FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Yetley, EA
   Pfeiffer, CM
   Phinney, KW
   Fazili, Z
   Lacher, DA
   Bailey, RL
   Blackmore, S
   Bock, JL
   Brody, LC
   Carmel, R
   Curtin, LR
   Durazo-Arvizu, RA
   Eckfeldt, JH
   Green, R
   Gregory, JF
   Hoofnagle, AN
   Jacobsen, DW
   Jacques, PF
   Molloy, AM
   Massaro, J
   Mills, JL
   Nexo, E
   Rader, JI
   Selhub, J
   Sempos, C
   Shane, B
   Stabler, S
   Stover, P
   Tamura, T
   Tedstone, A
   Thorpe, SJ
   Coates, PM
   Johnson, CL
   Picciano, MF
AF Yetley, Elizabeth A.
   Pfeiffer, Christine M.
   Phinney, Karen W.
   Fazili, Zia
   Lacher, David A.
   Bailey, Regan L.
   Blackmore, Sheena
   Bock, Jay L.
   Brody, Lawrence C.
   Carmel, Ralph
   Curtin, L. Randy
   Durazo-Arvizu, Ramon A.
   Eckfeldt, John H.
   Green, Ralph
   Gregory, Jesse F., III
   Hoofnagle, Andrew N.
   Jacobsen, Donald W.
   Jacques, Paul F.
   Molloy, Anne M.
   Massaro, Joseph
   Mills, James L.
   Nexo, Ebba
   Rader, Jeanne I.
   Selhub, Jacob
   Sempos, Christopher
   Shane, Barry
   Stabler, Sally
   Stover, Patrick
   Tamura, Tsunenobu
   Tedstone, Alison
   Thorpe, Susan J.
   Coates, Paul M.
   Johnson, Clifford L.
   Picciano, Mary Frances
TI Biomarkers of folate status in NHANES: a roundtable summary
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; FOLIC-ACID FORTIFICATION; WHOLE-BLOOD FOLATE;
   BIO-RAD RADIOASSAY; B-VITAMIN STATUS; HUMAN SERUM; MICROBIOLOGIC ASSAY;
   INTERNATIONAL STANDARD; UNITED-STATES; HUMAN PLASMA
AB A roundtable to discuss the measurement of folate status biomarkers in NHANES took place in July 2010. NHANES has measured serum folate since 1974 and red blood cell (RBC) folate since 1978 with the use of several different measurement procedures. Data on serum 5-methyltetrahydrofolate (5MTHF) and folic acid (FA) concentrations in persons aged >= 60 y are available in NHANES 1999-2002. The roundtable reviewed data that showed that folate concentrations from the Bio-Rad Quantaphase II procedure (Bio-Rad Laboratories, Hercules, CA; used in NHANES 1991-1994 and NHANES 1999-2006) were, on average, 29% lower for serum and 45% lower for RBC than were those from the microbiological assay (MA), which was used in NHANES 2007-2010. Round-table experts agreed that these differences required a data adjustment for time-trend analyses. The roundtable reviewed the possible use of an isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurement procedure for future NHANES and agreed that the close agreement between the MA and LC-MS/MS results for serum folate supported conversion to the LC-MS/MS procedure. However, for RBC folate, the MA gave 25% higher concentrations than did the LC-MS/MS procedure. The roundtable agreed that the use of the LC-MS/MS procedure to measure RBC folate is premature at this time. The roundtable reviewed the reference materials available or under development at the National Institute of Standards and Technology and recognized the challenges related to, and the scientific need for, these materials. They noted the need for a commutability study for the available reference materials for serum 5MTHF and FA. Am J Clin Nutr 2011;94(suppl):303S-12S.
C1 [Yetley, Elizabeth A.; Bailey, Regan L.; Sempos, Christopher; Coates, Paul M.; Picciano, Mary Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
   [Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   [Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
   [Pfeiffer, Christine M.; Fazili, Zia] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA.
   [Phinney, Karen W.] NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA.
   [Lacher, David A.; Curtin, L. Randy; Johnson, Clifford L.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
   [Blackmore, Sheena] United Kingdom Natl External Qual Assessment Serv, Dept Haematol, Sutton, Coldfield, England.
   [Bock, Jay L.] SUNY Stony Brook, Dept Pathol, Med Ctr, Stony Brook, NY 11794 USA.
   [Carmel, Ralph] New York Methodist Hosp, Dept Med, Brooklyn, NY USA.
   [Carmel, Ralph] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
   [Durazo-Arvizu, Ramon A.] Loyola Univ Chicago, Stritch Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL USA.
   [Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
   [Green, Ralph] Univ Calif Davis, Dept Med Pathol & Lab Med & Med, Sacramento, CA 95817 USA.
   [Gregory, Jesse F., III] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA.
   [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
   [Hoofnagle, Andrew N.] Univ Washington, Dept Med, Seattle, WA USA.
   [Jacobsen, Donald W.] Case Western Reserve Univ, Lerner Coll Med, Dept Mol Med, Cleveland Clin, Cleveland, OH 44106 USA.
   [Jacobsen, Donald W.] Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44106 USA.
   [Jacques, Paul F.; Selhub, Jacob] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   [Molloy, Anne M.] Trinity Coll Dublin, Sch Med, Dept Clin Med, Dublin, Ireland.
   [Massaro, Joseph] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
   [Nexo, Ebba] Aarhus Univ Hosp, Dept Clin Biochem, DK-8000 Aarhus, Denmark.
   [Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
   [Shane, Barry] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
   [Stabler, Sally] Univ Colorado, Hlth Sci Ctr, Div Hematol, Dept Med, Aurora, CO USA.
   [Stover, Patrick] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
   [Tamura, Tsunenobu] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA.
   [Tedstone, Alison] Dept Hlth, London SE1 6TE, England.
RP Coates, PM (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Room 3B01,MSC 7517, Bethesda, MD 20892 USA.
EM beth@yetley.com; coatesp@od.nih.gov
RI Thorpe, Susan/E-1808-2013; 
OI Molloy, Anne/0000-0002-1688-9049
FU National Center for Health Statistics, Centers for Disease Control and
   Prevention; Office of Dietary Supplements, NIH
FX Supported by the National Center for Health Statistics, Centers for
   Disease Control and Prevention, and the Office of Dietary Supplements,
   NIH.
NR 52
TC 39
Z9 40
U1 0
U2 11
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
   USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUL
PY 2011
VL 94
IS 1
BP 303S
EP 312S
DI 10.3945/ajcn.111.013011
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 779QK
UT WOS:000291794800045
PM 21593502
ER

PT J
AU Yetley, EA
   Pfeiffer, CM
   Phinney, KW
   Bailey, RL
   Blackmore, S
   Bock, JL
   Brody, LC
   Carmel, R
   Curtin, LR
   Durazo-Arvizu, R
   Eckfeldt, JH
   Green, R
   Gregory, JF
   Hoofnagle, AN
   Jacobsen, DW
   Jacques, PF
   Lacher, DA
   Molloy, AM
   Massaro, J
   Mills, JL
   Nexo, E
   Rader, JI
   Selhub, J
   Sempos, C
   Shane, B
   Stabler, S
   Stover, P
   Tamura, T
   Tedstone, A
   Thorpe, SJ
   Coates, PM
   Johnson, CL
   Picciano, MF
AF Yetley, Elizabeth A.
   Pfeiffer, Christine M.
   Phinney, Karen W.
   Bailey, Regan L.
   Blackmore, Sheena
   Bock, Jay L.
   Brody, Lawrence C.
   Carmel, Ralph
   Curtin, L. Randy
   Durazo-Arvizu, Ramon
   Eckfeldt, John H.
   Green, Ralph
   Gregory, Jesse F., III
   Hoofnagle, Andrew N.
   Jacobsen, Donald W.
   Jacques, Paul F.
   Lacher, David A.
   Molloy, Anne M.
   Massaro, Joseph
   Mills, James L.
   Nexo, Ebba
   Rader, Jeanne I.
   Selhub, Jacob
   Sempos, Christopher
   Shane, Barry
   Stabler, Sally
   Stover, Patrick
   Tamura, Tsunenobu
   Tedstone, Alison
   Thorpe, Susan J.
   Coates, Paul M.
   Johnson, Clifford L.
   Picciano, Mary Frances
TI Biomarkers of vitamin B-12 status in NHANES: a roundtable summary
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID PLASMA METHYLMALONIC ACID; TANDEM MASS-SPECTROMETRY; 3RD
   NATIONAL-HEALTH; TOTAL HOMOCYSTEINE; LIQUID-CHROMATOGRAPHY; COGNITIVE
   IMPAIRMENT; BIOCHEMICAL INDICATORS; SRM-1955 HOMOCYSTEINE;
   AUTOMATED-ASSAY; OLDER-ADULTS
AB A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12-related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES-serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)-and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12-related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA, which have been associated with cognitive dysfunction and anemia in NHANES and in other population-based studies, was preferable to provide continuity with past NHANES. Reliable measurement procedures are available, and National Institute of Standards and Technology reference materials are available or in development for serum vitamin B-12 and MMA. Am J Clin Nutr 2011;94(suppl):313S-21S.
C1 [Yetley, Elizabeth A.; Bailey, Regan L.; Sempos, Christopher; Coates, Paul M.; Picciano, Mary Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
   [Pfeiffer, Christine M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA.
   [Phinney, Karen W.] NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA.
   [Blackmore, Sheena] United Kingdom Natl External Qual Assessment Serv, Dept Haematol, Sutton, Coldfield, England.
   [Bock, Jay L.] SUNY Stony Brook, Dept Pathol, Med Ctr, Stony Brook, NY 11794 USA.
   [Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   [Carmel, Ralph] New York Methodist Hosp, Dept Med, Brooklyn, NY USA.
   [Carmel, Ralph] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
   [Curtin, L. Randy; Lacher, David A.; Johnson, Clifford L.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
   [Durazo-Arvizu, Ramon] Loyola Univ Chicago, Stritch Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL USA.
   [Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
   [Green, Ralph] Univ Calif Davis, Dept Med Pathol & Lab Med & Med, Sacramento, CA 95817 USA.
   [Gregory, Jesse F., III] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA.
   [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
   [Jacobsen, Donald W.] Case Western Reserve Univ, Lerner Coll Med, Cleveland Clin, Dept Mol Med, Cleveland, OH 44106 USA.
   [Jacobsen, Donald W.] Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44106 USA.
   [Jacques, Paul F.; Selhub, Jacob] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
   [Molloy, Anne M.] Trinity Coll Dublin, Dept Clin Med, Sch Med, Dublin, Ireland.
   [Massaro, Joseph] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
   [Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
   [Nexo, Ebba] Aarhus Univ Hosp, Dept Clin Biochem, DK-8000 Aarhus, Denmark.
   [Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
   [Shane, Barry] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
   [Stabler, Sally] Univ Colorado, Hlth Sci Ctr, Div Hematol, Dept Med, Aurora, CO USA.
   [Stover, Patrick] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
   [Tamura, Tsunenobu] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA.
   [Tedstone, Alison] Dept Hlth, London SE1 6TE, England.
   [Thorpe, Susan J.] Natl Inst Biol Stand & Controls, Potters Bar, Herts, England.
RP Coates, PM (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Room 3B01,MSC 7517, Bethesda, MD 20892 USA.
EM beth@yetley.com; coatesp@od.nih.gov
RI Thorpe, Susan/E-1808-2013; 
OI Molloy, Anne/0000-0002-1688-9049; Gregory, Jesse/0000-0002-9976-2085
FU National Center for Health Statistics, Centers for Disease Control and
   Prevention; Office of Dietary Supplements, National Institutes of
   Health; Axis Shield Diagnostics
FX Supported by the National Center for Health Statistics, Centers for
   Disease Control and Prevention, and MFP, CLJ, EAY, and PMC: conceived
   and sponsored the roundtable project; MFP, CLJ, EAY, PMC, RLB, DAL, AMM,
   JLM, CMP, KWP, CS, BS, and TT: served on the planning committee; EAY,
   CLJ, JHE, JM, RAD- A, CS, BS, CMP, KWP, JS, RC, EN, RLB, and DAL:
   presented data and backgroundinformation; EAY: drafted the manuscript
   with considerable input from CMP and KWP; EAY, CLJ, and PMC: had primary
   responsibility for the final manuscript content; and all authors: fully
   participated in the roundtable discussions and read and approved the
   final manuscript. RG and DWJ serve on the Scientific Advisory Boards of
   Emisphere Technologies Inc of Cedar Knolls, NJ, and PARPharmaceuticals
   of Woodcliff Lake, NJ. DWJ also serves on the Scientific Advisory Board
   of Diazyme-GA, La Jolla, CA. For the past 3 y, AMM carried out a
   research project that was funded by Axis Shield Diagnostics and also
   carried a consulting agreement with this firm. RC's hospital filed a
   patent application for his work on the genetics of transcobalamin I
   deficiency. None of the other authors had any personal or financial
   conflicts of interest.Office of Dietary Supplements, National Institutes
   of Health.
NR 58
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U1 0
U2 14
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
   USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUL
PY 2011
VL 94
IS 1
BP 313S
EP 321S
DI 10.3945/ajcn.111.013243
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 779QK
UT WOS:000291794800046
PM 21593512
ER

PT J
AU Yetley, EA
   Johnson, CL
AF Yetley, Elizabeth A.
   Johnson, Clifford L.
TI Folate and vitamin B-12 biomarkers in NHANES: history of their
   measurement and use
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; FOLIC-ACID
   FORTIFICATION; TOTAL HOMOCYSTEINE CONCENTRATIONS; SERUM
   25-HYDROXYVITAMIN D; UNITED-STATES; BIOCHEMICAL INDICATORS;
   CARDIOVASCULAR-DISEASE; COGNITIVE IMPAIRMENT; TOTAL HOMOCYST(E)INE
AB NHANES measured folate and vitamin B-12 status biomarkers, starting with serum folate from NHANES I (1974-1975) through 2010. Subsequent NHANES measured additional biomarkers [eg, red blood cell folate, serum vitamin B-12, total homocysteine (tHcy), methylmalonic acid, serum folic acid, and 5-methyltetrahydrofolic acid]. Examples of the uses of these data are wide ranging and include public policy applications, the derivation of reference intervals, and research. Periodically, the National Center for Health Statistics and its federal partners convene expert panels to review the use of the folate-and vitamin B-12-related biomarkers in NHANES. These panels have evaluated the need for results to be comparable across time and with published data and the use of crossover studies and adjustment equations to ensure comparability. With the recent availability of reference methods and materials for serum folate and tHcy, NHANES has started to use traceability approaches to enhance the accuracy and comparability of its results. A major user concern over the years has been the use of cutoffs to estimate the prevalence of inadequate folate and vitamin B-12 status. Because these cutoffs depend on the measurement procedure, several expert panels suggested approaches for dealing with cutoff challenges. This review summarizes the history and use of folate and vitamin B-12-related biomarkers beginning with NHANES I (1974-1975) through 2010. Am J Clin Nutr 2011;94(suppl):1S-10S.
C1 [Yetley, Elizabeth A.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
   [Johnson, Clifford L.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
EM beth@yetley.com
FU Office of Dietary Supplements, National Institutes of Health; National
   Center for Health Statistics, Centers for Disease Control and Prevention
FX Supported by the Office of Dietary Supplements, National Institutes of
   Health, and the National Center for Health Statistics, Centers for
   Disease Control and Prevention.
NR 68
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U2 7
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUL
PY 2011
VL 94
IS 1
DI 10.3945/ajcn.111.013300
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 779QK
UT WOS:000291794800047
PM 21593508
ER

PT J
AU Yau, JWY
   Xie, J
   Kawasaki, R
   Kramer, H
   Shlipak, M
   Klein, R
   Klein, B
   Cotch, MF
   Wong, TY
AF Yau, Joanne Wen Yee
   Xie, Jing
   Kawasaki, Ryo
   Kramer, Holly
   Shlipak, Michael
   Klein, Ronald
   Klein, Barbara
   Cotch, Mary Frances
   Wong, Tien Yin
TI Retinal Arteriolar Narrowing and Subsequent Development of CKD Stage 3:
   The Multi-Ethnic Study of Atherosclerosis (MESA)
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Microvascular changes; retinal microvascular caliber; chronic kidney
   disease
ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE;
   DIABETIC-RETINOPATHY; VESSEL DIAMETERS; MICROVASCULAR ABNORMALITIES;
   RENAL-INSUFFICIENCY; ASIAN POPULATION; RISK-FACTORS; HYPERTENSION;
   CALIBER
AB Background: Microvascular disease is a major pathogenic factor for chronic kidney disease (CKD) in persons with diabetes, but the role of microvascular disease in the development of CKD in the general population is unclear. The aim of this study is to examine whether microvascular disease precedes the development of CKD stage 3 in participants of the Multi-Ethnic Study of Atherosclerosis (MESA).
   Study Design: Population-based cohort study.
   Setting & Participants: MESA is a prospective cohort study of adults aged 45-84 years living in 6 US communities; 4,594 adults with estimated glomerular filtration rate (eGFR) >= 60 mL/min/1.73 m(2) when they underwent retinal photography (visit 2: in 2002-2004) were examined.
   Predictor: Retinal microvascular caliber measured from fundus photographs.
   Outcomes: Incident CKD stage 3 (ie, eGFR <60 mL/min/1.73 m(2)) at 2 subsequent follow-up examinations (visit 3 in 2004-2005, and visit 4 in 2005-2007) and an annual eGFR decrease >1 mL/min/1.73 m(2) computed using the CKD Epidemiology Collaboration (CKD-EPI) equation.
   Results: After a median follow-up of 4.8 years, there were 232 incident CKD stage 3 cases. Overall, retinal microvascular caliber was not associated with incident CKD stage 3. However, in race-stratified analysis, narrower arterioles in whites was associated with a higher risk of developing CKD stage 3 after adjusting for age, sex, blood pressure, diabetes, and other factors (HR, 1.78; 95% CI, 1.01-3.15; P = 0.04, lowest vs highest arteriolar caliber tertile). This association was seen even in whites without hypertension and diabetes (HR, 2.95; 95% CI, 1.10-7.98; P = 0.03). Retinal arteriolar caliber was not associated with incident CKD stage 3 in African Americans, Chinese, or Hispanics.
   Limitations: Analyses were based on a single eGFR measurement, and retinal microvascular caliber and eGFR measurements were not ascertained concurrently.
   Conclusion: Microvascular changes as manifest in the eye may contribute to the development of CKD stage 3 in whites. Am J Kidney Dis. 58(1):39-46. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use.
C1 [Yau, Joanne Wen Yee; Xie, Jing; Kawasaki, Ryo; Wong, Tien Yin] Univ Melbourne, Ctr Eye Res Australia, Royal Victorian Eye & Ear Hosp, Melbourne, Vic 3002, Australia.
   [Kramer, Holly] Loyola Med Ctr, Dept Prevent Med, San Francisco, CA USA.
   [Shlipak, Michael] Univ Calif San Francisco, Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
   [Klein, Ronald; Klein, Barbara] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA.
   [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
   [Wong, Tien Yin] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
RP Yau, JWY (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia.
EM jwyau@unimelb.edu.au
RI Xie, Jin/E-8193-2010; 
OI Cotch, Mary Frances/0000-0002-2046-4350; Kramer,
   Holly/0000-0002-6374-837X; Klein, Ronald/0000-0002-4428-6237
FU National Heart, Lung, and Blood Institute and National Institutes of
   Health (NIH) [N01-HC-95159, N01-HC-95165, N01-HC-95169]; National Eye
   Institute [Z01EY000403]; NIH [HL69979-03]; Centre for Clinical Research
   Excellence; Victorian government
FX This research was supported by contracts N01-HC-95159 through
   N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood
   Institute and National Institutes of Health (NIH) Intramural Research
   award Z01EY000403 from the National Eye Institute (M. F. C.). Additional
   support was provided by NIH grants HL69979-03 (Drs Klein and Wong) and
   the Centre for Clinical Research Excellence. The Centre for Eye Research
   Australia receives operational infrastructure support from the Victorian
   government.
NR 33
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PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD JUL
PY 2011
VL 58
IS 1
BP 39
EP 46
DI 10.1053/j.ajkd.2011.02.382
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 778RB
UT WOS:000291721200010
PM 21549464
ER

PT J
AU McFalls, EO
   Larsen, G
   Johnson, GR
   Apple, FS
   Goldman, S
   Arai, A
   Nallamothu, BK
   Jesse, R
   Holmstrom, ST
   Sinnott, PL
AF McFalls, Edward O.
   Larsen, Greg
   Johnson, Gary R.
   Apple, Fred S.
   Goldman, Steven
   Arai, Andrew
   Nallamothu, Brahmajee K.
   Jesse, Robert
   Holmstrom, Scott T.
   Sinnott, Patricia L.
TI Outcomes of Hospitalized Patients with Non-Acute Coronary Syndrome and
   Elevated Cardiac Troponin Level
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Cardiac imaging; Coronary artery disease; Non-acute coronary syndrome
   diagnosis; Outcomes; Troponins
ID CRITICALLY-ILL PATIENTS; ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT
   ELEVATION; HEART-FAILURE; MORTALITY; PREVALENCE; ASSOCIATION; STRATEGIES
AB OBJECTIVE: Cardiac troponin levels help risk-stratify patients presenting with an acute coronary syndrome. Although cardiac troponin levels may be elevated in patients presenting with non-acute coronary syndrome conditions, specific diagnoses and long-term outcomes within that cohort are unclear.
   METHODS: By using the Veterans Affairs centralized databases, we identified all hospitalized patients in 2006 who had a troponin assay obtained during their initial reference hospitalization. On the basis of the diagnostic codes of the International Classification of Diseases, 9th Revision, primary diagnoses were categorized as acute coronary syndrome or non-acute coronary syndrome conditions.
   RESULTS: Of a total of 21,668 patients with an elevated troponin level who were discharged from the hospital, 12,400 (57.2%) had a non-acute coronary syndrome condition. Among that cohort, the most common diagnostic category involved the cardiovascular system, and congestive heart failure (N = 1661) and chronic coronary artery disease (N = 1648) accounted for the major classifications. At 1 year after hospital discharge, mortality in patients with a non-acute coronary syndrome condition was 22.8% and was higher than in the acute coronary syndrome cohort (odds ratio 1.39; 95% confidence interval, 1.30-1.49). Despite the high prevalence of cardiovascular diseases in patients with a non-acute coronary syndrome diagnosis, use of cardiac imaging within 90 days of hospitalization was low compared with that in patients with acute coronary syndrome (odds ratio 0.25; 95% confidence interval, 0.23-0.27).
   CONCLUSIONS: Hospitalized patients with an elevated troponin level more often have a primary diagnosis that is not an acute coronary syndrome. Their long-term survival is poor and justifies novel diagnostic or therapeutic strategy-based studies to target the highest risk subsets before hospital discharge. Published by Elsevier Inc. The American Journal of Medicine (2011) 124, 630-635
C1 [McFalls, Edward O.] Vet Adm Med Ctr, Div Cardiol 111C, Cardiol Sect, Minneapolis, MN 55417 USA.
   [Larsen, Greg] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Cardiol Sect, Portland, OR 97201 USA.
   [Goldman, Steven] Vet Affairs Med Ctr, Cardiol Sect, Tucson, AZ USA.
   [Nallamothu, Brahmajee K.] Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA.
   [Jesse, Robert] Vet Affairs Med Ctr, Cardiol Sect, Richmond, VA USA.
   [Johnson, Gary R.] VA Connecticut Healthcare Syst, Cooperat Studies Program, Coordinating Ctr, West Haven, CT USA.
   [Apple, Fred S.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
   [Apple, Fred S.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA.
   [Arai, Andrew] NIH, Bethesda, MD 20892 USA.
   [Holmstrom, Scott T.; Sinnott, Patricia L.] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Menlo Pk, CA USA.
RP McFalls, EO (reprint author), Vet Adm Med Ctr, Div Cardiol 111C, Cardiol Sect, 1 Vet Dr, Minneapolis, MN 55417 USA.
EM mcfal00l@umn.edu
FU Department of Veterans Affairs; Office of Research and Development
FX Funding: Department of Veterans Affairs Cooperative Studies Program,
   Office of Research and Development.
NR 24
TC 18
Z9 18
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD JUL
PY 2011
VL 124
IS 7
BP 630
EP 635
DI 10.1016/j.amjmed.2011.02.024
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 778RG
UT WOS:000291721900020
PM 21601821
ER

PT J
AU Ripley, RT
   Kemp, CD
   Davis, JL
   Langan, RC
   Royal, RE
   Libutti, SK
   Steinberg, SM
   Wood, BJ
   Kammula, US
   Fojo, T
   Avital, I
AF Ripley, R. Taylor
   Kemp, Clinton D.
   Davis, Jeremy L.
   Langan, Russell C.
   Royal, Richard E.
   Libutti, Steven K.
   Steinberg, Seth M.
   Wood, Bradford J.
   Kammula, Udai S.
   Fojo, Tito
   Avital, Itzhak
TI Liver Resection and Ablation for Metastatic Adrenocortical Carcinoma
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID ADRENAL-CORTICAL CARCINOMA; CUSHINGS-SYNDROME; MANAGEMENT; SURVIVAL;
   SERIES
AB Background. Adrenocortical carcinoma (ACC) is a rare disease without effective chemotherapy treated most appropriately with resection. The aim of this study was to evaluate our experience with liver resection for metastatic ACC.
   Methods. This study is a retrospective review of patients who underwent liver resection or radiofrequency ablation (RFA) for ACC from 1979 to 2009.
   Results. A total of 27 patients were identified. Of the 27, 19 underwent liver resection. Of the 19, 10 had a single liver lesion, and 18 of 19 were rendered free of disease in the liver, although only 11 of 19 were rendered completely free of disease because of extrahepatic disease (EHD). Of the 19, 13 had synchronous EHD. Also, 6 of 17 remained disease free in the liver at a median follow-up of 6.2 years (status of 2 of 19 was unknown). Of the 27 patients, 8 underwent RFA, 7 of 8 became free of disease in the liver, and 5 of 7 had EHD. No patients responded to prior chemotherapy. Median overall survival and survival of patients who underwent liver resection or RFA were both 1.9 years (0.2-12 + years); 5-year actuarial survivals were 29% and 29%, respectively. Disease-free interval (DFI) greater than 9 months from primary resection was associated with longer survival (median 4.1 vs 0.9 years; P = .013).
   Conclusions. This study is a tertiary institution series of liver resection and RFA for ACC. Given the lack of effective systemic treatment options and the safety of resection and ablation, liver resection or RFA may be considered in selected patients with ACC metastatic to the liver especially with a long DFI.
C1 [Ripley, R. Taylor; Kemp, Clinton D.; Davis, Jeremy L.; Langan, Russell C.; Royal, Richard E.; Libutti, Steven K.; Kammula, Udai S.; Avital, Itzhak] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
   [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, NIH, Bethesda, MD 20892 USA.
   [Wood, Bradford J.] NCI, Dept Diagnost Radiol, NIH, Bethesda, MD 20892 USA.
   [Fojo, Tito] NCI, Med Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Ripley, RT (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM Taylor.Ripley@gmail.com
FU Intramural NIH HHS [ZIA BC010626-07, ZIA BC011003-04, ZID BC011242-02]
NR 19
TC 23
Z9 24
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUL
PY 2011
VL 18
IS 7
BP 1972
EP 1979
DI 10.1245/s10434-011-1564-z
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA 777VA
UT WOS:000291652000025
PM 21301973
ER

PT J
AU Shinmura, K
   Igarashi, H
   Goto, M
   Tao, H
   Yamada, H
   Matsuura, S
   Tajima, M
   Matsuda, T
   Yamane, A
   Funai, K
   Tanahashi, M
   Niwa, H
   Ogawa, H
   Sugimura, H
AF Shinmura, Kazuya
   Igarashi, Hisaki
   Goto, Masanori
   Tao, Hong
   Yamada, Hidetaka
   Matsuura, Shun
   Tajima, Mari
   Matsuda, Tomonari
   Yamane, Arito
   Funai, Kazuhito
   Tanahashi, Masayuki
   Niwa, Hiroshi
   Ogawa, Hiroshi
   Sugimura, Haruhiko
TI Aberrant Expression and Mutation-Inducing Activity of AID in Human Lung
   Cancer
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID INDUCED CYTIDINE DEAMINASE; CENTROSOME AMPLIFICATION; CHROMOSOMAL
   INSTABILITY; TUMOR-DEVELOPMENT; DIOL EPOXIDE; C-MYC; CELLS; GENE;
   HYPERMUTATION; P53
AB Activation-induced cytidine deaminase (AID) is expressed in B lymphocytes and triggers antibody diversification. Recent reports have indicated that the constitutive expression of AID in mice causes not only lymphomas, but also cancers of some organs including the lung, prompting us to investigate the expression and effect of AID on human lung cancer.
   We examined AID mRNA expression in 17 lung cancer cell lines and 51 primary lung cancers using a quantitative RT-PCR analysis. Next, we established H1299 lung cancer cells stably overexpressing AID and performed a supF forward mutation assay. We then examined AID protein expression and p53 mutation in 129 primary lung cancers by an immunohistochemical analysis and PCR-SSCP and sequencing analyses, respectively.
   Aberrant mRNA expression of AID was detected in 29% (5 of 17) of the lung cancer cell lines and 31% (16 of 51) of the primary lung cancers. AID-overexpressing H1299 clones showed a 5.0- to 6.1-fold higher mutation frequency than an empty vector-transfected H1299 clone, and about half of the AID-induced mutations were base substitutions, indicating that AID induces gene mutations in lung cancer cells. Furthermore, an association was found between the AID protein expression level and the p53 mutation status in an analysis of 129 primary lung cancers. A further expression analysis revealed that a portion of AID is localized at the centrosomes.
   Our current findings suggest that the aberrant expression of AID may be involved in a subset of human lung cancers as a result of its mutation-inducing activity.
C1 [Shinmura, Kazuya; Igarashi, Hisaki; Goto, Masanori; Tao, Hong; Yamada, Hidetaka; Matsuura, Shun; Tajima, Mari; Sugimura, Haruhiko] Hamamatsu Univ Sch Med, Dept Pathol 1, Hamamatsu, Shizuoka 4313192, Japan.
   [Matsuda, Tomonari] Kyoto Univ, Res Ctr Environm Qual Management, Otsu, Shiga, Japan.
   [Yamane, Arito] NIAMSD, NIH, Bethesda, MD 20892 USA.
   [Funai, Kazuhito] Hamamatsu Univ Sch Med, Dept Surg 1, Hamamatsu, Shizuoka 4313192, Japan.
   [Tanahashi, Masayuki; Niwa, Hiroshi] Seirei Mikatahara Gen Hosp, Div Thorac Surg, Resp Dis Ctr, Hamamatsu, Shizuoka, Japan.
   [Ogawa, Hiroshi] Seirei Mikatahara Gen Hosp, Div Pathol, Hamamatsu, Shizuoka, Japan.
RP Shinmura, K (reprint author), Hamamatsu Univ Sch Med, Dept Pathol 1, Hamamatsu, Shizuoka 4313192, Japan.
EM kzshinmu@hama-med.ac.jp
RI Shinmura, Kazuya /K-8940-2012; Yamane, Arito/A-2959-2013
OI Shinmura, Kazuya /0000-0003-4963-746X; 
FU MHLW [21-1]; JSPS [22590356]; MEXT [20014007, 221S0001]; Smoking
   Research Foundation
FX We are grateful to Dr. D.C. Gruenert (California Pacific Medical Center
   Research Institute, USA), Dr. T. Kaneko (Yokohama City University,
   School of Medicine, Japan), Dr. T. Niki (Jichi Medical University,
   Japan), and Dr. Y. Dobashi (Omiya Medical Center, Japan) for providing
   us with the cell lines. We acknowledge Ms. K. Nagura, Mr. K. Mizuno, and
   Ms. N. Sakamoto (Hamamatsu University School of Medicine) for their
   technical assistance. This work was supported by grants from the MHLW
   (21-1), the JSPS (22590356), the MEXT (20014007 and 221S0001), and the
   Smoking Research Foundation.
NR 35
TC 19
Z9 20
U1 0
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUL
PY 2011
VL 18
IS 7
BP 2084
EP 2092
DI 10.1245/s10434-011-1568-8
PG 9
WC Oncology; Surgery
SC Oncology; Surgery
GA 777VA
UT WOS:000291652000039
PM 21290192
ER

PT J
AU Lu, WX
   Salzwedel, K
   Wang, D
   Chakravarty, S
   Freed, EO
   Wild, CT
   Li, F
AF Lu, Wuxun
   Salzwedel, Karl
   Wang, Dan
   Chakravarty, Suvobrata
   Freed, Eric O.
   Wild, Carl T.
   Li, Feng
TI A Single Polymorphism in HIV-1 Subtype C SP1 Is Sufficient To Confer
   Natural Resistance to the Maturation Inhibitor Bevirimat
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; GAG SPACER PEPTIDE-1; HEALTHY-VOLUNTEERS;
   MOLECULAR CLONE; PA-457; SAFETY; PHARMACOKINETICS; INFECTION; BOUNDARY;
   STEP
AB 3-O-(3',3'-Dimethylsuccinyl) betulinic acid (DSB), also known as PA-457, bevirimat (BVM), or MPC-4326, is a novel HIV-1 maturation inhibitor. Unlike protease inhibitors, BVM blocks the cleavage of the Gag capsid precursor (CA-SP1) to mature capsid (CA) protein, resulting in the release of immature, noninfectious viral particles. Despite the novel mechanism of action and initial progress made in small-scale clinical trials, further development of bevirimat has encountered unexpected challenges, because patients whose viruses contain genetic polymorphisms in the Gag SP1 (positions 6 to 8) protein do not generally respond well to BVM treatment. To better define the role of amino acid residues in the HIV-1 Gag SP1 protein that are involved in natural polymorphisms to confer resistance to the HIV-1 maturation inhibitor BVM, a series of Gag SP1 chimeras involving BVM-sensitive (subtype B) and BVM-resistant (subtype C) viruses was generated and characterized for sensitivity to BVM. We show that SP1 residue 7 of the Gag protein is a primary determinant of SP1 polymorphism-associated drug resistance to BVM.
C1 [Lu, Wuxun; Wang, Dan; Li, Feng] S Dakota State Univ, Dept Biol & Microbiol, Brookings, SD 57007 USA.
   [Lu, Wuxun; Wang, Dan; Li, Feng] S Dakota State Univ, Dept Vet & Biomed Sci, Brookings, SD 57007 USA.
   [Salzwedel, Karl; Wild, Carl T.] Panacos Pharmaceut, Gaithersburg, MD 20877 USA.
   [Chakravarty, Suvobrata] S Dakota State Univ, Dept Chem & Biochem, Brookings, SD 57007 USA.
   [Freed, Eric O.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Li, F (reprint author), S Dakota State Univ, Dept Vet Sci, Brookings, SD 57007 USA.
EM feng.li@sdstate.edu
FU SDSU AES [3AH203]; Public Health Service [AI071788, AI076125]
FX This research was supported by the SDSU AES Fund (grant 3AH203 to F. L.)
   and by Public Health Service grants (AI071788 and AI076125) to F.L.
NR 21
TC 18
Z9 18
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JUL
PY 2011
VL 55
IS 7
BP 3324
EP 3329
DI 10.1128/AAC.01435-10
PG 6
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 778FK
UT WOS:000291687900034
PM 21502630
ER

PT J
AU Yannakopoulou, K
   Jicsinszky, L
   Aggelidou, C
   Mourtzis, N
   Robinson, TM
   Yohannes, A
   Nestorovich, EM
   Bezrukov, SM
   Karginov, VA
AF Yannakopoulou, Konstantina
   Jicsinszky, Laszlo
   Aggelidou, Crysie
   Mourtzis, Nikolaos
   Robinson, Tanisha M.
   Yohannes, Adiamseged
   Nestorovich, Ekaterina M.
   Bezrukov, Sergey M.
   Karginov, Vladimir A.
TI Symmetry Requirements for Effective Blocking of Pore-Forming Toxins:
   Comparative Study with alpha-, beta-, and gamma-Cyclodextrin Derivatives
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID ANTHRAX LETHAL TOXIN; PROTECTIVE ANTIGEN; INHIBITION
AB We compared the abilities of structurally related cationic cyclodextrins to inhibit Bacillus anthracis lethal toxin and Staphylococcus aureus alpha-hemolysin. We found that both beta- and gamma-cyclodextrin derivatives effectively inhibited anthrax toxin action by blocking the transmembrane oligomeric pores formed by the protective antigen (PA) subunit of the toxin, whereas alpha-cyclodextrins were ineffective. In contrast, alpha-hemolysin was selectively blocked only by beta-cyclodextrin derivatives, demonstrating that both symmetry and size of the inhibitor and the pore are important.
C1 [Robinson, Tanisha M.; Yohannes, Adiamseged; Karginov, Vladimir A.] Innovat Biolog Inc, Herndon, VA 20171 USA.
   [Yannakopoulou, Konstantina; Aggelidou, Crysie; Mourtzis, Nikolaos] Natl Ctr Sci Res Demokritos, Inst Phys Chem, Athens, Greece.
   [Jicsinszky, Laszlo] CYCLOLAB R&D Labs Ltd, H-1097 Budapest, Hungary.
   [Nestorovich, Ekaterina M.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
   [Nestorovich, Ekaterina M.] Catholic Univ Amer, Washington, DC 20064 USA.
RP Karginov, VA (reprint author), Innovat Biolog Inc, 13455 Sunrise Valley Dr,Suite 200, Herndon, VA 20171 USA.
EM vak@innovbio.com
RI Yannakopoulou, Konstantina/F-6673-2012; Jicsinszky, Laszlo/C-7805-2012
FU NIH [2R44AI052894-02]; Eunice Kennedy Shriver National Institute of
   Child Health and Human Development, National Institutes of Health;
   National Institute of Allergy and Infectious Diseases (NIAID); ARISTEIA
   ("Excellence in Research Institutes" of the Greek GSRT)
FX This research was supported by grant 2R44AI052894-02 from the NIH; by
   the Intramural Research Program of the Eunice Kennedy Shriver National
   Institute of Child Health and Human Development, National Institutes of
   Health, and the National Institute of Allergy and Infectious Diseases
   (NIAID) intramural biodefense research grant for an institute other than
   NIAID; and by the program ARISTEIA ("Excellence in Research Institutes"
   of the Greek GSRT).
NR 12
TC 12
Z9 12
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JUL
PY 2011
VL 55
IS 7
BP 3594
EP 3597
DI 10.1128/AAC.01764-10
PG 4
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 778FK
UT WOS:000291687900074
PM 21555769
ER

PT J
AU Kim, KI
   Simon, R
AF Kim, Kyung In
   Simon, Richard
TI Probabilistic classifiers with high-dimensional data
SO BIOSTATISTICS
LA English
DT Article
DE Gene expression analysis; High-dimensional data; Microarray;
   Probabilistic classification
ID GENE-EXPRESSION DATA; CLASSIFICATION
AB For medical classification problems, it is often desirable to have a probability associated with each class. Probabilistic classifiers have received relatively little attention for small n large p classification problems despite of their importance in medical decision making. In this paper, we introduce 2 criteria for assessment of probabilistic classifiers: well-calibratedness and refinement and develop corresponding evaluation measures. We evaluated several published high-dimensional probabilistic classifiers and developed 2 extensions of the Bayesian compound covariate classifier. Based on simulation studies and analysis of gene expression microarray data, we found that proper probabilistic classification is more difficult than deterministic classification. It is important to ensure that a probabilistic classifier is well calibrated or at least not "anticonservative" using the methods developed here. We provide this evaluation for several probabilistic classifiers and also evaluate their refinement as a function of sample size under weak and strong signal conditions. We also present a cross-validation method for evaluating the calibration and refinement of any probabilistic classifier on any data set.
C1 [Kim, Kyung In; Simon, Richard] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
RP Simon, R (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike,MSC 7434, Bethesda, MD 20892 USA.
EM rsimon@mail.nih.gov
RI Kim, Kyung In/L-2263-2016
OI Kim, Kyung In/0000-0002-4822-8333
NR 17
TC 9
Z9 9
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
J9 BIOSTATISTICS
JI Biostatistics
PD JUL
PY 2011
VL 12
IS 3
BP 399
EP 412
DI 10.1093/biostatistics/kxq069
PG 14
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 779BK
UT WOS:000291752900001
PM 21087946
ER

PT J
AU Huang, CY
   Luo, XH
   Follmann, DA
AF Huang, Chiung-Yu
   Luo, Xianghua
   Follmann, Dean A.
TI A model checking method for the proportional hazards model with
   recurrent gap time data
SO BIOSTATISTICS
LA English
DT Article
DE Correlated failure times; Induced-dependent censoring; Kaplan-Meier
   estimator; Renewal processes
ID MARTINGALE-BASED RESIDUALS; NONPARAMETRIC-ESTIMATION; MARGINAL
   REGRESSION; SURVIVAL FUNCTION; EVENT DATA; COX MODEL; RISK
AB Recurrent events are the natural outcome in many medical and epidemiology studies. To assess covariate effects on the gaps between consecutive recurrent events, the Cox proportional hazards model is frequently employed in data analysis. The validity of statistical inference, however, depends on the appropriateness of the Cox model. In this paper, we propose a class of graphical techniques and formal tests for checking the Cox model with recurrent gap time data. The building block of our model checking method is an averaged martingale-like process, based on which a class of multiparameter stochastic processes is proposed. This maneuver is very general and can be used to assess different aspects of model fit. Numerical simulations are conducted to examine finite-sample performance, and the proposed model checking techniques are illustrated with data from the Danish Psychiatric Central Register.
C1 [Huang, Chiung-Yu; Follmann, Dean A.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
   [Luo, Xianghua] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
RP Huang, CY (reprint author), NIAID, Biostat Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM huangchi@niaid.nih.gov
NR 20
TC 4
Z9 4
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
J9 BIOSTATISTICS
JI Biostatistics
PD JUL
PY 2011
VL 12
IS 3
BP 535
EP 547
DI 10.1093/biostatistics/kxq071
PG 13
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 779BK
UT WOS:000291752900010
PM 21138876
ER

PT J
AU Yu, K
   Liang, FM
   Ciampa, J
   Chatterjee, N
AF Yu, Kai
   Liang, Faming
   Ciampa, Julia
   Chatterjee, Nilanjan
TI Efficient p-value evaluation for resampling-based tests
SO BIOSTATISTICS
LA English
DT Article
DE Bootstrap procedures; Genetic association studies; p-value;
   Resampling-based tests; Stochastic approximation Markov chain Monte
   Carlo
ID GENOME-WIDE ASSOCIATION; CORRELATED TESTS; LINKAGE ANALYSIS;
   PROSTATE-CANCER; APPROXIMATION
AB The resampling-based test, which often relies on permutation or bootstrap procedures, has been widely used for statistical hypothesis testing when the asymptotic distribution of the test statistic is unavailable or unreliable. It requires repeated calculations of the test statistic on a large number of simulated data sets for its significance level assessment, and thus it could become very computationally intensive. Here, we propose an efficient p-value evaluation procedure by adapting the stochastic approximation Markov chain Monte Carlo algorithm. The new procedure can be used easily for estimating the p-value for any resampling-based test. We show through numeric simulations that the proposed procedure can be 100-500 000 times as efficient (in term of computing time) as the standard resampling-based procedure when evaluating a test statistic with a small p-value (e.g. less than 10 (- 6)). With its computational burden reduced by this proposed procedure, the versatile resampling-based test would become computationally feasible for a much wider range of applications. We demonstrate the application of the new method by applying it to a large-scale genetic association study of prostate cancer.
C1 [Yu, Kai; Ciampa, Julia; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
   [Liang, Faming] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
RP Yu, K (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
EM yuka@mail.nih.gov
FU National Institutes of Health; National Cancer Institute; National
   Science Foundation [DMS-0607755, CMMI-0926803]; King Abdullah University
   of Science and Technology [KUS-C1-016- 04]
FX Intramural Program of the National Institutes of Health and the National
   Cancer Institute to K.Y. and F.L.; The National Science Foundation
   (DMS-0607755, CMMI-0926803); and the award (KUS-C1-016- 04) made by the
   King Abdullah University of Science and Technology.
NR 19
TC 7
Z9 7
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1465-4644
J9 BIOSTATISTICS
JI Biostatistics
PD JUL
PY 2011
VL 12
IS 3
BP 582
EP 593
DI 10.1093/biostatistics/kxq078
PG 12
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 779BK
UT WOS:000291752900013
PM 21209154
ER

PT J
AU McPherson, CA
   Aoyama, M
   Harry, GJ
AF McPherson, C. A.
   Aoyama, M.
   Harry, G. J.
TI Interleukin (IL)-1 and IL-6 regulation of neural progenitor cell
   proliferation with hippocampal injury: Differential regulatory pathways
   in the subgranular zone (SGZ) of the adolescent and mature mouse brain
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Neurogenesis; Neurospheres; Hippocampus; Apoptosis; Neuroinflammation;
   SGZ; Interleukin-1; Interleukin-6; gp130
ID NECROSIS-FACTOR-ALPHA; CENTRAL-NERVOUS-SYSTEM; DENTATE GYRUS; ADULT
   NEUROGENESIS; MESSENGER-RNA; AGED MICE; RECEPTOR ANTAGONIST; RAT-BRAIN;
   STEM-CELL; IN-VIVO
AB Current data suggests an association between elevations in interleukin 1 (IL-1)alpha, IL-1 beta, and IL-6 and the proliferation of neural progenitor cells (NPCs) following brain injury. A limited amount of work implicates changes in these pro-inflammatory responses with diminished NPC proliferation observed as a function of aging. In the current study, adolescent (21 day-old) and 1 year-old CD-1 male mice were injected with trimethyltin (TMT, 2.3 mg/kg, i.p.) to produce acute apoptosis of hippocampal dentate granule cells. In this model, fewer 5-bromo-2'-deoxyuridine (BrdU)(+) NPC were observed in both naive and injured adult hippocampus as compared to the corresponding number seen in adolescent mice. At 48 h post-TMT, a similar level of neuronal death was observed across ages, yet activated ameboid microglia were observed in the adolescent and hypertrophic process-bearing microglia in the adult. IL-1 alpha mRNA levels were elevated in the adolescent hippocampus; IL-6 mRNA levels were elevated in the adult. In subgranular zone (SGZ) isolated by laser-capture microdissection, IL-1 beta was detected but not elevated by TMT, IL-1a was elevated at both ages, while IL-6 was elevated only in the adult. Naive NPCs isolated from the hippocampus expressed transcripts for IL-1R1, IL-6R alpha, and gp130 with significantly higher levels of IL-6R alpha mRNA in the adult. In vitro, IL-1 alpha (150 pg/ml) stimulated proliferation of adolescent NPCs; IL-6 (10 ng/ml) inhibited proliferation of adolescent and adult NPCs. Microarray analysis of SGZ post-TMT indicated a prominence of IL-1a/IL-1R1 signaling in the adolescent and IL-6/gp130 signaling in the adult. Published by Elsevier Inc.
C1 [McPherson, C. A.; Aoyama, M.; Harry, G. J.] Natl Inst Environm Hlth Sci, Neurotoxicol Grp, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
   [McPherson, C. A.] Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC USA.
   [Aoyama, M.] Nagoya City Univ, Dept Mol Neurobiol, Nagoya, Aichi, Japan.
RP Harry, GJ (reprint author), Natl Inst Environm Hlth Sci, Neurotoxicol Grp, Lab Toxicol & Pharmacol, NIH, POB 12233,MD C1-04, Res Triangle Pk, NC 27709 USA.
EM harry@niehs.nih.gov
FU division of intramural research of the National Institute of
   Environmental Health Science, National Institutes of Health, Department
   of Health and Human Services [ES101623, ES021164]
FX The authors thank Dr. Julia Gohlke and Ms. Jennifer Collins for their
   technical expertise in microarray analysis, Ms. Tiwanda Mishande for
   immunohistochemical expertise and Drs. Peter Mouton and Susan McGuire
   for their review of the final manuscript. This study was supported by
   the division of intramural research of the National Institute of
   Environmental Health Science, National Institutes of Health, Department
   of Health and Human Services Z# ES101623 and ES021164.
NR 77
TC 25
Z9 28
U1 1
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD JUL
PY 2011
VL 25
IS 5
SI SI
BP 850
EP 862
DI 10.1016/j.bbi.2010.09.003
PG 13
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 780EF
UT WOS:000291836600006
PM 20833246
ER

PT J
AU Butts, CL
   Jones, YL
   Lim, JK
   Salter, CE
   Belyavskaya, E
   Sternberg, EM
AF Butts, Cherie L.
   Jones, Yava L.
   Lim, Jean K.
   Salter, Caroline E.
   Belyavskaya, Elena
   Sternberg, Esther M.
TI Tissue expression of steroid hormone receptors is associated with
   differential immune responsiveness
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Steroid hormone receptors; T lymphocytes; Neuroimmunology; Viral
   infection
ID DENDRITIC CELL-FUNCTION; PITUITARY-ADRENAL AXIS; NILE-VIRUS-INFECTION;
   GLUCOCORTICOID-RECEPTOR; INCREASES SUSCEPTIBILITY; LETHAL TOXIN;
   PROGESTERONE; MICE; DEXAMETHASONE; AUTOIMMUNE
AB Glucocorticoids have been used as treatments against a number of diseases, especially autoimmune/inflammatory conditions in which the immune system is overactive. These treatments have varying degrees of responsiveness among individuals and in different tissues (including brain); therefore, it is important to determine what could account for these differences. In this study, we evaluated expression of stress hormone receptors in immune cells from lymphoid and non-lymphoid tissues (including brain) as a possible explanation. We analyzed leukocytes (CD45(+)) in kidney, liver, spleen, and thymus tissues from healthy mice for expression of the receptor for stress hormone (glucocorticoid-GR) as well as other steroid hormones (androgen-AR, progesterone-PR) and found that all tissues expressed these steroid hormone receptors but with varying patterns. To determine whether tissue-specific differences were related to immune cell composition, we examined steroid hormone receptor expression in T lymphocytes from each of these tissues and found similar patterns of expression in these cells regardless of tissue source. Because glucocorticoids can also impact brain function, we further examined expression of the stress hormone receptor in brain tissue and found GR expressed in immune cells at this site. In order to investigate the potential impact in an area of neuropathology, we utilized a mouse model of West Nile Virus (WNV). We observed pathological changes in brains of WNV-infected animals and T lymphocytes in the areas of inflammation; however, these cells did not express GR. These data indicate that tissue-specific differences in steroid hormone receptor expression by immune cells could determine responsiveness to steroid hormone treatment. Published by Elsevier Inc.
C1 [Sternberg, Esther M.] NIMH, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, NIH, Bethesda, MD 20892 USA.
   [Jones, Yava L.; Salter, Caroline E.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
   [Lim, Jean K.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, NIH, 5625 Fishers Lane,Room 4N15, Bethesda, MD 20892 USA.
EM cherie.butts@fda.hhs.gov; sternbee@mail.nih.gov
FU National Institute of Mental Health (NIMH)/NIH; National Institute of
   Allergy & Infectious Diseases (NIAID)/NIH
FX This work was supported by the Intramural Research Program of the
   National Institute of Mental Health (NIMH)/NIH and by a biodefense grant
   from the National Institute of Allergy & Infectious Diseases (NIAID)/NIH
   Intramural Research Program. We also thank Dr. Cecilia Tami for careful
   manuscript review.
NR 45
TC 5
Z9 6
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD JUL
PY 2011
VL 25
IS 5
SI SI
BP 1000
EP 1007
DI 10.1016/j.bbi.2010.11.003
PG 8
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 780EF
UT WOS:000291836600021
PM 21074604
ER

PT J
AU Jacobs, MA
   Ouwerkerk, R
   Wolff, AC
   Gabrielson, E
   Warzecha, H
   Jeter, S
   Bluemke, DA
   Wahl, R
   Stearns, V
AF Jacobs, Michael A.
   Ouwerkerk, Ronald
   Wolff, Antonio C.
   Gabrielson, Edward
   Warzecha, Hind
   Jeter, Stacie
   Bluemke, David A.
   Wahl, Richard
   Stearns, Vered
TI Monitoring of neoadjuvant chemotherapy using multiparametric, Na-23
   sodium MR, and multimodality (PET/CT/MRI) imaging in locally advanced
   breast cancer
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast; Magnetic resonance imaging; Sodium Na-23 MRI; PET; PET/CT;
   Response; Cancer
ID PATHOLOGICAL RESPONSE; FDG-PET; PREDICTIVE-VALUE; SOLID TUMORS;
   SPECTROSCOPY; RECIST; MANAGEMENT; CRITERIA; DISEASE; LESIONS
AB We prospectively investigated using advanced magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) to identify radiological biomarkers for treatment response in patients receiving preoperative systemic therapy (PST) for locally advanced breast cancer. Patients with a stage II or III breast cancer receiving PST were selected and underwent positron emission tomography (PET), magnetic resonance imaging (MRI), and breast biopsies at baseline and after the first cycle of PST (days 7-8) during the full course of treatment. PET/CT was acquired after injection of 2-deoxy-2-[18F]-fluoro-d-glucose ((18)FDG, 0.22 mCi/kg) and quantified with standardized uptake value assessment (SUV). Diagnostic breast MRI and sodium (Na-23) was acquired at 1.5 T. Total tissue sodium concentration (TSC), response criteria in solid tumors (RECIST), and volumes were quantified. Treatment response was determined by pathological assessment at surgery. Immunohistochemistry values of the proliferative index (Ki-67) were performed on biopsy specimens. Six of nineteen eligible women (43 +/- A 11 years) who received PST underwent radiological imaging of (18)FDG-PET/CT and MRI for at least two cycles of treatment. Five patients had a pathological partial response (pPR) and one had pathological non-response (pNR). TSC decreased 21% in responders with increases in the non-responder (P = 0.03). Greater reduction in SUV was observed in responders (38%) compared to the non-responder (22%; P = 0.03). MRI volumes decreased after cycle 1 by 42% (responders) and 35% (non-responder; P = 0.11). Proliferation index Ki-67 declined in responders in the first cycle (median = 47%, range = 29-20%), but increased (4%) in the non-responder. Significant decreases in TSC, SUV, and Ki-67 were observed in responders with increases in TSC and Ki-67 in non-responders. Our results demonstrate the feasibility of using multi-modality proton, Na-23 MRI, and PET/CT metrics as radiological biomarkers for monitoring response to PST in patients with operable breast cancer.
C1 [Jacobs, Michael A.] Johns Hopkins Univ, Sch Med, Dept Radiol & Oncol, Baltimore, MD 21205 USA.
   [Jacobs, Michael A.; Ouwerkerk, Ronald; Bluemke, David A.; Wahl, Richard] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA.
   [Jacobs, Michael A.; Wolff, Antonio C.; Gabrielson, Edward; Warzecha, Hind; Jeter, Stacie; Wahl, Richard; Stearns, Vered] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
   [Ouwerkerk, Ronald] NIDDK, Bethesda, MD 20892 USA.
   [Gabrielson, Edward; Warzecha, Hind] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
   [Wolff, Antonio C.; Jeter, Stacie; Stearns, Vered] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
   [Bluemke, David A.] Natl Inst Hlth Clin Ctr, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA.
RP Jacobs, MA (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol & Oncol, Traylor Blg,Rm 217,712 Rutland Ave, Baltimore, MD 21205 USA.
EM mikej@mri.jhu.edu
RI Jacobs, Michael/G-2901-2010; 
OI Wolff, Antonio/0000-0003-3734-1063
FU National Institute of Health [R01CA100184, P50CA103175]; Breast
   Specialized Program of Research Excellence [P50CA88843, 5P30CA006973,
   U01CA070095, U01CA140204, Avon:01-2009-031]; Damon Runyon Cancer
   Research Foundation [CI-3]
FX We thank all the patients for participating in these studies. We are
   grateful for the help of Mary McAllister, MA., Lucie Bower, Dr. Donald
   Peck, and Dr. Hamid Soltanian-Zadeh, Henry Ford Hospital, Detroit, MI
   for the Eigentool image analysis software used for image processing.
   Part of this work was funded in part by the National Institute of Health
   Grants: R01CA100184, P50CA103175, Breast Specialized Program of Research
   Excellence P50CA88843, 5P30CA006973, U01CA070095, U01CA140204, Avon:
   01-2009-031, and Damon Runyon-Lilly Clinical Investigator Award CI-3
   from the Damon Runyon Cancer Research Foundation.
NR 37
TC 30
Z9 32
U1 2
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUL
PY 2011
VL 128
IS 1
BP 119
EP 126
DI 10.1007/s10549-011-1442-1
PG 8
WC Oncology
SC Oncology
GA 777WQ
UT WOS:000291656200013
PM 21455671
ER

PT J
AU Naz, S
   Ali, S
   Riazuddin, SA
   Farooq, T
   Butt, NH
   Zafar, AU
   Khan, SN
   Husnain, T
   MacDonald, IM
   Sieving, PA
   Hejtmancik, JF
   Riazuddin, S
AF Naz, Shagufta
   Ali, Shahbaz
   Riazuddin, S. Amer
   Farooq, Tahir
   Butt, Nadeem H.
   Zafar, Ahmad U.
   Khan, Shaheen N.
   Husnain, Tayyab
   MacDonald, Ian M.
   Sieving, Paul A.
   Hejtmancik, J. Fielding
   Riazuddin, Sheikh
TI Mutations in RLBP1 associated with fundus albipunctatus in
   consanguineous Pakistani families
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID RETINALDEHYDE-BINDING PROTEIN; RETINITIS PUNCTATA ALBESCENS; RECESSIVE
   CONGENITAL CATARACT; RETINOL-BINDING; RDH5 GENE; PIGMENTOSA; PATIENT
AB Objective To identify disease-causing mutations in two consanguineous Pakistani families with fundus albipunctatus.
   Methods Affected individuals in both families underwent a thorough clinical examination including funduscopy and electroretinography. Blood samples were collected from all participating members and genomic DNA was extracted. Exclusion analysis was completed with microsatellite short tandem repeat markers that span all reported loci for fundus albipunctatus. Two-point logarithm of odds (LOD) scores were calculated, and coding exons and exon-intron boundaries of RLBP1 were sequenced bi-directionally.
   Results The ophthalmic examination of affected patients in both families was consistent with fundus albipunctatus. The alleles of markers on chromosome 15q flanking RLBP1 segregated with the disease phenotype in both families and linkage was further confirmed by two-point LOD scores. Bi-directional sequencing of RLBP1 identified a nonsense mutation (R156X) and a missense mutation (G116R) that segregated with the disease phenotype in their respective families.
   Conclusions These results strongly suggest that mutations in RLBP1 are responsible for fundus albipunctatus in the affected individuals of these consanguineous Pakistani families.
C1 [Naz, Shagufta; Ali, Shahbaz; Riazuddin, S. Amer; Zafar, Ahmad U.; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan.
   [Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
   [Farooq, Tahir] Layton Rahmatulla Benevolent Trust Hosp, Lahore, Pakistan.
   [Butt, Nadeem H.; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan.
   [MacDonald, Ian M.] Univ Alberta, Dept Ophthalmol, Edmonton, AB, Canada.
   [MacDonald, Ian M.; Sieving, Paul A.; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd, Lahore 53700, Pakistan.
EM riaz@aimrc.org
RI Nasim Khan, Shaheen/F-2135-2015; Husnain, Tayyab/G-3805-2015; 
OI MacDonald, Ian/0000-0001-7472-8385
FU Higher Education Commission, Islamabad, Pakistan; Ministry of Science
   and Technology, Islamabad, Pakistan
FX This work was supported in part by Higher Education Commission,
   Islamabad, Pakistan and Ministry of Science and Technology, Islamabad,
   Pakistan.
NR 22
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Z9 14
U1 0
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD JUL
PY 2011
VL 95
IS 7
BP 1019
EP 1024
DI 10.1136/bjo.2010.189076
PG 6
WC Ophthalmology
SC Ophthalmology
GA 778PX
UT WOS:000291717700026
PM 21447491
ER

PT J
AU Shikany, JM
   Flood, AP
   Kitahara, CM
   Hsing, AW
   Meyer, TE
   Willcox, BJ
   Redden, DT
   Ziegler, RG
AF Shikany, James M.
   Flood, Andrew P.
   Kitahara, Cari M.
   Hsing, Ann W.
   Meyer, Tamra E.
   Willcox, Bradley J.
   Redden, David T.
   Ziegler, Regina G.
TI Dietary carbohydrate, glycemic index, glycemic load, and risk of
   prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer
   Screening Trial (PLCO) cohort
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Prostatic neoplasms; Dietary carbohydrates; Glycemic index
ID INSULIN; GROWTH; VALUES; QUESTIONNAIRE; METAANALYSIS
AB To evaluate the associations between dietary carbohydrate, glycemic index (GI), glycemic load (GL), and incident prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort.
   Between September 1993 and September 2000, 38,343 men were randomized to the screening arm of the trial at one of 10 PLCO centers. A food frequency questionnaire administered at baseline assessed usual dietary intake over the preceding 12 months. Prostate cancer was ascertained by medical follow-up of suspicious screening results and annual mailed questionnaires and confirmed with medical records. Cox proportional hazards regression was used to model the associations of carbohydrate, GI, and GL with prostate cancer risk.
   During follow-up (median = 9.2 years), 2,436 incident prostate cancers were identified among 30,482 eligible participants. Overall, there were no associations of baseline carbohydrate, GI, or GL with incident prostate cancer in minimally or fully adjusted models. There were no associations when the 228 advanced and 2,208 non-advanced cancers were analyzed separately.
   Dietary carbohydrate, GI, and GL were not associated with incident prostate cancer in PLCO. The narrow range of GI in this cohort may have limited our ability to detect associations, an issue that future studies should address.
C1 [Shikany, James M.] Univ Alabama, Div Prevent Med, Sch Med, Birmingham, AL 35294 USA.
   [Flood, Andrew P.] Univ Minnesota, Dept Food Sci & Nutr, Div Epidemiol & Community Hlth, St Paul, MN 55454 USA.
   [Kitahara, Cari M.; Hsing, Ann W.; Meyer, Tamra E.; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
   [Willcox, Bradley J.] Queens Med Ctr, Pacific Hlth Res Inst, Honolulu, HI 96813 USA.
   [Redden, David T.] Univ Alabama, Dept Biostat, Sch Publ Hlth, Birmingham, AL 35294 USA.
RP Shikany, JM (reprint author), Univ Alabama, Div Prevent Med, Sch Med, 1530 3rd Ave S,MT 610, Birmingham, AL 35294 USA.
EM jshikany@dopm.uab.edu
RI Kitahara, Cari/R-8267-2016
FU US National Cancer Institute [N01CN75022]
FX Supported by the US National Cancer Institute (grant no. N01CN75022).
NR 21
TC 14
Z9 14
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUL
PY 2011
VL 22
IS 7
BP 995
EP 1002
DI 10.1007/s10552-011-9772-1
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 778XM
UT WOS:000291742700006
PM 21553078
ER

PT J
AU Kim, S
   Sandler, DP
   Carswell, G
   De Roo, LA
   Parks, CG
   Cawthon, R
   Weinberg, CR
   Taylor, JA
AF Kim, Sangmi
   Sandler, Dale P.
   Carswell, Gleta
   De Roo, Lisa A.
   Parks, Christine G.
   Cawthon, Richard
   Weinberg, Clarice R.
   Taylor, Jack A.
TI Telomere length in peripheral blood and breast cancer risk in a
   prospective case-cohort analysis: results from the Sister Study
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Breast cancer; Telomere length; Prospective study; Biomarker; qPCR
ID GENOME INSTABILITY; IN-SITU; CELLS; OBESITY; GENES; WOMEN
AB Telomeres are required for maintaining genomic integrity and may play a role in carcinogenesis. Some, but not all, epidemiologic studies have found that short telomeres in leukocytes are associated with an increased risk of breast cancer. To further elucidate this potential association, we examined telomere length in relation to breast cancer risk in prospectively collected blood samples from the Sister Study, a cohort of women aged 35-74 years who have a sister with breast cancer.
   We performed a case-cohort analysis comparing incident breast cancer cases (n = 342) with a subcohort (n = 735), randomly selected from 29,026 participants, enrolled by June 1, 2007. Relative telomere length in peripheral blood cells was estimated using a single-tube monochrome multiplex quantitative PCR assay.
   No association was observed between telomere length and breast cancer risk. Compared with the longest quartile, hazard ratios (HR) associated with the second, third, and the shortest quartile were 0.91 [95% confidence interval (95% CI): 0.62-1.34], 1.11 (95% CI: 0.77-1.60), and 0.93 (95% CI: 0.64-1.35), respectively. Subgroup analyses by menopausal status, invasiveness, or estrogen receptor status of breast cancer did not reveal evidence of association between telomere length in blood cells and subsequent breast cancer risk.
   This prospective investigation does not support telomere length in blood cells as a biomarker for breast cancer risk.
C1 [Kim, Sangmi; Taylor, Jack A.] NIEHS, Epidemiol Branch, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
   [Cawthon, Richard] Univ Utah, Salt Lake City, UT USA.
   [Weinberg, Clarice R.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Kim, S (reprint author), NIEHS, Epidemiol Branch, Mol Carcinogenesis Lab, POB 12233,MD A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM kims3@niehs.nih.gov
OI taylor, jack/0000-0001-5303-6398; Parks, Christine/0000-0002-5734-3456;
   Sandler, Dale/0000-0002-6776-0018
FU National Institutes of Health, National Institute of Environmental
   Health Sciences [Z01 ES044005, Z01 ES049033]
FX This research was supported by the Intramural Program of the National
   Institutes of Health, National Institute of Environmental Health
   Sciences (Z01 ES044005 and Z01 ES049033). Authors are grateful for
   technical support received from the Molecular Genetics Core Facility at
   NIEHS.
NR 22
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U1 0
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUL
PY 2011
VL 22
IS 7
BP 1061
EP 1066
DI 10.1007/s10552-011-9778-8
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 778XM
UT WOS:000291742700013
PM 21643930
ER

PT J
AU Shamy, JL
   Habeck, C
   Hof, PR
   Amaral, DG
   Fong, SG
   Buonocore, MH
   Stern, Y
   Barnes, CA
   Rapp, PR
AF Shamy, Jul Lea
   Habeck, Christian
   Hof, Patrick R.
   Amaral, David G.
   Fong, Sania G.
   Buonocore, Michael H.
   Stern, Yaakov
   Barnes, Carol A.
   Rapp, Peter R.
TI Volumetric Correlates of Spatiotemporal Working and Recognition Memory
   Impairment in Aged Rhesus Monkeys
SO CEREBRAL CORTEX
LA English
DT Article
DE age-related memory impairment; medial temporal lobe; MRI; prefrontal
   cortex; rhesus monkey
ID VOXEL-BASED MORPHOMETRY; DORSOLATERAL PREFRONTAL CORTEX; HIPPOCAMPAL
   NEURON NUMBERS; EMISSION TOMOGRAPHIC DATA; MYELINATED NERVE-FIBERS;
   HUMAN CEREBRAL-CORTEX; IN-VIVO MRI; MACAQUE MONKEYS; ALZHEIMERS-DISEASE;
   TEMPORAL-LOBE
AB Spatiotemporal and recognition memory are affected by aging in humans and macaque monkeys. To investigate whether these deficits are coupled with atrophy of memory-related brain regions, T(1)-weighted magnetic resonance images were acquired and volumes of the cerebrum, ventricles, prefrontal cortex (PFC), calcarine cortex, hippocampus, and striatum were quantified in young and aged rhesus monkeys. Subjects were tested on a spatiotemporal memory procedure (delayed response [DR]) that requires the integrity of the PFC and a medial temporal lobe-dependent recognition memory task (delayed nonmatching to sample [DNMS]). Region of interest analyses revealed that age inversely correlated with striatal, dorsolateral prefrontal cortex (dlPFC), and anterior cingulate cortex volumes. Hippocampal volume predicted acquisition of the DR task. Striatal volume correlated with DNMS acquisition, whereas total prefrontal gray matter, prefrontal white matter, and dlPFC volumes each predicted DNMS accuracy. A regional covariance analysis revealed that age-related volumetric changes could be captured in a distributed network that was coupled with declining performance across delays on the DNMS task. This volumetric analysis adds to growing evidence that cognitive aging in primates arises from region-specific morphometric alterations distributed across multiple memory-related brain systems, including subdivisions of the PFC.
C1 [Rapp, Peter R.] NIA, NIH, Lab Expt Gerontol, Baltimore, MD 21224 USA.
   [Shamy, Jul Lea; Hof, Patrick R.; Fong, Sania G.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA.
   [Shamy, Jul Lea; Hof, Patrick R.; Fong, Sania G.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA.
   [Habeck, Christian; Stern, Yaakov] Columbia Univ, Taub Inst, Cognit Neurosci Div, New York, NY 10032 USA.
   [Amaral, David G.] Univ Calif Davis, Med Invest Neurodev Disorders MIND Inst, Davis, CA 95817 USA.
   [Buonocore, Michael H.] UC Davis Sch Med, Dept Radiol, Sacramento, CA 95817 USA.
   [Buonocore, Michael H.] UC Davis Sch Med, Imaging Res Ctr, Sacramento, CA 95817 USA.
   [Barnes, Carol A.] Univ Arizona, Evelyn F McKnight Brain Inst, Tucson, AZ 85724 USA.
   [Barnes, Carol A.] Univ Arizona, ARL Div Neural Syst Memory & Aging, Tucson, AZ 85724 USA.
RP Rapp, PR (reprint author), NIA, NIH, Lab Expt Gerontol, 251 Bayview Blvd,Suite 100,Room 09C224, Baltimore, MD 21224 USA.
EM rappp@mail.nih.gov
FU National Institutes of Health [AG 003376, AG10606, AG09973, EB006204,
   NS32892, NS16980, MH58911, MH62448, RR-000169]; McKnight Brain Research
   Foundation; National Institute on Aging
FX National Institutes of Health (AG 003376 to C. A. B., AG10606 AG09973 to
   P. R. R., EB006204 to C. H., NS32892 and NS16980 to D. G. A., MH58911 to
   P. R. H., MH62448, RR-000169 to the California National Primate Research
   Center), the McKnight Brain Research Foundation (to C. A. B); the
   Intramural Research Program of the National Institute on Aging (to P. R.
   R.).
NR 99
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U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
J9 CEREB CORTEX
JI Cereb. Cortex
PD JUL
PY 2011
VL 21
IS 7
BP 1559
EP 1573
DI 10.1093/cercor/bhq210
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA 779AL
UT WOS:000291750400009
PM 21127015
ER

PT J
AU Ren, JQ
   Jin, P
   Sabatino, M
   Balakumaran, A
   Feng, J
   Kuznetsov, SA
   Klein, HG
   Robey, PG
   Stroncek, DF
AF Ren, Jiaqiang
   Jin, Ping
   Sabatino, Marianna
   Balakumaran, Arun
   Feng, Ji
   Kuznetsov, Sergei A.
   Klein, Harvey G.
   Robey, Pamela G.
   Stroncek, David F.
TI Global transcriptome analysis of human bone marrow stromal cells (BMSC)
   reveals proliferative, mobile and interactive cells that produce
   abundant extracellular matrix proteins, some of which may affect BMSC
   potency
SO CYTOTHERAPY
LA English
DT Article
DE bone marrow stromal cells; extracellular proteins; global transcriptome
   analysis; potency
ID MESENCHYMAL STEM-CELLS; TRAUMATIC BRAIN-INJURY; CORD BLOOD; CHONDROGENIC
   DIFFERENTIATION; EXPRESSION PATTERNS; THERAPEUTIC BENEFIT; INTEGRIN
   EXPRESSION; GROWTH; TISSUE; TRANSPLANTATION
AB Background aims. Bone marrow stromal cells (BMSC) are being used for immune modulatory, anti-inflammatory and tissue engineering applications, but the properties responsible for these effects are not completely understood. Human BMSC were characterized to identify factors that might be responsible for their clinical effects and biomarkers for assessing their quality. Methods. Early passage BMSC prepared from marrow aspirates of seven healthy subjects were compared with three human embryonic stem cell (hESC) samples, CD34(+) cells from three healthy subjects and three fibroblast cell lines. The cells were analyzed with oligonucleotide expression microarrays with more than 35 000 probes. Results. BMSC gene expression signatures of BMSC differed from those of hematopoietic stem cells (HSC), hESC and fibroblasts. Genes upregulated in BMSC were involved with cell movement, cell-to-cell signaling and interaction and proliferation. The upregulated genes most probably belonged to pathways for integrin signaling, integrin-linked kinase (ILK) signaling, NF-E2-related factor-2 (NFR2)-mediated oxidative stress response, regulation of actin-based motility by Rho, actin cytoskeletal signaling, caveolar-mediated endocytosis, clathrin-mediated endocytosis and Wingless-type MMTV integration site (Wnt/beta) catenin signaling. Among the most highly upregulated genes were structural extracellular matrix (ECM) proteins (alpha 5 and beta 5 integrin chains, fibronectin and collagen type III alpha 1 and V alpha 1) and functional EMC proteins [ connective tissue growth factor (CTGF), transforming growth factor beta-induced protein (TGFBI) and A disintegrin and metalloproteinase (ADAM12)]. Conclusions. Global analysis of human BMSC suggests that they are mobile, metabolically active, proliferative and interactive cells that make use of integrins and integrin signaling. They produce abundant ECM proteins that may contribute to their clinical immune modulatory and anti-inflammatory effects.
C1 [Ren, Jiaqiang; Jin, Ping; Sabatino, Marianna; Feng, Ji; Klein, Harvey G.; Stroncek, David F.] Natl Inst Dent & Craniofacial Res, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20892 USA.
   [Balakumaran, Arun; Kuznetsov, Sergei A.; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Stroncek, DF (reprint author), Natl Inst Dent & Craniofacial Res, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20892 USA.
EM DStroncek@cc.nih.gov
RI Robey, Pamela/H-1429-2011
OI Robey, Pamela/0000-0002-5316-5576
FU National Institute of Dental and Craniofacial Research, NIH; Department
   of Transfusion Medicine, Clinical Center, NIH
FX This research was supported in part by the Intramural Research Program
   of the National Institute of Dental and Craniofacial Research, NIH, and
   the Department of Transfusion Medicine, Clinical Center, NIH.
NR 48
TC 29
Z9 31
U1 0
U2 11
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-3249
J9 CYTOTHERAPY
JI Cytotherapy
PD JUL
PY 2011
VL 13
IS 6
BP 661
EP 674
DI 10.3109/14653249.2010.548379
PG 14
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
   Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
   & Experimental Medicine
GA 777XJ
UT WOS:000291658200003
PM 21250865
ER

PT J
AU Hurst, JA
   Jenkins, D
   Vasudevan, PC
   Kirchhoff, M
   Skovby, F
   Rieubland, C
   Gallati, S
   Rittinger, O
   Kroisel, PM
   Johnson, D
   Biesecker, LG
   Wilkie, AOM
AF Hurst, Jane A.
   Jenkins, Dagan
   Vasudevan, Pradeep C.
   Kirchhoff, Maria
   Skovby, Flemming
   Rieubland, Claudine
   Gallati, Sabina
   Rittinger, Olaf
   Kroisel, Peter M.
   Johnson, David
   Biesecker, Leslie G.
   Wilkie, Andrew O. M.
TI Metopic and sagittal synostosis in Greig cephalopolysyndactyly syndrome:
   five cases with intragenic mutations or complete deletions of GLI3
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE trigonocephaly; metopic synostosis; sagittal synostosis; Greig
   cephalopolysyndactyly syndrome; GLI3; Carpenter syndrome
ID CRANIOFACIAL ANOMALIES; ACROCALLOSAL SYNDROME; CRANIOSYNOSTOSIS; GENE;
   FAMILIES; 7P13; TRANSLOCATION; LOCALIZATION; PHENOTYPE
AB Greig cephalopolysyndactyly syndrome (GCPS) is a multiple congenital malformation characterised by limb and craniofacial anomalies, caused by heterozygous mutation or deletion of GLI3. We report four boys and a girl who were presented with trigonocephaly due to metopic synostosis, in association with pre- and post-axial polydactyly and cutaneous syndactyly of hands and feet. Two cases had additional sagittal synostosis. None had a family history of similar features. In all five children, the diagnosis of GCPS was confirmed by molecular analysis of GLI3 (two had intragenic mutations and three had complete gene deletions detected on array comparative genomic hybridisation), thus highlighting the importance of trigonocephaly or overt metopic or sagittal synostosis as a distinct presenting feature of GCPS. These observations confirm and extend a recently proposed association of intragenic GLI3 mutations with metopic synostosis; moreover, the three individuals with complete deletion of GLI3 were previously considered to have Carpenter syndrome, highlighting an important source of diagnostic confusion. European Journal of Human Genetics (2011) 19, 757-762; doi:10.1038/ejhg.2011.13; published online 16 February 2011
C1 [Jenkins, Dagan; Wilkie, Andrew O. M.] Univ Oxford, Weatherall Inst Mol Med, Oxford OX3 9DS, England.
   [Hurst, Jane A.; Wilkie, Andrew O. M.] Oxford Radcliffe Hosp NHS Trust, Dept Clin Genet, Oxford, England.
   [Hurst, Jane A.; Johnson, David; Wilkie, Andrew O. M.] Oxford Radcliffe Hosp NHS Trust, Craniofacial Unit, Oxford, England.
   [Vasudevan, Pradeep C.] Univ Hosp Leicester NHS Trust, Dept Clin Genet, Leicester, Leics, England.
   [Kirchhoff, Maria; Skovby, Flemming] Univ Copenhagen Hosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark.
   [Rieubland, Claudine; Gallati, Sabina] Univ Bern, Inselspital, Div Human Genet, CH-3010 Bern, Switzerland.
   [Rittinger, Olaf] Paracelsus Med Univ, Childrens Hosp, Salzburg, Austria.
   [Kroisel, Peter M.] Med Univ Graz, Inst Human Genet, Graz, Austria.
   [Biesecker, Leslie G.] NHGRI, Bethesda, MD 20892 USA.
RP Wilkie, AOM (reprint author), Univ Oxford, Weatherall Inst Mol Med, John Radcliffe Hosp, Oxford OX3 9DS, England.
EM awilkie@hammer.imm.ox.ac.uk
OI Wilkie, Andrew/0000-0002-2972-5481
FU Wellcome Trust [078666]; Medical Research Council [80106]
FX We thank all the families for their participation in this study, Sandra
   Bigi, Bruce Castle, Shincy John, Michael Parker and Oliver Quarrell for
   help with gathering clinical information and Bernard Conrad, Jennifer
   Johnston and Tracy Lester for assistance with molecular analysis. This
   work was supported by grants to AOMW from the Wellcome Trust (078666)
   and the Medical Research Council (80106).
NR 28
TC 10
Z9 10
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JUL
PY 2011
VL 19
IS 7
BP 757
EP 762
DI 10.1038/ejhg.2011.13
PG 6
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 778DA
UT WOS:000291678400009
PM 21326280
ER

PT J
AU Jiang, RF
   Dong, JP
   Joo, J
   Geller, NL
   Zheng, G
AF Jiang, Renfang
   Dong, Jianping
   Joo, Jungnam
   Geller, Nancy L.
   Zheng, Gang
TI Simple strategies for haplotype analysis of the X chromosome with
   application to age-related macular degeneration
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE case-control studies; GWAS; haplotype analysis; sex-linked genes
ID LINKAGE DISEQUILIBRIUM; ASSOCIATION; POPULATION; DISEASE; POLYMORPHISM;
   MARKERS
AB For haplotype analysis of the X chromosome, haplotype-sharing (HS) statistics with sliding windows are defined for males and females separately, which are then combined to a single HS test for the X chromosome. When independent replication samples are not available, the training-testing sets approach is used to validate this procedure and a permutation method is used to obtain its P-value. We applied this method to the X chromosome (with 1804 SNPs) for age-related macular degeneration (AMD). We found a window of five SNPs over a 272 kb region associated with AMD after Bonferroni correction. An examination of the odds ratio and the population attributable risks revealed a disease-preventive haplotype, ATGAC, on these five SNPs. For elderly females without this haplotype, the likelihood of AMD is increased by a factor of 4.75 with a 95% confidence interval (1.43, 15.82). The frequency of ATGAC in HapMap CEU is 0.276. These five SNPs are covered by the gene DIAPH2, which is known to cause premature ovarian failure (POF) in females. Our results indicated that DIAPH2 may be a polygenic pleiotropy for POF and AMD. European Journal of Human Genetics (2011) 19, 801-806; doi:10.1038/ejhg.2011.35; published online 9 March 2011
C1 [Geller, Nancy L.; Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
   [Jiang, Renfang; Dong, Jianping] Michigan Technol Univ, Dept Math Sci, Houghton, MI 49931 USA.
   [Joo, Jungnam] Natl Canc Ctr, Canc Biostat Branch, Geonggi Do, South Korea.
RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,MSC 7913, Bethesda, MD 20892 USA.
EM zhengg@nhlbi.nih.gov
NR 16
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD JUL
PY 2011
VL 19
IS 7
BP 801
EP 806
DI 10.1038/ejhg.2011.35
PG 6
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 778DA
UT WOS:000291678400016
PM 21386871
ER

PT J
AU Kvehaugen, AS
   Dechend, R
   Ramstad, HB
   Troisi, R
   Fugelseth, D
   Staff, AC
AF Kvehaugen, Anne Stine
   Dechend, Ralf
   Ramstad, Heidi Bente
   Troisi, Rebecca
   Fugelseth, Drude
   Staff, Anne Cathrine
TI Endothelial Function and Circulating Biomarkers Are Disturbed in Women
   and Children After Preeclampsia
SO HYPERTENSION
LA English
DT Article
DE preeclampsia; biomarkers; cardiovascular diseases; risk factors;
   endothelium
ID LOW-BIRTH-WEIGHT; CARDIOVASCULAR RISK-FACTORS; PLACENTAL GROWTH-FACTOR;
   FLOW-MEDIATED DILATION; C-REACTIVE PROTEIN; INFLAMMATORY MARKERS;
   INTRAUTERINE GROWTH; DIABETES-MELLITUS; POTENTIAL ROLE; PRETERM BIRTH
AB Preeclampsia is a long-term cardiovascular risk factor for the mother and possibly the offspring. Preeclampsia and cardiovascular diseases share common pathophysiological features, including endothelial dysfunction. We explored whether endothelial function, measured noninvasively, as well as circulating biomarkers reflecting lipid metabolism, angiogenesis, and inflammation, differed in paired mothers and offspring 5 to 8 years after delivery. Twenty-six mother and child pairs after pregnancies complicated by preeclampsia were compared with 17 mother and child pairs after uncomplicated pregnancies. In addition, we assessed whether concentrations of maternal circulating biomarkers at delivery predicted findings 5 to 8 years postpartum. We also included an assessment of early onset preeclampsia and specifically addressed the effects of small for gestational age. Endothelial function was significantly reduced in both mothers and children after preeclampsia when combined with a small-for-gestational-age infant compared with mothers and children after pregnancies without a small-for-gestational-age infant (mothers: P<0.001; children: P<0.05). Postpartum maternal soluble fms-like tyrosine kinase 1 (P=0.05) and high-sensitivity C-reactive protein (P=0.02) were elevated in the preeclampsia group compared with controls. High concentrations of these maternal biomarkers both at delivery and 5 to 8 years postpartum were also more frequent in preeclampsia compared with controls (P<0.05). The novelty of our study is the parallel finding of reduced endothelial function in mother and child pairs 5 to 8 years after small-for-gestational-age preeclamptic pregnancies, accompanied by increased inflammatory and antiangiogenic maternal biomarkers. This finding supports the concept of transgenerational risk of cardiovascular disease after preeclampsia. (Hypertension. 2011;58:63-69.)
C1 [Kvehaugen, Anne Stine; Staff, Anne Cathrine] Oslo Univ Hosp, Dept Obstet & Gynecol, N-0424 Oslo, Norway.
   [Ramstad, Heidi Bente] Oslo Univ Hosp, Dept Pediat, N-0424 Oslo, Norway.
   [Fugelseth, Drude] Oslo Univ Hosp, Dept Neonatal Intens Care, N-0424 Oslo, Norway.
   [Kvehaugen, Anne Stine; Fugelseth, Drude; Staff, Anne Cathrine] Univ Oslo, Fac Med, Oslo, Norway.
   [Dechend, Ralf] Max Delbruck Ctr, Expt & Clin Res Ctr, Berlin, Germany.
   HELIOS Klin, Fac Med Charite, Franz Volhard Clin, Berlin, Germany.
   [Troisi, Rebecca] NCI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Staff, AC (reprint author), Oslo Univ Hosp, Dept Obstet, POB 4950 Nydalen, N-0424 Oslo, Norway.
EM annetine.staff@ulleval.no
FU South-Eastern Norway Regional Health Authorities; Oslo University
   Hospital
FX The CHASE study (Cardiovascular health in mother and offspring after
   pregnancy complicated by preeclampsia or diabetes mellitus) has received
   research funding from the South-Eastern Norway Regional Health
   Authorities. A.C.S. has received funding from Oslo University Hospital.
NR 51
TC 42
Z9 48
U1 2
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0194-911X
EI 1524-4563
J9 HYPERTENSION
JI Hypertension
PD JUL
PY 2011
VL 58
IS 1
BP 63
EP 69
DI 10.1161/HYPERTENSIONAHA.111.172387
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 777WE
UT WOS:000291655000012
PM 21606387
ER

PT J
AU Khong, SML
   Andrews, KL
   Vaisman, BL
   Remaley, AT
   Chin-Dusting, J
AF Khong, S. M. L.
   Andrews, K. L.
   Vaisman, B. L.
   Remaley, A. T.
   Chin-Dusting, J.
TI ENDOTHELIAL OVEREXPRESSION OF ARGINASE II INDUCES ENDOTHELIAL
   DYSFUNCTION AND PROMOTES ATHEROSCLEROSIS
SO HYPERTENSION
LA English
DT Meeting Abstract
CT 32nd Annual Scientific Meeting of the High Blood Pressure Research
   Council of Australia
CY DEC 01-03, 2010
CL Melbourne, AUSTRALIA
SP High Blood Pressure Res Council Australia
C1 [Khong, S. M. L.; Andrews, K. L.; Chin-Dusting, J.] Baker IDI Heart & Diabet Res Inst, Melbourne, Vic, Australia.
   [Khong, S. M. L.] Monash Univ, Dept Med, CECS, Melbourne, Vic 3004, Australia.
   [Vaisman, B. L.; Remaley, A. T.] NHLBI, NIH, Bethesda, 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 0194-911X
J9 HYPERTENSION
JI Hypertension
PD JUL
PY 2011
VL 58
IS 1
MA 5
BP 115
EP 116
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 777WE
UT WOS:000291655000024
ER

PT J
AU Sengupta, M
   Austin, S
AF Sengupta, Manjistha
   Austin, Stuart
TI Prevalence and Significance of Plasmid Maintenance Functions in the
   Virulence Plasmids of Pathogenic Bacteria
SO INFECTION AND IMMUNITY
LA English
DT Review
ID PROGRAMMED CELL-DEATH; COMPLETE DNA-SEQUENCE; RESTRICTION-MODIFICATION
   SYSTEMS; ESCHERICHIA-COLI; P1 PLASMID; PARTITION SYSTEM; MULTIMER
   RESOLUTION; BACILLUS-ANTHRACIS; SHIGELLA-FLEXNERI; YERSINIA-PESTIS
AB Virulence functions of pathogenic bacteria are often encoded on large extrachromosomal plasmids. These plasmids are maintained at low copy number to reduce the metabolic burden on their host. Low-copy-number plasmids risk loss during cell division. This is countered by plasmid-encoded systems that ensure that each cell receives at least one plasmid copy. Plasmid replication and recombination can produce plasmid multimers that hinder plasmid segregation. These are removed by multimer resolution systems. Equitable distribution of the resulting monomers to daughter cells is ensured by plasmid partition systems that actively segregate plasmid copies to daughter cells in a process akin to mitosis in higher organisms. Any plasmid-free cells that still arise due to occasional failures of replication, multimer resolution, or partition are eliminated by plasmid-encoded postsegregational killing systems. Here we argue that all of these three systems are essential for the stable maintenance of large low-copy-number plasmids. Thus, they should be found on all large virulence plasmids. Where available, well-annotated sequences of virulence plasmids confirm this. Indeed, virulence plasmids often appear to contain more than one example conforming to each of the three system classes. Since these systems are essential for virulence, they can be regarded as ubiquitous virulence factors. As such, they should be informative in the search for new antibacterial agents and drug targets.
C1 [Sengupta, Manjistha; Austin, Stuart] NCI, Gene Regulat & Chromosome Biol Lab, CCR, Frederick, MD 21702 USA.
RP Austin, S (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, CCR, Frederick, MD 21702 USA.
EM austinst@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
   NIH, National Cancer Institute, Center for Cancer Research.
NR 74
TC 35
Z9 35
U1 5
U2 22
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 JUL
PY 2011
VL 79
IS 7
BP 2502
EP 2509
DI 10.1128/IAI.00127-11
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 779OO
UT WOS:000291788700001
PM 21555398
ER

PT J
AU Siberry, GK
   Patel, K
   Van Dyke, RB
   Hazra, R
   Burchett, SK
   Spector, SA
   Paul, ME
   Read, JS
   Wiznia, A
   Seage, GR
AF Siberry, George K.
   Patel, Kunjal
   Van Dyke, Russell B.
   Hazra, Rohan
   Burchett, Sandra K.
   Spector, Stephen A.
   Paul, Mary E.
   Read, Jennifer S.
   Wiznia, Andrew
   Seage, George R., III
CA PHACS
TI CD4(+) Lymphocyte-Based Immunologic Outcomes of Perinatally HIV-Infected
   Children During Antiretroviral Therapy Interruption
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV-1; children; adolescents; perinatal HIV infection; treatment
   interruption; CD4(+) T-cell percentage
ID LONG-TERM NONPROGRESSION; MORTALITY; ADOLESCENTS; PREDICTORS; INFANTS
AB Objective: To assess the characteristics and outcomes of antiretroviral treatment (ART) interruption (TI) in perinatally HIV-infected children.
   Design: The Adolescent Master Protocol (AMP) of the Pediatric HIV/AIDS Cohort Study is a prospective cohort study that enrolled 7- to 16-year-old perinatally HIV-infected children between 2007 and 2009 from 15 sites in the United States and Puerto Rico.
   Methods: TI was defined as ART discontinuation for >3 months after >= 6 months of continuous ART. Subjects with and without TI were compared. Rates of change (slopes) in CD4(+) T-lymphocyte (CD4) count and percentage (%) per month during TI were calculated. Factors related to CD4 slope in univariable analyses were included in multivariable linear regression.
   Results: Of 444 eligible AMP subjects, 101 (23%) had at least one TI. Subjects with TI were born in earlier years but were otherwise similar to those without TI. For 81 TI subjects with complete data, the median (range) CD4% and CD4 count slopes were -0.66% per month (-3.54% to +1.34% per month) and -12.7 cells per cubic millimeter per month (-148 cells/mm(3) to +31 cells/mm(3) per month), respectively. On multivariable linear regression, there was a trend for lower CD4% slope to be associated (P < 0.1) with female sex, higher CD4% at TI, and higher peak viral load before TI. Advanced HIV disease stage and numerous ART regimens were more common in TI subjects in the lowest (fastest declining) CD4% slope quartile.
   Conclusions: TIs in perinatally HIV-infected youth are common. During TIs, CD4 values decline on average but with high intersubject variability. Factors predicting CD4 slope during TI need further study.
C1 [Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS PAMA Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA.
   [Patel, Kunjal; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Patel, Kunjal; Seage, George R., III] Harvard Univ, Sch Publ Hlth, CBAR, Boston, MA 02115 USA.
   [Van Dyke, Russell B.] Tulane Univ Hlth Sci Ctr, New Orleans, LA USA.
   [Burchett, Sandra K.] Childrens Hosp, Boston, MA 02115 USA.
   [Burchett, Sandra K.] Harvard Univ, Sch Med, Boston, MA USA.
   [Spector, Stephen A.] Univ Calif San Diego, La Jolla, CA 92093 USA.
   [Spector, Stephen A.] Rady Childrens Hosp San Diego, San Diego, CA USA.
   [Paul, Mary E.] Baylor Coll Med, Houston, TX 77030 USA.
   [Wiznia, Andrew] Albert Einstein Coll Med, Jacobi Med Ctr, New York, NY USA.
RP Siberry, GK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS PAMA Branch, Ctr Res Mothers & Children, NIH, 6100 Execut Blvd,Room 4B11H, Bethesda, MD 20892 USA.
EM siberryg@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development; National Institute of Allergy and Infectious Diseases;
   National Institute on Drug Abuse; National Institute of Mental Health,
   National Institute of Deafness and Other Communication Disorders;
   National Heart Lung and Blood Institute, National Institute of
   Neurological Disorders and Stroke; National Institute on Alcohol Abuse
   and Alcoholism; Harvard University School of Public Health [U01
   HD052102-04]; Tulane University School of Medicine [U01 HD052104-01]
FX Supported by the Eunice Kennedy Shriver National Institute of Child
   Health and Human Development with cofunding from the National Institute
   of Allergy and Infectious Diseases, the National Institute on Drug
   Abuse, the National Institute of Mental Health, National Institute of
   Deafness and Other Communication Disorders, the National Heart Lung and
   Blood Institute, National Institute of Neurological Disorders and
   Stroke, and the National Institute on Alcohol Abuse and Alcoholism,
   through cooperative agreements with the Harvard University School of
   Public Health (U01 HD052102-04) (Principal Investigator: G.R.S.; Project
   Director: Julie Alperen) and the Tulane University School of Medicine
   (U01 HD052104-01) (Principal Investigator: R.B.D.; Co-Principal
   Investigator: Kenneth Rich.; Project Director: Patrick Davis.).
NR 19
TC 10
Z9 10
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 JUL 1
PY 2011
VL 57
IS 3
BP 223
EP 229
DI 10.1097/QAI.0b013e318218e068
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 778CM
UT WOS:000291676800017
PM 21423022
ER

PT J
AU Oh, SJ
   Hong, JJ
   Oh, CA
   Kim, DH
   Bae, YS
   Choi, SH
   Choi, MG
   Noh, JH
   Sohn, TS
   Bae, JM
   Kim, S
AF Oh, Seung Jong
   Hong, Jenny Jimmy
   Oh, Cheong Ah
   Kim, Dae Hoon
   Bae, Young Sik
   Choi, Seong Hee
   Choi, Min Gew
   Noh, Jae Hyung
   Sohn, Tae Sung
   Bae, Jae Moon
   Kim, Sung
TI Stapling Technique for Performing Billroth II Anastomosis After Distal
   Gastrectomy
SO JOURNAL OF GASTROINTESTINAL SURGERY
LA English
DT Article
DE Stomach neoplasm; Gastrectomy; Gastrojejunostomy; Surgical stapling
AB The circular stapling technique has been widely applied for gastrointestinal anastomosis in gastrectomies (open or laparoscopic) for distal gastric cancers. We describe this method for use in performing Billroth II anastomosis in distal gastrectomies. From 2002-2009, we report the results following the use of the circular stapling technique performed in 520 patients at a single institution. The median time of completing the anastomosis was shorter using the stapling technique compared to the hand-sewn technique. The use of the stapler resulted in two cases of minor intraluminal bleeding at the anastomotic site. The circular stapling method can be applied safely and more efficiently in performing Billroth II reconstruction after distal gastrectomy compared to the hand-sewn method in patients with gastric cancer.
C1 [Oh, Seung Jong; Oh, Cheong Ah; Kim, Dae Hoon; Bae, Young Sik; Choi, Min Gew; Noh, Jae Hyung; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Surg, Seoul 135710, South Korea.
   [Hong, Jenny Jimmy] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
   [Choi, Seong Hee] Sungkyunkwan Univ, Sch Med, Samsung Changwon Hosp, Dept Surg, Chang Won, South Korea.
RP Kim, S (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Surg, 50 Ilwon Dong, Seoul 135710, South Korea.
EM skim.kim@samsung.com
RI Kim, Sung/G-4114-2014
NR 4
TC 2
Z9 4
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1091-255X
J9 J GASTROINTEST SURG
JI J. Gastrointest. Surg.
PD JUL
PY 2011
VL 15
IS 7
BP 1244
EP 1246
DI 10.1007/s11605-010-1403-8
PG 3
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 778JU
UT WOS:000291700800028
PM 21170599
ER

PT J
AU Liu, CH
   Miller, H
   Hui, KL
   Grooman, B
   Bolland, S
   Upadhyaya, A
   Song, WX
AF Liu, Chaohong
   Miller, Heather
   Hui, King Lam
   Grooman, Brian
   Bolland, Silvia
   Upadhyaya, Arpita
   Song, Wenxia
TI A Balance of Bruton's Tyrosine Kinase and SHIP Activation Regulates B
   Cell Receptor Cluster Formation by Controlling Actin Remodeling
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID WISKOTT-ALDRICH-SYNDROME; IMMUNOLOGICAL-SYNAPSE FORMATION; INOSITOL
   PHOSPHATASE SHIP; IMMUNE SYNAPSE; LIVING CELLS; ANTIGEN; PROTEIN;
   MICROCLUSTERS; LYMPHOCYTES; MACROPHAGES
AB The activation of the BCR, which initiates B cell activation, is triggered by Ag-induced self-aggregation and clustering of receptors at the cell surface. Although Ag-induced actin reorganization is known to be involved in BCR clustering in response to membrane-associated Ag, the underlying mechanism that links actin reorganization to BCR activation remains unknown. In this study, we show that both the stimulatory Bruton's tyrosine kinase (Btk) and the inhibitory SHIP-1 are required for efficient BCR self-aggregation. In Btk-deficient B cells, the magnitude of BCR aggregation into clusters and B cell spreading in response to an Ag-tethered lipid bilayer is drastically reduced, compared with BCR aggregation observed in wild-type B cells. In SHIP-1(-/-) B cells, although surface BCRs aggregate into microclusters, the centripetal movement and growth of BCR clusters are inhibited, and B cell spreading is increased. The persistent BCR microclusters in SHIP-1(-/-) B cells exhibit higher levels of signaling than merged BCR clusters. In contrast to the inhibition of actin remodeling in Btk-deficient B cells, actin polymerization, F-actin accumulation, and Wiskott-Aldrich symptom protein phosphorylation are enhanced in SHIP-1(-/-) B cells in a Btk-dependent manner. Thus, a balance between positive and negative signaling regulates the spatiotemporal organization of the BCR at the cell surface by controlling actin remodeling, which potentially regulates the signal transduction of the BCR. This study suggests a novel feedback loop between BCR signaling and the actin cytoskeleton. The Journal of Immunology, 2011, 187: 230-239.
C1 [Liu, Chaohong; Miller, Heather; Song, Wenxia] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA.
   [Hui, King Lam; Grooman, Brian; Upadhyaya, Arpita] Univ Maryland, Dept Phys, College Pk, MD 20742 USA.
   [Bolland, Silvia] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Song, WX (reprint author), Univ Maryland, Dept Mol Genet & Cell Biol, 1133A Microbiol Bldg, College Pk, MD 20742 USA.
EM wenxsong@umd.edu
FU National Institute of Allergy and Infectious Diseases, National
   Institutes of Health [AI059617]
FX This work was supported by Grant AI059617 (to W.S.) and Intramural
   Research Program (to S.B.) of the National Institute of Allergy and
   Infectious Diseases, National Institutes of Health.
NR 40
TC 24
Z9 25
U1 1
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 1
PY 2011
VL 187
IS 1
BP 230
EP 239
DI 10.4049/jimmunol.1100157
PG 10
WC Immunology
SC Immunology
GA 779RQ
UT WOS:000291799300029
PM 21622861
ER

