Number AAG-P-0098-00005 and by the United
States Army Medical Research and Materiel Command.
NR 38
TC 13
Z9 14
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD SEP 18
PY 2009
VL 27
IS 41
BP 5700
EP 5708
DI 10.1016/j.vaccine.2009.06.059
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 497OW
UT WOS:000270070400022
PM 19576940
ER
PT J
AU Stumpo, DJ
Broxmeyer, HE
Ward, T
Cooper, S
Hangoc, G
Chung, YJ
Shelley, WC
Richfield, EK
Ray, MK
Yoder, MC
Aplan, PD
Blackshear, PJ
AF Stumpo, Deborah J.
Broxmeyer, Hal E.
Ward, Toni
Cooper, Scott
Hangoc, Giao
Chung, Yang Jo
Shelley, William C.
Richfield, Eric K.
Ray, Manas K.
Yoder, Mervin C.
Aplan, Peter D.
Blackshear, Perry J.
TI Targeted disruption of Zfp36l2, encoding a CCCH tandem zinc finger
RNA-binding protein, results in defective hematopoiesis
SO BLOOD
LA English
DT Article
ID MESSENGER-RNA; STEM-CELLS; PROGENITOR CELLS; YOLK-SAC; TRISTETRAPROLIN
FAMILY; CXC CHEMOKINES; MOUSE EMBRYO; EXPRESSION; REGULATOR; STABILITY
AB Members of the tristetraprolin family of tandem CCCH finger proteins can bind to AU-rich elements in the 3'-untranslated region of mRNAs, leading to their deadenylation and subsequent degradation. Partial deficiency of 1 of the 4 mouse tristetraprolin family members, Zfp36l2, resulted in complete female infertility because of early embryo death. We have now generated mice completely deficient in the ZFP36L2 protein. Homozygous Zfp36l2 knockout (KO) mice died within approximately 2 weeks of birth, apparently from intestinal or other hemorrhage. Analysis of peripheral blood from KO mice showed a decrease in red and white cells, hemoglobin, hematocrit, and platelets. Yolk sacs from embryonic day 11.5 (E11.5) Zfp36l2 KO mice and fetal livers from E14.5 KO mice gave rise to markedly reduced numbers of definitive multilineage and lineage-committed hematopoietic progenitors. Competitive reconstitution experiments demonstrated that Zfp36l2 KO fetal liver hematopoietic stem cells were unable to adequately reconstitute the hematopoietic system of lethally irradiated recipients. These data establish Zfp36l2 as a critical modulator of definitive hematopoiesis and suggest a novel regulatory pathway involving control of mRNA stability in the life cycle of hematopoietic stem and progenitor cells. (Blood. 2009; 114: 2401-2410)
C1 [Stumpo, Deborah J.; Ward, Toni; Blackshear, Perry J.] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
[Broxmeyer, Hal E.; Cooper, Scott; Hangoc, Giao] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA.
[Broxmeyer, Hal E.; Cooper, Scott; Hangoc, Giao] Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA.
[Chung, Yang Jo; Aplan, Peter D.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Shelley, William C.; Yoder, Mervin C.] Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
[Shelley, William C.; Yoder, Mervin C.] Indiana Univ, Sch Med, Wells Ctr Pediat Res, Indianapolis, IN 46202 USA.
[Richfield, Eric K.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pathol & Lab Med, New Brunswick, NJ USA.
[Richfield, Eric K.] Univ Med & Dent New Jersey, Mol Histol Ctr, Environm & Occupat Hlth Sci Inst, Piscataway, NJ 08854 USA.
[Ray, Manas K.] NIEHS, Knock Out Core, Res Triangle Pk, NC 27709 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Blackshear, Perry J.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA.
RP Blackshear, PJ (reprint author), NIEHS, Lab Signal Transduct, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM black009@niehs.nih.gov
RI Aplan, Peter/K-9064-2016
FU National Institutes of Health [R01 HL56416, R01 HL67384, R01 HL63169];
National Institute of Environmental Health Sciences; National Cancer
Institute
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Institute of Environmental
Health Sciences, National Cancer Institute, and National Institutes of
Health (grants R01 HL56416 and R01 HL67384, H.E.B.; grant R01 HL63169,
M.C.Y.).
NR 50
TC 60
Z9 61
U1 1
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 17
PY 2009
VL 114
IS 12
BP 2401
EP 2410
DI 10.1182/blood-2009-04-214619
PG 10
WC Hematology
SC Hematology
GA 495WD
UT WOS:000269925000008
PM 19633199
ER
PT J
AU Donahue, RE
Jin, P
Bonifacino, AC
Metzger, ME
Ren, JQ
Wang, E
Stroncek, DF
AF Donahue, Robert E.
Jin, Ping
Bonifacino, Aylin C.
Metzger, Mark E.
Ren, Jiaqiang
Wang, Ena
Stroncek, David F.
TI Plerixafor (AMD3100) and granulocyte colony-stimulating factor (G-CSF)
mobilize different CD34(+) cell populations based on global gene and
microRNA expression signatures
SO BLOOD
LA English
DT Article
ID HEMATOPOIETIC STEM-CELL; CXCR4 ANTAGONIST AMD3100; PROGENITOR CELLS;
RAPID MOBILIZATION; NONHUMAN-PRIMATES; NOD/SCID MICE; BONE-MARROW;
ENGRAFTMENT; VOLUNTEERS
AB Plerixafor (AMD3100) and granulocyte colony-stimulating factor (G-CSF) mobilize peripheral blood stem cells by different mechanisms. A rhesus macaque model was used to compare plerixafor and G-CSF-mobilized CD34(+) cells. Three peripheral blood stem cell concentrates were collected from 3 macaques treated with G-CSF, plerixafor, or plerixafor plus G-CSF. CD34(+) cells were isolated by immunoselection and were analyzed by global gene and microRNA (miR) expression microarrays. Unsupervised hierarchical clustering of the gene expression data separated the CD34(+) cells into 3 groups based on mobilization regimen. Plerixafor-mobilized cells were enriched for B cells, T cells, and mast cell genes, and G-CSF mobilized cells were enriched for neutrophils and mononuclear phagocyte genes. Genes up-regulated in plerixafor plus G-CSF-mobilized CD34(+) cells included many that were not up-regulated by either agent alone. Two hematopoietic progenitor cell miR, miR-10 and miR-126, and a dendritic cell miR, miR-155, were up-regulated in G-CSF-mobilized CD34(+) cells. A pre-B-cell acute lymphocytic leukemia miR, miR-143-3p, and a T-cell miR, miR-143-5p, were up-regulated in plerixafor plus G-CSF-mobilized cells. The composition of CD34(+) cells is dependent on the mobilization protocol. Plerixafor-mobilized CD34(+) cells include more B-, T-, and mast cell precursors, whereas G-CSF-mobilized cells have more neutrophil and mononuclear phagocyte precursors. (Blood. 2009; 114: 2530-2541)
C1 [Jin, Ping; Ren, Jiaqiang; Wang, Ena; Stroncek, David F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Donahue, Robert E.; Bonifacino, Aylin C.; Metzger, Mark E.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Ctr Clin, 10 Ctr Dr,Bldg 10,Rm 1C711, Bethesda, MD 20892 USA.
EM dstroncek@cc.nih.gov
FU Hematology Branch, National Heart, Lung, and Blood Institute; National
Institutes of Health; Department of Transfusion Medicine; Clinical
Center
FX This study was funded by the Hematology Branch, National Heart, Lung,
and Blood Institute, National Institutes of Health, and the Department
of Transfusion Medicine, Clinical Center, National Institutes of Health.
NR 30
TC 56
Z9 57
U1 0
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 17
PY 2009
VL 114
IS 12
BP 2530
EP 2541
DI 10.1182/blood-2009-04-214403
PG 12
WC Hematology
SC Hematology
GA 495WD
UT WOS:000269925000022
PM 19602709
ER
PT J
AU Monaco, A
Marincola, FM
Sabatino, M
Pos, Z
Tornesello, ML
Stroncek, DF
Wang, E
Lewis, GK
Buonaguro, FM
Buonaguro, L
AF Monaco, Alessandro
Marincola, Francesco M.
Sabatino, Marianna
Pos, Zoltan
Tornesello, Maria Lina
Stroncek, David F.
Wang, Ena
Lewis, George K.
Buonaguro, Franco M.
Buonaguro, Luigi
TI Molecular immune signatures of HIV-1 vaccines in human PBMCs
SO FEBS LETTERS
LA English
DT Article
DE Immunogenomics; Vaccine; HIV-1; Peripheral blood mononuclear cell
ID VIRUS-LIKE PARTICLES; BLOOD MONONUCLEAR-CELLS; GENE-EXPRESSION PROFILE;
NEUTRALIZING ANTIBODIES; DENDRITIC CELLS; INNATE IMMUNITY; CLADE-A;
STIMULATION; INDUCTION; PATTERNS
AB The global transcriptional pro. le of peripheral blood mononuclear cells (PBMCs) stimulated with HIV candidate vaccine (virus-like particles, VLPs) has been evaluated in HIV-infected patients with low/high viral load compared to healthy volunteers. Baseline activation of chemokine production was observed in PBMC from HIV-infected patients and innate immune stimulation with HIV-VLPs was not blunted. The immune pro. le among HIV-infected patients was found to be qualitatively similar but quantitatively extremely variable. This diversity was independent of viral load and it might be dependent on individual immunogenetic traits or concurrent immunological status.
This ex vivo screening strategy represents an efficient tool for guiding modi. cations/optimizations of vaccination strategies and understanding failures in individuals enrolled in clinical trials. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
C1 [Monaco, Alessandro; Marincola, Francesco M.; Sabatino, Marianna; Pos, Zoltan; Stroncek, David F.; Wang, Ena] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Monaco, Alessandro] IRCCS Ist Nazl Tumori Giovanni Paolo II, Bari, Italy.
[Tornesello, Maria Lina; Buonaguro, Franco M.; Buonaguro, Luigi] Ist Nazl Tumori Fdn G Pascale, Lab Mol Biol & Viral Oncogenesis, I-80131 Naples, Italy.
[Tornesello, Maria Lina; Buonaguro, Franco M.; Buonaguro, Luigi] Ist Nazl Tumori Fdn G Pascale, AIDS Reference Ctr, I-80131 Naples, Italy.
[Buonaguro, Luigi] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA.
[Buonaguro, Luigi] Sch Med, Baltimore, MD USA.
RP Buonaguro, L (reprint author), Ist Nazl Tumori Fdn G Pascale, Lab Mol Biol & Viral Oncogenesis, Via Mariano Semmola 1, I-80131 Naples, Italy.
EM irccsvir@unina.it
RI Tornesello, Maria Lina/A-1564-2009; Pos, Zoltan/C-3623-2014; Monaco,
Alessandro/O-5338-2015;
OI Tornesello, Maria Lina/0000-0002-3523-3264; Pos,
Zoltan/0000-0002-2574-7616; Monaco, Alessandro/0000-0002-9941-7003;
Buonaguro, Luigi/0000-0002-6380-7114
FU Ministero Italiano Universita e Ricerca; Ministero Italiano della
Sanita; Institute of Human Virology; NIH
FX This study was supported by grants from the Ministero Italiano
Universita e Ricerca (MIUR, 2004), the Ministero Italiano della Sanita
(Ricerca Corrente and Progetto Finalizzato AIDS 2006), and the Institute
of Human Virology and the NIH (NIH grants to G. K. L.).
NR 24
TC 18
Z9 19
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD SEP 17
PY 2009
VL 583
IS 18
BP 3004
EP 3008
DI 10.1016/j.febslet.2009.07.060
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 512XB
UT WOS:000271284200006
PM 19665024
ER
PT J
AU Mateja, A
Szlachcic, A
Downing, ME
Dobosz, M
Mariappan, M
Hegde, RS
Keenan, RJ
AF Mateja, Agnieszka
Szlachcic, Anna
Downing, Maureen E.
Dobosz, Malgorzata
Mariappan, Malaiyalam
Hegde, Ramanujan S.
Keenan, Robert J.
TI The structural basis of tail-anchored membrane protein recognition by
Get3
SO NATURE
LA English
DT Article
ID MITOCHONDRIAL OUTER-MEMBRANE; ARSA-ATPASE; CRYSTALLOGRAPHIC STRUCTURE;
ENDOPLASMIC-RETICULUM; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; SIGNAL;
PARTICLE; INSERTION; BINDING
AB Targeting of newly synthesized membrane proteins to the endoplasmic reticulum is an essential cellular process. Most membrane proteins are recognized and targeted co-translationally by the signal recognition particle. However, nearly 5% of membrane proteins are 'tail-anchored' by a single carboxy-terminal transmembrane domain that cannot access the co-translational pathway. Instead, tail-anchored proteins are targeted post-translationally by a conserved ATPase termed Get3. The mechanistic basis for tail-anchored protein recognition or targeting by Get3 is not known. Here we present crystal structures of yeast Get3 in 'open' (nucleotide-free) and 'closed' (ADP center dot AlF(4)(-)-bound) dimer states. In the closed state, the dimer interface of Get3 contains an enormous hydrophobic groove implicated by mutational analyses in tail-anchored protein binding. In the open state, Get3 undergoes a striking rearrangement that disrupts the groove and shields its hydrophobic surfaces. These data provide a molecular mechanism for nucleotide-regulated binding and release of tail-anchored proteins during their membrane targeting by Get3.
C1 [Mateja, Agnieszka; Szlachcic, Anna; Downing, Maureen E.; Dobosz, Malgorzata; Keenan, Robert J.] Univ Chicago, Dept Biochem & Mol Biol, Gordon Ctr Integrat Sci, Chicago, IL 60637 USA.
[Mariappan, Malaiyalam; Hegde, Ramanujan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Szlachcic, Anna] Univ Wroclaw, Fac Biotechnol, Dept Prot Engn, PL-50137 Wroclaw, Poland.
[Dobosz, Malgorzata] Jagiellonian Univ, Fac Chem, PL-30060 Krakow, Poland.
RP Keenan, RJ (reprint author), Univ Chicago, Dept Biochem & Mol Biol, Gordon Ctr Integrat Sci, Room W238,920 E 57th St, Chicago, IL 60637 USA.
EM bkeenan@uchicago.edu
RI mariappan, malaiyalam/K-9024-2012;
OI Hegde, Ramanujan/0000-0001-8338-852X
FU US Department of Energy, Office of Science, Office of Basic Energy
Sciences [DE-AC02-06CH11357]; Edward Mallinckrodt, Jr. Foundation;
National Institutes of Health
FX Data were collected at beamlines 21-IDG and 23-IDD at the Advanced
Photon Source (APS), Argonne National Laboratory, and we thank the
beamline staff for support. Use of the APS was supported by the US
Department of Energy, Office of Science, Office of Basic Energy
Sciences, under contract no. DE-AC02-06CH11357. We thank B. Glick and R.
Strack for reagents and advice, X. Li for assay characterization, and A.
Shiau and T. Steck for comments on the manuscript. This work was
supported by a grant from the Edward Mallinckrodt, Jr. Foundation (to R.
J. K.) and by the Intramural Research Program of the National Institutes
of Health (to R. S. H.).
NR 40
TC 80
Z9 82
U1 1
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD SEP 17
PY 2009
VL 461
IS 7262
BP 361
EP U58
DI 10.1038/nature08319
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100032
PM 19675567
ER
PT J
AU Lauchle, JO
Kim, D
Le, DT
Akagi, K
Crone, M
Krisman, K
Warner, K
Bonifas, JM
Li, Q
Coakley, KM
Diaz-Flores, E
Gorman, M
Przybranowski, S
Tran, M
Kogan, SC
Roose, JP
Copeland, NG
Jenkins, NA
Parada, L
Wolff, L
Sebolt-Leopold, J
Shannon, K
AF Lauchle, Jennifer O.
Kim, Doris
Le, Doan T.
Akagi, Keiko
Crone, Michael
Krisman, Kimberly
Warner, Kegan
Bonifas, Jeannette M.
Li, Qing
Coakley, Kristen M.
Diaz-Flores, Ernesto
Gorman, Matthew
Przybranowski, Sally
Tran, Mary
Kogan, Scott C.
Roose, Jeroen P.
Copeland, Neal G.
Jenkins, Nancy A.
Parada, Luis
Wolff, Linda
Sebolt-Leopold, Judith
Shannon, Kevin
TI Response and resistance to MEK inhibition in leukaemias initiated by
hyperactive Ras
SO NATURE
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MALIGNANT MYELOID DISORDERS; BCR-ABL;
HEMATOPOIETIC-CELLS; KINASE INHIBITORS; TYROSINE KINASE; BLAST CRISIS;
BONE-MARROW; CHILDREN; PATHWAY
AB The cascade comprising Raf, mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) is a therapeutic target in human cancers with deregulated Ras signalling, which includes tumours that have inactivated the Nf1 tumour suppressor(1,2). Nf1 encodes neurofibromin, a GTPase-activating protein that terminates Ras signalling by stimulating hydrolysis of Ras-GTP. We compared the effects of inhibitors of MEK in a myeloproliferative disorder (MPD) initiated by inactivating Nf1 in mouse bone marrow and in acute myeloid leukaemias (AMLs) in which cooperating mutations were induced by retroviral insertional mutagenesis. Here we show that MEK inhibitors are ineffective in MPD, but induce objective regression of many Nf1-deficient AMLs. Drug resistance developed because of outgrowth of AML clones that were present before treatment. We cloned clone-specific retroviral integrations to identify candidate resistance genes including Rasgrp1, Rasgrp4 and Mapk14, which encodes p38 alpha. Functional analysis implicated increased RasGRP1 levels and reduced p38 kinase activity in resistance to MEK inhibitors. This approach represents a robust strategy for identifying genes and pathways that modulate how primary cancer cells respond to targeted therapeutics and for probing mechanisms of de novo and acquired resistance.