PT J
AU Grignol, VP
   Olencki, T
   Relekar, K
   Taylor, C
   Kibler, A
   Kefauver, C
   Wei, L
   Walker, MJ
   Chen, HX
   Kendra, K
   Carson, WE
AF Grignol, Valerie P.
   Olencki, Thomas
   Relekar, Kiran
   Taylor, Cynthia
   Kibler, Amanda
   Kefauver, Cheryl
   Wei, Lai
   Walker, Michael J.
   Chen, Helen X.
   Kendra, Kari
   Carson, William E., III
TI A Phase 2 Trial of Bevacizumab and High-dose Interferon Alpha 2B in
   Metastatic Melanoma
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE bevacizumab; vascular endothelial growth factor; angiogenesis;
   interferon alpha 2b; metastatic melanoma; phase 2 clinical trial
ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; MALIGNANT-MELANOMA; III
   TRIAL; WEEKLY PACLITAXEL; COMBINATION; EXPRESSION; THERAPY; ALPHA;
   PROGRESSION
AB Bevacizumab is a humanized recombinant monoclonal antibody that neutralizes vascular endothelial growth factor, an agent with proangiogenic effects in melanoma. Interferon alpha (IFN-alpha) has antiangiogenic properties through its ability to down-regulate basic-fibroblast growth factor levels. We hypothesized that the coadministration of these agents would lead to tumor regression. Patients with metastatic melanoma received bevacizumab 15 mg/kg intravenously on day 1 of the 2-week cycle. IFN-alpha was administered thrice weekly at 5MU/m(2) subcutaneously during cycle 1 and was increased to 10MU/m(2) during cycle 2. Patients were restaged every 6 cycles. Patients with stable disease or a response continued with therapy. Baseline serum vascular endothelial growth factor and fibroblast growth factor were measured. Twenty-five patients were accrued. Mean age was 58.4 years. Eleven patients required IFN-alpha dose reductions due to toxicity. Common grade 3 toxicities associated with IFN-alpha included fatigue and myalgia. Bevacizumab administration was associated with grade 2-3 proteinuria in 6 patients. Grade 4 adverse events were pulmonary embolus (1), myocardial infarction (1), and stroke (1). Six patients had a partial response, and 5 patients exhibited stable disease that lasted more than 24 weeks (range: 30 to 122 wk). Median progression-free survival and overall survival were 4.8 and 17 months, respectively. Significantly lower fibroblast growth factor levels were observed in patients with a partial response compared to those with stable or progressive disease (P = 0.040). Administration of bevacizumab with IFN led to a clinical response in 24% of patients with stage IV melanoma and stabilization of disease in another 20% of patients. This regimen has activity in advanced melanoma.
C1 [Grignol, Valerie P.; Relekar, Kiran; Walker, Michael J.; Carson, William E., III] Ohio State Univ, Div Surg Oncol, Columbus, OH 43210 USA.
   [Olencki, Thomas; Kendra, Kari] Ohio State Univ, Div Hematol & Oncol, Columbus, OH 43210 USA.
   [Taylor, Cynthia; Kibler, Amanda; Kefauver, Cheryl] Ohio State Univ, Clin Trial Off, Columbus, OH 43210 USA.
   [Wei, Lai] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA.
   [Chen, Helen X.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Carson, WE (reprint author), Ohio State Univ, Div Surg Oncol, N924 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA.
EM william.carson@osumc.edu
RI Carson, William/E-2846-2011
FU NIH [U01 CA76576, P01 CA095426, P30 CA16058, PPG 6001409, T32 CA009338,
   K24 CA093670, N01CM62207]; Genentech
FX Supported by NIH Grants: U01 CA76576, P01 CA095426, P30 CA16058, PPG
   6001409, T32 CA009338, K24 CA093670, N01CM62207.; William E. Carson III
   has a prior consultant/advisory board role with Genentech to disclose.
   Thomas Olencki has consultant/advisory role, honoraria and research
   funding relationship with Genentech. All other authors have declared
   there are no financial conflicts of interest to disclose.
NR 34
TC 23
Z9 24
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1524-9557
EI 1537-4513
J9 J IMMUNOTHER
JI J. Immunother.
PD JUL-AUG
PY 2011
VL 34
IS 6
BP 509
EP 515
DI 10.1097/CJI.0b013e31821dcefd
PG 7
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 778CA
UT WOS:000291675600005
PM 21654521
ER

PT J
AU Resnik, DB
   Master, Z
AF Resnik, David B.
   Master, Zubin
TI Authorship policies of bioethics journals
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
ID MEDICAL JOURNALS; GHOST AUTHORSHIP; PREVALENCE; HONORARY; TRENDS
AB Inappropriate authorship is a common problem in biomedical research and may be becoming one in bioethics, due to the increase in multiple authorship. This paper investigates the authorship policies of bioethics journals to determine whether they provide adequate guidance for researchers who submit articles for publication, which can help deter inappropriate authorship. It was found that 63.3% of bioethics journals provide no guidance on authorship; 36.7% provide guidance on which contributions merit authorship, 23.3% provide guidance on which contributions do not merit authorship, 23.3% require authors to take responsibility for their contributions or for the article as a whole, 20% provide guidance on which contributions merit an acknowledgement but not authorship, 6.7% require authors to describe their contributions, and only 3.3% distinguish between authorship in empirical and conceptual research. To provide authors with effective guidance and promote integrity in bioethics research, bioethics journals should adopt authorship policies that address several important topics, such as the qualifications for authorship, describing authorship contributions, taking responsibility for the research and the difference between authorship in empirical and conceptual research.
C1 [Resnik, David B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
   [Master, Zubin] Univ Alberta, Hlth Law Inst, Edmonton, AB, Canada.
   [Master, Zubin] Univ Ottawa, Ottawa Hosp, Res Inst, Sprott Ctr Stem Cell Res,Regenerat Med Program, Ottawa, ON, Canada.
RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
FU National Institute of Environmental Health Sciences (NIEHS); National
   Institutes of Health (NIH)
FX This research was supported, in part, by the National Institute of
   Environmental Health Sciences (NIEHS) and National Institutes of Health
   (NIH). It does not represent the views of the NIEHS, NIH, Health Canada
   or the US or Canadian governments. At the time of performing this study,
   ZM was also affiliated with the Sprott Centre for Stem Cell Research and
   the Regenerative Medicine Program of the Ottawa Hospital Research
   Institute, University of Ottawa.
NR 28
TC 5
Z9 6
U1 0
U2 2
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 JUL
PY 2011
VL 37
IS 7
BP 424
EP 428
DI 10.1136/jme.2010.040675
PG 5
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
   Biomedical Social Sciences
GA 778PS
UT WOS:000291717200009
PM 21266387
ER

PT J
AU Resnik, DB
   Master, Z
AF Resnik, David B.
   Master, Zubin
TI Bioethics authorship guidelines Response
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Letter
C1 [Resnik, David B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
   [Master, Zubin] Univ Alberta, Hlth Law Inst, Edmonton, AB, Canada.
   [Master, Zubin] Univ Ottawa, Ottawa Hosp, Res Inst, Sprott Ctr Stem Cell Res,Regenerat Med Program, Ottawa, ON, Canada.
RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA.
EM resnikd@niehs.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
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 JUL
PY 2011
VL 37
IS 7
BP 449
EP 449
DI 10.1136/jme.2011.044461
PG 1
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
   Biomedical Social Sciences
GA 778PS
UT WOS:000291717200016
ER

PT J
AU Force, J
   Rajan, A
   Dombi, E
   Steinberg, SM
   Giaccone, G
AF Force, Jeremy
   Rajan, Arun
   Dombi, Eva
   Steinberg, Seth M.
   Giaccone, Giuseppe
TI Assessment of Objective Responses Using Volumetric Evaluation in
   Advanced Thymic Malignancies and Metastatic Non-small Cell Lung Cancer
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Thymic malignancy; Thymic cancer; Thymoma; Three-dimensional;
   Volumetric; RECIST; Non-small cell lung cancer; Computed tomography
ID PLEURAL MESOTHELIOMA; TUMOR VOLUME; RECIST CRITERIA; SOLID TUMORS; CT;
   CARCINOMA; DIAMETER; THYMOMA
AB Introduction: Measurement of tumor response by standard response criteria is challenging in thymic malignancies, especially when the pleura is involved, as it often is in stage IV disease. In this study, we aimed to determine the effectiveness of volumetric response evaluation criteria in solid tumors (volumetrics) for evaluating response in patients with thymic malignancies treated on a phase II study of belinostat.
   Methods: We evaluated the tumor responses of 25 patients with thymic cancer using computed tomography-based RECIST, World Health Organization (WHO), modified RECIST, and volumetrics. As a control, we assessed 37 patients with non-small cell lung cancer (NSCLC) with RECIST and volumetrics.
   Results: Agreement analyses in 23 patients with thymic cancer at the time of RECIST-determined progressive disease (PD) compared volumetrics with RECIST, modified RECIST, and WHO criteria. Use of volumetrics was associated with 22% discordance compared with RECIST, 15% versus modified RECIST, and 22% versus WHO criteria. Volumetrics revealed PD 72 days earlier than RECIST (p = 0.016). In another cohort of 35 patients with NSCLC, there was 9% discordance between volumetrics and RECIST at the time of PD. Volumetrics demonstrated PD 32 days earlier than RECIST in NSCLC (p = 0.0078).
   Conclusions: Our study suggests that volumetrics might improve detection of PD. Prospective evaluation of this technique in a larger series of patients with thymic malignancies will be required.
C1 [Force, Jeremy; Rajan, Arun; Giaccone, Giuseppe] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Dombi, Eva] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 10 Ctr Dr,Room 12N226, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU National Cancer Institute, National Institutes of Health; NIH; Pfizer
   Inc.
FX Supported in whole or in part with federal funds from the National
   Cancer Institute, National Institutes of Health. This work was supported
   by the Clinical Research Training Program, a public-private partnership
   supported jointly by the NIH and Pfizer Inc. (through a grant to the
   Foundation for NIH from Pfizer Inc.).
NR 21
TC 6
Z9 7
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD JUL
PY 2011
VL 6
IS 7
BP 1267
EP 1273
DI 10.1097/JTO.0b013e3182199be2
PG 7
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 778CY
UT WOS:000291678200017
PM 21610525
ER

PT J
AU Conti, HR
   Baker, O
   Freeman, AF
   Jang, WS
   Holland, SM
   Li, RA
   Edgerton, M
   Gaffen, SL
AF Conti, H. R.
   Baker, O.
   Freeman, A. F.
   Jang, W. S.
   Holland, S. M.
   Li, R. A.
   Edgerton, M.
   Gaffen, S. L.
TI New mechanism of oral immunity to mucosal candidiasis in hyper-IgE
   syndrome
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; HOST-DEFENSE; TH17 CELLS;
   ANTIMICROBIAL PEPTIDES; FUNGAL-INFECTIONS; PROTECTIVE IMMUNITY; NLRP3
   INFLAMMASOME; INNATE IMMUNITY; HUMAN DECTIN-1; ALBICANS
AB Oropharyngeal candidiasis (OPC, thrush) is an opportunistic infection caused by the commensal fungus Candida albicans. An understanding of immunity to Candida has recently begun to unfold with the identification of fungal pattern-recognition receptors such as C-type lectin receptors, which trigger protective T-helper (Th)17 responses in the mucosa. Hyper-IgE syndrome (HIES/Job's syndrome) is a rare congenital immunodeficiency characterized by dominant-negative mutations in signal transducer and activator of transcription 3, which is downstream of the Th17-inductive cytokines interleukin (IL)-6 and IL-23, and hence patients with HIES exhibit dramatic Th17 deficits. HIES patients develop oral and mucocutaneous candidiasis, supporting a protective role for Th17 cells in immunity to OPC. However, the Th17-dependent mechanisms of antifungal immunity in OPC are still poorly defined. An often unappreciated aspect of oral immunity is saliva, which is rich in antimicrobial proteins (AMPs) and exerts direct antifungal activity. In this study, we show that HIES patients show significant impairment in salivary AMPs, including beta-defensin 2 and Histatins. This tightly correlates with reduced candidacidal activity of saliva and concomitantly elevated colonization with Candida. Moreover, IL-17 induces histatins in cultured salivary gland cells. This is the first demonstration that HIES is associated with defective salivary activity, and provides a mechanism for the severe susceptibility of these patients to OPC.
C1 [Conti, H. R.; Baker, O.; Jang, W. S.; Li, R. A.; Edgerton, M.; Gaffen, S. L.] SUNY Buffalo, Dept Oral Biol, Buffalo, NY 14260 USA.
   [Freeman, A. F.; Holland, S. M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD USA.
   [Gaffen, S. L.] Univ Pittsburgh, Dept Med, Div Rheumatol & Clin Immunol, Pittsburgh, PA USA.
RP Edgerton, M (reprint author), SUNY Buffalo, Dept Oral Biol, Buffalo, NY 14260 USA.
EM edgerto@buffalo.edu; sig65@pitt.edu
FU NIAID, NIH, Bethesda, MD [20892]; Amgen;  [DE018822];  [AR054389]; 
   [AI89768];  [DE019721];  [DE007034]
FX SLG and ME were supported by DE018822, and SLG was also supported by
   AR054389 and AI89768. OB was supported by DE019721. HRC was supported by
   a training grant to the Department of Oral Biology at SUNY Buffalo
   (DE007034). SMH and AFF were supported by the Intramural Research
   Program of NIAID, NIH, Bethesda, MD 20892. The views expressed in this
   article are those of the authors and do not reflect the official policy
   of the US. Government. We thank S. Khader, AC Peterson, N
   Hernandez-Santos, and A. Ray for critical reading. We also thank S.
   Velichko and R. Wu for sharing insights regarding STAT3 sites within the
   BD2 promoter.; SLG has received a research grant from Amgen, and
   consults for Kinex BioPharma and Lycera Corporation.
NR 56
TC 47
Z9 48
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD JUL
PY 2011
VL 4
IS 4
BP 448
EP 455
DI 10.1038/mi.2011.5
PG 8
WC Immunology
SC Immunology
GA 778RD
UT WOS:000291721500010
PM 21346738
ER

PT J
AU Vasilakis, N
   Cardosa, J
   Hanley, KA
   Holmes, EC
   Weaver, SC
AF Vasilakis, Nikos
   Cardosa, Jane
   Hanley, Kathryn A.
   Holmes, Edward C.
   Weaver, Scott C.
TI Fever from the forest: prospects for the continued emergence of sylvatic
   dengue virus and its impact on public health
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Review
ID LAND-USE CHANGE; HEMORRHAGIC-FEVER; ANTIGENIC RELATIONSHIPS;
   SOUTHEASTERN SENEGAL; TRANSMISSION CYCLES; ENCEPHALITIS-VIRUS;
   SEROLOGICAL SURVEY; VECTOR COMPETENCE; ANTIBODY-RESPONSE; DISEASE
   SEVERITY
AB The four dengue virus (DENV) serotypes that circulate among humans emerged independently from ancestral sylvatic progenitors that were present in non-human primates, following the establishment of human populations that were large and dense enough to support continuous inter-human transmission by mosquitoes. This ancestral sylvatic-DENV transmission cycle still exists and is maintained in non-human primates and Aedes mosquitoes in the forests of Southeast Asia and West Africa. Here, we provide an overview of the ecology and molecular evolution of sylvatic DENV and its potential for adaptation to human transmission. We also emphasize how the study of sylvatic DENV will improve our ability to understand, predict and, ideally, avert further DENV emergence.
C1 [Vasilakis, Nikos; Weaver, Scott C.] Univ Texas Med Branch, Dept Pathol, Ctr Biodef & Emerging Infect Dis, Inst Human Infect & Immun, Galveston, TX 77555 USA.
   [Vasilakis, Nikos; Weaver, Scott C.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA.
   [Cardosa, Jane] Univ Sarawak Malaysia UNIMAS, Inst Hlth & Community Med, Kota Samarahan 94300, Sarawak, Malaysia.
   [Hanley, Kathryn A.] New Mexico State Univ, Dept Biol, Las Cruces, NM 88003 USA.
   [Holmes, Edward C.] Penn State Univ, Mueller Lab, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
   [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Vasilakis, N (reprint author), Univ Texas Med Branch, Dept Pathol, Ctr Biodef & Emerging Infect Dis, Inst Human Infect & Immun, Galveston, TX 77555 USA.
EM nivasila@utmb.edu
RI Weaver, Scott/D-6490-2011; 
OI Holmes, Edward/0000-0001-9596-3552
FU Department of Pathology, University of Texas Medical Branch; Universiti
   Malaysia Sarawak; US National Institutes of Health (NIH) [R01AI069145,
   P20RR016480]; NIH [R01GM080533, R01GM83224, AI069145]; John Sealy
   Distinguished University Chair in Human Infections and Immunity
FX N.V. is supported by start-up funds provided by the Department of
   Pathology, University of Texas Medical Branch. J.C. has been supported
   in part by operational funds from Universiti Malaysia Sarawak. K.A.H. is
   supported by US National Institutes of Health (NIH) grants R01AI069145
   and P20RR016480. E.C.H. is supported in part by NIH grants R01GM080533
   and R01GM83224. S.C.W. is supported for dengue research by NIH grant
   AI069145 and by the John Sealy Distinguished University Chair in Human
   Infections and Immunity. Special thanks to S. Rossi for providing the
   design on which figure 1 is based.
NR 128
TC 82
Z9 85
U1 5
U2 39
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
EI 1740-1534
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD JUL
PY 2011
VL 9
IS 7
BP 532
EP 541
DI 10.1038/nrmicro2595
PG 10
WC Microbiology
SC Microbiology
GA 780JQ
UT WOS:000291852300020
PM 21666708
ER

PT J
AU Lee, J
   van Gelderen, P
   Kuo, LW
   Merkle, H
   Silva, AC
   Duyn, JH
AF Lee, Jongho
   van Gelderen, Peter
   Kuo, Li-Wei
   Merkle, Hellmut
   Silva, Afonso C.
   Duyn, Jeff H.
TI T-2*-based fiber orientation mapping
SO NEUROIMAGE
LA English
DT Article
DE T*(2) relaxation; R*(2); Fiber tracking; Magnetic susceptibility
   anisotropy in white matter; Susceptibility tensor imaging (STI);
   Diffusion tensor imaging (DTI)
ID WHITE-MATTER; HUMAN BRAIN; MAGNETIC-ANISOTROPY; MULTIPLE-SCLEROSIS;
   LECITHIN MEMBRANES; RELAXATION-TIMES; MRI; IRON; FIELD; HETEROGENEITY
AB Recent MRI studies at high field have observed that, in certain white matter fiber bundles, the signal in T*(2)-weighted MRI (i.e. MRI sensitized to apparent transverse relaxivity) is dependent on fiber orientation theta relative to B-0. In this study, the characteristics of this dependency are quantitatively investigated at 7 T using ex-vivo brain specimens, which allowed a large range of rotation angles to be measured. The data confirm the previously suggested variation of R*(2) (=1/T-2*) with theta and also indicate that this dependency takes the shape of a combination of sin2 theta and sin4 theta functions, with modulation amplitudes (=Delta R*(2)) reaching 6.44 +/- 0.15 Hz (or Delta T*(2) = 2.91 +/- 0.33 ms) in the major fiber bundles of the corpus callosum. This particular dependency can be explained by a model of local, sub-voxel scale magnetic field changes resulting from magnetic susceptibility sources that are anisotropic. As an illustration of a potential use of the orientation dependence of R*(2), the feasibility of generating fiber orientation maps from R*(2) data is investigated. Published by Elsevier Inc.
C1 [Lee, Jongho; van Gelderen, Peter; Kuo, Li-Wei; Merkle, Hellmut; Duyn, Jeff H.] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
   [Lee, Jongho] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
   [Silva, Afonso C.] NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Lee, J (reprint author), 3 W Gates Bldg,3400 Spruce St, Philadelphia, PA 19104 USA.
EM jonghoyi@gmail.com
RI Kuo, Li-Wei/G-4007-2011
FU NIH, NINDS
FX This research was supported (in part) by the Intramural Research Program
   of the NIH, NINDS.
NR 38
TC 46
Z9 46
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JUL 1
PY 2011
VL 57
IS 1
BP 225
EP 234
DI 10.1016/j.neuroimage.2011.04.026
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
   Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 777MC
UT WOS:000291624100026
PM 21549203
ER

PT J
AU Zeng, HM
   Yu, H
   Lu, LG
   Jain, D
   Kidd, MS
   Saif, MW
   Chanock, SJ
   Hartge, P
   Risch, HA
AF Zeng, Hongmei
   Yu, Herbert
   Lu, Lingeng
   Jain, Dhanpat
   Kidd, Mark S.
   Saif, M. Wasif
   Chanock, Stephen J.
   Hartge, Patricia
   Risch, Harvey A.
CA PanScan Consortium
TI Genetic Effects and Modifiers of Radiotherapy and Chemotherapy on
   Survival in Pancreatic Cancer
SO PANCREAS
LA English
DT Article
DE pancreatic neoplasms; survival; genetic heterogeneity; polymorphism;
   single nucleotide; prognosis
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; ENDOTHELIAL GROWTH-FACTOR; GENOME-WIDE
   ASSOCIATION; S-TRANSFERASE-PI; INCREASED EXPRESSION; GEMCITABINE;
   ADENOCARCINOMA; TRIAL; ALPHA-1-ANTITRYPSIN; SUSCEPTIBILITY
AB Objectives: Germ-line genetic variation may affect clinical outcomes of cancer patients. We applied a candidate-gene approach to evaluate the effect of putative markers on survival of patients with pancreatic cancer. We also examined gene-radiotherapy and gene-chemotherapy interactions, aiming to explain interindividual differences in treatment outcomes.
   Methods: In total, 211 patients with pancreatic cancer were recruited in a population-based study. Sixty-four candidate genes associated with cancer survival or treatment response were selected from existing publications. Genotype information was obtained from a previous genome-wide association study data set. The main effects of genetic variation and gene-specific treatment interactions on overall survival were examined by proportional hazards regression models.
   Results: Fourteen genes showed evidence of association with pancreatic cancer survival. Among these, rs1760217, located at the DPYD gene; rs17091162 at SERPINA3; and rs2231164 at ABCG2 had the lowest P of 10(-4.60), 0.0013, and 0.0023, respectively. We also observed that 2 genes, RRM1 and IQGAP2, had significant interactions with radiotherapy in association with survival, and 2 others, TYMS and MET, showed evidence of interaction with 5-fluorouracil and erlotinib, respectively.
   Conclusions: Our study suggested significant associations between germ-line genetic polymorphisms and overall survival in pancreatic cancer, as well as survival interactions between various genes and radiotherapy and chemotherapy.
C1 [Zeng, Hongmei; Yu, Herbert; Lu, Lingeng; Risch, Harvey A.] Yale Univ, Dept Epidemiol & Publ Hlth, Sch Publ Hlth, New Haven, CT 06520 USA.
   [Zeng, Hongmei] Peking Univ, Key Lab Carcinogenesis & Translat Res, Beijing Canc Hosp & Inst, Minist Educ,Dept Canc Epidemiol,Sch Oncol, Beijing 100871, Peoples R China.
   [Jain, Dhanpat] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA.
   [Kidd, Mark S.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06520 USA.
   [Saif, M. Wasif] Columbia Univ Coll Phys & Surg, Dept Med, Div Hematol Oncol, New York, NY 10032 USA.
   [Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Natl Inst Hlth,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Risch, HA (reprint author), Yale Univ, Dept Epidemiol & Publ Hlth, Sch Publ Hlth, POB 208034, New Haven, CT 06520 USA.
EM harvey.risch@yale.edu
FU US National Cancer Institute, National Institutes of Health
   [5R01-CA098870, HHSN261200800001E]; China Scholarship Council, Beijing,
   China
FX This study was funded by the US National Cancer Institute, National
   Institutes of Health (grant 5R01-CA098870 to H.A.R. and contract
   HHSN261200800001E to S.J.C.) and by the Overseas Study Program of the
   China Scholarship Council, Beijing, China (to H.Z.).
NR 40
TC 6
Z9 6
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD JUL
PY 2011
VL 40
IS 5
BP 657
EP 663
DI 10.1097/MPA.0b013e31821268d1
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 777PP
UT WOS:000291635800004
PM 21487324
ER

PT J
AU Mathews, LA
   Cabarcas, SM
   Hurt, EM
   Zhang, XH
   Jaffee, EM
   Farrar, WL
AF Mathews, Lesley A.
   Cabarcas, Stephanie M.
   Hurt, Elaine M.
   Zhang, Xiaohu
   Jaffee, Elizabeth M.
   Farrar, William L.
TI Increased Expression of DNA Repair Genes in Invasive Human Pancreatic
   Cancer Cells
SO PANCREAS
LA English
DT Article
DE pancreatic cancer; invasion; DNA repair; gemcitabine; tumor-initiating
   cells
ID EPITHELIAL-MESENCHYMAL TRANSITION; STEM-CELLS; BREAST-CANCER;
   DRUG-RESISTANCE; METASTASIS; PROSTATE; ADENOCARCINOMA; IDENTIFICATION;
   PROPAGATION; SIGNATURE
AB Objective: Pancreatic cancer was the fourth leading cause of cancer death in the United States in 2010. Recurrence of disease after resection occurs because of neoplastic cell survival. To better understand these highly aggressive cells, gene expression microarrays were performed.
   Methods: Using the established lines HPAC and PANC1 and a Matrigel assay, genome expression arrays were performed to analyze patterns between invasive and total cells.
   Results: Significant increases in the expression of genes related to DNA repair were observed. A number of the same genes also demonstrated an increase in expression when comparing bulk cells to a putative tumor-initiating cell (TIC) population. The TIC population was isolated using the spheroid technique, and compared with bulk cells, spheroid cells functionally repair breaks in DNA faster after challenge with the drug gemcitabine. Finally, using Oncomine, we observed a significant increase in DNA copy number of BRCA1 and RAD51 in tissue isolated from metastatic pancreatic cancer compared with tissue isolated from the primary site.
   Conclusions: From these data, we conclude that the most invasive cells within a pancreatic tumor are able to thrive because of their increased genomic stability. These cells have also been linked to the TIC population in a tumor.
C1 [Mathews, Lesley A.; Cabarcas, Stephanie M.; Farrar, William L.] Natl Canc Inst Frederick, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
   [Hurt, Elaine M.] MedImmune LLC, Gaithersburg, MD USA.
   [Zhang, Xiaohu] Natl Canc Inst Frederick, Canc Stem Cell Sect, Lab Canc Prevent, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Jaffee, Elizabeth M.] Johns Hopkins Med Inst, Dept Oncol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA.
   [Jaffee, Elizabeth M.] Johns Hopkins Med Inst, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA.
RP Farrar, WL (reprint author), Natl Canc Inst Frederick, Canc Stem Cell Sect, Lab Canc Prevent, Ctr Canc Res, 1050 Boyles St,Bldg 560,Room 21-81, Frederick, MD 21702 USA.
EM farrarw@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; National Institutes of Health, 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 HHSN261200800001E. 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 46
TC 19
Z9 19
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0885-3177
J9 PANCREAS
JI Pancreas
PD JUL
PY 2011
VL 40
IS 5
BP 730
EP 739
DI 10.1097/MPA.0b013e31821ae25b
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 777PP
UT WOS:000291635800016
PM 21633318
ER

PT J
AU Evans, S
   Shergill, SS
   Chouhan, V
   Bristow, E
   Collier, T
   Averbeck, BB
AF Evans, S.
   Shergill, S. S.
   Chouhan, V.
   Bristow, E.
   Collier, T.
   Averbeck, B. B.
TI Patients with schizophrenia show increased aversion to angry faces in an
   associative learning task
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Decision making; emotions; faces; reward
ID FACIAL AFFECT RECOGNITION; EMOTION RECOGNITION; SCHIZOAFFECTIVE
   DISORDER; PARKINSONS-DISEASE; DECISION-MAKING; DOPAMINE; EXPRESSION;
   REINFORCEMENT; PSYCHOPATHOLOGY; DISCRIMINATION
AB Background. We were interested in examining the relationship between socially relevant stimuli and decision processes in patients with schizophrenia.
   Method. We tested patients with schizophrenia and healthy controls on a stochastically rewarded associative learning task. Participants had to determine, through trial and error, which of two faces was associated with a higher chance of reward : one face was angry, the other happy.
   Results. Both patients and healthy controls were able to perform the task at above-chance accuracy, and there was no significant difference in overall accuracy between the groups. Both groups also reliably preferred the happy face, such that they selected it more often than the angry face on the basis of the same amount of positive versus negative feedback. However, patients were significantly more averse to the angry face, such that they chose it less often than control participants when the reward feedback strongly supported the angry face as the best choice.
   Conclusions. Patients show an increased aversion to angry faces, in a task in which they must learn to associate rewards with expressions.
C1 [Averbeck, B. B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
   [Evans, S.; Averbeck, B. B.] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London, England.
   [Shergill, S. S.; Chouhan, V.; Bristow, E.; Collier, T.] Kings Coll London, Inst Psychiat, Dept Psychosis Studies, Cognit Schizophrenia & Imaging Lab, London WC2R 2LS, England.
RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
EM averbeckbb@mail.nih.gov
RI Shergill, Sukhi/G-7725-2011
FU Welcome Trust; Medical Research Council (MRC); National Institute of
   Mental Health (NIMH), National Institutes of Health (NIH)
FX This work was supported by a Welcome Trust Project Grant to B.B.A., a
   Higher Education Funding Council for England (HEFCE) Clinical Senior
   Lecturer Award to S. S. S. and Medical Research Council (MRC) funding
   within the UCL 3-year PhD in Neuroscience to S.E. This work was also
   supported in part by the Intramural Research Program of the National
   Institute of Mental Health (NIMH), National Institutes of Health (NIH).
NR 44
TC 10
Z9 10
U1 2
U2 4
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD JUL
PY 2011
VL 41
IS 7
BP 1471
EP 1479
DI 10.1017/S0033291710001960
PG 9
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 780KL
UT WOS:000291854700014
PM 20961475
ER

PT J
AU Grossman, CI
   Forsyth, A
   Purcell, DW
   Allison, S
   Toledo, C
   Gordon, CM
AF Grossman, Cynthia I.
   Forsyth, Andrew
   Purcell, David W.
   Allison, Susannah
   Toledo, Carlos
   Gordon, Christopher M.
TI Advancing Novel HIV Prevention Intervention Research with MSM-Meeting
   Report
SO PUBLIC HEALTH REPORTS
LA English
DT Article
ID UNITED-STATES; PUBLIC-HEALTH; MEN; SEX; HIV/AIDS; RISK; BEHAVIORS;
   EPIDEMIC; AMERICA; IMPACT
AB HIV continues to exact an enormous toll on society and to disproportionately affect gay and bisexual men and other men who have sex with men (MSM). Innovative prevention interventions are needed to reverse this trend. In August 2009, the U.S. National Institute of Mental Health and the Centers for Disease Control and Prevention convened a meeting of scientists, community representatives, advocates, and federal partners to discuss innovative prevention-intervention science. The meeting was structured to maximize discussion of (1) healthy sex interventions, (2) community and structural interventions, (3) integrated biomedical and behavioral interventions, and (4) interventions to improve uptake of HIV testing. Presentations and discussion focused on research gaps in designing risk-reducing and sexual health-promoting interventions for MSM, including interventions to address mental health, substance use, disclosure, and stigma. This article summarizes the meeting proceedings, highlights key points, and outlines future directions.
C1 [Grossman, Cynthia I.; Forsyth, Andrew; Allison, Susannah; Gordon, Christopher M.] NIMH, NIH, Bethesda, MD 20892 USA.
   [Purcell, David W.; Toledo, Carlos] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Grossman, CI (reprint author), NIMH, NIH, 6001 Execut Blvd,Room 6201, Bethesda, MD 20892 USA.
EM grossmanc@mail.nih.gov
OI Purcell, David/0000-0001-8125-5168
NR 30
TC 16
Z9 16
U1 1
U2 2
PU ASSOC SCHOOLS PUBLIC HEALTH
PI WASHINGTON
PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA
SN 0033-3549
J9 PUBLIC HEALTH REP
JI Public Health Rep.
PD JUL-AUG
PY 2011
VL 126
IS 4
BP 472
EP 479
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 777ZS
UT WOS:000291665600004
PM 21800742
ER

PT J
AU Gulley, SP
   Rasch, EK
   Chan, L
AF Gulley, Stephen P.
   Rasch, Elizabeth K.
   Chan, Leighton
TI The Complex Web of Health: Relationships Among Chronic Conditions,
   Disability, and Health Services
SO PUBLIC HEALTH REPORTS
LA English
DT Article
ID IMPROVING PRIMARY-CARE; UNITED-STATES; CHRONIC ILLNESS; CHRONIC DISEASE;
   DIABETES CARE; MEDICAL HOME; NEEDS; DEPRESSION; CHILDREN; EXPENDITURES
AB Objectives. A critical issue in health-care reform concerns how to realign health-care delivery systems to manage medical care services for people with ongoing and costly needs for care. We examined the overlapping health-care needs of two such population groups among the U.S. working-age population (those aged 18-64 years): people with chronic medical conditions and people with disabilities.
   Methods. Using the Medical Expenditure Panel Survey (2002-2004), we examined differences in health status, service use, and access to care among and between working-age adults reporting disabilities and/or one or more chronic conditions. We also analyzed people with three key chronic conditions: arthritis, diabetes, and depression.
   Results. More than half of working-age people with disabilities reported having more than one chronic condition. Among those with activities of daily living or instrumental activities of daily living limitations, 35% reported four or more chronic conditions at a time. We found considerable variability in access problems and service use depending on how we accounted for the overlap of multiple conditions among people with arthritis, diabetes, and depression. However, disability consistently predicted higher emergency department use, higher hospitalization rates, and greater access problems.
   Conclusions. The overall prevalence of chronic conditions among the U.S. working-age population, coupled with the high concentration of multiple chronic conditions among those with disabilities, underscores the importance of reforming health-care delivery systems to provide person-centered care over time. New policy-relevant measures that transcend diagnosis are required to track the ongoing needs for health services that these populations present.
C1 [Gulley, Stephen P.; Rasch, Elizabeth K.; Chan, Leighton] NIH, Mark O Hatfield Clin Res Ctr, Dept Rehabil Med, Bethesda, MD 20892 USA.
   [Gulley, Stephen P.] Brandeis Univ, Heller Sch Social Policy & Management, Waltham, MA USA.
RP Gulley, SP (reprint author), NIH, Mark O Hatfield Clin Res Ctr, Dept Rehabil Med, Bldg 10,CRC,Room 1-1469,10 Ctr Dr,MSC-1604, Bethesda, MD 20892 USA.
EM gulley@brandeis.edu
NR 52
TC 34
Z9 34
U1 1
U2 11
PU ASSOC SCHOOLS PUBLIC HEALTH
PI WASHINGTON
PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA
SN 0033-3549
J9 PUBLIC HEALTH REP
JI Public Health Rep.
PD JUL-AUG
PY 2011
VL 126
IS 4
BP 495
EP 507
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 777ZS
UT WOS:000291665600006
PM 21800744
ER

PT J
AU Dunkers, JP
   Lee, HJ
   Matos, MA
   Pakstis, LM
   Taboas, JM
   Hudson, SD
   Cicerone, MT
AF Dunkers, J. P.
   Lee, H-J.
   Matos, M. A.
   Pakstis, L. M.
   Taboas, J. M.
   Hudson, S. D.
   Cicerone, M. T.
TI Effect of surface modification on protein retention and cell
   proliferation under strain
SO ACTA BIOMATERIALIA
LA English
DT Article
DE Equibiaxial strain; Laminin; Polydimethylsiloxane; Smooth muscle cells;
   X-ray reflectivity
ID VASCULAR SMOOTH-MUSCLE; X-RAY REFLECTIVITY; FIBRONECTIN ADSORPTION;
   IN-VITRO; LAMININ; MEMBRANES; ADHESION; NETWORK; PEPTIDE; BILAYER
AB When culturing cells on flexible surfaces, it is important to consider extracellular matrix treatments that will remain on the surface under mechanical strain. Here we investigate differences in laminin deposited on oxidized polydimethylsiloxane (PDMS) with plasma treatment (plasma-only) vs. plasma and aminopropyltrimethoxysilane treatment (silane-linked). We use specular X-ray reflectivity (SXR), transmission electron microscopy (TEM), and immunofluorescence to probe the quantity and uniformity of laminin. The surface coverage of laminin is approximately 45% for the plasma-only and 50% for the silane-linked treatment as determined by SXR. TEM and immunofluorescence reveal additional islands of laminin aggregates on the plasma-only PDMS compared with the relatively smooth and uniform silane-linked laminin surface. We also examine laminin retention under strain and vascular smooth muscle cell viability and proliferation under static and strain conditions. Equibiaxial stretching of the PDMS surfaces shows greatly improved retention of the silane-linked laminin over plasma-only. There are significantly more cells on the silane-linked surface after 4 days of equibiaxial strain. Published by Elsevier Ltd. on behalf of Acta Materialia Inc.
C1 [Dunkers, J. P.; Lee, H-J.; Matos, M. A.; Pakstis, L. M.; Hudson, S. D.; Cicerone, M. T.] Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA.
   [Taboas, J. M.] NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bethesda, MD 20892 USA.
RP Dunkers, JP (reprint author), Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA.
EM joy.dunkers@nist.gov
RI Sanders, Susan/G-1957-2011
NR 28
TC 4
Z9 4
U1 0
U2 12
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1742-7061
J9 ACTA BIOMATER
JI Acta Biomater.
PD JUL
PY 2011
VL 7
IS 7
BP 2902
EP 2909
DI 10.1016/j.actbio.2011.04.005
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 785JT
UT WOS:000292226000015
PM 21515419
ER

PT J
AU Becker, KG
AF Becker, Kevin G.
TI Autism, immune dysfunction and Vitamin D
SO ACTA PSYCHIATRICA SCANDINAVICA
LA English
DT Letter
ID ORIGIN
C1 NIA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
RP Becker, KG (reprint author), NIA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
EM beckerk@grc.nia.nih.gov
OI Becker, Kevin/0000-0002-6794-6656
FU Intramural NIH HHS
NR 5
TC 3
Z9 3
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0001-690X
J9 ACTA PSYCHIAT SCAND
JI Acta Psychiatr. Scand.
PD JUL
PY 2011
VL 124
IS 1
BP 74
EP 74
DI 10.1111/j.1600-0447.2011.01688.x
PG 1
WC Psychiatry
SC Psychiatry
GA 784IE
UT WOS:000292149500011
PM 21395563
ER

PT J
AU Wele, M
   Djimde, AA
   Guindo, A
   Beavogui, AH
   Traore, IZ
   Sadou, A
   Blaise, D
   Diallo, DA
   Wellems, TE
   Doumbo, OK
AF Wele, Mamadou
   Djimde, Abdoulaye A.
   Guindo, Aldiouma
   Beavogui, Abdoul H.
   Traore, Isaac Z.
   Sadou, Aboubacar
   Blaise, Dackouo
   Diallo, Dapa A.
   Wellems, Thomas E.
   Doumbo, Ogobara K.
TI High frequency of PfCRT 76T in two Malian villages and its prevalence in
   severe relative to non-severe malaria
SO ACTA TROPICA
LA English
DT Article
DE Severe malaria; Non-severe malaria; PfCRT 76T; Drug resistance
ID PLASMODIUM-FALCIPARUM; CHLOROQUINE RESISTANCE; VAR GENES; CHILDREN;
   PARASITES; EFFICACY; DISEASE; AREA
AB We investigated PfCRT 76T mutation in severe and non-severe malaria in Southern Mali. One hundred and ninety three severe malaria cases were each matched against two non-severe malaria cases. Patients with G6PD deficiency and any known hemoglobin abnormality were excluded. PfCRT 76T was present in 60.8% (n = 386) non-severe malaria cases and in 77.2% (n = 193) severe malaria cases (p < 0.0001). In children 5 years or younger, these proportions were 62.9% (n = 294) vs. 73.5% (n = 147), respectively (p < 0.01). PfCRT 76T was therefore associated with malaria severity in this setting of Mali. (C) 2011 Elsevier By. All rights reserved.
C1 [Wele, Mamadou; Djimde, Abdoulaye A.; Guindo, Aldiouma; Beavogui, Abdoul H.; Traore, Isaac Z.; Sadou, Aboubacar; Blaise, Dackouo; Diallo, Dapa A.; Doumbo, Ogobara K.] Univ Bamako, Fac Med Pharm & Dent, Dept Epidemiol Parasit Dis, Malaria Res & Training Ctr, Bamako, Mali.
   [Wellems, Thomas E.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Djimde, AA (reprint author), Univ Bamako, Fac Med Pharm & Odontostomatol, Malaria Res & Training Ctr, Dept Epidemiol Parasit Dis, POB 1805, Bamako, Mali.
EM adjimde@icermali.org
FU International Atomic Energy Agency (IAEA) [RAF/6025];
   MIM-UNICEF-UNDP-World Bank-WHO; TDR [A20238]; NIAID/NIH [5 RO1
   A144824-03]; European and Developing Countries Clinical Trail
   Partnership Senior Fellowship [2004.2.C.f1]; Howard Hughes Medical
   Institution [55005502]; University of Bamako
FX Financially supported by grants from International Atomic Energy Agency
   (IAEA) RAF/6025; MIM-UNICEF-UNDP-World Bank-WHO Special Programme for
   Research and TDR Grant # A20238. NIAID/NIH Supplement Award 5 RO1
   A144824-03, European and Developing Countries Clinical Trail Partnership
   Senior Fellowship (Grant # 2004.2.C.f1), Howard Hughes Medical
   Institution International Schlorship (Grant # 55005502), Training grant
   from University of Bamako. Mali and PER-AUF Agence Universitaire de la
   Francophonie, and the Intramural Research Program of the NIH, NIAID,
   USA.
NR 17
TC 6
Z9 6
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0001-706X
J9 ACTA TROP
JI Acta Trop.
PD JUL
PY 2011
VL 119
IS 1
BP 11
EP 13
DI 10.1016/j.actatropica.2011.01.002
PG 3
WC Parasitology; Tropical Medicine
SC Parasitology; Tropical Medicine
GA 787DU
UT WOS:000292357600003
PM 21300016
ER

PT J
AU Justinova, Z
   Ferre, S
   Redhi, GH
   Mascia, P
   Stroik, J
   Quarta, D
   Yasar, S
   Muller, CE
   Franco, R
   Goldberg, SR
AF Justinova, Zuzana
   Ferre, Sergi
   Redhi, Godfrey H.
   Mascia, Paola
   Stroik, Jessica
   Quarta, Davide
   Yasar, Sevil
   Mueller, Christa E.
   Franco, Rafael
   Goldberg, Steven R.
TI Reinforcing and neurochemical effects of cannabinoid CB1 receptor
   agonists, but not cocaine, are altered by an adenosine A2A receptor
   antagonist
SO ADDICTION BIOLOGY
LA English
DT Article
DE Adenosine A2A receptor; anandamide; dopamine; reinforcement;
   reinstatement; THC
ID RAT NUCLEUS-ACCUMBENS; MESOLIMBIC DOPAMINE TRANSMISSION; ACID AMIDE
   HYDROLASE; SQUIRREL-MONKEYS; A(2A) RECEPTORS;
   DELTA(9)-TETRAHYDROCANNABINOL THC; STRIATAL FUNCTION; SEEKING BEHAVIOR;
   BASAL GANGLIA; BRAIN REWARD
AB Several recent studies suggest functional and molecular interactions between striatal adenosine A2A and cannabinoid CB1 receptors. Here, we demonstrate that A2A receptors selectively modulate reinforcing effects of cannabinoids. We studied effects of A2A receptor blockade on the reinforcing effects of delta-9-tetrahydrocannabinol (THC) and the endogenous CB1 receptor ligand anandamide under a fixed-ratio schedule of intravenous drug injection in squirrel monkeys. A low dose of the selective adenosine A2A receptor antagonist MSX-3 (1 mg/kg) caused downward shifts of THC and anandamide dose-response curves. In contrast, a higher dose of MSX-3 (3 mg/kg) shifted THC and anandamide dose-response curves to the left. MSX-3 did not modify cocaine or food pellet self-administration. Also, MSX-3 neither promoted reinstatement of extinguished drug-seeking behavior nor altered reinstatement of drug-seeking behavior by non-contingent priming injections of THC. Finally, using in vivo microdialysis in freely-moving rats, a behaviorally active dose of MSX-3 significantly counteracted THC-induced, but not cocaine-induced, increases in extracellular dopamine levels in the nucleus accumbens shell. The significant and selective results obtained with the lower dose of MSX-3 suggest that adenosine A2A antagonists acting preferentially at presynaptic A2A receptors might selectively reduce reinforcing effects of cannabinoids that lead to their abuse. However, the appearance of potentiating rather than suppressing effects on cannabinoid reinforcement at the higher dose of MSX-3 would likely preclude the use of such a compound as a medication for cannabis abuse. Adenosine A2A antagonists with more selectivity for presynaptic versus postsynaptic receptors could be potential medications for treatment of cannabis abuse.
C1 [Justinova, Zuzana; Ferre, Sergi; Redhi, Godfrey H.; Mascia, Paola; Stroik, Jessica; Quarta, Davide; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,US Dept HHS,BRC, Baltimore, MD 21224 USA.
   [Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
   [Yasar, Sevil] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21218 USA.
   [Mueller, Christa E.] Univ Bonn, Inst Pharmaceut, PharmaCtr Bonn, D-5300 Bonn, Germany.
   [Franco, Rafael] Univ Barcelona, Dept Biochem & Mol Biol, E-08007 Barcelona, Spain.
RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,US Dept HHS,BRC, 251 Bayview Blvd,Suite 200 NIDA,Rm 05A711, Baltimore, MD 21224 USA.
EM sgoldber@mail.nih.gov
RI Justinova, Zuzana/A-9109-2011; Ferre, Sergi/K-6115-2014; Franco,
   Rafael/C-3694-2015; Muller, Christa/C-7748-2014
OI Justinova, Zuzana/0000-0001-5793-7484; Ferre, Sergi/0000-0002-1747-1779;
   Franco, Rafael/0000-0003-2549-4919; Muller, Christa/0000-0002-0013-6624
FU National Institute on Drug Abuse, National Institutes of Health,
   Department of Health and Human Services, Baltimore, MD
FX This research was supported by the Intramural Research Program of the
   National Institute on Drug Abuse, National Institutes of Health,
   Department of Health and Human Services, Baltimore, MD.
NR 48
TC 31
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U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1369-1600
J9 ADDICT BIOL
JI Addict. Biol.
PD JUL
PY 2011
VL 16
IS 3
BP 405
EP 415
DI 10.1111/j.1369-1600.2010.00258.x
PG 11
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 783QL
UT WOS:000292098900005
PM 21054689
ER

PT J
AU Camp, MC
   Feyder, M
   Ihne, J
   Palachick, B
   Hurd, B
   Karlsson, RM
   Noronha, B
   Chen, YC
   Coba, MP
   Grant, SGN
   Holmes, A
AF Camp, Marguerite C.
   Feyder, Michael
   Ihne, Jessica
   Palachick, Benjamin
   Hurd, Benita
   Karlsson, Rose-Marie
   Noronha, Bianca
   Chen, Yi-Chyan
   Coba, Marcelo P.
   Grant, Seth G. N.
   Holmes, Andrew
TI A novel role for PSD-95 in mediating ethanol intoxication, drinking and
   place preference
SO ADDICTION BIOLOGY
LA English
DT Article
DE Alcohol; alcoholism; glutamate; MAGUK; mouse; synapse
ID NMDA RECEPTOR NR2A; DRUG-ADDICTION; POSTSYNAPTIC DENSITY; GLUTAMATE
   RECEPTORS; KNOCKOUT MICE; ALCOHOLISM; SENSITIVITY; PLASTICITY;
   SEROTONIN; PROTEINS
AB The synaptic signaling mechanisms mediating the behavioral effects of ethanol (EtOH) remain poorly understood. Post-synaptic density 95 (PSD-95, SAP-90, Dlg4) is a key orchestrator of N-methyl-D-aspartate receptors (NMDAR) and glutamatergic synapses, which are known to be major sites of EtOH's behavioral actions. However, the potential contribution of PSD-95 to EtOH-related behaviors has not been established. Here, we evaluated knockout (KO) mice lacking PSD-95 for multiple measures of sensitivity to the acute intoxicating effects of EtOH (ataxia, hypothermia, sedation/hypnosis), EtOH drinking under conditions of free access and following deprivation, acquisition and long-term retention of EtOH conditioned place preference (CPP) (and lithium chloride-induced conditioned taste aversion), and intoxication-potentiating responses to NMDAR antagonism. PSD-95 KO exhibited increased sensitivity to the sedative/hypnotic, but not ataxic or hypothermic, effects of acute EtOH relative to wild-type controls (WT). PSD-95 KO consumed less EtOH than WT, particularly at higher EtOH concentrations, although increases in KO drinking could be induced by concentration-fading and deprivation. PSD-95 KO showed normal EtOH CPP 1 day after conditioning, but showed significant aversion 2 weeks later. Lithium chloride-induced taste aversion was impaired in PSD-95 KO at both time points. Finally, the EtOH-potentiating effects of the NMDAR antagonist MK-801 were intact in PSD-95 KO at the dose tested. These data reveal a major, novel role for PSD-95 in mediating EtOH behaviors, and add to growing evidence that PSD-95 is a key mediator of the effects of multiple abused drugs.
C1 [Camp, Marguerite C.; Feyder, Michael; Ihne, Jessica; Palachick, Benjamin; Hurd, Benita; Karlsson, Rose-Marie; Noronha, Bianca; Holmes, Andrew] NIAAA, NIH, Sect Behav Sci & Genet, Lab Integrat Neurosci, Rockville, MD 20852 USA.
   [Chen, Yi-Chyan] Buddhist Tzu Chi Gen Hosp, Taipei Branch, Hualien, Taiwan.
   [Coba, Marcelo P.] Wellcome Trust Sanger Inst, Cambridge, England.
RP Camp, MC (reprint author), NIAAA, NIH, Sect Behav Sci & Genet, Lab Integrat Neurosci, 5625 Fishers Ln, Rockville, MD 20852 USA.
EM campmc@mail.nih.gov
OI Reed, Jessica/0000-0003-0550-7284
FU National Institute of Alcohol Abuse and Alcoholism [Z01-AA000411];
   Wellcome Trust
FX We are very grateful to Christina Gremel for helpful discussions.
   Research supported by the National Institute of Alcohol Abuse and
   Alcoholism Intramural Research Program (Z01-AA000411) and the Wellcome
   Trust Genes to Cognition Programme.
NR 41
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U1 2
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1355-6215
J9 ADDICT BIOL
JI Addict. Biol.
PD JUL
PY 2011
VL 16
IS 3
BP 428
EP 439
DI 10.1111/j.1369-1600.2010.00282.x
PG 12
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 783QL
UT WOS:000292098900007
PM 21309945
ER

PT J
AU Griner, R
   Williams, PL
   Read, JS
   Seage, GR
   Crain, M
   Yogev, R
   Hazra, R
   Rich, K
AF Griner, Raymond
   Williams, Paige L.
   Read, Jennifer S.
   Seage, George R., III
   Crain, Marilyn
   Yogev, Ram
   Hazra, Rohan
   Rich, Kenneth
TI In Utero and Postnatal Exposure to Antiretrovirals Among HIV-Exposed But
   Uninfected Children in the United States
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID TENOFOVIR DISOPROXIL FUMARATE; INFECTED WOMEN; MACACA-MULATTA;
   TRANSMISSION; PREVENTION; PREGNANCY; TRENDS; BIRTH
AB An increasing number of antiretroviral agents (ARVs) are approved for use, but their use during pregnancy in the United States has not been completely described. We used data from the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring for ART Toxicities (SMARTT) study, a United States-based prospective cohort study of HIV-exposed but uninfected children, to assess temporal trends and maternal characteristics associated with the use of ARVs during pregnancy. The proportion of children exposed in utero to ARVs was calculated over time. A multivariable logistic regression model was used to estimate associations of maternal characteristics with use of highly active antiretroviral therapy (HAART) during pregnancy. We studied 1768 HIV-exposed but uninfected children born between 1995 and 2009 and enrolled in SMARTT. Prenatal HAART exposure increased from 19% in 1997 to 88% in 2009. Of children born in 2009, 99% had prenatal exposure to NRTIs (including zidovudine, 73%; lamivudine, 72%; tenofovir, 39%; and emtricitabine, 37%). Exposure to protease inhibitors increased from 15% in 1997 to 86% in 2009, while exposure to non-nucleoside reverse transcriptase inhibitors (NNRTIs) declined from 33% in 2003 to 11% in 2009. Higher maternal HIV RNA viral load (VL) concentration, lower maternal CD4 count, and earlier timing of the first maternal CD4 or VL measurement during pregnancy were associated with increased odds of HAART exposure. Prenatal HAART exposure has increased but is not universal. As ARV use during pregnancy continues to evolve, follow-up of children is needed to assess long-term effects of ARV exposures.
C1 [Griner, Raymond; Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02135 USA.
   [Read, Jennifer S.; Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
   [Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02135 USA.
   [Crain, Marilyn] Univ Alabama, Med Sch Birmingham, Birmingham, AL USA.
   [Yogev, Ram] Childrens Mem Hosp, Chicago, IL 60614 USA.
   [Rich, Kenneth] Univ Illinois, Chicago Coll Med, Chicago, IL USA.
RP Griner, R (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 651 Huntington Ave, Boston, MA 02135 USA.
EM rgriner@sdac.harvard.edu
FU Eunice Kennedy Shriver National Institute of Child Health; National
   Institute of Allergy and Infectious Diseases; National Institute on Drug
   Abuse; National Institute of Mental Health; National Institute of
   Deafness and Other Communication Disorders; National Heart Lung and
   Blood Institute; National Institute of Neurological Disorders and
   Stroke; National Institute on Alcohol Abuse and Alcoholism; Harvard
   University School of Public Health [U01 HD052102-04]; Tulane University
   School of Medicine [U01 HD052104-01]
FX We thank the children and families for their participation in the PHACS
   protocol "Surveillance Monitoring for ART Toxicities" (SMARTT), and the
   individuals and institutions involved in the conduct of PHACS SMARTT.
   The study was supported by the Eunice Kennedy Shriver National Institute
   of Child Health and Human Development with co-funding from the National
   Institute of Allergy and Infectious Diseases, the National Institute on
   Drug Abuse, the National Institute of Mental Health, National Institute
   of Deafness and Other Communication Disorders, the National Heart Lung
   and Blood Institute, National Institute of Neurological Disorders and
   Stroke, and the National Institute on Alcohol Abuse and Alcoholism,
   through cooperative agreements with the Harvard University School of
   Public Health (U01 HD052102-04) (Principal Investigator: George R. Seage
   III; Project Director: Julie Alperen) and the Tulane University School
   of Medicine (U01 HD052104-01) (Principal Investigator: Russell Van Dyke;
   Co-Principal Investigator: Kenneth Rich; Project Director: Patrick
   Davis). Data management services were provided by Frontier Science and
   Technology Research Foundation (PI: Suzanne Siminski), and regulatory
   services and logistical support were provided by Westat, Inc (PI: Mercy
   Swatson). The conclusions and opinions expressed in this article are
   those of the authors and do not necessarily reflect those of the
   National Institutes of Health or U.S. Department of Health and Human
   Services.
NR 18
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U1 0
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD JUL
PY 2011
VL 25
IS 7
BP 385
EP 394
DI 10.1089/apc.2011.0068
PG 10
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 784DW
UT WOS:000292135900001
PM 21992592
ER

PT J
AU Mellins, CA
   Tassiopoulos, K
   Malee, K
   Moscicki, AB
   Patton, D
   Smith, R
   Usitalo, A
   Allison, SM
   Van Dyke, R
   Seage, GR
AF Mellins, Claude A.
   Tassiopoulos, Katherine
   Malee, Kathleen
   Moscicki, Anna-Barbara
   Patton, Doyle
   Smith, Renee
   Usitalo, Ann
   Allison, Susannah M.
   Van Dyke, Russell
   Seage, George R., III
CA Pediat Hiv Aids Cohort Study
TI Behavioral Health Risks in Perinatally HIV-Exposed Youth: Co-Occurrence
   of Sexual and Drug Use Behavior, Mental Health Problems, and
   Nonadherence to Antiretroviral Treatment
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; PATIENT-RELATED RISKS; INFECTED YOUTH;
   MEDICATION ADHERENCE; UNITED-STATES; PSYCHIATRIC-DISORDERS; REPORTED
   ADHERENCE; CHILDREN; ADOLESCENTS; THERAPY
AB In a sample of perinatally HIV-infected (PHIV +) and perinatally HIV-exposed, uninfected (PHEU) adolescents, we examined the co-occurrence of behavioral health risks including mental health problems, onset of sexual and drug use behaviors, and (in PHIV + youth) nonadherence to antiretroviral therapy (ART). Participants, recruited from 2007 to 2010, included 349 youth, ages 10-16 years, enrolled in a cohort study examining the impact of HIV infection and ART. Measures of the above behavioral health risks were administered to participants and primary caregivers. Nearly half the participants met study criteria for at least one behavioral health risk, most frequently, mental health problems (28%), with the onset of sexual activity and substance use each reported by an average of 16%. Among the sexually active, 65% of PHIV + and 50% of PHEU youth reported unprotected sex. For PHIV + youth, 34% reported recent ART nonadherence, of whom 45% had detectable HIV RNA levels. Between 16% (PHIV +) and 11% (PHEU) of youth reported at least two behavioral health risks. Older age, but not HIV status, was associated with having two or more behavioral health risks versus none. Among PHIV + youth, living with a birth mother (versus other caregivers) and detectable viral load were associated with co-occurrence of behavioral health risks. In conclusion, this study suggests that for both PHIV + and PHEU youth, there are multiple behavioral health risks, particularly mental health problems, which should be targeted by service systems that can integrate prevention and treatment efforts.
C1 [Mellins, Claude A.] New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, New York, NY 10032 USA.
   [Mellins, Claude A.] Columbia Univ, New York, NY USA.
   [Tassiopoulos, Katherine; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   [Malee, Kathleen] NW Univ Feinberg, Sch Med, Dept Child & Adolescent Psychiat, Chicago, IL USA.
   [Moscicki, Anna-Barbara] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
   [Patton, Doyle] Childrens Diagnost Treatment Ctr, Ft Lauderdale, FL USA.
   [Smith, Renee] Univ Illinois, Dept Pediat, Chicago, IL USA.
   [Usitalo, Ann] Univ Florida, Dept Pediat, Jacksonville, FL USA.
   [Allison, Susannah M.] NIMH, Bethesda, MD 20892 USA.
   [Van Dyke, Russell] Tulane Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA 70118 USA.
RP Mellins, CA (reprint author), New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, Box 15,1051 Riverside Dr, New York, NY 10032 USA.
EM cam14@columbia.edu
RI Hunter, Scott/S-7866-2016
OI Hunter, Scott/0000-0001-7434-2327
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development; National Institute of Allergy and Infectious Diseases;
   National Institute on Drug Abuse; National Institute of Mental Health;
   National Institute of Deafness; National Heart Lung and Blood Institute;
   National Institute of Neurological Disorders and Stroke; National
   Institute on Alcohol Abuse and Alcoholism; Harvard University School of
   Public Health [U01 HD052102-04]; Tulane University School of Medicine
   [U01 HD052104-01]
FX We thank the children and families for their participation in the PHACS
   Adolescent Master Protocol (AMP), and the individuals and institutions
   involved in the conduct of PHACS AMP. The study was supported by the
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development with cofunding from the National Institute of Allergy and
   Infectious Diseases, the National Institute on Drug Abuse, the National
   Institute of Mental Health, National Institute of Deafness and Other
   Communication Disorders, the National Heart Lung and Blood Institute,
   National Institute of Neurological Disorders and Stroke, and the
   National Institute on Alcohol Abuse and Alcoholism, through cooperative
   agreements with the Harvard University School of Public Health (U01
   HD052102-04; Principal Investigator: George Seage; Project Director:
   Julie Alperen) and the Tulane University School of Medicine (U01
   HD052104-01; Principal Investigator: Russell Van Dyke; Co-Principal
   Investigator: Kenneth Rich; Project Director: Patrick Davis). Data
   management services were provided by Frontier Science and Technology
   Research Foundation (Principal Investigator: Suzanne Siminski), and
   regulatory services and logistical support were provided by Westat, Inc.
   (Principal Investigator: Mercy Swatson).
NR 59
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U1 2
U2 7
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD JUL
PY 2011
VL 25
IS 7
BP 413
EP 422
DI 10.1089/apc.2011.0025
PG 10
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 784DW
UT WOS:000292135900004
PM 21992620
ER

PT J
AU Young, JM
   Turpin, JA
   Musib, R
   Sharma, OK
AF Young, Janet M.
   Turpin, Jim A.
   Musib, Runa
   Sharma, Opendra K.
TI Outcomes of a National Institute of Allergy and Infectious Diseases
   Workshop on Understanding HIV-Exposed but Seronegative Individuals
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HOMOSEXUAL-MEN; TYPE-1 TRANSMISSION;
   IN-VITRO; RESISTANCE; ACQUISITION; EXPRESSION; CHILDREN; PARTNERS; RISK
AB The fascinating conundrum that some individuals who are exposed to HIV in ways that would make viral transmission highly likely, yet are able to remain uninfected, has been appreciated for many years. As early as the late 1980s, reports of such individuals began appearing in the HIV/AIDS literature. Despite the critical importance of understanding possible mechanisms of natural HIV resistance for developing effective prevention strategies, numerous obstacles have prevented this essential area of scientific exploration from moving forward. The Workshop held on July 8-9, 2010 and supported by the Office of AIDS Research (OAR), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute on Drug Abuse (NIDA) at the NIH hosted 200 participants and utilized the expertise of 42 AIDS researchers as invited speakers, session chairs, and discussion leaders for presentations and breakout sessions in an attempt to remove some of those obstacles. Accomplishments of the participants included developing a consensus for a new general term for the field, HIV-exposed seronegative (HESN), while recognizing the necessity to identify and utilize secondary descriptive criteria such as exposure level, risk group, duration of seronegativity, or natural resistance. Three key questions for future research were also identified by the group: (1) What is different in HESN versus those who get infected? (2) What is the immune response in HESN and is it just a marker of exposure or a correlate of protection? (3) What are the HESN host factors that help HESN resist infection? This report briefly summarizes the presentations, and describes future directions for addressing these questions and challenges.
C1 [Young, Janet M.; Sharma, Opendra K.] NIAID, Pathogenesis & Basic Res Branch, Basic Sci Program, Div Aids,NIH,HHS, Bethesda, MD 20892 USA.
   [Turpin, Jim A.] NIAID, Microbicide Res Branch, Prevent Sci Program, Div Aids,NIH,HHS, Bethesda, MD 20892 USA.
   [Musib, Runa] NIAID, Henry M Jackson Fdn Advancement Mil Med, Contractor Vaccine Res Program, Div Aids,NIH,HHS, Bethesda, MD 20892 USA.
RP Young, JM (reprint author), 6700-B Rockledge Dr,Room 4152, Bethesda, MD 20892 USA.
EM janet@goldray.com
FU NIH Office of AIDS Research; NIAID Division of AIDS; NIDA
FX We thank Sunil Ahuja, Grace Aldrovandi, Galit Alter, Aftab Ansari, Blake
   Ball, Mike Betts, Persephone Borrow, Kristina Broliden, Mary Carrington,
   Mario Clerici, Myron Cohen, Cynthia Derdeyn, Don Des Jarlais, Roger
   Detels, Carl Dieffenbach, Daniel Douek, Jake Estes, Sarah Fidler, Keith
   Fowke, David Goldstein, Richard Kaslow, Rupert Kaul, Alan Landay,
   Michael Lederman, Jeffrey Lifson, Jairam Lingappa, Jiri Mestecky, Mike
   McCune, Julie McElrath, Andrew McMichael, James Mullins, Thumbi Ndung'u,
   Doug Nixon, Philip Norris, Frank Plummer, Rafik Sekaly, George Shaw,
   Gene Shearer, Georgia Tomaras, Steven Wolinsky, Mark Wainberg, and Bruce
   Walker for their participation as speakers, session chairs, discussants,
   and/or for leading breakout sessions. This workshop was supported by
   funds from the NIH Office of AIDS Research, NIAID Division of AIDS, and
   NIDA. We thank the NIH Scientific Organizing Committee: James Cumins,
   Diana Finzi, Jag Khalsa, Rosemary McKaig, Stuart Shapiro, Opendra
   Sharma, Gene Shearer, Jim Turpin, Fulvia Veronese, and Janet Young. We
   also thank Michael Perez with the Seamon Corporation for logistics and
   Kathleen Muldoon and Cherie Jones for making travel arrangements. We are
   grateful to Susan Plaeger for reviewing this manuscript.
NR 27
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PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD JUL
PY 2011
VL 27
IS 7
BP 737
EP 743
DI 10.1089/aid.2010.0313
PG 7
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 783MO
UT WOS:000292087600006
PM 21142412
ER

PT J
AU George, J
   Cofano, EB
   Lybarger, E
   Louder, M
   Lafont, BAP
   Mascola, JR
   Robert-Guroff, M
   Mattapallil, JJ
AF George, Jeffy
   Cofano, Egidio Brocca
   Lybarger, Elizabeth
   Louder, Mark
   Lafont, Bernard A. P.
   Mascola, John R.
   Robert-Guroff, Marjorie
   Mattapallil, Joseph J.
TI Early Short-Term Antiretroviral Therapy Is Associated with a Reduced
   Prevalence of CD8(+)FoxP3(+) T Cells in Simian Immunodeficiency
   Virus-Infected Controller Rhesus Macaques
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID DEPENDENT CELLULAR CYTOTOXICITY; ACUTE HIV-1 INFECTION; ACUTE SIV
   INFECTION; GASTROINTESTINAL-TRACT; DISEASE PROGRESSION; VIRAL
   REPLICATION; PERIPHERAL-BLOOD; PROTECTIVE EFFICACY; ANTIBODY ACTIVITIES;
   IMMUNE ACTIVATION
AB Regulatory T cells contain a mix of CD4 and CD8 T cell subsets that can suppress immune activation and at the same time suppress immune responses, thereby contributing to disease progression. Recent studies have shown that an increased prevalence of CD8(+)FoxP3(+) T regulatory cells was associated with immune suppression and diminished viral control in simian immunodeficiency virus (SIV)-infected rhesus macaques. Preventing an increase in the prevalence of CD8 T regulatory subsets is likely to lead to a better long-term outcome. Here we show that short-term antiretroviral therapy initiated within 1 week after SIV infection was associated with lower viral set point and immune activation after withdrawal of therapy as compared to untreated animals. Early short-term treated controller animals were found to have better SIV-specific immune responses and a significantly lower prevalence of immunosuppressive CD8(+)FoxP3(+) T cells. Lower levels of CD8(+)FoxP3(+) T cells coincided with preservation of CD4(+)FoxP3(+) T cells at homeostatic levels, and significantly correlated with lower immune activation, suggesting a role for viral infection-driven immune activation in the expansion of CD8(+)FoxP3(+) T cells. Interestingly, initiation of continuous therapy later in infection did not reduce the increased prevalence of CD8(+)FoxP3(+) T cells to homeostatic levels. Taken together, our results suggest that early antiretroviral therapy preserves the integrity of the immune system leading to a lower viral set point in controller animals, and prevents alterations in the homeostatic balance between CD4(+) and CD8(+) T regulatory cells that could aid in better long-term outcome.
C1 [George, Jeffy; Mattapallil, Joseph J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
   [Cofano, Egidio Brocca; Robert-Guroff, Marjorie] NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Lybarger, Elizabeth; Louder, Mark; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Lafont, Bernard A. P.] NIAID, Mol Microbiol Lab, NIH, 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
RI Lafont, Bernard/B-7236-2014
FU National Institutes of Allergy and Infectious diseases (NIAID)
   [AI07812]; National Institute of Dental and Craniofacial Research
   (NIDCR) [DE018339, DE019397]; NIH-NIAID; NCI
FX We thank Sandra Bixler, Andrew Moore, and Muhamuda Kader at Uniformed
   Services University for assistance in processing some of the samples and
   assays; Jeffrey Lifson and Michael Piatak for assistance with plasma
   viral load assays; Malcolm Martin at the Laboratory of Molecular
   Microbiology for some uninfected samples; Karen Wolcott and Kateryna
   Lund at the Biomedical Instrumentation Center; and Dr. Deborah Weiss and
   Jim Treece at ABL, Inc., Rockville, MD for expert assistance with the
   animals. The studies described here were supported by Grants AI07812
   from National Institutes of Allergy and Infectious diseases (NIAID) and
   DE018339 and DE019397 from the National Institute of Dental and
   Craniofacial Research (NIDCR) awarded to J.J.M. This research was
   supported in part by the Intramural Research Program of the NIH-NIAID
   and NCI. The content is solely the responsibility of the authors and
   does not necessarily represent the official views of NIAID, NIDCR, NCI,
   or the National Institutes of Health.
NR 72
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U2 4
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PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD JUL
PY 2011
VL 27
IS 7
BP 763
EP 775
DI 10.1089/aid.2010.0251
PG 13
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 783MO
UT WOS:000292087600010
PM 21142402
ER

PT J
AU Buadi, F
   Hsing, AW
   Katzmann, JA
   Pfeiffer, RM
   Waxman, A
   Yeboah, ED
   Biritwum, RB
   Tettey, Y
   Adjei, A
   Chu, LW
   DeMarzo, A
   Netto, GJ
   Dispenzieri, A
   Kyle, RA
   Rajkumar, SV
   Landgren, O
AF Buadi, Francis
   Hsing, Ann W.
   Katzmann, Jerry A.
   Pfeiffer, Ruth M.
   Waxman, Adam
   Yeboah, Edward D.
   Biritwum, Richard B.
   Tettey, Yao
   Adjei, Andrew
   Chu, Lisa W.
   DeMarzo, Angelo
   Netto, George J.
   Dispenzieri, Angela
   Kyle, Robert A.
   Rajkumar, S. Vincent
   Landgren, Ola
TI High prevalence of polyclonal hypergamma-globulinemia in adult males in
   Ghana, Africa
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY;
   IMMUNE-SYSTEM; UNITED-STATES; SERUM IMMUNOGLOBULINS; RACIAL-DIFFERENCES;
   CIGARETTE-SMOKING; 2 PARTS; RISK
AB Chronic antigenic stimulation is associated with hypergamma-globulinemia. Higher rates of hypergamma-globulinemia in tropical populations are maintained even with migration to temperate regions. We conducted a population-based screening study to assess the prevalence and risk factors for hypergamma-globulinemia in Ghana, Africa. 917 Ghanaian males (50-74 years) underwent in-person interviews and health examinations. Serum from all persons was analyzed by electrophoresis performed on agarose gel; serum with a discrete/localized band was subjected to immunofixation. 54 persons with monoclonal proteins were excluded and 17 samples were insufficient for analysis. Using logistic regression and Chi-square statistics we analyzed patterns of hypergamma-globulinemia. Among 846 study subjects, the median gamma-globulin level was 1.86 g/dL. On the basis of a U.S. reference, 616 (73%) had hypergamma-globulinemia (>1.6 g/dL) and 178 (21%) had gamma-globulin levels >2.17 gm/dl. On multivariate analyses, lower education status (P = 0.0013) and never smoking (P = 0.038) were associated with increased gamma-globulin levels. Self-reported history of syphilis was associated with hypergamma-globulinemia. We conclude that three quarters of this population-based adult Ghanaian male sample had hypergamma-globulinemia with gamma-globulin levels >1.6 g/dL. Future studies are needed to uncover genetic and environmental underpinnings of our finding, and to define the relationship between hypergamma-globulinemia, monoclonal gammopathy of undetermined significance (MGUS), and multiple myeloma. Am. J. Hematol. 86:554-558, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Buadi, Francis; Katzmann, Jerry A.; Dispenzieri, Angela; Kyle, Robert A.; Rajkumar, S. Vincent] Mayo Clin, Div Hematol, Dept Internal Med, Coll Med, Rochester, MN 55905 USA.
   [Hsing, Ann W.] NCI, Infect & Immunol Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Waxman, Adam; Landgren, Ola] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
   [Waxman, Adam] NIH, Clin Res Training Program, Ctr Clin, Bethesda, MD 20892 USA.
   [Yeboah, Edward D.; Biritwum, Richard B.; Tettey, Yao; Adjei, Andrew; Chu, Lisa W.] Univ Ghana, Sch Med, Dept Med, Accra, Ghana.
   [DeMarzo, Angelo; Netto, George J.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21205 USA.
   [DeMarzo, Angelo] Johns Hopkins Univ Hosp, Dept Urol, Baltimore, MD 21205 USA.
   [DeMarzo, Angelo] Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21205 USA.
RP Buadi, F (reprint author), Mayo Clin, Div Hematol, Dept Internal Med, Coll Med, 200 1st St SW, Rochester, MN 55905 USA.
EM Buadi.Francis@mayo.edu; landgreo@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011; 
OI Rajkumar, S. Vincent/0000-0002-5862-1833; Dispenzieri,
   Angela/0000-0001-8780-9512
FU National Cancer Institute [CA 62242, CA 107-476-03]; National Cancer
   Institute, National Institutes of Health, Bethesda, Maryland
FX Contract grant sponsor: National Cancer Institute; Contract grant
   numbers: CA 62242, CA 107-476-03; Contract grant sponsor: Intramural
   Program of the National Cancer Institute, National Institutes of Health,
   Bethesda, Maryland, The facilities and resources of University of Ghana
   Medical School, Ghana, The Divisions of Hematology, Biostatistics,
   Clinical Biochemistry and Immunology, and Epidemiology at the Mayo
   Clinic, Rochester, Minnesota.
NR 36
TC 3
Z9 3
U1 2
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUL
PY 2011
VL 86
IS 7
BP 554
EP 558
DI 10.1002/ajh.22040
PG 5
WC Hematology
SC Hematology
GA 781MX
UT WOS:000291938000006
PM 21674575
ER

PT J
AU Click, ES
   Cox, B
   Olson, SB
   Grompe, M
   Akkari, Y
   Moreau, LA
   Shimamura, A
   Sternen, DL
   Liu, YJJ
   Leppig, KA
   Matthews, DC
   Parisi, MA
AF Click, Eleanor S.
   Cox, Barbara
   Olson, Susan B.
   Grompe, Markus
   Akkari, Yassmine
   Moreau, Lisa A.
   Shimamura, Akiko
   Sternen, Darci L.
   Liu, Yajuan J.
   Leppig, Kathleen A.
   Matthews, Dana C.
   Parisi, Melissa A.
TI Fanconi Anemia-Like Presentation in an Infant with Constitutional
   Deletion of 21q Including the RUNX1 Gene
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE chromosome breakage; chromosome 21q; thrombocytopenia; Fanconi anemia;
   intellectual disability; chromosome microarray; RUNX1
ID ACUTE MYELOGENOUS LEUKEMIA; FAMILIAL PLATELET DISORDER; ACUTE
   MYELOID-LEUKEMIA; DOWN-SYNDROME; MENTAL-RETARDATION; POINT MUTATIONS;
   THROMBOCYTOPENIA; PREDISPOSITION; CHROMOSOME-21; PHENOTYPE
AB We describe a newborn female with a de novo interstitial deletion of chromosome 21q21.1-22.12 including the RUNX1 gene who had developmental delay, multiple congenital anomalies, tetralogy of Fallot, anemia, and chronic thromobocytopenia requiring frequent platelet transfusions from birth. Because of her physical and hematologic abnormalities, she was tested for Fanconi anemia (FA). Lymphocytes and fibroblasts from this patient demonstrated increased chromosome breakage with exposure to the clastogen mitomycin C, but not, in contrast to most FA patients, to diepoxybutane. Further testing by Western analysis and complementation testing did not show a defect in the function of known Fanconi proteins. Her constitutional deletion was later found to span 13.2Mb by chromosome microarray analysis, encompassing the RUNX1 gene that has been implicated in thrombocytopenia and predisposition to acute myelogenous leukemia (AML) when in the haploinsufficient state. We compare her phenotype to other individuals with similar 21q deletions and thrombocytopenia, as well as those with FA. We suggest that deletion of RUNX1 or another critical gene within the deleted region may result in chromosomal instability similar to that seen in FA. (C) 2011 Wiley-Liss, Inc.
C1 [Parisi, Melissa A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intellectual & Dev Disabil Branch, Ctr Dev Biol & Perinatal Med, Bethesda, MD 20892 USA.
   [Click, Eleanor S.; Shimamura, Akiko; Sternen, Darci L.; Matthews, Dana C.] Seattle Childrens Hosp, Seattle, WA USA.
   [Cox, Barbara; Olson, Susan B.; Grompe, Markus] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
   [Akkari, Yassmine] Legacy Hlth, Legacy Lab Serv, Portland, OR USA.
   [Moreau, Lisa A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Liu, Yajuan J.; Leppig, Kathleen A.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
   [Leppig, Kathleen A.] Grp Hlth Cooperat Puget Sound, Seattle, WA USA.
RP Parisi, MA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intellectual & Dev Disabil Branch, Ctr Dev Biol & Perinatal Med, 6100 Execut Blvd,Room 4B09,MSC 7510, Bethesda, MD 20892 USA.
EM parisima@mail.nih.gov
FU NCRR NIH HHS [UL1 RR024140]
NR 38
TC 11
Z9 11
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUL
PY 2011
VL 155A
IS 7
BP 1673
EP 1679
DI 10.1002/ajmg.a.34024
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 781OZ
UT WOS:000291944700027
PM 21626672
ER

PT J
AU Romero, R
AF Romero, Roberto
TI A celebration of Steven Gabbe's contributions and accomplishments:
   Associate Editor, American Journal of Obstetrics and Gynecology, 1990
   through 2010
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
ID GESTATIONAL DIABETES-MELLITUS; PRESIDENTIAL-ADDRESS; PLACENTAL VILLI;
   ORGAN CULTURE; PREGNANCY; DIAGNOSIS; PROGESTERONE; MANAGEMENT;
   METABOLISM; OUTCOMES
C1 [Romero, Roberto] NICHD, Intramural Div, NIH, DHHS, Bethesda, MD USA.
   [Romero, Roberto] NICHD, Intramural Div, NIH, DHHS, Detroit, MI USA.
   [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
   [Romero, Roberto] Michigan State Univ, E Lansing, MI 48824 USA.
RP Romero, R (reprint author), NICHD, Intramural Div, NIH, DHHS, Bethesda, MD USA.
FU Intramural NIH HHS [Z99 HD999999]
NR 39
TC 0
Z9 0
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JUL
PY 2011
VL 205
IS 1
BP 1
EP 4
DI 10.1016/j.ajog.2011.05.029
PG 4
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 783KX
UT WOS:000292082400013
PM 22088891
ER

PT J
AU Caritis, SN
   Sharma, S
   Venkataramanan, R
   Rouse, DJ
   Peaceman, AM
   Sciscione, A
   Spong, CY
   Varner, MW
   Malone, FD
   Iams, JD
   Mercer, BM
   Thorp, JM
   Sorokin, Y
   Carpenter, M
   Lo, J
   Ramin, S
   Harper, M
AF Caritis, Steve N.
   Sharma, Shringi
   Venkataramanan, Raman
   Rouse, Dwight J.
   Peaceman, Alan M.
   Sciscione, Anthony
   Spong, Catherine Y.
   Varner, Michael W.
   Malone, Fergal D.
   Iams, Jay D.
   Mercer, Brian M.
   Thorp, John M., Jr.
   Sorokin, Yoram
   Carpenter, Marshall
   Lo, Julie
   Ramin, Susan
   Harper, Margaret
CA Eunice Kennedy Shriver Natl Inst
TI Pharmacokinetics of 17-hydroxyprogesterone caproate in multifetal
   gestation
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE 17-hydroxyprogesterone caproate; multifetal gestation; pharmacokinetics
ID ALPHA-HYDROXYPROGESTERONE CAPROATE; 17-ALPHA-HYDROXYPROGESTERONE
   CAPROATE; PRETERM BIRTH; CONTROLLED-TRIAL; PREVENTION; WOMEN;
   PROGESTERONE; RITODRINE; DELIVERY; CERCLAGE
AB OBJECTIVE: The purpose of this study was to define the pharmacokinetic parameters of 17-hydroxyprogesterone caproate (17-OHPC) in multifetal gestation.
   STUDY DESIGN: Blood was obtained at 24-28 weeks' gestation and at 32-35 weeks gestation in 97 women with twin and 26 women with triplet gestation who were receiving 17-OHPC. Six of the women with twins had daily blood sampling for 7 days between 24 and 28 weeks' gestation, and pharmacokinetic parameters were estimated with the use of noncompartmental analysis. Modeling was applied to estimate the population parameters and to simulate various treatment scenarios.
   RESULTS: The apparent half-life of 17-OHPC was 10 days. Body mass index significantly impacted 17-OHPC concentrations, but fetal number and parity did not. Apparent clearance was significantly greater in African American than in white women (P = .025).
   CONCLUSION: This is the first pharmacokinetic analysis of 17-OHPC in pregnant women. Determination of half-life, covariates that affect plasma 17-OHPC concentrations, and the modeling of drug behavior provide insights into this drug's pharmacologic properties during multifetal pregnancy.
C1 [Caritis, Steve N.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA.
   [Venkataramanan, Raman] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA.
   [Sharma, Shringi; Venkataramanan, Raman] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
   [Rouse, Dwight J.] Univ Alabama, Dept Obstet, Birmingham, AL USA.
   [Rouse, Dwight J.] Univ Alabama, Dept Gynecol, Birmingham, AL USA.
   [Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA.
   [Sciscione, Anthony] Drexel Univ, Philadelphia, PA 19104 USA.
   [Varner, Michael W.] Univ Utah, Salt Lake City, UT USA.
   [Malone, Fergal D.] Columbia Univ, New York, NY USA.
   [Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA.
   [Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
   [Thorp, John M., Jr.] Univ N Carolina, Chapel Hill, NC USA.
   [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
   [Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA.
   [Lo, Julie] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
   [Ramin, Susan] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
   [Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
   [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Caritis, SN (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA.
RI Malone, Fergal/D-6233-2012; Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850;
   Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development [HD27869, HD21410, HD40512, HD34136, HD34208, HD40485,
   HD27915, HD40544, HD40560, HD27917, HD40500, HD34116, HD40545, HD27860,
   HD36801]
FX Supported by grants from the Eunice Kennedy Shriver National Institute
   of Child Health and Human Development (HD27869, HD21410, HD40512,
   HD34136, HD34208, HD40485, HD27915, HD40544, HD40560, HD27917, HD40500,
   HD34116, HD40545, HD27860, HD36801) and does not necessarily represent
   the official views of the National Institute of Child Health and Human
   Development or the National Institutes of Health.
NR 22
TC 5
Z9 5
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JUL
PY 2011
VL 205
IS 1
AR 40.e1
DI 10.1016/j.ajog.2011.03.028
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 783KX
UT WOS:000292082400024
PM 21620357
ER

PT J
AU Clark, EAS
   Mele, L
   Wapner, RJ
   Spong, CY
   Sorokin, Y
   Peaceman, A
   Iams, JD
   Leveno, KJ
   Harper, M
   Caritis, SN
   Mercer, BM
   Thorp, JM
   Ramin, SM
   Carpenter, M
   Rouse, DJ
AF Clark, Erin A. S.
   Mele, Lisa
   Wapner, Ronald J.
   Spong, Catherine Y.
   Sorokin, Yoram
   Peaceman, Alan
   Iams, Jay D.
   Leveno, Kenneth J.
   Harper, Margaret
   Caritis, Steve N.
   Mercer, Brian M.
   Thorp, John M.
   Ramin, Susan M.
   Carpenter, Marshall
   Rouse, Dwight J.
CA Eunice Kennedy Shriver Natl Inst
TI Repeated course antenatal steroids, inflammation gene polymorphisms, and
   neurodevelopmental outcomes at age 2
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE antenatal corticosteroids; gene polymorphisms; inflammation;
   interleukin-6; neurodevelopmental delay
ID RANDOMIZED CONTROLLED-TRIAL; PRETERM BIRTH; PROMOTER POLYMORPHISM;
   INTERLEUKIN-6 GENE; MULTIPLE COURSES; CORTICOSTEROIDS; TRANSCRIPTION;
   METAANALYSIS; ASSOCIATION; HAPLOTYPES
AB OBJECTIVE: We sought to evaluate the interaction between repeated-course antenatal corticosteroids and inflammation gene polymorphisms with neurodevelopmental outcomes at age 2 years.
   STUDY DESIGN: We conducted nested case-control analysis of a randomized controlled trial of single-vs repeated-course antenatal corticosteroids. Cases had mental and/or psychomotor delay at age 2 years. Controls had normal neurodevelopment. Previous analyses of 125 cases and 147 controls identified 4 inflammation gene polymorphisms associated with neurodevelopmental delay at age 2 years.
   RESULTS: The interaction between repeated-course corticosteroids and the interleukin (IL)-6-174 genotype with neurodevelopmental delay was significant (P = .046). The IL-6-174 GG genotype was associated with neurodevelopmental delay at age 2 years in the single-course corticosteroid group (odds ratio, 6.47; 95% confidence interval, 1.86-22.50). Exposure to repeated-course antenatal corticosteroids abrogated this genotype effect (odds ratio, 1.30; 95% confidence interval, 0.48-3.54). Results were unchanged after controlling for potential confounders.
   CONCLUSION: Repeated-course antenatal steroids may reduce the increased risk of neurodevelopmental delay at age 2 years associated with IL-6-174 GG genotype.
C1 [Clark, Erin A. S.] Univ Utah, Dept Obstet, Sch Med, Salt Lake City, UT 84132 USA.
   [Clark, Erin A. S.] Univ Utah, Dept Gynecol, Sch Med, Salt Lake City, UT 84132 USA.
   [Wapner, Ronald J.] Drexel Univ, Philadelphia, PA 19104 USA.
   [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
   [Peaceman, Alan] Northwestern Univ, Chicago, IL 60611 USA.
   [Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA.
   [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
   [Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
   [Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
   [Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
   [Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA.
   [Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
   [Carpenter, Marshall] Brown Univ, Providence, RI 02912 USA.
   [Rouse, Dwight J.] Univ Alabama, Birmingham, AL USA.
   [Mele, Lisa] George Washington Univ, Ctr Biostat, Washington, DC USA.
   [Spong, Catherine Y.] NICHHD, Maternal Fetal Med Units Network, Bethesda, MD 20892 USA.
RP Clark, EAS (reprint author), Univ Utah, Dept Obstet, Sch Med, Suite 2B200,30 N 1900 E, Salt Lake City, UT 84132 USA.
EM erin.clark@hsc.utah.edu
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development [HD21410, HD27869, HD27917, HD27860, HD27915, HD34116,
   HD34208, HD34136, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512,
   HD36801]; National Center for Research Resources [M01-RR-000080]
FX Supported by grants from the Eunice Kennedy Shriver National Institute
   of Child Health and Human Development (HD21410, HD27869, HD27917,
   HD27860, HD27915, HD34116, HD34208, HD34136, HD40500, HD40485, HD40544,
   HD40545, HD40560, HD40512, HD36801) and M01-RR-000080 from the National
   Center for Research Resources.
NR 21
TC 0
Z9 0
U1 0
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JUL
PY 2011
VL 205
IS 1
AR 79.e1
DI 10.1016/j.ajog.2011.02.061
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 783KX
UT WOS:000292082400041
PM 21529753
ER

PT J
AU Hamill, N
   Yeo, L
   Romero, R
   Hassan, SS
   Myers, SA
   Mittal, P
   Kusanovic, JP
   Balasubramaniam, M
   Chaiworapongsa, T
   Vaisbuch, E
   Espinoza, J
   Gotsch, F
   Goncalves, LF
   Lee, W
AF Hamill, Neil
   Yeo, Lami
   Romero, Roberto
   Hassan, Sonia S.
   Myers, Stephen A.
   Mittal, Pooja
   Kusanovic, Juan Pedro
   Balasubramaniam, Mamtha
   Chaiworapongsa, Tinnakorn
   Vaisbuch, Edi
   Espinoza, Jimmy
   Gotsch, Francesca
   Goncalves, Luis F.
   Lee, Wesley
TI Fetal cardiac ventricular volume, cardiac output, and ejection fraction
   determined with 4-dimensional ultrasound using spatiotemporal image
   correlation and virtual organ computer-aided analysis
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE contour finder; fetal echocardiography; fetus; 4-dimensional; prenatal
   diagnosis; sonography; spatiotemporal image correlation; STIC; stroke
   volume; 3-dimensional; ultrasound; virtual organ computer-aided
   analysis; VOCAL
ID INTRAUTERINE GROWTH RESTRICTION; NORMAL HUMAN-FETUS; BLOOD-FLOW;
   ECHOCARDIOGRAPHIC EVALUATION; DOPPLER ULTRASONOGRAPHY; UMBILICAL ARTERY;
   REFERENCE RANGES; GESTATIONAL-AGE; STROKE VOLUME; HEART
AB OBJECTIVE: The objective of this study was to quantify fetal cardiovascular parameters using spatiotemporal image correlation (STIC) and virtual organ computer-aided analysis (VOCAL).
   STUDY DESIGN: A cross-sectional study was performed in normal pregnancies (19-42 weeks) to evaluate ventricular volume, stroke volume (SV), cardiac output (CO), and ejection fraction (EF). The CO was also expressed as a function of estimated fetal weight and biometric parameters.
   RESULTS: The following results were found: (1) 184 STIC datasets; (2) with advancing gestation, ventricular volume, SV, CO, and adjusted CO increased, whereas EF decreased; (3) right ventricular (RV) volume was larger than the left ventricular (LV) volume in systole (0.50 vs 0.27 mL; P < .001) and diastole (1.20 vs 1.03 mL; P < .001); (4) there were no differences between the LV and RV in SV, CO, or adjusted CO; and (5) LV EF was greater than the RV EF (72.2 vs 62.4%; P < .001).
   CONCLUSION: Normal fetal cardiovascular physiology is characterized by a larger RV volume and a greater LV EF, resulting in similar LV and RV SV and CO.
C1 [Hamill, Neil; Yeo, Lami; Romero, Roberto; Hassan, Sonia S.; Mittal, Pooja; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Vaisbuch, Edi; Espinoza, Jimmy; Gotsch, Francesca; Goncalves, Luis F.] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   [Hamill, Neil; Yeo, Lami; Romero, Roberto; Hassan, Sonia S.; Mittal, Pooja; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Vaisbuch, Edi; Espinoza, Jimmy; Gotsch, Francesca; Goncalves, Luis F.] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.
   [Hamill, Neil; Yeo, Lami; Romero, Roberto; Hassan, Sonia S.; Mittal, Pooja; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Vaisbuch, Edi; Espinoza, Jimmy; Goncalves, Luis F.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
   [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
   [Balasubramaniam, Mamtha; Lee, Wesley] William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48072 USA.
   [Myers, Stephen A.] Case MetroHlth, Cleveland, OH USA.
RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHHD, Dept Hlth & Human Serv,Hutzel Womens Hosp,NIH, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM prbchiefstaff@med.wayne.edu
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, Department of Health and
   Human Services
FX This study was supported in part by the Perinatology Research Branch,
   Division of Intramural Research, Eunice Kennedy Shriver National
   Institute of Child Health and Human Development, National Institutes of
   Health, Department of Health and Human Services.
NR 56
TC 6
Z9 9
U1 0
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD JUL
PY 2011
VL 205
IS 1
AR 76.e1
DI 10.1016/j.ajog.2011.02.028
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 783KX
UT WOS:000292082400040
PM 21531373
ER

PT J
AU Balaban, RS
   Koretsky, AP
AF Balaban, R. S.
   Koretsky, A. P.
TI Interpretation of P-31 NMR saturation transfer experiments: what you
   can't see might confuse you. Focus on "Standard magnetic resonance-based
   measurements of the P-i -> ATP rate do not index the rate of oxidative
   phosphorylation in cardiac and skeletal muscles"
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Editorial Material
ID CREATINE-KINASE REACTION; IN-VIVO; INVERSION-TRANSFER;
   ADENOSINE-DIPHOSPHATE; EXCHANGE-REACTIONS; KINETICS; ATP; INVIVO; CELLS;
   HEART
C1 [Balaban, R. S.] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Koretsky, A. P.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Balaban, RS (reprint author), NHLBI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rsb@nih.gov
RI Koretsky, Alan/C-7940-2015
OI Koretsky, Alan/0000-0002-8085-4756
NR 40
TC 20
Z9 20
U1 1
U2 6
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD JUL
PY 2011
VL 301
IS 1
BP C12
EP C15
DI 10.1152/ajpcell.00100.2011
PG 4
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 783LN
UT WOS:000292084300002
PM 21490314
ER

PT J
AU Clatworthy, MR
AF Clatworthy, M. R.
TI Targeting B Cells and Antibody in Transplantation
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Review
DE Alloantibody; antibody-mediated rejection; B cells; desensitization;
   regulatory B cells; intravenous immunoglobulin; rituximab
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ACUTE CELLULAR REJECTION; FC-GAMMA-RIIB;
   MEDIATED REJECTION; INTRAVENOUS IMMUNOGLOBULIN; ALLOGRAFT-REJECTION;
   RENAL-TRANSPLANTATION; PROTEASOME INHIBITION; ORGAN-TRANSPLANTATION;
   RHEUMATOID-ARTHRITIS
AB There has been increasing interest in the role played by B cells, plasma cells and their associated antibody in the immune response to an allograft, driven by the need to undertake antibody-incompatible transplantation and evidence suggesting that B cells play a role in acute cellular rejection and in acute and chronic antibody-mediated rejection. A number of immunosuppressive agents have emerged which target B cells, plasma cells and/or antibody, for example, the B cell-depleting CD20 antibody rituximab. This review describes recent developments in the use of such agents, our understanding of the role of B cells in alloimmunity and the application of this knowledge toward novel therapies in transplantation. It also considers the evidence to date suggesting that B cells may act as regulators of an alloimmune response. Thus, future attempts to target B cells will need to address the problem of how to inhibit effector B cells, while enhancing those with regulatory capacity.
C1 [Clatworthy, M. R.] Univ Cambridge Sch Clin Med, Cambridge Inst Med Res, Addenbrookes Hosp, Cambridge CB2 0XY, England.
RP Clatworthy, MR (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM mrc38@cam.ac.uk
FU Wellcome Trust [WT081020]
FX Dr. Clatworthy is funded by a Wellcome Trust Intermediate Fellowship
   (WT081020).
NR 54
TC 56
Z9 59
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUL
PY 2011
VL 11
IS 7
BP 1359
EP 1367
DI 10.1111/j.1600-6143.2011.03554.x
PG 9
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 785WR
UT WOS:000292264000006
PM 21668625
ER

PT J
AU Tvrdonova, V
   Rokic, M
   Kuzyk, P
   Stojilkovic, SS
   Zemkova, H
AF Tvrdonova, V.
   Rokic, M.
   Kuzyk, P.
   Stojilkovic, S. S.
   Zemkova, H.
TI Role of low-conserved areas of extracellular vestibule in function of
   purinergic P2X4 receptor
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Tvrdonova, V.; Rokic, M.; Kuzyk, P.; Zemkova, H.] Acad Sci Czech Republic, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, Prague 4, Czech Republic.
   [Stojilkovic, S. S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RI Tvrdonova Stillerova, Vendula/G-3060-2014; ROKIC, MILOS/O-7204-2014
OI Tvrdonova Stillerova, Vendula/0000-0001-5295-2837; ROKIC,
   MILOS/0000-0002-9148-2716
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD JUL
PY 2011
VL 41
SU 1
BP S46
EP S46
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 972JI
UT WOS:000306273000146
ER

PT J
AU Nilubol, N
   Kebebew, E
AF Nilubol, Naris
   Kebebew, Electron
TI Personalizing Thyroid Cancer Care: Are We There Yet?
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Editorial Material
ID PAPILLARY CARCINOMA; BRAF MUTATION; EXPRESSION
C1 [Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Nilubol, N (reprint author), NCI, Endocrine Oncol Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
NR 7
TC 1
Z9 1
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUL
PY 2011
VL 18
IS 7
BP 1819
EP 1820
DI 10.1245/s10434-011-1735-y
PG 2
WC Oncology; Surgery
SC Oncology; Surgery
GA 777VA
UT WOS:000291652000005
PM 21537869
ER