C1 [Lauchle, Jennifer O.; Kim, Doris; Le, Doan T.; Crone, Michael; Krisman, Kimberly; Warner, Kegan; Bonifas, Jeannette M.; Diaz-Flores, Ernesto; Gorman, Matthew; Tran, Mary; Shannon, Kevin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Li, Qing] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Coakley, Kristen M.; Roose, Jeroen P.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
[Kogan, Scott C.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Akagi, Keiko] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
[Przybranowski, Sally; Sebolt-Leopold, Judith] Pfizer Global Res & Dev, Ann Arbor, MI 48105 USA.
[Copeland, Neal G.; Jenkins, Nancy A.] Inst Mol & Cell Biol, Singapore 138673, Singapore.
[Parada, Luis] Univ Texas SW, Dallas, TX 75235 USA.
[Wolff, Linda] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA.
RP Shannon, K (reprint author), Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
EM shannonk@peds.ucsf.edu
RI ASTAR, IMCB/E-2320-2012
FU National Institutes of Health [U01 CA84221, R37 CA72614, T32 CA09043,
T32 HD044331, K08 CA119105]; Leukemia and Lymphoma Society [LLS
7019-04]; US Army Neurofibromatosis Research Program [DAMD
17-02-1-0638]; Ronald McDonald House Charities of Southern
California/Couples Against Leukemia; Jeffrey and Karen Peterson Family
Foundation; Frank A. Campini Foundation
FX We are grateful to B. Braun, J. Downing, S. Lowe and C. Sawyers for
discussion and advice throughout the project. We are thankful for C.
Hartzell for studies on RasGRP protein expression. This work was
supported by National Institutes of Health grants U01 CA84221, R37
CA72614, T32 CA09043, T32 HD044331 and K08 CA119105, by a Specialized
Center of Research award from the Leukemia and Lymphoma Society (LLS
7019-04), by the US Army Neurofibromatosis Research Program (Project
DAMD 17-02-1-0638), by the Ronald McDonald House Charities of Southern
California/Couples Against Leukemia, by the Jeffrey and Karen Peterson
Family Foundation and by the Frank A. Campini Foundation. S. C. K. is a
Scholar of the Leukemia and Lymphoma Society of America. J. P. R. is a
Kimmel Foundation Scholar. The Intramural Research Program of the
National Cancer Institute's Center for Cancer Research supports research
in the laboratory of L. W. at the National Institutes of Health.
NR 25
TC 64
Z9 65
U1 2
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD SEP 17
PY 2009
VL 461
IS 7262
BP 411
EP U110
DI 10.1038/nature08279
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100043
PM 19727076
ER
PT J
AU Zofall, M
Fischer, T
Zhang, K
Zhou, M
Cui, BW
Veenstra, TD
Grewal, SIS
AF Zofall, Martin
Fischer, Tamas
Zhang, Ke
Zhou, Ming
Cui, Bowen
Veenstra, Timothy D.
Grewal, Shiv I. S.
TI Histone H2A.Z cooperates with RNAi and heterochromatin factors to
suppress antisense RNAs
SO NATURE
LA English
DT Article
ID FISSION YEAST; QUALITY CONTROL; NONCODING RNAS; VARIANT; TRANSCRIPTION;
CHROMATIN; GENOME; DROSOPHILA; COMPLEX; EXOSOME
AB Eukaryotic transcriptomes are characterized by widespread transcription of noncoding and antisense RNAs(1-3), which is linked to key chromosomal processes, such as chromatin remodelling, gene regulation and heterochromatin assembly(4-7). However, these transcripts can be deleterious, and their accumulation is suppressed by several mechanisms including degradation by the nuclear exosome(8,9). The mechanisms by which cells differentiate coding RNAs from transcripts targeted for degradation are not clear. Here we show that the variant histone H2A.Z, which is loaded preferentially at the 5' ends of genes by the Swr1 complex containing a JmjC domain protein, mediates suppression of antisense transcripts in the fission yeast Schizosaccharomyces pombe genome. H2A.Z is partially redundant in this regard with the Clr4 (known as SUV39H in mammals)-containing heterochromatin silencing complex that is also distributed at euchromatic loci, and with RNA interference component Argonaute (Ago1). Loss of Clr4 or Ago1 alone has little effect on antisense transcript levels, but cells lacking either of these factors and H2A.Z show markedly increased levels of antisense RNAs that are normally degraded by the exosome. These analyses suggest that as well as performing other functions, H2A.Z is a component of a genome indexing mechanism that cooperates with heterochromatin and RNAi factors to suppress read-through antisense transcripts.
C1 [Zofall, Martin; Fischer, Tamas; Zhang, Ke; Cui, Bowen; Grewal, Shiv I. S.] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Zhou, Ming; Veenstra, Timothy D.] NCI Frederick, SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA.
RP Grewal, SIS (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM grewals@mail.nih.gov
RI Cui, Bowen/F-1038-2011; Fischer, Tamas/A-7729-2016
OI Fischer, Tamas/0000-0002-7996-4042
FU National Institutes of Health [N01-CO-12400]; National Cancer Institute
FX Acknowledgements We thank K. Noma for strain constructions, D.
McPheeters for the run-on protocol, M. Lichten, F. Reyes-Turcu, E.
Bartlett and H. Cam for comments on the manuscript, P. Fitzgerald for
designing microarrays, and D. Venzon for advice with data analyses. This
research was supported by the Intramural Research Program, and under
Contract N01-CO-12400 of the National Institutes of Health, National
Cancer Institute.
NR 30
TC 89
Z9 90
U1 5
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD SEP 17
PY 2009
VL 461
IS 7262
BP 419
EP U120
DI 10.1038/nature08321
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 494QB
UT WOS:000269828100045
PM 19693008
ER
PT J
AU Strebel, K
Luban, J
Jeang, KT
AF Strebel, Klaus
Luban, Jeremy
Jeang, Kuan-Teh
TI Human cellular restriction factors that target HIV-1 replication
SO BMC MEDICINE
LA English
DT Review
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 VPU PROTEIN; APOBEC3G CATALYTIC
DOMAIN; RNA SILENCING SUPPRESSOR; VIRAL PARTICLE RELEASE; SMALL
INTERFERING RNAS; AMINO-ACID-RESIDUES; PIG-TAILED MACAQUES; CD4(+)
T-CELLS; CYCLOPHILIN-A
AB Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G), bone marrow stromal cell antigen 2 (BST-2), cyclophilin A, tripartite motif protein 5 alpha (Trim5 alpha), and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of these cellular restriction functions.
C1 [Strebel, Klaus; Jeang, Kuan-Teh] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Luban, Jeremy] Univ Geneva, Dept Microbiol & Med, Geneva, Switzerland.
RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Kstrebel@NIH.gov; Jeremy.Luban@unige.ch; Kjeang@NIH.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU NIAID; NIH [RO1AI36199]; Swiss National Science Foundation office of the
Director NIH [3100A0-113558]
FX Work in the laboratories of KS and KTJ was supported by intramural
funding from NIAID, NIH and the Intramural AIDS Targeted Antiviral
Program (IATAP) of the office of the Director NIH. Work in the JL
laboratory was supported by the National Institutes of Health grant
RO1AI36199 and the Swiss National Science Foundation grant
3100A0-113558. We are grateful to D Schmidt for his assistance with
Figure 5.
NR 208
TC 99
Z9 100
U1 2
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7015
J9 BMC MED
JI BMC Med.
PD SEP 16
PY 2009
VL 7
AR 48
DI 10.1186/1741-7015-7-48
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA 512GS
UT WOS:000271234900001
PM 19758442
ER
PT J
AU Bushel, PR
Heard, NA
Gutman, R
Liu, LW
Peddada, SD
Pyne, S
AF Bushel, Pierre R.
Heard, Nicholas A.
Gutman, Roee
Liu, Liwen
Peddada, Shyamal D.