PT J
AU Swanson, SA
   Crow, SJ
   Le Grange, D
   Swendsen, J
   Merikangas, KR
AF Swanson, Sonja A.
   Crow, Scott J.
   Le Grange, Daniel
   Swendsen, Joel
   Merikangas, Kathleen R.
TI Prevalence and Correlates of Eating Disorders in Adolescents Results
   From the National Comorbidity Survey Replication Adolescent Supplement
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID CANADIAN COMMUNITY SAMPLE; OTHERWISE SPECIFIED EDNOS; FAMILY-BASED
   TREATMENT; MENTAL-HEALTH SURVEY; DSM-IV DISORDERS; ANOREXIA-NERVOSA;
   BULIMIA-NERVOSA; NCS-A; LIFETIME PREVALENCE; PSYCHIATRIC-DISORDER
AB Context: Eating disorders are severe conditions, but little is known about the prevalence or correlates of these disorders from population-based surveys of adolescents.
   Objectives: To examine the prevalence and correlates of eating disorders in a large, reprefentative sample of US adolescents.
   Design: Cross-sectional survey of adolescents with face-to-face interviews using a modified version of the Composite International Diagnostic Interview.
   Setting: Combined household and school adolescent samples.
   Participants: Nationally representative sample of 10 123 adolescents aged 13 to 18 years.
   Main Outcome Measures: Prevalence and correlates of eating disorders and subthreshold conditions.
   Results: Lifetime prevalence estimates of anorexia nervosa, bulimia nervosa, and binge-eating disorder were 0.3%, 0.9%, and 1.6%, respectively. Important differences were observed between eating disorder subtypes concerning sociodemographic correlates, psychiatric comorbidity, role impairment, and suicidality. Although the majority of adolescents with an eating disorder sought some form of treatment, only a minority received treatment specifically for their eating or weight problems. Analyses of 2 related subthreshold conditions suggest that these conditions are often clinically significant.
   Conclusions: Eating disorders and subthreshold eating conditions are prevalent in the general adolescent population. Their impact is demonstrated by generally strong associations with other psychiatric disorders, role impairment, and suicidality. The unmet treatment needs in the adolescent population place these disorders as important public health concerns.
C1 [Swanson, Sonja A.; Merikangas, Kathleen R.] NIMH, Intramural Res Program, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
   [Crow, Scott J.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA.
   [Le Grange, Daniel] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
   [Swendsen, Joel] Natl Ctr Sci Res, Bordeaux, France.
RP Merikangas, KR (reprint author), NIMH, Intramural Res Program, Genet Epidemiol Res Branch, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA.
EM kathleen.merikangas@nih.gov
FU National Institute of Mental Health [Z08-MH002808, U01-MH60220, R01
   MH079979]; Pfizer; GlaxoSmithKline; Ortho-McNeil; Baker Foundation
   (Australia)
FX This work was supported by the Intramural Research Program, National
   Institute of Mental Health. The NCS-A is supported by grants
   Z08-MH002808 and U01-MH60220 from the National Institute of Mental
   Health. Dr Crow is supported by Pfizer, GlaxoSmithKline, and
   Ortho-McNeil. Dr Le Grange is supported by grant R01 MH079979 from the
   National Institute of Mental Health and by the Baker Foundation
   (Australia).
NR 55
TC 336
Z9 346
U1 11
U2 98
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-990X
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD JUL
PY 2011
VL 68
IS 7
BP 714
EP 723
DI 10.1001/archgenpsychiatry.2011.22
PG 10
WC Psychiatry
SC Psychiatry
GA 787DK
UT WOS:000292356600007
PM 21383252
ER

PT J
AU Cheung, HH
   Rennert, OM
AF Cheung, Hoi-Hung
   Rennert, Owen M.
TI Generation of fertile sperm in a culture dish: clinical implications
SO ASIAN JOURNAL OF ANDROLOGY
LA English
DT Editorial Material
ID IN-VITRO DIFFERENTIATION; CELLS
C1 [Cheung, Hoi-Hung; Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Clin & Dev Genom, Bethesda, MD 20892 USA.
RP Rennert, OM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Clin & Dev Genom, Bethesda, MD 20892 USA.
EM rennerto@mail.nih.gov
RI Cheung, Hoi-Hung/G-7605-2011
NR 6
TC 1
Z9 1
U1 0
U2 2
PU SHANGHAI INST MATERIA MEDICA
PI SHANGHAI
PA 555 ZU CHONG ZHI RD, ZHANG JIANG HI-TECH PARK, SHANGHAI, PUDONG 201203,
   PEOPLES R CHINA
SN 1008-682X
J9 ASIAN J ANDROL
JI Asian J. Androl.
PD JUL
PY 2011
VL 13
IS 4
BP 618
EP 619
DI 10.1038/aja.2011.52
PG 2
WC Andrology; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA 786PZ
UT WOS:000292321700024
PM 21642995
ER

PT J
AU Di Lisa, F
   Schulz, R
   Murphy, E
AF Di Lisa, Fabio
   Schulz, Rainer
   Murphy, Elizabeth
TI Preface to Mitochondria and Cardioprotection
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Editorial Material
C1 [Di Lisa, Fabio] Univ Padua, Dept Biomed Sci, I-35131 Padua, Italy.
   [Di Lisa, Fabio] Univ Padua, CNR, Inst Neurosci, I-35131 Padua, Italy.
   [Schulz, Rainer] Univ Giessen, Inst Physiol, D-35390 Giessen, Germany.
   [Murphy, Elizabeth] NHLBI, Cardiac Physiol Sect, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Di Lisa, F (reprint author), Univ Padua, Dept Biomed Sci, Viale G Colombo 3, I-35131 Padua, Italy.
EM dilisa@bio.unipd.it; rainer.schulz@physiologie.med.uni-giessen.de;
   murphy1@nhlbi.nih.gov
OI Di Lisa, Fabio/0000-0001-9757-8818
NR 0
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD JUL
PY 2011
VL 1813
IS 7
SI SI
BP 1261
EP 1262
DI 10.1016/j.bbamcr.2011.05.011
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 784SA
UT WOS:000292177300001
PM 21641495
ER

PT J
AU Sack, MN
AF Sack, Michael N.
TI Caloric excess or restriction mediated modulation of metabolic enzyme
   acetylation-proposed effects on cardiac growth and function
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Review
DE Sirtuins; Acetyltransferase; NAD(+); Acetyl-CoA; Cardiac contraction;
   Cardiac hypertrophy
ID MYOCARDIAL TRIGLYCERIDE CONTENT; ACTIVATED PROTEIN-KINASE; FATTY-ACID
   OXIDATION; STRESS-RESPONSIVE DEACETYLASE; LYSINE ACETYLATION; DIASTOLIC
   FUNCTION; HEART-FAILURE; MITOCHONDRIAL-FUNCTION; SKELETAL-MUSCLE;
   DEPENDENT DEACETYLASE
AB Caloric excess has been postulated to disrupt cardiac function via (i) the generation of toxic intermediates, (ii) via protein glycosylation and (iii) through the generation of reactive oxygen species. It is now increasingly being recognized that the nutrient intermediates themselves may modulate metabolic pathways through the post-translational modifications of metabolic enzymes. In light of the high energy demand of the heart, these nutrient mediated modulations in metabolic pathway functioning may play an important role in cardiac function and in the capacity of the heart to adapt to biomechanical stressors. In this review the role of protein acetylation and deacetylation in the control of metabolic programs is explored. Although not extensively investigated directly in the heart, the emerging data support that these nutrient mediated post-translational regulatory events (i) modulate cardiac metabolic pathways, (ii) integrate nutrient flux mediated post-translational effects with cardiac function and (iii) may be important in the development of cardiac pathology. Areas of investigation that need to be explored are highlighted. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection. Published by Elsevier B.V.
C1 NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10-CRC,Room 5-3150,10 Ctr Dr, Bethesda, MD 20892 USA.
EM sackm@nhlbi.nih.gov
FU Division of Intramural Research of the National Heart Lung and Blood
   Institute of the National Institutes of Health
FX M.N.S. is funded by the Division of Intramural Research of the National
   Heart Lung and Blood Institute of the National Institutes of Health.
NR 100
TC 9
Z9 9
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD JUL
PY 2011
VL 1813
IS 7
SI SI
BP 1279
EP 1285
DI 10.1016/j.bbamcr.2011.01.032
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 784SA
UT WOS:000292177300004
PM 21295620
ER

PT J
AU Murphy, E
   Steenbergen, C
AF Murphy, Elizabeth
   Steenbergen, Charles
TI What makes the mitochondria a killer? Can we condition them to be less
   destructive?
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
LA English
DT Review
DE Mitochondria; Nitric oxide; Phosphorylation; Calcium; Reactive oxygen
   species; Cardioprotection
ID PERMEABILITY TRANSITION PORE; ISCHEMIA-REPERFUSION INJURY; CA-2&-INDUCED
   MEMBRANE TRANSITION; GLYCOGEN-SYNTHASE KINASE-3-BETA; ADENINE-NUCLEOTIDE
   TRANSLOCASE; KINASE-C-EPSILON; NITRIC-OXIDE; ISCHEMIA/REPERFUSION
   INJURY; HEART-MITOCHONDRIA; S-NITROSYLATION
AB Cardioprotection, such as preconditioning and postconditioning, has been shown to result in a significant reduction in cell death. Many of the signaling pathways activated by cardioprotection have been elucidated, but there is still a lack of understanding of the mechanisms by which these signaling pathways reduce cell death. Mitochondria have been reported to be an important player in many types of apoptotic and necrotic cell death. If mitochondria play an important role in cell death, then it seems reasonable to consider that cardioprotective mechanisms might act, at least in part, by opposing mitochondrial cell death pathways. One of the major mechanisms of cell death in ischemia-reperfusion is suggested to be the opening of a large conductance pore in the inner mitochondrial membrane, known as the mitochondrial permeability transition pore. Inhibition of this mitochondrial pore appears to be one of the major mechanisms by which cardioprotection reduces cell death. Cardioprotection activates a number of signaling pathways that reduce the level of triggers (reactive oxygen species and calcium) or enhances inhibitors of the mitochondrial permeability transition pore at the start of reperfusion. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection. (C) 2010 Published by Elsevier B.V.
C1 [Murphy, Elizabeth] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
   JHMI, Dept Pathol, Baltimore, MD USA.
RP Murphy, E (reprint author), NHLBI, Translat Med Branch, NIH, Room 8N202,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM murphy1@nhlbi.nih.gov
FU Intramural NIH HHS [ZIA HL002066-04, ZIA HL002065-04, ZIA HL006059-02];
   NHLBI NIH HHS [R01 HL039752]
NR 96
TC 26
Z9 27
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-4889
J9 BBA-MOL CELL RES
JI Biochim. Biophys. Acta-Mol. Cell Res.
PD JUL
PY 2011
VL 1813
IS 7
SI SI
BP 1302
EP 1308
DI 10.1016/j.bbamcr.2010.09.003
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 784SA
UT WOS:000292177300007
PM 20837069
ER

PT J
AU Zanni, KL
   Chan, GK
AF Zanni, Karen L.
   Chan, Garrett K.
TI Laser Capture Microdissection: Understanding the Techniques and
   Implications for Molecular Biology in Nursing Research Through Analysis
   of Breast Cancer Tumor Samples
SO BIOLOGICAL RESEARCH FOR NURSING
LA English
DT Article
DE laser capture microdissection; cell lines; authentication
ID POLYMERASE-CHAIN-REACTION; CELL-LINES; CONTAMINATION
AB Aim: The purpose of this paper is to review the techniques and implications of laser capture microdissection (LCM) to isolate tissue and DNA of interest using breast biopsy tissue as an example. Background: Tissues are a heterogeneous mix of different cell types, and molecular alterations are often specific to a single cell type. An accurate correlation of molecular and morphologic pathologies requires the ability to procure pure populations of morphologically similar cells for molecular analysis. LCM is a technique for isolating highly pure cell populations of morphologically similar cells from a heterogeneous tissue section. Method: Nine invasive, paraffin-embedded breast biopsy specimens were obtained and analyzed. Depending on the size of the lesion, 500-1,000 shots using the 7.5- or 15-mu mm infrared laser beam were utilized to obtain an average of 2,000 cells. DNA was isolated from normal tissue and carcinomas and polymerase chain reaction (PCR) amplification was examined by agarose gel electrophoresis. The HER2/neu gene was amplified by standard PCR. A second round of PCR using nested primers to reamplify the HER2/neu fragment was performed. Results: Amplification of the HER2/neu gene with DNA isolated from pure cell populations by LCM was performed. The results indicated that 22% of the cases studied were positive for HER2/neu amplifications, which corresponds to the literature regarding HER2/neu amplification/overexpression. HER2/neu amplification could be detected as early as the ductal carcinoma in situ (DCIS) stage. Conclusion: LCM is an accurate and reliable method to acquire nucleic acid and protein profiles from a specific cell population in heterogeneous tissue.
C1 [Chan, Garrett K.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA.
   [Zanni, Karen L.] Binghamton Univ, Decker Sch Nursing, Binghamton, NY USA.
   [Zanni, Karen L.; Chan, Garrett K.] NINR, Summer Genet Inst, Bethesda, MD 20892 USA.
   [Chan, Garrett K.] Stanford Hosp & Clin, Emergency Dept Observat Unit, Stanford, CA USA.
RP Chan, GK (reprint author), Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA.
EM garrett.chan@nursing.ucsf.edu
NR 19
TC 4
Z9 4
U1 1
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1099-8004
J9 BIOL RES NURS
JI Biol. Res. Nurs.
PD JUL
PY 2011
VL 13
IS 3
BP 297
EP 305
DI 10.1177/1099800411402054
PG 9
WC Nursing
SC Nursing
GA 783AB
UT WOS:000292052800010
PM 21444330
ER

PT J
AU Bhandari, R
   Clement, TM
   Sadler-Riggleman, I
   Skinner, MK
AF Bhandari, Ramji
   Clement, Tracy M.
   Sadler-Riggleman, Ingrid
   Skinner, Michael K.
TI Basic Helix-Loop-Helix Transcription Factor Tcf21 Is a Downstream Target
   of SRY
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 Washington State Univ, Pullman, WA 99164 USA.
   NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 114
PG 1
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200491
ER

PT J
AU Binder, AK
   Burns, KA
   Rodriguez, KF
   Korach, KS
AF Binder, April K.
   Burns, Katherine A.
   Rodriguez, Karina F.
   Korach, Kenneth S.
TI Abnormal Appearance and Function of Ovaries from Ex3AlphaBeta Estrogen
   Receptor Double Knockout Animals
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 [Binder, April K.; Burns, Katherine A.; Rodriguez, Karina F.; Korach, Kenneth S.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 704
PG 1
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200042
ER

PT J
AU Burns, KA
   Rodriguez, KF
   Hewitt, SC
   Young, SL
   Korach, KS
AF Burns, Katherine A.
   Rodriguez, Karina F.
   Hewitt, Sylvia C.
   Young, Steven L.
   Korach, Kenneth S.
TI Establishment and Proliferation of Endometriotic-Like Lesions in
   Estrogen Receptor Deficient Mouse Models Is Host and Donor Specific
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 NIEHS, Washington, DC USA.
   Univ N Carolina, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 380
PG 2
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200123
ER

PT J
AU Chen, LY
   Brown, P
   Willis, W
   Eddy, EM
AF Chen, Liang-Yu
   Brown, Paula
   Willis, William
   Eddy, Edward M.
TI Testosterone Regulates Growth Factors Acting Through Peritubular Myoid
   Cells to Influence Spermatogonial Stem Cell
   Proliferation/Differentiation in the Testis Niche
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 [Chen, Liang-Yu; Brown, Paula; Willis, William; Eddy, Edward M.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 762
PG 2
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200367
ER

PT J
AU Clement, T
   Inselman, A
   Willis, W
   Goulding, E
   Eddy, M
AF Clement, Tracy
   Inselman, Amy
   Willis, William
   Goulding, Eugenia
   Eddy, Mitch
TI Male Meiotic Progression Is Arrested at Diplotene Leading to Male
   Infertility in Cyclin Dependant Kinase 1 (Cdk1) Mutant Mice
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
   US FDA, Jefferson, AR USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 139
PG 2
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200515
ER

PT J
AU Dean, J
AF Dean, Jurrien
TI Evolving Paradigms of Gamete Recognition in Mice
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 [Dean, Jurrien] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 158
PG 1
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200731
ER

PT J
AU Heard, M
   Pabona, JM
   Clayberger, C
   Krensky, AM
   Simmen, FA
   Simmen, RCM
AF Heard, Melissa
   Pabona, John Mark
   Clayberger, Carol
   Krensky, Alan M.
   Simmen, Frank A.
   Simmen, Rosalia C. M.
TI The Reproductive Phenotype of Mice Null for Transcription Factor
   Kruppel-Like Factor 13 ( KLF13) Reveals Functions Distinct from Its
   Family Member KLF9 in Normal Female Fertility
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
   NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 464
PG 2
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200126
ER

PT J
AU Hewitt, SC
   Li, LP
   Li, Y
   Chen, Y
   Fargo, D
   Liu, LW
   Korach, KS
AF Hewitt, Sylvia C.
   Li, Leping
   Li, Yin
   Chen, Yu
   Fargo, David
   Liu, Liwen
   Korach, Kenneth S.
TI Whole-Genome ERalpha Binding in Mouse Uterine Tissue.
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 [Hewitt, Sylvia C.; Li, Leping; Li, Yin; Chen, Yu; Fargo, David; Liu, Liwen; Korach, Kenneth S.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 25
PG 2
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200214
ER

PT J
AU Kaur, J
   Barsoum, IB
   Yao, HHC
   Cooke, PS
AF Kaur, Jaspreet
   Barsoum, Ivraym B.
   Yao, Humphrey H. C.
   Cooke, Paul S.
TI Ectopic Activation of Hedgehog Signaling Pathway in Steroidogenic Factor
   1-Positive Cells in the Fetal Testis Interstitium Does Not Affect
   Development of Adult Leydig Cells
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 Univ Illinois, Urbana, IL USA.
   NIEHS, Res Triangle Pk, NC 27709 USA.
   Univ Florida, Gainesville, FL USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 561
PG 2
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200427
ER

PT J
AU Law, SM
   Nelson, KJ
   Brooks, KE
   Li, H
   Willis, WD
   Goulding, EH
   Eddy, EM
   Kim, KH
AF Law, Sze Ming
   Nelson, Kylie J.
   Brooks, Kelsey E.
   Li, Hui
   Willis, William D.
   Goulding, Eugenia H.
   Eddy, E. Mitch
   Kim, Kwan Hee
TI Retinoic Acid Receptor Alpha in Germ Cells Is Important for the
   Organization of Germ Cell Layers in the Seminiferous Tubules
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 Washington State Univ, Pullman, WA 99164 USA.
   Queens Univ, Kingston, ON, Canada.
   NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 584
PG 1
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200156
ER

PT J
AU Liu, C
   Yao, HHC
AF Liu, Chang
   Yao, Humphrey H. -C.
TI Extra-Gonadal Sources of Gli1-Expressing Cells Contribute to Theca Cell
   Development in the Mouse Ovary.
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 Univ Illinois, Urbana, IL USA.
   NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 30
PG 2
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200220
ER

PT J
AU Miao, YL
   Williams, CJ
AF Miao, Yi-Liang
   Williams, Carmen J.
TI Outside-in Calcium Signaling Is Required for Mouse Egg Activation.
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 [Miao, Yi-Liang; Williams, Carmen J.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 601
PG 1
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200568
ER

PT J
AU Monti, M
   Zanoni, M
   Benazzi, L
   Basilico, F
   Ko, M
   Mauri, P
   Redi, CA
AF Monti, Manuela
   Zanoni, Mario
   Benazzi, Louise
   Basilico, Fabrizio
   Ko, Minoru
   Mauri, Pierluigi
   Redi, Carlo Alberto
TI SN Versus NSN Oocytes: The Endless Battle for the Achievement of the
   Developmental Competence
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 San Matteo Fdn Hlth Hospitalizat & Care, Pavia, Italy.
   Univ Pavia, I-27100 Pavia, Italy.
   CNR, ITB, Segrate, Italy.
   NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 326
PG 2
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200102
ER

PT J
AU Nakamura, BN
   Fielder, TJ
   Hoang, YD
   Lim, J
   McConnachie, LA
   Kavanagh, TJ
   Luderer, U
AF Nakamura, Brooke N.
   Fielder, Thomas J.
   Hoang, Yvonne D.
   Lim, Jinhwan
   McConnachie, Lisa A.
   Kavanagh, Terrance J.
   Luderer, Ulrike
TI Premature Ovarian Failure and Abnormal Preimplantation Development in
   Female Mice Deficient in Glutathione Synthesis
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 Univ Calif Irvine, Irvine, CA USA.
   Univ Calif San Diego, San Diego, CA 92103 USA.
   NIA, Bethesda, MD 20892 USA.
   Univ Washington, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 71
PG 2
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200255
ER

PT J
AU Rodriguez, K
   Stockton, PS
   Hamilton, KJ
   Reed, CE
   Korach, KS
AF Rodriguez, Karina
   Stockton, Patricia S.
   Hamilton, Katherine J.
   Reed, Casey E.
   Korach, Kenneth S.
TI The Absence of ERbeta Results in Altered Gene Expression in Ovarian
   Granulosa and Theca Cells from In-Vivo Preovulatory Follicles
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 [Rodriguez, Karina; Stockton, Patricia S.; Hamilton, Katherine J.; Reed, Casey E.; Korach, Kenneth S.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 707
PG 2
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200183
ER

PT J
AU Williams, CJ
   Padilla-Banks, E
   Gerrish, K
   Jefferson, WN
AF Williams, Carmen J.
   Padilla-Banks, Elizabeth
   Gerrish, Kevin
   Jefferson, Wendy N.
TI Neonatal Phytoestrogen Exposure Causes Posterior Patterning and Altered
   Immune Responses in the Adult Oviduct
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 [Williams, Carmen J.; Padilla-Banks, Elizabeth; Gerrish, Kevin; Jefferson, Wendy N.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 296
PG 2
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200101
ER

PT J
AU Winuthayanon, W
   Hewitt, SC
   Padilla-Banks, E
   Orvis, GD
   Behringer, RR
   Williams, CJ
   Korach, KS
AF Winuthayanon, Wipawee
   Hewitt, Sylvia Curtis
   Padilla-Banks, Elizabeth
   Orvis, Grant D.
   Behringer, Richard R.
   Williams, Carmen J.
   Korach, Kenneth S.
TI Roles of Epithelial Estrogen Receptor Alpha in the Oviduct During Gamete
   Fertilization and Embryo Development
SO BIOLOGY OF REPRODUCTION
LA English
DT Meeting Abstract
CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR)
CY 2011
CL Portland, OR
SP Soc Study Reproduct
C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
   Slone Kettering Inst, New York, NY USA.
   Univ Texas Houston, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
J9 BIOL REPROD
JI Biol. Reprod.
PD JUL
PY 2011
VL 85
SI SI
MA 126
PG 1
WC Reproductive Biology
SC Reproductive Biology
GA 032VC
UT WOS:000310746200502
ER

PT J
AU Luo, WM
   Yu, QS
   Salcedo, I
   Holloway, HW
   Lahiri, DK
   Brossi, A
   Tweedie, D
   Greig, NH
AF Luo, Weiming
   Yu, Qian-Sheng
   Salcedo, Isidro
   Holloway, Harold W.
   Lahiri, Debomoy K.
   Brossi, Arnold
   Tweedie, David
   Greig, Nigel H.
TI Design, synthesis and biological assessment of novel N-substituted
   3-(phthalimidin-2-yl)-2,6-dioxopiperidines and 3-substituted
   2,6-dioxopiperidines for TNF-alpha inhibitory activity
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Thalidomide; Revlimid; N-substituted EM-12; Dithiocarbamates;
   3-Substituted 2,6-dioxopiperidines; Iminium rearrangement;
   Neurodegenerative diseases; TNF-alpha inhibition
ID MESSENGER-RNA STABILITY; NECROSIS-FACTOR-ALPHA; POTENT INHIBITORS;
   BINDING PROTEINS; THALIDOMIDE; ANALOGS; TUMOR; LENALIDOMIDE; DISEASE;
   MODULATION
AB Eight novel 2-(2,6-dioxopiperidin-3-yl) phthalimidine EM-12 dithiocarbamates 9 and 10, N-substituted 3-(phthalimidin-2-yl)-2,6-dioxopiperidines 11-14 and 3-substituted 2,6-dioxopiperidines 16and 18were synthesized as tumor necrosis factor-alpha (TNF-alpha) synthesis inhibitors. Synthesis involved utilization of a novel condensation approach, a one-pot reaction involving addition, iminium rearrangement and elimination, to generate the phthalimidine ring required for the creation of compounds 9-14. Agents were, thereafter, quantitatively assessed for their ability to suppress the synthesis on TNF-alpha in a lipopolysaccharide (LPS)-challenged mouse macrophage-like cellular screen, utilizing cultured RAW 264.7 cells. Whereas compounds 9, 14 and 16 exhibited potent TNF-alpha lowering activity, reducing TNF-alpha by up to 48% at 30 mu M, compounds 12, 17and 18 presented moderate TNF-alpha inhibitory action. The TNF-alpha lowering properties of these analogs proved more potent than that of revlimid (3) and thalidomide (1). In particular, N-dithiophthalimidomethyl-3-(phthalimidin-2-yl)-2,6-dioxopiperidine 14 not only possessed the greatest potency of the analogs to reduce TNF-alpha synthesis, but achieved this with minor cellular toxicity at 30 mu M. The pharmacological focus of the presented compounds is towards the development of well-tolerated agents to ameliorate the neuroinflammation, that is, commonly associated with neurodegenerative disorders, epitomized by Alzheimer's disease and Parkinson's disease. (C) 2011 Published by Elsevier Ltd.
C1 [Luo, Weiming; Yu, Qian-Sheng; Salcedo, Isidro; Holloway, Harold W.; Tweedie, David; Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
   [Lahiri, Debomoy K.] Indiana Univ Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA.
   [Brossi, Arnold] Univ N Carolina, Sch Pharm, Chapel Hill, NC 27599 USA.
RP Greig, NH (reprint author), NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program,NIH, BRC Room 05C220,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM greign@grc.nia.nih.gov
FU National Institute on Aging, National Institutes of Health (NIH); NIH
   [AG18379, AG18884]
FX This work was supported in part by the Intramural Research Program of
   the National Institute on Aging, National Institutes of Health (NIH) and
   by NIH Grants (AG18379 and AG18884) to D.K.L. The authors declare that
   they have no conflicts of interest regarding the contents of this
   manuscript, and are grateful to Dr. Amy Newman and colleagues of the
   Medicinal Chemistry Section, National Institute on Drug Abuse, NIH, for
   use of NMR equipment.
NR 46
TC 14
Z9 15
U1 1
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 1
PY 2011
VL 19
IS 13
BP 3965
EP 3972
DI 10.1016/j.bmc.2011.05.029
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
   Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 781LU
UT WOS:000291934700010
PM 21658960
ER

PT J
AU Nishizawa, R
   Nishiyama, T
   Hisaichi, K
   Minamoto, C
   Murota, M
   Takaoka, Y
   Nakai, H
   Tada, H
   Sagawa, K
   Shibayama, S
   Fukushima, D
   Maeda, K
   Mitsuya, H
AF Nishizawa, Rena
   Nishiyama, Toshihiko
   Hisaichi, Katsuya
   Minamoto, Chiaki
   Murota, Masayuki
   Takaoka, Yoshikazu
   Nakai, Hisao
   Tada, Hideaki
   Sagawa, Kenji
   Shibayama, Shiro
   Fukushima, Daikichi
   Maeda, Kenji
   Mitsuya, Hiroaki
TI Discovery of
   4-[4-({(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-tr
   iazaspiro[5.5]undec-9-yl}methyl)phenoxy]benzoic acid hydrochloride: A
   highly potent orally available CCR5 selective antagonist
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE CCR5; Chemokine; Anti-HIV-1
ID CHEMOKINE RECEPTOR CCR5; HIV ENTRY INHIBITORS; SMALL-MOLECULE; VIRAL
   ENTRY; IN-VITRO; INFECTION; UK-427,857; CORECEPTOR; COFACTOR; DISEASE
AB Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Nishizawa, Rena; Nishiyama, Toshihiko; Hisaichi, Katsuya; Minamoto, Chiaki; Murota, Masayuki; Takaoka, Yoshikazu; Nakai, Hisao] Ono Pharmaceut Co Ltd, Med Chem Res Lab, Osaka 6188585, Japan.
   [Tada, Hideaki; Sagawa, Kenji; Shibayama, Shiro; Fukushima, Daikichi] Ono Pharmaceut Co Ltd, Exploratory Res Lab, Ibaraki 300424, Japan.
   [Maeda, Kenji; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Internal Med 2, Kumamoto 8600811, Japan.
   [Maeda, Kenji; Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
RP Nishizawa, R (reprint author), Ono Pharmaceut Co Ltd, Med Chem Res Lab, Osaka 6188585, Japan.
EM r.nishizawa@ono.co.jp
NR 32
TC 5
Z9 6
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 1
PY 2011
VL 19
IS 13
BP 4028
EP 4042
DI 10.1016/j.bmc.2011.05.022
PG 15
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
   Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 781LU
UT WOS:000291934700017
PM 21658961
ER

PT J
AU Guha, R
   Dexheimer, TS
   Kestranek, AN
   Jadhav, A
   Chervenak, AM
   Ford, MG
   Simeonov, A
   Roth, GP
   Thomas, CJ
AF Guha, Rajarshi
   Dexheimer, Thomas S.
   Kestranek, Aimee N.
   Jadhav, Ajit
   Chervenak, Andrew M.
   Ford, Michael G.
   Simeonov, Anton
   Roth, Gregory P.
   Thomas, Craig J.
TI Exploratory analysis of kinetic solubility measurements of a small
   molecule library
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Aqueous solubility; Physicochemical properties; High-throughput
   screening; Medicinal chemistry; Drug discovery
ID HIGH-THROUGHPUT; DRUG DISCOVERY; PREDICTION; AGGREGATION; CHEMISTRY;
   SCREEN; ASSAYS
AB Kinetic solubility measurements using prototypical assay buffer conditions are presented for a similar to 58,000 member library of small molecules. Analyses of the data based upon physical and calculated properties of each individual molecule were performed and resulting trends were considered in the context of commonly held opinions of how physicochemical properties influence aqueous solubility. We further analyze the data using a decision tree model for solubility prediction and via a multi-dimensional assessment of physicochemical relationships to solubility in the context of specific 'rule-breakers' relative to common dogma. The role of solubility as a determinant of assay outcome is also considered based upon each compound's cross-assay activity score for a collection of publicly available screening results. Further, the role of solubility as a governing factor for colloidal aggregation formation within a specified assay setting is examined and considered as a possible cause of a high cross-assay activity score. The results of this solubility profile should aid chemists during library design and optimization efforts and represent a useful training set for computational solubility prediction. Published by Elsevier Ltd.
C1 [Roth, Gregory P.] Conrad Prebys Ctr Chem Genom, Sanford Burnham Med Res Inst Lake Nona, Orlando, FL 32827 USA.
   [Guha, Rajarshi; Dexheimer, Thomas S.; Jadhav, Ajit; Simeonov, Anton; Thomas, Craig J.] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
   [Kestranek, Aimee N.; Chervenak, Andrew M.; Ford, Michael G.] Analiza Inc, Cleveland, OH 44114 USA.
RP Roth, GP (reprint author), Conrad Prebys Ctr Chem Genom, Sanford Burnham Med Res Inst Lake Nona, 6400 Sanger Rd, Orlando, FL 32827 USA.
EM groth@sanfordburnham.org; craigt@mail.nih.gov
FU Molecular Libraries Initiative of the National Institutes of Health
   Roadmap for Medical Research [U54 HG005033-02]; National Human Genome
   Research Institute at the National Institutes of Health
FX The authors would like to thank Dr. Douglas Livingston, Dr. Timothy
   Lease and the staff at Biofocus DPI for their assistance with compound
   management. We further acknowledge Dr. Jamie Driscoll for support of
   this effort. We thank Dr. Ed Kearns for helpful discussion during the
   writing of this manuscript. This research was supported by the Molecular
   Libraries Initiative of the National Institutes of Health Roadmap for
   Medical Research grants U54 HG005033-02 to G.P.R. and the Intramural
   Research Program of the National Human Genome Research Institute at the
   National Institutes of Health.
NR 28
TC 2
Z9 2
U1 1
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 1
PY 2011
VL 19
IS 13
BP 4127
EP 4134
DI 10.1016/j.bmc.2011.05.005
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
   Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 781LU
UT WOS:000291934700028
PM 21640593
ER

PT J
AU Jiang, S
   Liu, XD
   Sun, J
   Yuan, LX
   Sun, LG
   Wang, YH
AF Jiang, Shan
   Liu, Xiaodong
   Sun, Jing
   Yuan, Linxi
   Sun, Liguang
   Wang, Yuhong
TI A multi-proxy sediment record of late Holocene and recent climate change
   from a lake near Ny-Alesund, Svalbard
SO BOREAS
LA English
DT Article
ID RECENT ENVIRONMENTAL-CHANGE; LAST GLACIAL MAXIMUM; ATMOSPHERIC
   CONTAMINATION; SEA-ICE; WESTERN SPITSBERGEN; ELLESMERE-ISLAND;
   ORGANIC-MATTER; ARCTIC CANADA; BAFFIN-ISLAND; HISTORY
AB The Arctic constitutes a unique and important environment with a significant role in the dynamics and evolution of the earth system. Arctic lake sediments, which accumulate slowly over time, contain abundant information about the biological communities that lived within the water body, as well as in the surrounding catchment. In this study, we collected a sediment core from Ny-Alesund, Svalbard, performed multi-proxy analyses on sediment pigments, mineral magnetic susceptibility, various sediment quality (i.e. organic matter content, CaCO3 content, carbon and nitrogen isotope), and diatom composition, and reconstructed the history of ecosystem responses to environmental variations, especially regarding aquatic productivity and lake catchment surface processes. Ny-Alesund has undergone distinct ecological and climatic changes. During the Little Ice Age, the cold climate was unfavourable for the growth of lake algae, and therefore the lake primary productivity declined. After about AD 1890 and during the 20th century, the warming climate and reduced ice cover led to rapid lithological change and growth of lake algae, enhanced lake primary productivity, and increased input of nutrients derived from increased chemical weathering into the lake. The lake ecosystem on Ny-Alesund has had rapid responses to climatic and environmental changes in the Arctic.
C1 [Jiang, Shan; Liu, Xiaodong; Yuan, Linxi; Sun, Liguang] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China.
   [Sun, Jing] Columbia Univ, Lamont Doherty Earth Observ, Palisades, NY 10964 USA.
   [Wang, Yuhong] NIH, Bethesda, MD 20892 USA.
RP Jiang, S (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China.
EM ycx@ustc.edu.cn
RI Sun, Jing /B-9248-2017
OI Sun, Jing /0000-0002-0129-5184
FU National Natural Science Foundation [40876096, 41076123, 40730107];
   Fundamental Research Funds for the Central Universities; State Key
   Laboratory of Environmental Chemistry and Ecotoxicology [KP2010-08];
   CAAA [20070202]; Chinese Academy of Sciences
FX We would like to thank the Chinese Antarctic and Arctic Administration
   of the National Oceanic Bureau for logistical support. We especially
   appreciate Dr. A. Werner, Professor Jan A. Piotrowski and an anonymous
   reviewer for their critical reviews, which led to improvements in the
   manuscript. This study was supported by the National Natural Science
   Foundation (Grant Nos 40876096, 41076123 and 40730107), the Fundamental
   Research Funds for the Central Universities, open fund from State Key
   Laboratory of Environmental Chemistry and Ecotoxicology (KP2010-08), the
   young fund for strategetic research of Chinese polar sciences from CAAA
   (No. 20070202) and a special fund for excellent PhD thesis of the
   Chinese Academy of Sciences.
NR 82
TC 6
Z9 7
U1 1
U2 26
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-9483
J9 BOREAS
JI Boreas
PD JUL
PY 2011
VL 40
IS 3
BP 468
EP 480
DI 10.1111/j.1502-3885.2010.00198.x
PG 13
WC Geography, Physical; Geosciences, Multidisciplinary
SC Physical Geography; Geology
GA 783TL
UT WOS:000292106800006
ER

PT J
AU Hubener, J
   Vauti, F
   Funke, C
   Wolburg, H
   Ye, YH
   Schmidt, T
   Wolburg-Buchholz, K
   Schmitt, I
   Gardyan, A
   Driessen, S
   Arnold, HH
   Nguyen, HP
   Riess, O
AF Huebener, Jeannette
   Vauti, Franz
   Funke, Claudia
   Wolburg, Hartwig
   Ye, Yihong
   Schmidt, Thorsten
   Wolburg-Buchholz, Karen
   Schmitt, Ina
   Gardyan, Adriane
   Driessen, Stefan
   Arnold, Hans-Henning
   Huu Phuc Nguyen
   Riess, Olaf
TI N-terminal ataxin-3 causes neurological symptoms with inclusions,
   endoplasmic reticulum stress and ribosomal dislocation
SO BRAIN
LA English
DT Article
DE ataxin-3; calpain cleavage; endoplasmic reticulum stress; gene trap
   model; Josephin domain
ID JOSEPH-DISEASE GENE; VALOSIN-CONTAINING PROTEIN; LIPOFUSCIN PIGMENT
   ACCUMULATION; POLYGLUTAMINE-EXPANDED ATAXIN-3; HUNTINGTONS-DISEASE;
   INTRANUCLEAR INCLUSIONS; FRONTOTEMPORAL DEMENTIA; MEDIATED PROTEOLYSIS;
   MUTANT HUNTINGTIN; TRANSGENIC MICE
AB Mutant ataxin-3 is aberrantly folded and proteolytically cleaved in spinocerebellar ataxia type 3. The C-terminal region of the protein includes a polyglutamine stretch that is expanded in spinocerebellar ataxia type 3. Here, we report on the analysis of an ataxin-3 mutant mouse that has been obtained by gene trap integration. The ataxin-3 fusion protein encompasses 259 N-terminal amino acids including the Josephin domain and an ubiquitin-interacting motif but lacks the C-terminus with the polyglutamine stretch, the valosin-containing protein binding region and part of the ubiquitin-interacting motif 2. Homozygous ataxin-3 mutant mice were viable and showed no apparent anatomical defects at birth. However, at the age of 9 months, homozygous and heterozygous mutant mice revealed significantly altered behaviour and progressing deficits of motor coordination followed by premature death at similar to 12 months. At this time, prominent extranuclear protein aggregates and neuronal cell death was found in mutant mice. This was associated with disturbances of the endoplasmic reticulum-mediated unfolded protein response, consistent with the normal role of ataxin-3 in endoplasmic reticulum homeostasis. Thus, the ataxin-3 gene trap model provides evidence for a contribution of the non-polyglutamine containing ataxin-3 N-terminus, which mimics a calpain fragment that has been observed in spinocerebellar ataxia type 3. Consistent with the disease in humans, gene trap mice develop cytoplasmic inclusion bodies and implicate impaired unfolded protein response in the pathogenesis of spinocerebellar ataxia type 3.
C1 [Huebener, Jeannette; Funke, Claudia; Schmidt, Thorsten; Gardyan, Adriane; Driessen, Stefan; Huu Phuc Nguyen; Riess, Olaf] Univ Tubingen, Dept Med Genet, D-72076 Tubingen, Germany.
   [Vauti, Franz; Arnold, Hans-Henning] Tech Univ Carolo Wilhelmina Braunschweig, Dept Cell & Mol Biol, Inst Biochem & Biotechnol, D-38106 Braunschweig, Germany.
   [Wolburg, Hartwig; Wolburg-Buchholz, Karen] Univ Tubingen, Dept Pathol, D-72076 Tubingen, Germany.
   [Ye, Yihong] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Schmitt, Ina] Univ Bonn, Dept Neurol, D-53105 Bonn, Germany.
RP Riess, O (reprint author), Univ Tubingen, Dept Med Genet, Calwerstr 7, D-72076 Tubingen, Germany.
EM olaf.riess@med.uni-tuebingen.de
RI Nguyen, Huu Phuc/F-5390-2015
OI Nguyen, Huu Phuc/0000-0001-6139-788X
FU European Union
FX European Union to OR (6th frame work programme, EuroSCA).
NR 65
TC 25
Z9 25
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD JUL
PY 2011
VL 134
BP 1925
EP 1942
DI 10.1093/brain/awr118
PN 7
PG 18
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 782YV
UT WOS:000292049600010
PM 21653538
ER

PT J
AU Nicholson, G
   Lenk, GM
   Reddel, SW
   Grant, AE
   Towne, CF
   Ferguson, CJ
   Simpson, E
   Scheuerle, A
   Yasick, M
   Hoffman, S
   Blouin, R
   Brandt, C
   Coppola, G
   Biesecker, LG
   Batish, SD
   Meisler, MH
AF Nicholson, Garth
   Lenk, Guy M.
   Reddel, Stephen W.
   Grant, Adrienne E.
   Towne, Charles F.
   Ferguson, Cole J.
   Simpson, Ericka
   Scheuerle, Angela
   Yasick, Michelle
   Hoffman, Stuart
   Blouin, Randall
   Brandt, Carla
   Coppola, Giovanni
   Biesecker, Leslie G.
   Batish, Sat D.
   Meisler, Miriam H.
TI Distinctive genetic and clinical features of CMT4J: a severe neuropathy
   caused by mutations in the PI(3,5)P-2 phosphatase FIG4
SO BRAIN
LA English
DT Article
DE Charcot-Marie-Tooth disease; neurodegenerative disorders; clinical
   characteristics; demyelinating disease; molecular genetics
ID MARIE-TOOTH DISEASE; PHOSPHOINOSITIDE PHOSPHATASE; GENOME;
   NEURODEGENERATION; DEGENERATION; MECHANISM; ABUNDANCE; VAC14; MOUSE;
   YEAST
AB Charcot-Marie-Tooth disease is a genetically heterogeneous group of motor and sensory neuropathies associated with mutations in more than 30 genes. Charcot-Marie-Tooth disease type 4J (OMIM 611228) is a recessive, potentially severe form of the disease caused by mutations of the lipid phosphatase FIG4. We provide a more complete view of the features of this disorder by describing 11 previously unreported patients with Charcot-Marie-Tooth disease type 4J. Three patients were identified from a small cohort selected for screening because of their early onset disease and progressive proximal as well as distal weakness. Eight patients were identified by large-scale exon sequencing of an unselected group of 4000 patients with Charcot-Marie-Tooth disease. In addition, 34 new FIG4 variants were detected. Ten of the new CMT4J cases have the compound heterozygous genotype FIG4(I41T/null) described in the original four families, while one has the novel genotype FIG4(L17P/null). The population frequency of the I41T allele was found to be 0.001 by genotyping 5769 Northern European controls. Thirty four new variants of FIG4 were identified. The severity of Charcot-Marie-Tooth disease type 4J ranges from mild clinical signs to severe disability requiring the use of a wheelchair. Both mild and severe forms have been seen in patients with the same genotype. The results demonstrate that Charcot-Marie-Tooth disease type 4J is characterized by highly variable onset and severity, proximal as well as distal and asymmetric muscle weakness, electromyography demonstrating denervation in proximal and distal muscles, and frequent progression to severe amyotrophy. FIG4 mutations should be considered in Charcot-Marie-Tooth patients with these characteristics, especially if found in combination with sporadic or recessive inheritance, childhood onset and a phase of rapid progression.
C1 [Meisler, Miriam H.] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
   [Nicholson, Garth; Reddel, Stephen W.] Univ Sydney, Dept Neurol, ANZAC Inst, Concord Hosp, Sydney, NSW 2139, Australia.
   [Towne, Charles F.; Batish, Sat D.] Athena Diagnost Inc, Worcester, MA 01605 USA.
   [Simpson, Ericka] Methodist Neurol Inst, Houston, TX 77030 USA.
   [Scheuerle, Angela] Tesserae Genet, Dallas, TX 75230 USA.
   [Yasick, Michelle; Hoffman, Stuart] Geisinger Med Ctr, Danville, PA 17822 USA.
   [Blouin, Randall] Greenville Hosp Syst, Med Univ Ctr, Greenville, SC 29615 USA.
   [Brandt, Carla] Midwest Neurol, Evansville, IN 47716 USA.
   [Coppola, Giovanni] Univ Calif Los Angeles, Neurogenet Program, Los Angeles, CA 90095 USA.
   [Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Meisler, MH (reprint author), Univ Michigan, Sch Med, Dept Human Genet, 4909 Buhl Box 5618, Ann Arbor, MI 48109 USA.
EM meislerm@umich.edu
RI Lenk, Guy/Q-1226-2016
OI Lenk, Guy/0000-0001-8092-1405
FU National Institutes of Health research [R01 GM24872];
   Charcot-Marie-Tooth disease Association of Australia; NHMRC of Australia
   [APP1007705]; MDA USA [158509]; Hartwell Foundation; University of
   Michigan (NIH) [T32 GM07863]; National Institute on Aging (NIA) [U24
   AG21886]; Massachusetts General Hospital [MH 63420]
FX National Institutes of Health research (grant R01 GM24872) (to M. H.
   M.); the Charcot-Marie-Tooth disease Association of Australia (to G.N.);
   the NHMRC of Australia (Grant number APP1007705 to G.N.); MDA USA (grant
   number 158509 to G.N.); Hartwell Foundation (to G. M. L., postdoctoral
   fellowship); Medical Scientist Training Program at the University of
   Michigan (NIH T32 GM07863 to C.J.F.). The National Cell Repository for
   Alzheimer's Disease (NCRAD) receives government support under a
   cooperative agreement grant (U24 AG21886) awarded by the National
   Institute on Aging (NIA).; Lieberman for critical reading of the
   manuscript. For the population screen of I41T frequency, DNA from normal
   controls was obtained from the following sources. We thank contributors,
   including the Alzheimer's Disease Centres who collected samples used in
   this study, as well as patients and their families, whose help and
   participation made this work possible. The National Institute of Mental
   Health Schizophrenia Genetics Initiative (NIMH-GI) data and biomaterials
   were collected by the Molecular Genetics of Schizophrenia II (MGS-2)
   collaboration. The investigators and co-investigators are:
   ENH/Northwestern University, Evanston, IL, MH059571, Pablo V. Gejman, M.
   D. (Collaboration Coordinator; PI), Alan R. Sanders, MD; Emory
   University School of Medicine, Atlanta, GA, MH59587, Farooq Amin, MD
   (PI); Louisiana State University Health Sciences Centre; New Orleans,
   Louisiana, MH067257, Nancy Buccola APRN, BC, MSN (PI); University of
   California-Irvine, Irvine, CA, MH60870, William Byerley, MD (PI);
   Washington University, St Louis, MO, U01, MH060879, C. Robert Cloninger,
   MD (PI); University of Iowa, Iowa, IA, MH59566, Raymond Crowe, MD (PI),
   Donald Black, MD; University of Colorado, Denver, CO, MH059565, Robert
   Freedman, MD (PI); University of Pennsylvania, Philadelphia, PA,
   MH061675, Douglas Levinson MD (PI); University of Queensland,
   Queensland, Australia, MH059588, Bryan Mowry, MD (PI); Mt. Sinai School
   of Medicine, New York, NY, MH59586, Jeremy Silverman, PhD (PI). In
   addition, cord blood samples were collected by V L Nimgaonkar's group at
   the University of Pittsburgh, as part of a multi-institutional
   collaborative research project with J Smoller, MD DSc and P Sklar, MD
   PhD (Massachusetts General Hospital) (grant MH 63420).
NR 21
TC 39
Z9 42
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD JUL
PY 2011
VL 134
BP 1959
EP 1971
DI 10.1093/brain/awr148
PN 7
PG 13
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 782YV
UT WOS:000292049600012
PM 21705420
ER

PT J
AU Costigan, M
   Belfer, I
   Griffin, RS
   Dai, F
   Barrett, LB
   Coppola, G
   Wu, TX
   Kiselycznyk, C
   Poddar, M
   Lu, Y
   Diatchenko, L
   Smith, S
   Cobos, EJ
   Zaykin, D
   Allchorne, A
   Gershon, E
   Livneh, J
   Shen, PH
   Nikolajsen, L
   Karppinen, J
   Mannikko, M
   Kelempisioti, A
   Goldman, D
   Maixner, W
   Geschwind, DH
   Max, MB
   Seltzer, Z
   Woolf, CJ
AF Costigan, Michael
   Belfer, Inna
   Griffin, Robert S.
   Dai, Feng
   Barrett, Lee B.
   Coppola, Giovanni
   Wu, Tianxia
   Kiselycznyk, Carly
   Poddar, Minakshi
   Lu, Yan
   Diatchenko, Luda
   Smith, Shad
   Cobos, Enrique J.
   Zaykin, Dmitri
   Allchorne, Andrew
   Gershon, Edith
   Livneh, Jessica
   Shen, Pei-Hong
   Nikolajsen, Lone
   Karppinen, Jaro
   Mannikko, Minna
   Kelempisioti, Anthi
   Goldman, David
   Maixner, William
   Geschwind, Daniel H.
   Max, Mitchell B.
   Seltzer, Ze'ev
   Woolf, Clifford J.
TI Multiple chronic pain states are associated with a common amino acid
   changing allele in KCNS1 (vol 133, pg 2519, 2010)
SO BRAIN
LA English
DT Correction
C1 [Costigan, Michael; Griffin, Robert S.; Barrett, Lee B.; Cobos, Enrique J.; Allchorne, Andrew; Woolf, Clifford J.] Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA.
   [Costigan, Michael; Griffin, Robert S.; Barrett, Lee B.; Cobos, Enrique J.; Allchorne, Andrew; Woolf, Clifford J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Belfer, Inna; Dai, Feng; Poddar, Minakshi; Max, Mitchell B.] Univ Pittsburgh, Mol Epidemiol Pain Program, Dept Anaesthesiol, Pittsburgh, PA 15261 USA.
   [Coppola, Giovanni; Geschwind, Daniel H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
   [Wu, Tianxia] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
   [Kiselycznyk, Carly; Shen, Pei-Hong; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20892 USA.
   [Lu, Yan; Seltzer, Ze'ev] Univ Toronto, Comparat Pain Phen & Genom Lab, Ctr Study Pain, Fac Dent, Toronto, ON M5G 1G6, Canada.
   [Lu, Yan; Seltzer, Ze'ev] Univ Toronto, Comparat Pain Phen & Genom Lab, Ctr Study Pain, Fac Med, Toronto, ON M5G 1G6, Canada.
   [Diatchenko, Luda; Smith, Shad; Maixner, William] Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA.
   [Zaykin, Dmitri] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
   [Gershon, Edith] Hebrew Univ Jerusalem, Fac Dent, IL-91904 Jerusalem, Israel.
   [Livneh, Jessica] Sheba Med Ctr, Ctr Canc, IL-52621 Tel Hashomer, Israel.
   [Nikolajsen, Lone] Aarhus Univ Hosp, Danish Pain Res Ctr, DK-8000 Aarhus, Denmark.
   [Karppinen, Jaro; Mannikko, Minna; Kelempisioti, Anthi] Univ Oulu, Dept Med Biochem & Mol Biol, Oulu 90014, Finland.
RP Costigan, M (reprint author), Childrens Hosp, FM Kirby Neurobiol Ctr, 300 Longwood Ave, Boston, MA 02115 USA.
NR 1
TC 0
Z9 0
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD JUL
PY 2011
VL 134
BP 2186
EP 2186
DI 10.1093/brain/awq387
PN 7
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 782YV
UT WOS:000292049600031
ER

PT J
AU Samarasinghe, V
   Murphy, HR
   Judge, M
   Verbov, J
   Clayton, T
AF Samarasinghe, V.
   Murphy, H. R.
   Judge, M.
   Verbov, J.
   Clayton, T.
TI A case of mosaic focal dermal hypoplasia in a female child with mild
   phenotypic features and review of the literature
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Meeting Abstract
CT 91st Annual Meeting of the British-Association-of-the-Dermatologists
CY JUL 05-07, 2011
CL London, ENGLAND
SP British Assoc Dermatol
C1 [Samarasinghe, V.; Judge, M.; Clayton, T.] Salford Royal Hosp NHS Fdn Trust, Dermatol Ctr, Manchester, Lancs, England.
   [Murphy, H. R.] Manchester Acad Hlth Sci Ctr, Dept Med Genet, Cent Manchester Hosp NHS Fdn Trust, Manchester, Lancs, England.
   [Murphy, H. R.] Biomed Res Ctr, Baltimore, MD USA.
   [Verbov, J.] Royal Liverpool Childrens Hosp, Dept Paediat Dermatol, Liverpool L7 7DG, Merseyside, England.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-0963
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD JUL
PY 2011
VL 165
SU 1
SI SI
BP 128
EP 128
PG 1
WC Dermatology
SC Dermatology
GA 788PD
UT WOS:000292456000267
ER

PT J
AU Keating, NL
   O'Malley, AJ
   Murabito, JM
   Smith, KP
   Christakis, NA
AF Keating, Nancy L.
   O'Malley, A. James
   Murabito, Joanne M.
   Smith, Kirsten P.
   Christakis, Nicholas A.
TI Minimal Social Network Effects Evident in Cancer Screening Behavior
SO CANCER
LA English
DT Article
DE cancer screening; mammography; prostate specific antigen; social
   networks
ID COLORECTAL-CANCER; BREAST-CANCER; AFRICAN-AMERICAN; PROSTATE-CANCER;
   WOMEN; MAMMOGRAPHY; POPULATION; GUIDELINES; SUPPORT; HEALTH
AB BACKGROUND: Social networks may influence screening behaviors. We assessed whether screening for breast, prostate, or colorectal cancer is influenced by the actual screening behaviors of siblings, friends, spouses, and coworkers. METHODS: We conducted an observational study using Framingham Heart Study data to assess screening for eligible individuals during the late 1990s. We used logistic regression to determine whether the probability of screening for breast, prostate, or colorectal cancer was influenced by the proportion of siblings, friends, and coworkers who had the same screening, as well as spouse's screening for colorectal cancer, adjusting for other factors that might influence screening rates. RESULTS: Among 1660 women aged 41-70 years, 71.7% reported mammography in the previous year; among 1217 men aged 51-70 years, 43.3% reported prostate-specific antigen testing in the previous year; and among 1426 men and women aged 51-80 years, 46.9% reported stool blood testing and/or sigmoidoscopy in the previous year. An increasing proportion of sisters who had mammography in the previous year was associated with mammography screening in the ego (odds ratio [OR], 1.034; 95% confidence interval [CI], 1.000-1.065 for each 10% increase). A spouse with recent screening was associated with more colorectal cancer screening (OR, 1.65; 95% CI, 1.39-1.98 vs unmarried). Otherwise, screening behaviors of siblings, friends, and coworkers were not associated with screening in the ego. CONCLUSIONS: Aside from a slight increase in breast cancer screening among women whose sisters were screened and colorectal cancer screening if spouses were screened, the screening behavior of siblings, friends, or coworkers did not influence cancer screening behaviors. Cancer 2011;117:3045-52. (c) 2011 American Cancer Society
C1 [Keating, Nancy L.; O'Malley, A. James; Smith, Kirsten P.; Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
   [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA.
   [Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA.
   [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
   [Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   [Christakis, Nicholas A.] Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA.
RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
EM keating@hcp.med.harvard.edu
OI Murabito, Joanne/0000-0002-0192-7516
FU National Institute on Aging [R-01 AG-24448, P01 AG-031093]; National
   Heart, Lung, and Blood Institute Framingham Heart Study [N01-HC-25195]
FX This study was funded by the National Institute on Aging (grant nos.
   R-01 AG-24448 and P01 AG-031093) and the National Heart, Lung, and Blood
   Institute Framingham Heart Study (contract no. N01-HC-25195). N.A.C. has
   an equity stake in a company, MedNetworks, that is licensed by Harvard
   to apply some of the ideas embodied in work on social networks.
NR 48
TC 16
Z9 16
U1 1
U2 16
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUL 1
PY 2011
VL 117
IS 13
BP 3045
EP 3052
DI 10.1002/cncr.25849
PG 8
WC Oncology
SC Oncology
GA 783BJ
UT WOS:000292056200026
PM 21264828
ER

PT J
AU Tsuchiya, N
   Izumiya, M
   Ogata-Kawata, H
   Okamoto, K
   Fujiwara, Y
   Nakai, M
   Okabe, A
   Schetter, AJ
   Bowman, ED
   Midorikawa, Y
   Sugiyama, Y
   Aburatani, H
   Harris, CC
   Nakagama, H
AF Tsuchiya, Naoto
   Izumiya, Masashi
   Ogata-Kawata, Hiroko
   Okamoto, Koji
   Fujiwara, Yuko
   Nakai, Makiko
   Okabe, Atsushi
   Schetter, Aaron J.
   Bowman, Elise D.
   Midorikawa, Yutaka
   Sugiyama, Yasuyuki
   Aburatani, Hiroyuki
   Harris, Curtis C.
   Nakagama, Hitoshi
TI Tumor Suppressor miR-22 Determines p53-Dependent Cellular Fate through
   Post-transcriptional Regulation of p21
SO CANCER RESEARCH
LA English
DT Article
ID HUMAN CANCER-CELLS; ANIMAL DEVELOPMENT; MICRORNA TARGETS; BREAST-CANCER;
   GROWTH ARREST; P53 PATHWAY; DNA-DAMAGE; APOPTOSIS; GENE; SENESCENCE
AB Selective activation of p53 target genes in response to various cellular stresses is a critical step in determining the ability to induce cell-cycle arrest or apoptosis. Here we report the identification of the microRNA miR-22 as a p53 target gene that selectively determines the induction of p53-dependent apoptosis by repressing p21. Combinatorial analyses of the AGO2 immunocomplex and gene expression profiles identified p21 as a direct target of miR-22. Induction of p21 was inhibited by miR-22 after exposure to the genotoxic agent Adriamycin (doxorubicin; Bedford Laboratories), sensitizing cells to p53-dependent apoptosis. Interestingly, the activation of miR-22 depended on the intensity of the stresses that induced cells to undergo apoptosis in the presence of p21 suppression. Our findings define an intrinsic molecular switch that determines p53-dependent cellular fate through post-transcriptional regulation of p21. Cancer Res; 71(13); 4628-39. (C)2011 AACR.
C1 [Tsuchiya, Naoto; Izumiya, Masashi; Ogata-Kawata, Hiroko; Fujiwara, Yuko; Nakai, Makiko; Nakagama, Hitoshi] Natl Canc Ctr, Res Inst, Div Canc Dev Syst, Tsukiji, Japan.
   [Okamoto, Koji] Natl Canc Ctr, Res Inst, Div Canc Differentiat, Tsukiji, Japan.
   [Okabe, Atsushi; Aburatani, Hiroyuki] Univ Tokyo, Adv Sci & Technol Res Ctr, Genome Sci Div, Tokyo, Japan.
   [Midorikawa, Yutaka; Sugiyama, Yasuyuki] Teikyo Univ, Sch Med, Univ Hosp, Kawasaki, Kanagawa, Japan.
   [Schetter, Aaron J.; Bowman, Elise D.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Nakagama, H (reprint author), Natl Canc Ctr, Res Inst, 1-1 Tsukiji 5 Chome, Tokyo 1040045, Japan.
EM hnakagam@ncc.go.jp
FU National Institute of Biomedical Innovation (NIBIO); Ministry of Health,
   Labor and Welfare, Japan; Takeda Science Foundation; Ministry of
   Education, Culture, Sports & Technology of Japan; Foundation for
   Promotion of Cancer Research Japan
FX This work is supported by the Program for Promotion of Fundamental
   Studies in Health Sciences of the National Institute of Biomedical
   Innovation (NIBIO), a Grant-in-Aid for 3rd Term Comprehensive 10-Year
   Strategy for Cancer Control from the Ministry of Health, Labor and
   Welfare, Japan, a grant from Takeda Science Foundation (H. Nakagama),
   and a Grant-in-Aid for Scientific Research from the Ministry of
   Education, Culture, Sports & Technology of Japan (N. Tsuchiya). H.
   Ogata-Kawata is an awardee of the Research Resident Fellowship from the
   Foundation for Promotion of Cancer Research Japan for the 3rd Term
   Comprehensive 10-Year Strategy for Cancer Control.
NR 50
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U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 1
PY 2011
VL 71
IS 13
BP 4628
EP 4639
DI 10.1158/0008-5472.CAN-10-2475
PG 12
WC Oncology
SC Oncology
GA 786EY
UT WOS:000292287300032
PM 21565979
ER

PT J
AU Hindorff, LA
   Gillanders, EM
   Manolio, TA
AF Hindorff, Lucia A.
   Gillanders, Elizabeth M.
   Manolio, Teri A.
TI Genetic architecture of cancer and other complex diseases: lessons
   learned and future directions
SO CARCINOGENESIS
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; CELL LUNG-CANCER; PROSTATE-CANCER;
   SUSCEPTIBILITY LOCI; COMMON CANCERS; BREAST-CANCER; LARGE-SCALE;
   INHERITED SUSCEPTIBILITY; ENVIRONMENT INTERACTIONS; DIVERSE POPULATIONS
AB Genome-wide association studies have broadened our understanding of the genetic architecture of cancer to include common variants, in addition to the rare variants previously identified by linkage analysis. We review current knowledge on the genetic architecture of four cancers-breast, lung, prostate and colorectal-for which the balance of common and rare alleles identified ranges from fewer common alleles (lung cancer) to more common alleles (prostate cancer). Although most variants are cancer specific, pleiotropy has been observed for several variants, for example, variants at the 8q24 locus and breast, ovarian and prostate cancers or variants in KITLG in relation to hair color and testicular cancer. Although few studies have been adequately powered to investigate heterogeneity among ancestry groups, effect sizes associated with common variants have been reported to be fairly homogenous among ethnic groups. Some associations appear to be ancestry specific, such as HNF1B, which is associated with prostate cancer in European Americans and Latinos but not in African-Americans. Studies of cancer and other complex diseases suggest that a simple dichotomy between rare and common allelic architectures may be too simplistic and that future research is needed to characterize a fuller spectrum of allele frequency (common (>5%), uncommon (1-5%) and rare (<< 1%) alleles) and effect size. In addition, a broadening of the concept of genetic architecture to encompass both population architecture, which reflects differences in exposures, genetic factors and population level risk among diverse groups of people, and genomic architecture, which includes structural, epigenomic and somatic variation, is envisioned.
C1 [Hindorff, Lucia A.; Manolio, Teri A.] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA.
   [Gillanders, Elizabeth M.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Hindorff, LA (reprint author), 5635 Fishers Lane,Suite 3058,MSC 9307, Bethesda, MD 20892 USA.
EM hindorffl@mail.nih.gov
NR 83
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U1 0
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD JUL
PY 2011
VL 32
IS 7
BP 945
EP 954
DI 10.1093/carcin/bgr056
PG 10
WC Oncology
SC Oncology
GA 786WE
UT WOS:000292337800001
PM 21459759
ER

PT J
AU Chen, L
   Li, HZ
   Liu, WL
   Zhu, JQ
   Zhao, XC
   Wright, E
   Cao, L
   Ding, I
   Rodgers, GP
AF Chen, Ling
   Li, Hongzhen
   Liu, Wenli
   Zhu, Jianqiong
   Zhao, Xiongce
   Wright, Elizabeth
   Cao, Liu
   Ding, Ivan
   Rodgers, Griffin P.
TI Olfactomedin 4 suppresses prostate cancer cell growth and metastasis via
   negative interaction with cathepsin D and SDF-1
SO CARCINOGENESIS
LA English
DT Article
ID DIFFERENTIALLY EXPRESSED GENES; BREAST-CANCER; IN-VIVO; ASPARTIC
   PROTEASE; CXCL12 SDF-1; TUMOR-GROWTH; IDENTIFICATION; CHEMOKINES; HGC-1;
   ANGIOGENESIS
AB The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected control cells. Mechanistic studies revealed that OLFM4 may exhibit its anticancer effects through regulating cell autophagy by targeting cathepsin D, as OLFM4 reduced cathepsin D protein levels and enzymatic activity and attenuated cathepsin D-induced cancer cell proliferation. In addition, overexpression of OLFM4 abrogated stromal cell derived factor-1 (SDF-1)induced PC-3 cell invasiveness in a Matrigel invasion assay, partially through blocking SDF-1-mediated AKT phosphorylation. Coimmunoprecipitation and immunofluorescence staining studies in OLFM4-expressing PC-3 cells demonstrated a direct interaction between OLFM4 and cathepsin D or SDF-1. Taken together, these results suggest that OLFM4 negatively interacts with cathepsin D and SDF-1 and inhibits prostate cancer growth and bone metastasis.
C1 [Chen, Ling; Li, Hongzhen; Liu, Wenli; Zhu, Jianqiong; Rodgers, Griffin P.] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
   [Zhao, Xiongce; Wright, Elizabeth; Rodgers, Griffin P.] NIDDKD, NIH, Bethesda, MD 20892 USA.
   [Cao, Liu] China Med Univ, Key Lab Cell Biol, Minist Publ Hlth, Shenyang, Peoples R China.
   [Ding, Ivan] NCI, Translat Res Program, NIH, Bethesda, MD 20892 USA.
RP Rodgers, GP (reprint author), NHLBI, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N119,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gr5n@nih.gov
FU Intramural Research Program; National Institutes of Health/National
   Institute of Diabetes and Digestive and Kidney Diseases
FX Intramural Research Program, National Institutes of Health/National
   Institute of Diabetes and Digestive and Kidney Diseases.
NR 47
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U1 0
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD JUL
PY 2011
VL 32
IS 7
BP 986
EP 994
DI 10.1093/carcin/bgr065
PG 9
WC Oncology
SC Oncology
GA 786WE
UT WOS:000292337800006
PM 21470957
ER

PT J
AU Berger, VW
AF Berger, Vance W.
TI Assessing the success of masking in acupuncture trials: Further insight
SO CHINESE JOURNAL OF INTEGRATIVE MEDICINE
LA English
DT Letter
DE allocation concealment; Berger-Exner test; clinical trial; selection
   bias
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 1
Z9 1
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1672-0415
J9 CHIN J INTEGR MED
JI Chin. J. Integr. Med.
PD JUL
PY 2011
VL 17
IS 7
BP 546
EP 546
DI 10.1007/s11655-011-0790-3
PG 1
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA 786KA
UT WOS:000292305400011
PM 21725882
ER

PT J
AU Miller, WG
   Myers, GL
   Remaley, AT
AF Miller, W. Greg
   Myers, Gary L.
   Remaley, Alan T.
TI Limitations of Direct Methods and the Reference Method for Measuring HDL
   and LDL Cholesterol Reply
SO CLINICAL CHEMISTRY
LA English
DT Letter
C1 [Miller, W. Greg] Virginia Commonwealth Univ, Dept Pathol, Richmond, VA 23298 USA.
   [Myers, Gary L.] AACC, Washington, DC USA.
   [Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
RP Miller, WG (reprint author), Virginia Commonwealth Univ, Dept Pathol, POB 980286, Richmond, VA 23298 USA.
EM gmiller@vcu.edu
NR 1
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD JUL
PY 2011
VL 57
IS 7
BP 1083
EP 1083
DI 10.1373/clinchem.2011.163386
PG 1
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 784DL
UT WOS:000292134400030
ER

PT J
AU Stanley, RJ
   De, S
   Demner-Fushman, D
   Antani, S
   Thoma, GR
AF Stanley, R. Joe
   De, Soumya
   Demner-Fushman, Dina
   Antani, Sameer
   Thoma, George R.
TI An image feature-based approach to automatically find images for
   application to clinical decision support
SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS
LA English
DT Article
DE Computer-assisted; Image processing; Medical informatics computing;
   Information storage and retrieval; Image interpretation
AB The illustrations in biomedical publications often provide useful information in aiding clinicians' decisions when full text searching is performed to find evidence in support of a clinical decision. In this research, image analysis and classification techniques are explored to automatically extract information for differentiating specific modalities to characterize illustrations in biomedical publications, which may assist in the evidence finding process.
   Global, histogram-based, and texture image illustration features were compared to basis function luminance histogram correlation features for modality-based discrimination over a set of 742 manually annotated images by modality (radiological, photo, etc.) selected from the 2004-2005 issues of the British Journal of Oral and Maxillofacial Surgery. Using a mean shifting supervised clustering technique, automatic modality-based discrimination results as high as 95.57% were obtained using the basis function features. These results compared favorably to other feature categories examined. The experimental results show that image-based features, particularly correlation-based features, can provide useful modality discrimination information. (C) 2010 Elsevier Ltd. All rights reserved.
C1 [Stanley, R. Joe; De, Soumya] Missouri Univ Sci & Technol, Dept Elect & Comp Engn, Rolla, MO 65409 USA.
   [Demner-Fushman, Dina; Antani, Sameer; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, NIH, DHHS, Bethesda, MD 20894 USA.
RP Stanley, RJ (reprint author), Missouri Univ Sci & Technol, Dept Elect & Comp Engn, Rolla, MO 65409 USA.
EM stanleyj@mst.edu
OI Antani, Sameer/0000-0002-0040-1387
FU NLM [276200800413P]; National Institutes of Health (NIH); Lister Hill
   National Center for Biomedical Communications (LHNCBC)
FX This work was supported by NLM under contract number 276200800413P and
   the Intramural Research Program of the National Institutes of Health
   (NIH), NLM, and Lister Hill National Center for Biomedical
   Communications (LHNCBC).
NR 28
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U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-6111
EI 1879-0771
J9 COMPUT MED IMAG GRAP
JI Comput. Med. Imaging Graph.
PD JUL
PY 2011
VL 35
IS 5
BP 365
EP 372
DI 10.1016/j.compmedimag.2010.11.008
PG 8
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 781FQ
UT WOS:000291916400003
PM 21144707
ER

PT J
AU Bastian, LA
   Fish, LJ
   Peterson, BL
   Biddle, AK
   Garst, J
   Lyna, P
   Molner, S
   Bepler, G
   Kelley, M
   Keefe, FJ
   McBride, CM
AF Bastian, Lori A.
   Fish, Laura J.
   Peterson, Bercedis L.
   Biddle, Andrea K.
   Garst, Jennifer
   Lyna, Pauline
   Molner, Stephanie
   Bepler, Gerold
   Kelley, Mike
   Keefe, Francis J.
   McBride, Colleen M.
TI Proactive recruitment of cancer patients' social networks into a smoking
   cessation trial
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Recruitment; Social network; Smoking cessation; Lung cancer
ID LUNG-CANCER; INTERVENTION; PREDICTORS; DIAGNOSIS; RELATIVES; PARENTS;
   PROGRAM; FRIENDS; FAMILY
AB Background: This report describes the characteristics associated with successful enrollment of smokers in the social networks (i.e., family and close friends) of patients with lung cancer into a smoking cessation intervention.
   Methods: Lung cancer patients from four clinical sites were asked to complete a survey enumerating their family members and close friends who smoke, and provide permission to contact these potential participants. Family members and close friends identified as smokers were interviewed and offered participation in a smoking cessation intervention. Repeated measures logistic regression model examined characteristics associated with enrollment.
   Results: A total of 1062 eligible lung cancer patients were identified and 516 patients consented and completed the survey. These patients identified 1325 potentially eligible family and close friends. Of these, 496 consented and enrolled in the smoking cessation program. Network enrollment was highest among patients who were white and had late-stage disease. Social network members enrolled were most likely to be female, a birth family, immediate family, or close friend, and live in close geographic proximity to the patient.
   Conclusions: Proactive recruitment of smokers in the social networks of lung cancer patients is challenging. In this study, the majority of family members and friends declined to participate. Enlisting immediate female family members and friends, who live close to the patient as agents to proactively recruit other network members into smoking cessation trials could be used to extend reach of cessation interventions to patients_' social networks. Moreover, further consideration should be given to the appropriate timing of approaching network smokers to consider cessation. Published by Elsevier Inc.
C1 [Bastian, Lori A.; Kelley, Mike] Durham Vet Affairs Med Ctr, Durham, NC 27705 USA.
   [Bastian, Lori A.; Fish, Laura J.; Peterson, Bercedis L.; Garst, Jennifer; Lyna, Pauline; Molner, Stephanie; Kelley, Mike; Keefe, Francis J.] Duke Univ, Med Ctr, Canc Prevent Detect & Control Res Program, Duke Comprehens Canc Ctr, Durham, NC 27710 USA.
   [Bastian, Lori A.; Garst, Jennifer; Kelley, Mike] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
   [Biddle, Andrea K.] Univ N Carolina, Dept Hlth Policy & Adm, Chapel Hill, NC USA.
   [Bepler, Gerold] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Thorac Oncol, Tampa, FL 33612 USA.
   [McBride, Colleen M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
RP Bastian, LA (reprint author), Durham VA, 508 Fulton St 152, Durham, NC 27705 USA.
EM basti001@mc.duke.edu
OI Biddle, Andrea/0000-0003-0273-7439; Kelley, Michael/0000-0001-9523-6080
FU National Cancer Institute [5UO1-CA-92622]; National Human Genome
   Research Institute, National Institutes of Health
FX This work was supported by the National Cancer Institute grant
   5UO1-CA-92622.; This research Was also supported [in part] by the
   Intramural Program of the National Human Genome Research Institute,
   National Institutes of Health. The content is solely the responsibility
   of the authors and does not necessarily represent the official views of
   the NCI, NHGRI, NIH or the Department of Veterans Affairs.
NR 27
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U1 1
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD JUL
PY 2011
VL 32
IS 4
BP 498
EP 504
DI 10.1016/j.cct.2011.03.006
PG 7
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 785JY
UT WOS:000292226500006
PM 21382509
ER

PT J
AU Williams, GC
   Patrick, H
   Niemiec, CP
   Ryan, RM
   Deci, EL
   Lavigne, HM
AF Williams, Geoffrey C.
   Patrick, Heather
   Niemiec, Christopher P.
   Ryan, Richard M.
   Deci, Edward L.
   Lavigne, Holly McGregor
TI The Smoker's Health Project: A self-determination theory intervention to
   facilitate maintenance of tobacco abstinence
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Autonomy; Perceived competence; Pragmatic comparative effectiveness
   trial; Self-determination theory; Tobacco abstinence
ID RANDOMIZED CONTROLLED-TRIAL; SMOKING-CESSATION INTERVENTION;
   CLINICAL-TRIAL; PHYSICAL-ACTIVITY; WEIGHT CONTROL; PROCESS MODEL;
   MORTALITY; RISK; ASSOCIATION; MOTIVATION
AB A previous randomized clinical trial based on self-determination theory (SOT) and consistent with the Public Health Service (PHS) Guideline for Treating Tobacco Use and Dependence demonstrated that an intensive intervention could change autonomous self-regulation and perceived competence, which in part facilitated long-term tobacco abstinence. The current article describes a pragmatic comparative effectiveness trial of three SDT-based intensive tobacco-dependence interventions. Eligible participants are randomized to one of the three treatment conditions designed to facilitate long-term maintenance of tobacco abstinence, namely, Community Care (CC). which includes the 6 month SDT-based intervention previously shown to promote autonomous self-regulation, perceived competence, medication use, and tobacco abstinence; Extended Need Support (ENS), which extends the 6 month SDT-based intervention to 12 months and trains an important other to provide support for smokers' basic psychological needs; and Harm Reduction (HR), which provides extended need support and recommends medication use for participants who do not want to stop smoking completely within 30 days but who are willing to reduce their cigarette use by half. The primary outcome is 12 month prolonged abstinence from tobacco, which is assessed one year following termination of treatment (two years post-randomization). Secondary outcomes include 7- and 30 day point prevalence tobacco abstinence, number of days using smoking-cessation medication, change in autonomous self-regulation and perceived competence, and perceived need support from important others. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Williams, Geoffrey C.; Lavigne, Holly McGregor] Univ Rochester, Ctr Community Hlth, Hlth Living Ctr, Rochester, NY 14607 USA.
   [Niemiec, Christopher P.; Ryan, Richard M.; Deci, Edward L.] Univ Rochester, Dept Clin & Social Sci Psychol, Rochester, NY 14627 USA.
   [Patrick, Heather] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Williams, GC (reprint author), Univ Rochester, Ctr Community Hlth, Hlth Living Ctr, 46 Prince St,Suite 3001, Rochester, NY 14607 USA.
EM Geoffrey_Williams@URMC.Rochester.edu
OI Ryan, Richard M/0000-0002-2355-6154
FU National Cancer Institute [R01-CA106668, R01-MH059594]; National
   Institute of Mental Health; National Center for Research Resources
   [M01-RR00044]; National Center for Research Resources ARRA Supplement
   [UL1RR024160]
FX This research was supported by grants from the National Cancer Institute
   [R01-CA106668] awarded to Dr. Geoffrey Williams, MD, PhD; the National
   Institute of Mental Health and the National Cancer Institute
   [R01-MH059594] awarded to Dr. Geoffrey Williams, MD, PhD; the National
   Center for Research Resources [M01-RR00044] awarded to the University of
   Rochester General Clinical Research Center; and the National Center for
   Research Resources ARRA Supplement [UL1RR024160] awarded to the
   University of Rochester's Clinical and Translational Science Institute.
NR 52
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U1 3
U2 22
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD JUL
PY 2011
VL 32
IS 4
BP 535
EP 543
DI 10.1016/j.cct.2011.03.002
PG 9
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 785JY
UT WOS:000292226500012
PM 21382516
ER

PT J
AU Nelson, EE
   Guyer, AE
AF Nelson, Eric E.
   Guyer, Amanda E.
TI The development of the ventral prefrontal cortex and social flexibility
SO DEVELOPMENTAL COGNITIVE NEUROSCIENCE
LA English
DT Review
DE Childhood; Adolescence; Emotion; Affiliative
AB Over the last several years a number of studies in both humans and animals have suggested that the orbitofrontal and ventrolateral prefrontal cortices play an important role in generating flexible behavior. We suggest that input from these brain regions contribute to three functions involved in generating flexible behavior within social contexts: valuation, inhibition, and rule use. Recent studies have also demonstrated that the prefrontal cortex undergoes a prolonged course of maturation that extends well after puberty. Here, we review evidence that the prolonged development of these prefrontal regions parallels a slowly emerging ability for flexible social behavior. We also speculate on the possibility that sensitive periods for organizing social behavior may be embedded within this developmental time-fame. Finally, we discuss the role of prefrontal cortex in adolescent mood and anxiety disorders, particularly as orbitofrontal and ventrolateral prefrontal cortices are engaged in a social context. Published by Elsevier Ltd.
C1 [Nelson, Eric E.] NIMH, Sect Dev Affect Neurosci, Bethesda, MD 20892 USA.
   [Guyer, Amanda E.] Univ Calif Davis, Dept Human & Community Dev, Ctr Mind & Brain, Davis, CA 95618 USA.
RP Nelson, EE (reprint author), NIMH, Sect Dev Affect Neurosci, Bethesda, MD 20892 USA.
EM nelsone@mail.nih.gov
OI Nelson, Eric/0000-0002-3376-2453
FU National Institute of Mental Health; NIH [K99 MH080076, R00 MH080076]
FX The authors report no financial relationships with commercial interests.
   This research was supported by the Intramural Research Program of the
   National Institute of Mental Health and NIH Career Development Grants to
   A.E.G. (K99 MH080076 and R00 MH080076).
NR 126
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U1 9
U2 25
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1878-9293
J9 DEV COGN NEUROS-NETH
JI Dev. Cogn. Neurosci.
PD JUL
PY 2011
VL 1
IS 3
BP 233
EP 245
DI 10.1016/j.dcn.2011.01.002
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA V28AK
UT WOS:000208653500003
PM 21804907
ER

PT J
AU Prawitt, J
   Abdelkarim, M
   Stroeve, JHM
   Popescu, I
   Duez, H
   Velagapudi, VR
   Dumont, J
   Bouchaert, E
   van Dijk, TH
   Lucas, A
   Dorchies, E
   Daoudi, M
   Lestavel, S
   Gonzalez, FJ
   Oresic, M
   Cariou, B
   Kuipers, F
   Caron, S
   Staels, B
AF Prawitt, Janne
   Abdelkarim, Mouaadh
   Stroeve, Johanna H. M.
   Popescu, Iuliana
   Duez, Helene
   Velagapudi, Vidya R.
   Dumont, Julie
   Bouchaert, Emmanuel
   van Dijk, Theo H.
   Lucas, Anthony
   Dorchies, Emilie
   Daoudi, Mehdi
   Lestavel, Sophie
   Gonzalez, Frank J.
   Oresic, Matej
   Cariou, Bertrand
   Kuipers, Folkert
   Caron, Sandrine
   Staels, Bart
TI Farnesoid X Receptor Deficiency Improves Glucose Homeostasis in Mouse
   Models of Obesity
SO DIABETES
LA English
DT Article
ID BILE-ACIDS; INSULIN-RESISTANCE; ADIPOCYTE DIFFERENTIATION;
   CARBOHYDRATE-METABOLISM; TRIGLYCERIDE LEVELS; MICE; FXR; ACTIVATION;
   HYPERGLYCEMIA; SENSITIVITY
AB OBJECTIVE-Bile acids (BA) participate in the maintenance of metabolic homeostasis acting through different signaling pathways. The nuclear BA receptor farnesoid X receptor (FXR) regulates pathways in BA, lipid, glucose, and energy metabolism, which become dysregulated in obesity. However, the role of FXR in obesity and associated complications, such as dyslipidemia and insulin resistance, has not been directly assessed.
   RESEARCH DESIGN AND METHODS-Here, we evaluate the consequences of FXR deficiency on body weight development, lipid metabolism, and insulin resistance in murine models of genetic and diet-induced obesity.
   RESULTS-FXR deficiency attenuated body weight gain and reduced adipose tissue mass in both models. Surprisingly, glucose homeostasis improved as a result of an enhanced glucose clearance and adipose tissue insulin sensitivity. In contrast, hepatic insulin sensitivity did not change, and liver steatosis aggravated as a result of the repression of beta-oxidation genes. In agreement, liver-specific FXR deficiency did not protect from diet-induced obesity and insulin resistance, indicating a role for nonhepatic FXR in the control of glucose homeostasis in obesity. Decreasing elevated plasma BA concentrations in obese FXR-deficient mice by administration of the BA sequestrant colesevelarn improved glucose homeostasis in a FXR-dependent manner, indicating that the observed improvements by FXR deficiency are not a result of indirect effects of altered BA metabolism.
   CONCLUSIONS-Overall, FXR deficiency in obesity beneficially affects body weight development and glucose homeostasis.Diabetes 60:1861-1871, 2011
C1 [Prawitt, Janne; Abdelkarim, Mouaadh; Popescu, Iuliana; Duez, Helene; Dumont, Julie; Bouchaert, Emmanuel; Lucas, Anthony; Dorchies, Emilie; Daoudi, Mehdi; Lestavel, Sophie; Cariou, Bertrand; Caron, Sandrine; Staels, Bart] Univ Lille Nord France, INSERM, UDSL, Inst Pasteur Lille,UMR1011, Lille, France.
   [Stroeve, Johanna H. M.; van Dijk, Theo H.; Kuipers, Folkert] Univ Groningen, Univ Med Ctr Groningen, Ctr Liver Digest & Metab Dis, Pediat Lab, NL-9713 AV Groningen, Netherlands.
   [Velagapudi, Vidya R.; Oresic, Matej] VTT Tech Res Ctr Finland, Espoo, Finland.
   [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Cariou, Bertrand] Univ Nantes, INSERM, U915,Univ Hosp Ctr Nantes, Fac Med,Thorax Inst,Clin Endocrinol, Nantes, France.
RP Staels, B (reprint author), Univ Lille Nord France, INSERM, UDSL, Inst Pasteur Lille,UMR1011, Lille, France.
EM bart.staels@pasteur-lille.fr
RI Velagapudi, Vidya/L-7278-2015; Lestavel, Sophie/B-4658-2017; 
OI Velagapudi, Vidya/0000-0002-8261-7164; Lestavel,
   Sophie/0000-0001-7839-4757; Oresic, Matej/0000-0002-2856-9165; Staels,
   Bart/0000-0002-3784-1503
FU European Union [018734]; Agence Nationale de la Recherche [A05056GS];
   COST [Action BM0602]
FX This study was supported by the European Union Grant HEPADIP (No.
   018734), the Agence Nationale de la Recherche (No. A05056GS), and COST
   (Action BM0602).
NR 34
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U1 3
U2 22
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD JUL
PY 2011
VL 60
IS 7
BP 1861
EP 1871
DI 10.2337/db11-0030
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 788DO
UT WOS:000292425800007
PM 21593203
ER

PT J
AU Aygun, O
AF Ayguen, Ozan
TI Theoretically European, practically overseas
SO EMBO REPORTS
LA English
DT Letter
C1 NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Aygun, O (reprint author), NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
EM ozan.aygun@nih.gov
NR 3
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1469-221X
J9 EMBO REP
JI EMBO Rep.
PD JUL
PY 2011
VL 12
IS 7
BP 623
EP 623
DI 10.1038/embor.2011.103
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 786RN
UT WOS:000292325700009
PM 21720448
ER

PT J
AU Blair, RJR
AF Blair, R. J. R.
TI Moral Judgment and Psychopathy
SO EMOTION REVIEW
LA English
DT Article
DE amygdala; different forms of morality; psychopathic tendencies
ID CORTEX
AB Recent interest in emotion as the basis for moral development began with work involving individuals with psychopathic tendencies, and a recent paper with this population has allowed fresh insights (Glenn, Iyer, Graham, Koleva, & Haidt, 2009). Two main conclusions suggested by this paper are: (i) that systems involved in different forms of morality can be differentiated; and (ii) that systems involved in justice reasoning likely include amygdala and/or ventromedial prefrontal cortex, even if the specifics of their functional contribution to justice development remain unidentified.
C1 [Blair, R. J. R.] NIMH, Bethesda, MD 20892 USA.
RP Blair, RJR (reprint author), 10 Ctr Dr, Bethesda, MD 20892 USA.
EM JamesBlair@mail.nih.gov
NR 13
TC 5
Z9 5
U1 2
U2 16
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1754-0739
J9 EMOT REV
JI Emot. Rev.
PD JUL
PY 2011
VL 3
IS 3
BP 296
EP 298
DI 10.1177/1754073911406297
PG 3
WC Psychology, Multidisciplinary
SC Psychology
GA 972JY
UT WOS:000306274600022
ER

PT J
AU de Oliveira-Souza, R
   Moll, J
   Grafman, J
AF de Oliveira-Souza, Ricardo
   Moll, Jorge
   Grafman, Jordan
TI Emotion and Social Cognition: Lessons from Contemporary Human
   Neuroanatomy
SO EMOTION REVIEW
LA English
DT Article
DE altruism; human brain evolution; human nature; limbic system; neural
   reorganization
ID PREFRONTAL CORTEX; MORAL JUDGMENT; HUMAN BRAIN; DAMAGE
AB Two paradigms have guided emotion research over the past decades. The dual-system view embraces the long-held Western belief, espoused most prominently by decision-making and social cognition researchers, that emotion and reason are often at odds. The integrative view, which asserts that emotion and cognition work synergistically, has been less explored experimentally. However, the integrative view (a) may help explain several findings that are not easily accounted for by the dual-system approach, and (b) is better supported by a growing body of evidence from human neuroanatomy that has often been overlooked by experimental neuroscience.
C1 [de Oliveira-Souza, Ricardo; Moll, Jorge] DOr Inst Res & Educ IDOR, Ctr Neurosci, Cognit & Behav Neurosci Unit, BR-22281100 Rio De Janeiro, RJ, Brazil.
   [Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
RP de Oliveira-Souza, R (reprint author), DOr Inst Res & Educ IDOR, Ctr Neurosci, Cognit & Behav Neurosci Unit, Rua Diniz Cordeiro 30,3 Andar Botafogo, BR-22281100 Rio De Janeiro, RJ, Brazil.
EM rdeoliveira@gmail.com
RI Moll, Jorge/B-2654-2013; Neurociencia, Inct/I-1011-2013; 
OI Grafman, Jordan H./0000-0001-8645-4457
NR 24
TC 8
Z9 8
U1 1
U2 9
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1754-0739
J9 EMOT REV
JI Emot. Rev.
PD JUL
PY 2011
VL 3
IS 3
BP 310
EP 312
DI 10.1177/1754073911402399
PG 3
WC Psychology, Multidisciplinary
SC Psychology
GA 972JY
UT WOS:000306274600027
ER

PT J
AU Azevedo, MF
   Stratakis, CA
AF Azevedo, Monalisa F.
   Stratakis, Constantine A.
TI THE TRANSCRIPTOME THAT MEDIATES INCREASED CYCLIC ADENOSINE MONOPHOSPHATE
   SIGNALING IN PRKAR1A DEFECTS AND OTHER SETTINGS
SO ENDOCRINE PRACTICE
LA English
DT Review
AB Objective: To review current knowledge on the involvement of cyclic adenosine monophosphate (cAMP) and interacting signaling pathways in predisposition to tumor formation in primary pigmented nodular adrenocortical disease (PPNAD), a type of bilateral adrenal hyperplasia (BAH) related to the multiple endocrine neoplasia Carney complex, and also in isolated PPNAD and other BAHs.
   Methods: We review the pertinent literature and discuss genetic defects associated with various endocrine and nonendocrine tumors.
   Results: A decade ago, we discovered that PPNAD and the Carney complex are caused by PRKAR1A mutations. PRKAR1A encodes the protein kinase A (PKA) regulatory subunit type IA, an important regulator of cAMP signaling in most cells. Recently, we described PKA or PRKAR1A abnormalities in a variety of other BAHs; in some of these cases, mutations in additional genes of the cAMP signaling pathway, the phosphodiesterases, were identified. Transcriptomic analyses of human lesions or animal models showed that abnormal cAMP/PKA signaling in the adrenal glands, and also in other tissues such as bone, leads to proliferation of tissue-specific pluripotential cells through activation of Wnt signaling.
   Conclusion: Recent findings indicate the relevance of cAMP signaling in the pathogenesis of adrenocortical disease and point to the Wnt signaling pathway as a potential important mediator of tumorigenesis related to increased cAMP or PKA signaling (or both).
C1 [Azevedo, Monalisa F.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
   [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD USA.
RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH,CRC, Bldg 10,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU Intramural NIH HHS [ZIA HD008920-01]
NR 54
TC 2
Z9 2
U1 0
U2 2
PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS
PI JACKSONVILLE
PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA
SN 1530-891X
EI 1934-2403
J9 ENDOCR PRACT
JI Endocr. Pract.
PD JUL-AUG
PY 2011
VL 17
SU 3
BP 2
EP 7
DI 10.4158/EP10412.RA
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V28YL
UT WOS:000208716000002
PM 21454229
ER

PT J
AU Marx, SJ
AF Marx, Stephen J.
TI HYPERPARATHYROID GENES: SEQUENCES REVEAL ANSWERS AND QUESTIONS
SO ENDOCRINE PRACTICE
LA English
DT Review
ID MULTIPLE ENDOCRINE NEOPLASIA; FAMILIAL HYPOCALCIURIC HYPERCALCEMIA;
   CALCIUM-SENSING RECEPTOR; GERM-LINE MUTATIONS; NEONATAL SEVERE
   HYPERPARATHYROIDISM; VITAMIN-D-RECEPTOR; JAW TUMOR SYNDROME;
   CA2+-SENSING RECEPTOR; PARATHYROID ADENOMAS; RET PROTOONCOGENE
AB Objective: To review hyperparathyroid syndromes and genes.
   Methods: Pertinent original studies from the literature are discussed.
   Results: Six main hyperparathyroid syndromes are recognized; 5 are from germline mutations in 4 genes-CASR, MEN1, RET, and HRPT2. Each hyperparathyroid syndrome was first described around 1965; the main gene for each syndrome was identified about 30 years later. Gene identification addressed clinical issues. (1) Testing for mutation carriers among affected probands or among unaffected relatives is more robust than prior methods, which were based on syndromal traits such as serum calcium. (2) Interpreting a gene test (RET) could guide an important intervention; other gene tests could yield useful information for patients and physicians. (3) Proving the roles of each gene (in particular, MEN1 somatic mutations) provided insights about contributions to many common tumors. (4) Clarifying molecular pathways and drugs led, for example, to the CASR-aided development of calcimimetic and calcilytic drugs. (5) Explaining novel features, such as the CASR gene encoding a membrane calcium-sensing receptor and its mutations resulting in nonsuppressed parathyroid hormone secretion uncoupled from proliferation, characterized familial hypocalciuric hypercalcemia. (6) Disclosing probands without an identifiable mutation promoted searches for other syndromal genes. Subsequently, rare multiple endocrine neoplasia type 1-like families were shown to have inactivating germline mutations, first of p27 and subsequently of p15, p18, or p21.
   Conclusion: The next frontier in mutation detection is arriving, with possible sequencing of the whole exome or even the whole genome for 1 case or 1 tumor at an affordable cost.
C1 [Marx, Stephen J.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA.
   [Marx, Stephen J.] NIDDK, Endocrinol Sect, NIH, Bethesda, MD USA.
RP Marx, SJ (reprint author), NIH, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA.
EM MarxS@mail.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX Many colleagues, particularly on the National Institutes of Health
   campus, have contributed. I am indebted in particular to the late Gerald
   Aurbach, Allen Spiegel, Francis Collins, Sunita Agarwal, Edward Brown,
   William Simonds, and Settara Chandrasekharappa. I thank also the
   faculty, trainees, and patients in the National Institutes of Health
   Interinstitute Endocrine Training Program. This work has been funded
   mainly by the intramural program of the National Institute of Diabetes
   and Digestive and Kidney Diseases.
NR 74
TC 15
Z9 16
U1 0
U2 2
PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS
PI JACKSONVILLE
PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA
SN 1530-891X
EI 1934-2403
J9 ENDOCR PRACT
JI Endocr. Pract.
PD JUL-AUG
PY 2011
VL 17
SU 3
BP 18
EP 27
DI 10.4158/EP11067.RA
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA V28YL
UT WOS:000208716000004
PM 21454225
ER

PT J
AU Yuan, LX
   Sun, LG
   Wei, GJ
   Long, NY
   Xie, ZQ
   Wang, YH
AF Yuan, Linxi
   Sun, Liguang
   Wei, Gangjian
   Long, Nanye
   Xie, Zhouqing
   Wang, Yuhong
TI 9,400 yr B.P.: the mortality of mollusk shell (Mya truncata) at high
   Arctic is associated with a sudden cooling event
SO ENVIRONMENTAL EARTH SCIENCES
LA English
DT Article
DE 9,400 yr BP; Cooling event; Shell fragments; delta(18)O; Ny-Alesund
ID GREENLAND ICE-CORE; NORTH-ATLANTIC; HOLOCENE CLIMATE; NORWEGIAN SEA;
   PHACOSOMA-JAPONICUM; WESTERN SPITSBERGEN; SVALBARD; KONGSFJORDEN;
   RECORDS; SEDIMENT
AB An 118-cm-long, well-preserved sediment profile was collected from a paleo-notch formed by ocean wave action before rising to the terrace on Ny-lesund, Svalbard, Norway. A large number of mollusk shell fragments, predominantly Mya truncata, were found in the sediment profile. AMS (14)C dating and stable oxygen and carbon isotope analyses were performed on the shell fragments samples. The reservoir-corrected radiocarbon ages averaged similar to 9,400 yr B.P., which accurately dates the raised terrace and the upper marine limit after Kongsfjorden was completely deglaciated. The calibrated aragonite isotopic temperature equation was established for Ny-lesund by comparing the delta(18)O profiles of modern mollusks as follows: T (A degrees C) = 16.26 - 3.68(delta(18)O(aragonite-PDB) - delta(18)O(water-VSMOW)). The reconstructed paleotemperature range was -0.52 to +4.78A degrees C, warmer than today by about 1A degrees C, which was further confirmed by reconstructed sea surface temperature (SST) in west Svalbard. Moreover, the mortality of mollusks was very likely caused by an abrupt cooling event at about 9,400 yr B.P., which was triggered by reduced insolation, weakened thermohaline circulation, and abruptly decreased SST. More evidences for this distinct but short cooling event centered at about 9,400 yr B.P. were found in Northern Siberia, North Atlantic, Alps, and Eastern Europe.
C1 [Yuan, Linxi; Sun, Liguang; Xie, Zhouqing] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China.
   [Wei, Gangjian] Chinese Acad Sci, Key Lab Marginal Sea Geol, Guangzhou 510640, Guangdong, Peoples R China.
   [Long, Nanye] Univ Wisconsin, Dept Anim Sci, Madison, WI 53706 USA.
   [Wang, Yuhong] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China.
EM slg@ustc.edu.cn
FU Chinese Arctic and Antarctic Administration (CAAA); 973 Program
   [2010CB428902]
FX We appreciate Prof. Steven D. Emslie (North Carolina State University)
   for their critical comments and revision to improve this manuscript.
   Thanks are sent to Prof. Fridtjof Mehlum (University of Oslo) for
   helpful discussion during Arctic Science Submit Week 2009 (ASSW2009). We
   also thank an anonymous reviewer for his valuable critical comments in
   improving manuscript. Authors wish to thank the Chinese Arctic and
   Antarctic Administration (CAAA) for supporting. This research was funded
   by 973 Program (Grant No 2010CB428902).
NR 58
TC 3
Z9 3
U1 2
U2 20
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1866-6280
J9 ENVIRON EARTH SCI
JI Environ. Earth Sci.
PD JUL
PY 2011
VL 63
IS 6
BP 1385
EP 1393
DI 10.1007/s12665-010-0808-8
PG 9
WC Environmental Sciences; Geosciences, Multidisciplinary; Water Resources
SC Environmental Sciences & Ecology; Geology; Water Resources
GA 782WJ
UT WOS:000292043100019
ER

PT J
AU Brenner, AV
   Tronko, MD
   Hatch, M
   Bogdanova, TI
   Oliynik, VA
   Lubin, JH
   Zablotska, LB
   Tereschenko, VP
   McConnell, RJ
   Zamotaeva, GA
   O'Kane, P
   Bouville, AC
   Chaykovskaya, LV
   Greenebaum, E
   Paster, IP
   Shpak, VM
   Ron, E
AF Brenner, Alina V.
   Tronko, Mykola D.
   Hatch, Maureen
   Bogdanova, Tetyana I.
   Oliynik, Valery A.
   Lubin, Jay H.
   Zablotska, Lydia B.
   Tereschenko, Valery P.
   McConnell, Robert J.
   Zamotaeva, Galina A.
   O'Kane, Patrick
   Bouville, Andre C.
   Chaykovskaya, Ludmila V.
   Greenebaum, Ellen
   Paster, Ihor P.
   Shpak, Victor M.
   Ron, Elaine
TI I-131 Dose Response for Incident Thyroid Cancers in Ukraine Related to
   the Chornobyl Accident
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE Chernobyl nuclear accident; Chornobyl; Ukraine; 1986; dose-response
   relationship; incidence; thyroid neoplasms/epidemiology; iodine;
   radioactive; radiation
ID POWER-STATION ACCIDENT; ATOMIC-BOMB SURVIVORS; IODINE DEFICIENCY; POOLED
   ANALYSIS; RISK; DISEASES; RADIATION; EXPOSURE; COHORT; PREVALENCE
AB BACKGROUND: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case-control studies, and studies of prevalent cancers.
   OBJECTIVE: To address this limitation, we evaluated the dose-response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study.
   METHODS: The cohort consists of individuals < 18 years of age on 26 April 1986 who resided in three contaminated oblasts (states) of Ukraine and underwent up to four thyroid screening examinations between 1998 and 2007 (n = 12,514). Thyroid doses of I-131 were estimated based on individual radio-activity measurements taken within 2 months after the accident, environmental transport models, and interview data. Excess radiation risks were estimated using Poisson regression models.
   RESULTS: Sixty-five incident thyroid cancers were diagnosed during the second through fourth screenings and 73,004 person-years (PY) of observation. The dose-response relationship was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than did the excess absolute risk (EAR) model. The ERR per gray was 1.91 [95% confidence interval (CI), 0.43-6.34], and the EAR per 10(4) PY/Gy was 2.21 (95% CI, 0.04-5.78). The ERR per gray varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size.
   CONCLUSIONS: I-131-related thyroid cancer risks persisted for two decades after exposure, with no evidence of decrease during the observation period. The radiation risks, although smaller, are compatible with those of retrospective and ecological post-Chornobyl studies.
C1 [Brenner, Alina V.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
   [Tronko, Mykola D.; Bogdanova, Tetyana I.; Oliynik, Valery A.; Tereschenko, Valery P.; Zamotaeva, Galina A.; Chaykovskaya, Ludmila V.; Paster, Ihor P.; Shpak, Victor M.] Inst Endocrinol & Metab, Kiev, Ukraine.
   [Zablotska, Lydia B.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   [McConnell, Robert J.] Columbia Univ, Coll Phys & Surg, Thyroid Clin, Dept Med, New York, NY USA.
   [O'Kane, Patrick] Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA.
   [Greenebaum, Ellen] Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA.
RP Brenner, AV (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, MS 7238,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM brennera@mail.nih.gov
FU U.S. National Institutes of Health (NIH) Fogarty International Center;
   National Cancer Institute, NIH; Department of Energy; U.S. Nuclear
   Regulatory Commission
FX We are indebted to I. Masnyk (National Cancer Institute), former project
   director, for management of the diplomatic, financial, and contractual
   aspects of the study. We thank the Louise Hamilton, Kyiv Data Management
   Center of the University of Illinois at Chicago, supported in part by
   the U.S. National Institutes of Health (NIH) Fogarty International
   Center, and its head, O. Zvinchuk, for database management. We owe
   special acknowledgment to the late G.R. Howe (Columbia University), who
   was co-principal investigator for the Ukrainian-American Thyroid Study
   until his death in 2006. We also thank the late O. Epshtein (Institute
   of Endocrinology and Metabolism, Kyiv, Ukraine) and D.J. Fink (Columbia
   University) for laboratory expertise and support, and J. Robbins
   (National Institute of Diabetes and Digestive and Kidney Diseases) for
   endocrinological expertise. We are grateful to R. Brill (Vanderbilt
   University Medical Center) for contribution in organizing the ultrasound
   screening and quality control procedures. We acknowledge the
   confirmation of thyroid cancer diagnoses provided by the International
   Pathology Panel of the Chornobyl Tissue Bank: A. Abrosimov, T.
   Bogdanova, M. Ito, V. LiVolsi, J. Rosai, and E.D. Williams. We are
   grateful to I. Likhtarev (Radiation Protection Institute, Ukrainian
   Academy of Technological Sciences, Kyiv, Ukraine) for critical review of
   the manuscript and helpful comments.; This research was supported by the
   Intramural Research Program of the National Cancer Institute, NIH, and
   the Department of Energy. The U.S. Nuclear Regulatory Commission
   provided the initial funds for equipment purchase.
NR 33
TC 68
Z9 71
U1 4
U2 13
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUL
PY 2011
VL 119
IS 7
BP 933
EP 939
DI 10.1289/ehp.1002674
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 786IT
UT WOS:000292299300024
PM 21406336
ER

PT J
AU Gunier, RB
   Ward, MH
   Airola, M
   Bell, EM
   Colt, J
   Nishioka, M
   Buffler, PA
   Reynolds, P
   Rull, RP
   Hertz, A
   Metayer, C
   Nuckols, JR
AF Gunier, Robert B.
   Ward, Mary H.
   Airola, Matthew
   Bell, Erin M.
   Colt, Joanne
   Nishioka, Marcia
   Buffler, Patricia A.
   Reynolds, Peggy
   Rull, Rudolph P.
   Hertz, Andrew
   Metayer, Catherine
   Nuckols, John R.
TI Determinants of Agricultural Pesticide Concentrations in Carpet Dust
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE agriculture; dust; exposure; GIS; pesticides
ID CENTRAL VALLEY; RESIDENTIAL PROXIMITY; EXPOSURE ASSESSMENT; MATERNAL
   RESIDENCE; SPRAY DRIFT; CALIFORNIA; CHILDREN; HOMES; CHLORPYRIFOS;
   COMMUNITY
AB BACKGROUND: Residential proximity to agricultural pesticide applications has been used as a surrogate for exposure in epidemiologic studies, although little is known about the relationship with levels of pesticides in homes.
   OBJECTIVE: We identified determinants of concentrations of agricultural pesticides in dust.
   METHODS: We collected samples of carpet dust and mapped crops within 1,250 m of 89 residences in California. We measured concentrations of seven pesticides used extensively in agriculture (carbaryl, chlorpyrifos, chlorthal-dimethyl, diazinon, iprodione, phosmet, and simazine). We estimated use of agricultural pesticides near residences from a statewide database alone and by linking the database with crop maps. We calculated the density of pesticide use within 500 and 1,250 m of residences for 180, 365, and 730 days before collection of dust and evaluated relationships between agricultural pesticide use estimates and pesticide concentrations in carpet dust.
   RESULTS: For five of the seven pesticides evaluated, residences with use of agricultural pesticides within 1,250 m during the previous 365 days had significantly higher concentrations of pesticides than did residences with no nearby use. The highest correlation with concentrations of pesticides was generally for use reported within 1,250 m of the residence and 730 days before sample collection. Regression models that also accounted for occupational and home use of pesticides explained only a modest amount of the variability in pesticide concentrations (4-28%).
   CONCLUSIONS: Agricultural pesticide use near residences was a significant determinant of concentrations of pesticides in carpet dust for five of seven pesticides evaluated.
C1 [Gunier, Robert B.; Reynolds, Peggy; Rull, Rudolph P.; Hertz, Andrew] Canc Prevent Inst Calif, Berkeley, CA 94704 USA.
   [Ward, Mary H.; Colt, Joanne] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
   [Airola, Matthew] Westat Corp, Rockville, MD USA.
   [Bell, Erin M.] SUNY Albany, Albany, NY 12222 USA.
   [Nishioka, Marcia] Battelle Mem Inst, Columbus, OH 43201 USA.
   [Buffler, Patricia A.; Metayer, Catherine] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
   [Nuckols, John R.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA.
RP Gunier, RB (reprint author), Canc Prevent Inst Calif, 2001 Ctr St,Ste 700, Berkeley, CA 94704 USA.
EM robert.gunier@cpic.org
RI Rull, Rudolph/B-8121-2013; 
OI Rull, Rudolph/0000-0003-0989-3629; Gunier, Robert/0000-0001-5485-9919
FU National Cancer Institute [1R01-CA92674, 5R01-CA092683, N02-CP-11015];
   National Institute of Environmental Health Sciences [2R01-ES09137];
   National Cancer Institute
FX This work was funded by National Cancer Institute grants 1R01-CA92674
   and 5R01-CA092683 and contract N02-CP-11015 and by National Institute of
   Environmental Health Sciences grant 2R01-ES09137. This work was also
   funded by the Intramural Research Program of the National Cancer
   Institute.
NR 42
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U1 1
U2 25
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD JUL
PY 2011
VL 119
IS 7
BP 970
EP 976
DI 10.1289/ehp.1002532
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 786IT
UT WOS:000292299300030
PM 21330232
ER

PT J
AU Raffa, D
   Maggio, B
   Plescia, F
   Cascioferro, S
   Plescia, S
   Raimondi, MV
   Daidone, G
   Tolomeo, M
   Grimaudo, S
   Di Cristina, A
   Pipitone, RM
   Bai, R
   Hamel, E
AF Raffa, Demetrio
   Maggio, Benedetta
   Plescia, Fabiana
   Cascioferro, Stella
   Plescia, Salvatore
   Raimondi, Maria Valeria
   Daidone, Giuseppe
   Tolomeo, Manlio
   Grimaudo, Stefania
   Di Cristina, Antonietta
   Pipitone, Rosaria Maria
   Bai, Ruoli
   Hamel, Ernest
TI Synthesis, antiproliferative activity, and mechanism of action of a
   series of 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides
SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
DE 2-{[2E]-3-phenylprop-2-enoylamino}benzamides; Antimitotic agents;
   Cytotoxic activity
ID ANTIMITOTIC AGENTS; TUBULIN; DERIVATIVES; CELLS
AB Several new 2-{[(2E)-3-phenylprop-2-enoyl]amino}benzamides 12a-s and 17t-v were synthesized by stirring in pyridine the (E)-3-(2-R1-3-R2-4-R3-phenyl)acrylic acid chlorides 11c-k and 11t-v with the appropriate anthranilamide derivatives 10a-c or the 5-iodoanthranilic acid 13. Some of the synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell line panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). COMPARE analysis, effects on tubulin polymerization in cells and with purified tubulin, and effects on cell cycle distribution for 17t, the most active of the series, indicate that these new antiproliferative compounds act as antitubulin agents. (C) 2011 Elsevier Masson SAS. All rights reserved.
C1 [Raffa, Demetrio; Maggio, Benedetta; Plescia, Fabiana; Cascioferro, Stella; Plescia, Salvatore; Raimondi, Maria Valeria; Daidone, Giuseppe] Dipartimento Sci & Tecnol Mol & Biomol, I-90123 Palermo, Italy.
   [Tolomeo, Manlio; Grimaudo, Stefania; Di Cristina, Antonietta; Pipitone, Rosaria Maria] Univ Palermo, Ctr Interdipartimentale Ric Oncol Clin, Palermo, Italy.
   [Tolomeo, Manlio; Grimaudo, Stefania; Di Cristina, Antonietta; Pipitone, Rosaria Maria] Univ Palermo, Dipartimento Biomed Med Interna & Specialist, Palermo, Italy.
   [Bai, Ruoli; Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
RP Raffa, D (reprint author), Dipartimento Sci & Tecnol Mol & Biomol, Via Archirafi 32, I-90123 Palermo, Italy.
EM demraffa@unipa.it
RI antonietta, di cristina/I-9251-2012; 
OI Daidone, Giuseppe/0000-0002-9529-8449; PIPITONE, Rosaria
   Maria/0000-0002-6721-3962; Raffa, Demetrio/0000-0002-1073-7706;
   Grimaudo, Stefania/0000-0003-3225-4112
FU MIUR
FX Financial support from MIUR (40% funding) is gratefully acknowledged.
   The authors wish to thank the Developmental Therapeutics Program of the
   National Cancer Institute of the United States of America for performing
   the antiproliferative screening of compounds.
NR 20
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U1 0
U2 2
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0223-5234
J9 EUR J MED CHEM
JI Eur. J. Med. Chem.
PD JUL
PY 2011
VL 46
IS 7
BP 2786
EP 2796
DI 10.1016/j.ejmech.2011.03.067
PG 11
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 780XS
UT WOS:000291895200015
PM 21530013
ER

PT J
AU Yang, M
   Gao, HK
   Yan, YJ
   Sun, XL
   Chen, K
   Quan, QM
   Lang, LX
   Kiesewetter, D
   Niu, G
   Chen, XY
AF Yang, Min
   Gao, Haokao
   Yan, Yongjun
   Sun, Xilin
   Chen, Kai
   Quan, Qimeng
   Lang, Lixin
   Kiesewetter, Dale
   Niu, Gang
   Chen, Xiaoyuan
TI PET imaging of early response to the tyrosine kinase inhibitor ZD4190
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE Positron emission tomography (PET); Antiangiogenic treatment; (18)F-FDG;
   (18)F-FLT; (18)F-FPPRGD2; Integrin; Therapy response; Tyrosine kinase
   inhibitor
ID ENDOTHELIAL GROWTH-FACTOR; POSITRON-EMISSION-TOMOGRAPHY; CELL
   LUNG-CANCER; TUMOR ANGIOGENESIS; IN-VIVO; THERAPY; VEGF;
   ALPHA(V)BETA(3); REPRODUCIBILITY; F-18-AH111585
AB Purpose We evaluated noninvasive positron emission tomography (PET) imaging for monitoring tumor response to the VEGFR-2 tyrosine kinase (TK) inhibitor ZD4190 during cancer therapy.
   Experimental design Orthotopic MDA-MB-435 tumor-bearing mice were treated with ZD4190 (100 mg/kg orally per day for three consecutive days). Tumor growth was monitored by caliper measurement. During the therapeutic period, longitudinal PET scans were acquired using (18)F-FDG, (18)F-FLT and (18)F-FPPRGD2 as imaging tracers to evaluate tumor glucose metabolism, tumor cell proliferation, and angiogenesis, respectively. Imaging metrics were validated by immunohistochemical analysis of Ki67, GLUT-1, F4/80, CD31, murine integrin beta 3, and human integrin alpha nu beta 3.
   Results Three consecutive daily oral administrations of 100 mg/kg of ZD4190 were effective in delaying MDA-MB-435 tumor growth. A significant difference in tumor volume was observed on day 7 between the treatment group and the control group (p<0.01). After the final treatment, tumor growth resumed after a short delay. In the control tumors, (18)F-FPPRGD2 uptake was stable between days 0 and 7. In ZD4190-treated tumors, (18)F-FPPRGD2 uptake had decreased significantly relative to baseline by 26.74 +/- 8.12% (p<0.05) on day 1 and by 41.19 +/- 6.63% (p<0.01) on day 3, then had returned to baseline on day 7. Tumor uptake of (18)F-FLT had also decreased on both day 1 and day 3 after initiation of ZD4190 treatment. No significant change in (18)F-FDG uptake in ZD4190-treated tumors was observed, however, compared with the control group. All of the imaging findings were supported by ex vivo analysis of related biomarkers.
   Conclusion The longitudinal imaging results demonstrated the usefulness of quantitative (18)F-FLT and (18)F-FPPRGD2 PET imaging in evaluating the early antiproliferative and antiangiogenic effects of ZD4190. The quantification data from the PET imaging were consistent with the pattern of initial growth inhibition with treatment, followed by tumor relapse after treatment cessation.
C1 [Yang, Min; Gao, Haokao; Yan, Yongjun; Sun, Xilin; Chen, Kai; Quan, Qimeng; Lang, Lixin; Kiesewetter, Dale; Niu, Gang; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA.
   [Yang, Min] Jiangsu Inst Nucl Med, Jiangsu Key Lab Mol Nucl Med, Minist Hlth, Key Lab Nucl Med, Wuxi, Jiangsu, Peoples R China.
   [Gao, Haokao] Fourth Mil Med Univ, Xijing Hosp, Dept Cardiol, Xian 710032, Peoples R China.
RP Niu, G (reprint author), NIBIB, LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA.
EM niug@mail.nih.gov; shawn.chen@nih.gov
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB),
   National Institutes of Health (NIH); National Science Foundation of
   China (NSFC) [81028009]; Outstanding Professionals Foundation of the
   Jiangsu Health Bureau [RC2007096]; IRP/NIBIB, NIH; Radiology and Imaging
   Sciences Department, NIH Clinical Center
FX This project was supported by the Intramural Research Program (IRP) of
   the National Institute of Biomedical Imaging and Bioengineering (NIBIB),
   National Institutes of Health (NIH), and the International Cooperative
   Program of the National Science Foundation of China (NSFC) (81028009).
   M.Y. is partly supported by the Outstanding Professionals Foundation of
   the Jiangsu Health Bureau (grant no. RC2007096). G.N. is currently an
   Imaging Sciences Training Program (ISTP) Fellow jointly supported by the
   Radiology and Imaging Sciences Department, NIH Clinical Center and the
   IRP/NIBIB, NIH. We acknowledge the NIH/CC cyclotron facility for isotope
   production and Dr. Henry S. Eden for proofreading the manuscript.
NR 48
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U1 0
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD JUL
PY 2011
VL 38
IS 7
BP 1237
EP 1247
DI 10.1007/s00259-011-1742-z
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 786AB
UT WOS:000292273400006
PM 21360246
ER

PT J
AU Ungvari, Z
   Sonntag, WE
   de Cabo, R
   Baur, JA
   Csiszar, A
AF Ungvari, Zoltan
   Sonntag, William E.
   de Cabo, Rafael
   Baur, Joseph A.
   Csiszar, Anna
TI Mitochondrial Protection by Resveratrol
SO EXERCISE AND SPORT SCIENCES REVIEWS
LA English
DT Review
DE senescence; bioenergetics; mitochondria; aging; caloric restriction;
   cardiovascular disease; phytochemicals
ID SMALL-MOLECULE ACTIVATORS; LIFE-SPAN; CALORIE RESTRICTION; OXIDATIVE
   STRESS; SKELETAL-MUSCLE; IN-VIVO; ENDOTHELIAL-CELLS; SIRT1; BIOGENESIS;
   MICE
AB UNGVARI, Z., W. E. SONNTAG, R. DE CABO, J.A. BAUR, and A. CSISZAR. Mitochondrial protection by resveratrol. Exerc. Sport. Sci. Rev., Vol. 39, No. 3, pp. 128-132, 2011. Mitochondrial dysfunction and oxidative stress are thought to play important roles in mammalian aging. Resveratrol is a plant-derived polyphenol that exerts diverse antiaging activities, mimicking some of the molecular and functional effects of dietary restriction. This review focuses on the molecular mechanisms underlying the mitochondrial protective effects of resveratrol, which could be exploited for the prevention or amelioration of age-related diseases in the elderly.
C1 [Ungvari, Zoltan; Sonntag, William E.; Csiszar, Anna] Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Dept Geriatr Med, Oklahoma City, OK 73104 USA.
   [Ungvari, Zoltan; Sonntag, William E.; Csiszar, Anna] Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Oklahoma City, OK 73104 USA.
   [de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
   [Baur, Joseph A.] Univ Penn, Raymond & Ruth Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
   [Baur, Joseph A.] Univ Penn, Raymond & Ruth Perelman Sch Med, Dept Physiol, Philadelphia, PA 19104 USA.
RP Ungvari, Z (reprint author), Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Dept Geriatr Med, 975 NE 10th St,BRC 1303, Oklahoma City, OK 73104 USA.
EM zoltan-ungvari@ouhsc.edu
RI Baur, Joseph/D-8163-2011; de Cabo, Rafael/J-5230-2016; 
OI de Cabo, Rafael/0000-0002-3354-2442; Baur, Joseph/0000-0001-8262-6549; ,
   rafael/0000-0003-2830-5693
FU American Diabetes Association; American Federation for Aging Research;
   University of Oklahoma College of Medicine Alumni Association; National
   Institutes of Health [AG031085, AT006526, HL077256, AG031182, P01
   AG11370]; National Institute on Aging
FX The authors acknowledge the work of their colleagues, whose ideas
   contributed to the understanding of the role of resveratrol in
   prevention of age-related pathologies but whose publications could not
   be cited because of the limits imposed by the journal. This work was
   supported by grants from the American Diabetes Association (to Z.U.),
   American Federation for Aging Research (to A. C.), the University of
   Oklahoma College of Medicine Alumni Association (to A. C.), the National
   Institutes of Health (AG031085 to A. C.; AT006526 and HL077256 to Z.U.;
   AG031182 to J.A.B.; P01 AG11370 to W. E. S.), and the Intramural
   Research Program of the National Institute on Aging (R.d.C.).
NR 36
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U1 2
U2 22
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0091-6331
J9 EXERC SPORT SCI REV
JI Exerc. Sport Sci. Rev.
PD JUL
PY 2011
VL 39
IS 3
BP 128
EP 132
DI 10.1097/JES.0b013e3182141f80
PG 5
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA 782QO
UT WOS:000292024900005
PM 21383627
ER

PT J
AU Ashkenazi, A
   Viard, M
   Wexler-Cohen, Y
   Blumenthal, R
   Shai, Y
AF Ashkenazi, Avraham
   Viard, Mathias
   Wexler-Cohen, Yael
   Blumenthal, Robert
   Shai, Yechiel
TI Viral envelope protein folding and membrane hemifusion are enhanced by
   the conserved loop region of HIV-1 gp41
SO FASEB JOURNAL
LA English
DT Article
DE HIV-1 fusion inhibitor; peptide-membrane interaction
ID IMMUNODEFICIENCY-VIRUS TYPE-1; DISULFIDE-ISOMERASE; MEDIATED FUSION;
   TRANSMEMBRANE GLYCOPROTEIN; INFLUENZA HEMAGGLUTININ; RECEPTOR-BINDING;
   ATOMIC-STRUCTURE; 6-HELIX BUNDLE; CORE STRUCTURE; CELL FUSION
AB Fusion of human immunodeficiency virus (HIV-1) with target cells is mediated by the gp41 transmembrane envelope protein. The loop region within gp41 contains 2 crucial cysteines that play an unknown role in HIV-cell fusion. On the basis of cell-cell fusion assay, using human T-cell lines [Jurkat E6-1 and Jurkat HXBc2(4)], and virus-cell fusion assay, using fully infectious HIV-1 HXBc2 virus and TZM-bl human cell line, we provide evidence that the oxidation state of the disulfide bond within a loop domain peptide determines its activity. The oxidized (closed) form inhibits fusion, while the reduced (opened) form enhances hemifusion. These opposite activities reach 60% difference in viral fusion. Both forms of the loop domain interact with gp41: the opened form enhances gp41 folding into a bundle, whereas the closed form inhibits this folding. Therefore, the transformation of the cysteines from a reduced to an oxidized state enables the loop to convert from opened to closed conformations, which assists gp41 to fold and induces hemifusion. The significant conservation of the loop region within many envelope proteins suggests a general mechanism, which is exploited by viruses to enhance entry into their host cells.-Ashkenazi, A., Viard, M., Wexler-Cohen, Y., Blumenthal, R., Shai, Y. Viral envelope protein folding and membrane hemifusion are enhanced by the conserved loop region of HIV-1 gp41. FASEB J. 25, 2156-2166 (2011). www.fasebj.org
C1 [Ashkenazi, Avraham; Wexler-Cohen, Yael; Shai, Yechiel] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
   [Viard, Mathias; Blumenthal, Robert] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21701 USA.
   [Viard, Mathias] Natl Canc Inst Frederick, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21701 USA.
RP Shai, Y (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
EM yechiel.shai@weizmann.ac.il
FU Israel Science Foundation; National Cancer Institute, U.S. National
   Institutes of Health (NIH) [HHSN26120080001E]; NIH, National Cancer
   Institute, Center for Cancer Research
FX The authors thank Batya Zarmi for her valuable help with peptide
   purification, Dr. Ayala Sharp and Eitan Ariel, and the staff of the flow
   cytometry unit at the Weizmann Institute of Science for their valuable
   technical assistance and advice. This study was supported by the Israel
   Science Foundation and also has been funded, in part, with federal funds
   from the National Cancer Institute, U.S. National Institutes of Health
   (NIH), under contract HHSN26120080001E. The content of this publication
   does not necessarily reflect the views or policies of the Department of
   Health and Human Services, nor does it mention any trade names,
   commercial products, or organizations or 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. Y.S. is the incumbent of the Harold S. and Harriet B.
   Brady Professorial Chair in Cancer Research.
NR 70
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U2 7
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD JUL
PY 2011
VL 25
IS 7
BP 2156
EP 2166
DI 10.1096/fj.10-175752
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA 785PY
UT WOS:000292242200008
PM 21429941
ER

PT J
AU Kasaikina, MV
   Kravtsova, MA
   Lee, BC
   Seravalli, J
   Peterson, DA
   Walter, J
   Legge, R
   Benson, AK
   Hatfield, DL
   Gladyshev, VN
AF Kasaikina, Marina V.
   Kravtsova, Marina A.
   Lee, Byung Cheon
   Seravalli, Javier
   Peterson, Daniel A.
   Walter, Jens
   Legge, Ryan
   Benson, Andrew K.
   Hatfield, Dolph L.
   Gladyshev, Vadim N.
TI Dietary selenium affects host selenoproteome expression by influencing
   the gut microbiota
SO FASEB JOURNAL
LA English
DT Article
DE selenoproteins; germ-free mice; high-throughput sequencing
ID HUMAN HEALTH; DISEASE; MICE; BACTERIA; METABOLISM; MODULATION; OBESITY;
   COLON
AB Colonization of the gastrointestinal tract and composition of the microbiota may be influenced by components of the diet, including trace elements. To understand how selenium regulates the intestinal microflora, we used high-throughput sequencing to examine the composition of gut microbiota of mice maintained on selenium-deficient, selenium-sufficient, and selenium-enriched diets. The microbiota diversity increased as a result of selenium in the diet. Specific phylotypes showed differential effects of selenium, even within a genus, implying that selenium had unique effects across microbial taxa. Conventionalized germfree mice subjected to selenium diets gave similar results and showed an increased diversity of the bacterial population in animals fed with higher levels of selenium. Germ-free mice fed selenium diets modified their selenoproteome expression similar to control mice but showed higher levels and activity of glutathione peroxidase 1 and methionine-R-sulfoxide reductase 1 in the liver, suggesting partial sequestration of selenium by the gut microorganisms, limiting its availability for the host. These changes in the selenium status were independent of the levels of other trace elements. The data show that dietary selenium affects both composition of the intestinal microflora and colonization of the gastrointestinal tract, which, in turn, influence the host selenium status and selenoproteome expression.-Kasaikina, M. V., Kravtsova, M. A., Lee, B. C., Seravalli, J., Peterson, D. A., Walter, J., Legge, R., Benson, A. K., Hatfield, D. L., Gladyshev, V. N. Dietary selenium affects host selenoproteome expression by influencing the gut microbiota. FASEB J. 25, 2492-2499 (2011). www.fasebj.org
C1 [Kasaikina, Marina V.; Lee, Byung Cheon; Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
   [Kasaikina, Marina V.; Lee, Byung Cheon; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
   [Kasaikina, Marina V.; Kravtsova, Marina A.; Lee, Byung Cheon; Seravalli, Javier; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA.
   [Kasaikina, Marina V.; Kravtsova, Marina A.; Lee, Byung Cheon; Seravalli, Javier; Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68583 USA.
   [Peterson, Daniel A.; Walter, Jens; Legge, Ryan; Benson, Andrew K.] Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA.
   [Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Gladyshev, VN (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, New Res Bldg,Rm 435,77 Ave Louis Pasteur, Boston, MA 02115 USA.
EM vgladyshev@rics.bwh.harvard.edu
RI Gladyshev, Vadim/A-9894-2013
FU U.S. National Institutes of Health (NIH) [GM061603, AG021518]; Center
   for Cancer Research, National Cancer Institute, NIH
FX This study was supported by U.S. National Institutes of Health (NIH)
   grants GM061603 and AG021518 (to V.N.G.) and the Intramural Research
   Program of the Center for Cancer Research, National Cancer Institute,
   NIH (to D.L.H.).
NR 27
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U1 1
U2 25
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD JUL
PY 2011
VL 25
IS 7
BP 2492
EP 2499
DI 10.1096/fj.11-181990
PG 8
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA 785PY
UT WOS:000292242200039
PM 21493887
ER

PT J
AU Meldrum, DR
   DeCherney, AH
AF Meldrum, David R.
   DeCherney, Alan H.
TI The WHO, WHY, WHAT, WHEN, WHERE, and HOW of clinical trial registries
SO FERTILITY AND STERILITY
LA English
DT Article
DE Clinical trial registry; FDA clinical trial registry requirements
AB Clinical trials must be appropriately registered prior to patient enrollment to be considered for publication by most top journals, including Fertility and Sterility. Clinical trials involving FDA regulated drugs, whether investigational or already approved, must be registered by law, and summary results must be posted in the registry whether ultimately published or not. This review provides detailed information for authors regarding these requirements and a discussion as to their importance for acceptance of a manuscript and for reviewers to be assured of the integrity of the trial design, execution, and analysis. The accompanying review on study design and statistics is meant to illustrate the difficulties reviewers experience in evaluating a manuscript that does not follow these requirements. The editors of Fertility and Sterility reiterate that clinical trials that have not been registered will not be accepted for review. (Fertil Steril (R) 2011;96:2-5. (C) 2011 by American Society for Reproductive Medicine.)
C1 [Meldrum, David R.] Reprod Partners Med Grp, Redondo Beach, CA 90277 USA.
   [DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Reprod Biol & Med Branch, NIH, Bethesda, MD USA.
RP Meldrum, DR (reprint author), Reprod Partners Med Grp, 510 N Prospect Ave 202, Redondo Beach, CA 90277 USA.
EM davidmeldrum@earthlink.net
NR 11
TC 4
Z9 4
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUL
PY 2011
VL 96
IS 1
BP 2
EP 5
DI 10.1016/j.fertnstert.2011.05.028
PG 4
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 786DH
UT WOS:000292283000021
PM 21621769
ER

PT J
AU Schlaff, WD
   Zhang, HP
   Diamond, MP
   Coutifaris, C
   Casson, PR
   Brzyski, RG
   Christman, GM
   Barnhart, KT
   Trussell, JC
   Krawetz, SA
   Snyder, PJ
   Ohl, D
   Santoro, N
   Eisenberg, E
   Huang, H
   Legro, RS
AF Schlaff, William D.
   Zhang, Heping
   Diamond, Michael P.
   Coutifaris, Christos
   Casson, Peter R.
   Brzyski, Robert G.
   Christman, Gregory M.
   Barnhart, Kurt T.
   Trussell, J. C.
   Krawetz, Stephen A.
   Snyder, Peter J.
   Ohl, Dana
   Santoro, Nanette
   Eisenberg, Esther
   Huang, Hao
   Legro, Richard S.
CA Reprod Med Network
TI Increasing burden of institutional review in multicenter clinical trials
   of infertility: the Reproductive Medicine Network experience with the
   Pregnancy in Polycystic Ovary Syndrome (PPCOS) I and II studies
SO FERTILITY AND STERILITY
LA English
DT Article
DE Multicenter clinical trials; ethical review; institutional review
   boards; human experimentation
ID CONSENT DOCUMENTS; BOARD; PARTICIPANTS
AB Many clinical investigators think that the burden of Institutional Review Board (IRB) requirements has been consistently increasing over recent years, although there are few objective data describing these trends. Over a period of 7 years, the Reproductive Medicine Network observed a significant increase in the size and requirements of IRB submissions and significant variability of IRB performance in reviewing multicenter trials. These additional regulatory and administrative demands represent substantial burdens to researchers and to the IRBs themselves. It is timely to consider whether these changes better protect the interests and safety of human research participants. Clinical trial registration: ClinicalTrials. gov NCT00068861 and NCT00719186. (Fertil Steril (R) 2011; 96: 15-8. (C) 2011 by American Society for Reproductive Medicine.)
C1 [Schlaff, William D.; Santoro, Nanette] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA.
   [Zhang, Heping; Huang, Hao] Yale Univ, Sch Publ Hlth, Collaborat Ctr Stat Sci, New Haven, CT USA.
   [Diamond, Michael P.; Krawetz, Stephen A.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
   [Coutifaris, Christos; Barnhart, Kurt T.; Snyder, Peter J.] Univ Penn, Philadelphia, PA 19104 USA.
   [Casson, Peter R.] Univ Vermont, Dept Med & Obstet & Gynecol, Burlington, VT USA.
   [Brzyski, Robert G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA.
   [Christman, Gregory M.] Univ Michigan, Dept Obstet & Gynecol, Reprod Sci Program, Ann Arbor, MI 48109 USA.
   [Trussell, J. C.] SUNY Syracuse, Upstate Sch Med, Dept Urol, Syracuse, NY USA.
   [Ohl, Dana] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
   [Eisenberg, Esther] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Sci Branch, Bethesda, MD USA.
   [Legro, Richard S.] Penn State Univ, Dept Obstet & Gynecol, Hershey, PA USA.
RP Schlaff, WD (reprint author), Univ Colorado, Sch Med, Dept Obstet & Gynecol, Acad Off Bldg 1,12631 E 17th Ave, Aurora, CO 80045 USA.
EM william.schlaff@ucdenver.edu
OI Diamond, Michael/0000-0001-6353-4489
FU National Institutes of Health (NIH)/National Institute of Child Health
   and Human Development (NICHD) [U10 HD38998, U10HD055925, U10 HD39005,
   U10 HD27049, H10 HD055944, U10 HD055942, U10 HD055936, U10 HD38992];
   General Clinical Research Center [MO1RR10732]; Pennsylvania State
   University [C06 RR016499]
FX Supported by National Institutes of Health (NIH)/National Institute of
   Child Health and Human Development (NICHD) grants U10 HD38998 (W.D.S.),
   U10HD055925 (H.Z.), U10 HD39005 (M.P.D.), U10 HD27049 (C.C.), H10
   HD055944 (P.R.C.), U10 HD055942 (R.G.B.), U10 HD055936 (G.M.C.), U10
   HD38992 (R.S.L.), and General Clinical Research Center grant MO1RR10732
   and construction grant C06 RR016499 to Pennsylvania State University.
   The content is solely the responsibility of the authors and does not
   necessarily represent the official views of the NICHD or NIH.
NR 20
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUL
PY 2011
VL 96
IS 1
BP 15
EP 18
DI 10.1016/j.fertnstert.2011.05.069
PG 4
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 786DH
UT WOS:000292283000024
PM 21645894
ER

PT J
AU Browne, HN
   Moon, KS
   Mumford, SL
   Schisterman, EF
   DeCherney, AH
   Segars, JH
   Armstrong, AY
AF Browne, Hyacinth N.
   Moon, Kimberly S.
   Mumford, Sunni L.
   Schisterman, Enrique F.
   DeCherney, Alan H.
   Segars, James H.
   Armstrong, Alicia Y.
TI Is anti-Mullerian hormone a marker of acute cyclophosphamide-induced
   ovarian follicular destruction in mice pretreated with cetrorelix?
SO FERTILITY AND STERILITY
LA English
DT Article
DE GnRH antagonist; cyclophosphamide; primordial follicles; DNA damage;
   anti-Mullerian hormone
ID GONADOTROPIN-RELEASING-HORMONE; GNRH-ANTAGONIST CETRORELIX; BLOOD-FLOW;
   DOWN-REGULATION; YOUNG-WOMEN; CHEMOTHERAPY; FERTILITY; CANCER;
   PRESERVATION; STIMULATION
AB Objective: To define whether anti-Mullerian hormone (AMH) may be a marker of acute cyclophosphamide (CTX)-induced germ cell destruction in mice pretreated with the GnRH antagonist, cetrorelix.
   Design: Controlled, experimental study.
   Setting: Research laboratory in a federal research facility.
   Animal(s): Balb/c female mice (6 weeks old).
   Intervention(s): Mice were treated with GnRH antagonist (cetrorelix) or saline for 15 days followed by 75 mg/kg or 100 mg/kg of CTX or saline control on day 9.
   Main Outcome Measure(s): Number of primordial follicles (PMF), DNA damage, AMH protein expression, and AMH serum levels.
   Result(s): Ovaries in mice pretreated with cetrorelix had significantly more PMFs and reduced DNA damage compared with those exposed to CTX alone. Immunohistochemical staining for AMH expression and serum AMH levels did not differ significantly between treatment groups.
   Conclusion(s): Cetrorelix protected PMFs and reduced DNA damage in follicles of mice treated with CTX, but AMH levels in tissue and serum did not correlate with germ cell destruction. Further research is needed to determine the mechanism responsible for the protective effects on PMF counts observed with cetrorelix. (Fertil Steril (R) 2011;96:180-6. (C) 2011 by American Society for Reproductive Medicine.)
C1 [Browne, Hyacinth N.; Moon, Kimberly S.; DeCherney, Alan H.; Segars, James H.; Armstrong, Alicia Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
   [Browne, Hyacinth N.] SIRM Westchester, New York, NY USA.
   [Mumford, Sunni L.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
RP Armstrong, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, 10 Ctr Dr,Room 1-3140,MSC 1109, Bethesda, MD 20892 USA.
EM armstroa@mail.nih.gov
OI Schisterman, Enrique/0000-0003-3757-641X
FU National Institute of Child Health and Human Development, National
   Institutes of Health, Bethesda, Maryland [Z01-HD-008737-09]
FX Supported by research grant Z01-HD-008737-09, Intramural Research
   Program in Reproductive and Adult Endocrinology, National Institute of
   Child Health and Human Development, National Institutes of Health,
   Bethesda, Maryland.
NR 35
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U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUL
PY 2011
VL 96
IS 1
BP 180
EP U608
DI 10.1016/j.fertnstert.2011.04.008
PG 9
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 786DH
UT WOS:000292283000054
PM 21550044
ER

PT J
AU Kang, B
   Pu, MT
   Hu, GQ
   Wen, WH
   Dong, ZG
   Zhao, KJ
   Stillman, B
   Zhang, ZG
AF Kang, Bin
   Pu, Mintie
   Hu, Gangqing
   Wen, Weihong
   Dong, Zigang
   Zhao, Keji
   Stillman, Bruce
   Zhang, Zhiguo
TI Phosphorylation of H4 Ser 47 promotes HIRA-mediated nucleosome assembly
SO GENES & DEVELOPMENT
LA English
DT Article
DE CAF-1; HIRA; nucleosome assembly; PAK2; histone H3.3; histone variant
ID HISTONE VARIANT H3.3; DNA-REPLICATION; CHROMATIN; COMPLEXES; PROTEIN;
   REPAIR; ACETYLATION; ACTIVATION; DEPOSITION; LYSINE-56
AB Histone H3 variant H3.3, while differing from canonical H3 (H3.1) by only five amino acids, is assembled into nucleosomes, along with histone H4, at genic regions by the histone chaperone HIRA, whereas H3.1 is assembled into nucleosomes in a CAF-1-dependent reaction. Here, we show that phosphorylation of histone H4 Ser 47 (H4S47ph), catalyzed by the PAK2 kinase, promotes nucleosome assembly of H3.3-H4 and inhibits nucleosome assembly of H3.1-H4 by increasing the binding affinity of HIRA to H3.3-H4 and reducing association of CAF-1 with H3.1-H4. These results reveal a mechanism whereby H4S47ph distinctly regulates nucleosome assembly of H3.1 and H3.3.
C1 [Kang, Bin; Pu, Mintie; Zhang, Zhiguo] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
   [Hu, Gangqing; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
   [Wen, Weihong; Dong, Zigang] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA.
   [Stillman, Bruce] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA.
RP Zhang, ZG (reprint author), Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
EM Zhang.Zhiguo@mayo.edu
RI HU, GANGQING/K-5849-2012; Pu, Mintie/R-7757-2016; 
OI Pu, Mintie/0000-0001-9654-8633; Stillman, Bruce/0000-0002-9453-4091
FU NIH [GM72719/GM81838, GM45436/CA13016]
FX We thank Drs. Peter Adams, Yoshihiro Nakatani, Alain Verreault,
   Genevieve Almouzni, and Scott Lowe for plasmids and antibodies used in
   this study. We thank Michelle Zeman and Erika Cline, two summer
   students, for cloning and making Asf1a and Asf1b stable cell lines, and
   Hui Zhou for purifying H3.3-H4 tetramers. We thank Qing Li and Rebecca
   Burgess for their critical reading of this manuscript. This work was
   supported by NIH grants GM72719/GM81838 to Z.Z. and GM45436/CA13016 to
   B.S. Z.Z. is a scholar of the Leukemia and Lymphoma Society.
NR 27
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U2 8
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
J9 GENE DEV
JI Genes Dev.
PD JUL 1
PY 2011
VL 25
IS 13
BP 1359
EP 1364
DI 10.1101/gad.2055511
PG 6
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 786IE
UT WOS:000292297200002
PM 21724829
ER

PT J
AU McGuire, AL
   Basford, M
   Dressler, LG
   Fullerton, SM
   Koenig, BA
   Li, RL
   McCarty, CA
   Ramos, E
   Smith, ME
   Somkin, CP
   Waudby, C
   Wolf, WA
   Clayton, EW
AF McGuire, Amy L.
   Basford, Melissa
   Dressler, Lynn G.
   Fullerton, Stephanie M.
   Koenig, Barbara A.
   Li, Rongling
   McCarty, Cathy A.
   Ramos, Erin
   Smith, Maureen E.
   Somkin, Carol P.
   Waudby, Carol
   Wolf, Wendy A.
   Clayton, Ellen Wright
TI Ethical and practical challenges of sharing data from genome-wide
   association studies: The eMERGE Consortium experience
SO GENOME RESEARCH
LA English
DT Article
ID ELECTRONIC MEDICAL-RECORDS; HIPAA PRIVACY RULE; PARTICIPANTS; DISEASE
AB In 2007, the National Human Genome Research Institute (NHGRI) established the Electronic MEdical Records and GEnomics (eMERGE) Consortium (www.gwas.net) to develop, disseminate, and apply approaches to research that combine DNA biorepositories with electronic medical record (EMR) systems for large-scale, high-throughput genetic research. One of the major ethical and administrative challenges for the eMERGE Consortium has been complying with existing data-sharing policies. This paper discusses the challenges of sharing genomic data linked to health information in the electronic medical record (EMR) and explores the issues as they relate to sharing both within a large consortium and in compliance with the National Institutes of Health (NIH) data-sharing policy. We use the eMERGE Consortium experience to explore data-sharing challenges from the perspective of multiple stakeholders (i.e., research participants, investigators, and research institutions), provide recommendations for researchers and institutions, and call for clearer guidance from the NIH regarding ethical implementation of its data-sharing policy.
C1 [McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA.
   [Basford, Melissa; Clayton, Ellen Wright] Vanderbilt Univ, Med Ctr, Nashville, TN 37232 USA.
   [Dressler, Lynn G.] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
   [Fullerton, Stephanie M.] Univ Washington, Sch Med, Seattle, WA 98195 USA.
   [Koenig, Barbara A.] Mayo Clin, Rochester, MN 55905 USA.
   [Li, Rongling; Ramos, Erin] NHGRI, NIH, Bethesda, MD 20892 USA.
   [McCarty, Cathy A.; Waudby, Carol] Marshfield Clin Res Fdn, Marshfield, WI 54449 USA.
   [Smith, Maureen E.] Northwestern Univ, Ctr Genet Med, Chicago, IL 60611 USA.
   [Somkin, Carol P.] Kaiser Permanente, Oakland, CA 94611 USA.
   [Wolf, Wendy A.] Childrens Hosp Boston, Div Genet, Boston, MA 02115 USA.
RP McGuire, AL (reprint author), Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA.
EM amcguire@bcm.edu
FU NHGRI [R01HG004333]; National Institute of General Medical Sciences
   (NIGMS) through Group Health Cooperative [U01-HG-004610]; National
   Institute of General Medical Sciences (NIGMS) through Marshfield Clinic
   [U01-HG-004608]; National Institute of General Medical Sciences (NIGMS)
   through Mayo Clinic [U01-HG-04599]; National Institute of General
   Medical Sciences (NIGMS) through Northwestern University
   [U01-HG-004609]; National Institute of General Medical Sciences (NIGMS)
   through Vanderbilt University [U01-HG-04603]; National Center for
   Research Resources [UL 1 RR024150]; University of North Carolina Center
   for Genomics and Society NHGRI [P50HG004488]; Institute of Translational
   Health Sciences (NCRR) [UL1RR025014]; Center for Genomics and Health
   Care Equality (NHGRI) [P50HG003374]; Wayne and Gladys Valley Foundation
   [03-071]; Ellison Medical Foundation [AG-IA-0046-04]; RWJ Foundation
   [64362]; KP Community Benefit
FX The eMERGE Network was initiated and funded by NHGRI, in conjunction
   with additional funding from the National Institute of General Medical
   Sciences (NIGMS) through the following grants: U01-HG-004610 (Group
   Health Cooperative); U01-HG-004608 (Marshfield Clinic); U01-HG-04599
   (Mayo Clinic); U01-HG-004609 (Northwestern University); and U01-HG-04603
   (Vanderbilt University, also serving as the Administrative Coordinating
   Center). Additional funding provided by the Clinic Center for
   Translational Science Activities (UL 1 RR024150) from the National
   Center for Research Resources (B. K.); NHGRI R01HG004333 (A. L. M.);
   University of North Carolina Center for Genomics and Society NHGRI
   P50HG004488 (L. D.); the Institute of Translational Health Sciences
   UL1RR025014 (NCRR) and the Center for Genomics and Health Care Equality
   P50HG003374 (NHGRI) (S. M. F.); the Wayne and Gladys Valley Foundation
   03-071, the Ellison Medical Foundation AG-IA-0046-04, the RWJ Foundation
   64362, and a generous grant from KP Community Benefit (C. P. S.). The
   content of this article is solely the responsibility of the authors and
   does not necessarily represent the official views of the National Human
   Genome Research Institute or the National Institutes of Health. We thank
   Veida Elliott and Kyle Brothers (Vanderbilt University), Jill Oliver
   (Baylor College of Medicine), and Joel Wu (Mayo Clinic) for research
   assistance and editorial support.
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PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD JUL
PY 2011
VL 21
IS 7
BP 1001
EP 1007
DI 10.1101/gr.120329.111
PG 7
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
GA 786IM
UT WOS:000292298000001
PM 21632745
ER

PT J
AU Taher, L
   McGaughey, DM
   Maragh, S
   Aneas, I
   Bessling, SL
   Miller, W
   Nobrega, MA
   McCallion, AS
   Ovcharenko, I
AF Taher, Leila
   McGaughey, David M.
   Maragh, Samantha
   Aneas, Ivy
   Bessling, Seneca L.
   Miller, Webb
   Nobrega, Marcelo A.
   McCallion, Andrew S.
   Ovcharenko, Ivan
TI Genome-wide identification of conserved regulatory function in diverged
   sequences
SO GENOME RESEARCH
LA English
DT Article
ID TRANSCRIPTION-FACTOR-BINDING; NONCODING DNA; EMBRYONIC-DEVELOPMENT;
   GENE-EXPRESSION; HEART ENHANCERS; EVOLUTION; ELEMENTS; SITES; ALIGNMENT;
   DROSOPHILA
AB Plasticity of gene regulatory encryption can permit DNA sequence divergence without loss of function. Functional information is preserved through conservation of the composition of transcription factor binding sites (TFBS) in a regulatory element. We have developed a method that can accurately identify pairs of functional noncoding orthologs at evolutionarily diverged loci by searching for conserved TFBS arrangements. With an estimated 5% false-positive rate (FPR) in approximately 3000 human and zebrafish syntenic loci, we detected approximately 300 pairs of diverged elements that are likely to share common ancestry and have similar regulatory activity. By analyzing a pool of experimentally validated human enhancers, we demonstrated that 7/8 (88%) of their predicted functional orthologs retained in vivo regulatory control. Moreover, in 5/7 (71%) of assayed enhancer pairs, we observed concordant expression patterns. We argue that TFBS composition is often necessary to retain and sufficient to predict regulatory function in the absence of overt sequence conservation, revealing an entire class of functionally conserved, evolutionarily diverged regulatory elements that we term "covert.''
C1 [McGaughey, David M.; Maragh, Samantha; Bessling, Seneca L.; McCallion, Andrew S.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Taher, Leila; Ovcharenko, Ivan] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
   [Maragh, Samantha] NIST, Div Biochem Sci, Gaithersburg, MD 20899 USA.
   [Aneas, Ivy; Nobrega, Marcelo A.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
   [Miller, Webb] Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA.
RP McCallion, AS (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
EM andy@jhmi.edu; ovcharei@ncbi.nlm.nih.gov
FU NIH; National Library of Medicine; National Institute of Neurological
   Disease and Stroke (NINDS, NIH) [R01 NS062972]
FX We gratefully acknowledge three anonymous reviewers for helpful
   suggestions that greatly improved the manuscript. This research was
   supported by the Intramural Research Program of the NIH, National
   Library of Medicine to I.O.; and by the National Institute of
   Neurological Disease and Stroke (R01 NS062972; NINDS, NIH) to A. S. M.
   Disclaimer: Certain commercial equipment or materials are identified in
   this report to specify adequately the experimental procedures. Such
   identification does not imply recommendation or endorsement by the
   National Institute of Standards and Technology, nor does it imply that
   the materials or equipment identified are necessarily the best available
   for the purpose.
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PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD JUL
PY 2011
VL 21
IS 7
BP 1139
EP 1149
DI 10.1101/gr.119016.110
PG 11
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
GA 786IM
UT WOS:000292298000014
PM 21628450
ER

PT J
AU Mannel, RS
   Brady, MF
   Kohn, EC
   Hanjani, P
   Hiura, M
   Lee, R
   DeGeest, K
   Cohn, DE
   Monk, BJ
   Michael, H
AF Mannel, Robert S.
   Brady, Mark F.
   Kohn, Elise C.
   Hanjani, Parviz
   Hiura, Masamichi
   Lee, Roger
   DeGeest, Koen
   Cohn, David E.
   Monk, Bradley J.
   Michael, Helen
TI A randomized phase III trial of IV carboplatin and paclitaxel x 3
   courses followed by observation versus weekly maintenance low-dose
   paclitaxel in patients with early-stage ovarian carcinoma: A Gynecologic
   Oncology Group Study
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE IV carboplatin and paclitaxel early stage ovarian carcinoma; GOG
ID ADJUVANT TREATMENT; COMPARING CISPLATIN; NEOPLASM TRIAL; CANCER;
   ANGIOGENESIS; CHEMOTHERAPY; CYCLOPHOSPHAMIDE; EXPRESSION; PLATINUM;
   SURVIVAL
AB Objective. To compare the recurrence-free interval (RFI) and safety profile in patients with completely resected high-risk early-stage ovarian cancer treated with intravenous (IV) carboplatin and paclitaxel with or without maintenance low-dose paclitaxel for 24 weeks.
   Methods. Eligibility was limited to patients with stage IA/B (grade 3 or clear cell), all IC or II epithelial ovarian cancer. All patients were to receive carboplatin AUC 6 and paclitaxel 175 mg/m(2) q3 weeks x 3 courses with random assignment to either observation or maintenance paclitaxel 40 mg/m(2)/week x 24 weeks. Recurrence required clinical or radiological evidence of new tumor.
   Results. There were 571 patients enrolled onto this study, of whom 29 were deemed ineligible due to inappropriate stage or pathology, leaving 542 patients. At least 3 cycles of treatment were administered to 524/542 (97%) of patients, and among those assigned to maintenance paclitaxel, 80% completed the regimen. The incidence of grade 2 or worse peripheral neuropathy (15.5% vs. 6%), infection/fever (19.9% vs. 8.7%), and dermatologic events (70.8% vs. 52.1%) was higher on the maintenance regimen (p<0.001). The cumulative probability of recurring within 5 years for the maintenance paclitaxel regimen is 20% vs. 23% for surveillance (hazard ratio 0.807; 95% CI: 0.565-1.15). The probability of surviving 5 years was 85.4% and 86.2%, respectively.
   Conclusion. Maintenance paclitaxel at 40 mg/m(2)/week x 24 weeks added to standard dose AUC6 and paclitaxel 175 mg/m(2) x 3 doses provides no significant increase in RFI. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Mannel, Robert S.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73190 USA.
   [Brady, Mark F.] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA.
   [Kohn, Elise C.] NCI, Bethesda, MD 20892 USA.
   [Hanjani, Parviz] Abington Mem Hosp, Abington, PA 19001 USA.
   [Hiura, Masamichi] Shikoku Canc Ctr, Shikoku, Ehime, Japan.
   [Lee, Roger] Tacoma Gen Hosp, Tacoma, WA USA.
   [DeGeest, Koen] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA.
   [Cohn, David E.] Ohio State Univ, Columbus, OH 43210 USA.
   [Monk, Bradley J.] Univ Calif Irvine, Irvine Med Ctr, Orange, CA 92668 USA.
   [Michael, Helen] Indiana Univ, Sch Med, Indianapolis, IN USA.
RP Mannel, RS (reprint author), Univ Oklahoma, Hlth Sci Ctr, POB 26901,Williams Pavil,Room WP-2410, Oklahoma City, OK 73190 USA.
EM robert-mannel@ouhsc.edu
FU National Cancer Institute [CA 27469]; Gynecologic Oncology Group
   Statistical Office [CA 37517]
FX This study was supported by National Cancer Institute grants to the
   Gynecologic Oncology Group Administrative Office (CA 27469) and the
   Gynecologic Oncology Group Statistical Office (CA 37517). This trial was
   registered with the NCI on November 1, 1999 (NCT 00003644). Further
   details about the protocol are available at www.clinicaltrials.gov.
NR 27
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U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD JUL
PY 2011
VL 122
IS 1
BP 89
EP 94
DI 10.1016/j.ygyno.2011.03.013
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 781BW
UT WOS:000291906600019
PM 21529904
ER

PT J
AU Lozier, JN
   Rosenberg, PS
   Goedert, JJ
   Menashe, I
AF Lozier, J. N.
   Rosenberg, P. S.
   Goedert, J. J.
   Menashe, I.
TI A case-control study reveals immunoregulatory gene haplotypes that
   influence inhibitor risk in severe haemophilia A
SO HAEMOPHILIA
LA English
DT Article
DE haemophilia A; inhibitor; factor VIII; IL10; IL2; IL12; IL1
ID INTERFERON-GAMMA-PRODUCTION; FACTOR-VIII; T-CELLS; INTERLEUKIN-10 IL-10;
   ANTIBODY-RESPONSE; HIV-INFECTION; IL10; POLYMORPHISMS; ASSOCIATION;
   COHORT
AB Several genes that modify risk of factor VIII (FVIII) inhibitors in haemophilia A patients have been identified. Aside from the underlying mutations that cause haemophilia A, inhibitor risk appears to be modified by polymorphisms in various cytokines and immunomodulators including IL10, TNF alpha and CTLA4. HLA haplotypes have not been strong determinants of inhibitor risk. We sought to confirm previous observations on FVIII inhibitor risk-modifying genes and to test new candidate genes encoding various otherTH1/TH2 cytokines. We also sought to determine whether normal FVIII gene polymorphisms affect inhibitor risk in caucasians. We studied 915 caucasian, severe haemophilia A patients (282 inhibitor cases and 633 non-inhibitor controls). Genes were analysed using 368 tagging single nucleotide polymorphisms starting 20 kb 5' and ending 10 kb 3' of each gene's coding sequence; four other polymorphisms (factor V Leiden & prothrombin 20210 polymorphisms and two in HFE) were also evaluated. Haplotypes that increased inhibitor risk were found in IL10 (OR = 1.33, P = 0.04), IL12 (OR = 1.31, P = 0.04) and IL1 alpha (OR = 2.16, P = 0.034). Protective haplotypes were seen in IL2 (OR = 0.69, P = 0.008) and IL1 beta (OR = 0.75, P = 0.02). One rare haplotype in the FVIII gene increased the risk of inhibitor development by nearly fourfold (OR = 3.8, P = 0.004). We replicate previous findings for IL10; identify new associations with IL1, IL2 and IL12; and identify a rare FVIII haplotype in caucasians that is associated with increased inhibitor risk.
C1 [Lozier, J. N.] NIH Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA.
   [Rosenberg, P. S.; Goedert, J. J.; Menashe, I.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Lozier, JN (reprint author), NIH Clin Ctr, Dept Lab Med, Bldg 10,Rm 2C306,MSC1508,10 Ctr Dr, Bethesda, MD 20892 USA.
EM lozierjn@mail.nih.gov
FU National Hemophilia Foundation; National Cancer Institute; NIH Clinical
   Center and National Cancer Institute; National Heart, Lung and Blood
   Institute
FX Supported by the National Hemophilia Foundation Career Development Award
   (JNL), and the National Cancer Institute Intramural Research Program
   (PSR, JJG, IM); We would like to acknowledge the National Hemophilia
   Foundation for funding of this project (through a Career Development
   Award to JNL), the NIH Clinical Center and National Cancer Institute for
   salary support and additional research support. Partial support for the
   cohort was also provided by the National Heart, Lung and Blood
   Institute. We would like to acknowledge Barbara Kroner, Susan Wilson and
   Liliana Preiss of RTI International for management of research subject
   samples and information. Finally, we would like to acknowledge and thank
   the MHCS I-II patients, investigators and staff, without whom this
   research could not have been carried out.
NR 30
TC 23
Z9 24
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-8216
J9 HAEMOPHILIA
JI Haemophilia
PD JUL
PY 2011
VL 17
IS 4
BP 641
EP 649
DI 10.1111/j.1365-2516.2010.02473.x
PG 9
WC Hematology
SC Hematology
GA 784JZ
UT WOS:000292154700011
PM 21362111
ER

PT J
AU Hossain, A
   Chen, A
   Ivy, P
   Lenihan, DJ
   Kaltman, J
   Taddei-Peters, W
   Remick, SC
AF Hossain, Akm
   Chen, Alice
   Ivy, Percy
   Lenihan, Daniel J.
   Kaltman, Jonathan
   Taddei-Peters, Wendy
   Remick, Scot C.
TI The Importance of Clinical Grading of Heart Failure and Other Cardiac
   Toxicities During Chemotherapy: Updating the Common Terminology Criteria
   for Clinical Trial Reporting
SO HEART FAILURE CLINICS
LA English
DT Article
DE Common terminology criteria for adverse events; Cardiac side effects of
   chemotherapy; Cardiooncology; Adverse events
ID METASTATIC BREAST-CANCER; TYROSINE KINASE INHIBITOR; ACUTE PROMYELOCYTIC
   LEUKEMIA; MULTIPLE-MYELOMA; CHILDHOOD-CANCER; ARSENIC TRIOXIDE; THERAPY;
   CARDIOTOXICITY; DYSFUNCTION; DOXORUBICIN
AB Although the use of chemotherapy and targeted therapy has improved the clinical benefit, progression-free survival, and overall survival of various cancers in recent years, old and new toxicities have limited their use. To balance the risk with the benefit of treatment, Common Toxicity Criteria and now Common Terminology Criteria for Adverse Events (CTCAE) have been used by the oncology community for more than 20 years to assess toxicity from cancer treatment. This article details the description and grading of cardiac toxicities reported in association with cancer treatment and the use of CTCAE to assess them.
C1 [Chen, Alice; Ivy, Percy] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA.
   [Hossain, Akm] Univ Missouri, Dept Med, Ellis Fischel Canc Ctr, Columbia, MO 65203 USA.
   [Hossain, Akm] Univ Missouri, Dept Hematol, Ellis Fischel Canc Ctr, Columbia, MO 65203 USA.
   [Hossain, Akm] Univ Missouri, Dept Oncol, Ellis Fischel Canc Ctr, Columbia, MO 65203 USA.
   [Lenihan, Daniel J.] Vanderbilt Heart & Vasc Inst, Nashville, TN 37232 USA.
   [Kaltman, Jonathan] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
   [Taddei-Peters, Wendy] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20817 USA.
   [Remick, Scot C.] W Virginia Univ, Dept Med, Sch Med, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA.
RP Chen, A (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Suite 7131,6130 Execut Blvd, Rockville, MD 20852 USA.
EM chenali@mail.nih.gov
NR 36
TC 9
Z9 9
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7136
J9 HEART FAIL CLIN
JI Heart Fail. Clin.
PD JUL
PY 2011
VL 7
IS 3
BP 373
EP +
DI 10.1016/j.hfc.2011.03.008
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 988MI
UT WOS:000307494700010
PM 21749889
ER

PT J
AU Biankin, AV
   Chanock, SJ
AF Biankin, Andrew V.
   Chanock, Stephen J.
TI The road ahead: less travelled and more arduous than initially
   envisioned
SO HUMAN GENETICS
LA English
DT Editorial Material
C1 [Biankin, Andrew V.] St Vincents Hosp, Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW 2010, Australia.
   [Biankin, Andrew V.] Bankstown Hosp, Dept Surg, Bankstown, NSW 2200, Australia.
   [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Biankin, AV (reprint author), St Vincents Hosp, Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW 2010, Australia.
EM a.biankin@garvan.org.au; chanocks@mail.nih.gov
OI Biankin, Andrew/0000-0002-0362-5597
NR 0
TC 3
Z9 3
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD JUL
PY 2011
VL 130
IS 1
SI SI
BP 1
EP 2
DI 10.1007/s00439-011-1046-1
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA 786MR
UT WOS:000292313000001
PM 21713432
ER

PT J
AU Chung, CC
   Chanock, SJ
AF Chung, Charles C.
   Chanock, Stephen J.
TI Current status of genome-wide association studies in cancer
SO HUMAN GENETICS
LA English
DT Review
ID COPY NUMBER VARIATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; IDIOPATHIC
   PULMONARY-FIBROSIS; AGGRESSIVE PROSTATE-CANCER; SQUAMOUS-CELL CARCINOMA;
   NAT2 SLOW ACETYLATION; RISK-ASSOCIATED LOCI; BREAST-CANCER;
   SUSCEPTIBILITY LOCI; LUNG-CANCER
AB Genome-wide association studies in cancer have already identified over 150 regions associated with two dozen specific cancers. Already, a handful of multi-cancer susceptibility regions have been uncovered, providing new insights into perhaps common mechanisms of carcinogenesis. For each new susceptibility allele, investigators now face the arduous task of interrogating each region beginning with fine mapping prior to pursuing the biological basis for the direct association of one or more variants. It appears that there may be a significant number of common alleles that contribute to the heritability of a specific cancer. Since each region confers a small contribution to the risk for cancer, it is daunting to consider any single nucleotide polymorphism (SNP) as a clinical test. Since the complex genomic architecture of each cancer differs, additional genotyping and sequence analysis will be required to comprehensively catalog susceptibility alleles followed by the formidable task of understanding the interactions between genetic regions as well as the environment. It will be critical to assess the applicability of genetic tests in specific clinical settings, such as when to perform screening tests with calculable risks (e.g., biopsies or chemoprevention), before incorporating SNPs into clinical practice. To advance the current genomic observations to the clinical venue, new studies will need to be designed to validate the utility of known genetic variants in assessing risk for cancer as well as its outcomes.
C1 [Chung, Charles C.; Chanock, Stephen J.] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
RP Chanock, SJ (reprint author), NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
EM chanocks@mail.nih.gov
FU National Institutes of Health, National Cancer Institute; E. de
   Rothschild; Y Mayent Foundation of the Institut Curie, Paris, France
FX This work was supported by the intramural research program of the
   National Institutes of Health, National Cancer Institute. S.J.C. would
   like to acknowledge the receipt of a sabbatical position supported by
   the E. de Rothschild and Y Mayent Foundation of the Institut Curie,
   Paris, France. We thank Marie-Josephe Horner for editorial support.
NR 163
TC 88
Z9 95
U1 2
U2 23
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD JUL
PY 2011
VL 130
IS 1
SI SI
BP 59
EP 78
DI 10.1007/s00439-011-1030-9
PG 20
WC Genetics & Heredity
SC Genetics & Heredity
GA 786MR
UT WOS:000292313000009
PM 21678065
ER

PT J
AU Venkataraman, G
   Berkowitz, J
   Morris, JC
   Janik, JE
   Raffeld, MA
   Pittaluga, S
AF Venkataraman, Girish
   Berkowitz, Jonathan
   Morris, John C.
   Janik, John E.
   Raffeld, Mark A.
   Pittaluga, Stefania
TI Adult T-cell leukemia/lymphoma with Epstein-Barr virus-positive
   Hodgkin-like cells
SO HUMAN PATHOLOGY
LA English
DT Article
DE Adult T-Cell; Leukemia/Lymphoma; Epstein-Barr Virus; Flow Cytometry;
   Hodgkin-Like; Human T-Cell; Lymphotrophic Virus-1; Immunohistochemistry
ID HISTOLOGIC FEATURES; LEUKEMIA; LYMPHOMA; ATLL
AB Hodgkin-like cells have been described in a variety of non-Hodgkin lymphomas including chronic lymphocytic leukemia and peripheral T-cell lymphoma. There have been rare reports in the Japanese population of human T-cell lymphotrophic virus-1-associated adult T-cell leukemia/lymphoma harboring Hodgkin-like cells; however, no similar cases have been described in Western patients. We report a 53-year-old African American man who presented with progressive weakness and lethargy, and was found to have generalized lymphadenopathy and hypercalcemia. A lymph node biopsy showed involvement by adult T-cell leukemia/lymphoma with scattered Epstein-Barr virus positive cells, some of which resembled Hodgkin cells that had a B-cell phenotype, consistent with an Epstein-Barr virus-lymphoproliferative disorder. The patient had stage 4 disease with bone marrow involvement. In light of the associated B-cell lymphoproliferative process, the patient was treated with 6 cycles of intensive chemotherapy that targeted both the adult T-cell leukemia/lymphoma and the Epstein-Barr virus lymphoproliferative disorder that resulted in a complete response. An awareness of the association of Epstein-Barr virus lymphoproliferative disorder with Hodgkin-like cells in the context of adult T-cell leukemia/lymphoma is necessary to avoid potential misdiagnosis and to aid in therapeutic decisions. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Venkataraman, Girish; Raffeld, Mark A.; Pittaluga, Stefania] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Berkowitz, Jonathan; Morris, John C.; Janik, John E.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Venkataraman, G (reprint author), 2160 S 1st Ave,Bldg 110,Pathol Room 2222, Maywood, IL 60153 USA.
EM gvenkat@lumc.edu
OI Venkataraman, Girish/0000-0002-8674-2608
FU Intramural NIH HHS [Z99 CA999999]
NR 14
TC 6
Z9 6
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 0046-8177
J9 HUM PATHOL
JI Hum. Pathol.
PD JUL
PY 2011
VL 42
IS 7
BP 1042
EP 1046
DI 10.1016/j.humpath.2010.10.014
PG 5
WC Pathology
SC Pathology
GA 785LZ
UT WOS:000292231800017
PM 21315416
ER

PT J
AU Li, XG
   Yang, GT
   Zhao, G
   Wu, B
   Edin, ML
   Zeldin, DC
   Wang, DW
AF Li, Xuguang
   Yang, Guangtian
   Zhao, Gang
   Wu, Bin
   Edin, Matthew L.
   Zeldin, Darryl C.
   Wang, Dao Wen
TI Rosuvastatin attenuates the elevation in blood pressure induced by
   overexpression of human C-reactive protein
SO HYPERTENSION RESEARCH
LA English
DT Article
DE C-reactive protein; endothelial nitric oxide synthase; reactive oxygen
   species; statin
ID COA REDUCTASE INHIBITORS; VASCULAR SMOOTH-MUSCLE; NITRIC-OXIDE SYNTHASE;
   OXIDATIVE STRESS; ENDOTHELIAL DYSFUNCTION; ESSENTIAL-HYPERTENSION;
   SUPEROXIDE-PRODUCTION; KINASE CONTRIBUTES; MEDIATED DILATION; STATIN
   THERAPY
AB C-reactive protein (CRP) has been shown to function as an inflammatory factor to induce endothelial dysfunction and hypertension in rats. The anti-inflammatory effects of statins suggest that they may attenuate CRP-induced endothelial dysfunction and hypertension in Sprague-Dawley rats. Male Sprague-Dawley rats were injected with an adeno-associated virus (AAV) to induce overexpression of human CRP (AAV-hCRP) or green fluorescent protein (GFP) control (AAV-GFP). At 2 months after injection, rats were administered rosuvastatin by daily oral gavage (10 mg kg(-1)) for 2 additional months. Rosuvastatin administration attenuated the increased blood pressure and loss of vascular endothelial nitric oxide synthase expression in AAV-hCRP-treated rats, and N-nitro-L-arginine methyl ester blocked its hypotensive effect. Rosuvastatin also activated phosphoinositide 3-kinases/Akt, and inhibited Rho kinase activity in aorta. Rosuvastatin reduced the production of reactive oxygen species through downregulation of nicotinamide adenine dinucleotide phosphate oxidase subunits, p22 phox and gp91 phox, and upregulation of superoxide dismutase 1 expression. Rosuvastatin attenuated the increase in blood pressure in AAV-hCRP-treated rats through endothelial protection and antioxidant effects. Our data reveals a novel mechanism through which statins may lower blood pressure. Hypertension Research (2011) 34, 869-875; doi:10.1038/hr.2011.44; published online 12 May 2011
C1 [Li, Xuguang; Yang, Guangtian; Zhao, Gang; Wu, Bin; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med,Inst Hypertens, Wuhan 430030, Peoples R China.
   [Edin, Matthew L.; Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, Res Triangle Pk, NC USA.
RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med,Inst Hypertens, 1095 Jiefang Ave, Wuhan 430030, Peoples R China.
EM dwwang@tjh.tjmu.edu.cn
OI Edin, Matthew/0000-0002-7042-500X
FU '973' project [2007CB512004]; Wuhan City grants and Hubei Province
   project on risk prediction of Cardiovascular Diseases; NIH, National
   Institute of Environmental Health Sciences [Z01 ES025043]
FX This work was supported by '973' project (no. 2007CB512004), Wuhan City
   grants and Hubei Province project on risk prediction of Cardiovascular
   Diseases and the Intramural Research Program of the NIH, National
   Institute of Environmental Health Sciences (Z01 ES025043).
NR 49
TC 9
Z9 9
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0916-9636
J9 HYPERTENS RES
JI Hypertens. Res.
PD JUL
PY 2011
VL 34
IS 7
BP 869
EP 875
DI 10.1038/hr.2011.44
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 787PU
UT WOS:000292390000016
PM 21562509
ER

PT J
AU Yagi, R
   Zhu, JF
   Paul, WE
AF Yagi, Ryoji
   Zhu, Jinfang
   Paul, William E.
TI An updated view on transcription factor GATA3-mediated regulation of
   T(h)1 and T(h)2 cell differentiation
SO INTERNATIONAL IMMUNOLOGY
LA English
DT Review
DE cytokine; epigenetic modification; gene regulation
ID LOCUS-CONTROL REGION; CD4(+) T-CELLS; RANGE INTRACHROMOSOMAL
   INTERACTIONS; CYTOKINE GENE-CLUSTER; IFN-GAMMA PRODUCTION; DEVELOPING
   TH1 CELLS; LINEAGE COMMITMENT; FACTOR GATA-3; TH2-SPECIFIC EXPRESSION;
   CUTTING EDGE
AB CD4 T-h are critical for orchestrating adaptive immune responses. The expression of the transcription factor GATA3 (GATA-binding protein 3) is up-regulated or down-regulated during T(h)2 or T(h)1 cell differentiation, respectively. Furthermore, GATA3 is responsible for induction of T(h)2 differentiation and represses T(h)1 differentiation. In this review, we present an updated view on the molecular mechanisms through which GATA3 regulates T(h)1/T(h)2 differentiation. During T(h)2 cell differentiation, GATA3 directly binds to the T(h)2 cytokine gene locus at several regions and regulates expression. On the other hand, GATA3 inhibits T(h)1 cell differentiation by preventing up-regulation of IL-12 receptor beta 2 and STAT4 (signal transducer and activator of transcription 4) and neutralization of Runx3 (runt-related transcription factor 3) function through protein-protein interaction. GATA3 may also directly act on the Ifng gene. In summary, GATA3 serves as a transcriptional activator or repressor through direct action on transcriptional machinery and/or affecting chromatin remodeling at many critical loci encoding cytokines, cytokine receptors, signaling molecules as well as transcription factors that are involved in the regulation of T(h)1 and T(h)2 differentiation.
C1 [Yagi, Ryoji; Zhu, Jinfang; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N323,10 Ctr Dr MSC 1892, Bethesda, MD 20892 USA.
EM jfzhu@niaid.nih.gov
RI Zhu, Jinfang/B-7574-2012
FU National Institutes of Health [1ZIAAI000493-24]
FX National Institutes of Health (1ZIAAI000493-24).
NR 57
TC 68
Z9 72
U1 0
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0953-8178
J9 INT IMMUNOL
JI Int. Immunol.
PD JUL
PY 2011
VL 23
IS 7
BP 415
EP 420
DI 10.1093/intimm/dxr029
PG 6
WC Immunology
SC Immunology
GA 786NO
UT WOS:000292315400001
PM 21632975
ER

PT J
AU Yasinskaya, Y
   Plikaytis, B
   Sizemore, C
   Sacks, L
AF Yasinskaya, Y.
   Plikaytis, B.
   Sizemore, C.
   Sacks, L.
TI Advancing the development of diagnostic tests and biomarkers for
   tuberculosis
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Article
DE TB; tuberculosis; biomarkers
AB High costs and limited returns on investment have hampered progress in developing new diagnostic tests and treatments for tuberculosis (TB). We need new biomarkers to develop assays that can rapidly, efficiently and reliably detect Mycobacterium tuberculosis infection and disease, identify drug resistance and expedite drug and vaccine development. This can only be accomplished through cross-disciplinary collaborations to facilitate access to human specimens. The Food and Drug Administration, Centers for Disease Control and Prevention, National Institutes of Health, the industry and academia experts came together in a June 2010 workshop to examine the field of TB diagnostic test development and biomarker discovery, identify areas of most urgent need and formulate strategies to address those needs.
C1 [Yasinskaya, Y.; Sacks, L.] US FDA, Off Crit Path Programs, Silver Spring, MD 20903 USA.
   [Plikaytis, B.] Ctr Dis Control & Prevent, Mycobacteriol Lab Branch, Atlanta, GA USA.
   [Sizemore, C.] NIAID, TB & Other Mycobacterial Dis Sect, NIH, Bethesda, MD 20892 USA.
RP Yasinskaya, Y (reprint author), US FDA, Off Crit Path Programs, Rm 4110,Bldg 32,10903 New Hampshire Ave, Silver Spring, MD 20903 USA.
EM Yuliya.Yasinskaya@fda.hhs.gov
NR 4
TC 5
Z9 5
U1 0
U2 1
PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
PI PARIS
PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE
SN 1027-3719
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD JUL
PY 2011
VL 15
IS 7
BP 985
EP 987
DI 10.5588/ijtld.10.0712
PG 3
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA 785MV
UT WOS:000292234000023
PM 21682977
ER

PT J
AU Rivera-Goba, MV
   Dominguez, DC
   Stoll, P
   Grady, C
   Ramos, C
   Mican, JM
AF Rivera-Goba, Migdalia V.
   Dominguez, Dinora C.
   Stoll, Pamela
   Grady, Christine
   Ramos, Catalina
   Mican, Joann M.
TI Exploring Decision-Making of HIV-Infected Hispanics and African
   Americans Participating in Clinical Trials
SO JANAC-JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE
LA English
DT Article
DE African American/Black; clinical research; decision-making; health
   disparities; Hispanic/Latino; HIV
AB Underrepresentation of HIV-infected Hispanics and African Americans in clinical trials seriously limits our understanding of the benefits and risks of treatment in these populations. This qualitative study examined factors that racial/ethnic minority patients consider when making decisions regarding research participation. A total of 35 HIV-infected Hispanic and African American patients enrolled in clinical research protocols at the National Institutes of Health were recruited to participate in focus groups and in-depth interviews. The sample included mostly male participants (n = 22), had a mean age of 45, had nearly equal representation of race/ethnicity, and were diagnosed 2 to 22 years earlier. Baseline questionnaires included demographics and measures of social support and acculturation. Interviewers had similar racial/ethnic, cultural, and linguistic backgrounds as the participants. Four major themes related to the decisions of participants to enroll in clinical trials emerged, which are as follows: enhancers, barriers, beliefs, and psychosocial context. Results may help researchers develop strategies to facilitate inclusion of HIV-infected Hispanics and African Americans into clinical trials. Published by Elsevier Inc. on behalf of Association of Nurses in AIDS Care
C1 [Rivera-Goba, Migdalia V.; Stoll, Pamela] NIH, Nursing Care Serv, Ctr Clin, Bethesda, MD 20892 USA.
   [Rivera-Goba, Migdalia V.; Stoll, Pamela] NIH, Patient Care Serv, Ctr Clin, Bethesda, MD 20892 USA.
   [Dominguez, Dinora C.] NIH, Patient Recruitment & Publ Liaison Sect, Ctr Clin, Bethesda, MD 20892 USA.
   [Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
   [Ramos, Catalina] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
   [Mican, Joann M.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
RP Rivera-Goba, MV (reprint author), NIH, Nursing Care Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural Research Program of the National Institutes of Health
   Clinical Center
FX The authors report no real or perceived vested interests that relate to
   this article (including relationships with pharmaceutical companies,
   biomedical device manufacturers, grantors, or other entities whose
   products or services are related to topics covered in this manuscript)
   that could be construed as a conflict of interest. This research was
   supported by the Intramural Research Program of the National Institutes
   of Health Clinical Center.
NR 32
TC 7
Z9 7
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1055-3290
J9 J ASSOC NURSE AIDS C
JI J. Assoc. Nurses Aids Care
PD JUL-AUG
PY 2011
VL 22
IS 4
BP 295
EP 306
DI 10.1016/j.jana.2010.10.007
PG 12
WC Nursing
SC Nursing
GA V29GW
UT WOS:000208737900006
PM 21256054
ER

PT J
AU Johnson, SRL
   Finigan, NM
   Bradshaw, CP
   Haynie, DL
   Cheng, TL
AF Johnson, Sarah R. Lindstrom
   Finigan, Nadine M.
   Bradshaw, Catherine P.
   Haynie, Denise L.
   Cheng, Tina L.
TI Examining the Link Between Neighborhood Context and Parental Messages to
   Their Adolescent Children About Violence
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Adolescents; Violence; Parenting; Collective efficacy; Parent-child
   communications
ID COMMUNITY VIOLENCE; COLLECTIVE EFFICACY; SOCIAL COGNITION; FAMILY;
   EXPOSURE; SCHOOL; AGGRESSION; MULTILEVEL; BEHAVIORS; ATTITUDES
AB Purpose: Living in violent neighborhoods has been shown to alter adolescent's social cognitions and increase aggressive behavior. A similar process may also occur for parents and result in parental support of aggressive behavior. This research examines the influence of perceived neighborhood violence and neighborhood collective efficacy on parental attitudes toward violence and the messages they give their adolescent children about how to resolve interpersonal conflict.
   Method: Data were collected from 143 African American parents and their adolescent children recruited from three inner-city middle schools to participate in a parenting intervention. Models were fit using structural equation modeling in Mplus.
   Results: Contrary to expectations, exposure to neighborhood violence was not predictive of either aggressive attitudes or conflict solutions for parents or adolescents. Rather, a mixed effect was found for neighborhood collective efficacy, with higher perceived neighborhood collective efficacy related to less violent attitudes for adolescents but not for parents. Collective efficacy also predicted the messages that parents gave their adolescents about interpersonal conflict, with higher collective efficacy related to messages that were less supportive of violence.
   Conclusion: Parent and adolescent perception of neighborhood collective efficacy influences the messages that adolescents receive about interpersonal conflict resolution. This suggests that for parents living in violent neighborhoods, their appraisal of the neighborhood is more important in shaping conflict resolution messages than their own experiences with violence. Parent-and family-based programs to prevent youth violence need to address neighborhood factors that influence the messages adolescents receive about how to resolve conflict. (C) 2011 Society for Adolescent Health and Medicine. All rights reserved.
C1 [Johnson, Sarah R. Lindstrom; Finigan, Nadine M.; Cheng, Tina L.] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD 21287 USA.
   [Bradshaw, Catherine P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
   [Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Div Epidemiol Stat & Prevent Res, Rockville, MD USA.
RP Johnson, SRL (reprint author), Johns Hopkins Sch Med, Dept Pediat, 200 N Wolfe St,Room 2088, Baltimore, MD 21287 USA.
EM slj@jhmi.edu
OI Haynie, Denise/0000-0002-8270-6079
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development (NICHD) [1K24HD052559]; NICHD; Health Research and Services
   Administration [T32 HP1004]; National Center on Minority Health and
   Health Disparities [P20 MD00165]; Centers for Disease Control and
   Prevention [U49CE000728]
FX This article was supported by the Eunice Kennedy Shriver National
   Institute of Child Health and Human Development (NICHD) grant number
   1K24HD052559 (Cheng) and the NICHD Intramural Research Program (Haynie),
   Health Research and Services Administration grant number T32 HP1004
   (Lindstrom Johnson), DC-Baltimore Research Center on Child Health
   Disparities grant number P20 MD00165 from the National Center on
   Minority Health and Health Disparities, and Centers for Disease Control
   and Prevention grant number U49CE000728. Its contents are solely the
   responsibility of the authors and do not necessarily represent the
   official views of the funding agencies.
NR 34
TC 15
Z9 15
U1 0
U2 10
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 JUL
PY 2011
VL 49
IS 1
BP 58
EP 63
DI 10.1016/j.jadohealth.2010.10.014
PG 6
WC Psychology, Developmental; Public, Environmental & Occupational Health;
   Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 782AA
UT WOS:000291978400012
ER

PT J
AU Pilkington, K
   Gamst, A
   Liu, I
   Ostermann, T
   Pinto, D
   Richardon, J
AF Pilkington, Karen
   Gamst, Are
   Liu, Irene
   Ostermann, Thomas
   Pinto, Dimity
   Richardon, Janet
TI The International Collaboration on Complementary Therapy Resources
   (ICCR): Working Together to Improve Online CAM Information
SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE
LA English
DT Article
ID ALTERNATIVE MEDICINE; QUALITY CRITERIA; WEB SITES; INTERNET; CANCER;
   EFFICACY; WEBSITES; ADVICE; SAFE
AB Background: Use of the Internet to find health information is increasing dramatically but the quality of information, particularly on complementary and alternative medicine (CAM) is variable. The International Collaboration on Complementary Therapy Resources (ICCR) involves collaboration between the national CAM information centers in Australia, Denmark, Norway, the United Kingdom, and the United States, and a CAM information service in Germany.
   Objectives: The study objectives were to compare the services and areas of expertise offered by each of the national CAM information services, to explore common challenges encountered in practice, and to establish specific objectives for the collaboration.
   Design: The workshop incorporated set templates for presentations, brainstorming, and analysis of notes to identify common themes.
   Results: Differences and similarities between the various services were revealed. Common challenges were identified under the main themes of overall context, users and needs, content and processes. Based on these themes, it was possible to agree on a number of specific objectives.
   Conclusions: The member organizations of the ICCR serve a range of different audiences and have varied remits to fulfill. For the international collaboration to be effective, it was necessary to identify common challenges and to agree on specific objectives and potential ways of working together. Progress to date is also discussed together with plans for the future.
C1 [Pilkington, Karen] Univ Westminster, Sch Life Sci, Dept Herbal Med & Nutr Therapy, London W1W 6UW, England.
   [Gamst, Are] Univ Tromso, NAFKAM, Norway NIFAB, Natl Informat Ctr Complementary & Alternat Med, Tromso, Norway.
   [Liu, Irene] NIH, Natl Ctr Complementary & Alternat Med, US Dept HHS, Bethesda, MD 20892 USA.
   [Ostermann, Thomas] Univ Witten Herdecke, Ctr Integrat Med, Fac Hlth, Herdecke, Germany.
   [Pinto, Dimity] Univ Western Sydney, NICM, Penrith, Australia.
   [Richardon, Janet] Univ Plymouth, Fac Hlth, Plymouth PL4 8AA, Devon, England.
RP Pilkington, K (reprint author), Univ Westminster, Sch Life Sci, Dept Herbal Med & Nutr Therapy, 115 New Cavendish St, London W1W 6UW, England.
EM k.pilkington@westminster.ac.uk
NR 16
TC 4
Z9 4
U1 1
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1075-5535
J9 J ALTERN COMPLEM MED
JI J. Altern. Complement Med.
PD JUL
PY 2011
VL 17
IS 7
BP 647
EP 653
DI 10.1089/acm.2010.0138
PG 7
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA 784UL
UT WOS:000292183600012
PM 21668372
ER

PT J
AU Burch, LH
   Zhang, LL
   Chao, FG
   Xu, H
   Drake, JW
AF Burch, Lauranell H.
   Zhang, Leilei
   Chao, Frank G.
   Xu, Hong
   Drake, John W.
TI The Bacteriophage T4 Rapid-Lysis Genes and Their Mutational Proclivities
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID PHAGE INFECTION CYCLE; DNA-POLYMERASE; FINE-STRUCTURE; HOLIN; T4;
   FIDELITY; INHIBITION; SEQUENCE; ANTIHOLIN; PROTEINS
AB Like most phages with double-stranded DNA, phage T4 exits the infected host cell by a lytic process requiring, at a minimum, an endolysin and a holin. Unlike most phages, T4 can sense superinfection (which signals the depletion of uninfected host cells) and responds by delaying lysis and achieving an order-of-magnitude increase in burst size using a mechanism called lysis inhibition (LIN). T4 r mutants, which are unable to conduct LIN, produce distinctly large, sharp-edged plaques. The discovery of r mutants was key to the foundations of molecular biology, in particular to discovering and characterizing genetic recombination in T4, to redefining the nature of the gene, and to exploring the mutation process at the nucleotide level of resolution. A number of r genes have been described in the past 7 decades with various degrees of clarity. Here we describe an extensive and perhaps saturating search for T4 r genes and relate the corresponding mutational spectra to the often imperfectly known physiologies of the proteins encoded by these genes. Focusing on r genes whose mutant phenotypes are largely independent of the host cell, the genes are rI (which seems to sense superinfection and signal the holin to delay lysis), rIII (of poorly defined function), rIV (same as sp and also of poorly defined function), and rV (same as t, the holin gene). We did not identify any mutations that might correspond to a putative rVI gene, and we did not focus on the famous rII genes because they appear to affect lysis only indirectly.
C1 [Burch, Lauranell H.; Zhang, Leilei; Chao, Frank G.; Xu, Hong; Drake, John W.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
RP Drake, JW (reprint author), NIEHS, Mol Genet Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM drake@niehs.nih.gov
OI Xu, Hong/0000-0003-1995-4675
FU NIH, National Institute of Environmental Health Sciences [Z01ES061054,
   Z01ES065011, Z01ES065016]
FX This research was supported by funds allocated to project numbers
   Z01ES061054, Z01ES065011, and Z01ES065016 of the Intramural Research
   Program of the NIH, National Institute of Environmental Health Sciences.
NR 54
TC 5
Z9 5
U1 1
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD JUL
PY 2011
VL 193
IS 14
BP 3537
EP 3545
DI 10.1128/JB.00138-11
PG 9
WC Microbiology
SC Microbiology
GA 784DQ
UT WOS:000292134900013
PM 21571993
ER

PT J
AU Yamaguchi, S
   Jha, A
   Li, Q
   Soyombo, AA
   Dickinson, GD
   Churamani, D
   Brailoiu, E
   Patel, S
   Muallem, S
AF Yamaguchi, Soichiro
   Jha, Archana
   Li, Qin
   Soyombo, Abigail A.
   Dickinson, George D.
   Churamani, Dev
   Brailoiu, Eugen
   Patel, Sandip
   Muallem, Shmuel
TI Transient Receptor Potential Mucolipin 1 (TRPML1) and Two-pore Channels
   Are Functionally Independent Organellar Ion Channels
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ADENINE-DINUCLEOTIDE PHOSPHATE; VARITINT-WADDLER PHENOTYPE; CYCLIC
   ADP-RIBOSE; INOSITOL TRISPHOSPHATE; MOBILIZES CALCIUM; ACIDIC
   ORGANELLES; PLASMA-MEMBRANE; RELEASE CHANNEL; CA2+ RELEASE; SEA-URCHIN
AB NAADP is a potent second messenger that mobilizes Ca(2+) from acidic organelles such as endosomes and lysosomes. The molecular basis for Ca(2+) release by NAADP, however, is uncertain. TRP mucolipins (TRPMLs) and two-pore channels (TPCs) are Ca(2+)-permeable ion channels present within the endolysosomal system. Both have been proposed as targets for NAADP. In the present study, we probed possible physical and functional association of these ion channels. Exogenously expressed TRPML1 showed near complete colocalization with TPC2 and partial colocalization with TPC1. TRPML3 overlap with TPC2 was more modest. TRPML1 and to some extent TRPML3 co-immuno-precipitated with TPC2 but less so with TPC1. Current recording, however, showed that TPC1 and TPC2 did not affect the activity of wild-type TRPML1 or constitutively active TRPML1(V432P). N-terminally truncated TPC2 (TPC2delN), which is targeted to the plasma membrane, also failed to affect TRPML1 and TRPML1(V432P) channel function or TRPML1(V432P)-mediated Ca(2+) influx. Whereas overexpression of TPCs enhanced NAADP-mediated Ca(2+) signals, overexpression of TRPML1 did not, and the dominant negative TRPML1(D471K) was without affect on endogenous NAADP-mediated Ca(2+) signals. Furthermore, the single channel properties of NAADP-activated TPC2delN were not affected by TRPML1. Finally, NAADP-evoked Ca(2+) oscillations in pancreatic acinar cells were identical in wild-type and TRPML1(-/-) cells. We conclude that although TRPML1 and TPCs are present in the same complex, they function as two independent organellar ion channels and that TPCs, not TRPMLs, are the targets for NAADP.
C1 [Dickinson, George D.; Churamani, Dev; Patel, Sandip] UCL, Dept Cell & Dev Biol, London WC1E 6BT, England.
   [Yamaguchi, Soichiro; Li, Qin; Soyombo, Abigail A.; Muallem, Shmuel] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75235 USA.
   [Jha, Archana] NIDCR, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
   [Brailoiu, Eugen] Temple Univ, Dept Pharmacol, Sch Med, Philadelphia, PA 19140 USA.
RP Patel, S (reprint author), UCL, Dept Cell & Dev Biol, Gower St, London WC1E 6BT, England.
EM patel.s@ucl.ac.uk; shmuel.muallem@nih.gov
RI Dickinson, George/H-6609-2016; Patel, Sandip/O-9591-2015
OI Dickinson, George/0000-0001-7711-0388; Patel, Sandip/0000-0001-7247-2013
FU National Institutes of Health [DE12309, DK38938, HL90804]; NIDCR/DIR
   [ZIA DE000735-01]; Biotechnology and Biological Sciences Research
   Council [BB/G013721/1]; Uehara Memorial Foundation (Tokyo, Japan)
FX This work was supported by National Institutes of Health Grants DE12309
   and DK38938 and the intramural NIDCR/DIR (Grant ZIA DE000735-01),
   National Institutes of Health (to S. M.) and HL90804 (to E. B.). This
   work was also supported by Biotechnology and Biological Sciences
   Research Council Grant BB/G013721/1 (to S. P.).; Supported by the Uehara
   Memorial Foundation (Tokyo, Japan).
NR 50
TC 41
Z9 41
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 1
PY 2011
VL 286
IS 26
BP 22934
EP 22942
DI 10.1074/jbc.M110.210930
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 782QP
UT WOS:000292025000028
PM 21540176
ER

PT J
AU Zhu, YB
   Sheng, ZH
AF Zhu, Yi-Bing
   Sheng, Zu-Hang
TI Increased Axonal Mitochondrial Mobility Does Not Slow Amyotrophic
   Lateral Sclerosis (ALS)-like Disease in Mutant SOD1 Mice
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MOTOR-NEURON DEGENERATION; ALS-LINKED SOD1; RESPIRATORY-CHAIN FUNCTION;
   WILD-TYPE; TRANSPORT DEFECTS; SKELETAL-MUSCLE; TRANSGENIC MICE;
   INHERITED ALS; MOUSE MODEL; DYNEIN
AB Reduced axonal mitochondrial transport has been observed in major neurodegenerative diseases, including fALS patients and SOD1(G93A) mice. However, it is unclear whether this defect plays a critical role in axonal degeneration or simply reflects sequelae of general transport alteration. Using genetic mouse models combined with time-lapse imaging of live neurons, we previously discovered that axon-targeted syntaphilin (SNPH) acts as a docking receptor specific for axonal mitochondria. Deletion of the snph gene in mice results in a substantially higher proportion of axonal mitochondria in the mobile state without any effect on the transport of other axonal organelles. Here we address whether increased (rescued) axonal mitochondrial mobility changes the disease course by crossing fALS-linked transgenic SOD1(G93A) and snph(-/-) knock-out mice. We found that a 2-fold increase in axonal mitochondrial mobility in SOD1(G93A)/snph(-/-) mice did not affect the onset of ALS-like symptoms. Both SOD1(G93A) and SOD1(G93A)/snph(-/-) mice exhibit similar weight loss, deterioration in motor function and motor neuron loss, significant gliosis, and a lifespan of 152-154 days. Thus, for the first time, our study provides genetic and pathological evidence that the impairment of mitochondrial transport seen in SOD1(G93A) mice plays a minimal role in the rapid-onset of fALS-linked pathology.
C1 [Zhu, Yi-Bing; Sheng, Zu-Hang] NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Sheng, ZH (reprint author), NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
EM shengz@ninds.nih.gov
FU NINDS, National Institutes of Health
FX This work was supported, in whole or in part, by the Intramural Research
   Program of the NINDS, National Institutes of Health (to Z.-H. S.).
NR 52
TC 26
Z9 26
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 1
PY 2011
VL 286
IS 26
BP 23432
EP 23440
DI 10.1074/jbc.M111.237818
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 782QP
UT WOS:000292025000074
PM 21518771
ER

PT J
AU Noinaj, N
   Bosserman, MA
   Schickli, MA
   Piszczek, G
   Kharel, MK
   Pahari, P
   Buchanan, SK
   Rohr, J
AF Noinaj, Nicholas
   Bosserman, Mary A.
   Schickli, M. Alexandra
   Piszczek, Grzegorz
   Kharel, Madan K.
   Pahari, Pallab
   Buchanan, Susan K.
   Rohr, Juergen
TI The Crystal Structure and Mechanism of an Unusual Oxidoreductase, GilR,
   Involved in Gilvocarcin V Biosynthesis
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BERBERINE BRIDGE ENZYME; COVALENTLY ATTACHED FAD; COMBINATORIAL
   BIOSYNTHESIS; ACLACINOMYCIN OXIDOREDUCTASE; ALIGNMENT EDITOR;
   VISIBLE-LIGHT; ACTIVE-SITE; DNA; BINDING; DRUG
AB GilR is a recently identified oxidoreductase that catalyzes the terminal step of gilvocarcin V biosynthesis and is a unique enzyme that establishes the lactone core of the polyketide-derived gilvocarcin chromophore. Gilvocarcin-type compounds form a small distinct family of anticancer agents that are involved in both photo-activated DNA-alkylation and histone H3 cross-linking. High resolution crystal structures of apoGilR and GilR in complex with its substrate pregilvocarcin V reveals that GilR belongs to the small group of a relatively new type of the vanillyl-alcohol oxidase flavoprotein family characterized by bicovalently tethered cofactors. GilR was found as a dimer, with the bicovalently attached FAD cofactor mediated through His-65 and Cys-125. Subsequent mutagenesis and functional assays indicate that Tyr-445 may be involved in reaction catalysis and in mediating the covalent attachment of FAD, whereas Tyr-448 serves as an essential residue initiating the catalysis by swinging away from the active site to accommodate binding of the 6R-configured substrate and consequently abstracting the proton of the hydroxyl residue of the substrate hemiacetal 6-OH group. These studies lay the groundwork for future enzyme engineering to broaden the substrate specificity of this bottleneck enzyme of the gilvocarcin biosynthetic pathway for the development of novel anti-cancer therapeutics.
C1 [Bosserman, Mary A.; Schickli, M. Alexandra; Kharel, Madan K.; Pahari, Pallab; Rohr, Juergen] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA.
   [Noinaj, Nicholas; Buchanan, Susan K.] NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA.
   [Piszczek, Grzegorz] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Rohr, J (reprint author), Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, 789 S Limestone St, Lexington, KY 40536 USA.
EM jrohr2@email.uky.edu
RI Rohr, Jurgen/G-5375-2014
OI Rohr, Jurgen/0000-0001-6447-5951
FU National Institutes of Health [CA102102, CA091901]
FX This work was supported, in whole or in part, by National Institutes of
   Health Grants CA102102 and CA091901 (to J. R.).
NR 71
TC 12
Z9 12
U1 3
U2 8
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 1
PY 2011
VL 286
IS 26
BP 23533
EP 23543
DI 10.1074/jbc.M111.247833
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 782QP
UT WOS:000292025000083
PM 21561854
ER