Pyne, Saumyadipta
TI Dissecting the fission yeast regulatory network reveals phase-specific
control elements of its cell cycle
SO BMC SYSTEMS BIOLOGY
LA English
DT Article
ID MESSENGER-RNA STABILITY; SCHIZOSACCHAROMYCES-POMBE; TRANSCRIPTION
FACTOR; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; RIBOSOME BIOGENESIS;
DIVISION CYCLE; GENOMIC SCALE; TIME-SERIES; PROTEIN
AB Background: Fission yeast Schizosaccharomyces pombe and budding yeast Saccharomyces cerevisiae are among the original model organisms in the study of the cell-division cycle. Unlike budding yeast, no large-scale regulatory network has been constructed for fission yeast. It has only been partially characterized. As a result, important regulatory cascades in budding yeast have no known or complete counterpart in fission yeast.
Results: By integrating genome-wide data from multiple time course cell cycle microarray experiments we reconstructed a gene regulatory network. Based on the network, we discovered in addition to previously known regulatory hubs in M phase, a new putative regulatory hub in the form of the HMG box transcription factor SPBC19G7.04. Further, we inferred periodic activities of several less known transcription factors over the course of the cell cycle, identified over 500 putative regulatory targets and detected many new phase-specific and conserved cis-regulatory motifs. In particular, we show that SPBC19G7.04 has highly significant periodic activity that peaks in early M phase, which is coordinated with the late G2 activity of the forkhead transcription factor fkh2. Finally, using an enhanced Bayesian algorithm to co-cluster the expression data, we obtained 31 clusters of co-regulated genes 1) which constitute regulatory modules from different phases of the cell cycle, 2) whose phase order is coherent across the 10 time course experiments, and 3) which lead to identification of phase-specific control elements at both the transcriptional and post-transcriptional levels in S. pombe. In particular, the ribosome biogenesis clusters expressed in G2 phase reveal new, highly conserved RNA motifs.
Conclusion: Using a systems-level analysis of the phase-specific nature of the S. pombe cell cycle gene regulation, we have provided new testable evidence for post-transcriptional regulation in the G2 phase of the fission yeast cell cycle. Based on this comprehensive gene regulatory network, we demonstrated how one can generate and investigate plausible hypotheses on fission yeast cell cycle regulation which can potentially be explored experimentally.
C1 [Bushel, Pierre R.; Liu, Liwen; Peddada, Shyamal D.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Heard, Nicholas A.] Univ London Imperial Coll Sci Technol & Med, Dept Math, London, England.
[Gutman, Roee] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA.
[Pyne, Saumyadipta] Harvard Univ, Cambridge Ctr 7, Cambridge, MA 02142 USA.
[Pyne, Saumyadipta] MIT, Broad Inst, Cambridge, MA 02142 USA.
[Bushel, Pierre R.] Harvard Univ, Sch Publ Hlth, Dept Stat, Boston, MA 02115 USA.
[Bushel, Pierre R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Pyne, Saumyadipta] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Bushel, PR (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA.
EM bushel@niehs.nih.gov; n.heard@imperial.ac.uk; rgutman@fas.harvard.edu;
liuliw@niehs.nih.gov; peddada@niehs.nih.gov;
Saumyadipta_Pyne@DFCI.HARVARD.EDU
RI Peddada, Shyamal/D-1278-2012; Gutman, Roee/J-2355-2014
OI Gutman, Roee/0000-0001-7095-3016
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01 ES101744-04]
FX Research of PRB, LL and SDP was supported by the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences
[Z01 ES101744-04]. We thank Jonathan H. Freedman and Reuben Thomas for
their review of the manuscript. SP thanks Aviv Regev and Ana Paula Leite
for programs on module network analysis. We also dearly thank James C.
Liao for his personal communication regarding NCA.
NR 65
TC 10
Z9 10
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1752-0509
J9 BMC SYST BIOL
JI BMC Syst. Biol.
PD SEP 16
PY 2009
VL 3
AR 93
DI 10.1186/1752-0509-3-93
PG 21
WC Mathematical & Computational Biology
SC Mathematical & Computational Biology
GA 506EE
UT WOS:000270755700001
PM 19758441
ER
PT J
AU Albanes, D
Weinstein, SJ
Wright, ME
Mannisto, S
Limburg, PJ
Snyder, K
Virtamo, J
AF Albanes, Demetrius
Weinstein, Stephanie J.
Wright, Margaret E.
Mannisto, Satu
Limburg, Paul J.
Snyder, Kirk
Virtamo, Jarmo
TI Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of
Prostate Cancer
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID GROWTH-FACTOR-I; DIABETES-MELLITUS; MALE SMOKERS; BINDING-PROTEINS;
OBESITY; HYPERINSULINEMIA; METAANALYSIS; ASSOCIATION; SURVIVAL; MEN
AB The mitogenic and growth-stimulatory effects of insulin-like growth factors appear to play a role in prostate carcinogenesis, yet any direct association of circulating insulin levels and risk of prostate cancer remains unclear.
We investigated the relationship of the level of serum insulin, glucose, and surrogate indices of insulin resistance (ie, the molar ratio of insulin to glucose and the homeostasis model assessment of insulin resistance [HOMA-IR]) to the development of prostate cancer in a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish men. We studied 100 case subjects with incident prostate cancer and 400 noncase subjects without prostate cancer from the larger cohort. Fasting serum was collected 5-12 years before diagnosis. We determined insulin concentrations with a double-antibody immunochemiluminometric assay and glucose concentrations with a hexokinase assay. Multivariable logistic regression models estimated relative risks as odds ratios (ORs), and all statistical tests were two-sided.
Insulin concentrations in fasting serum that was collected on average 9.2 years before diagnosis among case subjects were 8% higher than among noncase subjects, and the molar ratio of insulin to glucose and HOMA-IR were 10% and 6% higher, respectively, but these differences were not statistically significant. Among subjects in the second through fourth insulin quartiles, compared with those in the first quartile, increased insulin levels were associated with statistically significantly increased risks of prostate cancer (OR = 1.50, 95% confidence interval [CI] = 0.75 to 3.03; OR = 1.75, 95% CI = 0.86 to 3.56; and OR = 2.55, 95% CI = 1.18 to 5.51; for the second through fourth insulin quartiles, respectively; P-trend = .02). A similar pattern was observed with the HOMA-IR (OR = 2.10, 95% CI = 1.03 to 4.26; P-trend = .02) for the highest vs lowest quartiles. Risk varied inconsistently with glucose concentration (P-trend = .38). A stronger association between insulin level and prostate cancer risk was observed among leaner men and among men who were less physically active at work. Crude prostate cancer incidence was 154 prostate cancers per 100 000 person-years in the lowest quartile of fasting serum insulin vs 394 prostate cancers per 100 000 person-years in the highest quartile.
Elevated fasting levels of serum insulin (but not glucose) within the normal range appear to be associated with a higher risk of prostate cancer.
C1 [Albanes, Demetrius; Weinstein, Stephanie J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Wright, Margaret E.] Univ Illinois, Coll Med, Dept Pathol, Chicago, IL 60612 USA.
[Mannisto, Satu; Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Limburg, Paul J.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA.
[Snyder, Kirk] Informat Management Serv Inc, Silver Spring, MD USA.
RP Albanes, D (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Executive Blvd,Rm 3044, Bethesda, MD 20892 USA.
EM daa@nih.gov
RI Albanes, Demetrius/B-9749-2015;
OI Mannisto, Satu/0000-0002-8668-3046
FU National Cancer Institute, National Institutes of Health, Department of
Health and Human Services [N01-CN-45165, N01-RC-45035, N01-RC-37004]
FX The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was
supported in part by US Public Health Service contracts N01-CN-45165,
N01-RC-45035, and N01-RC-37004 from the National Cancer Institute,
National Institutes of Health, Department of Health and Human Services.
NR 32
TC 54
Z9 55
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD SEP 16
PY 2009
VL 101
IS 18
BP 1272
EP 1279
DI 10.1093/jnci/djp260
PG 8
WC Oncology
SC Oncology
GA 496YD
UT WOS:000270015400009
PM 19700655
ER
PT J
AU Chen, KG
Leapman, RD
Zhang, GF
Lai, B
Valencia, JC
Cardarelli, CO
Vieira, WD
Hearing, VJ
Gottesman, MM
AF Chen, Kevin G.
Leapman, Richard D.
Zhang, Guofeng
Lai, Barry
Valencia, Julio C.
Cardarelli, Carol O.
Vieira, Wilfred D.
Hearing, Vincent J.
Gottesman, Michael M.