PT J
AU Smith, AM
   Qualls, JE
   O'Brien, K
   Balouzian, L
   Johnson, PF
   Schultz-Cherry, S
   Smale, ST
   Murray, PJ
AF Smith, Amber M.
   Qualls, Joseph E.
   O'Brien, Kevin
   Balouzian, Liza
   Johnson, Peter F.
   Schultz-Cherry, Stacey
   Smale, Stephen T.
   Murray, Peter J.
TI A Distal Enhancer in Il12b Is the Target of Transcriptional Repression
   by the STAT3 Pathway and Requires the Basic Leucine Zipper (B-ZIP)
   Protein NFIL3
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DISEASE SUSCEPTIBILITY LOCI; INFLAMMATORY-BOWEL-DISEASE; GENOME-WIDE
   ASSOCIATION; T-HELPER-CELLS; ANTIINFLAMMATORY RESPONSE; INTESTINAL
   INFLAMMATION; CHRONIC ENTEROCOLITIS; PRIMARY MACROPHAGES; SIGNALING
   PATHWAY; CROHNS-DISEASE
AB Deregulated IL-12 and IL-23 production from activated myeloid lineage cells is a key driver of numerous T cell-dependent autoimmune and inflammatory diseases. IL-12 and IL-23 share a common p40 subunit encoded by Il12b, which is negatively regulated at the transcriptional level by the STAT3(signal transducer and activator of transcription 3)-activating anti-inflammatory cytokine IL-10. We found that IL-10 targets an enhancer 10 kb upstream of the Il12b transcriptional start site. Within the enhancer, a single 10-bp site is required for the inhibitory effects of IL-10 and is bound by NFIL3 (nuclear factor, interleukin 3-regulated), a B-ZIP transcription factor. Myeloid cells lacking NFIL3 produce excessive IL-12p40 and increased IL-12p70. Thus, the STAT3-dependent expression of NFIL3 is a key component of a negative feedback pathway in myeloid cells that suppresses proinflammatory responses.
C1 [Smith, Amber M.; Qualls, Joseph E.; O'Brien, Kevin; Balouzian, Liza; Schultz-Cherry, Stacey; Murray, Peter J.] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
   [Smith, Amber M.; Qualls, Joseph E.; Balouzian, Liza; Murray, Peter J.] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA.
   [Johnson, Peter F.] NCI, Lab Canc Prevent, Ctr Canc Res, Ft Detrick, MD 21702 USA.
   [Smale, Stephen T.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
RP Murray, PJ (reprint author), St Jude Childrens Hosp, Dept Infect Dis, Mail Stop 320,262 Danny Thomas Pl, Memphis, TN 38105 USA.
EM peter.murray@stjude.org
RI Johnson, Peter/A-1940-2012
OI Johnson, Peter/0000-0002-4145-4725
FU National Institutes of Health, National Cancer Institute, Center for
   Cancer Research; National Institutes of Health [F32 CA138064]; Hartwell
   Foundation; CORE grant [P30 CA21765]; American Lebanese Syrian
   Associated Charities
FX This work was supported, in whole or in part, by the National Institutes
   of Health Intramural Research Program, National Cancer Institute, Center
   for Cancer Research (to P. F. J.). This work was also supported by
   National Institutes of Health Grant F32 CA138064 (to J. E. Q.), The
   Hartwell Foundation (to P. J. M.), CORE grant P30 CA21765, and the
   American Lebanese Syrian Associated Charities.
NR 58
TC 23
Z9 23
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 1
PY 2011
VL 286
IS 26
BP 23582
EP 23590
DI 10.1074/jbc.M111.249235
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 782QP
UT WOS:000292025000088
PM 21566115
ER

PT J
AU Barbour, KE
   Zmuda, JM
   Boudreau, R
   Strotmeyer, ES
   Horwitz, MJ
   Evans, RW
   Kanaya, AM
   Harris, TB
   Bauer, DC
   Cauley, JA
AF Barbour, Kamil E.
   Zmuda, Joseph M.
   Boudreau, Robert
   Strotmeyer, Elsa S.
   Horwitz, Mara J.
   Evans, Rhobert W.
   Kanaya, Alka M.
   Harris, Tamara B.
   Bauer, Douglas C.
   Cauley, Jane A.
TI Adipokines and the Risk of Fracture in Older Adults
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE LEPTIN; ADIPONECTIN; INCIDENT FRACTURES; LONGITUDINAL; MEN
ID BONE-MINERAL DENSITY; HEALTHY POSTMENOPAUSAL WOMEN; SERUM LEPTIN LEVELS;
   ELDERLY-MEN; PREMENOPAUSAL WOMEN; VERTEBRAL FRACTURES; PLASMA
   ADIPONECTIN; HUMAN OSTEOBLASTS; BODY-COMPOSITION; GHRELIN LEVELS
AB Adiponectin and leptin are adipokines that influence bone metabolism in vitro and in animal models. However, less is known about the longitudinal association of leptin and adiponectin with fracture. We tested the hypothesis that low leptin and high adiponectin levels are each individually associated with fracture risk in a prospective cohort study in Memphis and Pittsburgh among 3075 women and men aged 70 to 79 years from the Health Aging and Body Composition (Health ABC) study. There were 406 incident fractures (334 nonvertebral and 72 vertebral) over a mean of 6.5 +/- 1.9 years. Cox regression was used to estimate the hazard ratios for fracture. Sex modified the association between adiponectin and fracture (p=.025 for interaction). Men with the highest adiponectin level (tertile 3) had a 94% higher risk of fracture (hazard ratio (HR) = 1.94; 95% confidence interval (Cl) 1.20-3.161 compared with the lowest tertile (tertile 1; p=.007 for trend) after adjusting age, race, body mass index (BMI), education, diabetes, weight change, and hip bone mineral density (BMD). Among women, after adjusting for age and race, this association was no longer significant (p=.369 for trend). Leptin did not predict fracture risk in women (p=.544 for trend) or men (p=.118 for trend) in the multivariate models. Our results suggest that adiponectin, but not leptin, may be a novel risk factor for increased fracture risk independent of body composition and BMD and that these relationships may be influenced by sex. More research is needed to understand the physiologic basis underlying these sex differences. (C) 2011 American Society for Bone and Mineral Research.
C1 [Barbour, Kamil E.; Zmuda, Joseph M.; Boudreau, Robert; Strotmeyer, Elsa S.; Evans, Rhobert W.; Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
   [Horwitz, Mara J.] Univ Pittsburgh, Sch Med, Div Endocrinol & Metab, Pittsburgh, PA 15213 USA.
   [Kanaya, Alka M.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
   [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
   [Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
   [Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
RP Barbour, KE (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 N Bellefield Ave, Pittsburgh, PA 15213 USA.
EM barbourk@edc.pitt.edu
RI Strotmeyer, Elsa/F-3015-2014; 
OI Strotmeyer, Elsa/0000-0002-4093-6036; Cauley, Jane
   A/0000-0003-0752-4408; Boudreau, Robert/0000-0003-0162-5187
FU Health Aging and Body Composition Study (Health ABC) [N01-AG-6-2101,
   N01-AG-6-2103, N01-AG-6-2106]; NIH/NIA [R01-AG028050]
FX The Health Aging and Body Composition Study (Health ABC) includes the
   contract numbers N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, and
   NIH/NIA R01-AG028050. This research was supported in part by the
   Intramural Research Program of the NIH, National Institute on Aging.
NR 43
TC 40
Z9 40
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD JUL
PY 2011
VL 26
IS 7
BP 1568
EP 1576
DI 10.1002/jbmr.361
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 783DJ
UT WOS:000292061400019
PM 21312272
ER

PT J
AU Halliburton, SS
   Abbara, S
   Chen, MY
   Gentry, R
   Mahesh, M
   Raff, GL
   Shaw, LJ
   Hausleiter, J
AF Halliburton, Sandra S.
   Abbara, Suhny
   Chen, Marcus Y.
   Gentry, Ralph
   Mahesh, Mahadevappa
   Raff, Gilbert L.
   Shaw, Leslee J.
   Hausleiter, Joerg
TI SCCT guidelines on radiation dose and dose-optimization strategies in
   cardiovascular CT
SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY
LA English
DT Article
DE Practice guideline; Radiation dose; Radiation protection; Radiation
   monitoring; Tomography, x-ray computed; Cardiac-gated imaging
   techniques; Coronary CT angiography; Coronary calcium scanning;
   Algorithms
ID DUAL-SOURCE CT; NONINVASIVE CORONARY-ANGIOGRAPHY; CARDIAC
   COMPUTED-TOMOGRAPHY; TUBE CURRENT MODULATION; STATISTICAL ITERATIVE
   RECONSTRUCTION; AMERICAN-HEART-ASSOCIATION; BISMUTH BREAST SHIELDS;
   IMPROVED IMAGE QUALITY; MULTISLICE HELICAL CT; MULTIDETECTOR ROW CT
AB Over the last few years, computed tomography (CT) has developed into a standard clinical test for a variety of cardiovascular conditions. The emergence of cardiovascular CT during a period of dramatic increase in radiation exposure to the population from medical procedures and heightened concern about the subsequent potential cancer risk has led to intense scrutiny of the radiation burden of this new technique. This has hastened the development and implementation of dose reduction tools and prompted closer monitoring of patient dose. In an effort to aid the cardiovascular CT community in incorporating patient-centered radiation dose optimization and monitoring strategies into standard practice, the Society of Cardiovascular Computed Tomography has produced a guideline document to review available data and provide recommendations regarding interpretation of radiation dose indices and predictors of risk, appropriate use of scanner acquisition modes and settings, development of algorithms for dose optimization, and establishment of procedures for dose monitoring. (C) 2011 Society of Cardiovascular Computed Tomography. All rights reserved.
C1 [Halliburton, Sandra S.] Cleveland Clin, Inst Heart & Vasc, Imaging Inst, Cleveland, OH 44195 USA.
   [Abbara, Suhny] Massachusetts Gen Hosp, Boston, MA 02114 USA.
   [Chen, Marcus Y.] NIH, Bethesda, MD 20892 USA.
   [Gentry, Ralph; Raff, Gilbert L.] William Beaumont Hosp, Royal Oak, MI 48072 USA.
   [Mahesh, Mahadevappa] Johns Hopkins Univ, Baltimore, MD USA.
   [Shaw, Leslee J.] Emory Univ, Atlanta, GA 30322 USA.
   [Hausleiter, Joerg] Deutsch Herzzentrum Munich, Munich, Germany.
RP Halliburton, SS (reprint author), Cleveland Clin, Inst Heart & Vasc, Imaging Inst, 9500 Euclid Ave,J1-4, Cleveland, OH 44195 USA.
EM hallibs@ccf.org
FU Intramural NIH HHS [Z99 HL999999]
NR 140
TC 191
Z9 204
U1 2
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-5925
J9 J CARDIOVASC COMPUT
JI J. Cardiovasc. Comput. Tomogr.
PD JUL-AUG
PY 2011
VL 5
IS 4
BP 198
EP 224
DI 10.1016/j.jcct.2011.06.001
PG 27
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
   Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
   Medical Imaging
GA 035HF
UT WOS:000310933300002
PM 21723512
ER

PT J
AU Ito, Y
   Ma, ZY
   Clary, R
   Powell, J
   Knight, M
   Finn, TM
AF Ito, Yoichiro
   Ma, Zhiyong
   Clary, Robert
   Powell, Jimmie
   Knight, Martha
   Finn, Thomas M.
TI Improved partition efficiency with threaded cylindrical column in vortex
   counter-current chromatography
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Vortex counter-current chromatography; Type-I coil planet centrifuge;
   Cylindrical vortex column; Threaded cylindrical vortex column
AB Type-I coil planet centrifuge produces a uniformly circulating centrifugal force field to produce vortex motion of two immiscible solvent phases in a cylindrical cavity of the separation column to perform efficient countercurrent chromatography. The partition efficiency obtained from the original vortex column was substantially improved by threading the cylindrical cavity to increase the area of mass transfer between the two phases. Partition efficiency of the threaded column was evaluated by three different two-phase solvent systems with a broad range of hydrophobicity each with a set of suitable test samples. Overall results of the present studies indicated that the threaded cylindrical column substantially improves the partition efficiency in terms of theoretical plate number, peak resolution, and height equivalent atone theoretical plate. The results also indicated that higher peak resolution is produced by eluting either the upper phase in the head to tail direction or the lower phase in the reversed direction. When there is a choice in the mobile phase, a better separation is achieved by using the less viscous phase as the mobile phase. Since the present system gives extremely low column pressure, it may be a potential alternative to the conventional type-J HSCCC system for a large-scale preparative separation. Published by Elsevier B.V.
C1 [Ito, Yoichiro; Ma, Zhiyong] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
   [Knight, Martha; Finn, Thomas M.] CCBiotech LLC, Rockville, MD USA.
   [Ma, Zhiyong] Harbin Med Coll, Coll Pharm, Harbin 150081, Peoples R China.
RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM itoy2@mail.nih.gov
OI Knight, Martha/0000-0003-4863-8858
FU Intramural NIH HHS [ZIA HL001060-01]
NR 9
TC 5
Z9 5
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD JUL 1
PY 2011
VL 1218
IS 26
BP 4065
EP 4070
DI 10.1016/j.chroma.2011.04.081
PG 6
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 784RF
UT WOS:000292175200016
PM 21616497
ER

PT J
AU Kardava, L
   Moir, S
   Wang, W
   Ho, J
   Buckner, CM
   Posada, JG
   O'Shea, MA
   Roby, G
   Chen, J
   Sohn, HW
   Chun, TW
   Pierce, SK
   Fauci, AS
AF Kardava, Lela
   Moir, Susan
   Wang, Wei
   Ho, Jason
   Buckner, Clarisa M.
   Posada, Jacqueline G.
   O'Shea, Marie A.
   Roby, Gregg
   Chen, Jenny
   Sohn, Hae Won
   Chun, Tae-Wook
   Pierce, Susan K.
   Fauci, Anthony S.
TI Attenuation of HIV-associated human B cell exhaustion by siRNA down
   regulation of inhibitory receptors
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID CHRONIC VIRAL-INFECTION; FC-GAMMA-RIIB; DISEASE PROGRESSION; ANTIGEN
   RECEPTOR; T-CELLS; INDIVIDUALS; DIFFERENTIATION; ACTIVATION; SURVIVAL;
   EXPRESSION
AB Chronic immune activation in HIV-infected individuals leads to accumulation of exhausted tissue-like memory B cells. Exhausted lymphocytes display increased expression of multiple inhibitory receptors, which may contribute to the inefficiency of HIV-specific antibody responses. Here, we show that downregulation of B cell inhibitory receptors in primary human B cells led to increased tissue-like memory B cell proliferation and responsiveness against HIV. In human B cells, siRNA knockdown of 9 known and putative B cell inhibitory receptors led to enhanced B cell receptor-mediated (BCR-mediated) proliferation of tissue-like memory but not other B cell subpopulations. The strongest effects were observed with the putative inhibitory receptors Fc receptor-like-4 (FCRL4) and sialic acid-binding Ig-like lectin 6 (Siglec-6). Inhibitory receptor downregulation also led to increased levels of HIV-specific antibody-secreting cells and B cell-associated chemokines and cytokines. The absence of known ligands for FCRL4 and Siglec-6 suggests these receptors may regulate BCR signaling through their own constitutive or tonic signaling. Furthermore, the extent of FCLR4 knockdown effects on BCR-mediated proliferation varied depending on the costimulatory ligand, suggesting that inhibitory receptors may engage specific pathways in inhibiting B cell proliferation. These findings on HIV-associated B cell exhaustion define potential targets for reversing the deleterious effect of inhibitory receptors on immune responses against persistent viral infections.
C1 [Kardava, Lela; Moir, Susan; Wang, Wei; Ho, Jason; Buckner, Clarisa M.; Posada, Jacqueline G.; O'Shea, Marie A.; Roby, Gregg; Chen, Jenny; Chun, Tae-Wook; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
   [Chen, Jenny] NIH, Howard Hughes Med Inst, Res Scholars Program, Chevy Chase, MD USA.
   [Sohn, Hae Won; Pierce, Susan K.] NIAID, Lab Immunogenet, NIH, Bethesda, MD 20892 USA.
RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike,Bldg 10,Room 6A02, Bethesda, MD 20892 USA.
EM smoir@niaid.nih.gov
FU NIAID, NIH
FX We thank Dean Follmann and Wenjuan Gu for advice on the statistical
   analyses. We thank Shyam Kottilil for overseeing the research protocol
   involving the enrollment of patients in our study. We thank Catherine
   Rehm, Emily Funk, and Amy Nelson for help in coordinating patient
   participation. We thank the patients for their willingness to
   participate in our study. The work was funded by the Intramural Research
   Program of the NIAID, NIH.
NR 40
TC 48
Z9 49
U1 0
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 JUL
PY 2011
VL 121
IS 7
BP 2614
EP 2624
DI 10.1172/JCI45685
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 787YQ
UT WOS:000292413000012
PM 21633172
ER

PT J
AU Cao, K
   Blair, CD
   Faddah, DA
   Kieckhaefer, JE
   Olive, M
   Erdos, MR
   Nabel, EG
   Collins, FS
AF Cao, Kan
   Blair, Cecilia D.
   Faddah, Dina A.
   Kieckhaefer, Julia E.
   Olive, Michelle
   Erdos, Michael R.
   Nabel, Elizabeth G.
   Collins, Francis S.
TI Progerin and telomere dysfunction collaborate to trigger cellular
   senescence in normal human fibroblasts
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID HUTCHINSON-GILFORD-PROGERIA; MOUSE MODEL; HUMAN-CELLS; NUCLEAR
   ARCHITECTURE; SYNDROME MUTATION; BINDING-PROTEINS; LIFE-SPAN; HNRNP A1;
   LAMIN; EXPRESSION
AB Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging disease, is caused by a point mutation in the lamin A gene (LMNA). This mutation constitutively activates a cryptic splice donor site, resulting in a mutant lamin A protein known as progerin. Recent studies have demonstrated that progerin is also produced at low levels in normal human cells and tissues. However, the cause-and-effect relationship between normal aging and progerin production in normal individuals has not yet been determined. In this study, we have shown in normal human fibroblasts that progressive telomere damage during cellular senescence plays a causative role in activating progerin production. Progressive telomere damage was also found to lead to extensive changes in alternative splicing in multiple other genes. Interestingly, elevated progerin production was not seen during cellular senescence that does not entail telomere shortening. Taken together, our results suggest a synergistic relationship between telomere dysfunction and progerin production during the induction of cell senescence, providing mechanistic insight into how progerin may participate in the normal aging process.
C1 [Cao, Kan; Blair, Cecilia D.; Faddah, Dina A.; Olive, Michelle; Erdos, Michael R.; Nabel, Elizabeth G.; Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   [Cao, Kan; Kieckhaefer, Julia E.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA.
RP Collins, FS (reprint author), NHGRI, Genome Technol Branch, NIH, 1 Ctr Dr,Room 126, Bethesda, MD 20892 USA.
EM Francis.Collins@nih.gov
FU NIA/NIH [R00AG029761]; National Human Genome Research Institute
FX We thank Stephen Wincovitch and Amalia Dutra for support of the
   quantitative telomere PNA-FISH experiments, Stacie Anderson for support
   of the FACS analysis, Abdel Elkahloun for support of the exon array
   experiment, Tyra Wolfsberg for help with GO analysis, Darryl Leja for
   help with figures, Thomas Misteli for the original splice reporter
   construct, Thomas Glover for the human TERT-immortalized fibroblast cell
   lines, Mary Armanios for the DC fibroblast cell lines and helpful
   discussions, Samir Kelada for statistical help, and Karima Djabali for
   the anti-progerin antibody. This work was supported by NIA/NIH grant
   R00AG029761 (to K. Cao) and by the intramural program of the National
   Human Genome Research Institute (to F.S. Collins).
NR 55
TC 105
Z9 108
U1 0
U2 23
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 JUL
PY 2011
VL 121
IS 7
BP 2833
EP 2844
DI 10.1172/JCI43578
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 787YQ
UT WOS:000292413000030
PM 21670498
ER

PT J
AU Sugui, JA
   Christensen, JA
   Bennett, JE
   Zelazny, AM
   Kwon-Chung, KJ
AF Sugui, Janyce A.
   Christensen, Jesica A.
   Bennett, John E.
   Zelazny, Adrian M.
   Kwon-Chung, Kyung J.
TI Hematogenously Disseminated Skin Disease Caused by Mucor velutinosus in
   a Patient with Acute Myeloid Leukemia
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID DISSEMINATED MUCORMYCOSIS; ZYGOMYCOSIS; CIRCINELLOIDES
AB We report here a case of disseminated skin infection caused by Mucor velutinosus, a recently described new species. We believe this to be the first published report of a clinical case of mucormycosis due to M. velutinosus, as well as a rare case of dissemination from a deep site to skin.
C1 [Kwon-Chung, Kyung J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20817 USA.
   [Christensen, Jesica A.] NIH, Helminth Immunol Sect, Parasitol Lab, Bethesda, MD 20817 USA.
   [Bennett, John E.] NIH, Clin Mycol Sect, Lab Clin Infect Dis, Bethesda, MD 20817 USA.
   [Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Bethesda, MD 20817 USA.
RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20817 USA.
EM June_kwon-chung@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
   Institutes of Health, Bethesda, MD
FX This study was supported by funds from the intramural program of the
   National Institute of Allergy and Infectious Diseases, National
   Institutes of Health, Bethesda, MD.
NR 16
TC 5
Z9 5
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD JUL
PY 2011
VL 49
IS 7
BP 2728
EP 2732
DI 10.1128/JCM.00387-11
PG 5
WC Microbiology
SC Microbiology
GA 786BC
UT WOS:000292276200063
PM 21543575
ER

PT J
AU de Groot, JF
   Lamborn, KR
   Chang, SM
   Gilbert, MR
   Cloughesy, TF
   Aldape, K
   Yao, J
   Jackson, EF
   Lieberman, F
   Robins, HI
   Mehta, MP
   Lassman, AB
   DeAngelis, LM
   Yung, WKA
   Chen, A
   Prados, MD
   Wen, PY
AF de Groot, John F.
   Lamborn, Kathleen R.
   Chang, Susan M.
   Gilbert, Mark R.
   Cloughesy, Timothy F.
   Aldape, Kenneth
   Yao, Jun
   Jackson, Edward F.
   Lieberman, Frank
   Robins, H. Ian
   Mehta, Minesh P.
   Lassman, Andrew B.
   DeAngelis, Lisa M.
   Yung, W. K. Alfred
   Chen, Alice
   Prados, Michael D.
   Wen, Patrick Y.
TI Phase II Study of Aflibercept in Recurrent Malignant Glioma: A North
   American Brain Tumor Consortium Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; GLIOBLASTOMA-MULTIFORME; VEGF TRAP;
   ANGIOGENESIS; EXPRESSION; BEVACIZUMAB; IRINOTECAN; INHIBITOR; THERAPY;
   SAMPLES
AB Purpose
   Antivascular endothelial growth factor (anti-VEGF) therapy is a promising treatment approach for patients with recurrent glioblastoma. This single-arm phase II study evaluated the efficacy of aflibercept (VEGF Trap), a recombinantly produced fusion protein that scavenges both VEGF and placental growth factor in patients with recurrent malignant glioma.
   Patients and Methods
   Forty-two patients with glioblastoma and 16 patients with anaplastic glioma who had received concurrent radiation and temozolomide and adjuvant temozolomide were enrolled at first relapse. Aflibercept 4 mg/kg was administered intravenously on day 1 of every 2-week cycle.
   Results
   The 6-month progression-free survival rate was 7.7% for the glioblastoma cohort and 25% for patients with anaplastic glioma. Overall radiographic response rate was 24% (18% for glioblastoma and 44% for anaplastic glioma). The median progression-free survival was 24 weeks for patients with anaplastic glioma (95% CI, 5 to 31 weeks) and 12 weeks for patients with glioblastoma (95% CI, 8 to 16 weeks). A total of 14 patients (25%) were removed from the study for toxicity, on average less than 2 months from treatment initiation. The main treatment-related National Cancer Institute Common Terminology Criteria grades 3 and 4 adverse events (38 total) included fatigue, hypertension, and lymphopenia. Two grade 4 CNS ischemias and one grade 4 systemic hemorrhage were reported. Aflibercept rapidly decreases permeability on dynamic contrast enhanced magnetic resonance imaging, and molecular analysis of baseline tumor tissue identified tumor-associated markers of response and resistance.
   Conclusion
   Aflibercept monotherapy has moderate toxicity and minimal evidence of single-agent activity in unselected patients with recurrent malignant glioma. J Clin Oncol 29:2689-2695. (C) 2011 by American Society of Clinical Oncology
C1 [de Groot, John F.] Univ Texas MD Anderson Canc Ctr, Unit 431, Houston, TX 77030 USA.
   [Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
   [Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   [Lieberman, Frank] Univ Pittsburgh, Pittsburgh, PA USA.
   [Robins, H. Ian] Univ Wisconsin Comprehens Canc Ctr, Madison, WI USA.
   [Mehta, Minesh P.] Northwestern Univ, Evanston, IL USA.
   [Lassman, Andrew B.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
   [Chen, Alice] NCI, Canc Treatment Expt Program, Bethesda, MD 20892 USA.
   [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Wen, Patrick Y.] Brigham & Womens Canc Ctr, Boston, MA USA.
RP de Groot, JF (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 431, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM jdegroot@mdanderson.org
RI Jackson, Edward/L-5159-2013; Gilbert, Mark/J-7494-2016; 
OI Gilbert, Mark/0000-0003-2556-9722; Jackson, Edward/0000-0002-5958-0076;
   mehta, minesh/0000-0002-4812-5713
FU North American Brain Tumor Coalition, National Institutes of Health
   [U01-CA62399]; National Cancer Institute [1R21A126127]; AstraZeneca;
   Adnexus Therapeutics; Exelixis; Novartis; Schering-Plough; Genentech;
   Keryx Biopharmaceuticals; Sigma Tau Pharmaceuticals; NovoCure
FX Supported by Grants No. U01-CA62399 from the North American Brain Tumor
   Coalition, National Institutes of Health and No. 1R21A126127 from the
   National Cancer Institute (J.D.G.).; Research Funding: John F. de Groot,
   AstraZeneca, Adnexus Therapeutics, Exelixis; Susan M. Chang, Novartis,
   Schering-Plough; Mark R. Gilbert, Genentech; Andrew B. Lassman, Keryx
   Biopharmaceuticals, Genentech, Sigma Tau Pharmaceuticals,
   Schering-Plough, Exelixis, NovoCure, AstraZeneca, Adnexus Therapeutics;
   W.K. Alfred Yung, Novartis
NR 33
TC 103
Z9 104
U1 0
U2 9
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 1
PY 2011
VL 29
IS 19
BP 2689
EP 2695
DI 10.1200/JCO.2010.34.1636
PG 7
WC Oncology
SC Oncology
GA 785EP
UT WOS:000292210500022
PM 21606416
ER

PT J
AU Koonin, EV
   Puigbo, P
   Wolf, YI
AF Koonin, Eugene V.
   Puigbo, Pere
   Wolf, Yuri I.
TI Comparison of Phylogenetic Trees and Search for a Central Trend in the
   "Forest of Life''
SO JOURNAL OF COMPUTATIONAL BIOLOGY
LA English
DT Article; Proceedings Paper
CT 2nd Meeting on Bioinformatics Education, Res in Computational Molecular
   Biology (RECOMB-BE)
CY MAY 22-23, 2010
CL San Diego, CA
DE evolution; genomics
ID EVOLUTION
AB The widespread exchange of genes among prokaryotes, known as horizontal gene transfer (HGT), is often considered to "uproot'' the Tree of Life (TOL). Indeed, it is by now fully clear that genes in general possess different evolutionary histories. However, the possibility remains that the TOL concept can be reformulated and remain valid as a statistical central trend in the phylogenetic "Forest of Life'' (FOL). This article describes a computational pipeline developed to chart the FOL by comparative analysis of thousands of phylogenetic trees. This analysis reveals a distinct, consistent phylogenetic signal that is particularly strong among the Nearly Universal Trees (NUTs), which correspond to genes represented in all or most of the analyzed organisms. Despite the substantial amount of apparent HGT seen even among the NUTs, these gene transfers appear to be distributed randomly and do not obscure the central tree-like trend.
C1 [Koonin, Eugene V.; Puigbo, Pere; 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
RI Puigbo, Pere/A-2214-2008
FU U.S. Department of Health and Human Services
FX We wish to thank Jian Ma and Pavel Pevzner for many helpful suggestions.
   Our research was supported by the intramural funds of the U.S.
   Department of Health and Human Services (National Library of Medicine).
NR 10
TC 12
Z9 12
U1 1
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1066-5277
EI 1557-8666
J9 J COMPUT BIOL
JI J. Comput. Biol.
PD JUL
PY 2011
VL 18
IS 7
BP 917
EP 924
DI 10.1089/cmb.2010.0185
PG 8
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 784YA
UT WOS:000292193400006
PM 21457008
ER

PT J
AU Nguyen, A
   Belgrave, F
AF Anh Nguyen
   Belgrave, Faye
TI ETHNIC IDENTITY AND SUBSTANCE USE AMONG AFRICAN AMERICAN WOMEN: THE
   MEDIATING INFLUENCE OF GENDER ROLES
SO JOURNAL OF DRUG ISSUES
LA English
DT Article
AB Ethnic identity is protective against substance use and other problem behaviors; however, some studies have implicated ethnic identity as a contributor to substance use. We hypothesized that the relationship between ethnic identity and substance use would be fully mediated by gender role orientation. Participants included 562 African American women in the south-eastern region of the United States. Participants completed the Multigroup Ethnic Identity Measure (MEIM) and the Personal Attributes Questionnaire and reported past 30-day drug use. We employed structural equation modeling. The composite model displayed acceptable global fit. Ethnic identity predicted African American females' identification with male gender roles. Identification with male gender roles was positively linked to perceptions of drug risk and past 30-day drug use. Perceptions of drug risk was negatively linked to past 30-day drug use. Identification with masculine gender roles as a significant drug risk factor suggests some implications for prevention programming.
C1 [Anh Nguyen] NCI, Bethesda, MD 20892 USA.
   [Belgrave, Faye] Ctr Cultural Experiences Prevent, Richmond, VA USA.
RP Nguyen, A (reprint author), NCI, Bethesda, MD 20892 USA.
NR 58
TC 0
Z9 0
U1 1
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-0426
EI 1945-1369
J9 J DRUG ISSUES
JI J. Drug Issues
PD JUL
PY 2011
VL 41
IS 3
BP 379
EP 400
DI 10.1177/002204261104100304
PG 22
WC Substance Abuse
SC Substance Abuse
GA V33PC
UT WOS:000209029700004
ER

PT J
AU Huestis, DL
   Yaro, AS
   Traore, AI
   Adamou, A
   Kassogue, Y
   Diallo, M
   Timbine, S
   Dao, A
   Lehmann, T
AF Huestis, Diana L.
   Yaro, Alpha S.
   Traore, Adama I.
   Adamou, Abdoulaye
   Kassogue, Yaya
   Diallo, Moussa
   Timbine, Seydou
   Dao, Adama
   Lehmann, Tovi
TI Variation in metabolic rate of Anopheles gambiae and A. arabiensis in a
   Sahelian village
SO JOURNAL OF EXPERIMENTAL BIOLOGY
LA English
DT Article
DE aestivation; gonotrophic cycle; malaria vector; respiration;
   seasonality; temperature
ID MOLECULAR-FORMS; DESICCATION RESISTANCE; DRY SEASON;
   PLASMODIUM-FALCIPARUM; INCIPIENT SPECIATION; DIPTERA-CULICIDAE;
   CULISETA-INORNATA; AN.-ARABIENSIS; SENSU-STRICTO; WEST-AFRICA
AB In the Sahel, the Anopheles gambiae complex consists of Anopheles arabiensis and the M and S molecular forms of A. gambiae sensu stricto. However, the composition of these malaria vectors varies spatially and temporally throughout the region and is thought to be linked to environmental factors such as rainfall, larval site characteristics and duration of the dry season. To examine possible physiological divergence between these taxa, we measured metabolic rates of mosquitoes during the wet season in a Sahelian village in Mali. To our knowledge, this study provides the first measurements of metabolic rates of A. gambiae and A. arabiensis in the field. The mean metabolic rate of A. arabiensis was higher than that of M-form A. gambiae when accounting for the effects of female gonotrophic status, temperature and flight activity. However, after accounting for their difference in body size, no significant difference in metabolic rate was found between these two species (whilst all other factors were found to be significant). Thus, body size may be a key character that has diverged in response to ecological differences between these two species. Alternatively, these species may display additional differences in metabolic rate only during the dry season. Overall, our results indicate that changes in behavior and feeding activity provide an effective mechanism for mosquitoes to reduce their metabolic rate, and provide insight into the possible strategies employed by aestivating individuals during the dry season. We hypothesize that female mosquitoes switch to sugar feeding while in dormancy because of elevated metabolism associated with blood digestion.
C1 [Huestis, Diana L.; Lehmann, Tovi] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
   [Yaro, Alpha S.; Traore, Adama I.; Adamou, Abdoulaye; Kassogue, Yaya; Diallo, Moussa; Timbine, Seydou; Dao, Adama] Univ Bamako, Malaria Res & Training Ctr, Bamako, Mali.
RP Huestis, DL (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA.
EM diana.huestis@nih.gov
OI Huestis, Diana/0000-0001-6649-4785
FU NIH, NIAID
FX We thank R. Gwadz, T. Wellems and R. Sakai for their assistance in
   facilitating this work, H. Ackerman for providing average blood
   chemistry data and K. Hines for use of the electrobalance. We also thank
   the inhabitants of M'Piabougou and Thierola, Mali, for their assistance
   and hospitality, without which this work would not have been possible.
   Comments from P. Armbruster, B. Oppert and two anonymous reviewers
   improved the quality of this manuscript. This research was supported by
   the Intramural Research Program of the NIH, NIAID. Deposited in PMC for
   release after 12 months.
NR 73
TC 22
Z9 22
U1 2
U2 12
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
   CAMBS, ENGLAND
SN 0022-0949
J9 J EXP BIOL
JI J. Exp. Biol.
PD JUL
PY 2011
VL 214
IS 14
BP 2345
EP 2353
DI 10.1242/jeb.054668
PG 9
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 781JL
UT WOS:000291927000010
PM 21697426
ER

PT J
AU Sherman, A
AF Sherman, Arthur
TI Dynamical systems theory in physiology
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Editorial Material
ID PANCREATIC BETA-CELL; PITUITARY-CELLS; MODEL; OSCILLATIONS; MEMBRANE
C1 NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA.
RP Sherman, A (reprint author), NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA.
EM sherman@helix.nih.gov
FU Intramural NIH HHS
NR 27
TC 10
Z9 10
U1 0
U2 2
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD JUL
PY 2011
VL 138
IS 1
BP 13
EP 19
DI 10.1085/jgp.201110668
PG 7
WC Physiology
SC Physiology
GA 784CL
UT WOS:000292131300002
PM 21708952
ER

PT J
AU Hsiao, CP
   Wang, D
   Kaushal, A
   Saligan, L
AF Hsiao, Chao-Pin
   Wang, Dan
   Kaushal, Aradhana
   Saligan, Leorey
TI Mitochondria-Related Gene Expression Changes Are Associated with Fatigue
   in Patients with Non-metastatic Prostate Cancer Receiving External Beam
   Radiation Therapy.
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Meeting Abstract
CT 64th Annual Meeting of the Society-of-General-Physiologists
CY SEP 08-12, 2010
CL Marine Biol Lab, Woods Hole, MA
SP Soc Gen Physiologists
HO Marine Biol Lab
C1 [Hsiao, Chao-Pin; Wang, Dan; Saligan, Leorey] NINR, Bethesda, MD 20892 USA.
   [Kaushal, Aradhana] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD JUL
PY 2011
VL 138
IS 1
BP 22A
EP 22A
PG 1
WC Physiology
SC Physiology
GA 784CL
UT WOS:000292131300059
ER

PT J
AU Pivovarova, NB
   Villanueva, I
   Stanika, RI
AF Pivovarova, N. B.
   Villanueva, I.
   Stanika, R. I.
TI Mitochondrial Dysfunction and Neuronal Injury Mediated by Voltage-Gated
   Calcium Channels.
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Meeting Abstract
CT 64th Annual Meeting of the Society-of-General-Physiologists
CY SEP 08-12, 2010
CL Marine Biol Lab, Woods Hole, MA
SP Soc Gen Physiologists
HO Marine Biol Lab
C1 [Pivovarova, N. B.; Villanueva, I.; Stanika, R. I.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD JUL
PY 2011
VL 138
IS 1
BP 22A
EP 23A
PG 2
WC Physiology
SC Physiology
GA 784CL
UT WOS:000292131300061
ER

PT J
AU Bosmans, F
   Puopolo, M
   Martin-Eauclaire, MF
   Bean, BP
   Swartz, KJ
AF Bosmans, Frank
   Puopolo, Michelino
   Martin-Eauclaire, Marie-France
   Bean, Bruce P.
   Swartz, Kenton J.
TI Functional properties and toxin pharmacology of a dorsal root ganglion
   sodium channel viewed through its voltage sensors
SO JOURNAL OF GENERAL PHYSIOLOGY
LA English
DT Article
ID DEPENDENT K+ CHANNEL; SHAKER POTASSIUM CHANNELS; PERFORMANCE
   LIQUID-CHROMATOGRAPHY; PERSISTENT NA+ CURRENT; ALPHA-SCORPION TOXIN;
   GATED ION CHANNELS; TETRODOTOXIN-RESISTANT; TARANTULA TOXINS;
   GATING-CHARGE; MOLECULAR DETERMINANTS
AB The voltage-activated sodium (Nav) channel Nav1.9 is expressed in dorsal root ganglion (DRG) neurons where it is believed to play an important role in nociception. Progress in revealing the functional properties and pharmacological sensitivities of this non-canonical Nav channel has been slow because attempts to express this channel in a heterologous expression system have been unsuccessful. Here, we use a protein engineering approach to dissect the contributions of the four Nav1.9 voltage sensors to channel function and pharmacology. We define individual S3b-S4 paddle motifs within each voltage sensor, and show that they can sense changes in membrane voltage and drive voltage sensor activation when transplanted into voltage-activated potassium channels. We also find that the paddle motifs in Nav1.9 are targeted by animal toxins, and that these toxins alter Nav1.9-mediated currents in DRG neurons. Our results demonstrate that slowly activating and inactivating Nav1.9 channels have functional and pharmacological properties in common with canonical Nav channels, but also show distinctive pharmacological sensitivities that can potentially be exploited for developing novel treatments for pain.
C1 [Bosmans, Frank; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Puopolo, Michelino; Bean, Bruce P.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   [Martin-Eauclaire, Marie-France] Univ Aix Marseille 2, Ctr Natl Rech Sci, UMR 6132, CRN2M,Inst Jean Roche, F-13916 Marseille 20, France.
RP Bosmans, F (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
EM Frank.Bosmans@nih.gov; Kenton.Swartz@nih.gov
RI Bosmans, Frank/A-9660-2013
OI Bosmans, Frank/0000-0002-6476-235X
FU National Institute of Neurological Disorders and Stroke, National
   Institutes of Health
FX This work was supported by the Intramural Research Program of the
   National Institute of Neurological Disorders and Stroke, National
   Institutes of Health.
NR 85
TC 25
Z9 25
U1 1
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1295
J9 J GEN PHYSIOL
JI J. Gen. Physiol.
PD JUL
PY 2011
VL 138
IS 1
BP 59
EP 72
DI 10.1085/jgp.201110614
PG 14
WC Physiology
SC Physiology
GA 784CL
UT WOS:000292131300006
PM 21670206
ER

PT J
AU Davis, JK
   Mittel, B
   Lowman, JJ
   Thomas, PJ
   Maney, DL
   Martin, CL
   Thomas, JW
AF Davis, Jamie K.
   Mittel, B.
   Lowman, Josh J.
   Thomas, Pamela J.
   Maney, Donna L.
   Martin, Christa L.
   Thomas, James W.
CA NISC Comparative Sequencing Progra
TI Haplotype-Based Genomic Sequencing of a Chromosomal Polymorphism in the
   White-Throated Sparrow (Zonotrichia albicollis)
SO JOURNAL OF HEREDITY
LA English
DT Article
DE chromosomal polymorphism; evolutionary genetics; haplotype-based
   sequencing; inversion
ID WIDE LINKAGE DISEQUILIBRIUM; T-COMPLEX; EVOLUTION; INVERSION; GMELIN;
   GENE; RECOMBINATION; SUBSTITUTIONS; ALIGNMENTS; LIKELIHOOD
AB Inversion polymorphisms have been linked to a variety of fundamental biological and evolutionary processes. Yet few studies have used large-scale genomic sequencing to directly compare the haplotypes associated with the standard and inverted chromosome arrangements. Here we describe the targeted genomic sequencing and comparison of haplotypes representing alternative arrangements of a common inversion polymorphism linked to a suite of phenotypes in the white-throated sparrow (Zonotrichia albicollis). More than 7.4 Mb of genomic sequence was generated and assembled from both the standard (ZAL2) and inverted (ZAL2(m)) arrangements. Sequencing of a pair of inversion breakpoints led to the identification of a ZAL2-specific segmental duplication, as well as evidence of breakpoint reusage. Comparison of the haplotype-based sequence assemblies revealed low genetic differentiation outside versus inside the inversion indicative of historical patterns of gene flow and suppressed recombination between ZAL2 and ZAL2(m). Finally, despite ZAL2(m) being maintained in a near constant state of heterozygosity, no signatures of genetic degeneration were detected on this chromosome. Overall, these results provide important insights into the genomic attributes of an inversion polymorphism linked to mate choice and variation in social behavior.
C1 [Davis, Jamie K.; Mittel, B.; Lowman, Josh J.; Thomas, James W.] Emory Univ, Dept Human Genet, Sch Med, Atlanta, GA 30322 USA.
   [Thomas, Pamela J.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   [Thomas, Pamela J.; NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
   [Maney, Donna L.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
RP Thomas, JW (reprint author), Emory Univ, Dept Human Genet, Sch Med, 615 Michael St,Suite 301, Atlanta, GA 30322 USA.
EM jthomas@genetics.emory.edu
RI Maney, Donna/G-3706-2011
FU National Institutes of Health (NIH) [1R21MH082046]; Center for
   Behavioral Neuroscience; National Human Genome Research Institute of the
   NIH
FX National Institutes of Health (NIH) (1R21MH082046) and the Center for
   Behavioral Neuroscience to J.K.D., J.J.L., D.L.M, C.L.M., and J.W.T.
   Intramural Research Program of the National Human Genome Research
   Institute of the NIH to NIH Intramural Sequencing Center.
NR 55
TC 16
Z9 16
U1 0
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1503
EI 1465-7333
J9 J HERED
JI J. Hered.
PD JUL-AUG
PY 2011
VL 102
IS 4
BP 380
EP 390
DI 10.1093/jhered/esr043
PG 11
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA 784CI
UT WOS:000292130800002
PM 21613376
ER

PT J
AU Yu, HF
   Tawab-Amiri, A
   Dzutsev, A
   Sabatino, M
   Aleman, K
   Yarchoan, R
   Terabe, M
   Sui, YJ
   Berzofsky, JA
AF Yu, Huifeng
   Tawab-Amiri, Abdul
   Dzutsev, Amiran
   Sabatino, Marianna
   Aleman, Karen
   Yarchoan, Robert
   Terabe, Masaki
   Sui, Yongjun
   Berzofsky, Jay A.
TI IL-15 ex vivo overcomes CD4(+) T cell deficiency for the induction of
   human antigen-specific CD8(+) T cell responses
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE primary cells; dendritic cells; lymphoid cell-mediated immunity
ID MATURE DENDRITIC CELLS; DISEASE PROGRESSION; VACCINE DEVELOPMENT;
   CYTOKINE PRODUCTION; MEDIATED APOPTOSIS; CD8-T-CELL MEMORY; CD4-T-CELL
   HELP; INTERLEUKIN-15; HIV; LYMPHOCYTES
AB CD4(+) Th cells are important for the induction and maintenance of antigen-specific CD8(+) T cell function, so their loss or dysfunction in HIV-infected or cancer patients could reduce the patients' ability to control viral infection. Previous work in murine systems indicated that IL-15 codelivered with vaccines could overcome CD4(+) Th cell deficiency for induction of functionally efficient CD8(+) T cells and maintenance of viral-specific CTLs, but its efficacy in helping primary human CD8(+) T cell responses is unknown. In the present study, a peptide-pulsed, DC-based human coculture ex vivo system was used to study the role of IL-15 in overcoming CD4(+) Th deficiency to elicit CD8(+) T cell responses in CD4-depleted PBMCs from healthy individuals and PBMCs from HIV-1-infected patients. We found that IL-15 could overcome CD4(+) Th deficiency to induce primary and recall memory CD8(+) T cell responses in healthy individuals. Moreover, in CD4-deficient, HIV-1-infected patients with diminished CD8(+) T cell responses, IL-15 greatly enhanced CD8(+) T cell responses to alloantigen. These results suggest that IL-15 may be useful in the development of therapeutic and preventive vaccines against cancers and viral infections in patients defective in CD4(+) Th cell. J. Leukoc. Biol. 90: 205-214; 2011.
C1 [Yu, Huifeng; Dzutsev, Amiran; Terabe, Masaki; Sui, Yongjun; Berzofsky, Jay A.] Natl Canc Inst, Vaccine Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Tawab-Amiri, Abdul; Sabatino, Marianna] Natl Canc Inst, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
   [Aleman, Karen; Yarchoan, Robert] Natl Canc Inst, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Sui, YJ (reprint author), Natl Canc Inst, Vaccine Branch, Ctr Canc Res, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM suiy@mail.nih.gov; berzofsj@mail.nih.gov
FU Center for Cancer Research, NCI, NIH
FX This work was supported by the Intramural Research Program of the Center
   for Cancer Research, NCI, NIH. We are grateful to Dr. Thomas A. Waldmann
   (Metabolism Branch, NCI, NIH) and Dr. Giorgio Trinchieri (Laboratory of
   Experimental Immunology, NCI, NIH) for critical review of this
   manuscript and helpful discussion.
NR 54
TC 6
Z9 6
U1 0
U2 2
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 JUL
PY 2011
VL 90
IS 1
BP 205
EP 214
DI 10.1189/jlb.1010579
PG 10
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 785QQ
UT WOS:000292244200022
PM 21474552
ER

PT J
AU McMaster, ML
   Goldstein, AM
   Parry, DM
AF McMaster, Mary L.
   Goldstein, Alisa M.
   Parry, Dilys M.
TI Clinical features distinguish childhood chordoma associated with
   tuberous sclerosis complex (TSC) from chordoma in the general paediatric
   population
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID FAMILIAL CHORDOMA; CLIVUS CHORDOMA; NEUROFIBROMATOSIS; DYSREGULATION;
   PATHOGENESIS; CHILDREN; PATHWAY; PATIENT
AB Background Chordoma, an age-dependent rare cancer, arises from notochordal remnants. Fewer than 5% of chordomas occur in children. Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome characterised by abnormal tissue growths in multiple organ systems. Reports of chordoma in children with TSC suggest that TSC1 and TSC2 mutations may contribute to chordoma aetiology.
   Methods To determine whether the 10 TSC-associated childhood chordomas reported in the literature are representative of chordoma in the general paediatric population, the authors compared age at diagnosis, primary site and outcome in them with results from a systematic assessment of 65 paediatric chordoma cases reported to the US population-based cancer registries contributing to the SEER Program of the National Cancer Institute.
   Results TSC-associated paediatric chordomas differed from chordomas in the general paediatric population: median age at diagnosis (6.2 months, TSC, vs 12.5 years, SEER); anatomical site (40% sacral, TSC, vs 9.4% sacral, SEER); and site-specific age at diagnosis (all four sacral chordomas diagnosed during the fetal or neonatal period, TSC, vs all six sacral chordomas diagnosed at >15 years, SEER). Finally, three of four patients with TSC-associated sacral chordoma were alive and tumour-free at 2.2, 8 and 19 years after diagnosis versus a median survival of 36 months among paediatric patients with sacral chordoma in SEER.
   Conclusions These results strengthen the association between paediatric chordoma and TSC. Future clinical and molecular studies documenting the magnitude and clinical spectrum of the joint occurrence of these two diseases should provide the basis for delineating the biological relationship between them.
C1 [McMaster, Mary L.; Goldstein, Alisa M.; Parry, Dilys M.] NCI, Genet Epidemiol Branch, Human Genet Program, Div Canc Epidemiol & Genet,NIH,Dept Hlth & Human, Bethesda, MD 20892 USA.
   [McMaster, Mary L.] US PHS, Commissioned Corps, Dept Hlth & Human Serv, Washington, DC USA.
RP Parry, DM (reprint author), 6120 Execut Blvd,Room 7124,MSC 7236, Bethesda, MD 20892 USA.
EM parryd@mail.nih.gov
FU National Cancer Institute, NIH
FX This research was supported by the Intramural Research Program of the
   National Cancer Institute, NIH.
NR 40
TC 13
Z9 13
U1 0
U2 3
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
J9 J MED GENET
JI J. Med. Genet.
PD JUL
PY 2011
VL 48
IS 7
BP 444
EP 449
DI 10.1136/jmg.2010.085092
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 781JK
UT WOS:000291926800003
PM 21266383
ER

PT J
AU Zacharin, M
   Bajpai, A
   Chow, CW
   Catto-Smith, A
   Stratakis, C
   Wong, MW
   Scott, R
AF Zacharin, Margaret
   Bajpai, Anurag
   Chow, Chung Wo
   Catto-Smith, Anthony
   Stratakis, Constantine
   Wong, Michelle W.
   Scott, Rodney
TI Gastrointestinal polyps in McCune Albright syndrome
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID ACTIVATING MUTATIONS; GENE; HYPERPLASIA; CHAIN; CELLS; BONE; GS
AB Background McCune Albright syndrome (MAS), a disorder caused by somatic activating mutations in the GNAS gene, usually presents with cutaneous, skeletal, and endocrine manifestations. While focal lesions involving multiple tissues have been identified in MAS, almost nothing is known about gastrointestinal lesions in this disease.
   Methods Two MAS patients with perioral freckling, resembling Peutze-Jeghers syndrome (PJS), and two MAS patients without similar pigmentation underwent gastrointestinal endoscopy to establish if they had coexisting hamartomatous polyposis. Three of 4 subjects had documented GNAS mutations in peripheral blood. Genetic testing for STK11 and PRKAR1A genes was performed to exclude presence of coexistent PJS and Carney complex. Genetic testing of biopsy material was also performed.
   Results Hamartomatous gastrointestinal polyps with histological features similar to those in PJS were observed in all 4 subjects, only in the stomach and/or upper duodenum. Activating GNAS mutations were found in the polyps or adjacent mucosa in 3 of 4 subjects. One patient each had mutation only in the blood or tissue, while 2 patients had both. No subject harboured any detectable PRKARIA or STK11 mutation as determined by direct DNA sequencing and copy number variation analysis.
   Conclusions These findings confirm that gastrointestinal polyps are a common manifestation of MAS, indicate an overlap between MAS and PJS, and point towards a putative interaction between the GNAS and STK11 genes in the pathogenesis of these two disorders. The findings suggest a need for routine gastrointestinal endoscopy in patients with MAS, to establish the true incidence of polyps in these patients.
C1 [Zacharin, Margaret] Royal Childrens Hosp, Dept Endocrinol & Diabet, Melbourne, Vic 3052, Australia.
   [Zacharin, Margaret] Royal Childrens Hosp, Dept Paediat, Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia.
   [Bajpai, Anurag] Kanpur Hosp, Regency Hosp Ltd, Kanpur, Uttar Pradesh, India.
   [Chow, Chung Wo] Royal Childrens Hosp, Dept Anat Pathol, Melbourne, Vic 3052, Australia.
   [Catto-Smith, Anthony] Royal Childrens Hosp, Dept Gastroenterol & Clin Nutr, Melbourne, Vic 3052, Australia.
   [Stratakis, Constantine] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Rockville, MD USA.
   [Wong, Michelle W.; Scott, Rodney] Univ Newcastle, Dept Genet, Sch Biomed Sci, Callaghan, NSW 2308, Australia.
RP Zacharin, M (reprint author), Royal Childrens Hosp, Dept Endocrinol & Diabet, Flemington Rd, Melbourne, Vic 3052, Australia.
EM margaret.zacharin@rch.org.au
RI Catto-Smith, Anthony/H-3698-2012
FU Intramural NIH HHS [ZIA HD000642-13]
NR 20
TC 8
Z9 8
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
EI 1468-6244
J9 J MED GENET
JI J. Med. Genet.
PD JUL
PY 2011
VL 48
IS 7
BP 458
EP 461
DI 10.1136/jmg.2010.086330
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 781JK
UT WOS:000291926800005
PM 21357941
ER

PT J
AU Kratz, CP
   Han, SS
   Rosenberg, PS
   Berndt, SI
   Burdett, L
   Yeager, M
   Korde, LA
   Mai, PL
   Pfeiffer, R
   Greene, MH
AF Kratz, Christian P.
   Han, Summer S.
   Rosenberg, Philip S.
   Berndt, Sonja I.
   Burdett, Laurie
   Yeager, Meredith
   Korde, Larissa A.
   Mai, Phuong L.
   Pfeiffer, Ruth
   Greene, Mark H.
TI Variants in or near KITLG, BAK1, DMRT1, and TERT-CLPTM1L predispose to
   familial testicular germ cell tumour
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID CANCER; RISK; ASSOCIATION; PREVALENCE; ETIOLOGY; TWINS; MEN
AB Background Familial testicular germ cell tumours (TGCTs) and bilateral TGCTs comprise 1-2% and 5% of all TGCTs, respectively, but their genetic basis remains largely unknown.
   Aim To investigate the contribution of known testicular cancer risk variants in familial and bilateral TGCTs.
   Methods and results The study genotyped 106 single nucleotide polymorphisms (SNPs) in four regions (BAK1, DMRT1, KITLG, TERT-CLPTM1L) previously identified from genome-wide association studies of TGCT, including risk single nucleotide polymorphisms (SNPs) rs210138 (BAK1), rs755383 (DMRT1), rs4635969 (TERT-CLPTM1L) in 97 cases with familial TGCT and 22 affected individuals with sporadic bilateral TGCT as well as 871 controls. Using a generalised estimating equations method that takes into account blood relationships among cases, the associations with familial and bilateral TGCT were analysed. Three previously identified risk SNPs were found to be associated with familial and bilateral TGCT (rs210138: OR 1.80, CI 1.35 to 2.41, p=7.03x10(-5); rs755383: OR 1.67, CI 1.23 to 2.22, p=6.70x10(-4); rs4635969: OR 1.59, CI 1.16 to 2.19, p =4.07x10(-3)). Evidence for a second independent association was found for an SNP in TERT (rs4975605: OR 1.68, CI 1.23 to 2.29, p=1.24x10(-3)). Another association with an SNP was identified in KITLG (rs2046971: OR 2.33, p=1.28x10(-3)); this SNP is in high linkage disequilibrium (LD) with reported risk variant rs995030.
   Conclusion This study provides evidence for replication of recent genome-wide association studies results and shows that variants in or near BAK1, DMRT1, TERT-CLPTM1L, and KITLG predispose to familial and bilateral TGCT. These findings imply that familial TGCT and sporadic TGCT share a common genetic basis.
C1 [Kratz, Christian P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
   [Burdett, Laurie; Yeager, Meredith] NCI, Core Genotyping Facil, SAIC Frederick, Gaithersburg, MD USA.
RP Kratz, CP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7018, Rockville, MD 20852 USA.
EM kratzcp@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011
FU National Institutes of Health; National Cancer Institute; Westat
   [N02-CP-65504]
FX This work was supported by the Intramural Research Program of the
   National Institutes of Health and the National Cancer Institute, and by
   a support services contract with Westat (N02-CP-65504).
NR 22
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U2 0
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
J9 J MED GENET
JI J. Med. Genet.
PD JUL
PY 2011
VL 48
IS 7
BP 473
EP 476
DI 10.1136/jmedgenet-2011-100001
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 781JK
UT WOS:000291926800008
PM 21617256
ER

PT J
AU Lin, WY
   Camp, NJ
   Cannon-Albright, LA
   Allen-Brady, K
   Balasubramanian, S
   Reed, MWR
   Hopper, JL
   Apicella, C
   Giles, GG
   Southey, MC
   Milne, RL
   Arias-Perez, JI
   Menendez-Rodriguez, P
   Benitez, J
   Grundmann, M
   Dubrowinskaja, N
   Park-Simon, TW
   Dork, T
   Garcia-Closas, M
   Figueroa, J
   Sherman, M
   Lissowska, J
   Easton, DF
   Dunning, AM
   Rajaraman, P
   Sigurdson, AJ
   Doody, MM
   Linet, MS
   Pharoah, PD
   Schmidt, MK
   Cox, A
AF Lin, Wei-Yu
   Camp, Nicola J.
   Cannon-Albright, Lisa A.
   Allen-Brady, Kristina
   Balasubramanian, Sabapathy
   Reed, Malcolm W. R.
   Hopper, John L.
   Apicella, Carmel
   Giles, Graham G.
   Southey, Melissa C.
   Milne, Roger L.
   Arias-Perez, Jose I.
   Menendez-Rodriguez, Primitiva
   Benitez, Javier
   Grundmann, Magdalena
   Dubrowinskaja, Natalia
   Park-Simon, Tjoung-Won
   Doerk, Thilo
   Garcia-Closas, Montserrat
   Figueroa, Jonine
   Sherman, Mark
   Lissowska, Jolanta
   Easton, Douglas F.
   Dunning, Alison M.
   Rajaraman, Preetha
   Sigurdson, Alice J.
   Doody, Michele M.
   Linet, Martha S.
   Pharoah, Paul D.
   Schmidt, Marjanka K.
   Cox, Angela
TI A role for XRCC2 gene polymorphisms in breast cancer risk and survival
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID HOMOLOGOUS RECOMBINATIONAL REPAIR; SINGLE-NUCLEOTIDE POLYMORPHISMS;
   GENOME-WIDE ASSOCIATION; DOUBLE-STRAND BREAKS; DNA-REPAIR;
   MAMMALIAN-CELLS; CHROMOSOME STABILITY; RAD51 PARALOGS; PATHWAY GENES;
   CROSS-LINKS
AB Background The XRCC2 gene is a key mediator in the homologous recombination repair of DNA double strand breaks. It is hypothesised that inherited variants in the XRCC2 gene might also affect susceptibility to, and survival from, breast cancer.
   Methods The study genotyped 12 XRCC2 tagging single nucleotide polymorphisms (SNPs) in 1131 breast cancer cases and 1148 controls from the Sheffield Breast Cancer Study (SBCS), and examined their associations with breast cancer risk and survival by estimating ORs and HRs, and their corresponding 95% CIs. Positive findings were further investigated in 860 cases and 869 controls from the Utah Breast Cancer Study (UBCS) and jointly analysed together with available published data for breast cancer risk. The survival findings were further confirmed in studies (8074 cases) from the Breast Cancer Association Consortium (BCAC).
   Results The most significant association with breast cancer risk in the SBCS dataset was the XRCC2 rs3218408 SNP (recessive model p=2.3x10(-4), minor allele frequency (MAF)=0.23). This SNP yielded an ORrec of 1.64 (95% CI 1.25 to 2.16) in a two-site analysis of SBCS and UBCS, and a meta-ORrec of 1.33 (95% CI 1.12 to 1.57) when all published data were included. This SNP may mark a rare risk haplotype carried by two in 1000 of the control population. Furthermore, the XRCC2 coding R188H SNP (rs3218536, MAF=0.08) was significantly associated with poor survival, with an increased per-allele HR of 1.58 (95% CI 1.01 to 2.49) in a multivariate analysis. This effect was still evident in a pooled meta-analysis of 8781 breast cancer patients from the BCAC (HR 1.19, 95% CI 1.05 to 1.36; p=0.01).
   Conclusions These findings suggest that XRCC2 SNPs may influence breast cancer risk and survival.
C1 [Cox, Angela] Univ Sheffield, Sheffield Med Sch, Inst Canc Studies, Dept Oncol, Sheffield S10 2RX, S Yorkshire, England.
   [Camp, Nicola J.; Cannon-Albright, Lisa A.; Allen-Brady, Kristina] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT USA.
   [Balasubramanian, Sabapathy; Reed, Malcolm W. R.] Univ Sheffield, Dept Oncol, Acad Unit Surg Oncol, Sheffield S10 2RX, S Yorkshire, England.
   [Hopper, John L.; Apicella, Carmel; Milne, Roger L.] Univ Melbourne, Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Carlton, Vic 3053, Australia.
   [Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia.
   [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Carlton, Vic 3053, Australia.
   [Milne, Roger L.] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain.
   [Arias-Perez, Jose I.; Menendez-Rodriguez, Primitiva] Hosp Monte Naranco, Oviedo, Spain.
   [Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid, Spain.
   [Grundmann, Magdalena; Dubrowinskaja, Natalia; Park-Simon, Tjoung-Won; Doerk, Thilo] Hannover Med Sch, Clin Obstet & Gynaecol, D-3000 Hannover, Germany.
   [Garcia-Closas, Montserrat] Inst Canc Res, Epidemiol Sect, Surrey, England.
   [Garcia-Closas, Montserrat] Inst Canc Res, Genet Sect, Surrey, England.
   [Figueroa, Jonine; Sherman, Mark] NCI, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA.
   [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
   [Easton, Douglas F.; Dunning, Alison M.; Pharoah, Paul D.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
   [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
   [Easton, Douglas F.; Dunning, Alison M.] Univ Cambridge, Dept Oncol, Cambridge, England.
   [Rajaraman, Preetha; Sigurdson, Alice J.; Doody, Michele M.; Linet, Martha S.] NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Rockville, MD USA.
   [Schmidt, Marjanka K.] Netherlands Canc Inst, Amsterdam, Netherlands.
RP Cox, A (reprint author), Univ Sheffield, Sheffield Med Sch, Inst Canc Studies, Dept Oncol, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England.
EM a.cox@shef.ac.uk
RI Garcia-Closas, Montserrat /F-3871-2015; Lin, Wei-Yu/F-4505-2010; Dork,
   Thilo/J-8620-2012; 
OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Lin,
   Wei-Yu/0000-0002-9267-7988; Lissowska, Jolanta/0000-0003-2695-5799;
   Dunning, Alison Margaret/0000-0001-6651-7166; albright,
   lisa/0000-0003-2602-3668; Cox, Angela/0000-0002-5138-1099; Giles,
   Graham/0000-0003-4946-9099
FU Breast Cancer Campaign [2000:146]; Yorkshire Cancer Research; Susan G.
   Komen Breast Cancer Foundation [BCTR0706911]; Avon Foundation
   [02-2009-080]; NCI [P30 CA42014, HHSN261201000026C]; University of Utah;
   National Health and Medical Research Council of Australia; New South
   Wales Cancer Council; Victorian Health Promotion Foundation (Australia);
   National Cancer Institute, National Institutes of Health
   [RFA-CA-06-503]; Red Tematica de Investigacion Cooperativa en Cancer;
   Asociacion Espanola Contra Cancer; Fondo de Investigacion Santiario
   [PI081583, PI081120]; Cancer Research UK [C490/A10124]; Cambridge NIHR
   Biomedical Research Centre; National Cancer Institute, Department of
   Health and Human Services, USA; Division of Cancer Epidemiology and
   Genetics, National Cancer Institute, National Institutes of Health
FX The SBCS study was funded by the Breast Cancer Campaign (grants 2000:146
   and 2004 Nov 49), and Yorkshire Cancer Research core funding. The UBCS
   was supported by the Susan G. Komen Breast Cancer Foundation
   (BCTR0706911 to NJC) and the Avon Foundation (02-2009-080 to NJC). Data
   collection in Utah was made possible by the Utah Population Database
   (UPDB) and the Utah Cancer Registry (UCR). Partial support for all
   datasets within the UPDB was provided by the University of Utah Huntsman
   Cancer Institute (HCI) and the HCI Cancer Center Support grant, P30
   CA42014 from the NCI. The UCR is funded by contract HHSN261201000026C
   from the NCI SEER program with additional support from the Utah State
   Department of Health and the University of Utah. The Australian Breast
   Cancer Family Study was supported by the National Health and Medical
   Research Council of Australia, the New South Wales Cancer Council, the
   Victorian Health Promotion Foundation (Australia), and the National
   Cancer Institute, National Institutes of Health under RFA-CA-06-503 and
   through cooperative agreements with members of the Breast Cancer Family
   Registry (CFR) and principal investigators. The University of Melbourne
   (U01 CA69638) contributed data to this study. The content of this
   manuscript does not necessarily reflect the views or the policies of the
   National Cancer Institute or any of the collaborating centres in the
   CFR, nor does mention of trade names, commercial products or
   organisations imply endorsement by the US government or the CFR. JLH is
   a National Health and Medical Research Council Australia Fellow. MCS is
   a National Health and Medical Research Council Senior Research Fellow.
   JLH and MCS are both group leaders of the Victoria Breast Cancer
   Research Consortium. The CNIO-BCS work was partly funded by the Red
   Tematica de Investigacion Cooperativa en Cancer, the Asociacion Espanola
   Contra Cancer and grants from the Fondo de Investigacion Santiario
   (PI081583 to RLM and PI081120 to JB). SEARCH is funded by Cancer
   Research UK (C490/A10124) and the Cambridge NIHR Biomedical Research
   Centre. The PBCS was funded by Intramural Research Funds of the National
   Cancer Institute, Department of Health and Human Services, USA. The USRT
   study was funded by the Intramural Research Program of the Division of
   Cancer Epidemiology and Genetics, National Cancer Institute, National
   Institutes of Health.
NR 51
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U2 7
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
J9 J MED GENET
JI J. Med. Genet.
PD JUL
PY 2011
VL 48
IS 7
BP 477
EP 484
DI 10.1136/jmedgenet-2011-100018
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 781JK
UT WOS:000291926800009
PM 21632523
ER

PT J
AU Parto, JA
   Evans, MK
   Zonderman, AB
AF Parto, Jacklyn A.
   Evans, Michele K.
   Zonderman, Alan B.
TI Symptoms of Posttraumatic Stress Disorder Among Urban Residents
SO JOURNAL OF NERVOUS AND MENTAL DISEASE
LA English
DT Article
DE Symptoms of posttraumatic stress disorder; civilians; urban residents
ID NATIONAL COMORBIDITY SURVEY; PRIMARY-CARE; PSYCHOMETRIC PROPERTIES;
   AFRICAN-AMERICANS; TRAUMA EXPOSURE; PTSD CHECKLIST; LOW-INCOME; HEALTH;
   WOMEN; POPULATION
AB Previous studies indicate a high risk of Posttraumatic Stress Disorder (PTSD) among women and low-income, urban-residing African-Americans. This study examined PTSD symptoms among urban-residing, socioeconomically diverse, working-age African-Americans and whites. The participants completed the PTSD Checklist-Civilian Version. Of the 2104 participants, 268 (12.7%) were screened positive for PTSD symptoms. Women (13.8%) were more likely than men (11.3%), white participants (13.8%) were more likely than African-Americans (11.9%), and younger participants (16.1%) were more likely than older participants (10.2%) to screen positive for PTSD symptoms. A significant interaction (p = 0.05) revealed that white women living below the 125% poverty level were most likely to report PTSD symptoms. These findings highlight the importance of PTSD screening in low-income urban neighborhoods.
C1 [Parto, Jacklyn A.; Zonderman, Alan B.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA.
   [Evans, Michele K.] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
RP Parto, JA (reprint author), Suite 100,Room 04B330,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM partoja@mail.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institutes of Health, National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
   of the National Institutes of Health, National Institute on Aging.
NR 28
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U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3018
J9 J NERV MENT DIS
JI J. Nerv. Ment. Dis.
PD JUL
PY 2011
VL 199
IS 7
BP 436
EP 439
DI 10.1097/NMD.0b013e3182214154
PG 4
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 786EV
UT WOS:000292287000002
PM 21716054
ER

PT J
AU Lonser, RR
   Song, DK
   Klapper, J
   Hagan, M
   Auh, S
   Kerr, PB
   Citrin, DE
   Heiss, JD
   Camphausen, K
   Rosenberg, SA
AF Lonser, Russell R.
   Song, Debbie K.
   Klapper, Jacob
   Hagan, Marygrace
   Auh, Sungyoung
   Kerr, P. Benjamin
   Citrin, Deborah E.
   Heiss, John D.
   Camphausen, Kevin
   Rosenberg, Steven A.
TI Surgical management of melanoma brain metastases in patients treated
   with immunotherapy
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE immunotherapy; melanoma; metastasis; radiation; surgery; oncology
ID GAMMA-KNIFE RADIOSURGERY; SOLID TUMOR-METASTASIS; MALIGNANT-MELANOMA;
   STEREOTACTIC RADIOSURGERY; RADIATION-THERAPY; INTERLEUKIN-2 THERAPY;
   PROGNOSTIC-FACTORS; COMPARATIVE RISK; RESECTION; CANCER
AB Object. Despite the increasing use of immunotherapy in the treatment of metastatic melanoma, the effects of this therapy on the management of patients with associated brain metastases are not completely defined. The authors undertook this study to determine the effectiveness of resection and the effects of immunotherapy on brain metastasis management.
   Methods. The authors analyzed data pertaining to consecutive patients with metastatic melanoma treated with immunotherapy within 3 months of discovery of brain metastases that were surgically resected.
   Results. Forty-one patients (median age 44.4 years, range 19.2-63.1 years) underwent resection of 53 brain metastases (median number of metastases 1, range 1-4). The median metastasis volume was 2.5 cm(3). Fifteen patients underwent whole-brain radiation therapy (WBRT) and 26 patients did not. Duration of survival from brain metastasis diagnosis was not significantly different between patients who received WBRT (mean 24.9 months) and those who did not (mean 23.3 months) (p > 0.05). Local and distant brain recurrence rates were not statistically different between the WBRT (7.1% and 28.6%, respectively) and non-WBRT (7.7% and 41.0%) groups for the duration of follow-up (p > 0.05). An objective systemic response to immunotherapy was associated with increased duration of survival (p < 0.05).
   Conclusions. Resection of melanoma brain metastases in patients treated with immunotherapy provides excellent local control with low morbidity. An objective response to systemic immunotherapy is associated with a prolonged survival in patients who have undergone resection of melanoma brain metastases. Moreover, adjuvant WBRT in melanoma immunotherapy patients with limited metastatic disease to the brain does not appear to provide a significant survival benefit. (DOI: 10.3171/2011.3.JNS091107)
C1 [Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
   [Auh, Sungyoung] NINDS, Off Clin Director, Bethesda, MD 20892 USA.
   [Klapper, Jacob; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
   [Citrin, Deborah E.; Camphausen, Kevin] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 3D20, Bethesda, MD 20892 USA.
EM lonserr@ninds.nih.gov
OI Heiss, John/0000-0002-3890-0165
FU National Institute of Neurologic Disorders and Stroke; National Cancer
   Institute at the NIH
FX The authors report no conflict of interest concerning the materials or
   methods used in this study or the findings specified in this paper. This
   research was supported by the Intramural Research Programs of the
   National Institute of Neurologic Disorders and Stroke and the National
   Cancer Institute at the NIH.
NR 31
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U2 1
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD JUL
PY 2011
VL 115
IS 1
BP 30
EP 36
DI 10.3171/2011.3.JNS091107
PG 7
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 782JO
UT WOS:000292004700009
PM 21476810
ER

PT J
AU Pfeiffer, CM
   Zhang, M
   Lacher, DA
   Molloy, AM
   Tamura, T
   Yetley, EA
   Picciano, MF
   Johnson, CL
AF Pfeiffer, Christine M.
   Zhang, Mindy
   Lacher, David A.
   Molloy, Anne M.
   Tamura, Tsunenobu
   Yetley, Elizabeth A.
   Picciano, Mary-Frances
   Johnson, Clifford L.
TI Comparison of Serum and Red Blood Cell Folate Microbiologic Assays for
   National Population Surveys
SO JOURNAL OF NUTRITION
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; BIO-RAD RADIOASSAY; WHOLE-BLOOD; INTERNATIONAL
   STANDARD; LC-MS/MS; VITAMIN-B-12; PLASMA
AB Three laboratories participated with their laboratory-specific microbiologic growth assays (MA) in the NHANES 2007-2008 to assess whether the distributions of serum (n = 2645) and RBC folate (n = 2613) for the same one-third sample of participants were comparable among laboratories. Laboratory (L) 2 produced the highest and L1 the lowest serum and RBC folate geometric means (nmol/L) in the NHANES sample (serum: L1, 39.5; L2, 59.2; L3, 47.7; and RBC: L1, 1120; L2, 1380; L3, 1380). Each laboratory produced different reference intervals for the central 95% of the population. Pearson correlation coefficients were highest between L3 and L1 (serum, r = 0.95; RBC, r = 0.92) and lowest between L2 and L1 (serum, r = 0.81; RBC, r = 0.65). Notable procedural differences among the laboratories were the Lactobacillus rhamnosus microorganism (L1 and L3: chloramphenicol resistant, L2: wild type) and the calibrator [L1: [6S]5-methyltetrahydrofolate (5-methylTHF), L2: [6R,S] 5-formyltetrahydrofolate ([6R,S] 5-formyITHF), L3: folic acid (FA)]. Compared with 5-methylTHF as calibrator, the folate results were 22-32% higher with FA as calibrator and 8% higher with 5-formyITHF as calibrator, regardless of the matrix (n = 30 serum, n = 28 RBC). The use of different calibrators explained most of the differences in results between L3 and L1 but not between L2 and L1. The use of the wild-type L. rhamnosus by L2 appeared to be the main reason for the differences in results between L2 and the other 2 laboratories. These findings indicate how assay variations influence MA folate results and how those variations can affect population data. To ensure data comparability, better assay harmonization is needed. J. Nutr. 141: 1402-1409, 2011.
C1 [Pfeiffer, Christine M.; Zhang, Mindy] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA.
   [Lacher, David A.; Johnson, Clifford L.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
   [Molloy, Anne M.] Trinity Coll Dublin, Inst Mol Med, Dublin, Ireland.
   [Tamura, Tsunenobu] Univ Alabama, Birmingham, AL 35294 USA.
   [Yetley, Elizabeth A.; Picciano, Mary-Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Pfeiffer, CM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA.
EM CPfeiffer@cdc.gov
OI Molloy, Anne/0000-0002-1688-9049
FU Office of Dietary Supplements, NIH
FX Supported by the Office of Dietary Supplements, NIH. The findings and
   conclusions in this report are those of the authors and do not
   necessarily represent the official views or positions of the CDC/Agency
   for Toxic Substances and Disease Registry, the NIH, or the Department of
   Health and Human Services.
NR 23
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U2 0
PU AMER SOC NUTRITIONAL SCIENCE
PI BETHESDA
PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD JUL
PY 2011
VL 141
IS 7
BP 1402
EP 1409
DI 10.3945/jn.111.141515
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 783DL
UT WOS:000292061600028
PM 21613453
ER

PT J
AU Kenney, S
   Vistica, DT
   Stockwin, LH
   Burkett, S
   Hollingshead, MG
   Borgel, SD
   Butcher, DO
   Schrump, DS
   Shoemaker, RH
AF Kenney, Susan
   Vistica, David T.
   Stockwin, Luke H.
   Burkett, Sandra
   Hollingshead, Melinda G.
   Borgel, Suzanne D.
   Butcher, Donna O.
   Schrump, David S.
   Shoemaker, Robert H.
TI ASPS-1, A Novel Cell Line Manifesting Key Features of Alveolar Soft Part
   Sarcoma
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Article
DE sarcoma; ASPS; alveolar soft part sarcoma cell line (ASPS-1)
ID HYPOXIA-INDUCIBLE FACTOR-1; BINDING-PROTEIN MIBP; PROPROTEIN
   CONVERTASES; MEDIATED INHIBITION; CANCER-THERAPY; GENE; ANGIOGENESIS;
   TOPOTECAN; TRANSCRIPTION; CAMPTOTHECIN
AB In vitro growth of alveolar soft part sarcoma (ASPS) and establishment of an ASPS cell line, ASPS-1, are described in this study. Using a recently developed xenograft model of ASPS derived from a lymph node metastasis, organoid nests consisting of 15 to 25 ASPS cells were isolated from ASPS xenograft tumors by capture on 70 mm filters and plated in vitro. After attachment to the substratum, these nests deposited small aggregates of ASPS cells. These cells grew slowly and were expanded over a period of 3 years and have maintained characteristics consistent with those of both the original ASPS tumor from the patient and the xenograft tumor including (1) presence of the alveolar soft part locus-transcription factor E3 type 1 fusion transcript and nuclear expression of the alveolar soft part locus-transcription factor E3 type 1 fusion protein; (2) maintenance of the t(X;17)(p11;q25) translocation characteristic of ASPS; and (3) expression of upregulated ASPS transcripts involved in angiogenesis (ANGPTL2, HIF-1-alpha, MDK, c-MET, VEGF, and TIMP-2), cell proliferation (PRL, PCSK1), metastasis (ADAM9), as well as the transcription factor BHLHB3 and the muscle-specific transcripts TRIM63 and ITG beta 1BP3. This ASPS cell line forms colonies in soft agar and retains the ability to produce highly vascularized ASPS tumors in NOD.SCID/NCr mice. Immunohistochemistry of selected ASPS markers on these tumors indicated similarity to those of the original patient tumor as well as to the xenografted ASPS tumor. We anticipate that this ASPS cell line will accelerate investigations into the biology of ASPS including identification of new therapeutic approaches for treatment of this slow growing soft tissue sarcoma.
C1 [Vistica, David T.] NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA.
   [Hollingshead, Melinda G.] NCI, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21702 USA.
   [Butcher, Donna O.] NCI, Pathol Histotechnol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Burkett, Sandra] NCI, Comparat Mol Cytogenet Core Facil, Ctr Canc Res, Frederick, MD 21702 USA.
   [Schrump, David S.] NCI, Surg Branch, Thorac Oncol Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Vistica, DT (reprint author), NCI, Screening Technol Branch, Dev Therapeut Program, Bldg 322,Room 104, Frederick, MD 21702 USA.
EM visticad@mail.nih.gov
FU National Cancer Institute, the National Institutes of Health
   [N01-CO-12400]; National Cancer Institute; The Alliance Against Alveolar
   Soft Part Sarcoma (TAAASPS); Association for Assessment and
   Accreditation of Laboratory Animal Care International (AALAC)
FX This project has been funded in whole or in part with federal funds from
   the National Cancer Institute, the National Institutes of Health under
   contract N01-CO-12400, the Developmental Therapeutics Program in the
   Division of Cancer Treatment and Diagnosis of the National Cancer
   Institute, and The Alliance Against Alveolar Soft Part Sarcoma
   (TAAASPS). The content of this publication does not necessarily reflect
   the views or policies of the Department of Health and Human Services,
   nor does the mention of trade names, commercial products, or
   organizations imply endorsement by the US Government. National Cancer
   Institute (NCI)-Frederick is accredited by Association for Assessment
   and Accreditation of Laboratory Animal Care International (AALAC).
NR 33
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U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1077-4114
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD JUL
PY 2011
VL 33
IS 5
BP 360
EP 368
DI 10.1097/MPH.0b013e3182002f9f
PG 9
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 781IS
UT WOS:000291924700020
PM 21552147
ER

PT J
AU Prevoo, B
   Miller, DS
   van de Water, FM
   Wever, KE
   Russel, FGM
   Flik, G
   Masereeuw, R
AF Prevoo, Brigitte
   Miller, David S.
   van de Water, Femke M.
   Wever, Kimberley E.
   Russel, Frans G. M.
   Flik, Gert
   Masereeuw, Rosalinde
TI Rapid, Nongenomic Stimulation of Multidrug Resistance Protein 2 (Mrp2)
   Activity by Glucocorticoids in Renal Proximal Tubule
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID PREGNANE-X-RECEPTOR; CONSTITUTIVE-ANDROSTANE RECEPTOR; ORGANIC ANION
   SECRETION; SHORT-TERM; CONFOCAL MICROSCOPY; NUCLEAR RECEPTORS; DRUG
   EFFLUX; IN-VITRO; TRANSPORT; KINASE
AB In renal proximal tubule, multidrug resistance protein 2 (Mrp2) actively transports many organic anions into urine, including drugs and metabolic wastes. Upon exposure to nephrotoxicants or during endotoxemia, both Mrp2 activity and expression are up-regulated. This may result from induced de novo synthesis of Mrp2 or post-transcriptional events involving specific signaling pathways. Here, we investigated glucocorticoid signaling to Mrp2 in killifish renal proximal tubules, a model system in which transport activity can be measured using a fluorescent substrate and confocal imaging. Exposure of tubules to dexamethasone rapidly increased Mrp2-mediated fluorescein methotrexate transport. Other glucocorticoid receptor (GR) ligands, cortisol and triamcinolone acetonide, also stimulated Mrp2-mediated transport. The GR antagonist, mifepristone 17 beta-hydroxy-11 beta-[4-dimethylamino phenyl]-17 alpha-[1-propynyl]estra-4,9-dien-3-one (RU486), abolished stimulation by all three ligands, whereas the mineralocorticoid receptor antagonist, spironolactone, was ineffective. Consistent with action through a nongenomic mechanism, dexamethasone stimulation of Mrp2-mediated transport was insensitive to cycloheximide and actinomycin D, and immunohistochemistry revealed no alterations in Mrp2 expression at the luminal membrane. (9S-(9 alpha,10 alpha,12 alpha))-2,3,9,10,11,12-hexahydro-10-hydroxy-10-(methoxycarbonyl)-9-methyl-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocin-1-one (K252a), an inhibitor of the tyrosine receptor kinase subfamily, reduced the dexamethasone effect, as did the specific hepatocyte growth factor receptor (c-Met) tyrosine kinase inhibitor, (2R)-1-[[5-[(Z)-[5-[[(2,6-dichlorophenyl)methyl]sulfonyl]-1,2-dihydro-2-oxo-3H-indol-3-ylidene]methyl]-2,4-dimethyl-1H-pyrrol-3-yl]carbonyl]-2-(1-pyrrolidinylmethyl)pyrrolidine (PHA-665752). Hepatocyte growth factor (HGF), an endogenous ligand for c-Met, stimulated Mrp2-mediated transport. This effect was reversed by PHA-665752 but not by RU486. Inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK 1/2) also abolished the effects of dexamethasone and HGF. Our results disclose a novel mechanism by which glucocorticoids acting through GR, c-Met, and MEK1/2 cause rapid, nongenomic stimulation of Mrp2-mediated transport in renal proximal tubules. This up-regulation may be nephroprotective, enhancing efflux of metabolic wastes and toxicants during cell and tissue stress.
C1 [Prevoo, Brigitte; van de Water, Femke M.; Wever, Kimberley E.; Russel, Frans G. M.; Masereeuw, Rosalinde] Radboud Univ Nijmegen, Med Ctr, Dept Pharmacol & Toxicol, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands.
   [Prevoo, Brigitte; Flik, Gert] Radboud Univ Nijmegen, Fac Sci, Inst Water & Wetland Res, Dept Anim Physiol, NL-6500 HB Nijmegen, Netherlands.
   [Miller, David S.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
   [Prevoo, Brigitte; van de Water, Femke M.; Masereeuw, Rosalinde] Mt Desert Isl Biol Lab, Salsbury Cove, ME USA.
RP Masereeuw, R (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Pharmacol & Toxicol 149, Nijmegen Ctr Mol Life Sci, POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM r.masereeuw@pharmtox.umcn.nl
RI Russel, Frans/B-3184-2014; Flik, Gert/C-8229-2011; Masereeuw,
   Roos/N-3582-2014; Wever, Kimberley/D-9705-2016; 
OI Russel, Frans/0000-0002-7959-2314; Flik, Gert/0000-0001-9285-7957;
   Wever, Kimberley/0000-0003-3635-3660; Masereeuw,
   Rosalinde/0000-0002-1560-1074
FU Blum Halsey Fund for the visiting scientific team of Mount Desert Island
   Biological Laboratory; National Institute of the Environmental Health
   Sciences/National Institute of Health; Radboud University, Nijmegen, The
   Netherlands [B090148]
FX This work was supported by the Blum Halsey Fund for the visiting
   scientific team of Mount Desert Island Biological Laboratory (to R.M.);
   the Intramural Research Program National Institute of the Environmental
   Health Sciences/National Institute of Health (to D.M.); and the Radboud
   University Study Fund, Nijmegen, The Netherlands [Grant B090148] (to
   B.P.).
NR 50
TC 7
Z9 7
U1 0
U2 3
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 JUL
PY 2011
VL 338
IS 1
BP 362
EP 371
DI 10.1124/jpet.111.179689
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 781IW
UT WOS:000291925300040
PM 21515814
ER

PT J
AU Colon-Saez, JO
   Yakel, JL
AF Colon-Saez, Jose O.
   Yakel, Jerrel L.
TI The alpha 7 nicotinic acetylcholine receptor function in hippocampal
   neurons is regulated by the lipid composition of the plasma membrane
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Article
ID M4 TRANSMEMBRANE DOMAIN; ION-CHANNEL FUNCTION; TRYPTOPHAN SUBSTITUTIONS;
   ALLOSTERIC MODULATION; RAPID DESENSITIZATION; CHOLESTEROL CONTENT;
   ALZHEIMERS-DISEASE; BINDING-AFFINITY; MOUSE MODEL; MUTATIONS
AB The alpha 7 nicotinic acetylcholine receptors (nAChRs) play an important role in cellular events such as neurotransmitter release, second messenger cascades, cell survival and apoptosis. In addition, they are a therapeutic target for the treatment of neurological disorders such as Alzheimer's disease and schizophrenia, and drugs that potentiate alpha 7 nAChRs through the regulation of desensitization are currently being developed. Recently, these channels were found to be localized into lipid rafts. Here we show that the disruption of lipid rafts in rat primary hippocampal neurons, through cholesterol-scavenging drugs (methyl-beta-cyclodextrin) and the enzymatic breakdown of sphingomyelin (sphingomyelinase), results in significant changes in the desensitization kinetics of native and expressed alpha 7 nAChRs. These effects can be prevented by cotreatment with cholesterol and sphingomyelin, and can be mimicked by treatment with cholesterol and sphingomyelin synthesis inhibitors (mevastatin and myriocin, respectively), suggesting that the effects on desensitization kinetics are indeed due to changes in the levels of cholesterol and sphingomyelin in the plasma membrane. These data provide new insights into the mechanism of desensitization of alpha 7 nAChRs by providing evidence that the lipid composition of the plasma membrane can modulate the activity of the alpha 7 nAChRs.
C1 [Colon-Saez, Jose O.; Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA.
EM yakel@niehs.nih.gov
FU NIEHS/NIH
FX This work was supported by the Intramural Research Program of the
   NIEHS/NIH. The authors also thank Dr Sindura Ganapathi and Dr Christian
   Erxleben for their helpful insights and suggestions in the manuscript
   preparation process; Pattie Lamb for preparing all the constructs used
   in this study; Dr Steve Shears for allowing use of the microplate
   reader; and Dr Angelika Zaremba for her technical help.
NR 43
TC 19
Z9 20
U1 2
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD JUL 1
PY 2011
VL 589
IS 13
BP 3163
EP 3174
DI 10.1113/jphysiol.2011.209494
PG 12
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 785DE
UT WOS:000292206800013
PM 21540349
ER

PT J
AU Wang, J
   Iannotti, RJ
   Luk, JW
AF Wang, Jing
   Iannotti, Ronald J.
   Luk, Jeremy W.
TI Peer Victimization and Academic Adjustment Among Early Adolescents:
   Moderation by Gender and Mediation by Perceived Classmate Support
SO JOURNAL OF SCHOOL HEALTH
LA English
DT Article
DE peer victimization; academic adjustment; peer support; gender
   differences
ID PSYCHOSOCIAL ADJUSTMENT; CLASSROOM ENGAGEMENT; SCHOOL ADJUSTMENT;
   ELEMENTARY-SCHOOL; MIDDLE SCHOOL; ACHIEVEMENT; PERFORMANCE; REJECTION;
   YOUTH; EXPERIENCES
AB BACKGROUND: This study examined the moderating role of gender and the mediating role of perceived peer support in the association between peer victimization and academic adjustment.
   METHODS: Data were obtained from adolescents in grades 7 and 8 in the US 2005/2006 Health Behavior in School-aged Children study (N = 3436; mean age = 13.6 years).
   RESULTS: The magnitude of correlation between victimization and academic adjustment was -.155 for males and -.337 for females. After controlling for the socio-demographic variables, victimization had a significantly stronger influence on academic adjustment in females than in males. For both genders, perceived classmate support was negatively associated with peer victimization and positively associated with academic adjustment. Classmate support mediated the association between victimization and academic adjustment in males and was a partial mediator for females.
   CONCLUSION: These results provide support for efforts reducing victimization of female adolescents and fostering peer support in the school setting.
C1 [Wang, Jing; Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD 20892 USA.
   [Luk, Jeremy W.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA.
RP Wang, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, 6100 Bldg,Room 7B13,MSC 7510, Bethesda, MD 20892 USA.
EM wangji2@mail.nih.gov; ri25j@nih.gov; jwluk@uw.edu
NR 28
TC 9
Z9 9
U1 1
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-4391
J9 J SCHOOL HEALTH
JI J. Sch. Health
PD JUL
PY 2011
VL 81
IS 7
BP 386
EP 392
DI 10.1111/j.1746-1561.2011.00606.x
PG 7
WC Education & Educational Research; Education, Scientific Disciplines;
   Health Care Sciences & Services; Public, Environmental & Occupational
   Health
SC Education & Educational Research; Health Care Sciences & Services;
   Public, Environmental & Occupational Health
GA 782WM
UT WOS:000292043400003
PM 21668878
ER

PT J
AU Graber, T
   Anderson, S
   Brewer, H
   Chen, YS
   Cho, HS
   Dashdorj, N
   Henning, RW
   Kosheleva, I
   Macha, G
   Meron, M
   Pahl, R
   Ren, Z
   Ruan, S
   Schotte, F
   Rajer, VS
   Viccaro, PJ
   Westferro, F
   Anfinrud, P
   Moffat, K
AF Graber, T.
   Anderson, S.
   Brewer, H.
   Chen, Y. -S.
   Cho, H. S.
   Dashdorj, N.
   Henning, R. W.
   Kosheleva, I.
   Macha, G.
   Meron, M.
   Pahl, R.
   Ren, Z.
   Ruan, S.
   Schotte, F.
   Rajer, V. S.
   Viccaro, P. J.
   Westferro, F.
   Anfinrud, P.
   Moffat, K.
TI BioCARS: a synchrotron resource for time-resolved X-ray science
SO JOURNAL OF SYNCHROTRON RADIATION
LA English
DT Article
DE synchrotron beamline; Laue crystallography; time-resolved
   crystallography; X-ray optics
ID PHOTOACTIVE YELLOW PROTEIN; LAUE CRYSTALLOGRAPHY; STRUCTURAL DYNAMICS;
   DESIGN PARAMETERS; LIGAND MIGRATION; MOLECULAR MOVIE; REAL-TIME;
   NANOSECOND; MYOGLOBIN; DIFFRACTION
AB BioCARS, a NIH-supported national user facility for macromolecular time-resolved X-ray crystallography at the Advanced Photon Source (APS), has recently completed commissioning of an upgraded undulator-based beamline optimized for single-shot laser-pump X-ray-probe measurements with time resolution as short as 100 ps. The source consists of two in-line undulators with periods of 23 and 27 mm that together provide high-flux pink-beam capability at 12 keV as well as first-harmonic coverage from 6.8 to 19 keV. A high-heat-load chopper reduces the average power load on downstream components, thereby preserving the surface figure of a Kirkpatrick-Baez mirror system capable of focusing the X-ray beam to a spot size of 90 mu m horizontal by 20 mu m vertical. A high-speed chopper isolates single X-ray pulses at 1 kHz in both hybrid and 24-bunch modes of the APS storage ring. In hybrid mode each isolated X-ray pulse delivers up to similar to 4 x 10(10) photons to the sample, thereby achieving a time-averaged flux approaching that of fourth-generation X-FEL sources. A new high-power picosecond laser system delivers pulses tunable over the wavelength range 450-2000 nm. These pulses are synchronized to the storage-ring RF clock with long-term stability better than 10 ps RMS. Monochromatic experimental capability with Biosafety Level 3 certification has been retained.
C1 [Graber, T.; Anderson, S.; Brewer, H.; Chen, Y. -S.; Henning, R. W.; Kosheleva, I.; Macha, G.; Meron, M.; Pahl, R.; Ren, Z.; Ruan, S.; Rajer, V. S.; Viccaro, P. J.; Westferro, F.; Moffat, K.] Univ Chicago, Ctr Adv Radiat Sources, Chicago, IL 60637 USA.
   [Cho, H. S.; Dashdorj, N.; Schotte, F.; Anfinrud, P.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Graber, T (reprint author), Univ Chicago, Ctr Adv Radiat Sources, Chicago, IL 60637 USA.
EM graber@cars.uchicago.edu
FU US Department of Energy, Basic Energy Sciences, Office of Science
   [DE-AC02-06CH11357]; National Institutes of Health, National Center for
   Research Resources [RR007707]; NIH/NIDDK
FX Use of the Advanced Photon Source was supported by the US Department of
   Energy, Basic Energy Sciences, Office of Science, under Contract No.
   DE-AC02-06CH11357. Use of the BioCARS sector 14 was supported by the
   National Institutes of Health, National Center for Research Resources,
   under grant number RR007707. The time-resolved set-up at sector 14 was
   funded in part by NIH/NIDDK. We thank all APS personnel who supported
   this upgrade project, specifically Efim Gluskin, Roger Dejus and
   Elizabeth Moog for collaborating on the design of the new undulator
   system and partially funding its procurement. We also thank Dana
   Capatina and Yifei Jaski for their FEA analysis of the HHL components,
   and Troy Lutes, our APS interface for the project. We also wish to
   acknowledge former BioCARS staff Michael Bolbat and Jay VonOsinski for
   their expert assistance during the 14-ID upgrade.
NR 36
TC 38
Z9 38
U1 1
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0909-0495
J9 J SYNCHROTRON RADIAT
JI J. Synchrot. Radiat.
PD JUL
PY 2011
VL 18
BP 658
EP 670
DI 10.1107/S0909049511009423
PN 4
PG 13
WC Instruments & Instrumentation; Optics; Physics, Applied
SC Instruments & Instrumentation; Optics; Physics
GA 783SY
UT WOS:000292105500017
PM 21685684
ER

PT J
AU David, CN
   Greenstein, D
   Clasen, L
   Gochman, P
   Miller, R
   Tossell, JW
   Mattai, AA
   Gogtay, N
   Rapoport, JL
AF David, Christopher N.
   Greenstein, Deanna
   Clasen, Liv
   Gochman, Pete
   Miller, Rachel
   Tossell, Julia W.
   Mattai, Anand A.
   Gogtay, Nitin
   Rapoport, Judith L.
TI Childhood Onset Schizophrenia: High Rate of Visual Hallucinations
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE childhood onset schizophrenia (COS); visual hallucinations; IQ; severity
ID PHENOMENOLOGY; DISORDERS; SYMPTOMS; CHILDREN
AB Objective: To document high rates and clinical correlates of nonauditory hallucinations in childhood onset schizophrenia (COS). Method: Within a sample of 117 pediatric patients (mean age 13.6 years), diagnosed with COS, the presence of auditory, visual, somatic/tactile, and olfactory hallucinations was examined using the Scale for the Assessment of Positive Symptoms (SAPS). We also compared hallucination modality membership (presence/absence) groups on gender, socioeconomic status, ethnicity, age of onset (of psychosis), Full Scale IQ, Verbal IQ, and clinical severity (Children's Global Assessment Scale [CGAS) and Scale for the Assessment of Negative Symptoms [SANS]). Results: A total of 111 COS patients (94.9%) had auditory and 94 patients (80.3%) had visual hallucinations. Somatic/tactile (60.7%) and olfactory (29.9%) hallucinations occurred almost exclusively in patients who also had visual hallucinations. Children who had visual hallucinations had lower IQ, earlier age of onset, and more severe illness relative to children who did not have visual hallucinations. Conclusions: In this study, we observed that patients with COS have high rates of hallucinations across all modalities. An increased rate of visual hallucinations is associated with greater clinical impairment and greater compromise in overall brain functioning. Somatic and olfactory hallucinations reflect an additive rather than alternative symptom pattern. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(7):681-686.
C1 [David, Christopher N.] Natl Inst Mental Hlth, Child Psychiat Blanch, Bethesda, MD 20892 USA.
RP David, CN (reprint author), Natl Inst Mental Hlth, Child Psychiat Blanch, Bldg 10,Room 3N202, Bethesda, MD 20892 USA.
EM davidcn@mail.nih.gov
RI Gogtay, Nitin/A-3035-2008
FU National Institute of Mental Health, Bethesda, MD
FX This research was funded through the Intramural Program at the National
   Institute of Mental Health, Bethesda, MD.
NR 24
TC 28
Z9 28
U1 3
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD JUL
PY 2011
VL 50
IS 7
BP 681
EP 686
DI 10.1016/j.jaac.2011.03.020
PG 6
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 786CC
UT WOS:000292279100008
PM 21703495
ER

PT J
AU Mattai, AA
   Weisinger, B
   Greenstein, D
   Stidd, R
   Clasen, L
   Miller, R
   Tossell, JW
   Rapoport, JL
   Gogtay, N
AF Mattai, Anand A.
   Weisinger, Brian
   Greenstein, Deanna
   Stidd, Reva
   Clasen, Liv
   Miller, Rachel
   Tossell, Julia W.
   Rapoport, Judith L.
   Gogtay, Nitin
TI Normalization of Cortical Gray Matter Deficits in Nonpsychotic Siblings
   of Patients With Childhood-Onset Schizophrenia
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE childhood-onset schizophrenia; cortical thickness; endophenotype; gray
   matter
ID AUTOMATED 3-D EXTRACTION; VOXEL-BASED MORPHOMETRY; HEALTHY SIBLINGS;
   PERSONALITY-DISORDERS; SYNAPTIC PLASTICITY; BRAIN ABNORMALITIES;
   LONGITUDINAL MRI; CEREBRAL-CORTEX; WHITE-MATTER; RELATIVES
AB Objective: Cortical gray matter (GM) abnormalities in patients with childhood-onset schizophrenia (COS) progress during adolescence ultimately localizing to prefrontal and temporal cortices by early adult age. A previous study of 52 nonpsychotic siblings of COS probands had significant prefrontal and temporal GM deficits that appeared to "normalize" by age 17 years. Here we present a replication with nonoverlapping groups of healthy full siblings and healthy controls. Method: Using an automated measure and prospectively acquired anatomical brain magnetic resonance images, we mapped cortical GM thickness in nonpsychotic full siblings (n = 43, 68 scans; ages 5 through 26 years) of patients with COS, contrasting them with age-, gender-, and scan interval matched healthy controls (n = 86, 1.36 scans). The false-discovery rate procedure was used to control for type I errors due to multiple comparisons. Results: As in our previous study, young nonpsychotic siblings (<17 years) showed significant GM deficits in bilateral prefrontal and left temporal cortices and, in addition, smaller deficits in the parietal and right inferior temporal cortices. These deficits in nonpsychotic siblings normalized with age with minimal abnormalities remaining by age 17. Conclusions: Our results support previous findings showing nonpsychotic siblings of COS probands to have early GM deficits that ameliorate with time. At early ages, prefrontal and/or temporal loss may serve as a familial/trait marker for COS. Late adolescence appears to be a critical period for greatest localization of deficits in probands or normalization in nonpsychotic siblings. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(7):697-704.
C1 [Mattai, Anand A.; Weisinger, Brian; Greenstein, Deanna; Stidd, Reva; Clasen, Liv; Miller, Rachel; Tossell, Julia W.; Rapoport, Judith L.; Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
RP Mattai, AA (reprint author), NIH, Child Psychiat Branch, Bldg 10,Room 3N202,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mattaia@mail.nih.gov
RI Gogtay, Nitin/A-3035-2008
FU Intramural NIH HHS [ZIA MH002581-21]
NR 52
TC 29
Z9 29
U1 3
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD JUL
PY 2011
VL 50
IS 7
BP 697
EP 704
DI 10.1016/j.jaac.2011.03.016
PG 8
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 786CC
UT WOS:000292279100010
PM 21703497
ER