TI Influence of Melanosome Dynamics on Melanoma Drug Sensitivity
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID BINDING CASSETTE TRANSPORTER; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN;
MALIGNANT-MELANOMA; CYTOTOXIC DRUGS; CELLS; TYROSINASE; CISPLATIN;
CANCER; MELANOCYTES
AB Malignant melanomas are intrinsically resistant to many conventional treatments, such as radiation and chemotherapy, for reasons that are poorly understood. Here we propose and test a model that explains drug resistance or sensitivity in terms of melanosome dynamics.
The growth and sensitivity to cisplatin of MNT-1 cells, which are melanotic and enriched with mature stage III and IV melanosomes, and SK-MEL-28 cells, which have only immature stage I and II melanosomes, were compared using clonogenic assays. Differences in pigmentation, melanosome stages, melanosome number, and cellular structures in different cell lines in response to various treatments were examined by electron microscopy. The relative numbers of melanosomes of different stages were compared after treatment with 1-phenyl-2-thiourea. The relationship between drug transporter function and endogenous melanogenic toxicity was assessed by treating cells with the cyclosporin analog PSC-833 and by assessing vacuole formation and cell growth inhibition. All statistical tests were two-sided.
Endogenous melanogenic cytotoxicity, produced by damaged melanosomes, resulted in pronounced cell growth inhibition in MNT-1 cells compared with amelanotic SK-MEL-28 cells. The sensitivity to CDDP of MNT-1 cells was 3.8-fold higher than that of SK-MEL-28 cells (mean IC(50) for SK-MEL-28 and MNT-1 = 2.13 mu M and 0.56 mu M, respectively; difference = 1.57 mu M, 95% confidence interval = 1.45 to 1.69; P = .0017). After treatment with 6.7 mu M CDDP for 72 hours, the number of stage II-III melanosomes in surviving MNT-1 cells was 6.8-fold that of untreated cells. Modulation of MNT-1 cells to earlier-stage (II, II-III, III) melanosomes by treatment with the tyrosinase inhibitor 1-phenyl-2-thiourea dramatically increased CDDP resistance. Furthermore, PSC-833 principally suppressed MNT-1 melanotic cell growth via an elevation of autophagosome-like vacuolar structures, possibly by inhibiting melanosome membrane transporters.
Melanosome dynamics (including their biogenesis, density, status, and structural integrity) regulate the drug resistance of melanoma cells. Manipulation of melanosome functions may be an effective way to enhance the therapeutic activity of anticancer drugs against melanoma.
C1 [Chen, Kevin G.; Valencia, Julio C.; Cardarelli, Carol O.; Vieira, Wilfred D.; Hearing, Vincent J.; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Leapman, Richard D.; Zhang, Guofeng] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA.
[Lai, Barry] Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 2108, Bethesda, MD 20892 USA.
EM mgottesman@nih.gov
RI Chen, Kevin/D-6769-2011
OI Chen, Kevin/0000-0003-2983-6330
FU Intramural NIH HHS [Z99 NS999999]
NR 40
TC 21
Z9 21
U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD SEP 16
PY 2009
VL 101
IS 18
BP 1259
EP 1271
DI 10.1093/jnci/djp259
PG 13
WC Oncology
SC Oncology
GA 496YD
UT WOS:000270015400008
PM 19704071
ER
PT J
AU Landgren, O
Dunleavy, K
Wilson, WH
AF Landgren, Ola
Dunleavy, Kieron
Wilson, Wyndham H.
TI Re: Rituximab Maintenance for the Treatment of Patients With Follicular
Lymphoma: Systematic Review and Meta-analysis of Randomized trials
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
ID RESPONSE DURATION; FREE SURVIVAL; CYCLOPHOSPHAMIDE; PROGRESSION; THERAPY
C1 [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Landgren, O (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10-Rm 13N240F, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
NR 7
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD SEP 16
PY 2009
VL 101
IS 18
BP 1287
EP 1288
DI 10.1093/jnci/djp255
PG 3
WC Oncology
SC Oncology
GA 496YD
UT WOS:000270015400014
PM 19687413
ER
PT J
AU Jeang, KT
AF Jeang, Kuan-Teh
TI The importance of individualized article-specific metrics for evaluating
research productivity
SO RETROVIROLOGY
LA English
DT Editorial Material
ID 2007 RETROVIROLOGY PRIZE; H-INDEX; SCIENCE; WINS; CALL; LIFE
AB This editorial discusses the rationale for using article-specific rather than journal-specific metrics for evaluating highly published authors.
C1 NIH, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM kj7e@nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
NR 10
TC 2
Z9 2
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD SEP 16
PY 2009
VL 6
AR 82
DI 10.1186/1742-4690-6-82
PG 4
WC Virology
SC Virology
GA 509KN
UT WOS:000271015500001
PM 19758447
ER
PT J
AU Platt, RW
Schisterman, EF
Cole, SR
AF Platt, Robert W.
Schisterman, Enrique F.
Cole, Stephen R.
TI Time-modified Confounding
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE bias (epidemiology); confounding factors (epidemiology); structural
model
ID MARGINAL STRUCTURAL MODELS; PROPORTIONAL HAZARDS MODEL; CAUSAL
INFERENCE; EPIDEMIOLOGY; DEFINITION; MORTALITY; KNOWLEDGE; RATIO; BIAS
AB According to the authors, time-modified confounding occurs when the causal relation between a time-fixed or time-varying confounder and the treatment or outcome changes over time. A key difference between previously described time-varying confounding and the proposed time-modified confounding is that, in the former, the values of the confounding variable change over time while, in the latter, the effects of the confounder change over time. Using marginal structural models, the authors propose an approach to account for time-modified confounding when the relation between the confounder and treatment is modified over time. An illustrative example and simulation show that, when time-modified confounding is present, a marginal structural model with inverse probability-of-treatment weights specified to account for time-modified confounding remains approximately unbiased with appropriate confidence limit coverage, while models that do not account for time-modified confounding are biased. Correct specification of the treatment model, including accounting for potential variation over time in confounding, is an important assumption of marginal structural models. When the effect of confounders on either the treatment or outcome changes over time, time-modified confounding should be considered.
C1 [Platt, Robert W.] McGill Univ, Dept Pediat & Epidemiol, Montreal, PQ, Canada.
[Platt, Robert W.] McGill Univ, Dept Biostat, Montreal, PQ, Canada.
[Platt, Robert W.] McGill Univ, Dept Occupat Hlth, Montreal, PQ, Canada.
[Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Rockville, MD USA.
[Cole, Stephen R.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
RP Platt, RW (reprint author), Montreal Childrens Hosp, Res Inst, 4060 Ste Catherine St W,205, Westmount, PQ H3Z 2Z3, Canada.
EM robert.platt@mcgill.ca
RI Platt, Robert/G-5847-2012;
OI Platt, Robert/0000-0002-5981-8443; Schisterman,
Enrique/0000-0003-3757-641X
FU Fonds de Recherche en Santedu Quebec (FRSQ); Intramural Research Program
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, National Institutes of Health; National Institutes of
Health [R03-AI-071763, R01-AA-017594, P30-AI-50410]; American Chemistry
Council; Thrasher Research Fund; National Health Research and
Development Program (Health Canada); United Nations Children's Fund;
European Regional Office of the World Health Organization
FX Robert Platt is supported by a salary award from the Fonds de Recherche
en Santedu Quebec (FRSQ) and is a member of the Research Institute of
the McGill University Health Centre, which is supported in part by the
FRSQ. Enrique F. Schisterman is supported by the Intramural Research
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development, National Institutes of Health. Stephen R. Cole
was partially supported by National Institutes of Health grants
R03-AI-071763, R01-AA-017594, and P30-AI-50410. The authors were
partially funded by a grant from the American Chemistry Council to
Enrique Schisterman. PROBIT was supported by grants from the Thrasher
Research Fund, the National Health Research and Development Program
(Health Canada), the United Nations Children's Fund, and the European
Regional Office of the World Health Organization.
NR 33
TC 19
Z9 19
U1 1
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD SEP 15
PY 2009
VL 170
IS 6
BP 687
EP 694
DI 10.1093/aje/kwp175
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 491UX
UT WOS:000269606900003
PM 19675141
ER
PT J
AU Wilson, RT
Wang, JY
Chinchilli, V
Richie, JP
Virtamo, J
Moore, LE
Albanes, D
AF Wilson, Robin Taylor
Wang, Jiangyue
Chinchilli, Vernon
Richie, John P.
Virtamo, Jarmo
Moore, Lee E.