PT J
AU Nieman, LK
AF Nieman, Lynnette K.
TI Consequences of systemic absorption of topical glucocorticoids
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Editorial Material
ID CUSHINGS-SYNDROME; CORTICOSTEROIDS; MISUSE
C1 [Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Nieman, LK (reprint author), CRC, Bldg 10,1 East,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM NiemanL@nih.gov
FU Intramural NIH HHS [Z01 HD000638-14]
NR 11
TC 4
Z9 4
U1 0
U2 7
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 JUL
PY 2011
VL 65
IS 1
BP 250
EP 252
DI 10.1016/j.jaad.2010.12.037
PG 3
WC Dermatology
SC Dermatology
GA 785IH
UT WOS:000292222200056
PM 21679844
ER

PT J
AU Pathak, J
   Wang, J
   Kashyap, S
   Basford, M
   Li, RL
   Masys, DR
   Chute, CG
AF Pathak, Jyotishman
   Wang, Janey
   Kashyap, Sudha
   Basford, Melissa
   Li, Rongling
   Masys, Daniel R.
   Chute, Christopher G.
TI Mapping clinical phenotype data elements to standardized metadata
   repositories and controlled terminologies: the eMERGE Network experience
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID POST-COORDINATION; SNOMED CT; FUTURE
AB Background Systematic study of clinical phenotypes is important for a better understanding of the genetic basis of human diseases and more effective gene-based disease management. A key aspect in facilitating such studies requires standardized representation of the phenotype data using common data elements (CDEs) and controlled biomedical vocabularies. In this study, the authors analyzed how a limited subset of phenotypic data is amenable to common definition and standardized collection, as well as how their adoption in large-scale epidemiological and genome-wide studies can significantly facilitate cross-study analysis.
   Methods The authors mapped phenotype data dictionaries from five different eMERGE (Electronic Medical Records and Genomics) Network sites studying multiple diseases such as peripheral arterial disease and type 2 diabetes. For mapping, standardized terminological and metadata repository resources, such as the caDSR (Cancer Data Standards Registry and Repository) and SNOMED CT (Systematized Nomenclature of Medicine), were used. The mapping process comprised both lexical (via searching for relevant pre-coordinated concepts and data elements) and semantic (via post-coordination) techniques. Where feasible, new data elements were curated to enhance the coverage during mapping. A web-based application was also developed to uniformly represent and query the mapped data elements from different eMERGE studies.
   Results Approximately 60% of the target data elements (95 out of 157) could be mapped using simple lexical analysis techniques on pre-coordinated terms and concepts before any additional curation of terminology and metadata resources was initiated by eMERGE investigators. After curation of 54 new caDSR CDEs and nine new NCI thesaurus concepts and using post-coordination, the authors were able to map the remaining 40% of data elements to caDSR and SNOMED CT. A web-based tool was also implemented to assist in semi-automatic mapping of data elements.
   Conclusion This study emphasizes the requirement for standardized representation of clinical research data using existing metadata and terminology resources and provides simple techniques and software for data element mapping using experiences from the eMERGE Network.
C1 [Pathak, Jyotishman; Chute, Christopher G.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
   [Wang, Janey; Kashyap, Sudha; Basford, Melissa; Masys, Daniel R.] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA.
   [Li, Rongling] NHGRI, Bethesda, MD 20892 USA.
RP Pathak, J (reprint author), Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, 200 1st St SW, Rochester, MN 55905 USA.
EM pathak.jyotishman@mayo.edu
FU NHGRI; NIGMS [U01-HG-004610]; Group Health Cooperative [U01-HG-004608];
   Marshfield Clinic [U01-HG-04599]; Mayo Clinic [U01HG004609];
   Northwestern University [U01-HG-04603]; Vanderbilt University, also
   serving as the Administrative Coordinating Center
FX The eMERGE Network was initiated and funded by NHGRI, in conjunction
   with additional funding from NIGMS through the following grants:
   U01-HG-004610 (Group Health Cooperative); U01-HG-004608 (Marshfield
   Clinic); U01-HG-04599 (Mayo Clinic); U01HG004609 (Northwestern
   University); U01-HG-04603 (Vanderbilt University, also serving as the
   Administrative Coordinating Center). JP's work is also funded in part by
   the Mayo Clinic Early Career Development Award.
NR 31
TC 45
Z9 45
U1 3
U2 17
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD JUL
PY 2011
VL 18
IS 4
BP 376
EP 386
DI 10.1136/amiajnl-2010-000061
PG 11
WC Computer Science, Information Systems; Computer Science,
   Interdisciplinary Applications; Information Science & Library Science;
   Medical Informatics
SC Computer Science; Information Science & Library Science; Medical
   Informatics
GA 783DM
UT WOS:000292061700008
PM 21597104
ER

PT J
AU Boyack, KW
   Jordan, P
AF Boyack, Kevin W.
   Jordan, Paul
TI Metrics associated with NIH funding: a high-level view
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID GASTROENTEROLOGY RESEARCH; IMPACT; EVOLUTION; SCIENCES; HEALTH
AB Objective To introduce the availability of grant-to-article linkage data associated with National Institutes of Health (NIH) grants and to perform a high-level analysis of the publication outputs and impacts associated with those grants.
   Design Articles were linked to the grants they acknowledge using the grant acknowledgment strings in PubMed using a parsing and matching process as embodied in the NIH Scientific Publication Information Retrieval & Evaluation System system. Additional data from PubMed and citation counts from Scopus were added to the linkage data. The data comprise 2 572 576 records from 1980 to 2009.
   Results The data show that synergies between NIH institutes are increasing over time; 29% of current articles acknowledge grants from multiple institutes. The median time lag to publication for a new grant is 3 years. Each grant contributes to approximately 1.7 articles per year, averaged over all grant types. Articles acknowledging US Public Health Service (PHS, which includes NIH) funding are cited twice as much as US-authored articles acknowledging no funding source. Articles acknowledging both PHS funding and a non-US government funding source receive on average 40% more citations that those acknowledging PHS funding sources alone.
   Conclusion The US PHS is effective at funding research with a higher-than-average impact. The data are amenable to further and much more detailed analysis.
C1 [Boyack, Kevin W.] SciTech Strategies, Albuquerque, NM 87122 USA.
   [Jordan, Paul] NIH, Off Res Informat Syst OD OER ORIS, Res Triangle Pk, NC USA.
RP Boyack, KW (reprint author), SciTech Strategies, 8421 Manuel Cia Pl NE, Albuquerque, NM 87122 USA.
EM kboyack@mapofscience.com
OI Boyack, Kevin/0000-0001-7814-8951
FU NSF [SBE-0738111]; SPIRES project
FX This work was partially supported by NSF award SBE-0738111.; We
   acknowledge B van Houten, former chief of the Program Analysis Branch at
   NIEHS, for his work and support at the genesis of the SPIRES project,
   and Y Gao and FO Finch, for their work on the SPIRES parsing and
   matching engines.
NR 19
TC 21
Z9 21
U1 1
U2 17
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD JUL
PY 2011
VL 18
IS 4
BP 423
EP 431
DI 10.1136/amiajnl-2011-000213
PG 9
WC Computer Science, Information Systems; Computer Science,
   Interdisciplinary Applications; Health Care Sciences & Services;
   Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
   Library Science; Medical Informatics
GA 783DM
UT WOS:000292061700013
PM 21527408
ER

PT J
AU Nelson, SJ
   Zeng, K
   Kilbourne, J
   Powell, T
   Moore, R
AF Nelson, Stuart J.
   Zeng, Kelly
   Kilbourne, John
   Powell, Tammy
   Moore, Robin
TI Normalized names for clinical drugs: RxNorm at 6 years
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID STANDARDS; SYSTEMS
AB Objective In the 6 years since the National Library of Medicine began monthly releases of RxNorm, RxNorm has become a central resource for communicating about clinical drugs and supporting interoperation between drug vocabularies.
   Materials and methods Built on the idea of a normalized name for a medication at a given level of abstraction, RxNorm provides a set of names and relationships based on 11 different external source vocabularies. The standard model enables decision support to take place for a variety of uses at the appropriate level of abstraction. With the incorporation of National Drug File Reference Terminology (NDF-RT) from the Veterans Administration, even more sophisticated decision support has become possible.
   Discussion While related products such as RxTerms, RxNav, MyMedicationList, and MyRxPad have been recognized as helpful for various uses, tasks such as identifying exactly what is and is not on the market remain a challenge.
C1 [Nelson, Stuart J.; Zeng, Kelly; Kilbourne, John; Powell, Tammy; Moore, Robin] NIH, US Natl Lib Med, Bethesda, MD 20892 USA.
RP Nelson, SJ (reprint author), NIH, US Natl Lib Med, Bldg 1DEM,Room 202G,6701 Democracy Blvd, Bethesda, MD 20892 USA.
EM nelson@nlm.nih.gov
NR 24
TC 61
Z9 61
U1 2
U2 11
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD JUL
PY 2011
VL 18
IS 4
BP 441
EP 448
DI 10.1136/amiajnl-2011-000116
PG 8
WC Computer Science, Information Systems; Computer Science,
   Interdisciplinary Applications; Information Science & Library Science;
   Medical Informatics
SC Computer Science; Information Science & Library Science; Medical
   Informatics
GA 783DM
UT WOS:000292061700015
PM 21515544
ER

PT J
AU Ackerman, M
   Locatis, C
AF Ackerman, Michael
   Locatis, Craig
TI Advanced networks and computing in healthcare
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Review
ID EMERGENCY MEDICAL-CARE; X-LINKED ADRENOLEUKODYSTROPHY; VOLUME
   VISUALIZATION; LEARNING ENVIRONMENTS; SURGICAL SIMULATION; VIDEO
   TECHNOLOGIES; VIRTUAL-REALITY; VISIBLE HUMAN; INFORMATION; TELEMEDICINE
AB As computing and network capabilities continue to rise, it becomes increasingly important to understand the varied applications for using them to provide healthcare. The objective of this review is to identify key characteristics and attributes of healthcare applications involving the use of advanced computing and communication technologies, drawing upon 45 research and development projects in telemedicine and other aspects of healthcare funded by the National Library of Medicine over the past 12 years. Only projects publishing in the professional literature were included in the review. Four projects did not publish beyond their final reports. In addition, the authors drew on their first-hand experience as project officers, reviewers and monitors of the work. Major themes in the corpus of work were identified, characterizing key attributes of advanced computing and network applications in healthcare. Advanced computing and network applications are relevant to a range of healthcare settings and specialties, but they are most appropriate for solving a narrower range of problems in each. Healthcare projects undertaken primarily to explore potential have also demonstrated effectiveness and depend on the quality of network service as much as bandwidth. Many applications are enabling, making it possible to provide service or conduct research that previously was not possible or to achieve outcomes in addition to those for which projects were undertaken. Most notable are advances in imaging and visualization, collaboration and sense of presence, and mobility in communication and information-resource use.
C1 [Ackerman, Michael; Locatis, Craig] Natl Lib Med, Off High Performance Comp & Commun, NIH, Bethesda, MD 20894 USA.
RP Locatis, C (reprint author), Natl Lib Med, Off High Performance Comp & Commun, NIH, Bldg 38A, Bethesda, MD 20894 USA.
EM locatis@nlm.nih.gov
FU NLM office
FX The research projects forming the basis of this review were funded by
   the NLM office in which the authors work, and the manuscript itself was
   generated as part of the National Library of Medicine/National
   Institutes of Health internal research program as part of their
   employment.
NR 106
TC 5
Z9 5
U1 3
U2 14
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD JUL
PY 2011
VL 18
IS 4
BP 523
EP 528
DI 10.1136/amiajnl-2010-000054
PG 6
WC Computer Science, Information Systems; Computer Science,
   Interdisciplinary Applications; Health Care Sciences & Services;
   Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
   Library Science; Medical Informatics
GA 783DM
UT WOS:000292061700027
PM 21486877
ER

PT J
AU Johnson, AD
AF Johnson, A. D.
TI Discovery of novel platelet aggregation and platelet function loci
   through genome-wide studies
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Meeting Abstract
C1 [Johnson, A. D.] NHLBI, Ctr Populat Studies, Framingham Heart Study, Bethesda, MD USA.
RI Johnson, Andrew/G-6520-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
EI 1538-7836
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD JUL
PY 2011
VL 9
SU 2
SI SI
MA SA-WE-005
BP 501
EP 501
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA V33AX
UT WOS:000208992801389
ER

PT J
AU DiMichele, DM
AF DiMichele, D. M.
TI Immune tolerance induction in hemophilia: evidence and the way forward
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Meeting Abstract
C1 [DiMichele, D. M.] NHLBI, NIH, DBDR, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
EI 1538-7836
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD JUL
PY 2011
VL 9
SU 2
SI SI
MA SA-TH-001
BP 714
EP 714
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA V33AX
UT WOS:000208992803010
ER

PT J
AU Mingozzi, F
   Chen, Y
   Zhou, S
   Murphy, SL
   Metzger, M
   Donahue, RE
   Wright, FJ
   Dunbar, CJ
   High, KA
AF Mingozzi, F.
   Chen, Y.
   Zhou, S.
   Murphy, S. L.
   Metzger, M.
   Donahue, R. E.
   Wright, F. J.
   Dunbar, C. J.
   High, K. A.
TI Inhibitor eradication and vector readministration in a non-human primate
   model of AAV-mediated liver gene transfer for hemophilia B
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Meeting Abstract
C1 [Mingozzi, F.; Chen, Y.; Zhou, S.; Murphy, S. L.; Wright, F. J.; High, K. A.] Childrens Hosp Philadelphia, Philadelphia, PA USA.
   [Metzger, M.; Donahue, R. E.; Dunbar, C. J.] NHLBI, Hematol Branch, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
EI 1538-7836
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD JUL
PY 2011
VL 9
SU 2
SI SI
MA O-TH-125
BP 762
EP 762
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA V33AX
UT WOS:000208992803156
ER

PT J
AU Mizurini, DM
   Calvo, E
   Francischetti, IM
   Monteiro, RQ
AF Mizurini, D. M.
   Calvo, E.
   Francischetti, I. M.
   Monteiro, R. Q.
TI Molecular mechanisms involved in the antithrombotic activity of
   aegyptin, a novel mosquito-derived collagen-binding protein
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Meeting Abstract
C1 [Mizurini, D. M.; Monteiro, R. Q.] Univ Fed Rio de Janeiro, Inst Bioquim Med, BR-21941 Rio De Janeiro, Brazil.
   [Calvo, E.; Francischetti, I. M.] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
EI 1538-7836
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD JUL
PY 2011
VL 9
SU 2
SI SI
MA P-TH-013
BP 773
EP 773
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA V33AX
UT WOS:000208992803187
ER

PT J
AU Nichols, TC
   Lozier, JN
   Kloos, MT
   Merricks, EP
   Raymer, RA
   Lemoine, N
   Bellinger, D
AF Nichols, T. C.
   Lozier, J. N.
   Kloos, M. T.
   Merricks, E. P.
   Raymer, R. A.
   Lemoine, N.
   Bellinger, D.
TI Severe hemophilia A in a male dog with a C to T transition in exon 12 of
   factor VIII gene leading to a premature stop codon
SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS
LA English
DT Meeting Abstract
C1 [Nichols, T. C.; Kloos, M. T.; Merricks, E. P.; Raymer, R. A.; Bellinger, D.] Univ N Carolina, Francis Owen Blood Res Lab, Chapel Hill, NC USA.
   [Lozier, J. N.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
   [Lemoine, N.] North Carolina Sch Sci & Math, Durham, NC USA.
NR 0
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1538-7933
EI 1538-7836
J9 J THROMB HAEMOST
JI J. Thromb. Haemost.
PD JUL
PY 2011
VL 9
SU 2
SI SI
MA P-TH-236
BP 843
EP 843
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA V33AX
UT WOS:000208992804025
ER

PT J
AU Sun, Y
   Asmal, M
   Lane, S
   Permar, SR
   Schmidt, SD
   Mascola, JR
   Letvin, NL
AF Sun, Yue
   Asmal, Mohammed
   Lane, Sophie
   Permar, Sallie R.
   Schmidt, Stephen D.
   Mascola, John R.
   Letvin, Norman L.
TI Antibody-Dependent Cell-Mediated Cytotoxicity in Simian Immunodeficiency
   Virus-Infected Rhesus Monkeys
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIV-INFECTION; MONOCLONAL-ANTIBODIES; NEUTRALIZING ANTIBODY; DENDRITIC
   CELLS; EFFECTOR-CELLS; FC-RECEPTOR; BREAST-MILK; NK CELLS; TYPE-1;
   RESPONSES
AB With the recent demonstration in the RV144 Thai trial that a vaccine regimen that does not elicit neutralizing antibodies or cytotoxic T lymphocytes may confer protection against human immunodeficiency virus type 1 (HIV-1) infection, attention has turned to nonneutralizing antibodies as a possible mechanism of vaccine protection. In the current study, we evaluated the kinetics of the antibody-dependent cell-mediated cytotoxicity (ADCC) response during acute and chronic SIVmac251 infection of rhesus monkeys. We first adapted a flow cytometry-based ADCC assay, evaluating the use of different target cells as well as different strategies for quantitation of activated natural killer (NK) cells. We found that the use of SIVmac251 Env gp130-coated target cells facilitates analyses of ADCC activity with a higher degree of sensitivity than the use of simian immunodeficiency virus (SIV)-infected target cells; however, the kinetics of the measured responses were the same using these different target cells. By comparing NK cell expression of CD107a with NK cell expression of other cytokines or chemokine molecules, we found that measuring CD107a expression is sufficient for evaluating the anti-SIV function of NK cells. We also showed that ADCC responses can be detected as early as 3 weeks after SIVmac251 infection and that the magnitude of this antibody response is inversely associated with plasma viral RNA levels in animals with moderate to high levels of viral replication. However, we also demonstrated an association between NK cell-mediated ADCC responses and the amount of SIVmac251 gp140 binding antibody that developed after viral infection. This final observation raises the possibility that the antibodies that mediate ADCC are a subset of the antibodies detected in a binding assay and arise within weeks of infection.
C1 [Letvin, Norman L.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis,Dept Med,Ctr Life Sci, Boston, MA 02115 USA.
   [Schmidt, Stephen D.; Mascola, John R.] 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,Ctr Life Sci, 330 Brookline Ave, Boston, MA 02115 USA.
EM nletvin@bidmc.harvard.edu
RI Schmidt, Stephen/B-5398-2012
FU Vaccine Research Center, NIAID, NIH; Harvard Medical School CFAR
   [AI060354]; Harvard Medical School CHAVI [AI06785]; NIH
   [HHSN272201000028C]
FX This work was supported in part by funds from the intramural research
   program of the Vaccine Research Center, NIAID, NIH; Harvard Medical
   School CFAR grant AI060354; CHAVI grant AI06785; and NIH grant
   HHSN272201000028C.
NR 27
TC 44
Z9 44
U1 1
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUL
PY 2011
VL 85
IS 14
BP 6906
EP 6912
DI 10.1128/JVI.00326-11
PG 7
WC Virology
SC Virology
GA 781LA
UT WOS:000291932400008
PM 21593181
ER

PT J
AU Holmes, EC
   Ghedin, E
   Halpin, RA
   Stockwell, TB
   Zhang, XQ
   Fleming, R
   Davey, R
   Benson, CA
   Mehta, S
   Taplitz, R
   Liu, YT
   Brouwer, KC
   Wentworth, DE
   Lin, XD
   Schooley, RT
AF Holmes, Edward C.
   Ghedin, Elodie
   Halpin, Rebecca A.
   Stockwell, Timothy B.
   Zhang, Xing-Quan
   Fleming, Regina
   Davey, Richard
   Benson, Constance A.
   Mehta, Sanjay
   Taplitz, Randy
   Liu, Yu-Tseung
   Brouwer, Kimberly C.
   Wentworth, David E.
   Lin, Xudong
   Schooley, Robert T.
CA INSIGHT FLU002 Study Grp
TI Extensive Geographical Mixing of 2009 Human H1N1 Influenza A Virus in a
   Single University Community
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PANDEMIC INFLUENZA; MIXED INFECTION; EMERGENCE; REVEALS
AB Despite growing interest in the molecular epidemiology of influenza virus, the pattern of viral spread within individual communities remains poorly understood. To determine the phylogeography of influenza virus in a single population, we examined the spatial diffusion of H1N1/09 influenza A virus within the student body of the University of California, San Diego (UCSD), sampling for a 1-month period between October and November 2009. Despite the highly focused nature of our study, an analysis of complete viral genome sequences revealed between 24 and 33 independent introductions of H1N1/09 into the UCSD community, comprising much of the global genetic diversity in this virus. These data were also characterized by a relatively low level of on-campus transmission as well as extensive spatial mixing, such that there was little geographical clustering by either student residence or city ZIP code. Most notably, students experiencing illness on the same day and residing in the same dorm possessed phylogenetically distinct lineages. H1N1/09 influenza A virus is therefore characterized by a remarkable spatial fluidity, which is likely to impede community-based methods for its control, including class cancellations, quarantine, and chemoprophylaxis.
C1 [Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
   [Holmes, Edward C.] NCI, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Ghedin, Elodie; Halpin, Rebecca A.; Stockwell, Timothy B.] J Craig Venter Inst, Rockville, MD 20850 USA.
   [Ghedin, Elodie] Univ Pittsburgh, Sch Med, Ctr Vaccine Res, Dept Computat & Syst Biol, Pittsburgh, PA 15261 USA.
   [Wentworth, David E.; Lin, Xudong] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA.
   [Zhang, Xing-Quan; Benson, Constance A.; Mehta, Sanjay; Taplitz, Randy; Liu, Yu-Tseung; Schooley, Robert T.] Univ Calif San Diego, Dept Med, Div Infect Dis, La Jolla, CA 92093 USA.
   [Fleming, Regina] Univ Calif San Diego, Student Hlth Serv, La Jolla, CA 92093 USA.
   [Davey, Richard] NIAID, Ctr Clin, NIH, Baltimore, MD 21205 USA.
   [Brouwer, Kimberly C.] Univ Calif San Diego, Div Global Publ Hlth, Dept Med, La Jolla, CA 92093 USA.
RP Holmes, EC (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM ech15@psu.edu
OI Wentworth, David/0000-0002-5190-980X; Holmes, Edward/0000-0001-9596-3552
FU NIH [R01 GM080533, K01DA020364, UOI-AI068641]; NIAID/NIH
   [HHSN272200900007]; INSIGHT Network; SAIC-Frederick, Inc.
   [HHSN261200800001E]; NCI-Frederick, Frederick, MD;  [U01 AI074521]
FX We thank all the UCSD students who took part in this study. We also
   thank Tari Gilbert, Jill Kunkel, Linda Meixner, and Edward Seefried of
   the UCSD Antiviral Research Center and Rubina Ghazaraian for sample and
   data collection. E. C. H. is supported in part by NIH grant R01
   GM080533. Support was also provided in part by NIAID/NIH contract
   HHSN272200900007 to E. C. H., E. G., R. A. H., and T. B. S., by
   cooperative agreement U01 AI074521 to R. T. S., by NIH grant K01DA020364
   to K. C. B., and by support from the INSIGHT Network. INSIGHT is funded
   by NIH grant UOI-AI068641, and the FLU002 study is funded by
   SAIC-Frederick, Inc., prime contract HHSN261200800001E, NCI-Frederick,
   Frederick, MD.
NR 27
TC 19
Z9 20
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUL
PY 2011
VL 85
IS 14
BP 6923
EP 6929
DI 10.1128/JVI.00438-11
PG 7
WC Virology
SC Virology
GA 781LA
UT WOS:000291932400010
PM 21593168
ER

PT J
AU Miller, MM
   Iglesias, DM
   Zhang, Z
   Corsini, R
   Chu, LL
   Murawski, I
   Gupta, I
   Somlo, S
   Germino, GG
   Goodyer, PR
AF Miller, Michelle M.
   Iglesias, Diana M.
   Zhang, Zhao
   Corsini, Rachel
   Chu, LeeLee
   Murawski, Inga
   Gupta, Indra
   Somlo, Stefan
   Germino, Gregory G.
   Goodyer, Paul R.
TI T-cell factor/beta-catenin activity is suppressed in two different
   models of autosomal dominant polycystic kidney disease
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE ADPKD; cell signaling; cystic kidney; genetics and development; kidney
   development
ID BETA-CATENIN; TRANSGENIC MICE; MOUSE; GENE; MORPHOGENESIS; INACTIVATION;
   PATHWAYS; CILIA
AB During murine kidney development, canonical WNT signaling is highly active in tubules until about embryonic days E16-E18. At this time, beta-catenin transcriptional activity is progressively restricted to the nephrogenic zone. The cilial protein genes PKD1 and PKD2 are known to be mutated in autosomal dominant polycystic kidney disease (ADPKD), and previous studies proposed that these mutations could lead to a failure to suppress canonical WNT signaling activity. Several in vitro studies have found a link between cilial signaling and beta-catenin regulation, suggesting that aberrant activity might contribute to the cystic phenotype. To study this, we crossed T-cell factor (TCF)/beta-catenin-lacZ reporter mice with mice having Pkd1 or Pkd2 mutations and found that there was no beta-galactosidase staining in cells lining the renal cysts. Thus, suppression of canonical WNT activity, defined by the TCF/beta-catenin-lacZ reporter, is normal in these two different models of polycystic kidney disease. Hence, excessive beta-catenin transcriptional activity may not contribute to cystogenesis in these models of ADPKD. Kidney International (2011) 80, 146-153; doi:10.1038/ki.2011.56; published online 9 March 2011
C1 [Miller, Michelle M.; Murawski, Inga; Goodyer, Paul R.] McGill Univ, Ctr Hlth, Res Inst, Dept Human Genet, Montreal, PQ H3Z 2Z3, Canada.
   [Miller, Michelle M.; Murawski, Inga; Goodyer, Paul R.] McGill Univ, Montreal Childrens Hosp, Montreal, PQ H3Z 2Z3, Canada.
   [Iglesias, Diana M.; Zhang, Zhao; Corsini, Rachel; Chu, LeeLee; Gupta, Indra] McGill Univ, Dept Pediat, Montreal Childrens Hosp, Res Inst,McGill Univ Hlth Ctr Res Inst, Montreal, PQ, Canada.
   [Somlo, Stefan] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
   [Somlo, Stefan] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
   [Germino, Gregory G.] NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Goodyer, PR (reprint author), McGill Univ, Ctr Hlth, Res Inst, Dept Human Genet, 4060 St Catherine St W, Montreal, PQ H3Z 2Z3, Canada.
EM paul.goodyer@mcgill.ca
FU Canadian Institutes of Health Research [MOP 82904]; Fonds de Recherches
   en Sante du Quebec; National Science and Engineering Research Council;
   Kidney Foundation of Canada; NIH [DK48006]; NIH (NIDDK)
FX This work was supported by an operating grant from the Canadian
   Institutes of Health Research (MOP 82904) and an infrastructure support
   grant to the McGill University Health Centre Research Institute from the
   Fonds de Recherches en Sante du Quebec. MMM was a recipient of a
   National Science and Engineering Research Council postgraduate
   fellowship. DMI was a recipient of a Kidney Foundation of Canada
   postdoctoral fellowship. GGG was funded by the NIH Grant DK48006 and in
   part by the Intramural Research Program of the NIH (NIDDK). PRG was the
   recipient of a CIHR James McGill Research Chair.
NR 30
TC 16
Z9 16
U1 1
U2 1
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 JUL
PY 2011
VL 80
IS 2
BP 147
EP 154
DI 10.1038/ki.2011.56
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 785QR
UT WOS:000292244300005
PM 21389971
ER

PT J
AU Gray, GE
   Allen, M
   Moodie, Z
   Churchyard, G
   Bekker, LG
   Nchabeleng, M
   Mlisana, K
   Metch, B
   de Bruyn, G
   Latka, MH
   Roux, S
   Mathebula, M
   Naicker, N
   Ducar, C
   Carter, DK
   Puren, A
   Eaton, N
   McElrath, MJ
   Robertson, M
   Corey, L
   Kublin, JG
AF Gray, Glenda E.
   Allen, Mai
   Moodie, Zoe
   Churchyard, Gavin
   Bekker, Linda-Gail
   Nchabeleng, Maphoshane
   Mlisana, Koleka
   Metch, Barbara
   de Bruyn, Guy
   Latka, Mary H.
   Roux, Surita
   Mathebula, Matsontso
   Naicker, Nivashnee
   Ducar, Constance
   Carter, Donald K.
   Puren, Adrien
   Eaton, Niles
   McElrath, M. Julie
   Robertson, Michael
   Corey, Lawrence
   Kublin, James G.
CA HVTN 503 Phambili Study Team
TI Safety and efficacy of the HVTN 503/Phambili Study of a clade-B-based
   HIV-1 vaccine in South Africa: a double-blind, randomised,
   placebo-controlled test-of-concept phase 2h study
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID CYTOTOXIC T-LYMPHOCYTE; HERPES-SIMPLEX VIRUS-2; CELL-MEDIATED-IMMUNITY;
   NEUTRALIZING ANTIBODIES; TYPE-1 INFECTION; RESPONSES; ACQUISITION;
   TRIAL; GAG; IMMUNOGENICITY
AB Background The MRKAd5 HIV-1 gag/pol/nef subtype B vaccine was designed to elicit T-cell-mediated immune responses capable of providing complete or partial protection from HIV-1 infection or a decrease in viral load after acquisition. We aim to assess the safety and efficacy of the vaccine in South Africa, where the major circulating clade is subtype C.
   Methods We did a phase 2b double-blind, randomised test-of-concept study in sexually active HIV-1 seronegative participants at five sites in South Africa. Randomisation was by a computer-generated random number sequence. The vaccine and placebo were given by intramuscular injection on a 0,1,6 month schedule. Our coprimary endpoints were a vaccine-induced reduction in HIV-1 acquisition and viral-load setpoint. These endpoints were assessed independently in the modified intention-to-treat (MITT) cohort with two-tailed significance tests stratified by sex. We assessed immunogenicity by interferon-gamma ELISPOT in peripheral-blood mononuclear cells. After the lack of efficacy of the MRKAd5 HIV-1 vaccine in the Step study, enrolment and vaccination in our study was halted, treatment allocations were unmasked, and follow-up continued. This study is registered with the South Africa National Health Research Database, number DOH-27-0207-1539, and ClinicalTrials.gov, number NCT00413725.
   Findings 801 of a scheduled 3000 participants, of whom 360 (45%) were women, were randomly assigned to receive either vaccine or placebo. 445 participants (56%) had adenovirus serotype 5 (Ad5) titres greater than 200, and 129 men (29%) were circumcised. 34 MITT participants in the vaccine group were diagnosed with HIV-1 (incidence rate 4.54 per 100 person-years) and 28 in the placebo group (3.70 per 100 person-years). There was no evidence of vaccine efficacy; the hazard ratio adjusted for sex was 1.25 (95% CI 0.76-2.05). Vaccine efficacy did not differ by Ad5 titre, sex, age, herpes simplex virus type 2 status, or circumcision. The geometric mean viral-load setpoint was 20 483 copies per mL (n=33) in the vaccine group and 34032 copies per mL (n=28) in the placebo group (p=0.39). The vaccine elicited interferon-gamma-secreting T cells that recognised both clade B (89%) and C (77%) antigens.
   Interpretation The MRKAd5 HIV-1 vaccine did not prevent HIV-1 infection or lower viral-load setpoint; however, stopping our trial early probably compromised our ability to draw conclusions. The high incidence rates noted in South Africa highlight the crucial need for intensified efforts to develop an efficacious vaccine.
C1 [Gray, Glenda E.; de Bruyn, Guy] Univ Witwatersrand, Perinatal HIV Res Unit, ZA-1864 Johannesburg, South Africa.
   [Allen, Mai] NIAID, NIH, Bethesda, MD 20892 USA.
   [Moodie, Zoe; Metch, Barbara] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA.
   [Moodie, Zoe; Metch, Barbara; Ducar, Constance; Carter, Donald K.; Eaton, Niles; McElrath, M. Julie; Corey, Lawrence; Kublin, James G.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
   [Churchyard, Gavin; Latka, Mary H.] Aurum Inst Hlth Res, Johannesburg, South Africa.
   [Bekker, Linda-Gail; Roux, Surita] Univ Cape Town, Desmond Tutu HIV Fdn, ZA-7925 Cape Town, South Africa.
   [Nchabeleng, Maphoshane; Mathebula, Matsontso] Univ Limpopo, Medunsa HIV Clin Res Unit, Limpopo, South Africa.
   [Mlisana, Koleka; Naicker, Nivashnee] Univ KwaZulu Natal, Ctr AIDS Programme Res S Africa, Durban, South Africa.
   [Latka, Mary H.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
   [Puren, Adrien] Natl Inst Communicable Dis, Johannesburg, South Africa.
   [Robertson, Michael] Merck & Co Inc, Iccines Clin Res, Whitehouse Stn, NJ USA.
RP Gray, GE (reprint author), Univ Witwatersrand, Perinatal HIV Res Unit, Chris Hani Baragwanath Hosp, POB 114, ZA-1864 Johannesburg, South Africa.
EM gray@pixie.co.za
FU US National Institute of Allergy and Infectious Disease; Merck and Co
   Inc.; National Institute of Allergy and Infectious Diseases [5U01
   AI068614, 5U01 AI068618, 5U01 AI068635, 5U01 AI069453, 5U01 AI069519,
   5U01 AI069469]; South African AIDS Vaccine initiative (SAAVI)
FX The US National Institute of Allergy and Infectious Disease and Merck
   and Co Inc.; Our study was funded by grants from the National Institute
   of Allergy and Infectious Diseases to the HIV Vaccine Trials Network
   (5U01 AI068614, 5U01 AI068618, 5U01 AI068635, 5U01 AI069453, 5U01
   AI069519, 5U01 AI069469) as well as Merck and Co Inc. The South African
   AIDS Vaccine initiative (SAAVI) provided support to the clinical trial
   sites. We thank the Phambili Study volunteers and the staff and
   community members at each of the Phambili Study sites. The opinions
   expressed in this Article are those of the authors and do not represent
   the official views of the US National Institute of Allergy and
   Infectious Diseases.
NR 33
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U1 3
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUL
PY 2011
VL 11
IS 7
BP 507
EP 515
DI 10.1016/S1473-3099(11)70098-6
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA 783ZT
UT WOS:000292124100018
PM 21570355
ER

PT J
AU Zhang, FJ
   Dou, ZH
   Ma, Y
   Zhang, Y
   Zhao, Y
   Zhao, DC
   Zhou, ST
   Bulterys, M
   Zhu, H
   Chen, RY
AF Zhang, Fujie
   Dou, Zhihui
   Ma, Ye
   Zhang, Yao
   Zhao, Yan
   Zhao, Decai
   Zhou, Shuntai
   Bulterys, Marc
   Zhu, Hao
   Chen, Ray Y.
TI Effect of earlier initiation of antiretroviral treatment and increased
   treatment coverage on HIV-related mortality in China: a national
   observational cohort study
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID RAPID SCALE-UP; INCOME COUNTRIES; PUBLIC-HEALTH; THERAPY; CARE;
   INFECTION; PROGRAM; MORBIDITY; BARRIERS; OUTCOMES
AB Background Overall HIV mortality rates in China have not been reported. In this analysis we assess overall mortality in treatment-eligible adults with HIV and attempt to identify risk factors for HIV-related mortality.
   Methods We used data from the national HIV epidemiology and treatment databases to identify individuals aged 15 years or older with HIV who were eligible for highly active antiretroviral therapy between 1985 and 2009. Mortality rates were calculated in terms of person-years, with risk factors determined by Cox proportional hazard regression. Treatment coverage was calculated as the proportion of time that patients who were eligible for treatment received treatment, with risk factors for not receiving treatment identified by use of logistic regression.
   Findings Of 323 252 people reported as having HIV in China by the end of 2009, 145 484 (45%) were identified as treatment-eligible and included in this analysis. Median CD4 count was 201 cells per mu L (IQR 71-315) at HIV diagnosis and 194 cells per mu L (73-293) when first declared eligible for treatment. Overall mortality decreased from 39.3 per 100 person-years in 2002 to 14.2 per 100 person-years in 2009, with treatment coverage concomitantly increasing from almost zero to 63.4%. By 2009, mortality was higher and treatment coverage lower in injecting drug users (15.9 deaths per 100 person-years; 42.7% coverage) and those infected sexually (17.5 deaths per 100 person-years; 61.7% coverage), compared with those infected through plasma donation or blood transfusion (6.7 deaths per 100 person-years; 80.2% coverage). The two strongest risk factors for HIV-related mortality were not receiving highly active antiretroviral therapy (adjusted hazard ratio 4.35, 95% CI 4.10-4.62) and having a CD4 count of less than 50 cells per mu L when first declared eligible for treatment (7.92, 7.33-8.57).
   Interpretation An urgent need exists for earlier HIV diagnosis and better access to treatment for injecting drug users and patients infected with HIV sexually, especially before they become severely immunosuppressed.
C1 [Zhang, Fujie; Dou, Zhihui; Ma, Ye; Zhang, Yao; Zhao, Yan; Zhao, Decai; Zhou, Shuntai; Zhu, Hao] Chinese Ctr Dis Control & Prevent, Natl Ctr AIDS STD Control & Prevent, Beijing, Peoples R China.
   [Zhang, Fujie] Capital Med Univ, Ditan Hosp, Beijing, Peoples R China.
   [Bulterys, Marc] US Ctr Dis Control & Prevent, Global AIDS Program, Beijing, Peoples R China.
   [Chen, Ray Y.] NIAID, US Natl Inst Hlth, Beijing, Peoples R China.
   [Zhu, Hao] Univ N Carolina, Chapel Hill, NC USA.
RP Zhang, FJ (reprint author), China CDC, Div Treatment & Care, Natl Ctr AIDS STD Control & Prevent, 27 Nanwei Rd, Beijing 100027, Peoples R China.
EM zhang.fujie.t@gmail.com
RI Zhou, Shuntai/R-4367-2016; 
OI Chen, Ray/0000-0001-6344-1442
FU National Centre for AIDS/STD Control and Prevention of the Chinese
   Centre for Disease Control and Prevention
FX The National Centre for AIDS/STD Control and Prevention of the Chinese
   Centre for Disease Control and Prevention.
NR 46
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Z9 147
U1 2
U2 21
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD JUL
PY 2011
VL 11
IS 7
BP 516
EP 524
DI 10.1016/S1473-3099(11)70097-4
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA 783ZT
UT WOS:000292124100019
PM 21600849
ER

PT J
AU Rice, C
   Jin, N
   Cocco, P
   Dosemeci, M
   Buncher, CR
AF Rice, Carol
   Jin, Na
   Cocco, P.
   Dosemeci, M.
   Buncher, C. R.
TI The exposuremetric: does including time since exposure in the
   calculation of working lifetime exposure provide a better understanding
   of disease risk than the cumulative exposure?
SO MEDICINA DEL LAVORO
LA English
DT Article
DE Exposure assessment; silica; pulmonary disease
ID VERMONT GRANITE SHEDS; POTTERY FACTORIES; SILICA EXPOSURE; DUST
   EXPOSURE; LUNG-CANCER; WORKERS; CHINA; MINES
AB Background: When exposure measurements are available for occupational epidemiology studies, the cumulative exposure (the sum of the products of duration and exposure intensity at all jobs) is generally selected as the summary metric for chronic diseases. For silica exposures, a metric that weights each exposure by the number of years since it occurred has been suggested as more biologically relevant. Comparative reports of analyses using both metrics have not been found in the literature, however. Methods: We calculated both metrics for silica exposure, and evaluated exposure-response relations for lung cancer and silicosis in two separate case-control studies. Results: Generally the results were consistent, due to the high correlation between the two metrics and the fact that the rate of time away from work during the employment years was low. Conclusion: The significant relation between exposure and silicosis using the weighted metric provides additional point estimates of risk, adding to the understanding of exposure-response.
C1 [Rice, Carol; Jin, Na; Buncher, C. R.] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH 45267 USA.
   [Cocco, P.] Univ Cagliari, Sez Med Lavoro, Dipartimento Sanita Pubbl, I-09124 Cagliari, Italy.
   [Dosemeci, M.] NCI, Occupat & Environm Epidemiol Branch, NIH, DHHS, Bethesda, MD 20892 USA.
RP Rice, C (reprint author), Univ Cincinnati, Dept Environm Hlth, POB 670056, Cincinnati, OH 45267 USA.
EM alerdilr@uc.edu
FU NCI [1 P01 CA096964-01 A1]; National Institute for Occupational Safety
   and Health [OH 01121]; E.I.duPont de Nemours Company
FX Partial support was provided through an NCI Interagency Personnel
   Agreement (C. Rice), a University of Cincinnati Graduate Assistantship
   (N. Jin) and NCI grant 1 P01 CA096964-01 A1(C. R. Buncher). The work on
   the cumulative metric was conducted under National Institute for
   Occupational Safety and Health grant OH 01121 and a grant from the
   E.I.duPont de Nemours & Company Educational Aid Program (C. Rice).
NR 23
TC 1
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U1 1
U2 4
PU MATTIOLI 1885
PI FIDENZA
PA VIA CODURO 1-B, FIDENZA, 43046 PR, ITALY
SN 0025-7818
J9 MED LAV
JI Med. Lav.
PD JUL-AUG
PY 2011
VL 102
IS 4
BP 343
EP 349
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 785YR
UT WOS:000292269600005
PM 21834271
ER

PT J
AU Vermeulen, R
   Rothman, N
   Lan, Q
AF Vermeulen, R.
   Rothman, N.
   Lan, Q.
TI Coal combustion and lung cancer risk in XuanWei: a possible role of
   silica?
SO MEDICINA DEL LAVORO
LA English
DT Article
DE PAHs; silica; lung cancer
ID POLYCYCLIC AROMATIC-HYDROCARBONS; BREAST-CANCER; EXPOSURE; CHINA; WEI;
   EMISSIONS; WORKERS
AB Background: XuanWei County, Yunnan province, has the highest lung cancer mortality rates among men and women in China. The high mortality has been linked to the use of smoky (bituminous) coal for heating and cooking. Research to date has suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) is one of the main contributors to the observed risk. More recently exposure to crystalline silica has been suggested as another contributing factor. Methods: We used data of indoor benzo[a] pyrene (BaP) and silica level and lung cancer mortality at the communal level from previous reports to discuss etiological hypotheses on the lung cancer epidemics in XuanWei County. Results: We estimated that PAH exposure as measured by benzo[a] pyrene (BaP) can explain a significant part of the excess risk but not fully (Odd Ratio (OR) similar to 3 as compared to an observed OR=8 for smoky coal users versus smokeless coal users). This leaves open the possibility of other contributing exposures. Exposure to crystalline silica however would likely only result in an increased risk (OR) of less than 1.5 and as such silica seems not to be the main exposure of interest. However, this does not exclude that risks are present because of the specific physic-chemical characteristics of the silica in smoky coal or that there is an interaction between silica and PAH exposures. Conclusion: More detailed exposure assessment of indoor air pollution due to the use of smoky coal and subsequent linkage on an individual level to ongoing epidemiological studies should provide more insight in the etiology of lung cancer in this region.
C1 [Vermeulen, R.] Univ Utrecht, IRAS, Div Environm Epidemiol, NL-3584 CK Utrecht, Netherlands.
   [Rothman, N.; Lan, Q.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
RP Vermeulen, R (reprint author), Univ Utrecht, IRAS, Div Environm Epidemiol, Jenalaan 18D, NL-3584 CK Utrecht, Netherlands.
EM R.C.H.Vermeulen@uu.nl
RI Vermeulen, Roel/F-8037-2011
OI Vermeulen, Roel/0000-0003-4082-8163
NR 22
TC 6
Z9 6
U1 0
U2 4
PU MATTIOLI 1885
PI FIDENZA
PA VIA CODURO 1-B, FIDENZA, 43046 PR, ITALY
SN 0025-7818
J9 MED LAV
JI Med. Lav.
PD JUL-AUG
PY 2011
VL 102
IS 4
BP 362
EP 367
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 785YR
UT WOS:000292269600007
PM 21834273
ER

PT J
AU Infante, PF
   Huff, J
AF Infante, P. F.
   Huff, J.
TI Cancer incidence among petrochemical workers in the Porto Torres
   industrial area
SO MEDICINA DEL LAVORO
LA English
DT Letter
ID BENZENE EXPOSURE; OCCUPATIONAL-EXPOSURE; PETROLEUM REFINERY; LYMPHOMA
   SUBTYPES; METAANALYSIS; MORTALITY; RISK; SOLVENTS; COHORT
C1 [Infante, P. F.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Environm & Occupat Hlth, Washington, DC 20037 USA.
   [Huff, J.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Infante, PF (reprint author), George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Environm & Occupat Hlth, Washington, DC 20037 USA.
EM pinfante@starpower.net
NR 13
TC 1
Z9 1
U1 0
U2 0
PU MATTIOLI 1885
PI FIDENZA
PA VIA CODURO 1-B, FIDENZA, 43046 PR, ITALY
SN 0025-7818
J9 MED LAV
JI Med. Lav.
PD JUL-AUG
PY 2011
VL 102
IS 4
BP 382
EP 383
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 785YR
UT WOS:000292269600010
PM 21834276
ER

PT J
AU Hortobagyi, T
   Richardson, SP
   Lomarev, M
   Shamim, E
   Meunier, S
   Russman, H
   Dang, N
   Hallett, M
AF Hortobagyi, Tibor
   Richardson, Sarah Pirio
   Lomarev, Mikhael
   Shamim, Ejaz
   Meunier, Sabine
   Russman, Heike
   Dang, Nguyet
   Hallett, Mark
TI Interhemispheric Plasticity in Humans
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE MUSCLE; FORCE; MOTOR CORTEX; EXCITABILITY; MOTOR CONTROL
ID PRIMARY MOTOR CORTEX; CORTICOSPINAL EXCITABILITY; CROSS-EDUCATION; HAND
   MOVEMENTS; INHIBITION; ACTIVATION; LIMB; MUSCLE; CONTRACTIONS;
   MECHANISMS
AB HORTOBAGYI, T., S. P. RICHARDSON, M. LOMAREV, E. SHAMIM, S. MEUNIER, H. RUSSMAN, N. DANG, and M. HALLETT. Interhemispheric Plasticity in Humans. Med. Sci. Sports Exerc., Vol. 43, No. 7, pp. 1188-1199, 2011. Introduction: Chronic unimanual motor practice increases the motor output not only in the trained but also in the nonexercised homologous muscle in the opposite limb. We examined the hypothesis that adaptations in motor cortical excitability of the nontrained primary motor cortex (iM1) and in interhemispheric inhibition from the trained to the nontrained M1 mediate this interlimb cross education. Methods: Healthy, young volunteers (n = 12) performed 1000 submaximal voluntary contractions (MVC) of the right first dorsal interosseus (FDI) at 80% MVC during 20 sessions. Results: Trained FDI's MVC increased 49.9%, and the untrained FDI's MVC increased 28.1%. Although corticospinal excitability in iM1, measured with transcranial magnetic stimulation (TMS) before and after every fifth session, increased 6% at rest, these changes, as those in intracortical inhibition and facilitation, did not correlate with cross education. When weak and strong TMS of iM1 were delivered on a background of a weak and strong muscle contraction, respectively, of the right FDI, excitability of iM1 increased dramatically after 20 sessions. Interhemispheric inhibition decreased 8.9% acutely within sessions and 30.9% chronically during 20 sessions and these chronic reductions progressively became more strongly associated with cross education. There were no changes in force or TMS measures in the trained group's left abductor minimi digiti and there were no changes in the nonexercising control group (n = 8). Conclusions: The findings provide the first evidence for plasticity of interhemispheric connections to mediate cross education produced by a simple motor task.
C1 [Hortobagyi, Tibor] E Carolina Univ, Dept Exercise & Sport Sci, Greenville, NC 27858 USA.
   [Richardson, Sarah Pirio] Univ New Mexico, Albuquerque, NM 87131 USA.
   [Lomarev, Mikhael] Bekhterev Neuropsychol Inst, St Petersburg, Russia.
   [Shamim, Ejaz; Dang, Nguyet; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
   [Meunier, Sabine] UPMC, INSERM, U731, Serv Readaptat Fonct, Paris, France.
   [Russman, Heike] Zentrum Psychiat Rehabil, Tagesklin, Zurich, Switzerland.
RP Hortobagyi, T (reprint author), E Carolina Univ, Dept Exercise & Sport Sci, 332A Ward Sports Med Bldg, Greenville, NC 27858 USA.
EM hortobagyit@ecu.edu
RI meunier, sabine/G-7622-2014
OI meunier, sabine/0000-0002-6167-4602
FU National Institutes of Health [NS049783]; National Institute of
   Neurological Disorders and Stroke; East Carolina University
FX Supported in part by National Institutes of Health NS049783, National
   Institutes of Health, National Institute of Neurological Disorders and
   Stroke intramural program, and an East Carolina University Research
   Development Award.
NR 40
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U1 1
U2 6
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 JUL
PY 2011
VL 43
IS 7
BP 1188
EP 1199
DI 10.1249/MSS.0b013e31820a94b8
PG 12
WC Sport Sciences
SC Sport Sciences
GA 781IQ
UT WOS:000291924500008
PM 21200340
ER

PT J
AU Gross, KL
   Oakley, RH
   Scoltock, AB
   Jewell, CM
   Cidlowski, JA
AF Gross, Katherine L.
   Oakley, Robert H.
   Scoltock, Alyson B.
   Jewell, Christine M.
   Cidlowski, John A.
TI Glucocorticoid Receptor alpha Isoform-Selective Regulation of
   Antiapoptotic Genes in Osteosarcoma Cells: A New Mechanism for
   Glucocorticoid Resistance
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID NF-KAPPA-B; ACUTE LYMPHOBLASTIC-LEUKEMIA; MULTIPLE-MYELOMA CELLS;
   TRANSCRIPTION FACTOR; DNA-BINDING; HEMATOLOGICAL MALIGNANCIES;
   CONSTITUTIVE ACTIVATION; ANTIINFLAMMATORY ACTION; TRANSACTIVATION
   DOMAIN; NUCLEAR-LOCALIZATION
AB Glucocorticoids regulate a variety of physiological processes and are commonly used to treat disorders of inflammation, autoimmune diseases, and cancer. Glucocorticoid action is predominantly mediated through the classic glucocorticoid receptor (GR)alpha isoform. Recent data suggest that the mature GR alpha mRNA is translated into multiple N-terminal isoforms that have distinct biochemical properties and gene regulatory profiles. Interestingly, osteosarcoma cells stably expressing the GR alpha-D translational isoform are unique in that they are resistant to glucocorticoid-induced apoptosis. In this study, we investigate whether GR alpha isoform-specific differences in the regulation of antiapoptotic genes contribute to this resistant phenotype. We now show that GR alpha-D, unlike the other receptor isoforms, does not inhibit the activity of a nuclear factor kappa B (NF-kappa B)-responsive reporter gene and does not efficiently repress either the transcription or protein production of the antiapoptotic genes Bcl-xL, cellular inhibitor of apoptosis protein 1, and survivin. The inability of GR alpha-D to down-regulate the expression of these genes appears to be associated with a diminished interaction between GR alpha-D and NF-kappa B that is observed in cells, but not in vitro, and likely reflects the sequestration of GR alpha-D in the nucleus. Deletion of the GR alpha N-terminal amino acids 98-335 also results in a nuclear resident GR, which fails to interact with NF-kappa B in cells and promote apoptosis in response to glucocorticoids. These data suggest that the N-terminal translational isoforms of GR alpha selectively regulate antiapoptotic genes and that the GR alpha-D isoform may contribute to the resistance of certain cancer cells to glucocorticoid-induced apoptosis. (Molecular Endocrinology 25: 1087-1099, 2011)
C1 [Gross, Katherine L.; Oakley, Robert H.; Scoltock, Alyson B.; Jewell, Christine M.; Cidlowski, John A.] Natl Inst Environm Hlth Sci, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), Natl Inst Environm Hlth Sci, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, POB 12233,Mail Drop F3-07, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
FU National Institute of Environmental Health Sciences, National Institutes
   of Health
FX This work was supported by the Intramural Research Program of the
   National Institute of Environmental Health Sciences, National Institutes
   of Health.
NR 65
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U1 1
U2 4
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD JUL
PY 2011
VL 25
IS 7
BP 1087
EP 1099
DI 10.1210/me.2010-0051
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 784DF
UT WOS:000292133500002
PM 21527497
ER

PT J
AU Segel, R
   Anikster, Y
   Zevin, S
   Steinberg, A
   Gahl, WA
   Fisher, D
   Staretz-Chacham, O
   Zimran, A
   Altarescu, G
AF Segel, Reeval
   Anikster, Yair
   Zevin, Shoshana
   Steinberg, Avraham
   Gahl, William A.
   Fisher, Drora
   Staretz-Chacham, Orna
   Zimran, Ari
   Altarescu, Gheona
TI A safety trial of high dose glyceryl triacetate for Canavan disease
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Canavan disease; Aspartoacylase deficiency; ASPA; Glyceryltriacetate;
   GTA; Safety
ID N-ACETYLASPARTATE; CHAIN TRIGLYCERIDES; NERVOUS-SYSTEM; TREMOR RAT;
   BRAIN; ACETATE; DEGENERATION; THERAPY; JEWISH
AB Canavan disease (CD MIM#271900) is a rare autosomal recessive neurodegenerative disorder presenting in early infancy. The course of the disease is variable, but it is always fatal. CD is caused by mutations in the ASPA gene, which codes for the enzyme aspartoacylase (ASPA), which breaks down N-acetylaspartate (NAA) to acetate and aspartic acid. The lack of NAA-degrading enzyme activity leads to excess accumulation of NAA in the brain and deficiency of acetate, which is necessary for myelin lipid synthesis.
   Glyceryltriacetate (GTA) is a short-chain triglyceride with three acetate moieties on a glycerol backbone and has proven an effective acetate precursor. Intragastric administration of GTA to tremor mice results in greatly increased brain acetate levels, and improved motor functions. GTA given to infants with CD at a low dose (up to 0.25 g/kg/d) resulted in no improvement in their clinical status, but also no detectable toxicity. We present for the first time the safety profile of high dose GTA (4.5 g/kg/d) in 2 patients with CD. We treated 2 infants with CD at ages 8 months and 1 year with high dose GTA, for 4.5 and 6 months respectively. No significant side effects and no toxicity were observed. Although the treatment resulted in no motor improvement, it was well tolerated. The lack of clinical improvement might be explained mainly by the late onset of treatment, when significant brain damage was already present. Further larger studies of CD patients below age 3 months are required in order to test the long-term efficacy of this drug. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Segel, Reeval; Altarescu, Gheona] Shaare Zedek Med Ctr, Inst Med Genet, IL-91031 Jerusalem, Israel.
   [Segel, Reeval; Steinberg, Avraham] Shaare Zedek Med Ctr, Dept Pediat, IL-91031 Jerusalem, Israel.
   [Segel, Reeval; Fisher, Drora; Zimran, Ari; Altarescu, Gheona] Hebrew Univ Jerusalem, Sch Med, IL-91010 Jerusalem, Israel.
   [Anikster, Yair] Edmond & Lily Safra Childrens Hosp, Sheba Med Ctr, Metab Dis Unit, Tel Aviv, Israel.
   [Anikster, Yair] Sackler Sch Med, Tel Aviv, Israel.
   [Zevin, Shoshana] Shaare Zedek Med Ctr, Dept Internal Med, IL-91031 Jerusalem, Israel.
   [Steinberg, Avraham] Shaare Zedek Med Ctr, Med Eth Unit, IL-91031 Jerusalem, Israel.
   [Gahl, William A.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Fisher, Drora] Shaare Zedek Med Ctr, Pediat Radiol Unit, IL-91031 Jerusalem, Israel.
   [Staretz-Chacham, Orna] Ben Gurion Univ Negev, Dept Neonatol, Soroka Med Ctr, Fac Hlth Sci, IL-84105 Beer Sheva, Israel.
   [Zimran, Ari] Shaare Zedek Med Ctr, Gaucher Unit, IL-91031 Jerusalem, Israel.
RP Segel, R (reprint author), Shaare Zedek Med Ctr, Inst Med Genet, POB 3235, IL-91031 Jerusalem, Israel.
EM Reevals@szmc.org.il
NR 18
TC 22
Z9 22
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JUL
PY 2011
VL 103
IS 3
BP 203
EP 206
DI 10.1016/j.ymgme.2011.03.012
PG 4
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 781GV
UT WOS:000291919500001
PM 21474353
ER

PT J
AU Markello, TC
   St Hilaire, C
   Ziegler, SG
   Nussbaum, RL
   Boehm, M
   Gahl, WA
AF Markello, Thomas C.
   St Hilaire, Cynthia
   Ziegler, Shira G.
   Nussbaum, Robert L.
   Boehm, Manfred
   Gahl, William A.
TI Reply to Professor Leftheriotis et al.
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Letter
ID KNOCKOUT; PROTEINS
C1 [Markello, Thomas C.; Ziegler, Shira G.; Boehm, Manfred; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Markello, Thomas C.; Gahl, William A.] NIH, NIH Undiagnosed Dis Program, Off Rare Dis Res, Bethesda, MD 20892 USA.
   [Markello, Thomas C.; Gahl, William A.] NIH, NIH Clin Ctr, Bethesda, MD 20892 USA.
   [St Hilaire, Cynthia] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Markello, TC (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,Bldg 10-10C103, Bethesda, MD 20892 USA.
EM markellot@mail.nih.gov
RI St. Hilaire, Cynthia/I-4713-2014; 
OI St. Hilaire, Cynthia/0000-0003-1871-6915
FU NIGMS NIH HHS [T32 GM007814]
NR 11
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD JUL
PY 2011
VL 103
IS 3
BP 305
EP 305
DI 10.1016/j.ymgme.2011.04.008
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 781GV
UT WOS:000291919500018
PM 21592834
ER

PT J
AU Bourret, TJ
   Boylan, JA
   Lawrence, KA
   Gherardini, FC
AF Bourret, Travis J.
   Boylan, Julie A.
   Lawrence, Kevin A.
   Gherardini, Frank C.
TI Nitrosative damage to free and zinc-bound cysteine thiols underlies
   nitric oxide toxicity in wild-type Borrelia burgdorferi
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID II FRUCTOSE-1,6-BISPHOSPHATE ALDOLASE; OXIDATIVE STRESS-RESPONSE;
   ESCHERICHIA-COLI; LYME-DISEASE; DNA-DAMAGE; MYCOBACTERIUM-TUBERCULOSIS;
   SULFUR CLUSTERS; REACTIVE OXYGEN; HEME PROTEIN; METALLOTHIONEIN
AB Borrelia burgdorferi encounters potentially harmful reactive nitrogen species (RNS) throughout its infective cycle. In this study, diethylamine NONOate (DEA/NO) was used to characterize the lethal effects of RNS on B. burgdorferi. RNS produce a variety of DNA lesions in a broad spectrum of microbial pathogens; however, levels of the DNA deamination product, deoxyinosine, and the numbers of apurinic/apyrimidinic (AP) sites were identical in DNA isolated from untreated and DEA/NO-treated B. burgdorferi cells. Strains with mutations in the nucleotide excision repair (NER) pathway genes uvrC or uvrB treated with DEA/NO had significantly higher spontaneous mutation frequencies, increased numbers of AP sites in DNA and reduced survival compared with wild-type controls. Polyunsaturated fatty acids in B. burgdorferi cell membranes, which are susceptible to peroxidation by reactive oxygen species (ROS), were not sensitive to RNS-mediated lipid peroxidation. However, treatment of B. burgdorferi cells with DEA/NO resulted in nitrosative damage to several proteins, including the zinc-dependent glycolytic enzyme fructose-1,6-bisphosphate aldolase (BB0445), the Borrelia oxidative stress regulator (BosR) and neutrophil-activating protein (NapA). Collectively, these data suggested that nitrosative damage to proteins harbouring free or zinc-bound cysteine thiols, rather than DNA or membrane lipids underlies RNS toxicity in wild-type B. burgdorferi.
C1 [Bourret, Travis J.; Boylan, Julie A.; Lawrence, Kevin A.; Gherardini, Frank C.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Gherardini, FC (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM fgherardini@niaid.nih.gov
OI Bourret, Travis/0000-0002-4154-929X
FU Division of Intramural Research of the National Institute for Allergy
   and Infectious Diseases, National Institutes of Health
FX We would like to thank Dr David W. Dorward and the RML Electron
   Microscopy Unit for the EM images. We would also like to thank Dr Tom G.
   Schwan for assistance with fluorescent microscopy. This work was
   supported by the Division of Intramural Research of the National
   Institute for Allergy and Infectious Diseases, National Institutes of
   Health.
NR 49
TC 20
Z9 22
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0950-382X
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD JUL
PY 2011
VL 81
IS 1
BP 259
EP 273
DI 10.1111/j.1365-2958.2011.07691.x
PG 15
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 783TF
UT WOS:000292106200019
PM 21564333
ER

PT J
AU Hamilton, JP
   Chen, G
   Thomason, ME
   Schwartz, ME
   Gotlib, IH
AF Hamilton, J. P.
   Chen, G.
   Thomason, M. E.
   Schwartz, M. E.
   Gotlib, I. H.
TI Investigating neural primacy in Major Depressive Disorder: multivariate
   Granger causality analysis of resting-state fMRI time-series data
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE depression; fMRI; Granger causality; multivariate; dopamine; neural
   network
ID TREATMENT-RESISTANT DEPRESSION; FUNCTIONAL MAGNETIC-RESONANCE; SUBGENUAL
   PREFRONTAL CORTEX; DEEP BRAIN-STIMULATION; CEREBRAL-BLOOD-FLOW; MOOD
   DISORDERS; ANTIDEPRESSANT TREATMENT; ORBITOFRONTAL CORTEX; UNIPOLAR
   DEPRESSION; HIPPOCAMPAL VOLUME
AB Major Depressive Disorder (MDD) has been conceptualized as a neural network-level disease. Few studies of the neural bases of depression, however, have used analytical techniques that are capable of testing network-level hypotheses of neural dysfunction in this disorder. Moreover, of those that have, fewer still have attempted to determine the directionality of influence within functionally abnormal networks of structures. We used multivariate GC analysis, a technique that estimates the extent to which preceding neural activity in one or more seed regions predicts subsequent activity in target brain regions, to analyze blood-oxygen-level-dependent (BOLD) data collected during eyes-closed rest from depressed and never-depressed persons. We found that activation in the hippocampus predicted subsequent increases in ventral anterior cingulate cortex (vACC) activity in depression, and that activity in the medial prefrontal cortex and vACC were mutually reinforcing in MDD. Hippocampal and vACC activation in depressed participants predicted subsequent decreases in dorsal cortical activity. This study shows that, on a moment-by-moment basis, there is increased excitatory activity among limbic and paralimbic structures, as well as increased inhibition in the activity of dorsal cortical structures, by limbic structures in depression; these aberrant patterns of effective connectivity implicate disturbances in the mesostriatal dopamine system in depression. These findings advance the neural theory of depression by detailing specific patterns of limbic excitation in MDD, by making explicit the primary role of limbic inhibition of dorsal cortex in the cortico-limbic relation posited to underlie depression, and by presenting an integrated neurofunctional account of altered dopamine function in this disorder. Molecular Psychiatry (2011) 16, 763-772; doi:10.1038/mp.2010.46;published online 18 May 2010
C1 [Hamilton, J. P.; Thomason, M. E.; Schwartz, M. E.; Gotlib, I. H.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA.
   [Chen, G.] NIMH, Bethesda, MD 20892 USA.
RP Hamilton, JP (reprint author), Stanford Univ, Dept Psychol, 450 Serra Mall,Jordan Hall,Bldg 420, Stanford, CA 94305 USA.
EM paulhami@stanford.edu
FU National Institute of Mental Health [MH59259, MH079651]
FX We acknowledge the contributions of Becka Johnson, Emily Dennis, Sarah
   Victor, Melissa Henry and Lindsey Sherdell in assisting with the
   collection, analysis and presentation of data for the study. We thank
   Amit Etkin for his critique of an earlier version of this paper.
   Preparation of this paper was supported by Grant MH59259 from the
   National Institute of Mental Health awarded to Ian H Gotlib and Grant
   MH079651 from the National Institute of Mental Health awarded to J Paul
   Hamilton. All authors had full access to all of the data in the study
   and take responsibility for the integrity of the data and the accuracy
   of the data analysis.
NR 64
TC 120
Z9 125
U1 4
U2 32
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 JUL
PY 2011
VL 16
IS 7
BP 763
EP 772
DI 10.1038/mp.2010.46
PG 10
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 781YF
UT WOS:000291973300011
PM 20479758
ER

PT J
AU Cerio, RJ
   Roberts, JN
   Thompson, CD
   Lowy, DR
   Schiller, JT
AF Cerio, Rebecca J.
   Roberts, Jeffrey N.
   Thompson, Cynthia D.
   Lowy, Douglas R.
   Schiller, John T.
TI Human Papillomavirus Pseudoviruses as Gene Delivery Vectors for Murine
   and Human Tumors
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 14th Annual Meeting on the American-Society-of-Gene-and-Cell-Therapys
CY MAY 18-21, 2011
CL Seattle, WA
SP Amer Soc Gene & Cell Therapy
C1 [Cerio, Rebecca J.; Roberts, Jeffrey N.; Thompson, Cynthia D.; Lowy, Douglas R.; Schiller, John T.] NCI, Cellular Oncol Lab, 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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUL
PY 2011
VL 19
IS 7
MA 875
BP 1365
EP 1365
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA 786HU
UT WOS:000292295900032
ER

PT J
AU Grunseich, C
   Shi, YJ
   Fischbeck, KH
   Pierson, TM
AF Grunseich, Christopher
   Shi, Yijun
   Fischbeck, Kenneth H.
   Pierson, Tyler M.
TI Tight Regulation of Transgene Expression by Mifepristone-Inducible
   System after In Vitro Delivery by Lentiviral Vectors to Neural
   Progenitor Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 14th Annual Meeting on the American-Society-of-Gene-and-Cell-Therapys
CY MAY 18-21, 2011
CL Seattle, WA
SP Amer Soc Gene & Cell Therapy
C1 [Grunseich, Christopher; Shi, Yijun; Fischbeck, Kenneth H.; Pierson, Tyler M.] NINDS, Neurogenet Branch, 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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD JUL
PY 2011
VL 19
IS 7
MA 882
BP 1369
EP 1370
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA 786HU
UT WOS:000292295900039
ER

PT J
AU Makiela-Dzbenska, K
   Jonczyk, P
   Schaaper, RM
   Fijalkowska, IJ
AF Makiela-Dzbenska, K.
   Jonczyk, P.
   Schaaper, R. M.
   Fijalkowska, I. J.
TI Proofreading deficiency of Pol I increases the levels of spontaneous
   rpoB mutations in E. coli
SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
LA English
DT Article
DE DNA replication fidelity; DNA polymerase; Mutagenesis; Proofreading;
   Okazaki fragment
ID DNA-POLYMERASE-II; ESCHERICHIA-COLI; SPONTANEOUS MUTAGENESIS;
   REPLICATION FIDELITY; MISMATCH REPAIR; LAGGING-STRAND; TAU-SUBUNIT;
   MUTATOR; VIVO; CHROMOSOME
AB The fidelity role of DNA polymerase I in chromosomal DNA replication in E. coli was investigated using the rpoB forward target. These experiments indicated that in a strain carrying a proofreading-exonuclease-defective form of Pol I (polAexo mutant) the frequency of rpoB mutations increased by about 2-fold, consistent with a model that the fidelity of DNA polymerase I is important in controlling the overall fidelity of chromosomal DNA replication. DNA sequencing of rpoB mutants revealed that the Poll exonuclease deficiency lead to an increase in a variety of base-substitution mutations. A polAexo mutator effect was also observed in strains defective in DNA mismatch repair and carrying the dnaE915 antimutator allele. Overall, the data are consistent with a proposed role of Pol I in the faithful completion of Okazaki fragment gaps at the replication fork. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Makiela-Dzbenska, K.; Jonczyk, P.; Fijalkowska, I. J.] Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland.
   [Schaaper, R. M.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Fijalkowska, IJ (reprint author), Polish Acad Sci, Inst Biochem & Biophys, Pawinskiego 5A, PL-02106 Warsaw, Poland.
EM iwonaf@ibb.waw.pl
RI Makiela-Dzbenska, Karolina/E-6751-2016; Fijalkowska, Iwona/I-7796-2016
FU Polish Ministry of Science and Higher Education [N301 030034]; NIH,
   National Institute of Environmental Health Sciences [201 ES065086]
FX The authors thank Drs. S. Lujan and J. Stone of the NIEHS for their
   critical reading of the manuscript and helpful comments. This research
   was supported grant N301 030034 from the Polish Ministry of Science and
   Higher Education (to I. J. F. and K. M.) and by project no. 201 ES065086
   of the Intramural Research Program of the NIH, National Institute of
   Environmental Health Sciences.
NR 27
TC 5
Z9 5
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0027-5107
EI 1873-135X
J9 MUTAT RES-FUND MOL M
JI Mutat. Res.-Fundam. Mol. Mech. Mutagen.
PD JUL 1
PY 2011
VL 712
IS 1-2
BP 28
EP 32
DI 10.1016/j.mrfmmm.2011.03.011
PG 5
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 786YF
UT WOS:000292343100004
PM 21459099
ER

PT J
AU Chasman, DI
   Schurks, M
   Anttila, V
   de Vries, B
   Schminke, U
   Launer, LJ
   Terwindt, GM
   van den Maagdenberg, AMJM
   Fendrich, K
   Volzke, H
   Ernst, F
   Griffiths, LR
   Buring, JE
   Kallela, M
   Freilinger, T
   Kubisch, C
   Ridker, PM
   Palotie, A
   Ferrari, MD
   Hoffmann, W
   Zee, RYL
   Kurth, T
AF Chasman, Daniel I.
   Schuerks, Markus
   Anttila, Verneri
   de Vries, Boukje
   Schminke, Ulf
   Launer, Lenore J.
   Terwindt, Gisela M.
   van den Maagdenberg, Arn M. J. M.
   Fendrich, Konstanze
   Voelzke, Henry
   Ernst, Florian
   Griffiths, Lyn R.
   Buring, Julie E.
   Kallela, Mikko
   Freilinger, Tobias
   Kubisch, Christian
   Ridker, Paul M.
   Palotie, Aarno
   Ferrari, Michel D.
   Hoffmann, Wolfgang
   Zee, Robert Y. L.
   Kurth, Tobias
CA IHGC
TI Genome-wide association study reveals three susceptibility loci for
   common migraine in the general population
SO NATURE GENETICS
LA English
DT Article
ID GENOTYPE IMPUTATION; NEUROPATHIC PAIN; RECEPTOR; PACKAGE; COHORT;
   HEALTH; SNPS; TOOL
AB Migraine is a common, heterogeneous and heritable neurological disorder. Its pathophysiology is incompletely understood, and its genetic influences at the population level are unknown. In a population-based genome-wide analysis including 5,122 migraineurs and 18,108 non-migraineurs, rs2651899 (1p36.32, PRDM16), rs10166942 (2q37.1, TRPM8) and rs11172113 (12q13.3, LRP1) were among the top seven associations (P < 5 x 10(-6)) with migraine. These SNPs were significant in a meta-analysis among three replication cohorts and met genome-wide significance in a meta-analysis combining the discovery and replication cohorts (rs2651899, odds ratio (OR) = 1.11, P = 3.8 x 10(-9); rs10166942, OR = 0.85, P = 5.5 x 10(-12); and rs11172113, OR = 0.90, P = 4.3 x 10(-9)). The associations at rs2651899 and rs10166942 were specific for migraine compared with non-migraine headache. None of the three SNP associations was preferential for migraine with aura or without aura, nor were any associations specific for migraine features. TRPM8 has been the focus of neuropathic pain models, whereas LRP1 modulates neuronal glutamate signaling, plausibly linking both genes to migraine pathophysiology.
C1 [Chasman, Daniel I.; Schuerks, Markus; Buring, Julie E.; Ridker, Paul M.; Zee, Robert Y. L.; Kurth, Tobias] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA.
   [Chasman, Daniel I.; Ridker, Paul M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Donald W Reynolds Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA.
   [Schuerks, Markus] Univ Hosp Essen, Dept Neurol, Essen, Germany.
   [Anttila, Verneri; Palotie, Aarno] Wellcome Trust Sanger Inst, Cambridge, England.
   [Anttila, Verneri; Palotie, Aarno] Univ Helsinki, FIMM, Helsinki, Finland.
   [de Vries, Boukje; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
   [Schminke, Ulf] Ernst Moritz Arndt Univ Greifswald, Dept Neurol, Greifswald, Germany.
   [Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
   [Terwindt, Gisela M.; van den Maagdenberg, Arn M. J. M.; Ferrari, Michel D.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands.
   [Fendrich, Konstanze; Hoffmann, Wolfgang] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Sect Epidemiol Hlth Care & Community Hlth, Greifswald, Germany.
   [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Sect Clin Epidemiol Res, Greifswald, Germany.
   [Ernst, Florian] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
   [Griffiths, Lyn R.] Griffith Univ, Griffith Hlth Inst, Genom Res Ctr, Gold Coast, Qld, Australia.
   [Kallela, Mikko] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland.
   [Freilinger, Tobias] Univ Munich, Klinikum Grosshadern, Dept Neurol, Munich, Germany.
   [Freilinger, Tobias] Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.
   [Kubisch, Christian] Univ Ulm, Inst Human Genet, Ulm, Germany.
   [Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
   [Palotie, Aarno] Univ Helsinki, Cent Hosp, Dept Med Genet, Helsinki, Finland.
   [Palotie, Aarno] Broad Inst MIT & Harvard, Boston, MA USA.
   [Kurth, Tobias] INSERM, Neuroepidemiol U708, Paris, France.
   [Kurth, Tobias] Univ Paris 06, F-75005 Paris, France.
RP Schurks, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA.
EM markus.schuerks@post.harvard.edu; tobias.kurth@inserm.fr
RI Kubisch, Christian/F-1893-2011; Kurth, Tobias/A-9243-2012; Hoffmann,
   Wolfgang/E-6001-2013; 
OI Kubisch, Christian/0000-0003-4220-0978; Kurth,
   Tobias/0000-0001-7169-2620; Anttila, Verneri/0000-0002-0073-4675;
   Griffiths, Lyn/0000-0002-6774-5475
FU National Institute of Neurological Disorders and Stroke [NS-061836];
   National Heart, Lung, and Blood Institute [HL-043851, HL-080467,
   HL-099355]; National Cancer Institute [CA-47988]; Donald W. Reynolds
   Foundation; Leducq Foundation; Netherlands Organisation for Scientific
   Research (NWO) [918.56.602]; Spinoza grants; Center for Medical Systems
   Biology (CMSB) [050-060-409]; Ministry of Health, Welfare and Sport;
   National Institute of Public Health and the Environment, The
   Netherlands; Federal Ministry of Education and Research [01ZZ9603,
   01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs; Social
   Ministry of the Federal State of Mecklenburg-West Pomerania; Siemens
   Healthcare, Erlangen, Germany; Federal State of Mecklenburg-West
   Pomerania; Academy of Finland [200923]; Wellcome Trust [089062];
   European Community [FP7/2007-2013]; European Community (through the
   SYNSYS Consortium) [242167]; European Community (through the ENGAGE
   Consortium) [201413]; Helsinki University Central Hospital; Finnish
   Culture Foundation; German Federal Ministry of Education and Research
   (BMBF) within the National Genome Research Network [EMINet-01GS08120,
   01GS08121]; Deutsche Forschungsgemeinschaft; Center for Molecular
   Medicine Cologne
FX This study is supported by a grant from the National Institute of
   Neurological Disorders and Stroke (NS-061836). The Women's Health Study
   and the Women's Genome Health Study are supported by grants from the
   National Heart, Lung, and Blood Institute (HL-043851, HL-080467 and
   HL-099355) and the National Cancer Institute (CA-47988). Part of the
   research for this work was supported by grants from the Donald W.
   Reynolds Foundation and the Leducq Foundation. Genome-wide genotyping
   and collaborative scientific support was provided by Amgen.; Genotyping
   in the Genetic Epidemiology of Migraine Study was supported by the
   Netherlands Organisation for Scientific Research (NWO) VICI (918.56.602)
   and Spinoza (2009) grants and the Center for Medical Systems Biology
   (CMSB) established by the Netherlands Genomics Initiative/Netherlands
   Organisation for Scientific Research (NGI/NWO), project no. 050-060-409.
   The GEM study was supported by the Ministry of Health, Welfare and Sport
   and the National Institute of Public Health and the Environment, The
   Netherlands.; SHIP is part of the Community Medicine Research net of the
   University of Greifswald, Germany, which is funded by the Federal
   Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103 and
   01ZZ0403), the Ministry of Cultural Affairs as well as the Social
   Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide
   data have been supported by the Federal Ministry of Education and
   Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare,
   Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania.
   The SHIP authors are grateful to the contribution of A. Teumer, A.
   Hoffmann and A. Petersmann in generating the SNP data. The University of
   Greifswald is a member of the 'Center of Knowledge Interchange' program
   of Siemens AG.; The IHGC study was supported, among others, by the
   Academy of Finland (200923 to A.P.), the Wellcome Trust (grant number
   089062), the European Community's Seventh Framework Programme
   (FP7/2007-2013) (through the SYNSYS Consortium (grant agreement no.
   242167) and the ENGAGE Consortium (grant agreement no. 201413)), the
   Helsinki University Central Hospital (to M.K.) and the Finnish Culture
   Foundation (to V.A.). Funding by the German Federal Ministry of
   Education and Research (BMBF) within the National Genome Research
   Network (NGFNplus, EMINet-01GS08120 for C.K., 01GS08121 to M. Dichgans),
   the Deutsche Forschungsgemeinschaft (to C.K.) and the Center for
   Molecular Medicine Cologne (to C.K.). For a full list of
   acknowledgements, please see reference 5.
NR 26
TC 150
Z9 153
U1 1
U2 20
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 JUL
PY 2011
VL 43
IS 7
BP 695
EP U116
DI 10.1038/ng.856
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 784UV
UT WOS:000292184600016
PM 21666692
ER

PT J
AU Hoglinger, GU
   Melhem, NM
   Dickson, DW
   Sleiman, PMA
   Wang, LS
   Klei, L
   Rademakers, R
   de Silva, R
   Litvan, I
   Riley, DE
   van Swieten, JC
   Heutink, P
   Wszolek, ZK
   Uitti, RJ
   Vandrovcova, J
   Hurtig, HI
   Gross, RG
   Maetzler, W
   Goldwurm, S
   Tolosa, E
   Borroni, B
   Pastor, P
   Cantwell, LB
   Han, MR
   Dillman, A
   van der Brug, MP
   Gibbs, JR
   Cookson, MR
   Hernandez, DG
   Singleton, AB
   Farrer, MJ
   Yu, CE
   Golbe, LI
   Revesz, T
   Hardy, J
   Lees, AJ
   Devlin, B
   Hakonarson, H
   Muller, U
   Schellenberg, GD
AF Hoeglinger, Guenter U.
   Melhem, Nadine M.
   Dickson, Dennis W.
   Sleiman, Patrick M. A.
   Wang, Li-San
   Klei, Lambertus
   Rademakers, Rosa
   de Silva, Rohan
   Litvan, Irene
   Riley, David E.
   van Swieten, John C.
   Heutink, Peter
   Wszolek, Zbigniew K.
   Uitti, Ryan J.
   Vandrovcova, Jana
   Hurtig, Howard I.
   Gross, Rachel G.
   Maetzler, Walter
   Goldwurm, Stefano
   Tolosa, Eduardo
   Borroni, Barbara
   Pastor, Pau
   Cantwell, Laura B.
   Han, Mi Ryung
   Dillman, Allissa
   van der Brug, Marcel P.
   Gibbs, J. Raphael
   Cookson, Mark R.
   Hernandez, Dena G.
   Singleton, Andrew B.
   Farrer, Matthew J.
   Yu, Chang-En
   Golbe, Lawrence I.
   Revesz, Tamas
   Hardy, John
   Lees, Andrew J.
   Devlin, Bernie
   Hakonarson, Hakon
   Mueller, Ulrich
   Schellenberg, Gerard D.
CA PSP Genetics Study Grp
TI Identification of common variants influencing risk of the tauopathy
   progressive supranuclear palsy
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; UNFOLDED PROTEIN RESPONSE; ALZHEIMERS-DISEASE;
   CORTICOBASAL DEGENERATION; NEUROPATHOLOGIC CRITERIA; PARKINSONS-DISEASE;
   TAU-GENE; HAPLOTYPE; EXPRESSION; METAANALYSIS
AB Progressive supranuclear palsy (PSP) is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP (cases) and 3,247 controls (stage 1) followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the stage 1 SNPs that yielded P <= 10(-3). We found significant previously unidentified signals (P < 5 x 10(-8)) associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component.
C1 [Wang, Li-San; Cantwell, Laura B.; Han, Mi Ryung; Schellenberg, Gerard D.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
   [Hoeglinger, Guenter U.] Univ Marburg, Dept Neurol, Marburg, Germany.
   [Melhem, Nadine M.; Klei, Lambertus; Devlin, Bernie] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
   [Dickson, Dennis W.; Rademakers, Rosa] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
   [Sleiman, Patrick M. A.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
   [de Silva, Rohan; Vandrovcova, Jana; Gibbs, J. Raphael; Hernandez, Dena G.; Hardy, John; Lees, Andrew J.] UCL, Inst Neurol, Reta Lila Weston Inst, London, England.
   [Litvan, Irene] Univ Louisville, Div Movement Disorders, Dept Neurol, Louisville, KY 40292 USA.
   [Riley, David E.] Case Western Reserve Univ, Dept Neurol, Univ Hosp, Cleveland, OH 44106 USA.
   [van Swieten, John C.] Erasmus Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands.
   [Heutink, Peter] Vrije Univ VU Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands.
   [Wszolek, Zbigniew K.; Uitti, Ryan J.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
   [Hurtig, Howard I.; Gross, Rachel G.] Univ Penn Hlth Syst, Dept Neurol, Philadelphia, PA USA.
   [Maetzler, Walter] Univ Tubingen, Dept Neurodegenerat, Hertie Inst Clin Brain Res, Ctr Neurol, Tubingen, Germany.
   [Maetzler, Walter] Univ Tubingen, German Ctr Neurodegenerat Dis, Tubingen, Germany.
   [Goldwurm, Stefano] Ist Clin Perfezionamento, Parkinson Inst, Milan, Italy.
   [Tolosa, Eduardo] Univ Barcelona, IDIBAPS, CIBERNED, Neurol Serv,Hosp Clin, Barcelona, Spain.
   [Borroni, Barbara] Univ Brescia, Inst Neurol, Dept Med & Surg Sci, Brescia, Italy.
   [Pastor, Pau] Inst Salud Carlos III, CIBERNED, Madrid, Spain.
   [Pastor, Pau] Univ Navarra, Ctr Appl Med Res, Div Neurosci, Neurogenet Lab, E-31080 Pamplona, Spain.
   [Pastor, Pau] Univ Navarra, Clin Univ Navarra, Dept Neurol, E-31080 Pamplona, Spain.
   [Dillman, Allissa; Gibbs, J. Raphael; Cookson, Mark R.; Hernandez, Dena G.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   [van der Brug, Marcel P.] Scripps Res Inst, Dept Neurosci, Jupiter, FL USA.
   [Farrer, Matthew J.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada.
   [Yu, Chang-En] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
   [Yu, Chang-En] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA.
   [Golbe, Lawrence I.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA.
   [Revesz, Tamas; Lees, Andrew J.] UCL, UCL Inst Neurol, Dept Mol Neurosci, Queen Sq Brain Bank Neurol Disorders, London, England.
   [Mueller, Ulrich] Univ Giessen, Inst Humangenet, Giessen, Germany.
RP Schellenberg, GD (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
EM ulrich.mueller@humangenetik.med.uni-giessen.de;
   gerardsc@mail.med.upenn.edu
RI Silveira-Moriyama, Laura/G-4592-2014; Revesz, Tamas/A-8732-2010;
   Singleton, Andrew/C-3010-2009; Morris, Huw/B-8527-2008; Pastor,
   Pau/C-9834-2009; O'Sullivan, Sean/C-9333-2012; Hardy, John/C-2451-2009;
   Lees, Andrew/A-6605-2009; Ross, Owen/D-7573-2013; Melhem,
   Nadine/G-1510-2013; Troakes, Claire/K-4346-2015; Maetzler,
   Walter/A-6796-2011; Goldwurm, Stefano/Q-8978-2016
OI Silveira-Moriyama, Laura/0000-0002-8267-0977; Budka,
   Herbert/0000-0002-1933-1577; van Swieten, John /0000-0001-6278-6844;
   Geller, Evan/0000-0002-8035-8736; CILIA, ROBERTO/0000-0002-1990-1939;
   Pickering-Brown, Stuart/0000-0003-1561-6054; Litvan,
   Irene/0000-0002-3485-3445; Standaert, David/0000-0003-2921-8348; Revesz,
   Tamas/0000-0003-2501-0259; Morris, Huw/0000-0002-5473-3774; Pastor,
   Pau/0000-0002-7493-8777; Rohrer, Jonathan/0000-0002-6155-8417; Dickson,
   Dennis W/0000-0001-7189-7917; O'Sullivan, Sean/0000-0002-0583-7956;
   Goldwurm, Stefano/0000-0002-1651-567X
FU CurePSP Foundation; Peebler PSP Research Foundation; US National
   Institutes of Health (NIH) (National Institute on Aging (NIA)/NIH) [R37
   AG 11762, R01 PAS-03-092, P50 NS72187, P01 AG17216]; US National
   Institutes of Health (NIH) (National Institute of Mental Health (NIMH)
   [MH057881, MH077930]; NIA; German National Genome Research Network
   [01GS08136-4]; Deutsche Forschungsgemeinschaft [HO 2402/6-1]; Prinses
   Beatrix Fonds [01-0128]; Reta Lila Weston Trust; UK Medical Research
   Council [G0501560, G0400074]; Newcastle National Institute for Health
   Research (NIHR) Biomedical Research Centre in Ageing and Age Related
   Diseases; Alzheimer's Society; Alzheimer's Research Trust; TELETHON
   Italy [GTB07001]; Fondazione Grigioni per il Morbo di Parkinson;
   Wellcome Trust; Howard Hughes Medical Institute; Canadian Institute of
   Health Research; Federal Ministry of Education and Research (BMBF)
   [01GI0505]; PSP (Europe) Association; Cure PSP+; NIH/NINDS
   [1RC2NS070276, NS057567, P50NS072187]; Mayo Clinic Florida (MCF)
   Research Committee [90052030]; Government of Navarra; Division of
   Neuroscience, NIA; Division of Aging Biology and the Division of
   Geriatrics and Clinical Gerontology, NIA; National Human Genome Research
   Institute (NHGRI) [U01HG004608]; National Institute for General Medical
   Sciences (NIGMS); Marshfield Clinic, Health Resources Service
   Administration Office of Rural Health Policy [D1A RH00025]; Wisconsin
   Department of Commerce [TDF FYO10718]; NIH [U01HG004438]
FX We thank the subjects and their families that participated in this
   study. This work was funded by grants from the CurePSP Foundation, the
   Peebler PSP Research Foundation and US National Institutes of Health
   (NIH) grants R37 AG 11762, R01 PAS-03-092, P50 NS72187, P01 AG17216
   (National Institute on Aging (NIA)/NIH), MH057881 and MH077930 (National
   Institute of Mental Health (NIMH)). Work was also supported in part by
   the NIA Intramural Research Program, the German National Genome Research
   Network (01GS08136-4) and the Deutsche Forschungsgemeinschaft (HO
   2402/6-1), Prinses Beatrix Fonds (JCvS, 01-0128), the Reta Lila Weston
   Trust and the UK Medical Research Council (RdS: G0501560). The Newcastle
   Brain Tissue Resource provided tissue and is funded in part by a grant
   from the UK Medical Research Council (G0400074), by the Newcastle
   National Institute for Health Research (NIHR) Biomedical Research Centre
   in Ageing and Age Related Diseases to the Newcastle upon Tyne Hospitals
   National Health Service Foundation Trust and by a grant from the
   Alzheimer's Society and Alzheimer's Research Trust as part of the Brains
   for Dementia Research Project. We acknowledge the contribution of many
   tissue samples from the Harvard Brain Tissue Resource Center. We also
   acknowledge the 'Human Genetic Bank of Patients affected by Parkinson
   Disease and Parkinsonism' (http://www.parkinson.it/dnabank.html) of the
   Telethon Genetic Biobank Network, supported by TELETHON Italy (project
   no. GTB07001) and by Fondazione Grigioni per il Morbo di Parkinson. The
   University of Toronto sample collection was supported by grants from
   Wellcome Trust, Howard Hughes Medical Institute and the Canadian
   Institute of Health Research. Brain-Net-Germany is supported by the
   Federal Ministry of Education and Research (BMBF) (01GI0505). R.d.S.,
   A.J.L. and J.A.H. are funded by the Reta Lila Weston Trust and the PSP
   (Europe) Association. R.d.S. is funded by the UK Medical Research
   Council (Grant G0501560) and Cure PSP+. Z.K.W. is partially supported by
   the NIH/NINDS 1RC2NS070276, NS057567, P50NS072187, Mayo Clinic Florida
   (MCF) Research Committee CR programs (MCF #90052030 and MCF #90052030)
   and the gift from C. E. Bolch Jr. and S. B. Bolch (MCF #90052031/PAU #
   90052). The Mayo Clinic College of Medicine would like to acknowledge M.
   Baker, R. Crook, M. DeJesus-Hernandez and N. Rutherford for their
   preparation of samples. P. P. was supported by a grant from the
   Government of Navarra ('Ayudas para la Realizacion de Proyectos de
   Investigacion' 2006-2007) and acknowledges the 'Iberian Atypical
   Parkinsonism Study Group Researchers': M. A. Pastor, M. R. Luquin, M.
   Riverol, J.A. Obeso and M. C. Rodriguez-Oroz (Department of Neurology,
   Clinica Universitaria de Navarra, University of Navarra, Pamplona,
   Spain), M. Blazquez (Neurology Department, Hospital Universitario
   Central de Asturias, Oviedo, Spain), A. Lopez de Munain, B. Indakoetxea,
   J. Olaskoaga, J. Ruiz, J. Felix Marti Masso (Servicio de Neurologia,
   Hospital Donostia, San Sebastian, Spain), V. Alvarez (Genetics
   Department, Hospital Universitario Central de Asturias, Oviedo, Spain),
   T. Tu on (Banco de Tejidos Neurologicos, CIBERNED, Hospital de Navarra,
   Navarra, Spain), F. Moreno (Servicio de Neurologia, Hospital Ntra. Sra.
   de la Antigua, Zumarraga, Gipuzkoa, Spain), A. Alzualde (Neurogenetics
   Department, Hospital Donostia, San Sebastian, Spain). E. T. wishes to
   acknowledge the Banco de Tejidos Neurologicos de la Universidad de
   Barcelona-Hospital Clinic, which provided many tissue samples for the
   project. We also acknowledge E.; Loomis for providng technical support.;
   The datasets used for older controls were obtained from Database for
   Genotypes and Phenotypes (dbGap) at http://www.ncbi.nlm.nih.gov/gap/.
   Funding support for the 'Genetic Consortium for Late Onset Alzheimer's
   Disease' was provided through the Division of Neuroscience, NIA. The
   Genetic Consortium for Late Onset Alzheimer's Disease (study accession
   number: phs000168.v1.p1) includes a genome-wide association study funded
   as part of the Division of Neuroscience, NIA. Assistance with phenotype
   harmonization and genotype cleaning, as well as with general study
   coordination, was provided by Genetic Consortium for Late Onset
   Alzheimer's Disease. Funding support for the 'CIDR Visceral Adiposity
   Study' (study accession number: phs000169.v1.p1) was provided through
   the Division of Aging Biology and the Division of Geriatrics and
   Clinical Gerontology, NIA. The CIDR Visceral Adiposity Study includes a
   genome-wide association study funded as part of the Division of Aging
   Biology and the Division of Geriatrics and Clinical Gerontology, NIA.
   Assistance with phenotype harmonization and genotype cleaning, as well
   as with general study coordination, was provided by Heath ABC Study
   Investigators. Funding support for the Personalized Medicine Research
   Project (PMRP) was provided through a cooperative agreement
   (U01HG004608) with the National Human Genome Research Institute (NHGRI),
   with additional funding from the National Institute for General Medical
   Sciences (NIGMS). The samples used for PMRP analyses were obtained with
   funding from Marshfield Clinic, Health Resources Service Administration
   Office of Rural Health Policy grant number D1A RH00025 and Wisconsin
   Department of Commerce Technology Development Fund contract number TDF
   FYO10718. Funding support for genotyping, which was performed at Johns
   Hopkins University, was provided by the NIH (U01HG004438). Assistance
   with phenotype harmonization and genotype cleaning was provided by the
   eMERGE Administrative Coordinating Center (U01HG004603) and the National
   Center for Biotechnology Information (NCBI). The datasets used for the
   analyses described in this manuscript were obtained from dbGaP at
   http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number
   phs000170.v1.p1.
NR 46
TC 157
Z9 159
U1 2
U2 29
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 JUL
PY 2011
VL 43
IS 7
BP 699
EP U125
DI 10.1038/ng.859
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 784UV
UT WOS:000292184600017
PM 21685912
ER

PT J
AU Green, JA
   Suzuki, K
   Cho, B
   Willison, LD
   Palmer, D
   Allen, CDC
   Schmidt, TH
   Xu, Y
   Proia, RL
   Coughlin, SR
   Cyster, JG
AF Green, Jesse A.
   Suzuki, Kazuhiro
   Cho, Bryan
   Willison, L. David
   Palmer, Daniel
   Allen, Christopher D. C.
   Schmidt, Timothy H.
   Xu, Ying
   Proia, Richard L.
   Coughlin, Shaun R.
   Cyster, Jason G.
TI The sphingosine 1-phosphate receptor S1P(2) maintains the homeostasis of
   germinal center B cells and promotes niche confinement
SO NATURE IMMUNOLOGY
LA English
DT Article
ID CLASS-SWITCH RECOMBINATION; LYMPHOCYTE EGRESS; PROTEIN-KINASE;
   TRANSLATIONAL CONTROL; ENDOTHELIAL-CELLS; INHIBITION; MIGRATION; AKT;
   SPHINGOSINE-1-PHOSPHATE; PTEN
AB Mice deficient in sphingosine 1-phosphate receptor type 2 (S1P(2)) develop diffuse large B cell lymphoma. However, the role of S1P(2) in normal germinal center (GC) physiology is unknown. Here we show that S1P(2)-deficient GC B cells outgrew their wild-type counterparts in chronically established GCs. We found that antagonism of the kinase Akt mediated by S1P(2) and its downstream mediators G alpha(12), Ga alpha(13) and p115RhoGEF regulated cell viability and was required for growth control in chronically proliferating GCs. Moreover, S1P(2) inhibited GC B cell responses to follicular chemoattractants and helped confine cells to the GC. In addition, S1P(2) overexpression promoted the centering of activated B cells in the follicle. We suggest that by inhibiting Akt activation and migration, S1P(2) helps restrict GC B cell survival and localization to an S1P-low niche at the follicle center.
C1 [Green, Jesse A.; Suzuki, Kazuhiro; Cho, Bryan; Allen, Christopher D. C.; Schmidt, Timothy H.; Xu, Ying; Cyster, Jason G.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
   [Green, Jesse A.; Suzuki, Kazuhiro; Cho, Bryan; Allen, Christopher D. C.; Schmidt, Timothy H.; Xu, Ying; Cyster, Jason G.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
   [Cho, Bryan] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
   [Willison, L. David; Palmer, Daniel; Coughlin, Shaun R.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
   [Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA.
RP Cyster, JG (reprint author), Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
EM jason.cyster@ucsf.edu
RI Proia, Richard/A-7908-2012; Suzuki, Kazuhiro/B-3886-2012; Palmer,
   Daniel/Q-7595-2016
FU National Science Foundation; Howard Hughes Medical Institute; US
   National Institutes of Health [HL65590, HL44907, AI45073]
FX We thank N. Danial (Dana-Farber) for Bad-deficient bone marrow; K.
   Rajewsky (Children's Hospital and Immune Disease Institute, Harvard) for
   mice expressing the Cr2-Cre transgene; J. Browning (Biogen Idec) for
   lymphotoxin-beta receptor-Fc fusion protein; J. An for help with the
   mouse colony; and S. Schwab for critical reading of the manuscript.
   Supported by the National Science Foundation (J. A. G.), Howard Hughes
   Medical Institute (J. G. C.) and the US National Institutes of Health
   (Intramural Research Program; National Institute of Diabetes and
   Digestive and Kidney Diseases (R. L. P.); HL65590 and HL44907 to S. R.
   C.; and AI45073 to J.G.C.).
NR 50
TC 85
Z9 85
U1 2
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD JUL
PY 2011
VL 12
IS 7
BP 672
EP U128
DI 10.1038/ni.2047
PG 11
WC Immunology
SC Immunology
GA 781MJ
UT WOS:000291936400016
PM 21642988
ER

PT J
AU Paiardini, M
   Cervasi, B
   Reyes-Aviles, E
   Micci, L
   Ortiz, AM
   Chahroudi, A
   Vinton, C
   Gordon, SN
   Bosinger, SE
   Francella, N
   Hallberg, PL
   Cramer, E
   Schlub, T
   Chan, ML
   Riddick, NE
   Collman, RG
   Apetrei, C
   Pandrea, I
   Else, J
   Munch, J
   Kirchhoff, F
   Davenport, MP
   Brenchley, JM
   Silvestri, G
AF Paiardini, Mirko
   Cervasi, Barbara
   Reyes-Aviles, Elane
   Micci, Luca
   Ortiz, Alexandra M.
   Chahroudi, Ann
   Vinton, Carol
   Gordon, Shari N.
   Bosinger, Steven E.
   Francella, Nicholas
   Hallberg, Paul L.
   Cramer, Elizabeth
   Schlub, Timothy
   Chan, Ming Liang
   Riddick, Nadeene E.
   Collman, Ronald G.
   Apetrei, Cristian
   Pandrea, Ivona
   Else, James
   Munch, Jan
   Kirchhoff, Frank
   Davenport, Miles P.
   Brenchley, Jason M.
   Silvestri, Guido
TI Low levels of SIV infection in sooty mangabey central memory CD4(+) T
   cells are associated with limited CCR5 expression
SO NATURE MEDICINE
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; AFRICAN-GREEN MONKEYS; AIDS PATHOGENESIS;
   IMMUNE ACTIVATION; RHESUS MACAQUES; NONHUMAN-PRIMATES; DOWN-REGULATION;
   NATURAL HOSTS; DEPLETION; REPLICATION
AB Naturally simian immunodeficiency virus (SIV)-infected sooty mangabeys do not progress to AIDS despite high-level virus replication. We previously showed that the fraction of CD4(+)CCR5(+) T cells is lower in sooty mangabeys compared to humans and macaques. Here we found that, after in vitro stimulation, sooty mangabey CD4(+) T cells fail to upregulate CCR5 and that this phenomenon is more pronounced in CD4(+) central memory T cells (T-CM cells). CD4(+) T cell activation was similarly uncoupled from CCR5 expression in sooty mangabeys in vivo during acute SIV infection and the homeostatic proliferation that follows antibody-mediated CD4(+) T cell depletion. Sooty mangabey CD4(+) TCM cells that express low amounts of CCR5 showed reduced susceptibility to SIV infection both in vivo and in vitro when compared to CD4(+) TCM cells of rhesus macaques. These data suggest that low CCR5 expression on sooty mangabey CD4(+) T cells favors the preservation of CD4(+) T cell homeostasis and promotes an AIDS-free status by protecting CD4(+) TCM cells from direct virus infection.
C1 [Paiardini, Mirko; Cervasi, Barbara; Micci, Luca; Ortiz, Alexandra M.; Chahroudi, Ann; Gordon, Shari N.; Bosinger, Steven E.; Else, James; Silvestri, Guido] Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
   [Paiardini, Mirko; Cervasi, Barbara; Micci, Luca; Ortiz, Alexandra M.; Chahroudi, Ann; Gordon, Shari N.; Bosinger, Steven E.; Else, James; Silvestri, Guido] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA.
   [Paiardini, Mirko; Cervasi, Barbara; Reyes-Aviles, Elane; Ortiz, Alexandra M.; Gordon, Shari N.; Francella, Nicholas; Hallberg, Paul L.; Cramer, Elizabeth; Silvestri, Guido] Univ Penn, Sch Med, Dept Pathol, Philadelphia, PA 19104 USA.
   [Micci, Luca] Univ Urbino, I-61029 Urbino, Italy.
   [Vinton, Carol; Brenchley, Jason M.] US Natl Inst Hlth, Mol Microbiol Lab, Bethesda, MD USA.
   [Schlub, Timothy; Chan, Ming Liang; Davenport, Miles P.] Univ New S Wales, Ctr Vasc Res, Complex Syst Biol Grp, Kensington, NSW 2033, Australia.
   [Riddick, Nadeene E.; Collman, Ronald G.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
   [Apetrei, Cristian; Pandrea, Ivona] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA USA.
   [Munch, Jan; Kirchhoff, Frank] Univ Hosp Ulm, Inst Mol Virol, Ulm, Germany.
RP Silvestri, G (reprint author), Emory Univ, Yerkes Natl Primate Res Ctr, Emory Vaccine Ctr, Atlanta, GA 30322 USA.
EM mirko.paiardini@emory.edu; gsilves@emory.edu
FU  [R01-AI66998];  [P01-AI76074];  [R56-AI087186];  [P51-RR-00165]
FX We wish to thank L. Picker, D. Sodora and Z. Grossman for helpful
   discussions; F. Villinger, B. Lawson, F. Shaheen and J. Tilton for their
   technical support; and S. Ehnert and T. Meeker for their assistance with
   primate studies. We are grateful to the Emory Center for AIDS Research
   Virology Core and the Penn Center for AIDS Research Virology Core for
   their assistance. This work was supported by grant R01-AI66998 and
   P01-AI76074 (to G.S.), R56-AI087186 (to M.P.) and P51-RR-00165 (to
   Yerkes National Primate Research Center).
NR 34
TC 104
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U1 1
U2 7
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 JUL
PY 2011
VL 17
IS 7
BP 830
EP U197
DI 10.1038/nm.2395
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 789FT
UT WOS:000292500800037
PM 21706028
ER

PT J
AU Saha, RN
   Wissink, EM
   Bailey, ER
   Zhao, ML
   Fargo, DC
   Hwang, JY
   Daigle, KR
   Fenn, JD
   Adelman, K
   Dudek, SM
AF Saha, Ramendra N.
   Wissink, Erin M.
   Bailey, Emma R.
   Zhao, Meilan
   Fargo, David C.
   Hwang, Ji-Yeon
   Daigle, Kelly R.
   Fenn, J. Daniel
   Adelman, Karen
   Dudek, Serena M.
TI Rapid activity-induced transcription of Arc and other IEGs relies on
   poised RNA polymerase II
SO NATURE NEUROSCIENCE
LA English
DT Article
ID LONG-TERM POTENTIATION; IMMEDIATE-EARLY GENE; BREAST-CANCER CELLS;
   LATE-PHASE; HIPPOCAMPAL-NEURONS; DROSOPHILA-MELANOGASTER; PROTEIN
   EXPRESSION; HSP70 GENE; IN-VIVO; P-TEFB
AB Transcription of immediate early genes (IEGs) in neurons is highly sensitive to neuronal activity, but the mechanism underlying these early transcription events is largely unknown. We found that several IEGs, such as Arc (also known as Arg3.1), are poised for near-instantaneous transcription by the stalling of RNA polymerase II (Pol II) just downstream of the transcription start site in rat neurons. Depletion through RNA interference of negative elongation factor, a mediator of Pol II stalling, reduced the Pol II occupancy of the Arc promoter and compromised the rapid induction of Arc and other IEGs. In contrast, reduction of Pol II stalling did not prevent transcription of IEGs that were expressed later and largely lacked promoter-proximal Pol II stalling. Together, our data strongly indicate that the rapid induction of neuronal IEGs requires poised Pol II and suggest a role for this mechanism in a wide variety of transcription-dependent processes, including learning and memory.
C1 [Saha, Ramendra N.; Wissink, Erin M.; Bailey, Emma R.; Zhao, Meilan; Hwang, Ji-Yeon; Daigle, Kelly R.; Fenn, J. Daniel; Dudek, Serena M.] Natl Inst Environm Hlth Sci, Neurobiol Lab, US Natl Inst Hlth, Res Triangle Pk, NC 27709 USA.
   [Fargo, David C.] Natl Inst Environm Hlth Sci, Lib & Informat Serv, US Natl Inst Hlth, Res Triangle Pk, NC USA.
   [Adelman, Karen] Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, US Natl Inst Hlth, Res Triangle Pk, NC USA.
RP Dudek, SM (reprint author), Natl Inst Environm Hlth Sci, Neurobiol Lab, US Natl Inst Hlth, Res Triangle Pk, NC 27709 USA.
EM dudek@niehs.nih.gov
RI Saha, Ramendra/C-7000-2014; 
OI Saha, Ramendra/0000-0002-5494-2584; Dudek, Serena M./0000-0003-4094-8368
FU US National Institutes of Health, NIEHS [Z01 ES100221, Z01 ES101987]
FX We thank D. Armstrong, P. Wade and members of the Dudek laboratory for
   critical review of the manuscript, the National Institute of
   Environmental Health Sciences (NIEHS) Viral Vector Core for lentivirus
   preparations, the NIEHS Microarray Core for generating, processing and
   analyzing microarray data, the US National Institutes of Health
   Intramural Sequencing Center for ChIP-seq sample preparations and
   sequencing, and the NIEHS Imaging Center for assistance with confocal
   imaging. This research was supported by the Intramural Research Program
   of the US National Institutes of Health, NIEHS (Z01 ES100221 to S. M. D.
   and Z01 ES101987 to K.A.).
NR 46
TC 58
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U1 1
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD JUL
PY 2011
VL 14
IS 7
BP 848
EP U62
DI 10.1038/nn.2839
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 783KR
UT WOS:000292081700012
PM 21623364
ER

PT J
AU Komlodi-Pasztor, E
   Sackett, D
   Wilkerson, J
   Fojo, T
AF Komlodi-Pasztor, Edina
   Sackett, Dan
   Wilkerson, Julia
   Fojo, Tito
TI (Not) too early to say, "no targeting of mitosis!" Reply
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Letter
ID BREAST CARCINOMAS; TUMOR; APOPTOSIS; SURVIVAL; CANCER; INDEX
C1 [Komlodi-Pasztor, Edina; Wilkerson, Julia; Fojo, Tito] NCI, NIH, Bethesda, MD 20892 USA.
   [Sackett, Dan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Komlodi-Pasztor, E (reprint author), NCI, NIH, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM komlodie@mail.nih.gov
NR 13
TC 0
Z9 0
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD JUL
PY 2011
VL 8
IS 7
DI 10.1038/nrclinonc.2010.228-c2
PG 2
WC Oncology
SC Oncology
GA 784WG
UT WOS:000292188600014
ER

PT J
AU Love, PE
   Bhandoola, A
AF Love, Paul E.
   Bhandoola, Avinash
TI Signal integration and crosstalk during thymocyte migration and
   emigration
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID T-CELL DEVELOPMENT; COMMON LYMPHOID PROGENITORS; MOUSE BONE-MARROW;
   SPHINGOSINE 1-PHOSPHATE RECEPTOR; FETAL THYMUS COLONIZATION;
   HEMATOPOIETIC STEM-CELLS; CHEMOKINE RECEPTOR; NEGATIVE SELECTION;
   LINEAGE COMMITMENT; POSTNATAL THYMUS
AB The thymus produces self-tolerant functionally competent T cells. This process involves the import of multipotent haematopoietic progenitors that are then signalled to adopt the T cell fate. Expression of T cell-specific genes, including those encoding the T cell receptor (TCR), is followed by positive and negative selection and the eventual export of mature T cells. Significant progress has been made in elucidating the signals that direct progenitor cell trafficking to, within and out of the thymus. These advances are the subject of this Review, with a particular focus on the role of reciprocal cooperative and regulatory interactions between TCR- and chemokine receptor-mediated signalling.
C1 [Love, Paul E.] Eunice Kennedy Schriver Natl Inst Child Hlth & Hu, NIH, Bethesda, MD USA.
   [Bhandoola, Avinash] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
RP Love, PE (reprint author), Eunice Kennedy Schriver Natl Inst Child Hlth & Hu, NIH, Bethesda, MD USA.
EM lovep@mail.nih.gov
FU US National Institutes of Health [AI059621, RC1HL099758]; Leukemia and
   Lymphoma Society
FX The authors thank Y. Takahama, J. C. Zuniga-Pflucker, D. A. Zlotoff, S.
   Zhang, R. Lesourne, L. Li and K. Pfeifer for critical reading of and
   helpful suggestions on the manuscript. A. B. was supported by US
   National Institutes of Health grants AI059621 and RC1HL099758, and a
   Scholar Award from the Leukemia and Lymphoma Society.
NR 115
TC 70
Z9 75
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD JUL
PY 2011
VL 11
IS 7
BP 469
EP 477
DI 10.1038/nri2989
PG 9
WC Immunology
SC Immunology
GA 782QS
UT WOS:000292025300012
PM 21701522
ER

PT J
AU Hezroni, H
   Tzchori, I
   Davidi, A
   Mattout, A
   Biran, A
   Nissim-Rafinia, M
   Westphal, H
   Meshorer, E
AF Hezroni, Hadas
   Tzchori, Itai
   Davidi, Anna
   Mattout, Anna
   Biran, Alva
   Nissim-Rafinia, Malka
   Westphal, Heiner
   Meshorer, Eran
TI H3K9 histone acetylation predicts pluripotency and reprogramming
   capacity of ES cells
SO NUCLEUS
LA English
DT Article
DE chromatin plasticity; embryonic stem cells; histone acetylation; histone
   modifications
AB The pluripotent genome is characterized by unique epigenetic features and a decondensed chromatin conformation. However, the relationship between epigenetic regulation and pluripotency is not altogether clear. Here, using an enhanced MEF/ESC fusion protocol, we compared the reprogramming potency and histone modifications of different embryonic stem cell (ESC) lines (R1, J1, E14, C57BL/6) and found that E14 ESCs are significantly less potent, with significantly reduced H3K9ac levels. Treatment of E14 ESCs with histone deacetylase (HDAC) inhibitors (HDACi) increased H3K9ac levels and restored their reprogramming capacity. Microarray and H3K9ac ChIP-seq analyses, suggested increased extracellular matrix (ECM) activity following HDACi treatment in E14 ESCs. These data suggest that H3K9ac may predict pluripotency and that increasing pluripotency by HDAC inhibition acts through H3K9ac to enhance the activity of target genes involved in ECM production to support pluripotency.
C1 [Hezroni, Hadas; Mattout, Anna; Biran, Alva; Nissim-Rafinia, Malka; Meshorer, Eran] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel.
   [Tzchori, Itai; Davidi, Anna; Westphal, Heiner] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA.
RP Westphal, H (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA.
EM hw@mail.nih.gov; meshorer@cc.huji.ac.il
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development/NIH/HHS; Israel Science Foundation [215/07, 943/09]; Israel
   Ministry of Health [6007]; EU [IRG-206872, 238176]; ICRF; HUJI; Israeli
   Psychobiology Institute; Alon Fellowship
FX The authors would like to thank Asher Meshorer for histopathological
   analyses and Evgenia Leikina for technical assistant with the fusion
   protocols and for helpful comments. This work was supported by funds
   from the intramural research program of the Eunice Kennedy Shriver
   National Institute of Child Health and Human Development/NIH/HHS, the
   Israel Science Foundation (215/07 and 943/09) (to E.M.); the Israel
   Ministry of Health (6007) (to E.M.), the EU (IRG-206872 and 238176) (to
   E.M.), the ICRF (to A.M. and E.M.), The HUJI Internal Applicative
   Medical Grants (to E.M.), the Israeli Psychobiology Institute (to E.M.)
   and an Alon Fellowship (to E.M.). E.M. is a Joseph H. and Belle R. Braun
   Senior Lecturer in Life Sciences. H.H. is an Edmond J. Safra Fellow.
NR 44
TC 32
Z9 32
U1 0
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1949-1034
EI 1949-1042
J9 NUCLEUS-PHILA
JI Nucleus
PD JUL-AUG
PY 2011
VL 2
IS 4
BP 300
EP 309
DI 10.4161/nucl.2.4.16767
PG 10
WC Cell Biology
SC Cell Biology
GA V28GK
UT WOS:000208669100014
PM 21941115
ER

PT J
AU Grady, PA
AF Grady, Patricia A.
TI Advancing the health of our aging population: A lead role for nursing
   science
SO NURSING OUTLOOK
LA English
DT Editorial Material
C1 NINR, NIH, Bethesda, MD 20892 USA.
RP Grady, PA (reprint author), NINR, NIH, 31 Ctr Dr,Room 5B-10, Bethesda, MD 20892 USA.
EM info@ninr.nih.gov
FU Intramural NIH HHS [Z99 NR999999]
NR 5
TC 8
Z9 8
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0029-6554
J9 NURS OUTLOOK
JI Nurs. Outlook
PD JUL-AUG
PY 2011
VL 59
IS 4
SI SI
BP 207
EP 209
DI 10.1016/j.outlook.2011.05.017
PG 3
WC Nursing
SC Nursing
GA 797IY
UT WOS:000293118900009
PM 21757076
ER

PT J
AU Wickersham, K
   Colbert, A
   Caruthers, D
   Tamres, L
   Martino, A
   Erlen, JA
AF Wickersham, Karen
   Colbert, Alison
   Caruthers, Donna
   Tamres, Lisa
   Martino, Angela
   Erlen, Judith A.
TI Assessing Fidelity to an Intervention in a Randomized Controlled Trial
   to Improve Medication Adherence
SO NURSING RESEARCH
LA English
DT Article
DE HIV infection; intervention fidelity; medication adherence
ID BEHAVIOR-CHANGE; RECOMMENDATIONS
AB Background: Behavioral intervention effectiveness in randomized controlled trials requires fidelity to the protocol. Fidelity assessment tools tailored to the intervention may strengthen intervention research.
   Objective: The aim of this study was to describe the assessment of fidelity to the structured intervention protocol in an examination of a nurse-delivered telephone intervention designed to improve medication adherence.
   Methods: Fidelity assessment included random selection and review of approximately 10% of the audiorecorded intervention sessions, stratified by interventionist and intervention session. Audiotapes were reviewed along with field notes for percentage of agreement, addressing whether key components were covered during the sessions. Visual analog scales were used to provide summary scores (0 = low to 5 = high) of interaction characteristics of the interventionists and participants with respect to engagement, demeanor, listening skills, attentiveness, and openness.
   Results: Four nurse interventionists delivered 871 structured intervention sessions to 113 participants. Three trained graduate student researchers assessed 131 intervention sessions. The mean percentage of agreement was 92.0% (+/-10.5%), meeting the criteria of 90% congruence with the intervention protocol. The mean interventionist interaction summary score was 4.5 +/- 0.4, and the mean participant interaction summary score was 4.5 +/- 0.4.
   Discussion: Overall, the interventionists successfully delivered the structured intervention content, with some variability in both the percentage of agreement and quality of interaction scores. Ongoing assessment aids in ensuring fidelity to study protocol and having reliable study results.
C1 [Wickersham, Karen; Caruthers, Donna; Tamres, Lisa; Erlen, Judith A.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA.
   [Colbert, Alison] Duquesne Univ, Sch Nursing, Pittsburgh, PA 15219 USA.
   [Martino, Angela] NINR, NIH, Bethesda, MD 20892 USA.
RP Wickersham, K (reprint author), Univ Pittsburgh, Sch Nursing, 440 Victoria Bldg,3500 Victoria St, Pittsburgh, PA 15261 USA.
EM kew44@pitt.edu
FU National Institute for Nursing Research [2R01-NR004749]
FX Funding for this study was provided by the National Institute for
   Nursing Research (2R01-NR004749) to Judith A. Erlen, PhD, RN, FAAN
   (Principal Investigator). This paper was presented at the 22nd Annual
   Scientific Sessions of the Eastern Nursing Research Society in
   Providence, Rhode Island, on March 26, 2010.
NR 14
TC 8
Z9 8
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-6562
J9 NURS RES
JI Nurs. Res.
PD JUL-AUG
PY 2011
VL 60
IS 4
BP 264
EP 269
DI 10.1097/NNR.0b013e318221b6e6
PG 6
WC Nursing
SC Nursing
GA 786DB
UT WOS:000292282400008
PM 21677597
ER

PT J
AU Yanovski, JA
AF Yanovski, Jack A.
TI Intervening During Infancy to Prevent Pediatric Obesity
SO OBESITY
LA English
DT Editorial Material
ID CHILDHOOD OBESITY; GROWTH
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
EM jy15i@nih.gov
OI Yanovski, Jack/0000-0001-8542-1637
FU Intramural NIH HHS
NR 8
TC 7
Z9 7
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD JUL
PY 2011
VL 19
IS 7
BP 1321
EP 1322
DI 10.1038/oby.2010.235
PG 2
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 784CU
UT WOS:000292132300001
PM 21706036
ER

PT J
AU Skeens, HM
   Brooks, BP
   Holland, EJ
AF Skeens, Heather M.
   Brooks, Brian P.
   Holland, Edward J.
TI Congenital Aniridia Variant: Minimally Abnormal Irides with Severe
   Limbal Stem Cell Deficiency
SO OPHTHALMOLOGY
LA English
DT Article
ID AUTOSOMAL-DOMINANT KERATITIS; PAX6 GENE; MUTATION; DEFECTS
AB Purpose: To clinically and molecularly characterize a group of patients with progressive limbal stem cell deficiency (LSCD) due to aniridic keratopathy (AK), but with minimally affected irides.
   Design: Retrospective case series.
   Participants: A total of 12 eyes of 6 patients who underwent keratolimbal allograft (KLAL) for AK in the absence of the classic stigmata of aniridia at the Cincinnati Eye Institute/University of Cincinnati between 2000 and 2007.
   Methods: Retrospective chart review.
   Main Outcome Measures: Ocular surface stability after KLAL and change in visual acuity.
   Results: Subjects' mean age was 32.57 years, 66% were female, and mean follow-up was 64.4 months (range, 20-115 months). All patients presented with a decline in their vision secondary to LSCD. Average preoperative best-corrected visual acuity (BCVA) logarithm of the minimum angle of resolution (logMAR) was 1.4 (range, 0.10-2.8). All patients had minimally affected irides with subtle abnormal findings, including ectropion uveae and stromal atrophy. All patients developed severe LSCD and required KLAL. Average postoperative logMAR BCVA was 0.35 (range, 0.00-1.00). All ocular surfaces remained stable throughout the follow-up period. Family history consistent with autosomal dominant inheritance was positive in 4 of 6 patients. PAX6 genetic testing identified 2 pathologic mutations and 1 possible disease-causing variant.
   Conclusions: Aniridic keratopathy may present in the absence of other classic stigmata of aniridia and be associated with minimally affected irides. A subset of these patients has definitive mutations in PAX6 and once identified can be counseled appropriately. These patients respond well to KLAL and may therefore benefit from early detection.
C1 [Skeens, Heather M.] Med Univ S Carolina, Storm Eye Inst, Charleston, SC 29425 USA.
   [Brooks, Brian P.] NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA.
   [Holland, Edward J.] Univ Cincinnati, Cincinnati Eye Inst, Cincinnati, OH USA.
RP Skeens, HM (reprint author), Med Univ S Carolina, Storm Eye Inst, 167 Ashley Ave,MSC 676, Charleston, SC 29425 USA.
EM skeens@musc.edu
NR 9
TC 9
Z9 10
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2011
VL 118
IS 7
BP 1260
EP 1264
DI 10.1016/j.ophtha.2010.11.021
PG 5
WC Ophthalmology
SC Ophthalmology
GA 786JL
UT WOS:000292303000006
PM 21376398
ER

PT J
AU Whitson, EL
   Pluchino, KM
   Hall, MD
   McMahon, JB
   Mckee, TC
AF Whitson, Emily L.
   Pluchino, Kristen M.
   Hall, Matthew D.
   McMahon, James B.
   McKee, Tawnya C.
TI New Candidaspongiolides, Tedanolide Analogues That Selectively Inhibit
   Melanoma Cell Growth
SO ORGANIC LETTERS
LA English
DT Article
ID SPONGE MYCALE-ADHAERENS; CYTOTOXIC METABOLITES; ANTITUMOR MACROLIDE;
   13-DEOXYTEDANOLIDE; MYRIAPORONES; APOPTOSIS; POTENT
AB Extracts of the sponge genus Candidaspongia showed selective cytotoxicity toward melanoma cells in the NCI 60-cell-line screen. Continued investigation of the Candidaspongia sp. extracts led to the isolation of three new tedanolide analogues, precandidaspongiolides A (1) and B (2) and candidaspongiolide B (4), as well as candidaspongiolide A (3) and tedanolide (5). Semisynthetic derivatives were also generated to develop SAR. Candidaspongiolides A/B were the most potent and showed low nanomolar activity against several melanoma cell lines.
C1 [Whitson, Emily L.; McMahon, James B.; McKee, Tawnya C.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
   [Pluchino, Kristen M.; Hall, Matthew D.] NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Mckee, TC (reprint author), NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM mckeeta@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank P. Colin (CRRF) for sustained collecting efforts; P. Bergquist
   (U. of Auckland, deceased) and S. Sorokin (SARDI) for taxonomic analysis
   of the sponge samples; D. Newman (NPB) for contract collection; T.
   McCloud (NPSG) for extraction; and S. Tarasov and M. Dyba (Biophysics
   Resource Core, SBL, CCR) for assistance with high-resolution mass
   spectrometry. This research was supported by the Intramural Research
   Program of the NIH, National Cancer Institute, Center for Cancer
   Research.
NR 13
TC 16
Z9 16
U1 0
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1523-7060
J9 ORG LETT
JI Org. Lett.
PD JUL 1
PY 2011
VL 13
IS 13
BP 3518
EP 3521
DI 10.1021/ol201329p
PG 4
WC Chemistry, Organic
SC Chemistry
GA 781HG
UT WOS:000291920800059
PM 21644548
ER

PT J
AU Pearce, MS
   Salotti, JA
   McHugh, K
   Metcalf, W
   Kim, KP
   Craft, AW
   Parker, L
   Ron, E
AF Pearce, Mark S.
   Salotti, Jane A.
   McHugh, Kieran
   Metcalf, Wenhua
   Kim, Kwang P.
   Craft, Alan W.
   Parker, Louise
   Ron, Elaine
TI CT scans in young people in Northern England: trends and patterns
   1993-2002
SO PEDIATRIC RADIOLOGY
LA English
DT Article
DE Radiation dose; Computed tomography; Trends; Child
ID COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; CANCER-RISKS;
   PEDIATRIC-PATIENTS; HELICAL CT; X-RAY; CHILDREN; TRAUMA; UTILITY; BODY
AB Although CT can be greatly beneficial, its relatively high radiation doses have caused public health concerns.
   To assess patterns in CT usage among patients aged less than 22 years in Northern England during the period 1993-2002.
   Electronic data were obtained from radiology information systems of all nine National Health Service trusts in the region.
   A total of 38,681 scans had been performed in 20,483 patients aged less than 22 years. The number of CT examinations rose, with the steepest increase between 1997 and 2000. The number of patients scanned per year increased less dramatically, with 2.24/1,000 population aged less than 22 years having one scan or more in 1993 compared to 3.54/1,000 in 2002. This reflects an increase in the median number of scans per patient, which rose from 1 in 1993 to 2 by 1999. More than 70% of CT examinations were of the head, with the number of head examinations varying with time and patient age.
   The frequency of CT scans in this population more than doubled during the study period. This is partly, but not wholly, explained by an increase in the number of scans per patient.
C1 [Pearce, Mark S.; Salotti, Jane A.; Metcalf, Wenhua] Newcastle Univ, Royal Victoria Infirm, Sir James Spence Inst, Inst Hlth & Soc, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
   [McHugh, Kieran] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
   [Kim, Kwang P.] Kyung Hee Univ, Dept Nucl Engn, Gyeonggi Do, South Korea.
   [Craft, Alan W.] Newcastle Univ, Royal Victoria Infirm, Sir James Spence Inst, No Inst Canc Res, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
   [Parker, Louise] Dalhousie Univ, Populat Canc Res Program, Dept Med, Halifax, NS, Canada.
   [Parker, Louise] Dalhousie Univ, Populat Canc Res Program, Dept Paediat, Halifax, NS, Canada.
   [Parker, Louise] Canc Care Nova Scotia, Halifax, NS, Canada.
   [Ron, Elaine] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Pearce, MS (reprint author), Newcastle Univ, Royal Victoria Infirm, Sir James Spence Inst, Inst Hlth & Soc, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
EM m.s.pearce@ncl.ac.uk
FU United States National Cancer Institute [NO2-CP-75501]; United Kingdom
   Department of Health
FX This study was supported by contract NO2-CP-75501 from the United States
   National Cancer Institute and through funding from the Radiation
   Research Programme of the United Kingdom Department of Health. We thank
   the staff in radiology departments across the Northern Region of England
   who contributed data to this study and Mrs. Katharine Kirton and Mr.
   Richard Hardy for their assistance with the study. We also thank Dr.
   John Kotre for his comments on the paper.
NR 35
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U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-0449
EI 1432-1998
J9 PEDIATR RADIOL
JI Pediatr. Radiol.
PD JUL
PY 2011
VL 41
IS 7
BP 832
EP 838
DI 10.1007/s00247-011-2110-7
PG 7
WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging
GA 784OT
UT WOS:000292167300006
PM 21594548
ER

PT J
AU Raju, TNK
   Suresh, G
   Higgins, RD
AF Raju, Tonse N. K.
   Suresh, Gautham
   Higgins, Rosemary D.
TI Patient Safety in the Context of Neonatal Intensive Care: Research and
   Educational Opportunities
SO PEDIATRIC RESEARCH
LA English
DT Article
ID MEDICATION ERRORS; ADVERSE EVENTS; WORK HOURS; UNIT; FOCUS; MANAGEMENT;
   CHECKLIST; RISK; TIME
AB Case reports and observational studies continue to report adverse events from medical errors. However, despite considerable attention to patient safety in the popular media, this topic is not a regular component of medical education, and much research needs to be carried out to understand the causes, consequences, and prevention of healthcare-related adverse events during neonatal intensive care. To address the knowledge gaps and to formulate a research and educational agenda in neonatology, the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited a panel of experts to a workshop in August 2010. Patient safety issues discussed were the reasons for errors, including systems design, working conditions, and worker fatigue; a need to develop a "culture" of patient safety; the role of electronic medical records, information technology, and simulators in reducing errors; error disclosure practices; medicolegal concerns; and educational needs. Specific neonatology-related topics discussed were errors during resuscitation, mechanical ventilation, and performance of invasive procedures; medication errors including those associated with milk feedings; diagnostic errors; and misidentification of patients. This article provides an executive summary of the workshop. (Pediatr Res 70: 109-115, 2011)
C1 [Raju, Tonse N. K.; Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20952 USA.
   [Suresh, Gautham] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03756 USA.
RP Raju, TNK (reprint author), NICHD, 6100 Execut Blvd,Room 4B03, Bethesda, MD 20892 USA.
EM rajut@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 43
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U1 2
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0031-3998
EI 1530-0447
J9 PEDIATR RES
JI Pediatr. Res.
PD JUL
PY 2011
VL 70
IS 1
BP 109
EP 115
DI 10.1203/PDR.0b013e3182182853
PG 7
WC Pediatrics
SC Pediatrics
GA 782MZ
UT WOS:000292015100020
PM 21386749
ER

PT J
AU Shankaran, S
   Pappas, A
   McDonald, SA
   Laptook, AR
   Bara, R
   Ehrenkranz, RA
   Tyson, JE
   Goldberg, R
   Donovan, EF
   Fanaroff, AA
   Das, A
   Poole, WK
   Walsh, M
   Higgins, RD
   Welsh, C
   Salhab, W
   Carlo, WA
   Poindexter, B
   Stoll, BJ
   Guillet, R
   Finer, NN
   Stevenson, DK
   Bauer, CR
AF Shankaran, Seetha
   Pappas, Athina
   McDonald, Scott A.
   Laptook, Abbot R.
   Bara, Rebecca
   Ehrenkranz, Richard A.
   Tyson, Jon E.
   Goldberg, Ronald
   Donovan, Edward F.
   Fanaroff, Avroy A.
   Das, Abhik
   Poole, W. Kenneth
   Walsh, Michele
   Higgins, Rosemary D.
   Welsh, Cherie
   Salhab, Walid
   Carlo, Waldemar A.
   Poindexter, Brenda
   Stoll, Barbara J.
   Guillet, Ronnie
   Finer, Neil N.
   Stevenson, David K.
   Bauer, Charles R.
CA Eunice Kennedy Shriver Natl Inst C
TI Predictive Value of an Early Amplitude Integrated Electroencephalogram
   and Neurologic Examination
SO PEDIATRICS
LA English
DT Article
DE neonatal hypoxic-ischemic encephalopathy; amplitude integrated EEG
ID HYPOXIC-ISCHEMIC ENCEPHALOPATHY; FULL-TERM INFANTS; NEONATAL
   ENCEPHALOPATHY; PROGNOSTIC VALUE; SYSTEMIC HYPOTHERMIA; BIRTH ASPHYXIA;
   EEG; NEUROPROTECTION; NEWBORNS; OUTCOMES
AB OBJECTIVE: To examine the predictive validity of the amplitude integrated electroencephalogram (aEEG) and stage of encephalopathy among infants with hypoxic-ischemic encephalopathy (HIE) eligible for therapeutic whole-body hypothermia.
   DESIGN: Neonates were eligible for this prospective study if moderate or severe HIE occurred at <6 hours and an aEEG was obtained at <9 hours of age. The primary outcome was death or moderate/severe disability at 18 months.
   RESULTS: There were 108 infants (71 with moderate HIE and 37 with severe HIE) enrolled in the study. aEEG findings were categorized as normal, with continuous normal voltage (n = 12) or discontinuous normal voltage (n = 12), or abnormal, with burst suppression (n = 22), continuous low voltage (n = 26), or flat tracing (n = 36). At 18 months, 53 infants (49%) experienced death or disability. Severe HIE and an abnormal aEEG were related to the primary outcome with univariate analysis, whereas severe HIE alone was predictive of outcome with multivariate analysis. Addition of aEEG pattern to HIE stage did not add to the predictive value of the model; the area under the curve changed from 0.72 to 0.75 (P = .19).
   CONCLUSIONS: The aEEG background pattern did not significantly enhance the value of the stage of encephalopathy at study entry in predicting death and disability among infants with HIE. Pediatrics 2011; 128:e112-e120
C1 [Shankaran, Seetha; Pappas, Athina; Bara, Rebecca] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
   [McDonald, Scott A.; Das, Abhik; Poole, W. Kenneth] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
   [Laptook, Abbot R.] Brown Univ, Dept Pediat, Women & Infants Hosp, Providence, RI 02912 USA.
   [Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
   [Tyson, Jon E.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
   [Goldberg, Ronald] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
   [Donovan, Edward F.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA.
   [Fanaroff, Avroy A.; Walsh, Michele] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA.
   [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
   [Welsh, Cherie] Wake Forest Univ, Dept Pediat, Winston Salem, NC 27109 USA.
   [Salhab, Walid] Univ Texas SW Med Ctr, Dept Pediat, Dallas, TX USA.
   [Carlo, Waldemar A.] Univ Alabama, Dept Pediat, Birmingham, AL USA.
   [Poindexter, Brenda] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA.
   [Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
   [Guillet, Ronnie] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA.
   [Finer, Neil N.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA.
   [Stevenson, David K.] Stanford Univ, Dept Pediat, Palo Alto, CA 94304 USA.
   [Bauer, Charles R.] Univ Miami, Dept Pediat, Miami, FL 33152 USA.
RP Shankaran, S (reprint author), Childrens Hosp Michigan, 3901 Beaubien St,4 H46, Detroit, MI 48201 USA.
EM sshankar@med.wayne.edu
FU National Institutes of Health; NICHD
FX This work was supported by the National Institutes of Health and the
   NICHD. Participating NICHD NRN sites collected data and transmitted them
   to RTI International, the data-coordinating center for the network,
   which stored, managed, and analyzed the data for this study. On behalf
   of the NRN, Drs Das (PI) and Poole, and Mr McDonald (statistician) had
   full access to all the data in the study and take responsibility for the
   integrity of the data and accuracy of the data analysis.
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PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD JUL
PY 2011
VL 128
IS 1
BP E112
EP E120
DI 10.1542/peds.2010-2036
PG 9
WC Pediatrics
SC Pediatrics
GA 786IV
UT WOS:000292299500015
PM 21669899
ER

PT J
AU Rinker, JA
   Hutchison, MA
   Chen, SA
   Thorsell, A
   Heilig, M
   Riley, AL
AF Rinker, Jennifer A.
   Hutchison, Mary Anne
   Chen, Scott A.
   Thorsell, Annika
   Heilig, Markus
   Riley, Anthony L.
TI Exposure to nicotine during periadolescence or early adulthood alters
   aversive and physiological effects induced by ethanol
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE Periadolescence; Preexposure; Nicotine; Conditioned taste aversion;
   Alcohol; Rats
ID CONDITIONED TASTE-AVERSION; ACCUMBAL DOPAMINE OVERFLOW; STIMULUS
   PROPERTIES; EPIDEMIOLOGIC SURVEY; CIGARETTE-SMOKING; PLACE PREFERENCE;
   SEX-DIFFERENCES; C57BL/6 MICE; BRAIN LEVELS; RAT STRAINS
AB The majority of smokers begin their habit during adolescence, which often precedes experimentation with alcohol. Interestingly, very little preclinical work has been done examining how exposure to nicotine during periadolescence impacts the affective properties of alcohol in adulthood. Understanding how periadolescent nicotine exposure influences the aversive effects of alcohol might help to explain why it becomes more acceptable to this preexposed population. Thus, Experiment 1 exposed male Sprague Dawley rats to either saline or nicotine (0.4 mg/kg, IP) from postnatal days 34 to 43 (periadolescence) and then examined changes in the aversive effects of alcohol (0, 0.56, 1.0 and 1.8 g/kg. IP) in adulthood using the conditioned taste aversion (CIA) design. Changes in blood alcohol concentration (BAC) as well as alcohol-induced hypothermia and locomotor suppression were also assessed. To determine if changes seen were specific to nicotine exposure during periadolescence, the procedures were replicated in adults (Experiment 2). Preexposure to nicotine during periadolescence attenuated the acquisition of the alcohol-induced CTAs (at 1.0 g/kg) and the hypothermic effects of alcohol (1.0 g/kg). Adult nicotine preexposure produced similar attenuation in alcohol's aversive (at 1.8 g/kg) and hypothermic (1.8 g/kg) effects. Neither adolescent nor adult nicotine preexposure altered BACs or alcohol-induced locomotor suppression. These results suggest that nicotine may alter the aversive and physiological effects of alcohol, regardless of the age at which exposure occurs, possibly increasing its overall reinforcing value and making it more likely to be consumed. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Rinker, Jennifer A.; Hutchison, Mary Anne; Riley, Anthony L.] American Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA.
   [Chen, Scott A.] Natl Inst Drug Abuse, NIH, Rockville, MD USA.
   [Thorsell, Annika; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, Sect Mol Pathophysiol, NIH, Bethesda, MD USA.
RP Rinker, JA (reprint author), American Univ, Dept Psychol, Psychopharmacol Lab, 4400 Massachusetts Ave NW, Washington, DC 20016 USA.
EM jennifer.rinker@gmail.com
OI Heilig, Markus/0000-0003-2706-2482; Rinker,
   Jennifer/0000-0003-3738-3693; Thorsell, Annika/0000-0003-3535-3845
FU Mellon Foundation; National Institute on Alcohol Abuse and Alcoholism,
   National Institutes of Health, Public Health Service, US Department of
   Health and Human Services
FX We owe a great deal of thanks to Erick Singley for his technical
   expertise and time in analyzing samples on the gas chromatograph. This
   research was supported by a grant from the Mellon Foundation to A.L.R.
   and intramural funds from the National Institute on Alcohol Abuse and
   Alcoholism, National Institutes of Health, Public Health Service, US
   Department of Health and Human Services.
NR 88
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U2 6
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 JUL
PY 2011
VL 99
IS 1
BP 7
EP 16
DI 10.1016/j.pbb.2011.03.009
PG 10
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 781DD
UT WOS:000291909900002
PM 21420998
ER

PT J
AU Liu, MM
   Tuo, JS
   Chan, CC
AF Liu, Melissa M.
   Tuo, Jingsheng
   Chan, Chi-Chao
TI Republished review: Gene therapy for ocular diseases
SO POSTGRADUATE MEDICAL JOURNAL
LA English
DT Review
ID EPITHELIUM-DERIVED FACTOR; CILIARY NEUROTROPHIC FACTOR; LEBER CONGENITAL
   AMAUROSIS; RETINAL GANGLION-CELLS; INHIBITS CHOROIDAL
   NEOVASCULARIZATION; BOVINE IMMUNODEFICIENCY VIRUS; ADENOASSOCIATED VIRAL
   VECTOR; ADENOVIRUS-MEDIATED DELIVERY; RCS RAT MODEL; MOUSE MODEL
AB The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus-and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.
C1 [Liu, Melissa M.; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20895 USA.
RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Rm 10N103, Bethesda, MD 20895 USA.
EM chanc@nei.nih.gov
OI Tuo, Jingsheng/0000-0002-1372-7810
FU NEI; American Health Assistance Foundation [M2007037]; National
   Institutes of Health
FX This work was supported by the NEI Intramural Research Program and the
   American Health Assistance Foundation (M2007037). Other Funders:
   National Institutes of Health.
NR 104
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PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0032-5473
J9 POSTGRAD MED J
JI Postgrad. Med. J.
PD JUL
PY 2011
VL 87
IS 1029
BP 487
EP 495
DI 10.1136/pgmj.2009.174912rep
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 782TV
UT WOS:000292035700010
PM 21705775
ER

PT J
AU Palumbo, S
   Toscano, CD
   Parente, L
   Weigert, R
   Bosetti, F
AF Palumbo, S.
   Toscano, C. D.
   Parente, L.
   Weigert, R.
   Bosetti, F.
TI Time-dependent changes in the brain arachidonic acid cascade during
   cuprizone-induced demyelination and remyelination
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE Phospholipases A(2); Eicosanoids; Demyelination; Arachidonic acid;
   Cuprizone
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM;
   CYTOSOLIC PHOSPHOLIPASE A(2); MULTIPLE-SCLEROSIS; GENE-EXPRESSION;
   WHITE-MATTER; IN-VIVO; CYCLOOXYGENASE-2; INHIBITORS; MICE
AB Phospholipases A(2) (PLA(2)) are the enzymatic keys for the activation of the arachidonic acid (AA) cascade and the subsequent synthesis of pro-inflammatory prostanoids (prostaglandins and tromboxanes). Prostanoids play critical roles in the initiation and modulation of inflammation and their levels have been reported increased in several neurological and neurodegenerative disorders, including multiple sclerosis (MS).
   Here, we aimed to determine whether brain expression PLA(2) enzymes and the terminal prostagland in levels are changed during cuprizone-induced demyelination and in the subsequent remyelination phase.
   Mice were given the neurotoxicant cuprizone through the diet for six weeks to induce brain demyelination. Then, cuprizone was withdrawn and mice were returned to a normal diet for 6 weeks to allow spontaneous remyelination.
   We found that after 4-6 weeks of cuprizone, sPLA(2)(V) and cPLA(2), but not iPLA(2)(VI), gene expression was upregulated in the cortex, concomitant with an increase in the expression of astrocyte and microglia markers. Cyclooxygenase (COX)-2 gene expression was consistently upregulated during all the demyelination period, whereas COX-1 sporadically increased only at week 5 of cuprizone exposure. However, we found that at the protein level only sPLA(2)(V) and COX-1 were elevated during demyelination, with COX-1 selectively expressed by activated and infiltrated microglia/macrophages and astrocytes. Levels of PGE(2), PGD(2), PGI(2) and TXB(2) were also increased during demyelination. During remyelination, none of the PLA(2) isoforms was significantly changed, whereas COX-1 and -2 were sporadically upregulated only at the gene expression level. PGE(2), PGI(2) and PGD(2) levels returned to normal, whereas TXB(2) was still upregulated after 3 weeks of cuprizone withdrawal.
   Our study characterizes for the first time time-dependent changes in the AA metabolic pathway during cuprizone-induced demyelination and the subsequent remyelination and suggests that sPLA(2)(V) is the major isoform contributing to AA release. Published by Elsevier Ltd.
C1 [Palumbo, S.; Toscano, C. D.; Bosetti, F.] NIA, NIH, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA.
   [Parente, L.; Weigert, R.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
RP Bosetti, F (reprint author), NIA, NIH, Brain Physiol & Metab Sect, 9 Mem Dr,Bldg 9,Rm 1S126, Bethesda, MD 20892 USA.
EM frances@mail.nih.gov
RI palumbo, sara/B-1603-2013
OI palumbo, sara/0000-0002-3809-6058
FU NIH, National Institute on Aging and National Institute of Dental and
   Craniofacial Research
FX This research was supported by the Intramural Research Program of the
   NIH, National Institute on Aging and National Institute of Dental and
   Craniofacial Research.
NR 34
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD JUL
PY 2011
VL 85
IS 1
BP 29
EP 35
DI 10.1016/j.plefa.2011.04.001
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
   Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
   Metabolism
GA 785NS
UT WOS:000292236300004
PM 21530210
ER

PT J
AU Yoshikawa, K
   Palumbo, S
   Toscano, CD
   Bosetti, F
AF Yoshikawa, K.
   Palumbo, S.
   Toscano, C. D.
   Bosetti, F.
TI Inhibition of 5-lipoxygenase activity in mice during cuprizone-induced
   demyelination attenuates neuroinflammation, motor dysfunction and axonal
   damage
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article
DE 5-Lipoxygenase; Leukotriene; Multiple sclerosis; Cuprizone;
   Demyelination; Neuroinflammation; Axonal damage
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC
   ENCEPHALOMYELITIS; SPINAL-CORD-INJURY; MULTIPLE-SCLEROSIS LESIONS;
   CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION;
   LINOLEIC-ACID; GLUTAMATE EXCITOTOXICITY; INFLAMMATORY RESPONSE
AB Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Increased expression of 5-lipoxygenase (5-LO), a key enzyme in the biosynthesis of leukotrienes (LTs), has been reported in MS lesions and LT levels are elevated in the cerebrospinal fluid of MS patients. To determine whether pharmacological inhibition of 5-LO attenuates demyelination, MK886, a 5-LO inhibitor, was given to mice fed with cuprizone. Gene and protein expression of 5-LO were increased at the peak of cuprizone-induced demyelination. Although MK886 did not attenuate cuprizone-induced demyelination in the corpus callosum or in the cortex, it attenuated cuprizone-induced axonal damage and motor deficits and reduced microglial activation and IL-6 production. These data suggest that during cuprizone-induced demyelination, the 5-LO pathway contributes to microglial activation and neuroinflammation and to axonal damage resulting in motor dysfunction. Thus, 5-LO inhibition may be a useful therapeutic treatment in demyelinating diseases of the CNS. Published by Elsevier Ltd.
C1 [Yoshikawa, K.; Palumbo, S.; Toscano, C. D.; Bosetti, F.] NIA, Mol Neurosci Unit, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Bosetti, F (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Ctr Neurosci, Room 2118,6001 Execut Blvd, Bethesda, MD 20892 USA.
EM frances@mail.nih.gov
RI palumbo, sara/B-1603-2013
OI palumbo, sara/0000-0002-3809-6058
FU NIH, National Institute on Aging
FX This work was supported by Intramural Research Program of NIH, National
   Institute on Aging. We thank Drs. Sang-Ho Choi and Saba Aid for helpful
   discussion and technical advice. We thank Dr. Anthony Donsante for
   kindly providing the rotarod apparatus. We thank Drs. Mukoyama and
   Onitsuka for kindly providing the confocal microscope and technical
   advice.
NR 67
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD JUL
PY 2011
VL 85
IS 1
BP 43
EP 52
DI 10.1016/j.plefa.2011.04.022
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
   Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
   Metabolism
GA 785NS
UT WOS:000292236300006
PM 21555210
ER

PT J
AU Pletneva, NV
   Pletnev, VZ
   Shemiakina, II
   Chudakov, DM
   Artemyev, I
   Wlodawer, A
   Dauter, Z
   Pletnev, S
AF Pletneva, Nadya V.
   Pletnev, Vladimir Z.
   Shemiakina, Irina I.
   Chudakov, Dmitriy M.
   Artemyev, Igor
   Wlodawer, Alexander
   Dauter, Zbigniew
   Pletnev, Sergei
TI Crystallographic study of red fluorescent protein eqFP578 and its
   far-red variant Katushka reveals opposite pH-induced isomerization of
   chromophore
SO PROTEIN SCIENCE
LA English
DT Article
DE fluorescent proteins; biomarkers; chromophore; gene-engineered variants;
   crystal structure
ID TRANS-CIS ISOMERIZATION; CRYSTAL-STRUCTURE; IN-VIVO; STRUCTURAL BASIS;
   WHOLE-BODY; MATURATION; EQFP611; CHROMOPROTEINS; REFINEMENT; RESOLUTION
AB The wild type red fluorescent protein eqFP578 (from sea anemone Entacmaea quadricolor, lambda(ex) = 552 nm, lambda(em) = 578 nm) and its bright far-red fluorescent variant Katushka (lambda(ex) = 588 nm, lambda(em) = 635 nm) are characterized by the pronounced pH dependence of their fluorescence. The crystal structures of eqFP578f (eqFP578 with two point mutations improving the protein folding) and Katushka have been determined at the resolution ranging from 1.15 to 1.85 angstrom at two pH values, corresponding to low and high level of fluorescence. The observed extinguishing of fluorescence upon reducing pH in eqFP578f and Katushka has been shown to be accompanied by the opposite trans-cis and cis-trans chromophore isomerization, respectively. Asn143, Ser158, His197 and Ser143, Leu174, and Arg197 have been shown to stabilize the respective trans and cis fluorescent states of the chromophores in eqFP578f and Katushka at higher pH. The cis state has been suggested as being primarily responsible for the observed far-red shift of the emission maximum of Katushka relative to that of eqFP578f.
C1 [Dauter, Zbigniew; Pletnev, Sergei] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA.
   [Pletneva, Nadya V.; Pletnev, Vladimir Z.; Shemiakina, Irina I.; Chudakov, Dmitriy M.; Artemyev, Igor] Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia.
   [Pletnev, Vladimir Z.; Pletnev, Sergei] SAIC Frederick, Basic Res Program, Argonne, IL 60439 USA.
   [Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
RP Pletnev, S (reprint author), NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, 9700 S Cass Ave,Bld 202,Q-134, Argonne, IL 60439 USA.
EM pletnevs@mail.nih.gov
RI Chudakov, Dmitriy/G-7741-2014; Pletneva, Nadya/F-7839-2014; Pletnev,
   Vladimir/Q-6151-2016
OI Chudakov, Dmitriy/0000-0003-0430-790X; 
FU U.S. Department of Energy, Office of Science, Office of Basic Energy
   Sciences [W-31-109-Eng-38]; National Cancer Institute, National
   Institutes of Health (NIH) [HHSN261200800001E]; NIH, National Cancer
   Institute, Center for Cancer Research; Russian Federation
   [MK-539.2011.4]; Russian Foundation for Basic Research [11-04-00241MCB
   RAS]
FX Grant sponsor: U.S. Department of Energy, Office of Science, Office of
   Basic Energy Sciences; Grant number: W-31-109-Eng-38; Grant sponsor:
   National Cancer Institute, National Institutes of Health (NIH); Grant
   number: HHSN261200800001E; Grant sponsor: NIH, National Cancer
   Institute, Center for Cancer Research; Intramural Research Program;
   Grant sponsor: President of the Russian Federation; Grant number:
   MK-539.2011.4; Grant sponsor: The Russian Foundation for Basic Research;
   Grant number: 11-04-00241MCB RAS.
NR 39
TC 12
Z9 12
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
EI 1469-896X
J9 PROTEIN SCI
JI Protein Sci.
PD JUL
PY 2011
VL 20
IS 7
BP 1265
EP 1274
DI 10.1002/pro.654
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 785UV
UT WOS:000292257600019
PM 21563226
ER

PT J
AU Midthune, D
   Schatzkin, A
   Subar, AF
   Thompson, FE
   Freedman, LS
   Carroll, RJ
   Shumakovich, MA
   Kipnis, V
AF Midthune, Douglas
   Schatzkin, Arthur
   Subar, Amy F.
   Thompson, Frances E.
   Freedman, Laurence S.
   Carroll, Raymond J.
   Shumakovich, Marina A.
   Kipnis, Victor
TI Validating an FFQ for intake of episodically consumed foods: application
   to the National Institutes of Health-AARP Diet and Health Study
SO PUBLIC HEALTH NUTRITION
LA English
DT Article
DE Diet; Food; Epidemiological methods; Questionnaires; Validation studies
ID RETIRED-PERSONS DIET; FREQUENCY QUESTIONNAIRE; MEASUREMENT ERROR;
   PROSPECTIVE COHORT; AMERICAN-ASSOCIATION; CANCER; REPRODUCIBILITY;
   NUTRITION; VALIDITY; DESIGN
AB Objective: To develop a method to validate an FFQ for reported intake of episodically consumed foods when the reference instrument measures short-term intake, and to apply the method in a large prospective cohort.
   Design: The FFQ was evaluated in a sub-study of cohort participants who, in addition to the questionnaire, were asked to complete two non-consecutive 24 h dietary recalls (24HR). FFQ-reported intakes of twenty-nine food groups were analysed using a two-part measurement error model that allows for non-consumption on a given day, using 24HR as a reference instrument under the assumption that 24HR is unbiased for true intake at the individual level.
   Setting: The National Institutes of Health-AARP Diet and Health Study, a cohort of 567 169 participants living in the USA and aged 50-71 years at baseline in 1995.
   Subjects: A sub-study of the cohort consisting of 2055 participants.
   Results: Estimated correlations of true and FFQ-reported energy-adjusted intakes were 0.5 or greater for most of the twenty-nine food groups evaluated, and estimated attenuation factors (a measure of bias in estimated diet-disease associations) were 0.4 or greater for most food groups.
   Conclusions: The proposed methodology extends the class of foods and nutrients for which an FFQ can be evaluated in studies with short-term reference instruments. Although violations of the assumption that the 24HR is unbiased could be inflating some of the observed correlations and attenuation factors, results suggest that the FFQ is suitable for testing many, but not all, diet-disease hypotheses in a cohort of this size.
C1 [Midthune, Douglas; Shumakovich, Marina A.; Kipnis, Victor] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
   [Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Subar, Amy F.; Thompson, Frances E.] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Freedman, Laurence S.] Chaim Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, IL-52621 Tel Hashomer, Israel.
   [Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
RP Midthune, D (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA.
EM midthund@mail.nih.gov
FU National Cancer Institute [CA57030]
FX R.J.C.'s research was supported by a grant from the National Cancer
   Institute (CA57030). None of the authors have any conflict of interest.
   A. S. directed the study. A. S., A. F. S., F. E. T., L. S. F. and R.J.C.
   participated in the design of the study. D. M., L. S. F., R.J.C. and V.
   K. developed the statistical methodology and designed and reviewed the
   analysis. D. M. and M. A. S. carried out the analysis. D. M. had primary
   responsibility for writing the manuscript, but all authors contributed
   to its writing and revision.
NR 30
TC 9
Z9 9
U1 0
U2 5
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 1368-9800
J9 PUBLIC HEALTH NUTR
JI Public Health Nutr.
PD JUL
PY 2011
VL 14
IS 7
BP 1212
EP 1221
DI 10.1017/S1368980011000632
PG 10
WC Public, Environmental & Occupational Health; Nutrition & Dietetics
SC Public, Environmental & Occupational Health; Nutrition & Dietetics
GA 785ER
UT WOS:000292210700011
PM 21486523
ER

PT J
AU Thompson, FE
   Willis, GB
   Thompson, OM
   Yaroch, AL
AF Thompson, Frances E.
   Willis, Gordon B.
   Thompson, Olivia M.
   Yaroch, Amy L.
TI The meaning of 'fruits' and 'vegetables'
SO PUBLIC HEALTH NUTRITION
LA English
DT Article
DE Fruit and vegetables; Dietary assessment; Nutrition education; Dietary
   guidance; Cognitive research
ID CONSUMPTION
AB Objective: Fruit and vegetable consumption is a focus of research and nutrition education; yet, there is no universal agreement on the meaning of 'fruits' and 'vegetables'. Our objective was to describe survey respondent perceptions about a set of foods with regard to whether the food is a fruit, vegetable or something else.
   Design: Three cross-sectional studies.
   Setting: Two small studies involving cognitive interviewing sessions; and one large self-administered population survey.
   Subjects: US adults in two small studies (n 55 and 80) and one large survey (n 3312), all with multiple race/ethnicities.
   Results: Perceptions varied. In the survey, rice was considered a vegetable by about 20% of respondents. In one small study, Spanish speakers were more likely to consider rice a vegetable, and Chinese speakers less likely, than were English speakers. Black beans were frequently classified as something other than vegetable or fruit. Among Hispanics, Spanish speakers were less likely than English speakers to consider beans a vegetable. Overall, tomatoes were classified as both fruit and vegetable, and these perceptions varied by race/ethnicity.
   Conclusions: Substantial disagreement among the fruit, vegetable and other food domains highlights the importance of clearly defining the desired constructs. Foods that require specific instruction include rice, dried beans, potatoes, tomatoes and fruits and vegetables in mixtures and condiments. For measurement, additional questions or explanations may be needed to clarify which foods are of interest. For communication, the global message to increase consumption of fruit and vegetables should be reinforced with specific guidance.
C1 [Thompson, Frances E.; Willis, Gordon B.] US Natl Canc Inst, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Thompson, Olivia M.; Yaroch, Amy L.] US Natl Canc Inst, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Thompson, FE (reprint author), US Natl Canc Inst, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4095A,MSC 7344, Bethesda, MD 20892 USA.
EM thompsof@mail.nih.gov
FU US National Cancer Institute
FX All work was supported by the US National Cancer Institute. The authors
   have no conflict of interest to declare. All authors contributed to the
   analyses and the writing.
NR 16
TC 11
Z9 11
U1 2
U2 5
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 1368-9800
J9 PUBLIC HEALTH NUTR
JI Public Health Nutr.
PD JUL
PY 2011
VL 14
IS 7
BP 1222
EP 1228
DI 10.1017/S136898001000368X
PG 7
WC Public, Environmental & Occupational Health; Nutrition & Dietetics
SC Public, Environmental & Occupational Health; Nutrition & Dietetics
GA 785ER
UT WOS:000292210700012
PM 21272414
ER

PT J
AU Montoya, MJ
   Kent, EE
AF Montoya, Michael J.
   Kent, Erin E.
TI Dialogical Action: Moving From Community-Based to Community-Driven
   Participatory Research
SO QUALITATIVE HEALTH RESEARCH
LA English
DT Article
DE community capacity and development; focus groups; participatory action
   research (PAR)
ID QUALITATIVE METHODS; HEALTH RESEARCH; EPIDEMIOLOGY; CHALLENGES;
   KNOWLEDGE; POLICY
AB Proponents of community-based research advocate for the active involvement and engagement of community members, citing improved construct validity, intervention efficacy, and accountability. However, to create the conditions in which expertise is mutually constructed and in which no one is the object of research, a reconsideration of the fundamental ethos of community involvement and engagement is required. In this article, we seek to accomplish two goals: (a) to briefly assess the definitions of community health, focus groups, and dissemination that are often used in community-based research; and (b) to introduce an application of dialogical action that goes beyond traditional focus group methodology to promote the creation of an evolving and dynamic dialogue among campus and community stakeholders. An urban case study is presented.
C1 [Montoya, Michael J.] Univ Calif Irvine, Dept Anthropol, Irvine, CA 92697 USA.
   [Kent, Erin E.] NCI, NIH, Bethesda, MD 20892 USA.
RP Montoya, MJ (reprint author), Univ Calif Irvine, Dept Anthropol, 3312 Social & Behav Sci Gateway, Irvine, CA 92697 USA.
EM mmontoya@uci.edu
NR 39
TC 17
Z9 17
U1 1
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1049-7323
J9 QUAL HEALTH RES
JI Qual. Health Res.
PD JUL
PY 2011
VL 21
IS 7
BP 1000
EP 1011
DI 10.1177/1049732311403500
PG 12
WC Information Science & Library Science; Social Sciences,
   Interdisciplinary; Social Sciences, Biomedical
SC Information Science & Library Science; Social Sciences - Other Topics;
   Biomedical Social Sciences
GA 780NH
UT WOS:000291863900010
PM 21454885
ER

PT J
AU Choyke, PL
AF Choyke, Peter L.
TI Science to Practice: Pilot Study of FPPRGD2 for Imaging alpha(v)beta(3)
   Integrin-How Integral Are Integrins?
SO RADIOLOGY
LA English
DT Editorial Material
ID CANCER-PATIENTS
AB Mittra et al (1) describe a new positron emission tomographic (PET) radiopharmaceutical, fluorine 18 (18 F) 2-fluoropropionyl labeled PEGylated dimeric RGD peptide (FPPRGD2), a marker of alpha(v)beta(3) integrin expression, which they tested in five healthy volunteers. No adverse events were encountered, and the biodistribution suggested both a renal and a hepatobiliary excretory route. This early safety testing paves the way for future studies of patients with cancer who are undergoing antiangiogenic therapies. F-18-FPPRGD2 represents one of several integrin imaging agents that are moving closer to clinical reality.
C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
RP Choyke, PL (reprint author), NCI, Mol Imaging Program, 10 Ctr Dr,Bldg 10,Room B3B69F, Bethesda, MD 20892 USA.
EM pchoyke@nih.gov
NR 6
TC 9
Z9 9
U1 0
U2 1
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD JUL
PY 2011
VL 260
IS 1
BP 1
EP 2
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 781KZ
UT WOS:000291932300001
PM 21697304
ER

PT J
AU Steeden, JA
   Atkinson, D
   Hansen, MS
   Taylor, AM
   Muthurangu, V
AF Steeden, Jennifer A.
   Atkinson, David
   Hansen, Michael S.
   Taylor, Andrew M.
   Muthurangu, Vivek
TI Rapid Flow Assessment of Congenital Heart Disease with
   High-Spatiotemporal-Resolution Gated Spiral Phase-Contrast MR Imaging
SO RADIOLOGY
LA English
DT Article
ID CINE MAGNETIC-RESONANCE; BLOOD-FLOW; INVIVO VALIDATION; QUANTIFICATION;
   ARTERIES; SENSE; SHUNT
AB Purpose: To validate a prospectively triggered spiral phase-contrast magnetic resonance (MR) sequence accelerated with sensitivity encoding (SENSE) in a population of children and adults with congenital heart disease.
   Materials and Methods: The local research ethics committee approved this study, and written consent was obtained from all patients or guardians. Stroke volumes were quantified in 40 patients (mean age +/- standard deviation: 21.4 years +/- 13.8, age range: 3.0-61.3 years; 22 male patients aged 3.0-38.0 years [mean age, 17.2 years +/- 10.5], 18 female patients aged 4.7-61.3 years [mean age, 26.6 years +/- 15.9]) with congenital heart disease in the aorta (n = 40), main pulmonary artery (n = 38), right pulmonary artery (n = 22), and left pulmonary artery (n = 24). Stroke volumes were obtained with (a) breath-hold spiral phase-contrast MR imaging with SENSE, (b) conventional breath-hold cartesian phase-contrast MR imaging, and (c) reference free-breathing phase-contrast MR imaging. Stroke volumes were compared by using repeated-measures analysis of variance, Bland-Altman analysis, and correlation coefficients.
   Results: Imaging time with the breath-hold spiral phase-contrast MR sequence was significantly lower than that with the conventional breath-hold phase-contrast MR sequence (similar to 5 seconds vs similar to 16 seconds, respectively; P < .0001). There was excellent agreement in stroke volumes in all vessels between the reference free-breathing sequence (mean volume, 60.3 mL +/- 27.3) and the two breath-hold sequences-spiral SENSE phase-contrast MR imaging (mean volume, 59.5 mL +/- 27.1; P < .001) and conventional cartesian phase-contrast MR imaging (mean volume, 59.8 mL +/- 27.6; P = .268). The limits of agreement were smaller with the spiral breath-hold sequence than with the conventional breath-hold sequence (-4.4 mL, 2.9 mL vs -10.3 mL, 9.3 mL, respectively); correlation was similar (r = 0.998 vs r = 0.984, respectively).
   Conclusion: Flow volumes can be accurately and reliably quantified by using a spiral SENSE phase-contrast MR sequence, with high spatiotemporal resolution obtained in a short breath hold. (C) RSNA, 2011
C1 [Steeden, Jennifer A.; Hansen, Michael S.; Taylor, Andrew M.; Muthurangu, Vivek] Great Ormond St Hosp Sick Children, Ctr Cardiovasc MR, UCL Inst Child Hlth, London WC1N 3JH, England.
   [Steeden, Jennifer A.; Atkinson, David] Ctr Med Image Comp, UCL Dept Med Phys & Bioengn, London, England.
   [Hansen, Michael S.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Muthurangu, V (reprint author), Great Ormond St Hosp Sick Children, Ctr Cardiovasc MR, UCL Inst Child Hlth, Great Ormond St, London WC1N 3JH, England.
EM v.muthurangu@ich.ucl.ac.uk
RI Atkinson, David/C-2270-2008; Taylor, Andrew/C-4311-2008; Hansen,
   Michael/J-5391-2015
OI Atkinson, David/0000-0003-1124-6666; Hansen, Michael/0000-0002-8087-8731
FU Engineering and Physical Sciences Research Council; Siemens Healthcare;
   Siemens Medical Solutions; Medtronic
FX From the Centre for Medical Image Computing, UCL Department of Medical
   Physics & Bioengineering, London, England (J.A.S., D. A.); Centre for
   Cardiovascular MR, UCL Institute of Child Health, Great Ormond Street
   Hospital, Great Ormond St, London WC1N 3JH, England (J.A.S., M. S. H.,
   A. M. T., V. M.); and National Institutes of Health, NHLBI, Bethesda, Md
   (M. S. H.). Supported by the Engineering and Physical Sciences Research
   Council. Received September 14, 2010; revision requested November 10;
   revision received December 8; accepted December 29; final version
   accepted January 25, 2011.; J.A.S. Financial activities related to the
   present article: none to disclose. Financial activities not related to
   the present article: none to disclose. Other relationships: none to
   disclose. D. A. Financial activities related to the present article:
   none to disclose. Financial activities not related to the present
   article: institution received a grant or grants are pending from Siemens
   Healthcare. Other relationships: none to disclose. M. S. H. Financial
   activities related to the present article: none to disclose. Financial
   activities not related to the present article: none to disclose. Other
   relationships: none to disclose. A. M. T. Financial activities related
   to the present article: received a grant from Siemens Medical Solutions.
   Financial activities not related to the present article: none to
   disclose. Other relationships: none to disclose. V. M. Financial
   activities related to the present article: none to disclose. Financial
   activities not related to the present article: received payment for
   lectures including service on speakers bureaus from Medtronic. Other
   relationships: none to disclose.
NR 25
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U1 0
U2 1
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD JUL
PY 2011
VL 260
IS 1
BP 79
EP 87
DI 10.1148/radiol.11101844
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 781KZ
UT WOS:000291932300009
PM 21415248
ER

PT J
AU Mittra, ES
   Goris, ML
   Iagaru, AH
   Kardan, A
   Burton, L
   Berganos, R
   Chang, E
   Liu, SL
   Shen, B
   Chin, FT
   Chen, XY
   Gambhir, SS
AF Mittra, Erik S.
   Goris, Michael L.
   Iagaru, Andrei H.
   Kardan, Arash
   Burton, Lindee
   Berganos, Rhona
   Chang, Edwin
   Liu, Shuanglong
   Shen, Bin
   Chin, Frederick T.
   Chen, Xiaoyuan
   Gambhir, Sanjiv S.
TI Pilot Pharmacokinetic and Dosimetric Studies of F-18-FPPRGD2: A PET
   Radiopharmaceutical Agent for Imaging alpha(v)beta(3) Integrin Levels
SO RADIOLOGY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; ANGIOGENESIS IN-VIVO; GLY-ASP PEPTIDE;
   TUMOR ANGIOGENESIS; RGD PEPTIDES; EXPRESSION; MICROPET; MICROBUBBLES;
   BIODISTRIBUTION; THERAPIES
AB Purpose: To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fluorine 18 (F-18) FPPRGD2 (2-fluoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine-aspartic acid (RGD) peptide sequence and targets alpha(v)beta(3) integrin, in the first volunteers imaged with this tracer.
   Materials and Methods: The protocol was approved by the institutional review board, and written informed consent was obtained from all participants. Five healthy volunteers underwent whole-body combined PET-computed tomography 0.5, 1.0, 2.0, and 3.0 hours after tracer injection (mean dose, 9.5 mCi +/- 3.4 [standard deviation] [351.5 MBq perpendicular to 125.8]; mean specific radioactivity, 1200 mCi/mu mol +/- 714 [44.4 GBq/mu mol +/- 26.4]). During this time, standard vital signs, electrocardiographic (ECG) readings, and blood sample values (for chemistry, hematologic, and liver function tests) were checked at regular intervals and 1 and 7 days after the injection. These data were used to evaluate tracer biodistribution and dosimetric properties, time-activity curves, and the stability of laboratory values. Significant changes in vital signs and laboratory values were evaluated by using a combination of population-averaged generalized estimating equation regression and exact paired Wilcoxon tests.
   Results: The administration of F-18-FPPRGD2 was well tolerated, with no marked effects on vital signs, ECG readings, or laboratory values. The tracer showed the same pattern of biodistribution in all volunteers: primary clearance through the kidneys (0.360 rem/mCi +/- 0.185 [0.098 mSv/MBq +/- 0.050]) and bladder (0.862 rem/mCi +/- 0.436 [0.233 mSv/MBq +/- 0.118], voiding model) and uptake in the spleen (0.250 rem/mCi +/- 0.168 [0.068 mSv/MBq +/- 0.046]) and large intestine (0.529 rem/mCi 6 0.236 [0.143 mSv/MBq +/- 0.064]). The mean effective dose of F-18-FPPRGD2 was 0.1462 rem/mCi +/- 0.0669 (0.0396 mSv/MBq +/- 0.0181). With an injected dose of 10 mCi (370 MBq) and a 1-hour voiding interval, a patient would be exposed to an effective radiation dose of 1.5 rem (15 mSv). Above the diaphragm, there was minimal uptake in the brain ventricles, salivary glands, and thyroid gland. Time-activity curves showed rapid clearance from the vasculature, with a mean 26% +/- 17 of the tracer remaining in the circulation at 30 minutes and most of the activity occurring in the plasma relative to cells (mean whole blood-plasma ratio, 0.799 +/- 0.096).
   Conclusion: F-18-FPPRGD2 has desirable pharmacokinetic and biodistribution properties. The primary application is likely to be PET evaluation of oncologic patients-especially those with brain, breast, or lung cancer. Specific indications may include tumor staging, identifying patients who would benefit from antiangiogenesis therapy, and separating treatment responders from nonresponders early. (C) RSNA, 2011
C1 [Mittra, Erik S.; Goris, Michael L.; Iagaru, Andrei H.; Kardan, Arash; Burton, Lindee; Berganos, Rhona; Chang, Edwin; Liu, Shuanglong; Shen, Bin; Chin, Frederick T.; Gambhir, Sanjiv S.] Stanford Hosp & Clin, Mol Imaging Program, Dept Radiol, Div Nucl Med, Stanford, CA 94305 USA.
   [Gambhir, Sanjiv S.] Stanford Hosp & Clin, Bio X Program, Dept Bioengn, Stanford, CA 94305 USA.
   [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
RP Mittra, ES (reprint author), Stanford Hosp & Clin, Mol Imaging Program, Dept Radiol, Div Nucl Med, 300 Pasteur Dr,Room H2200, Stanford, CA 94305 USA.
EM erik.mittra@stanford.edu
RI Shen, Bin/F-8111-2014
FU Doris Duke Foundation; Canary Foundation; Ben & Katherine Ivy
   Foundation; National Institutes of Health [ICMIC P50CA114747]; Abbott
   Vascular
FX From the Molecular Imaging Program, Department of Radiology, Division of
   Nuclear Medicine (E. S. M., M. L. G., A. H. I., A. K., L. B., R. B., E.
   C., S. L., B. S., F. T. C., S. S. G.), and Bio-X Program, Department of
   Bioengineering (S. S. G.), Stanford Hospital and Clinics, 300 Pasteur
   Dr, Room H2200, Stanford, CA 94305-5281; and Laboratory for Molecular
   Imaging and Nanomedicine, National Institute of Biomedical Imaging and
   Bioengineering, National Institutes of Health, Bethesda, Md (X. C.).
   Received June 7, 2010; revision requested August 2; revision received
   December 29; accepted January 18, 2011; final version accepted February
   14. Supported in part by the Doris Duke Foundation, the Canary
   Foundation, and the Ben & Katherine Ivy Foundation. Address
   correspondence to E. S. M. (e-mail: erik.mittra@stanford.edu).; This
   research was supported by the National Institutes of Health (grant ICMIC
   P50CA114747).; Disclosures of Potential Conflicts of Interest: E. S. M.
   No potential conflicts of interest to disclose. M. L. G. No potential
   conflicts of interest to disclose. A. H. I. No potential conflicts of
   interest to disclose. A. K. No potential conflicts of interest to
   disclose. L. B. No potential conflicts of interest to disclose. R. B. No
   potential conflicts of interest to disclose. E. C. No potential
   conflicts of interest to disclose. S. L. No potential conflicts of
   interest to disclose. B. S. No potential conflicts of interest to
   disclose. F. T. C. Financial activities related to the present article:
   none to disclose. Financial activities not related to the present
   article: received a consulting fee from Abbott Vascular. Other
   relationships: none to disclose. X. C. No potential conflicts of
   interest to disclose. S. S. G. No potential conflicts of interest to
   disclose.
NR 37
TC 71
Z9 74
U1 2
U2 10
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD JUL
PY 2011
VL 260
IS 1
BP 182
EP 191
DI 10.1148/radiol.11101139
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 781KZ
UT WOS:000291932300021
PM 21502381
ER

PT J
AU Fauci, AS
AF Fauci, Anthony S.
TI AIDS: Let Science Inform Policy
SO SCIENCE
LA English
DT Editorial Material
C1 NIAID, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIAID, US Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM afauci@niaid.nih.gov
NR 0
TC 13
Z9 14
U1 0
U2 2
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUL 1
PY 2011
VL 333
IS 6038
BP 13
EP 13
DI 10.1126/science.1209751
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785UF
UT WOS:000292255400001
PM 21719646
ER

PT J
AU Paprotka, T
   Delviks-Frankenberry, KA
   Cingoz, O
   Martinez, A
   Kung, HJ
   Tepper, CG
   Hu, WS
   Fivash, MJ
   Coffin, JM
   Pathak, VK
AF Paprotka, Tobias
   Delviks-Frankenberry, Krista A.
   Cingoez, Oya
   Martinez, Anthony
   Kung, Hsing-Jien
   Tepper, Clifford G.
   Hu, Wei-Shau
   Fivash, Matthew J., Jr.
   Coffin, John M.
   Pathak, Vinay K.
TI Recombinant Origin of the Retrovirus XMRV
SO SCIENCE
LA English
DT Article
ID CHRONIC-FATIGUE-SYNDROME; MURINE LEUKEMIA-VIRUS; PROSTATE-CANCER; MOUSE
   DNA; CARCINOMA; CONTAMINATION; SEQUENCES; INFECTION; ANDROGEN; DISEASE
AB The retrovirus XMRV (xenotropic murine leukemia virus-related virus) has been detected in human prostate tumors and in blood samples from patients with chronic fatigue syndrome, but these findings have not been replicated. We hypothesized that an understanding of when and how XMRV first arose might help explain the discrepant results. We studied human prostate cancer cell lines CWR22Rv1 and CWR-R1, which produce XMRV virtually identical to the viruses recently found in patient samples, as well as their progenitor human prostate tumor xenograft (CWR22) that had been passaged in mice. We detected XMRV infection in the two cell lines and in the later passage xenografts, but not in the early passages. In particular, we found that the host mice contained two proviruses, PreXMRV-1 and PreXMRV-2, which share 99.92% identity with XMRV over >3.2-kilobase stretches of their genomes. We conclude that XMRV was not present in the original CWR22 tumor but was generated by recombination of two proviruses during tumor passaging in mice. The probability that an identical recombinant was generated independently is negligible (similar to 10(-12)); our results suggest that the association of XMRV with human disease is due to contamination of human samples with virus originating from this recombination event.
C1 [Paprotka, Tobias; Delviks-Frankenberry, Krista A.; Pathak, Vinay K.] NCI, HIV Drug Resistance Program, Viral Mutat Sect, Frederick, MD 21702 USA.
   [Hu, Wei-Shau] NCI, HIV Drug Resistance Program, Viral Recombinat Sect, Frederick, MD 21702 USA.
   [Cingoez, Oya; Coffin, John M.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
   [Cingoez, Oya; Coffin, John M.] Tufts Univ, Sch Med, Genet Program, Boston, MA 02111 USA.
   [Martinez, Anthony; Kung, Hsing-Jien; Tepper, Clifford G.] Univ Calif Davis, Dept Biochem & Mol Med, Sacramento, CA 95817 USA.
   [Kung, Hsing-Jien] Univ Calif Davis, Dept Urol, Sacramento, CA 95817 USA.
   [Fivash, Matthew J., Jr.] NCI, Data Management Serv Inc, Frederick, MD 21702 USA.
RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, Viral Mutat Sect, Frederick, MD 21702 USA.
EM vinay.pathak@nih.gov
RI Kung, Hsing-Jien/C-7651-2013; Delviks-Frankenberry, Krista/M-4822-2013
FU Center for Cancer Research, National Cancer Institute, NIH;
   Bench-to-Bedside Award [R37 CA 089441, R01CA150197]; F.M. Kirby
   Foundation
FX We thank W. Shao for analysis of MLV diversity, and E. Freed and S.
   Hughes for helpful discussions. This research was supported in part by
   the Intramural Research Program of the Center for Cancer Research,
   National Cancer Institute, NIH. 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 work was
   also supported in part by a Bench-to-Bedside Award to V.K.P., research
   grant R37 CA 089441 to J.M.C., and R01CA150197 to H.J.K. J.M.C. was a
   Research Professor of the American Cancer Society with support from the
   F.M. Kirby Foundation.
NR 25
TC 146
Z9 148
U1 2
U2 19
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUL 1
PY 2011
VL 333
IS 6038
BP 97
EP 101
DI 10.1126/science.1205292
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785UF
UT WOS:000292255400058
PM 21628392
ER

PT J
AU Ge, WS
   Shi, L
   Zhou, YS
   Liu, YS
   Ma, GE
   Jiang, Y
   Xu, YW
   Zhang, X
   Feng, HL
AF Ge, Wenshu
   Shi, Lei
   Zhou, Yongsheng
   Liu, Yunsong
   Ma, Gui-e
   Jiang, Yong
   Xu, Yongwei
   Zhang, Xiao
   Feng, Hailan
TI Inhibition of Osteogenic Differentiation of Human Adipose-Derived
   Stromal Cells by Retinoblastoma Binding Protein 2 Repression of
   RUNX2-Activated Transcription
SO STEM CELLS
LA English
DT Article
DE Human adipose-derived stromal cells; Retinoblastoma binding protein 2;
   Histone methylation; RUNX2; Osteogenic differentiation
ID MESENCHYMAL STEM-CELLS; TISSUE-ENGINEERED BONE;
   CELLULAR-DIFFERENTIATION; HISTONE DEMETHYLATION; LYSINE-4 METHYLATION;
   SKELETAL DEVELOPMENT; RUNX2; JMJD2A; SPECIFICITY; RECOGNITION
AB Histone methylation is regarded as an important type of histone modification defining the epigenetic program during the lineage differentiation of stem cells. A better understanding of this epigenetic mechanism that governs osteogenic differentiation of human adipose-derived stromal cells (hASCs) can improve bone tissue engineering and provide new insights into the modulation of hASC-based cell therapy. Retinoblastoma binding protein 2 (RBP2) is a histone demethylase that specifically catalyzes demethylation of dimethyl or trimethyl histone H3 lysine 4 (H3K4me2 or H3K4me3), which is normally associated with transcriptionally active genes. In this study, the roles of RBP2 in osteogenic differentiation of hASCs were investigated. We found that RBP2 knockdown by lentiviruses expressing small interfering RNA promoted osteogenic differentiation of hASCs in vitro and in vivo. In addition, we demonstrated that knockdown of RBP2 resulted in marked increases of mRNA expression of osteogenesis-associated genes such as alkaline phosphatase (ALP), osteocalcin (OC), and osterix (OSX). RBP2 was shown to occupy the promoters of OSX and OC to maintain the level of the H3K4me3 mark by chromatin immunoprecipitation assays. Furthermore, coimmunoprecipitation and luciferase reporter experiments suggested that RBP2 was physically and functionally associated with RUNX2, an essential transcription factor that governed osteoblastic differentiation. Significantly, RUNX2 knockdown impaired the repressive activity of RBP2 in osteogenic differentiation of hASCs. Altogether, our study is the first to demonstrate the functional and biological roles of H3K4 demethylase RBP2 in osteogenic differentiation of hASCs and to link RBP2 to the transcriptional regulation of RUNX2. STEM CELLS 2011;29:1112-1125
C1 [Ge, Wenshu; Zhou, Yongsheng; Liu, Yunsong; Xu, Yongwei; Zhang, Xiao; Feng, Hailan] Peking Univ, Dept Prosthodont, Sch Stomatol, Beijing 100081, Peoples R China.
   [Ge, Wenshu; Zhou, Yongsheng; Liu, Yunsong; Xu, Yongwei; Zhang, Xiao; Feng, Hailan] Peking Univ, Hosp Stomatol, Dept Prosthodont, Beijing 100081, Peoples R China.
   [Jiang, Yong] Peking Univ, Dept Gen Dent 2, Sch Stomatol, Beijing 100081, Peoples R China.
   [Jiang, Yong] Peking Univ, Dept Gen Dent 2, Hosp Stomatol, Beijing 100081, Peoples R China.
   [Shi, Lei] Natl Canc Inst, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD USA.
   [Ma, Gui-e] Chinese Acad Med Sci, Plast Surg Hosp, Body Sculpture Ctr, Beijing 100730, Peoples R China.
RP Zhou, YS (reprint author), Peking Univ, Dept Prosthodont, Sch Stomatol, 22 Zhongguancun Nandajie, Beijing 100081, Peoples R China.
EM kqzhouysh@hsc.pku.edu.cn
RI Liu, Yunsong /N-8091-2015
OI Liu, Yunsong /0000-0001-8364-1898
FU National Natural Science Foundation of China [81070809]
FX We thank Dr. Shenglin Li (Core Laboratory, Peking University School of
   Stomatology, Beijing, China) for her technical supports. This study was
   supported by a grant from the National Natural Science Foundation of
   China (No. 81070809).
NR 48
TC 27
Z9 35
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD JUL
PY 2011
VL 29
IS 7
BP 1112
EP 1125
DI 10.1002/stem.663
PG 14
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
   Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 784XQ
UT WOS:000292192400010
PM 21604327
ER

PT J
AU Gacchina, CE
   Deb, P
   Barth, JL
   Ramamurthi, A
AF Gacchina, Carmen E.
   Deb, Partha
   Barth, Jeremy L.
   Ramamurthi, Anand
TI Elastogenic Inductability of Smooth Muscle Cells from a Rat Model of
   Late Stage Abdominal Aortic Aneurysms
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID MATRIX METALLOPROTEINASES; HYALURONAN OLIGOMERS; ELASTIN; DOXYCYCLINE;
   INHIBITION; CALPONIN; STABILIZATION; REGENERATION; OSTEOPONTIN;
   GELATINASE
AB Although abdominal aortic aneurysms (AAA) can be potentially stabilized by inhibiting inflammatory cell recruitment and their release of proteolytic enzymes, active AAA regression is not possible without regeneration of new elastic matrix structures. Unfortunately, postneonatal vascular smooth muscle cells (SMCs), healthy, and likely more so, diseased cells, poorly synthesize or remodel elastic fibers, impeding any effort directed at regenerative AAA treatment. Previously, we determined the eleastogenic benefits of oligomers (HA-o; 4-6 mers) of the glycosaminoglycan, hyaluronan (HA) and transforming growth factor-beta 1 (TGF-beta 1) to healthy SMCs. Since AAAs are often diagnosed only late in development when matrix disruption is severe, we now determine if elastogenic upregulation of SMCs from late-stage AAAs (> 100% diameter increase) is possible. AAAs were induced by perfusion of rat infrarenal aortae with porcine pancreatic elastase. Elastic matrix degradation, vessel expansion (similar to 120%), inflammatory cell infiltration, and enhanced activity of matrix-metalloproteases (MMPs) 2 and 9 resulted, paralleling human AAAs. Aneurysmal SMCs (EaRASMCs) maintained a diseased phenotype in 2D cell culture and exhibited patterns of gene expression different from healthy rat aortic SMCs (RASMCs). Relative to passage-matched healthy RASMCs, unstimulated EaRASMCs produced far less tropoelastin and matrix elastin. Exogenous TGF-beta and HA-o (termed "factors") significantly decreased EaRASMC proliferation and enhanced tropoelastin synthesis, though only at the highest provided dose combination (20 mg/mL of HA-o, 10 ng/mL of TGF-beta); despite such enhancement, tropoelastin amounts were only similar to 40% of amounts synthesized by healthy RASMC cultures. Differently, elastic matrix synthesis was enhanced beyond amounts synthesized by healthy RASMCs (112%), even at lower doses of factors (2 mg/mL of HA-o and 5 ng/mL of TGF-beta). The factors also enhanced elastic fiber deposition over untreated EaRASMC cultures and restored several genes whose expression was altered in EaRASMC cultures back to levels expressed by healthy RASMCs. However, the activity of MMPs 2 and 9 generated by EaRASMC cultures was unaffected by the factors/factor dose. The study confirms that SMCs from advanced AAAs can be elastogenically induced, although much higher doses of elastogenic factors are required for induction relative to healthy SMCs. Also, the factors do not appear to inhibit MMP activity, vital to preserve existing elastic matrix structures that serve as nucleation sites for new elastic fiber deposition. Thus, to enhance net accumulation of newly regenerated elastic matrix, toward possibly regressing AAAs, codelivery of MMP inhibitors may be necessitated.
C1 [Ramamurthi, Anand] Cleveland Clin, Dept Biomed Engn, Cleveland, OH 44195 USA.
   [Gacchina, Carmen E.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
   [Gacchina, Carmen E.; Barth, Jeremy L.; Ramamurthi, Anand] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA.
   [Gacchina, Carmen E.; Ramamurthi, Anand] Clemson Univ, Dept Bioengn, Clemson, SC USA.
   [Deb, Partha; Ramamurthi, Anand] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA.
RP Ramamurthi, A (reprint author), Cleveland Clin, Dept Biomed Engn, 1500 Euclid Ave,ND 20, Cleveland, OH 44195 USA.
EM ramamua@ccf.org
FU National Institutes of Health [R21EB006078-01A1, RO1HL0092051-01A1,
   R01HL0092051-01S, T32 HL007260]
FX This study was funded by the National Institutes of Health
   R21EB006078-01A1, RO1HL0092051-01A1, and R01HL0092051-01S (Ramamurthi
   A). Gacchina C was supported by a National Institutes of Health
   predoctoral award T32 HL007260. The authors would like to acknowledge
   Dr. John Curci and Terri Ennis at Washington University in St. Louis for
   providing training on the elastase perfusion procedure on mice and
   Victor M. Fresco and the MUSC Proteogenomics Facility for assistance
   with the DNA microarray analysis.
NR 37
TC 15
Z9 15
U1 0
U2 1
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 JUL
PY 2011
VL 17
IS 13-14
BP 1699
EP 1711
DI 10.1089/ten.tea.2010.0526
PG 13
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
   Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 782PT
UT WOS:000292022300005
PM 21341992
ER

PT J
AU Acosta, MT
   Velez, JI
   Bustamante, ML
   Balog, JZ
   Arcos-Burgos, M
   Muenke, M
AF Acosta, M. T.
   Velez, J. I.
   Bustamante, M. L.
   Balog, J. Z.
   Arcos-Burgos, M.
   Muenke, M.
TI A two-locus genetic interaction between LPHN3 and 11q predicts ADHD
   severity and long-term outcome
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
DE ADHD; DRD2; epistasis; LPHN3; NCAM1; severity of symptoms
ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; CELL-ADHESION MOLECULE;
   QUALITY-OF-LIFE; DSM-IV ADHD; LATENT CLASS; SYMPTOM SEVERITY; POLYSIALIC
   ACID; POPULATION; CHILDREN; SUSCEPTIBILITY
AB The severity of attention-deficit/hyperactivity disorder (ADHD) symptoms is a major predictor of long-term ADHD outcome. To investigate if two-locus interactions might predict ADHD severity, we studied a sample of 1341 individuals from families clustering ADHD, using the Vanderbilt Assessment Scale for Parents. Latent class cluster analysis was used to construct symptom profiles and classify ADHD severity. Single nucleotide polymorphisms (SNPs) spanning ADHD-linked chromosomal regions on chromosomes 4, 5, 10, 11, 12 and 17 were genotyped. SNPs associated with ADHD severity were identified and potential two-locus genetic interactions were tested. We found that SNPs within the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 not only to increase the risk of developing ADHD but also to increase ADHD severity. All these genes are identified to have a major role in shaping both brain development and function. These findings demonstrate that genetic interactions may predict the severity of ADHD, which in turn may predict long-term ADHD outcome.
C1 [Acosta, M. T.; Velez, J. I.; Bustamante, M. L.; Balog, J. Z.; Arcos-Burgos, M.; Muenke, M.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Bustamante, M. L.] Univ Chile, Fac Med, Program Human Genet, Inst Biomed Sci, Santiago, Chile.
   [Bustamante, M. L.] Univ Chile, Fac Med, Dept Psychiat & Mental Hlth, Santiago, Chile.
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 arcosburgosm@mail.nih.gov; mamuenke@mail.nih.gov
RI Bustamante, Maria Leonor/H-3728-2014
OI Bustamante, Maria Leonor/0000-0001-9071-2463
FU Division of Intramural Research, National Human Genome Research
   Institute, National Institutes of Health; Department of Health and Human
   Services, USA; Ministerio de Educacion, Chile [MECESUP 0608]
FX We would like to extend our deepest gratitude to all patients and
   families who took part in our research on ADHD. We thank Dr Benjamin D
   Solomon for critical reading and input to this manuscript. This research
   was supported by the Division of Intramural Research, National Human
   Genome Research Institute, National Institutes of Health, and Department
   of Health and Human Services, USA. MLB was supported by Ministerio de
   Educacion, Chile, Grant MECESUP 0608. Julia Fekecs provided graphical
   assistance with the figures.
NR 36
TC 10
Z9 11
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD JUL
PY 2011
VL 1
AR e17
DI 10.1038/tp.2011.14
PG 8
WC Psychiatry
SC Psychiatry
GA V29SS
UT WOS:000208768700001
PM 22832519
ER

PT J
AU Wan, WZ
   Murphy, PM
AF Wan, Wuzhou
   Murphy, Philip M.
TI Regulation of Atherogenesis by Chemokine Receptor CCR6
SO TRENDS IN CARDIOVASCULAR MEDICINE
LA English
DT Review
ID SMOOTH-MUSCLE-CELLS; E-DEFICIENT MICE; RHEUMATOID-ARTHRITIS; T-CELLS;
   DENDRITIC CELLS; TH17 CELLS; ATHEROSCLEROSIS; DISEASE; INFLAMMATION;
   RECRUITMENT
AB Atherosclerosis is a complex vascular pathology characterized in part by accumulation of innate and adaptive inflammatory cells in arterial plaque. Molecular mediators responsible for inflammatory cell accumulation in plague include specific members of the chemokine family of leukocyte chemoattractants and their G protein-coupled receptors. Studies using the ApoE knockout mouse model have recently implicated chemokine receptor Ccr6 and its ligand Ccl20 as a nonredundant ligand-receptor pair in atherosclerosis, potentially operating at several stages of cell recruitment and on several leukocyte subtypes. (Trends Cardiovasc Med 2011;21:140-144) Published by Elsevier Inc.
C1 [Wan, Wuzhou; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Murphy, PM (reprint author), NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike,Bldg 10,Rm 11N113, Bethesda, MD 20892 USA.
EM pmm@nih.gov
RI Wan, Wuhzou/H-8556-2013
FU Division of Intramural Research, National Institute of Allergy and
   Infectious Diseases, National Institutes of Health
FX The authors thank the Intramural Research Program of the Division of
   Intramural Research, National Institute of Allergy and Infectious
   Diseases, National Institutes of Health for financial support.
NR 40
TC 7
Z9 7
U1 0
U2 2
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1050-1738
J9 TRENDS CARDIOVAS MED
JI Trends Cardiovasc. Med.
PD JUL
PY 2011
VL 21
IS 5
BP 140
EP 144
AR PII S1050-1738(12)00080-1
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 974SK
UT WOS:000306456600003
PM 22732549
ER

PT J
AU Hassan, SS
   Romero, R
   Vidyadhari, D
   Fusey, S
   Baxter, JK
   Khandelwal, M
   Vijayaraghavan, J
   Trivedi, Y
   Soma-Pillay, P
   Sambarey, P
   Dayal, A
   Potapov, V
   O'Brien, J
   Astakhov, V
   Yuzko, O
   Kinzler, W
   Dattel, B
   Sehdev, H
   Mazheika, L
   Manchulenko, D
   Gervasi, MT
   Sullivan, L
   Conde-Agudelo, A
   Phillips, JA
   Creasy, GW
AF Hassan, S. S.
   Romero, R.
   Vidyadhari, D.
   Fusey, S.
   Baxter, J. K.
   Khandelwal, M.
   Vijayaraghavan, J.
   Trivedi, Y.
   Soma-Pillay, P.
   Sambarey, P.
   Dayal, A.
   Potapov, V.
   O'Brien, J.
   Astakhov, V.
   Yuzko, O.
   Kinzler, W.
   Dattel, B.
   Sehdev, H.
   Mazheika, L.
   Manchulenko, D.
   Gervasi, M. T.
   Sullivan, L.
   Conde-Agudelo, A.
   Phillips, J. A.
   Creasy, G. W.
CA PREGNANT Trial
TI Vaginal progesterone reduces the rate of preterm birth in women with a
   sonographic short cervix: a multicenter, randomized, double-blind,
   placebo-controlled trial
SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY
LA English
DT Article
DE pregnancy; preterm delivery; preterm labor; progestins; progestogens;
   respiratory distress syndrome; transvaginal ultrasound; uterine cervix;
   vaginal administration
ID HUMAN MYOMETRIAL CELLS; HUMAN FETAL MEMBRANES; FACTOR-KAPPA-B; UTERINE
   CERVIX; RECEPTOR-A; 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; TRANSVAGINAL
   ULTRASOUND; ASYMPTOMATIC WOMEN; PREMATURE DELIVERY; INCOMPETENT CERVIX
AB Objectives Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix.
   Methods This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat.
   Results Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n = 235; placebo, n = 223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n = 21) vs 16.1% (n = 36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P = 0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P = 0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P = 0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P = 0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P = 0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P = 0.04) and birth weight < 1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P = 0.01). There were no differences in the incidence of treatment-related adverse events between the groups.
   Conclusions The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.
C1 [Hassan, S. S.; Romero, R.; Conde-Agudelo, A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
   [Hassan, S. S.] Wayne State Univ, Dept Obstet & Gynecol, Detroit Med Ctr, Hutzel Womens Hosp, Detroit, MI USA.
   [Romero, R.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
   [Romero, R.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA.
   [Baxter, J. K.] Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA.
   [Khandelwal, M.] Cooper Univ Hosp, Dept Obstet & Gynecol, Camden, NJ USA.
   [Soma-Pillay, P.] Steve Biko Acad Hosp, Dept Obstet & Gynaecol, Pretoria, South Africa.
   [Dayal, A.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA.
   [Potapov, V.] Municipal Estab City Matern Hosp 1, Dnepropetrovsk State Med Acad, Dept Obstet & Gynecol, Dnepropetrovsk, Ukraine.
   [O'Brien, J.] Cent Baptist Hosp, Perinatal Diagnost Ctr, Lexington, KY USA.
   [O'Brien, J.] Univ Kentucky, Dept Obstet & Gynecol, Lexington, KY USA.
   [Astakhov, V.] M Gorky Donetsk Natl Med Univ, Municipal Hosp Cent City Clin Hosp 6, Dept Obstet & Gynecol, Donetsk, Ukraine.
   [Yuzko, O.] PL Shupik Natl Acad Postgrad Educ, Ukrainian State Inst Human Reproductol, Pechersk Reg Antenatal Out Patients Clin 1, Dept Obstet & Gynecol 1, Kiev, Ukraine.
   [Kinzler, W.] Winthrop Univ Hosp, Clin Trials Ctr, Mineola, NY 11501 USA.
   [Dattel, B.] Eastern Virginia Med Sch, Dept Obstet & Gynecol, Norfolk, VA 23501 USA.
   [Sehdev, H.] Univ Penn Hlth Syst, Penn Hosp, Philadelphia, PA USA.
   [Mazheika, L.] Publ Hlth Serv Estab Minsk 1st City Clin, Minsk, Byelarus.
   [Manchulenko, D.] Municipal Hlth Care Estab City Matern Hosp 1, Dept Antenatal Day Hosp, Chernovtsy, Ukraine.
   [Gervasi, M. T.] Azienda Osped Padova, UO Ostetricial Ginecol, Padua, Italy.
   [Sullivan, L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
   [Phillips, J. A.] Sage Stat Solut Inc, Elfand, NC USA.
   [Creasy, G. W.] Columbia Labs Inc, Livingston, NJ USA.
   [Romero, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Perinatal Res & Obstet Intramural Div, NIH,Dept Hlth & Human Serv, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Perinatal Res & Obstet Intramural Div, NIH,Dept Hlth & Human Serv, 3990 John R, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov
OI Creasy, George/0000-0002-6645-4238; Sullivan, Lisa/0000-0003-0726-7149
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development/National Institutes of Health; Columbia Laboratories, Inc.;
   Preterm Birth Advisory Committee
FX The study was funded in part by the Intramural Program of the Eunice
   Kennedy Shriver National Institute of Child Health and Human
   Development/National Institutes of Health and Columbia Laboratories,
   Inc.; S.S.H., R.R., M.T.G., A.C.A., W.K. and L.S. have no financial
   interest. Author-investigators D.V., S.F., J.B., M.K., J.V., Y.T.,
   P.S.-P., P.S., A.D., V.P., J.O.'B., V.A., O.Y., B.D., H.S., L.M. and
   D.M. conducted this study with the support of grants awarded by Columbia
   Laboratories, Inc. for the specific purpose of conducting this trial.
   The terms and conditions for the awarding of the grants were consistent
   with those which are customary for this type of industry-sponsored trial
   and all payments were independent of the outcome of the trial. In
   addition, J.K.B. and J.O.'B. have also received consulting fees and
   travel expenses related to Preterm Birth Advisory Committee meetings
   related to the project. J.O.'B. is an inventor on a patent for the use
   of progesterone in the prevention of preterm birth. J.A.P. received
   remuneration as a statistical consultant to Columbia Laboratories, Inc.
   G.W.C. is an employee of Columbia Laboratories, Inc.
NR 102
TC 303
Z9 316
U1 2
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0960-7692
EI 1469-0705
J9 ULTRASOUND OBST GYN
JI Ultrasound Obstet. Gynecol.
PD JUL
PY 2011
VL 38
IS 1
BP 18
EP 31
DI 10.1002/uog.9017
PG 14
WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
   Medical Imaging
SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
   Medical Imaging
GA 785ZM
UT WOS:000292271800003
PM 21472815
ER