Albanes, Demetrius
TI Fish, Vitamin D, and Flavonoids in Relation to Renal Cell Cancer Among
Smokers
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE carcinoma (renal cell); fish products; flavonoids; vitamin D
ID PERSISTENT ORGANOCHLORINE COMPOUNDS; DIBENZO-P-DIOXINS;
CARDIOVASCULAR-DISEASE; RISK-FACTORS; BALTIC SEA; MYOCARDIAL-INFARCTION;
LIPID-PEROXIDATION; PANCREATIC-CANCER; SWEDISH FISHERMEN;
MERCURY-COMPOUNDS
AB Fish, vitamin D, flavonoids, and flavonoid-containing foods may have cardiovascular benefits and therefore may also reduce the risk of renal cell cancer. Risk was prospectively assessed in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study (1985-2002) cohort (N = 27,111; 15.2 mean person-years of follow-up). At enrollment, demographic, health, and dietary history information was recorded. Individuals who smoked less than 5 cigarettes/day, with chronic renal insufficiency or prior cancer, were excluded. Hazard ratios and 95% confidence intervals from Cox regression were used to compare upper quartiles (quartiles 2-4) with the lowest quartile (quartile 1) of dietary intake. Among 228 cases, risk (quartile 4 vs. quartile 1) was associated with consumption of the flavonoid quercetin (hazard ratio = 0.6, 95% confidence interval: 0.4, 0.9; P(trend) = 0.015) and Baltic herring (hazard ratio = 2.0, 95% confidence interval: 1.4, 3.0; P(trend) < 0.001), with adjustment for age, body mass index, smoking, blood pressure, alcohol use, physical activity, urban residence, and education. In geographically stratified models, the risks associated with herring and total fish intake appeared to be highest in the urban coast region, although the interaction was not statistically significant. These results suggest that the flavonoid quercetin may prevent renal cell cancer among male smokers. The possible risk associated with fish intake warrants further investigation before conclusions may be drawn.
C1 [Wilson, Robin Taylor; Wang, Jiangyue; Chinchilli, Vernon; Richie, John P.] Penn State Univ, Coll Med, Dept Publ Hlth Sci, Div Epidemiol, Hershey, PA 17033 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Moore, Lee E.; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Wilson, RT (reprint author), Penn State Univ, Coll Med, Dept Publ Hlth Sci, Div Epidemiol, 600 Ctr View Dr,Suite 2200,Mail Code A210, Hershey, PA 17033 USA.
EM rwilson@psu.edu
RI Albanes, Demetrius/B-9749-2015
FU Intramural Research Program of the National Institutes of Health; US
Public Health Service [N01-CN-45165, N01-RC45035, N01-RC-37004];
National Cancer Institute, Department of Health and Human Services
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, by a postdoctoral research
fellowship within the Division of Cancer Epidemiology and Genetics of
the National Cancer Institute, and by salary support from the
Pennsylvania State University. Additionally, this research was supported
by US Public Health Service contracts N01-CN-45165, N01-RC45035, and
N01-RC-37004 from the National Cancer Institute, Department of Health
and Human Services.
NR 79
TC 19
Z9 20
U1 0
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD SEP 15
PY 2009
VL 170
IS 6
BP 717
EP 729
DI 10.1093/aje/kwp178
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 491UX
UT WOS:000269606900007
PM 19651663
ER
PT J
AU Schunemann, HJ
Osborne, M
Moss, J
Manthous, C
Wagner, G
Sicilian, L
Ohar, J
McDermott, S
Lucas, L
Jaeschke, R
AF Schuenemann, Holger J.
Osborne, Molly
Moss, Joel
Manthous, Constantine
Wagner, Gregory
Sicilian, Leonard
Ohar, Jill
McDermott, Shane
Lucas, Lance
Jaeschke, Roman
CA ATS Ethics Conflict Interest Comm
Documents Dev Implementation Comm
TI An Official American Thoracic Society Policy Statement: Managing
Conflict of Interest in Professional Societies
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
ID PHYSICIAN-INDUSTRY RELATIONSHIPS
AB Background. Competing interests occur frequently in health care. This results in the potential for conflict of interest (COI). COI can lead to biased generation or assessment of evidence and misinform healthcare decision makers. Declaration of COI is insufficient to neutralize potentially harmful effects. Medical professional societies are obliged to develop robust mechanisms to "manage" COI, particularly in the development of official guidance documents that affect health care.
Purpose: This document describes the background, methods, and content of the new "American Thoracic Society (ATS) Policy on Management of COI in Official ATS Documents, Projects, and Conferences."
Methods: We used existing reviews on COI policies that were prepared for the World Health Organization and for an ATS guideline methodology workshop as the evidence base for this work. We reviewed existing policies of selected organizations and other relevant literature. Members of the ATS Documents Development and Implementation Committee and the ATS Ethics and COI Committee collaborated to draft a COI policy. We used face-to-face meetings, electronic correspondence, and teleconferences to finalize the draft. The policy then underwent review and ultimate approval by the ATS Board of Directors.
Results: The ATS developed a new policy and procedures for declaration and management of COL These procedures include: (1) self declaration of COI, (2) review of potential participants' COI, (3) disclosure of COI to project participants, (4) recusal or excusal from certain decisions or recommendations when appropriate, (5) disclosure of COI to users of documents or attendees of conferences, (6) handling disputes in COI resolution. This policy includes a tool that may be useful for supporting decision makers in management of COIs as they assess the value and relevance of conflicts.
Conclusions: The ATS Policy on Management of COI in Official ATS Documents, Projects, and Conferences, in effect since March 2008, promises greater organizational transparency. Application and ongoing evaluation of the policy will give the ATS the opportunity to determine its usefulness in specific settings.
C1 [Schuenemann, Holger J.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada.
[Schuenemann, Holger J.] SUNY Buffalo, Dept Med, Buffalo, NY 14260 USA.
[Schuenemann, Holger J.; Jaeschke, Roman] McMaster Univ, Dept Med, Hamilton, ON, Canada.
[Osborne, Molly] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Osborne, Molly] Portland VA Med Ctr, Portland, OR USA.
[Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Manthous, Constantine] Yale Univ, Sch Med, Bridgeport Hosp, New Haven, CT USA.
[Wagner, Gregory] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Sicilian, Leonard] Massachusetts Gen Hosp, Dept Med, Adult Cyst Fibrosis Program, Pulm & Crit Care Unit, Boston, MA 02114 USA.
[Ohar, Jill] Wake Forest Univ, Bowman Gray Sch Med, Sect Pulm Crit Care Allergy & Immunol Dis, Winston Salem, NC USA.
[McDermott, Shane] Off Eth & Conflict Interest Policies, New York, NY USA.
[Lucas, Lance] Amer Thorac Soc, Off Documents, New York, NY USA.
[Lucas, Lance] Amer Thorac Soc, Ad Hoc Projects, New York, NY USA.
RP Schunemann, HJ (reprint author), McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada.
NR 15
TC 34
Z9 35
U1 0
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD SEP 15
PY 2009
VL 180
IS 6
BP 564
EP 580
DI 10.1164/rccm.200901-0126ST
PG 17
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 496TV
UT WOS:000270002600013
PM 19734351
ER
PT J
AU Whellan, DJ
Ellis, SJ
Kraus, WE
Hawthorne, K
Pina, IL
Keteyian, SJ
Kitzman, DW
Cooper, L
Lee, K
O'Connor, CM
AF Whellan, David J.
Ellis, Stephen J.
Kraus, William E.
Hawthorne, Katie
Pina, Ileana L.
Keteyian, Steven J.
Kitzman, Dalane W.
Cooper, Lawton
Lee, Kerry
O'Connor, Christopher M.
TI Method for Establishing Authorship in a Multicenter Clinical Trial
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; HEART-FAILURE; HF-ACTION; GUIDELINES; TIME
AB With the emergence of large multicenter trials over the past 20 years, the numbers of investigators involved and publications resulting from each study have grown exponentially. An efficient, fair, and effective way to establish authorship on study-related manuscripts could diminish conflict among the investigators and help ensure robust and timely dissemination of study results. This article describes a process developed by the investigators in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial (ClinicalTrials. gov registration number: NCT00047437) to establish authorship of the manuscripts describing the baseline characteristics, study design, and trial outcomes in an equitable and transparent manner based on objective, quantifiable contributions to the study as a whole. The HF-ACTION investigators developed a scoring system that assigned points to investigators by using the criteria established for enrollment, adherence to the exercise program, data completion, committee service, and other trial efforts. The scoring system has been successfully implemented for baseline manuscripts and has allowed many investigators to participate in the HF-ACTION publication process.
C1 Duke Univ, Med Ctr, Durham, NC USA.
Duke Clin Res Inst, Durham, NC USA.
Wake Forest Univ, Sch Med, Winston Salem, NC USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Case Western Reserve Univ, Cleveland, OH 44106 USA.
Henry Ford Hosp, Detroit, MI 48202 USA.
NHLBI, NIH, Bethesda, MD 20892 USA.
[Whellan, David J.] Jefferson Med Coll, Dept Cardiol, Philadelphia, PA 19107 USA.
RP Whellan, DJ (reprint author), Jefferson Med Coll, Dept Cardiol, 1015 Chestnut St,Suite 317, Philadelphia, PA 19107 USA.
OI Kraus, William E/0000-0003-1930-9684
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[NIH/NHLBI U01HL063747]
FX By the National Heart, Lung, and Blood Institute, National Institutes of
Health, for the HF-ACTION trial (NIH/NHLBI U01HL063747).
NR 9
TC 12
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U1 0
U2 2
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD SEP 15
PY 2009
VL 151
IS 6
BP 414
EP W133
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 501OB
UT WOS:000270390100006
PM 19755366
ER
PT J
AU van Bemmel, DM
Brank, AS
Eritja, R
Marquez, VE
Christman, JK
AF van Bemmel, Dana M.
Brank, Adam S.
Eritja, Ramon
Marquez, Victor E.
Christman, Judith K.
TI DNA (Cytosine-C5) methyltransferase inhibition by
oligodeoxyribonucleotides containing 2-(1H)-pyrimidinone (zebularine
aglycon) at the enzymatic target site
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Zebularine; DNA methylation; 2(1H)-Pyrimidinone riboside; DNA
methyltransferase; 5-Aza-2 '-deoxycytidine
ID CELL LUNG-CANCER; CYTIDINE DEAMINASE; ESCHERICHIA-COLI; PHASE-II;
5-AZA-2'-DEOXYCYTIDINE DECITABINE; HHAI METHYLTRANSFERASE;
HYPOMETHYLATING AGENT; METHYLATION INHIBITOR; GENE-EXPRESSION;
5-AZACYTIDINE
AB Aberrant cytosine methylation in promoter regions leads to gene silencing associated with cancer progression. A number of DNA methyltransferase inhibitors are known to reactivate silenced genes: including 5-azacytidine and 2-(1H)-pyrimidinone riboside (zebularine). Zebularine is a more stable, less cytotoxic inhibitor compared to 5-azacytidine. To determine the mechanistic basis for this difference, we carried out a detailed comparisons of the interaction between purified DNA methyltransferases and oligodeoxyribonucleotides (ODNs) containing either 5-azacytosine or 2-(1H)-pyrimidinone in place of the cytosine targeted for methylation. When incorporated into small ODNs, the rate of C5 DNA methyltransferase inhibition by both nucleosides is essentially identical. However, the stability and reversibility of the enzyme complex in the absence and presence of cofactor differs. 5-Azacytosine ODNs form complexes with C5 DNA methyltransferases that are irreversible when the 5-azacytosine ring is intact. ODNs containing 2-(1H)-pyrimidinone at the enzymatic target site are competitive inhibitors of both prokaryotic and mammalian DNA C5 methyltransferases. We determined that the ternary complexes between the enzymes, 2-(1H)-pyrimidinone inhibitor, and the cofactor S-adenosyl methionine are maintained through the formation of a reversible covalent interaction. The differing stability and reversibility of the covalent bonds may partially account for the observed differences in cytotoxicity between zebularine and 5-azacytidine inhibitors. Published by Elsevier Inc.
C1 [van Bemmel, Dana M.; Brank, Adam S.; Christman, Judith K.] Dept Biochem & Mol Biol, Omaha, NE 68198 USA.
[Christman, Judith K.] Univ Nebraska, Med Ctr, Eppley Canc Ctr, Omaha, NE 68198 USA.
[Eritja, Ramon] CSIC, Ctr Invest & Desarrolo, E-08034 Barcelona, Spain.
[Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP van Bemmel, DM (reprint author), NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA.
EM vanbemmeld@mail.nih.gov
RI eritja, ramon/B-5613-2008
OI eritja, ramon/0000-0001-5383-9334
FU NIH/NCI [R21CA91315]; Graduate College at UNMC; Intramural Research
Program of the NIH; Center for Cancer Research; NCI Frederick
FX Partial support for this work was provided by a grant from the NIH/NCI
(R21CA91315) to j.K.C. and a fellowship from the Graduate College at
UNMC to D.V.B. We are grateful to S. Kumar of New England Biolabs for
providing us with Escherichia coli strain ER1727 containing the
pUHE25Hhal plasmid. This research was also supported in part with funds
from the Intramural Research Program of the NIH, Center for Cancer
Research, NCI Frederick. We also thank Dr. Michael Boland for critical
reading of the manuscript and careful comments.
NR 54
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U1 2
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD SEP 15
PY 2009
VL 78
IS 6
BP 633
EP 641
DI 10.1016/j.bcp.2009.05.017
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 482IB
UT WOS:000268877400010
PM 19467223
ER
PT J
AU Hobbs, CA
Deterding, LJ
Perera, L
Bobay, BG
Thompson, RJ
Darden, TA
Cavanagh, J
Tomer, KB
AF Hobbs, Carey A.
Deterding, Leesa J.
Perera, Lalith
Bobay, Benjamin G.
Thompson, Richele J.
Darden, Thomas A.
Cavanagh, John
Tomer, Kenneth B.
TI Structural Characterization of the Conformational Change in
Calbindin-D-28k upon Calcium Binding Using Differential Surface
Modification Analyzed by Mass Spectrometry
SO BIOCHEMISTRY
LA English
DT Article
ID NUCLEAR-MAGNETIC-RESONANCE; SELECTIVE CHEMICAL-MODIFICATION; MYOINOSITOL
MONOPHOSPHATASE; DIETHYL PYROCARBONATE; CA2+ BINDING; PROTEINS; D-28K;
PEPTIDE; DIVERSITY; TOPOLOGY
AB Calbindin-D-28k is a calcium binding protein with six EF hand domains. Calbindin-D-28k is unique in that it functions as both a calcium buffer and a sensor protein. It is found in many tissues, including brain, pancreas, kidney, and intestine, playing important roles in each. Calbindin-D-28k is known to bind four calcium ions and upon calcium binding undergoes a conformational change. The structure of apo calbindin-D-28k is in an ordered state, transitioning into a disordered state as calcium is bound. Once fully loaded with four calcium ions, it again takes on ail ordered state. The solution structure of disulfide-reduced holo-calbindin-D-28k has been determined by NMR, while the structure of apo calbindin-D-28k has yet to be determined. Differential surface modification of lysine and histidine residues analyzed by mass spectrometry has been used in this study to identify, for the first time, the specific regions of calbindin-D-28k undergoing conformational changes between the holo and apo states. Using differential Surface modification in combination with mass spectrometry, EF hands 1 and 4 as well as the linkers before EF hand 1 and the linkers between EF hands 4 and 5 and EF hands 5 and 6 were identified as regions of conformational change between apo and holo calbindin-D-28k. Under the experimental conditions employed, EF hands 2 and 6, which are known not to bind calcium, were unaffected in either form. EF hand 2 is highly accessible; however, EF hand 6 was determined not to be surface accessible in either form. Previous research has identified a disulfide bond between cysteines 94 and 100 in the holo state. Until now, it was unknown whether this bond also exists in the apo form. Our data confirm the presence of the disulfide bond between cysteines 94 and 100 in the holo form and indicate that there is predominantly no disulfide bond between these residues in the apoprotein.
C1 [Hobbs, Carey A.; Bobay, Benjamin G.; Thompson, Richele J.; Cavanagh, John] N Carolina State Univ, Dept Mol & Struct Biochem, Raleigh, NC 27695 USA.
[Deterding, Leesa J.; Perera, Lalith; Darden, Thomas A.; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Cavanagh, J (reprint author), N Carolina State Univ, Dept Mol & Struct Biochem, Raleigh, NC 27695 USA.
EM john_cavanagh@ncsu.edu; tomer@niehs.nih.gov
RI perera, Lalith/B-6879-2012; Tomer, Kenneth/E-8018-2013;
OI perera, Lalith/0000-0003-0823-1631; Bobay, Benjamin/0000-0003-4775-3686
FU Kenan Institute for Engineering, Technology and Science; National
Institute of Environmental Health Sciences/National Institutes of Health
[ES050127, ES04301023]
FX This research was supported by a grant from the Kenan Institute for
Engineering, Technology and Science and by the Intramural Research
Program of the National Institute of Environmental Health
Sciences/National Institutes of Health (Projects ES050127 and
ES04301023).
NR 51
TC 5
Z9 5
U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD SEP 15
PY 2009
VL 48
IS 36
BP 8603
EP 8614
DI 10.1021/bi900350q
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 490FV
UT WOS:000269485500013
PM 19658395
ER
PT J
AU Stojmirovic, A
Yu, YK
AF Stojmirovic, Aleksandar
Yu, Yi-Kuo
TI ITM Probe: analyzing information flow in protein networks
SO BIOINFORMATICS
LA English
DT Article
ID GENE ONTOLOGY; SOFTWARE; BIOLOGY
AB Founded upon diffusion with damping, ITM Probe is an application for modeling information flow in protein interaction networks without prior restriction to the sub-network of interest. Given a context consisting of desired origins and destinations of information, ITM Probe returns the set of most relevant proteins with weights and a graphical representation of the corresponding sub-network. With a click, the user may send the resulting protein list for enrichment analysis to facilitate hypothesis formation or confirmation.
C1 [Stojmirovic, Aleksandar; Yu, Yi-Kuo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Yu, YK (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM yyu@ncbi.nlm.nih.gov
OI Stojmirovic, Aleksandar/0000-0003-0957-6893
FU National Library of Medicine at National Institutes of Health
FX Intramural Research Program of the National Library of Medicine at
National Institutes of Health.
NR 11
TC 11
Z9 12
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD SEP 15
PY 2009
VL 25
IS 18
BP 2447
EP 2449
DI 10.1093/bioinformatics/btp398
PG 3
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 491VC
UT WOS:000269607700029
PM 19561335
ER
PT J
AU Sambataro, F
Reed, JD
Murty, VP
Das, S
Tan, HY
Callicott, JH
Weinberger, DR
Mattay, VS
AF Sambataro, Fabio
Reed, Jeff D.
Murty, Vishnu P.
Das, Saumitra
Tan, Hao Yang
Callicott, Joseph H.
Weinberger, Daniel R.
Mattay, Venkata S.
TI Catechol-O-Methyltransferase Valine(158)Methionine Polymorphism
Modulates Brain Networks Underlying Working Memory Across Adulthood
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Aging; COMT; functional magnetic resonance imaging; independent
component analysis; working memory
ID AGE-RELATED-CHANGES; PREFRONTAL CORTEX; FUNCTIONAL MRI; DOPAMINE
MODULATION; COMT GENOTYPE; SCHIZOPHRENIA; PERFORMANCE; COGNITION;
SYNCHRONIZATION; MANIPULATION
AB Background: Cognitive abilities decline with age with large individual variability. Genetic variations have been suggested to be an important source for some of this heterogeneity. Among these variations, those related to the dopaminergic system, particularly the valine (158)methionine polymorphism in catechol-O-methyltransferase (COMTval(158)met), have been implicated in modulating age-related changes in executive function.
Methods: We studied 75 subjects (age 21-90 years) using functional neuroimaging while they performed a low-level working memory (WM) task to explore the effects of aging, of the COMTval(158)met polymorphism, and their interactions on the physiological patterns of interconnected cortical activity engaged by WM.
Results: Our results show that val homozygotes and older subjects showed increased activity in dorsolateral prefrontal cortex (DLPFC) and decreased activity in ventrolateral prefrontal cortex (VLPFC) relative to met homozygotes and younger subjects, respectively. Interestingly, there were also independent effects of the COMTval(158)met polymorphism and age on the strength of connectivity between brain regions within the left prefrontal-parietal network; val homozygotes and older subjects showed greater connectivity between the DLPFC and other brain regions within the network and met homozygotes showed greater connectivity between the VLPFC and other brain regions within the network. Furthermore, the greater functional connectivity strength of DLPFC in val homozygotes relative to met homozygotes was much more pronounced in older adults
Conclusions: Our findings suggest that the COMTval(158)met polymorphism modulates both the activity and functional connectivity of brain regions within WM networks and most importantly that this effect is exaggerated with increasing age, contributing to the variability in age-related decline in executive cognition.
C1 [Sambataro, Fabio; Reed, Jeff D.; Murty, Vishnu P.; Das, Saumitra; Tan, Hao Yang; Callicott, Joseph H.; Weinberger, Daniel R.; Mattay, Venkata S.] NIMH, Genes Cognit & Psychosis Program, NIH, Clin Brain Disorders Branch,Intramural Res Progra, Bethesda, MD 20892 USA.
RP Mattay, VS (reprint author), NIMH, Genes Cognit & Psychosis Program, NIH, Clin Brain Disorders Branch,Intramural Res Progra, Bldg 10,Room 3C-108, Bethesda, MD 20892 USA.
EM vsm@mail.nih.gov
RI Sambataro, Fabio/E-3426-2010; Callicott, Joseph/C-9102-2009
OI Sambataro, Fabio/0000-0003-2102-416X; Callicott,
Joseph/0000-0003-1298-3334
FU National Institute of Mental Health
FX This work was supported by the National Institute of Mental Health
Intramural Research Program. The study protocol was approved by the
Intramural Review Board of the National Institute of Mental Health and
appropriate procedures were used concerning the human subjects involved.
NR 53
TC 33
Z9 34
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD SEP 15
PY 2009
VL 66
IS 6
BP 540
EP 548
DI 10.1016/j.biopsych.2009.04.014
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 490OO
UT WOS:000269510600003
PM 19539269
ER
PT J
AU Pettit, RK
Pettit, GR
Hamel, E
Hogan, F
Moser, BR
Wolf, S
Pon, S
Chapuis, JC
Schmidt, JM
AF Pettit, Robin K.
Pettit, George R.
Hamel, Ernest
Hogan, Fiona
Moser, Bryan R.
Wolf, Sonja
Pon, Sandy
Chapuis, Jean-Charles
Schmidt, Jean M.
TI E-Combretastatin and E-resveratrol structural modifications:
Antimicrobial and cancer cell growth inhibitory beta-E-nitrostyrenes
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Resveratrol; Combretastatin; beta-E-Nitrostyrene; Anticancer agent
ID ANTINEOPLASTIC AGENTS; A-4 PRODRUG; PHOSPHATE; TUBULIN; ANALOGS;
DERIVATIVES; NITROALKENES; POTENT; A4; PROLIFERATION
AB As part of a broad-based SAR investigation of E-resveratrol (strong sirtuin activator and antineoplastic) and the anticancer vascular-targeting combretastatin-type stilbenes, a series of twenty-three beta-E-nitrostyrenes was synthesized in order to evaluate potential antineoplastic, antitubulin, and antimicrobial activities. The beta-E-nitrostyrenes evaluated ranged from monosubstituted phenols to trimethoxy and 3-methoxy- 4,5-methylenedioxy derivatives. Two of the beta-nitrostyrenes were synthesized as water-soluble sodium phosphate derivatives (4t, 4v). All except four (4r, 4s, 4t, 4u) of the series significantly inhibited a minipanel of human cancer cell lines. All but eight led to an IC(50) of < 10 mu M for inhibition of tubulin polymerization, and all except three (4l, 4t, 4v) displayed antimicrobial activity. (C) 2009 Published by Elsevier Ltd.
C1 [Pettit, Robin K.; Pettit, George R.; Hogan, Fiona; Wolf, Sonja; Pon, Sandy; Chapuis, Jean-Charles; Schmidt, Jean M.] Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA.
[Pettit, Robin K.; Pettit, George R.; Hogan, Fiona; Wolf, Sonja; Pon, Sandy; Chapuis, Jean-Charles; Schmidt, Jean M.] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
[Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[Moser, Bryan R.] ARS, USDA, Natl Ctr Agr Utilizat Res, Peoria, IL 61604 USA.
RP Pettit, RK (reprint author), Arizona State Univ, Canc Res Inst, POB 871604, Tempe, AZ 85287 USA.
EM robin.pettit@asu.edu; bpettit@asu.edu
FU National Cancer Institute DHHS [CA44344-8-12, RO1 CA9044101-03, 5RO1 CA
090441-07]; Arizona Disease Control Research Commission; Robert B.
Dalton Endowment Fund; Caitlin Robb Foundation
FX The very necessary financial support was provided by Outstanding
Investigator Grant CA44344-8-12, Grant RO1 CA9044101-03, and Grant 5RO1
CA 090441-07 awarded to GRP by the Division of Cancer Treatment and
Diagnosis, National Cancer Institute DHHS; the Arizona Disease Control
Research Commission; the Robert B. Dalton Endowment Fund; and the
Caitlin Robb Foundation. For other helpful assistance, we thank Drs.
Michael D. Williams and Mathew D. Minardi, as well as Lee Williams.
NR 77
TC 20
Z9 22
U1 2
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD SEP 15
PY 2009
VL 17
IS 18
BP 6606
EP 6612
DI 10.1016/j.bmc.2009.07.076
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 489DK
UT WOS:000269399700014
PM 19709889
ER
EF