PT J
AU Neta, G
   Grewal, J
   Mikolajczyk, R
   Klebanoff, M
   Zhang, J
AF Neta, G.
   Grewal, J.
   Mikolajczyk, R.
   Klebanoff, M.
   Zhang, J.
TI Does the individualized reference outperform a simple ultrasound-based
   reference applied to birth weight in predicting child neurodevelopment?
SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY
LA English
DT Article
DE birth weight; fetal development; infant; small-for-gestational age;
   Wechsler scales
ID FOR-GESTATIONAL-AGE; INTRAUTERINE GROWTH-RETARDATION;
   CORONARY-HEART-DISEASE; BODY-MASS INDEX; FETAL-GROWTH;
   PERINATAL-MORTALITY; PRETERM INFANTS; WOMEN; COHORT; RISK
AB Objectives Being small-for-gestational age (SGA) is associated with an increased risk of morbidity, but questions remain about how best to diagnose SGA, and thus, predict poor health consequences. The authors sought to compare an individualized reference for defining SGA with simple birth weight-based and ultrasound-based references applied to birth weight in predicting poor cognitive development at age five.
   Methods The authors used data from the Successive SGA Births Study, a prospective study including 699 Alabaman and 618 Scandinavian women recruited from 1986 to 1988, and whose children had cognitive development scores measured at age five using the Wechsler Preschool and Primary Scale of Intelligence - Revised Intelligence Quotient. Sensitivity, specificity and positive predictive value (PPV) were estimated for each reference applied to birth weight using adverse cognitive development (score < 10(th) percentile) as the outcome. Relative risk of poor neurodevelopment was calculated, comparing infants classified as SGA by either the individualized or the simple ultrasound-based reference with infants not classified as SGA.
   Results The individualized reference had higher specificity and PPV in predicting poor neurodevelopment. Neonates defined as SGA by the individualized reference alone had a higher risk (RR = 2.20, 95% CI: 1.20, 4.00) of poor cognitive outcome, while those identified by the ultrasound-based reference alone did not (RR = 0.95, 95% CI: 0.45, 2.01). None of the references could predict poor neurodevelopment well at age five.
   Conclusions The individualized birth weight reference modestly outperforms the simple ultrasound-based reference in identifying SGA infants with poor child neurodevelopment. However, neither reference can predict child neurodevelopment well. Copyright (C) 2011 ISUOG. Published by John Wiley & Sons, Ltd.
C1 [Neta, G.; Grewal, J.; Klebanoff, M.; Zhang, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD USA.
   [Mikolajczyk, R.] Univ Bremen, Dept Clin Epidemiol, Bremen Inst Prevent Res & Social Med, Bremen, Germany.
RP Neta, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA.
EM netagil@mail.nih.gov
OI Mikolajczyk, Rafael/0000-0003-1271-7204; Grewal,
   Jagteshwar/0000-0002-0141-4876
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health
FX This study was supported by the Intramural Research Program of the
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development, National Institutes of Health.
NR 33
TC 3
Z9 3
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0960-7692
J9 ULTRASOUND OBST GYN
JI Ultrasound Obstet. Gynecol.
PD JUL
PY 2011
VL 38
IS 1
BP 62
EP 66
DI 10.1002/uog.8902
PG 5
WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
   Medical Imaging
SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
   Medical Imaging
GA 785ZM
UT WOS:000292271800009
PM 21154763
ER

PT J
AU Percopo, CM
   Dubovi, EJ
   Renshaw, RW
   Dyer, KD
   Domachowske, JB
   Rosenberg, HF
AF Percopo, Caroline M.
   Dubovi, Edward J.
   Renshaw, Randall W.
   Dyer, Kimberly D.
   Domachowske, Joseph B.
   Rosenberg, Helene F.
TI Canine pneumovirus replicates in mouse lung tissue and elicits
   inflammatory pathology
SO VIROLOGY
LA English
DT Article
DE Inflammation; Neutrophil; Cytokine; Respiratory virus
ID PNEUMONIA VIRUS; MICE PVM; IN-VIVO; RAT COLONIES; INFECTION; ANTIBODIES;
   RESPONSES; PROTECTS; HOST
AB Canine pneumovirus (CnPnV) was recently isolated from the respiratory tracts of shelter dogs and shares sequence similarity with the rodent pathogen, pneumonia virus of mice (PVM). We show here that CnPnV replicates in and can elicit local proinflammatory cytokine production and neutrophil recruitment to lung tissue and the airways. In contrast to PVM J3666 infection, fatal CnPnV infections are observed only in response to high titer intranasal inocula (>67 TCID(50) units). Sera from mice that recover from CnPnV infection contain antibodies that cross-react with PVM antigens; these mice are protected against lethal PVM infection. Given these findings, it will be intriguing to determine the relative role(s) of CnPnV and PVM in eliciting respiratory symptoms in susceptible canine species. (C) Published by Elsevier Inc.
C1 [Percopo, Caroline M.; Dyer, Kimberly D.; Rosenberg, Helene F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
   [Dubovi, Edward J.; Renshaw, Randall W.] Coll Vet Med Cornell, Anim Hlth Diagnost Ctr, Ithaca, NY 14853 USA.
   [Domachowske, Joseph B.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C215, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
FU NIAID [Z01-AI000943]; Children's Miracle Network of Central New York;
   Animal Health Diagnostic Center
FX The authors thank Ricardo Dreyfuss (NIAID, NIH) for preparation of the
   photomicrographs. Work presented in the manuscript is supported by funds
   from the NIAID Division of Intramural Research ProjectZ01-AI000943
   (HFR), Children's Miracle Network of Central New York (JBD), and
   discretionary funds of the Animal Health Diagnostic Center (EJD, RWR).
NR 26
TC 12
Z9 12
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 0042-6822
J9 VIROLOGY
JI Virology
PD JUL-AUG
PY 2011
VL 416
IS 1-2
BP 26
EP 31
DI 10.1016/j.virol.2011.04.010
PG 6
WC Virology
SC Virology
GA 781AR
UT WOS:000291903500004
PM 21600624
ER

PT J
AU Lee, SE
   Simons-Morton, BG
   Klauer, SE
   Ouimet, MC
   Dingus, TA
AF Lee, Suzanne E.
   Simons-Morton, Bruce G.
   Klauer, Sheila E.
   Ouimet, Marie Claude
   Dingus, Thomas A.
TI Naturalistic assessment of novice teenage crash experience
SO ACCIDENT ANALYSIS AND PREVENTION
LA English
DT Article
DE Naturalistic driving; Crashes; Exposure; Novice; Teenaged drivers
ID DRIVERS; RISK
AB Background: Crash risk is highest during the first months after licensure. Current knowledge about teenagers' driving exposure and the factors increasing their crash risk is based on self-reported data and crash database analyses. While these research tools are useful, new developments in naturalistic technologies have allowed researchers to examine newly-licensed teenagers' exposure and crash risk factors in greater detail. The Naturalistic Teenage Driving Study (NTDS) described in this paper is the first study to follow a group of newly-licensed teenagers continuously for 18 months after licensure. The goals of this paper are to compare the crash and near-crash experience of drivers in the NTDS to national trends, to describe the methods and lessons learned in the NTDS, and to provide initial data on driving exposure for these drivers.
   Methods: A data acquisition system was installed in the vehicles of 42 newly-licensed teenage drivers 16 years of age during their first 18 months of independent driving. It consisted of cameras, sensors (accelerometers, GPS, yaw, front radar, lane position, and various sensors obtained via the vehicle network), and a computer with removable hard drive. Data on the driving of participating parents was also collected when they drove the instrumented vehicle.
   Findings: The primary findings after 18 months included the following: (1) crash and near-crash rates among teenage participants were significantly higher during the first six months of the study than the final 12 months, mirroring the national trends: (2) crash and near-crash rates were significantly higher for teenage than adult (parent) participants, also reflecting national trends: (3) teenaged driving exposure averaged between 507 and 710 km (315-441 miles) per month over the study period, but varied substantially between participants with standard errors representing 8-14 percent of the mean: and (4) crash and near-crash types were very similar for male and female teenage drivers.
   Discussion: The findings are the first comparing crash and near-crash rates among novice teenage drivers with those of adults using the same vehicle over the same period of time. The finding of highly elevated crash rates of novice teenagers during the first six months of licensure are consistent with and confirm the archival crash data showing high crash risk for novice teenagers. The NTDS convenience sample of teenage drivers was similar to the US teenage driver population in terms of exposure and crash experience. The dataset is expected be a valuable resource for future in-depth analyses of crash risk, exposure to risky driving conditions, and comparisons of teenage and adult driving performance in various driving situations. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Lee, Suzanne E.; Klauer, Sheila E.; Dingus, Thomas A.] Virginia Tech, Transportat Inst, Blacksburg, VA 24061 USA.
   [Simons-Morton, Bruce G.; Ouimet, Marie Claude] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
   [Ouimet, Marie Claude] Univ Sherbrooke, Fac Med & Hlth Sci, Longueuil, PQ J4K 0A8, Canada.
RP Lee, SE (reprint author), Virginia Tech, Transportat Inst, 3500 Transportat Res Plaza, Blacksburg, VA 24061 USA.
EM slee@vtti.vt.edu
OI Simons-Morton, Bruce/0000-0003-1099-6617
FU Intramural NIH HHS [Z01 HD001707-10, Z01 HD001707-09, ZIA HD001707-13];
   NICHD NIH HHS [N01-HD-5-3405]
NR 22
TC 41
Z9 43
U1 4
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0001-4575
J9 ACCIDENT ANAL PREV
JI Accid. Anal. Prev.
PD JUL
PY 2011
VL 43
IS 4
BP 1472
EP 1479
DI 10.1016/j.aap.2011.02.026
PG 8
WC Ergonomics; Public, Environmental & Occupational Health; Social
   Sciences, Interdisciplinary; Transportation
SC Engineering; Public, Environmental & Occupational Health; Social
   Sciences - Other Topics; Transportation
GA 773GY
UT WOS:000291296200025
PM 21545880
ER

PT J
AU Marrone, GF
   Shakleya, DM
   Scheidweiler, KB
   Singleton, EG
   Huestis, MA
   Heishman, SJ
AF Marrone, Gina F.
   Shakleya, Diaa M.
   Scheidweiler, Karl B.
   Singleton, Edward G.
   Huestis, Marilyn A.
   Heishman, Stephen J.
TI Relative performance of common biochemical indicators in detecting
   cigarette smoking
SO ADDICTION
LA English
DT Article
DE Assays; biomarker; carbon monoxide; cigarette smokers; cotinine;
   nicotine; non-smokers; saliva; urine
ID IMMUNOASSAY TEST STRIPS; CARBON-MONOXIDE; SALIVA COTININE; NONSMOKERS;
   EXPOSURE; SMOKERS; CESSATION; PRISON; URINE; SERUM
AB Aims Many cities have banned indoor smoking in public places. Thus, an updated recommendation for a breath carbon monoxide (CO) cut-off is needed that optimally determines smoking status. We evaluated and compared the performance of breath CO and semiquantitative cotinine immunoassay test strips (urine and saliva NicAlert (R)) alone and in combination. Design Cross-sectional study. Setting Urban drug addiction research and treatment facility. Participants Ninety non-treatment-seeking smokers and 82 non-smokers. Measurements Participants completed smoking histories and provided breath CO, urine and saliva specimens. Urine and saliva specimens were assayed for cotinine by NicAlert (R) and liquid chromatography-tandem mass spectrometry (LCMSMS). Findings An optimal breath CO cut-off was established using self-report and LCMSMS analysis of cotinine, an objective indicator, as reference measures. Performance of smoking indicators and combinations were compared to the reference measures. Breath CO >= 5 parts per million (p.p.m.) optimally discriminated smokers from non-smokers. Saliva NicAlert (R) performance was less effective than the other indicators. Conclusions In surveys of smokers and non-smokers in areas with strong smoke-free laws, the breath carbon monoxide cut-off that discriminates most effectively appears to be >= 5 p.p.m. rather than the >= 10 p.p.m. cut-off often used. These findings may not generalize to clinical trials, regions with different carbon monoxide pollution levels or areas with less stringent smoke-free laws.
C1 [Marrone, Gina F.; Heishman, Stephen J.] NIDA, Nicotine Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Shakleya, Diaa M.; Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   [Singleton, Edward G.] Stevenson Univ, Dept Psychol, Stevenson, MD USA.
RP Heishman, SJ (reprint author), NIDA, Nicotine Psychopharmacol Sect, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM heishman@nih.gov
OI Singleton, Edward G./0000-0003-3442-877X
FU NIH, National Institute on Drug Abuse
FX This research was supported by the Intramural Research Program of the
   NIH, National Institute on Drug Abuse. We thank Rebecca Lange for
   assistance in conducting the study. We also thank Jaclyn Javerbaum and
   Rima Chakraborty for assistance with the NicAlert (R) assays.
NR 24
TC 13
Z9 13
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0965-2140
J9 ADDICTION
JI Addiction
PD JUL
PY 2011
VL 106
IS 7
BP 1325
EP 1334
DI 10.1111/j.1360-0443.2011.03441.x
PG 10
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 772VE
UT WOS:000291264700023
PM 21438939
ER

PT J
AU Aly, FZ
   Kleiner, DE
AF Aly, Fatima Zahra
   Kleiner, David E.
TI Update on Fatty Liver Disease and Steatohepatitis
SO ADVANCES IN ANATOMIC PATHOLOGY
LA English
DT Review
DE NASH; NAFLD; steatosis; steatohepatitis; adults; pediatric; pathology
ID TERM-FOLLOW-UP; NONALCOHOLIC STEATOHEPATITIS; HEPATIC IRON;
   INSULIN-RESISTANCE; METABOLIC SYNDROME; FIBROSIS; CHILDREN; ASSOCIATION;
   ADOLESCENTS; PREVALENCE
AB Non-alcoholic fatty liver disease (NAFLD) is a broad term that includes liver diseases characterized by abnormal hepatocellular accumulations of lipid that cannot be related to alcohol abuse. It may be found in both adults and children, particularly those who are obese or have insulin resistance. Steatohepatitis is a specific pattern of injury within the spectrum of NAFLD and this pattern is associated with fibrotic progression and cirrhosis. In addition to steatohepatitis, a distinct form of fibrotic fatty liver disease exists in children. There have been a number of recent advances in the characterization of histologic changes in NAFLD. In light of these recent reports, this study will: (1) review the histologic features of steatosis and nonalcoholic steatohepatitis in adults; (2) review the variation of histologic patterns of pediatric fatty liver disease; and (3) discuss the validity and use of the nonalcoholic fatty liver disease Activity Score.
C1 [Aly, Fatima Zahra; Kleiner, David E.] Natl Canc Inst, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Kleiner, DE (reprint author), Natl Canc Inst, Pathol Lab, NIH, Bethesda, MD 20892 USA.
EM kleinerd@mail.nih.gov
OI Kleiner, David/0000-0003-3442-4453
FU NIH, National Cancer Institute
FX Supported by the Intramural Research Program of the NIH, National Cancer
   Institute.
NR 49
TC 20
Z9 22
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-4109
J9 ADV ANAT PATHOL
JI Adv. Anat. Pathol.
PD JUL
PY 2011
VL 18
IS 4
BP 294
EP 300
DI 10.1097/PAP.0b013e318220f59b
PG 7
WC Pathology
SC Pathology
GA 774ZM
UT WOS:000291425500004
PM 21654360
ER

PT J
AU Huang, TTK
   Borowski, LA
   Liu, BM
   Galuska, DA
   Ballard-Barbash, R
   Yanovski, SZ
   Olster, DH
   Atienza, AA
   Smith, AW
AF Huang, Terry T-K
   Borowski, Laurel A.
   Liu, Benmei
   Galuska, Deborah A.
   Ballard-Barbash, Rachel
   Yanovski, Susan Z.
   Olster, Deborah H.
   Atienza, Audie A.
   Smith, Ashley Wilder
TI Pediatricians' and Family Physicians' Weight-Related Care of Children in
   the US
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID BODY-MASS INDEX; HEALTH-CARE; OVERWEIGHT CHILDREN; NATIONAL-SURVEY;
   OBESITY; ATTITUDES; ADOLESCENTS; PREVENTION; GUIDELINES; BARRIERS
AB Background: Few national data exist to assess primary care physicians' (PCPs') clinical practices with regard to childhood obesity.
   Purpose: To survey pediatricians and family practice physicians regarding their assessment, counseling, and management of diet, physical activity, and weight status among pediatric patients in the primary care setting.
   Methods: A nationally representative cross-sectional survey of pediatricians and family practice physicians sampled from the American Medical Association (AMA) Masterfile was conducted in 2008 and analyzed in 2010. Outcomes included physicians' self-reported practice behaviors regarding assessments of pediatric patients' weight status, counseling of diet and physical activity, and referrals and follow-ups.
   Results: Response rate excluding physicians listed as "no-contact" by the AMA was 73.7% among pediatricians and 66.9% among family physicians. Less than 50% of all PCPs assessed BMI percentiles regularly in children. Eighteen percent of all PCPs reported referring children for further evaluation or management. Fifty-eight percent of all PCPs reported never, rarely, or only sometimes tracking patients over time concerning weight or weight-related behaviors. Pediatricians were more likely than family physicians to assess weight status and provide behavioral counseling (p's<0.001).
   Conclusions: Active PCP participation in assessing or managing childhood obesity in the primary care setting appears low relative to the frequency of the problem in the U. S. Interventions to reduce the barriers to physician engagement in the assessment and management of healthy lifestyles are needed to prevent and control childhood obesity. (Am J Prev Med 2011; 41(1): 24-32) (C) 2011 Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine.
C1 [Smith, Ashley Wilder] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Huang, Terry T-K] Kennedy Shriver Natl Inst Child Hlth & Human Dev, Bethesda, MD USA.
   [Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD USA.
   [Olster, Deborah H.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
   [Huang, Terry T-K] Univ Nebraska Med Ctr, Dept Hlth Promot & Social & Behav Hlth, Coll Publ Hlth, Omaha, NE USA.
   [Galuska, Deborah A.] CDC, Div Nutr Phys Act & Obes, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
RP Smith, AW (reprint author), NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7344,Execut Plaza N,Room 409, Bethesda, MD 20892 USA.
EM smithas@mail.nih.gov
FU National Cancer Institute [N02-PC-61301]
FX Data collection for this survey was supported by the National Cancer
   Institute's Contract No. N02-PC-61301.
NR 30
TC 26
Z9 26
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUL
PY 2011
VL 41
IS 1
BP 24
EP 32
DI 10.1016/j.amepre.2011.03.016
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
   Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 775OC
UT WOS:000291468700006
PM 21665060
ER

PT J
AU Smith, AW
   Borowski, LA
   Liu, BM
   Galuska, DA
   Signore, C
   Klabunde, C
   Huang, TTK
   Krebs-Smith, SM
   Frank, E
   Pronk, N
   Ballard-Barbash, R
AF Smith, Ashley Wilder
   Borowski, Laurel A.
   Liu, Benmei
   Galuska, Deborah A.
   Signore, Caroline
   Klabunde, Carrie
   Huang, Terry T-K
   Krebs-Smith, Susan M.
   Frank, Erica
   Pronk, Nico
   Ballard-Barbash, Rachel
TI US Primary Care Physicians' Diet-, Physical Activity-, and
   Weight-Related Care of Adult Patients
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID NATIONAL TRENDS; PROFESSIONALS; ATTITUDES; OBESITY; PRACTITIONERS;
   SPECIALTY; BARRIERS; PROMOTE; WOMEN
AB Background: Overweight and obesity are substantial problems in the U. S., but few national studies exist on primary care physicians' (PCPs') clinical practices regarding overweight and obesity.
   Purpose: To profile diet, physical activity, and weight control practice patterns of PCPs who treat adults.
   Methods: A nationally representative survey of 1211 PCPs sampled from the American Medical Association's Masterfile was conducted in 2008 and analyzed in 2010. Outcomes included PCPs' assessment, counseling, referral, and follow-up of diet, physical activity, and weight control in adult patients with and without chronic disease and PCPs' use of pharmacologic treatments and surgical referrals for overweight and obesity.
   Results: The survey response rate was 64.5%. Half of PCPs (49%) reported recording BMI regularly. Fewer than 50% reported always providing specific guidance on diet, physical activity, or weight control. Regardless of patients' chronic disease status, <10% of PCPs always referred patients for further evaluation/management and <22% reported always systematically tracking patients over time concerning weight or weight-related behaviors. Overall, PCPs were more likely to counsel on physical activity than on diet or weight control (p's<0.05). More than 70% of PCPs reported ever using pharmacologic treatments to treat overweight and 86% had referred for obesity-related surgery.
   Conclusions: PCPs' assessment and behavioral management of overweight and obesity in adults is at a low level relative to the magnitude of the problem in the U. S. Further research is needed to understand barriers to providing care and to improve physician engagement in tracking and managing healthy lifestyles in U. S. adults. (Am J Prev Med 2011; 41(1): 33-42) (C) 2011 Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine.
C1 [Smith, Ashley Wilder] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [Signore, Caroline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Pregnancy & Perinatol Branch, Bethesda, MD USA.
   [Galuska, Deborah A.] CDC, Div Nutr Phys Act & Obes, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
   [Frank, Erica] Univ British Columbia, Dept Family Practice, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada.
   [Pronk, Nico] JourneyWell HealthPartners Res Fdn, Minneapolis, MN USA.
   [Pronk, Nico] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA.
RP Smith, AW (reprint author), NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7344,Execut Plaza N,Room 409, Bethesda, MD 20892 USA.
EM smithas@mail.nih.gov
FU National Cancer Institute [N02-PC-61301]
FX Data collection for this survey was supported by the National Cancer
   Institute's Contract No. N02-PC-61301.
NR 41
TC 35
Z9 38
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUL
PY 2011
VL 41
IS 1
BP 33
EP 42
DI 10.1016/j.amepre.2011.03.017
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
   Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 775OC
UT WOS:000291468700007
PM 21665061
ER

PT J
AU Brown, TM
   Fee, E
AF Brown, Theodore M.
   Fee, Elizabeth
TI Carl E. Taylor, (1916-2010): A Beloved Pioneer in International Health
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Brown, Theodore M.] Univ Rochester, Dept Hist, Rochester, NY 14627 USA.
   [Brown, Theodore M.] Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA.
   [Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA.
RP Brown, TM (reprint author), Univ Rochester, Dept Hist, 601 Elmwood Ave, Rochester, NY 14627 USA.
EM Theodore_Brown@urmc.rochester.edu
NR 3
TC 0
Z9 0
U1 0
U2 4
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2011
VL 101
IS 7
BP 1216
EP 1216
DI 10.2105/AJPH.2010.300036
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 776DG
UT WOS:000291514100017
PM 21653247
ER

PT J
AU Roth, GA
   Fee, E
AF Roth, Ginny A.
   Fee, Elizabeth
TI Smallpox: The First Vaccine
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Roth, Ginny A.; Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20984 USA.
RP Roth, GA (reprint author), NIH, Hist Med Div, Natl Lib Med, 8600 Rockville Pike,MSC-3819,Bldg 38,Room 1E-21, Bethesda, MD 20984 USA.
EM Ginny.Roth@nih.gov
NR 3
TC 2
Z9 2
U1 0
U2 2
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2011
VL 101
IS 7
BP 1217
EP 1217
DI 10.2105/AJPH.2010.300051
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 776DG
UT WOS:000291514100018
PM 21566041
ER

PT J
AU Louie, GH
   Ward, MM
AF Louie, Grant H.
   Ward, Michael M.
TI Socioeconomic and Ethnic Differences in Disease Burden and Disparities
   in Physical Function in Older Adults
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID LOWER-EXTREMITY FUNCTION; UNITED-STATES; CHRONIC DISABILITY;
   RACIAL/ETHNIC DIFFERENCES; NATIONAL-HEALTH; TRENDS; AGE; US; MORTALITY;
   POPULATION
AB Objectives. We investigated whether a greater burden of disease among poorer individuals and ethnic minorities accounted for socioeconomic and racial disparities in self-reported physical functioning among older adults.
   Methods. We used data from adults aged 60 years or older (n=5556) in the Third National Health and Nutrition Examination Survey, 1988-1994 to test associations between education level, poverty index, and race/ethnicity and limitations in 11 functions. We adjusted for demographic features and measures of disease burden (comorbid conditions, smoking, hemoglobin level, serum albumin level, knee pain, body mass index, and skeletal muscle index).
   Results. Associations between education and functional limitations were attenuated after adjustment, but those with 0-8 years of education were more likely than those with 13 or more years of education to have limitations in 3 functions. Poverty was associated with a higher likelihood of limitations despite adjustment. The likelihood of limitations among non-Hispanic Blacks and Mexican Americans was similar to that of non-Hispanic Whites after adjustment.
   Conclusions. Socioeconomic disparities in functional limitations among older Americans exist independent of disease burden, whereas socioeconomic differences and disease burden account for racial disparities. (Am J Public Health. 2011;101:1322-1329. doi:10.2105/AJPH.2010.199455)
C1 [Louie, Grant H.; Ward, Michael M.] NIAMSD, Intramural Res Program, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Louie, GH (reprint author), Johns Hopkins Univ, Div Rheumatol, 5200 Eastern Ave,Mason F Lord Bldg,Suite 4100, Baltimore, MD 21224 USA.
EM glouie2@jhmi.edu
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases at
   the National Institutes of Health
FX The Intramural Research Program of the National Institute of Arthritis
   and Musculoskeletal and Skin Diseases at the National Institutes of
   Health supported this research.
NR 49
TC 18
Z9 19
U1 1
U2 12
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD JUL
PY 2011
VL 101
IS 7
BP 1322
EP 1329
DI 10.2105/AJPH.2010.199455
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 776DG
UT WOS:000291514100035
PM 21164082
ER

PT J
AU Yin, DP
   Gao, Q
   Ma, LL
   Yan, WW
   Williams, PE
   McGuinness, OP
   Wasserman, DH
   Abumrad, NN
AF Yin, Deng Ping
   Gao, Qiang
   Ma, Lian Li
   Yan, Wenwei
   Williams, Phillip E.
   McGuinness, Owen P.
   Wasserman, David H.
   Abumrad, Naji N.
TI Assessment of Different Bariatric Surgeries in the Treatment of Obesity
   and Insulin Resistance in Mice
SO ANNALS OF SURGERY
LA English
DT Article
ID Y GASTRIC BYPASS; FACTOR-KAPPA-B; WEIGHT-LOSS; NONALCOHOLIC
   STEATOHEPATITIS; MODEL; FAT; INFLAMMATION; MECHANISMS; RATS;
   TROGLITAZONE
AB Objective: To assess the effects of different bariatric surgical procedures on the treatment of obesity and insulin resistance in high fat diet-induced obese (DIO) mice.
   Background: Bariatric surgery is currently considered the most effective treatment for morbid obesity and its comorbidities; however, a systematic study of their mechanisms is still lacking.
   Methods: We developed bariatric surgery models, including gastric banding, sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), modified RYGB (mRYGB) and biliopancreatic diversion (BPD), in DIO mice. Body weight, body fat and lean mass, liver steatosis, glucose tolerance and pancreatic beta cell function were examined.
   Results: All bariatric surgeries resulted in significant weight loss, reduced body fat and improved glucose tolerance in the short term (4 weeks), compared with mice with sham surgery. Of the bariatric surgery models, sleeve gastrectomy and mRYGB had higher success rates and lower mortalities and represent reliable restrictive and gastrointestinal (GI) bypass mouse bariatric surgery models, respectively. In the long term, the GI bypass procedure produced more profound weight loss, significant improvement of glucose tolerance and liver steatosis than the restrictive procedure. DIO mice had increased insulin promoter activity, suggesting overactivation of pancreatic beta cells, which was regulated by the mRYGB procedure. Compared with the restrictive procedure, the GI bypass procedure showed more severe symptoms of malnutrition following bariatric surgery.
   Discussions: Both restrictive and GI bypass procedures provide positive effects on weight loss, fat composition, liver steatosis and glucose tolerance; however, in the long term, the GI bypass shows better results than restrictive procedures.
C1 [Yin, Deng Ping; Gao, Qiang; Ma, Lian Li; Yan, Wenwei; Williams, Phillip E.; Abumrad, Naji N.] Vanderbilt Univ, Dept Surg, Med Ctr, Nashville, TN 37235 USA.
   [McGuinness, Owen P.; Wasserman, David H.] Vanderbilt Univ, Mouse Metab Phenotyping Ctr, Med Ctr, Nashville, TN USA.
RP Yin, DP (reprint author), Vanderbilt Univ, Dept Surg, Med Ctr, Nashville, TN 37235 USA.
EM dengping.yin@vanderbilt.edu
FU NIH [R37 DK050277, U24 DK059637, R01 DK070860]; JDRF [1-2008-159]
FX Supported by NIH grant R37 DK050277 and U24 DK059637 to D.W., JDRF grant
   1-2008-159 to D.Y. and NIH grant R01 DK070860 to N.N.A.
NR 48
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Z9 21
U1 0
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-4932
J9 ANN SURG
JI Ann. Surg.
PD JUL
PY 2011
VL 254
IS 1
BP 73
EP 82
DI 10.1097/SLA.0b013e3182197035
PG 10
WC Surgery
SC Surgery
GA 777BQ
UT WOS:000291588600013
PM 21522012
ER

PT J
AU Kaila, VRI
   Oksanen, E
   Goldman, A
   Bloch, DA
   Verkhovsky, MI
   Sundholm, D
   Wikstrom, M
AF Kaila, Ville R. I.
   Oksanen, Esko
   Goldman, Adrian
   Bloch, Dmitry A.
   Verkhovsky, Michael I.
   Sundholm, Dage
   Wikstrom, Marten
TI A combined quantum chemical and crystallographic study on the oxidized
   binuclear center of cytochrome c oxidase
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Article
DE Heme-copper oxidases; Oxygen binding; Density functional theory (DFT);
   X-ray refinement
ID DENSITY-FUNCTIONAL THEORY; BARRIER HYDROGEN-BONDS; AB-INITIO
   CALCULATIONS; HEME-COPPER OXIDASES; ELECTRONIC-STRUCTURE; PROTON
   TRANSLOCATION; PEROXY INTERMEDIATE; MOLECULAR-DYNAMICS;
   CORRELATION-ENERGY; CATALYTIC PATHWAY
AB Cytochrome c oxidase (CcO) is the terminal enzyme of the respiratory chain. By reducing oxygen to water, it generates a proton gradient across the mitochondrial or bacterial membrane. Recently, two independent Xray crystallographic studies ((Aoyama et al. Proc. Natl. Acad. Sci. USA 106 (2009) 2165-2169) and (Koepke et al. Biochim. Biophys. Acta 1787 (2009) 635-645)), suggested that a peroxide dianion might be bound to the active site of oxidized CcO. We have investigated this hypothesis by combining quantum chemical calculations with a re-refinement of the X-ray crystallographic data and optical spectroscopic measurements. Our data suggest that dianionic peroxide, superoxide, and dioxygen all form a similar superoxide species when inserted into a fully oxidized ferric/cupric binuclear site (BNC). We argue that stable peroxides are unlikely to be confined within the oxidized BNC since that would be expected to lead to bond splitting and formation of the catalytic P intermediate. Somewhat surprisingly, we find that binding of dioxygen to the oxidized binuclear site is weakly exergonic, and hence, the observed structure might have resulted from dioxygen itself or from superoxide generated from O-2 by the X-ray beam. We show that the presence of O-2 is consistent with the X-ray data. We also discuss how other structures, such as a mixture of the aqueous species (H2O + OH- and H2O) and chloride fit the experimental data. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Kaila, Ville R. I.; Bloch, Dmitry A.; Verkhovsky, Michael I.; Wikstrom, Marten] Univ Helsinki, Inst Biotechnol, Struct Biol & Biophys Programme, Helsinki Bioenerget Grp, FI-00014 Helsinki, Finland.
   [Kaila, Ville R. I.; Sundholm, Dage] Univ Helsinki, Dept Chem, FI-00014 Helsinki, Finland.
   [Oksanen, Esko; Goldman, Adrian] Univ Helsinki, Inst Biotechnol, Struct Biol & Biophys Programme, Macromol Struct Grp, FI-00014 Helsinki, Finland.
RP Kaila, VRI (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM ville.kaila@nih.gov
RI Oksanen, Esko/D-4639-2009; 
OI Oksanen, Esko/0000-0002-1841-4813; Sundholm, Dage Matts
   Borje/0000-0002-2367-9277
FU HENAKOTO; Academy of Finland; Sigrid Juselius Foundation; National
   Graduate School in Informational and Structural Biology; Academy of
   Finland through its Centers of Excellence
FX This research has been supported by HENAKOTO, the Academy of Finland
   (MW), the Sigrid Juselius Foundation, as well as by the Academy of
   Finland through its Centers of Excellence Programme 2006-2011 (DS). EO
   acknowledges the National Graduate School in Informational and
   Structural Biology for funding. CSC, the Finnish IT Center for Science,
   is acknowledged for computer time. MW is grateful to Dr. Shinya
   Yoshikawa and Dr. Margareta Blomberg for discussions.
NR 84
TC 17
Z9 17
U1 2
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD JUL
PY 2011
VL 1807
IS 7
BP 769
EP 778
DI 10.1016/j.bbabio.2010.12.016
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 776EX
UT WOS:000291518400001
PM 21211513
ER

PT J
AU Sharma, V
   Wikstrom, M
   Kaila, VRI
AF Sharma, Vivek
   Wikstrom, Marten
   Kaila, Ville R. I.
TI Stabilization of the peroxy intermediate in the oxygen splitting
   reaction of cytochrome cbb(3)
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Article
DE Density Functional Theory (DFT); cbb(3)-type cytochrome c oxidase;
   Oxygen activation; Oxygen affinity; Heme-copper oxidases
ID COUPLED ELECTRON-TRANSFER; DENSITY-FUNCTIONAL THEORY; PROTON-PUMPING
   MECHANISM; ACTIVE-SITE RESIDUE; GAUSSIAN-BASIS SETS; O BOND-CLEAVAGE;
   C-OXIDASE; RHODOBACTER-SPHAEROIDES; PARACOCCUS-DENITRIFICANS;
   THERMUS-THERMOPHILUS
AB The proton-pumping cbb(3)-type cytochrome c oxidases catalyze cell respiration in many pathogenic bacteria. For reasons not yet understood, the apparent dioxygen (O-2) affinity in these enzymes is very high relative to other members of the heme-copper oxidase (HCO) superfamily. Based on density functional theory (DFT) calculations on intermediates of the oxygen scission reaction in active-site models of cbb(3)- and aa(3)-type oxidases, we find that a transient peroxy intermediate (I-p, Fe[III]-OOH-) is similar to 6 kcal/mol more stable in the former case, resulting in more efficient kinetic trapping of dioxygen and hence in a higher apparent oxygen affinity. The major molecular basis for this stabilization is a glutamate residue, polarizing the proximal histidine ligand of heme b(3) in the active site. Published by Elsevier B.V.
C1 [Sharma, Vivek; Wikstrom, Marten; Kaila, Ville R. I.] Univ Helsinki, Inst Biotechnol, Programme Struct Biol & Biophys, Helsinki Bioenerget Grp, FIN-00014 Helsinki, Finland.
   [Kaila, Ville R. I.] Univ Helsinki, Dept Chem, FIN-00014 Helsinki, Finland.
   [Kaila, Ville R. I.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Sharma, V (reprint author), Univ Helsinki, Inst Biotechnol, Programme Struct Biol & Biophys, Helsinki Bioenerget Grp, PB 65,Viikinkaari 1, FIN-00014 Helsinki, Finland.
EM vivek.sharma@helsinki.fi; marten.wikstrom@helsinki.fi;
   ville.kaila@nih.gov
RI Sharma, Vivek/G-7383-2012; 
OI Sharma, Vivek/0000-0002-8838-3151
FU Viikki Graduate School in Molecular Biosciences; European Molecular
   Biology Organization (EMBO); National Institutes of Health, National
   Institute of Diabetes and Digestive and Kidney Diseases; Sigrid Juselius
   Foundation; Biocentrum Helsinki; Academy of Finland
FX V.S. is supported by the Viikki Graduate School in Molecular
   Biosciences. V.R.I.K. acknowledges the European Molecular Biology
   Organization (EMBO) for a Long-Term fellowship and the Intramural
   Research Program of the National Institutes of Health, National
   Institute of Diabetes and Digestive and Kidney Diseases for support. The
   work was supported by Sigrid Juselius Foundation, Biocentrum Helsinki
   and the Academy of Finland. Center for Scientific Computing (CSC),
   Finland is acknowledged for providing computing support.
NR 77
TC 5
Z9 5
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD JUL
PY 2011
VL 1807
IS 7
BP 813
EP 818
DI 10.1016/j.bbabio.2011.02.002
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 776EX
UT WOS:000291518400005
PM 21315685
ER

PT J
AU Insel, TR
   Morris, SE
   Heinssen, RK
AF Insel, Thomas R.
   Morris, Sarah E.
   Heinssen, Robert K.
TI Standardization, Integration, and Sharing-Leveraging Research
   Investments
SO BIOLOGICAL PSYCHIATRY
LA English
DT Editorial Material
ID CONSENSUS COGNITIVE BATTERY; NEUROCOGNITIVE DEFICITS; SCHIZOPHRENIA
C1 [Insel, Thomas R.; Morris, Sarah E.; Heinssen, Robert K.] NIMH, Bethesda, MD 20892 USA.
RP Morris, SE (reprint author), 6001 Execut Blvd,Room 7107, Bethesda, MD 20852 USA.
EM sarah.morris@nih.gov
NR 10
TC 2
Z9 2
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUL 1
PY 2011
VL 70
IS 1
BP 5
EP 6
DI 10.1016/j.biopsych.2011.05.004
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 776SX
UT WOS:000291559300004
PM 21672648
ER

PT J
AU Carter, CS
   Barch, DM
   Bullmore, ET
   Breiling, J
   Buchanan, RW
   Butler, P
   Cohen, JD
   Geyer, M
   Gollub, R
   Green, MF
   Jaeger, J
   Krystal, JH
   Moore, H
   Nuechterlein, K
   Robbins, T
   Silverstein, S
   Smith, EE
   Strauss, M
   Wykes, T
AF Carter, Cameron S.
   Barch, Deanna M.
   Bullmore, Edward T.
   Breiling, James
   Buchanan, Robert W.
   Butler, Pamela
   Cohen, Jonathan D.
   Geyer, Mark
   Gollub, Randy
   Green, Michael F.
   Jaeger, Judith
   Krystal, John H.
   Moore, Holly
   Nuechterlein, Keith
   Robbins, Trevor
   Silverstein, Steven
   Smith, Edward E.
   Strauss, Milton
   Wykes, Til
TI Cognitive Neuroscience Treatment Research to Improve Cognition in
   Schizophrenia II: Developing Imaging Biomarkers to Enhance Treatment
   Development for Schizophrenia and Related Disorders
SO BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE Biomarker; CNTRICS; cognition; schizophrenia; treatment
AB The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative, funded by an R13 from the National Institute of Mental Health, seeks to enhance translational research in treatment development for impaired cognition in schizophrenia by developing tools from cognitive neuroscience into useful measures of treatment effects on behavior and brain function. An initial series of meetings focused on the selection of a new set of tasks from cognitive neuroscience for the measurement of treatment effects on specific cognitive and neural systems. Subsequent validation and optimization studies are underway and a subset of validated measures with well-characterized psychometric properties will be generally available in 2011. This article describes results of the first meeting of the second phase of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia, which seeks to develop imaging biomarkers and improved animal models to enhance translational research. In this meeting, we considered issues related to the use of methods such as functional magnetic resonance imaging, electroencephalography, magnetoencephalography, and transcranial magnetic simulation as biomarkers for treatment development. We explored the biological nature of the signals measured by each method, their validity and reliability as measures of cognition-related neural activity, potential confounds related to drug effects on the signal of interest, and conceptual, methodological, and pragmatic issues related to their use in preclinical, first into human, and multicenter phase II and III studies. This overview article describes the background and goals of the meeting together with a summary of the major issues discussed in more detail in the accompanying articles appearing in this issue of Biological Psychiatry.
C1 [Carter, Cameron S.] Univ Calif Davis, UC Davis Imaging Res Ctr, Dept Psychiat, Sacramento, CA 95816 USA.
   [Barch, Deanna M.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA.
   [Barch, Deanna M.] Washington Univ, Dept Psychiat, St Louis, MO USA.
   [Bullmore, Edward T.; Robbins, Trevor] Univ Cambridge, Dept Psychiat, Cambridge, England.
   GlaxoSmithKline, Cambridge, England.
   [Breiling, James] NIMH, Bethesda, MD 20892 USA.
   [Buchanan, Robert W.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
   [Butler, Pamela] SUNY, Dept Psychiat, New York, NY USA.
   [Cohen, Jonathan D.] Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA.
   [Geyer, Mark] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
   [Gollub, Randy] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
   [Green, Michael F.] Univ Calif Los Angeles, Dept Psychiat, Semel Inst, Los Angeles, CA USA.
   [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
   [Jaeger, Judith] AstraZeneca, Wilmington, DE USA.
   [Krystal, John H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
   [Moore, Holly; Smith, Edward E.] Columbia Univ, Dept Psychiat, New York, NY USA.
   [Nuechterlein, Keith] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.
   [Silverstein, Steven] Univ Med & Dent New Jersey, Dept Psychiat, Newark, NJ 07103 USA.
   [Strauss, Milton] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA.
   [Wykes, Til] Kings Coll London, Inst Psychiat, London WC2R 2LS, England.
RP Carter, CS (reprint author), Univ Calif Davis, UC Davis Imaging Res Ctr, Dept Psychiat, 4701 X St, Sacramento, CA 95816 USA.
EM cameron.carter@ucdmc.ucdavis.edu
RI Wykes, Til/B-3812-2011; Barch, Deanna/G-8638-2013; Bullmore,
   Edward/C-1706-2012; 
OI Wykes, Til/0000-0002-5881-8003; Bullmore, Edward/0000-0002-8955-8283;
   Gollub, Randy L./0000-0002-9434-4044
FU US Department of Veterans Affairs Alcohol Research Center; National
   Center for Posttraumatic Stress Disorder; Clinical Neurosciences
   Division, West Haven Connecticut; National Center for Research
   Resources, a component of the National Institutes of Health [UL1
   RR024139]; National Institutes of Health Roadmap for Medical Research;
   GlaxoSmithKline; Allon; Novartis; Cambridge Enterprise Limited;
   University of Cambridge; Cypress Bioscience, Incorporated; Intracellular
   Therapeutics, Incorporated; Ortho-McNeil Janssen Scientific Affairs;
   Pfizer; Lundbeck; Eli Lilly
FX Dr. Krystal acknowledges support from US Department of Veterans Affairs
   Alcohol Research Center, National Center for Posttraumatic Stress
   Disorder, Clinical Neurosciences Division, West Haven, Connecticut, and
   Clinical and Translational Science Awards Grant Number UL1 RR024139 from
   the National Center for Research Resources, a component of the National
   Institutes of Health, and National Institutes of Health Roadmap for
   Medical Research. Its contents are solely the responsibility of the
   authors and do not necessarily represent the official view of National
   Center for Research Resources or National Institutes of Health.; Dr.
   Carter has served as a consultant for Pfizer, Roche, Lilly, Merck, and
   Servier and has received research funding from GlaxoSmithKline.; Dr.
   Barch has received grants from the Allon and Novartis.; Dr. Bullmore is
   an employee of the University of Cambridge (. 5 full-time equivalent)
   and GlaxoSmithKline (. 5 full-time equivalent); a stockholder in
   GlaxoSmithKline and the Brain Resource Company; and has received
   financial compensation resulting from a license agreement between
   Cambridge Enterprise Limited, University of Cambridge, and Cypress
   Bioscience, Incorporated.; Dr. Geyer has received contract research
   support from Intracellular Therapeutics, Incorporated, and compensation
   from Acadia, Addex, Amylin, Cerca Insights, Johnson & Johnson,
   Medivation, Merck, Omeros, Sepracor, Takeda, Teva, and Wyeth-Ayerst and
   holds an equity interest in San Diego Instruments.; Dr. Krystal is a
   consultant for Aisling Capital, LLC; AstraZeneca Pharmaceuticals;
   Brintnall & Nicolini, Incorporated; Easton Associates; Gilead Sciences,
   Incorporated; GlaxoSmithKline; Janssen Pharmaceuticals; Lundbeck
   Research USA; Medivation, Incorporated; Merz Pharmaceuticals; MK Medical
   Communications; Naurex, Incorporated; Pfizer Pharmaceuticals; F.
   Hoffmann-La Roche Ltd.; SK Holdings Company, Ltd.; TakedaIndustries;
   Teva Pharmaceutical Industries, Ltd.; and Transcept Pharmaceuticals and
   on the scientific advisory board of Abbott Laboratories, Bristol-Myers
   Squibb, Eli Lilly and Company, and Lohocla Research Corporation. Dr.
   Krystal also has exercisable warrant options for Tetragenex
   Pharmaceuticals (value less than $150). Research support to Department
   of Veterans Affairs for Janssen Research Foundation (provided drug and
   some study support to the Department of Veterans Affairs); derives
   income greater than $10,000 as the Editor of Biological Psychiatry;
   Board Of Directors for Coalition for Translational Research in Alcohol
   and Substance Use Disorders; President Elect of the American College of
   Neuropsychopharmacology (12-2010); on the Editorial Board of the
   Shanghai Archives of Psychiatry; and has the following patents and
   inventions: 1) Seibyl JP, Krystal JH, Charney DS. Dopamine and
   noradrenergic reuptake inhibitors in treatment of schizophrenia. Patent
   #: 5,447,948. September 5, 1995; 2) Dr. Krystal is aco-inventor with Dr.
   Gerard Sanacora on a filed patent application by Yale University related
   to targeting the glutamatergic system for the treatment of
   neuropsychiatric disorders (PCTWO06108055A1); and 3) Intranasal
   Administration of Ketamine to Treat Depression (pending).; Dr.
   Neuchterlein has received funding from Ortho-McNeil Janssen Scientific
   Affairs (the new name for Janssen, LP) and served as a consultant to
   Merck.; Dr. Robbins has stock options in Cambridge Cognition; serves as
   a consultant for Cambridge Cognition, Pfizer, Eli Lilly,
   GlaxoSmithKline, Wyeth, and Allon Therapeutics; and has received
   research Grants from Pfizer, GlaxoSmithKline, Lundbeck, and Eli Lilly.;
   Dr. Silverstein has received research funding from Pfizer and
   AstraZeneca.
NR 10
TC 36
Z9 37
U1 0
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUL 1
PY 2011
VL 70
IS 1
BP 7
EP 12
DI 10.1016/j.biopsych.2011.01.041
PG 6
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 776SX
UT WOS:000291559300005
PM 21529781
ER

PT J
AU Druz, A
   Chu, C
   Majors, B
   Santuary, R
   Betenbaugh, M
   Shiloach, J
AF Druz, Aliaksandr
   Chu, Chia
   Majors, Brian
   Santuary, Rodell
   Betenbaugh, Michael
   Shiloach, Joseph
TI A Novel MicroRNA mmu-miR-466h Affects Apoptosis Regulation in Mammalian
   Cells
SO BIOTECHNOLOGY AND BIOENGINEERING
LA English
DT Article
DE miRNA; apoptosis; CHO cells
ID HAMSTER OVARY CELLS; RNAI ENZYME COMPLEX; GLUCOSE DEPRIVATION;
   EXPRESSION SYSTEMS; PROTEIN-EXPRESSION; CULTURE-CONDITIONS; MYELOMA
   CELLS; LUNG-CANCER; C-MYC; DEATH
AB This study determined the changes in microRNA (miRs) expression in mammalian Chinese hamster ovary (CHO) cells undergoing apoptosis induced by exposing the cells to nutrient-depleted media. The apoptosis onset was confirmed by reduced cell viability and Caspase-3/7 activation. Microarray comparison of known mouse and rat miRs in CHO cells exposed to fresh or depleted media revealed up-regulation of the mouse miR-297-669 cluster in CHO cells subjected to depleted media. The mmu-miR-466h was chosen for further analysis as the member of this cluster with the highest overexpression and its up-regulation in depleted media was confirmed with qRT-PCR. Since miRs suppress mRNA translation, we hypothesized that up-regulated mmu-miR-466h inhibits anti-apoptotic genes and induces apoptosis. A combination of bioinformatics and experimental tools was used to predict and verify mmu-miR-466h anti-apoptotic targets. 8708 predicted targets were obtained from miRecords database and narrowed to 38 anti-apoptotic genes with DAVID NCBI annotation tool. Several genes were selected from this anti-apoptotic subset based on nucleotide pairing complimentarity between the mmu-miR-466h seed region and 3' UTR of the target mRNAs. The qRT-PCR analysis revealed reduced mRNA levels of bcl2l2, dad1, birc6, stat5a, and smo genes in CHO cells exposed to depleted media. The inhibition of the mmu-miR-466h increased the expression levels of those genes and resulted in increased cell viability and decreased Caspase-3/7 activation. The up-regulation of mmu-miR-466h in response to nutrients depletion causes the inhibition of several anti-apoptotic genes in unison. This suggests the pro-apoptotic role of mmu-miR-466h and its capability to modulate the apoptotic pathway in mammalian cells. Biotechnol. Bioeng. 2011; 108: 1651-1661. (C) 2011 Wiley Periodicals, Inc.
C1 [Druz, Aliaksandr; Chu, Chia; Majors, Brian; Santuary, Rodell; Betenbaugh, Michael] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
   [Druz, Aliaksandr; Chu, Chia; Shiloach, Joseph] NIDDKD, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
RP Betenbaugh, M (reprint author), Johns Hopkins Univ, Dept Chem & Biomol Engn, 3400 N Charles St,NEB 039, Baltimore, MD 21218 USA.
EM yossi@nih.gov; beten@jhu.edu
RI Betenbaugh, Michael J./A-3252-2010
OI Betenbaugh, Michael J./0000-0002-6336-4659
FU National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health
FX Funding was provided by the intramural program of the National Institute
   of Diabetes and Digestive and Kidney Diseases, National Institutes of
   Health.
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PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0006-3592
J9 BIOTECHNOL BIOENG
JI Biotechnol. Bioeng.
PD JUL
PY 2011
VL 108
IS 7
BP 1651
EP 1661
DI 10.1002/bit.23092
PG 11
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 775NV
UT WOS:000291467600017
PM 21337326
ER

PT J
AU Bodiga, S
   Zhong, JC
   Wang, W
   Basu, R
   Lo, J
   Liu, GC
   Guo, D
   Holland, SM
   Scholey, JW
   Penninger, JM
   Kassiri, Z
   Oudit, GY
AF Bodiga, Sreedhar
   Zhong, Jiu Chang
   Wang, Wang
   Basu, Ratnadeep
   Lo, Jennifer
   Liu, George C.
   Guo, Danny
   Holland, Steven M.
   Scholey, James W.
   Penninger, Josef M.
   Kassiri, Zamaneh
   Oudit, Gavin Y.
TI Enhanced susceptibility to biomechanical stress in ACE2 null mice is
   prevented by loss of the p47(phox) NADPH oxidase subunit
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Renin-angiotensin system; Angiotensin 1-7; Angiotensin-converting enzyme
   2; NADPH oxidase; Signalling
ID ANGIOTENSIN-CONVERTING ENZYME-2; OXIDATIVE STRESS; NAD(P)H OXIDASE;
   HEART-FAILURE; CARDIAC-HYPERTROPHY; MATRIX METALLOPROTEINASES;
   PATHOLOGICAL HYPERTROPHY; PRESSURE-OVERLOAD; VASCULAR O-2(-); ACTIVATION
AB Aims Angiotensin-converting enzyme 2 (ACE2) is an important negative regulator of the renin-angiotensin system. Loss of ACE2 enhances the susceptibility to heart disease but the mechanism remains elusive. We hypothesized that ACE2 deficiency activates the NADPH oxidase system in pressure overload-induced heart failure.
   Methods and results Using the aortic constriction model, we subjected wild-type (Ace2(+/y)), ACE2 knockout (ACE2KO, Ace2(-/y)), p47(phox) knockout (p47(phox)KO, p47(phox-/-)), and ACE2/p47(phox) double KO mice to pressure overload. We examined changes in peptide levels, NADPH oxidase activity, gene expression, matrix metalloproteinases (MMP) activity, pathological signalling, and heart function. Loss of ACE2 resulted in enhanced susceptibility to biomechanical stress leading to eccentric remodelling, increased pathological hypertrophy, and worsening of systolic performance. Myocardial angiotensin II (Ang II) levels were increased, whereas Ang 1-7 levels were lowered. Activation of Ang II-stimulated signalling pathways in the ACE2-deficient myocardium was associated with increased expression and phosphorylation of p47(phox), NADPH oxidase activity, and superoxide generation, leading to enhanced MMP-mediated degradation of the extracellular matrix. Additional loss of p47(phox) in the ACE2KO mice normalized the increased NADPH oxidase activity, superoxide production, and systolic dysfunction following pressure overload. Ang 1-7 supplementation suppressed the increased NADPH oxidase and rescued the early dilated cardiomyopathy in pressure-overloaded ACE2KO mice.
   Conclusion In the absence of ACE2, biomechanical stress triggers activation of the myocardial NAPDH oxidase system with a critical role of the p47(phox) subunit. Increased production of superoxide, activation of MMP, and pathological signalling leads to severe adverse myocardial remodelling and dysfunction in ACE2KO mice.
C1 [Bodiga, Sreedhar; Zhong, Jiu Chang; Wang, Wang; Lo, Jennifer; Guo, Danny; Oudit, Gavin Y.] Univ Alberta, Mazankowski Alberta Heart Inst, Dept Med, Div Cardiol, Edmonton, AB T6G 2S2, Canada.
   [Basu, Ratnadeep; Scholey, James W.; Kassiri, Zamaneh; Oudit, Gavin Y.] Univ Alberta, Dept Physiol, Edmonton, AB T6G 2S2, Canada.
   [Liu, George C.] Univ Toronto, Dept Med, Div Nephrol, Univ Hlth Network, Toronto, ON, Canada.
   [Holland, Steven M.] NIAID, Bethesda, MD 20892 USA.
   [Penninger, Josef M.] IMBA, Vienna, Austria.
RP Oudit, GY (reprint author), Univ Alberta, Mazankowski Alberta Heart Inst, Dept Med, Div Cardiol, Edmonton, AB T6G 2S2, Canada.
EM gavin.oudit@ualberta.ca
RI Penninger, Josef/I-6860-2013; 
OI Penninger, Josef/0000-0002-8194-3777; Bodiga,
   Sreedhar/0000-0001-5692-7700
FU National Natural Science Foundation of China; Canadian Institutes of
   Health Research [86602, 84279]; Alberta Innovates-Health Solutions
FX G.Y.O. is a Clinician-Investigator of the Alberta Innovates-Health
   Solutions and the Distinguish Clinician Scientist of the Heart and
   Stroke Foundation of Canada and Canadian Institutes of Health Research.
   Z.K. is a New Investigator of the Heart and Stroke Foundation of Canada
   and a Scholar of the Alberta Innovates-Health Solutions. S. B. and
   J.C.Z. are Fellows of Alberta Innovates-Health Solutions and J.C.Z. is
   also supported by the National Natural Science Foundation of China.; We
   acknowledge the financial support from the Canadian Institutes of Health
   Research (G.Y.O. grant 86602, Z.K. grant 84279) and Alberta
   Innovates-Health Solutions (G.Y.O., S. B., J.C.Z., and Z.K.).
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PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD JUL
PY 2011
VL 91
IS 1
BP 151
EP 161
DI 10.1093/cvr/cvr036
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 776OY
UT WOS:000291547500021
PM 21285291
ER

PT J
AU Liu, Z
   Yang, X
   Li, Z
   McMahon, C
   Sizer, C
   Barenboim-Stapleton, L
   Bliskovsky, V
   Mock, B
   Ried, T
   London, WB
   Maris, J
   Khan, J
   Thiele, CJ
AF Liu, Z.
   Yang, X.
   Li, Z.
   McMahon, C.
   Sizer, C.
   Barenboim-Stapleton, L.
   Bliskovsky, V.
   Mock, B.
   Ried, T.
   London, W. B.
   Maris, J.
   Khan, J.
   Thiele, C. J.
TI CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor
   growth through reprogramming gene expression
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
DE CASZ1; neuroblastoma; tumor suppressor; transcription factor;
   developmental gene; chromosome 1p
ID NEUROTROPHIN RECEPTOR; NERVOUS-SYSTEM; CELL-LINES; DROSOPHILA;
   DIFFERENTIATION; CANCER; CASTOR; METASTASIS; APOPTOSIS; 1P36
AB Neuroblastoma (NB) is a common childhood malignant tumor of the neural crest-derived sympathetic nervous system. In NB the frequent loss of heterozygosity (LOH) on chromosome 1p raises the possibility that this region contains tumor-suppressor genes whose inactivation contributes to tumorigenesis. The human homolog of the Drosophila neural fate determination gene CASZ1, a zinc-finger transcription factor, maps to chromosome 1p36.22, a region implicated in NB tumorigenesis. Quantitative real-time PCR analysis showed that low-CASZ1 expression is significantly correlated with increased age (>= 18 months), Children's Oncology Group high-risk classification, 1p LOH and MYCN amplification (all P<0.0002) and decreased survival probability (P=0.0009). CASZ1 was more highly expressed in NB with a differentiated histopathology (P<0.0001). Retinoids and epigenetic modification agents associated with regulation of differentiation induced CASZ1 expression. Expression profiling analysis revealed that CASZ1 regulates the expression of genes involved in regulation of cell growth and developmental processes. Specific restoration of CASZ1 in NB cells induced cell differentiation, enhanced cell adhesion, inhibited migration and suppressed tumorigenicity. These data are consistent with CASZ1 being a critical modulator of neural cell development, and that somatically acquired disruption of normal CASZ1 expression contributes to the malignant phenotype of human NB. Cell Death and Differentiation (2011) 18, 1174-1183; doi:10.1038/cdd.2010.187; published online 21 January 2011
C1 [Liu, Z.; Yang, X.; Li, Z.; McMahon, C.; Sizer, C.; Khan, J.; Thiele, C. J.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Barenboim-Stapleton, L.; Ried, T.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Bliskovsky, V.; Mock, B.] NCI, Genet Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
   [London, W. B.] Univ Florida, Childrens Oncol Grp, Stat & Data Ctr, Gainesville, FL USA.
   [Maris, J.] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
RP Thiele, CJ (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, Room 1W-3940,10 Ctr Dr, Bethesda, MD 20892 USA.
EM ct47a@nih.gov
RI Khan, Javed/P-9157-2014; Mock, Beverly/B-3110-2015
OI Khan, Javed/0000-0002-5858-0488; Mock, Beverly/0000-0003-2479-4549
FU NIH; National Cancer Institute; Center for Cancer Research; COG NB
   [2004-01]; COG [U10 CA98413]
FX We would like to thank the Children s Oncology Group (COG) Neuroblastoma
   Biology Group Committee for providing us with total RNA from
   neuroblastoma tumors from patients prior to chemotherapy. We thank Dr.
   Cris Q. Doe of Howard Hughes Medical Institute, University of Oregon for
   the critical reading of the manuscript. We would like to thank Drs.
   Chris Redfern, and Quentin Campbell Hewson of the Northern Institute for
   Cancer Research, Newcastle University, UK for providing us with the
   SY5Ytet (SY5Y<SUP>tet12</SUP>) cell line. The NGFR promoter - pGL3 basic
   vectors were generously provided by Philip Barker (Centre for Neuronal
   Survival, Montreal Neurological Institute, McGill University, Canada).
   The control vector pDest-30 with an out-of-frame CAT gene with no start
   codon was generously provided by Dominic Esposito (Protein Expression
   Laboratory, SAIC-Frederick, Inc.). We thank the CCR's Office of Science
   and Technology Partnerships, Drs. Shoshana Segal and David Goldstein for
   their coordination of the strategic partnerships that were key for
   microarray services. The authors thank Ms. Lauren Marks for her
   excellent support of the Cell and Molecular Biology Section, POB, CCR,
   NCI. This research was supported by the Intramural Research Program of
   the NIH, National Cancer Institute, Center for Cancer Research. The
   study of NB tumor samples was done through the COG NB Biology Project
   2004-01, with COG funding from grant number U10 CA98413.
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD JUL
PY 2011
VL 18
IS 7
BP 1174
EP 1183
DI 10.1038/cdd.2010.187
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 776RM
UT WOS:000291555100010
PM 21252912
ER

PT J
AU Zhao, BZ
   Ranguelova, K
   Jiang, JJ
   Mason, RP
AF Zhao, Baozhong
   Ranguelova, Kalina
   Jiang, JinJie
   Mason, Ronald P.
TI Studies on the photosensitized reduction of resorufin and implications
   for the detection of oxidative stress with Amplex Red
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Amplex Red; Resorufin; Photo-reduction; Free radical; NADH; superoxide;
   Hydrogen peroxide
ID ELECTRON-SPIN-RESONANCE; FLUORESCENT DYE 2'-7'-DICHLOROFLUORESCEIN;
   FREE-RADICAL FORMATION; HYDROGEN-PEROXIDE; HORSERADISH-PEROXIDASE;
   SINGLET OXYGEN; DIHYDRORHODAMINE 123; CATALYZED OXIDATION; IN-VIVO;
   SUPEROXIDE
AB The photosensitized reduction of resorufin (RSF), the fluorescent product of Amplex Red, was investigated using electron spin resonance (ESR), optical absorption/fluorescence, and oxygen consumption measurements. Anaerobic reaction of RSF in the presence of the electron donor reduced nicotinamide adenine dinucleotide (NADH) demonstrated that during visible light irradiation (lambda>300 nm), RSF underwent one-electron reduction to produce a semiquinoneimine-type anion radical (RSF(center dot-)) as demonstrated by direct ESR. Spin-trapping studies of incubations containing RSF, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and NADH demonstrated, under irradiation with visible light, the production of the superoxide dismutase (SOD)-sensitive DMPO/(center dot)OOH adduct. Both absorption and fluorescence spectra of RSF in the presence of NADH demonstrated that the RSF(center dot-) was further reduced during irradiation with formation of its colorless dihydroquinoneimine form, dihydroresorufin (RSFH(2)). Both RSF(center dot-) and RSFH(2), when formed in an aerobic system, were immediately oxidized by oxygen, which regenerated the dye and formed superoxide. Oxygen consumption measurements with a Clark-type oxygen electrode showed that molecular oxygen was consumed in a light-dependent process. The suppression of oxygen consumption by addition of SOD or catalase further confirmed the production of superoxide and hydrogen peroxide. Published by Elsevier Inc.
C1 [Zhao, Baozhong; Ranguelova, Kalina; Jiang, JinJie; Mason, Ronald P.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Zhao, BZ (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM zhaob2@niehs.nih.gov
RI Zhao, Baozhong/B-5865-2011
FU NIH, National Institute of Environmental Health Sciences
FX This research was supported by the Intramural Research Program of the
   NIH, National Institute of Environmental Health Sciences. The authors
   are indebted to Mrs. Mary Mason and Dr. Ann Motten for their critical
   reading of the manuscript.
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUL 1
PY 2011
VL 51
IS 1
BP 153
EP 159
DI 10.1016/j.freeradbiomed.2011.03.016
PG 7
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 777NP
UT WOS:000291628700015
PM 21419845
ER

PT J
AU Pendergrass, SA
   Brown-Gentry, K
   Dudek, SM
   Torstenson, ES
   Ambite, JL
   Avery, CL
   Buyske, S
   Cai, C
   Fesinmeyer, MD
   Haiman, C
   Heiss, G
   Hindorff, LA
   Hsu, CN
   Jackson, RD
   Kooperberg, C
   Le Marchand, L
   Lin, Y
   Matise, TC
   Moreland, L
   Monroe, K
   Reiner, AP
   Wallace, R
   Wilkens, LR
   Crawford, DC
   Ritchie, MD
AF Pendergrass, S. A.
   Brown-Gentry, K.
   Dudek, S. M.
   Torstenson, E. S.
   Ambite, J. L.
   Avery, C. L.
   Buyske, S.
   Cai, C.
   Fesinmeyer, M. D.
   Haiman, C.
   Heiss, G.
   Hindorff, L. A.
   Hsu, C. -N.
   Jackson, R. D.
   Kooperberg, C.
   Le Marchand, L.
   Lin, Y.
   Matise, T. C.
   Moreland, L.
   Monroe, K.
   Reiner, A. P.
   Wallace, R.
   Wilkens, L. R.
   Crawford, D. C.
   Ritchie, M. D.
TI The Use of Phenome-Wide Association Studies (PheWAS) for Exploration of
   Novel Genotype-Phenotype Relationships and Pleiotropy Discovery
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE genetic epidemiology; high throughput; phenomics; genetics; PheWAS
ID DISEASE; DESIGN; RISK; VARIANT; SCAN
AB The field of phenomics has been investigating network structure among large arrays of phenotypes, and genome-wide association studies (GWAS) have been used to investigate the relationship between genetic variation and single diseases/outcomes. A novel approach has emerged combining both the exploration of phenotypic structure and genotypic variation, known as the phenome-wide association study (PheWAS). The Population Architecture using Genomics and Epidemiology (PAGE) network is a National Human Genome Research Institute (NHGRI)-supported collaboration of four groups accessing eight extensively characterized epidemiologic studies. The primary focus of PAGE is deep characterization of well-replicated GWAS variants and their relationships to various phenotypes and traits in diverse epidemiologic studies that include European Americans, African Americans, Mexican Americans/Hispanics, Asians/Pacific Islanders, and Native Americans. The rich phenotypic resources of PAGE studies provide a unique opportunity for PheWAS as each genotyped variant can be tested for an association with the wide array of phenotypic measurements available within the studies of PAGE, including prevalent and incident status for multiple common clinical conditions and risk factors, as well as clinical parameters and intermediate biomarkers. The results of PheWAS can be used to discover novel relationships between SNPs, phenotypes, and networks of interrelated phenotypes; identify pleiotropy; provide novel mechanistic insights; and foster hypothesis generation. The PAGE network has developed infrastructure to support and perform PheWAS in a high-throughput manner. As implementing the PheWAS approach has presented several challenges, the infrastructure and methodology, as well as insights gained in this project, are presented herein to benefit the larger scientific community. Genet. Epidemiol. 35: 410-422, 2011. (C) 2011 Wiley-Liss, Inc.
C1 [Pendergrass, S. A.; Brown-Gentry, K.; Dudek, S. M.; Torstenson, E. S.; Crawford, D. C.; Ritchie, M. D.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37232 USA.
   [Ambite, J. L.; Cai, C.; Hsu, C. -N.] Univ So Calif, Inst Informat Sci, Marina Del Rey, CA 90292 USA.
   [Avery, C. L.; Heiss, G.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
   [Buyske, S.] Rutgers State Univ, Dept Stat, Piscataway, NJ USA.
   [Buyske, S.; Matise, T. C.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA.
   [Fesinmeyer, M. D.; Kooperberg, C.; Lin, Y.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
   [Haiman, C.; Monroe, K.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
   [Hindorff, L. A.] NHGRI, NIH, Bethesda, MD 20892 USA.
   [Jackson, R. D.] Ohio State Univ, Columbus, OH 43210 USA.
   [Le Marchand, L.; Wilkens, L. R.] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA.
   [Moreland, L.] Univ Pittsburgh, Pittsburgh, PA USA.
   [Reiner, A. P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Wallace, R.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
   [Wallace, R.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA.
   [Crawford, D. C.; Ritchie, M. D.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
RP Ritchie, MD (reprint author), Vanderbilt Univ, Ctr Human Genet Res, 2215 Garland Ave,519 Light Hall, Nashville, TN 37232 USA.
EM marylyn.ritchie@vanderbilt.edu
RI Crawford, Dana/C-1054-2012; Ritchie, Marylyn/C-1114-2012; 
OI Buyske, Steven/0000-0001-8539-5416
FU National Human Genome Research Institute (NHGRI) [U01HG004803,
   U01HG004798, U01HG004802, U01HG004790, U01HG004801]; NHGRI PAGE
   [U01HG004803, U01HG004802, U01HG004790, U01HG004798-01]; Centers for
   Disease Control and Prevention; Vanderbilt University Center for Human
   Genetics Research; Computational Genomics Core; NIH; National Institute
   of Neurological Disorders and Stroke; National Institutes of Mental
   Health; National Center for Research Resources [M01-RR00425]; National
   Institute of Diabetes and Digestive and Kidney Diseases [DK063491];
   NHLBI [N01-HC65233, N01-HC65234, N01-HC65235, N01-HC65236, N01-HC65237,
   U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, U01 HL65521];
   National Heart, Lung, and Blood Institute; U.S. Department of Health and
   Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13,
   32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; National Cancer
   Institute [R37CA54281, R01 CA63, P01CA33619, U01CA136792, U01CA98758]
FX Contract grant sponsor: National Human Genome Research Institute
   (NHGRI); Contract grant numbers: U01HG004803; U01HG004798; U01HG004802;
   U01HG004790; U01HG004801; Contract grant sponsor: NHGRI PAGE; Contract
   grant numbers: U01HG004798-01; U01HG004802; U01HG004790; U01HG004803;
   Contract grant sponsors: Centers for Disease Control and Prevention;
   Vanderbilt University Center for Human Genetics Research; Computational
   Genomics Core; NIH; National Institute of Neurological Disorders and
   Stroke; National Institutes of Mental Health; National Center for
   Research Resources; Contract grant number: M01-RR00425; Contract grant
   sponsor: National Institute of Diabetes and Digestive and Kidney
   Diseases; Contract grant number: DK063491; Contract grant sponsor:
   NHLBI; Contract grant numbers: N01-HC65233; N01-HC65234; N01-HC65235;
   N01-HC65236; N01-HC65237; U01 HL65520; U01 HL41642; U01 HL41652; U01
   HL41654; U01 HL65521; Contract grant sponsor: National Heart, Lung, and
   Blood Institute; Contract grant numbers: N01-HC-55015; N01-HC-55016;
   N01-HC-55018; N01-HC-55019; N01-HC-55020; N01-HC-55021; N01-HC-55022;
   N01-HC-95095; N01-HC-48047; N01-HC-48048; N01-HC-48049; N01-HC-48050;
   N01-HC-45134; N01-HC-05187; N01-HC-45205; N01-HC-85079; N01-HC-85086;
   N01-HC-35129; N01-HC-15103; N01 HC-55222; N01-HC-75150; N01-HC-45133;
   U01HL080295; R01 HL087652; Contract grant sponsor: U.S. Department of
   Health and Human Services; Contract grant numbers: N01WH22110; 24152;
   32100-2; 32105-6; 32108-9; 32111-13; 32115; 32118-32119; 32122;
   42107-26; 42129-32; 44221; Contract grant sponsor: National Cancer
   Institute; Contract grant numbers: R37CA54281; R01 CA63; P01CA33619;
   U01CA136792; U01CA98758.
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PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD JUL
PY 2011
VL 35
IS 5
BP 410
EP 422
DI 10.1002/gepi.20589
PG 13
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 777CI
UT WOS:000291591100013
PM 21594894
ER

PT J
AU Rouleau, C
   Smale, R
   Fu, YS
   Hui, G
   Wang, F
   Hutto, E
   Fogle, R
   Jones, CM
   Krumbholz, R
   Roth, S
   Curiel, M
   Ren, Y
   Bagley, RG
   Wallar, G
   Miller, G
   Schmid, S
   Horten, B
   Teicher, BA
AF Rouleau, Cecile
   Smale, Robert
   Fu, Yao-Shi
   Hui, Guodong
   Wang, Fei
   Hutto, Elizabeth
   Fogle, Robert
   Jones, Craig M.
   Krumbholz, Roy
   Roth, Stephanie
   Curiel, Maritza
   Ren, Yi
   Bagley, Rebecca G.
   Wallar, Gina
   Miller, Glenn
   Schmid, Steven
   Horten, Bruce
   Teicher, Beverly A.
TI Endosialin is expressed in high grade and advanced sarcomas: Evidence
   from clinical specimens and preclinical modeling
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE endosialin; sarcoma; histologic grade; age; gender
ID SOFT-TISSUE SARCOMAS; DEDIFFERENTIATED LIPOSARCOMA; ENDOTHELIAL-CELLS;
   SYNOVIAL SARCOMA; EWING SARCOMA; CHEST-WALL; TUMORS; RHABDOMYOSARCOMA;
   METASTASIS; MANAGEMENT
AB We previously surveyed the expression of endosialin/CD248/TEM-1 by immunohistochemistry in human clinical specimens of sarcomas and documented expression in tumor cells, stromal cells and vasculature. In the present study, we completed a retrospective analysis of the diagnostic reports available for these same samples in order to identify high-grade and metastatic disease. Our results show that endosialin can be detected in advanced disease. We screened human sarcoma cell lines in vitro for endosialin expression and developed preclinical human xenograft models of disseminated sarcoma. We found that 22 out of 42 human sarcoma cell lines were positive for endosialin with a positive correlation between mRNA and protein levels. When implanted in vivo, endosialin was expressed at all sites of dissemination. These data provide clinical and preclinical evidence that endosialin can be detected in advanced sarcoma. These results demonstrate for the first time that endosialin is a suitable therapeutic target for poor prognosis and advanced disease.
C1 [Rouleau, Cecile; Hui, Guodong; Wang, Fei; Hutto, Elizabeth; Fogle, Robert; Jones, Craig M.; Ren, Yi; Bagley, Rebecca G.; Teicher, Beverly A.] Genzyme Corp, Framingham, MA 01701 USA.
   [Smale, Robert; Fu, Yao-Shi; Curiel, Maritza; Wallar, Gina; Miller, Glenn] Genzyme Genet, Los Angeles, CA USA.
   [Krumbholz, Roy; Roth, Stephanie; Schmid, Steven] Genzyme Corp, San Antonio, TX USA.
   [Horten, Bruce] Genzyme Genet, New York, NY USA.
RP Teicher, BA (reprint author), NCI, Dev Therapeut Program, 6130 Execut Blvd, Rockville, MD 20852 USA.
EM beverly.teicher@nih.gov
NR 51
TC 12
Z9 13
U1 0
U2 0
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 JUL
PY 2011
VL 39
IS 1
BP 73
EP 89
DI 10.3892/ijo.2011.1020
PG 17
WC Oncology
SC Oncology
GA 775ZS
UT WOS:000291504900009
PM 21537839
ER

PT J
AU Wu, C
   Mishra, A
   Yang, J
   Cisar, JO
   Das, A
   Ton-That, H
AF Wu, Chenggang
   Mishra, Arunima
   Yang, Jinghua
   Cisar, John O.
   Das, Asis
   Ton-That, Hung
TI Dual Function of a Tip Fimbrillin of Actinomyces in Fimbrial Assembly
   and Receptor Binding
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID GRAM-POSITIVE BACTERIA; SALIVA-TREATED HYDROXYAPATITE; T14V TYPE-1
   FIMBRIAE; ORAL MICROBIAL COMMUNITIES; CELL-WALL POLYSACCHARIDES;
   PROLINE-RICH PROTEIN; CORYNEBACTERIUM-DIPHTHERIAE; VISCOSUS T14V;
   BIOFILM DEVELOPMENT; APATITIC SURFACES
AB Interaction of Actinomyces oris with salivary proline-rich proteins (PRPs), which serve as fimbrial receptors, involves type 1 fimbriae. Encoded by the gene locus fimQ-fimP-srtC1, the type 1 fimbria is comprised of the fimbrial shaft FimP and the tip fimbrillin FimQ. Fimbrial polymerization requires the fimbria-specific sortase SrtC1, which catalyzes covalent linkage of fimbrial subunits. Using genetics, biochemical methods, and electron microscopy, we provide evidence that the tip fimbrillin, FimQ, is involved in fimbrial assembly and interaction with PRPs. Specifically, while deletion of fimP completely abolished the type 1 fimbrial structures, surface display of monomeric FimQ was not affected by this mutation. Surprisingly, deletion of fimQ significantly reduced surface assembly of the type 1 fimbriae. This defect was rescued by recombinant FimQ ectopically expressed from a plasmid. In agreement with the role of type 1 fimbriae in binding to PRPs, aggregation of A. oris with PRP-coated beads was abrogated in cells lacking srtC1 or fimP. This aggregation defect of the Delta fimP mutant was mainly due to significant reduction of FimQ on the bacterial surface, as the aggregation was not observed in a strain lacking fimQ. Increasing expression of FimQ in the Delta fimP mutant enhanced aggregation, while overexpression of FimP in the Delta fimQ mutant did not. Furthermore, recombinant FimQ, not FimP, bound surface-associated PRPs in a dose-dependent manner. Thus, not only does FimQ function as the major adhesin of the type 1 fimbriae, it also plays an important role in fimbrial assembly.
C1 [Wu, Chenggang; Mishra, Arunima; Ton-That, Hung] Univ Texas Hlth Sci Ctr, Dept Microbiol & Mol Genet, Houston, TX 77030 USA.
   [Yang, Jinghua; Cisar, John O.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA.
   [Das, Asis] Univ Connecticut, Ctr Hlth, Dept Mol Microbial & Struct Biol, Farmington, CT USA.
RP Ton-That, H (reprint author), Univ Texas Hlth Sci Ctr, Dept Microbiol & Mol Genet, 6431 Fannin St,R224-MSE, Houston, TX 77030 USA.
EM ton-that.hung@uth.tmc.edu
OI Ton-That, Hung/0000-0003-1611-0469
FU National Institute of Dental and Craniofacial Research (NIDCR), NIH
   [DE017382]; NIDCR
FX This work was supported by the National Institute of Dental and
   Craniofacial Research (NIDCR), NIH, grant DE017382 to H.T.-T. and by the
   Intramural Research Program of NIDCR (J.O.C.).
NR 47
TC 13
Z9 14
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD JUL
PY 2011
VL 193
IS 13
BP 3197
EP 3206
DI 10.1128/JB.00173-11
PG 10
WC Microbiology
SC Microbiology
GA 777CS
UT WOS:000291592600004
PM 21531799
ER

PT J
AU Ming, M
   Shea, CR
   Feng, L
   Soltani, K
   He, YY
AF Ming, Mei
   Shea, Christopher R.
   Feng, Li
   Soltani, Keyoumars
   He, Yu-Ying
TI UVA Induces Lesions Resembling Seborrheic Keratoses in Mice with
   Keratinocyte-Specific PTEN Downregulation
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Letter
ID BENIGN SKIN TUMORS; FGFR3 MUTATIONS; PIK3CA MUTATIONS; EPIDERMAL NEVI;
   SUPPRESSION; FREQUENCY; SUNLIGHT
C1 [Ming, Mei; Shea, Christopher R.; Soltani, Keyoumars; He, Yu-Ying] Univ Chicago, Dept Med, Dermatol Sect, Chicago, IL 60637 USA.
   [Feng, Li] NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Ming, M (reprint author), Univ Chicago, Dept Med, Dermatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM yyhe@medicine.bsd.uchicago.edu
FU Intramural NIH HHS; NIEHS NIH HHS [R01 ES016936, ES016936, R01
   ES016936-01A2]
NR 19
TC 8
Z9 8
U1 2
U2 8
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 JUL
PY 2011
VL 131
IS 7
BP 1583
EP 1586
DI 10.1038/jid.2011.33
PG 4
WC Dermatology
SC Dermatology
GA 777SI
UT WOS:000291644900030
PM 21390050
ER

PT J
AU Ulatowski, L
   Parker, R
   Davidson, C
   Yanjanin, N
   Kelley, TJ
   Corey, D
   Atkinson, J
   Porter, F
   Arai, H
   Walkley, SU
   Manor, D
AF Ulatowski, L.
   Parker, R.
   Davidson, C.
   Yanjanin, N.
   Kelley, T. J.
   Corey, D.
   Atkinson, J.
   Porter, F.
   Arai, H.
   Walkley, S. U.
   Manor, D.
TI Altered vitamin E status in Niemann-Pick type C disease
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE nutrition; oxidized lipids; Niemann-Pick disease
ID TOCOPHEROL TRANSFER PROTEIN; DENSITY-LIPOPROTEIN UPTAKE; PURIFIED NPC1
   PROTEIN; VIRUS CORE PROTEIN; ALPHA-TOCOPHEROL; CHOLESTEROL ACCUMULATION;
   E-DEFICIENCY; INTRACELLULAR TRAFFICKING; HUMAN HEPATOCYTES; AXONAL
   DYSTROPHY
AB Vitamin E (alpha-tocopherol) is the major lipid-soluble antioxidant in many species. Niemann-Pick type C (NPC) disease is a lysosomal storage disorder caused by mutations in the NPC1 or NPC2 gene, which regulates lipid transport through the endocytic pathway. NPC disease is characterized by massive intracellular accumulation of unesterified cholesterol and other lipids in lysosomal vesicles. We examined the roles that NPC1/2 proteins play in the intracellular trafficking of tocopherol. Reduction of NPC1 or NPC2 expression or function in cultured cells caused a marked lysosomal accumulation of vitamin E in cultured cells. In vivo, tocopherol significantly accumulated in murine Npc1-null and Npc2-null livers, Npc2-null cerebella, and Npc1-null cerebral cortices. Plasma tocopherol levels were within the normal range in Npc1-null and Npc2-null mice, and in plasma samples from human NPC patients. The binding affinity of tocopherol to the purified sterol-binding domain of NPC1 and to purified NPC2 was significantly weaker than that of cholesterol (measurements kindly performed by R. Infante, University of Texas Southwestern Medical Center, Dallas, TX). Taken together, our observations indicate that functionality of NPC1/2 proteins is necessary for proper bio-availability of vitamin E and that the NPC pathology might involve tissue-specific perturbations of vitamin E status.-Ulatowski, L., R. Parker, C. Davidson, N. Yanjanin, T.J. Kelley, D. Corey, J. Atkinson, F. Porter, H. Arai, S. U. Walkley, and D. Manor. Altered vitamin E status in Niemann-Pick type C disease. J. Lipid Res. 2011. 52: 1400-1410.
C1 [Ulatowski, L.; Manor, D.] Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH 44106 USA.
   [Kelley, T. J.; Corey, D.] Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA.
   [Manor, D.] Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA.
   [Parker, R.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
   [Davidson, C.; Walkley, S. U.] Albert Einstein Coll Med, Rose F Kennedy Ctr Res Mental Retardat & Human De, Dept Neurosci, Bronx, NY 10467 USA.
   [Yanjanin, N.; Porter, F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
   [Atkinson, J.] Brock Univ, Dept Chem, St Catharines, ON L2S 3A1, Canada.
   [Arai, H.] Univ Tokyo, Dept Hlth Chem, Tokyo, Japan.
RP Manor, D (reprint author), Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH 44106 USA.
EM dxm178@case.edu
RI Davidson, Cristin/F-4889-2017; 
OI Davidson, Cristin/0000-0002-5508-8113; Atkinson,
   Jeffrey/0000-0003-3710-4893
FU National Institutes of Health [DK-067494, HD-045561]; National
   Institutes of Health, Office of Rare Diseases; National Institutes of
   Health, National Institute of Child Health and Human Development; Ara
   Parseghian Medical Research Foundation (Tucson, AZ); Dana Angel's
   Research Trust (Greenwich, CT)
FX This work was supported by National Institutes of Health Grants
   DK-067494 (D. M.) and HD-045561 (S. U. W.); Bench-to-Bedside Award (F.
   P.) from the National Institutes of Health, Office of Rare Diseases; and
   the Intramural Research Program (F. P.) of the National Institutes of
   Health, National Institute of Child Health and Human Development. Its
   contents are solely the responsibility of the authors and do not
   necessarily represent the official views of the National Institutes of
   Health or other granting agencies. N.Y. was supported by the Ara
   Parseghian Medical Research Foundation (Tucson, AZ) and Dana Angel's
   Research Trust (Greenwich, CT).
NR 89
TC 17
Z9 17
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
J9 J LIPID RES
JI J. Lipid Res.
PD JUL
PY 2011
VL 52
IS 7
BP 1400
EP 1410
DI 10.1194/jlr.M015560
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 775NL
UT WOS:000291466400011
PM 21550990
ER

PT J
AU Jiang, XT
   Sidhu, R
   Porter, FD
   Yanjanin, NM
   Speak, AO
   Vruchte, DTT
   Platt, FM
   Fujiwara, H
   Scherrer, DE
   Zhang, J
   Dietzen, DJ
   Schaffer, JE
   Ory, DS
AF Jiang, Xuntian
   Sidhu, Rohini
   Porter, Forbes D.
   Yanjanin, Nicole M.
   Speak, Anneliese O.
   Vruchte, Danielle Taylor Te
   Platt, Frances M.
   Fujiwara, Hideji
   Scherrer, David E.
   Zhang, Jessie
   Dietzen, Dennis J.
   Schaffer, Jean E.
   Ory, Daniel S.
TI A sensitive and specific LC-MS/MS method for rapid diagnosis of
   Niemann-Pick C1 disease from human plasma
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE cholesterol; diagnostic tools; liquid chromatography/tandem mass
   spectrometry; Niemann-Pick disease; oxysterols; neurodegeneration
ID DILUTION MASS-SPECTROMETRY; CHOLESTEROL TRAFFICKING; OXIDATION-PRODUCTS;
   GENE; IDENTIFICATION; OXYSTEROLS; PHENOTYPE; SERUM; MICE; NPC1
AB Niemann-Pick type C1 (NPC1) disease is a rare, progressively fatal neurodegenerative disease for which there are no FDA-approved therapies. A major barrier to developing new therapies for this disorder has been the lack of a sensitive and noninvasive diagnostic test. Recently, we demonstrated that two cholesterol oxidation products, specifically cholestane-3 beta,5 alpha,6 beta-triol (3 beta,5 alpha,6 beta-triol) and 7-ketocholesterol (7-KC), were markedly increased in the plasma of human NPC1 subjects, suggesting a role for these oxysterols in diagnosis of NPC1 disease and evaluation of therapeutics in clinical trials. In the present study, we describe the development of a sensitive and specific LC-MS/MS method for quantifying 3 beta,5 alpha,6 beta-triol and 7-KC human plasma after derivatization with N,N-dimethylglycine. We show that dimethylglycine derivatization successfully enhanced the ionization and fragmentation of 3 beta,5 alpha,6 beta-triol and 7-KC for mass spectrometric detection of the oxysterol species in human plasma. The oxysterol dimethylglycinates were resolved with high sensitivity and selectivity, and enabled accurate quantification of 3 beta,5 alpha,6 beta-triol and 7-KC concentrations in human plasma. The LC-MS/MS assay was able to discriminate with high sensitivity and specificity between control and NPC1 subjects, and offers for the first time a noninvasive, rapid, and highly sensitive method for diagnosis of NPC1 disease.-Jiang, X., R. Sidhu, F. D. Porter, N. M. Yanjanin, A. O. Speak, D. Taylor te Vruchte, F. M. Platt, H. Fujiwara, D. E. Scherrer, J. Zhang, D. J. Dietzen, J. E. Schaffer, and D. S. Ory. A sensitive and specifi c LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma. J. Lipid Res. 2011. 52: 1435-1445.
C1 [Jiang, Xuntian; Sidhu, Rohini; Fujiwara, Hideji; Scherrer, David E.; Zhang, Jessie; Schaffer, Jean E.; Ory, Daniel S.] Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO 63130 USA.
   [Dietzen, Dennis J.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
   [Porter, Forbes D.; Yanjanin, Nicole M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, US Dept HHS, Bethesda, MD USA.
   [Speak, Anneliese O.; Vruchte, Danielle Taylor Te; Platt, Frances M.] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England.
RP Ory, DS (reprint author), Washington Univ, Sch Med, Diabet Cardiovasc Dis Ctr, St Louis, MO 63130 USA.
EM dory@wustl.edu
RI Sidhu, Rohini/G-3547-2012; 
OI Speak, Anneliese/0000-0003-4890-4685
FU Washington University Specialized Centers of Clinically Oriented [P50
   HL083762]; Dana's Angels Research Trust; Ara Parseghian Medical Research
   Foundation; Medical Research Council, UK; Action Medical Research, UK;
   Eunice Kennedy Shriver National Institute of Child Health and Human
   Development; Office of Rare Diseases
FX This work was performed in the Metabolomics Facility at Washington
   University. The authors received support from the Washington University
   Specialized Centers of Clinically Oriented Research grant P50 HL083762
   (D.S.O.), Dana's Angels Research Trust (D.S.O. and N.Y.), Ara Parseghian
   Medical Research Foundation (D.S.O. and N.Y.), Medical Research Council,
   UK (A.S.), and Action Medical Research, UK (D.T.V.). This study was also
   supported by the intramural research program of the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development (F. D.
   P.) and a Bench to Bedside award from the Office of Rare Diseases
   (F.D.P. and D.S.O.).
NR 30
TC 89
Z9 92
U1 5
U2 11
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
J9 J LIPID RES
JI J. Lipid Res.
PD JUL
PY 2011
VL 52
IS 7
BP 1435
EP 1445
DI 10.1194/jlr.D015735
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 775NL
UT WOS:000291466400015
PM 21518695
ER

PT J
AU Yasunaga, J
   Lin, FC
   Lu, XB
   Jeang, KT
AF Yasunaga, Junichiro
   Lin, Frank C.
   Lu, Xiongbin
   Jeang, Kuan-Teh
TI Ubiquitin-Specific Peptidase 20 Targets TRAF6 and Human T Cell Leukemia
   Virus Type 1 Tax To Negatively Regulate NF-kappa B Signaling
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID DEUBIQUITINATING ENZYMES; ISOMERASE PIN1; HTLV-2 TAX2; ACTIVATION; A20;
   ONCOPROTEIN; PATHWAYS; PROTEIN; GENE; NEMO
AB NF-kappa B plays a key role in innate and acquired immunity. Its activity is regulated through intricate signaling networks. Persistent or excessive activation of NF-kappa B induces diseases, such as autoimmune disorders and malignant neoplasms. Infection by human T cell leukemia virus type 1 (HTLV-1) causes a fatal hematopoietic malignancy termed adult T cell leukemia (ATL). The HTLV-1 viral oncoprotein Tax functions pivotally in leukemogenesis through its potent activation of NF-kappa B. Recent findings suggest that protein ubiquitination is crucial for proper regulation of NF-kappa B signaling and for Tax activity. Here, we report that ubiquitin-specific peptidase USP20 deubiquitinates TRAF6 and Tax and suppresses interleukin 1 beta (IL-1 beta)- and Tax-induced NF-kappa B activation. Our results point to USP20 as a key negative regulator of Tax-induced NF-kappa B signaling.
C1 [Yasunaga, Junichiro; Lin, Frank C.; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
   [Lu, Xiongbin] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
RP Jeang, KT (reprint author), 9000 Rockville Pike,Bldg 4,Room 303, Bethesda, MD 20892 USA.
EM kjeang@niaid.nih.gov
RI Jeang, Kuan-Teh/A-2424-2008; 
OI Yasunaga, Jun-ichirou/0000-0002-7939-2080
FU NIAID; NIH; NCI/NIH [R01CA136549]
FX Work in K.-T.J.'s laboratory is supported in part by intramural funds
   from NIAID, NIH. Xiongbin Lu is supported by grant R01CA136549 from
   NCI/NIH.
NR 53
TC 40
Z9 41
U1 0
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 JUL
PY 2011
VL 85
IS 13
BP 6212
EP 6219
DI 10.1128/JVI.00079-11
PG 8
WC Virology
SC Virology
GA 775CG
UT WOS:000291434300013
PM 21525354
ER

PT J
AU Morner, A
   Jansson, M
   Bunnik, EM
   Scholler, J
   Vaughan, R
   Wang, YF
   Montefiori, DC
   Otting, N
   Bontrop, R
   Bergmeier, LA
   Singh, M
   Wyatt, RT
   Schuitemaker, H
   Biberfeld, G
   Thorstensson, R
   Lehner, T
AF Morner, Andreas
   Jansson, Marianne
   Bunnik, Evelien M.
   Scholler, Jorgen
   Vaughan, Robert
   Wang, Yufei
   Montefiori, David C.
   Otting, Nel
   Bontrop, Ronald
   Bergmeier, Lesley A.
   Singh, Mahavir
   Wyatt, Richard T.
   Schuitemaker, Hanneke
   Biberfeld, Gunnel
   Thorstensson, Rigmor
   Lehner, Thomas
TI Immunization with Recombinant HLA Classes I and II, HIV-1 gp140, and SIV
   p27 Elicits Protection against Heterologous SHIV Infection in Rhesus
   Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; ANTIBODY-RESPONSES;
   LEUKOCYTE ANTIGEN; IMMUNE-RESPONSES; VACCINE; COMPLEMENT; CHALLENGE;
   TYPE-1; NEUTRALIZATION
AB Major histocompatibility complex (MHC) molecules expressed on the surface of human immunodeficiency virus (HIV) are potential targets for neutralizing antibodies. Since MHC molecules are polymorphic, nonself MHC can also be immunogenic. We have used combinations of novel recombinant HLA class I and II and HIV/simian immunodeficiency virus (SIV) antigens, all linked to dextran, to investigate whether they can elicit protective immunity against heterologous simian/human immunodeficiency virus (SHIV) challenge in rhesus macaques. Three groups of animals were immunized with HLA (group 1, n = 8), trimeric YU2 HIV type 1 (HIV-1) gp140 and SIV p27 (HIV/SIV antigens; group 2, n = 8), or HLA plus HIV/SIV antigens (group 3, n = 8), all with Hsp70 and TiterMax Gold adjuvant. Another group (group 4, n = 6) received the same vaccine as group 3 without TiterMax Gold. Two of eight macaques in group 3 were completely protected against intravenous challenge with 18 50% animal infective doses (AID(50)) of SHIV-SF162P4/C grown in human cells expressing HLA class I and II lineages represented in the vaccine, while the remaining six macaques showed decreased viral loads compared to those in unimmunized animals. Complement-dependent neutralizing activity in serum and high levels of anti-HLA antibodies were elicited in groups 1 and 3, and both were inversely correlated with the plasma viral load at 2 weeks postchallenge. Antibody-mediated protection was strongly supported by the fact that transfer of pooled serum from the two challenged but uninfected animals protected two naive animals against repeated low-dose challenge with the same SHIV stock. This study demonstrates that immunization with recombinant HLA in combination with HIV-1 antigens might be developed into an alternative strategy for a future AIDS vaccine.
C1 [Morner, Andreas; Jansson, Marianne; Biberfeld, Gunnel; Thorstensson, Rigmor] Swedish Inst Communicable Dis Control, Vaccinol Unit, S-17182 Solna, Sweden.
   [Jansson, Marianne; Biberfeld, Gunnel] Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Solna, Sweden.
   [Bunnik, Evelien M.; Schuitemaker, Hanneke] Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam, Dept Expt Immunol,Landsteiner Lab, NL-1105 AZ Amsterdam, Netherlands.
   [Scholler, Jorgen] Immudex, Copenhagen, Denmark.
   [Vaughan, Robert] Kings Coll London, Guys Hosp, Dept Tissue Typing, London WC2R 2LS, England.
   [Wang, Yufei; Lehner, Thomas] Kings Coll London, Guys Hosp, Mucosal Immunol Unit, London WC2R 2LS, England.
   [Montefiori, David C.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA.
   [Otting, Nel; Bontrop, Ronald] Biomed Primate Res Ctr, Dept Comparat Genet & Refinement, Rijswijk, Netherlands.
   [Bergmeier, Lesley A.] Univ London, Barts & London Sch Med, Ctr Clin & Diagnost Oral Sci, London, England.
   [Bergmeier, Lesley A.] Univ London, Barts & London Sch Dent, Ctr Clin & Diagnost Oral Sci, London, England.
   [Singh, Mahavir] Lionex GmbH, Braunschweig, Germany.
   [Wyatt, Richard T.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Morner, A (reprint author), Swedish Inst Communicable Dis Control, Vaccinol Unit, S-17182 Solna, Sweden.
EM andreas.morner@smi.se; thomas.lehner@kcl.ac.uk
RI Bontrop, Ronald/J-3628-2012; 
OI Bontrop, Ronald/0000-0003-0874-6467; Morner, Andreas/0000-0002-3654-1728
FU Bill & Melinda Gates Foundation [38608]; NIH
FX This study was funded by Bill & Melinda Gates Foundation grant 38608 as
   part of the Collaboration for AIDS Vaccine Discovery (CAVD). Development
   and production of trimeric HIV-1 gp140 was supported by the NIH
   intramural research program.
NR 47
TC 6
Z9 6
U1 0
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 JUL
PY 2011
VL 85
IS 13
BP 6442
EP 6452
DI 10.1128/JVI.00129-11
PG 11
WC Virology
SC Virology
GA 775CG
UT WOS:000291434300033
PM 21490092
ER

PT J
AU Kumar, S
   Nayak, B
   Collins, PL
   Samal, SK
AF Kumar, Sachin
   Nayak, Baibaswata
   Collins, Peter L.
   Samal, Siba K.
TI Evaluation of the Newcastle Disease Virus F and HN Proteins in
   Protective Immunity by Using a Recombinant Avian Paramyxovirus Type 3
   Vector in Chickens
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID COMPLETE GENOME SEQUENCE; HEMAGGLUTININ-NEURAMINIDASE PROTEIN; FUSION
   PROTEIN; FOWLPOX VIRUS; FOREIGN GENE; CLONED CDNA;
   MONOCLONAL-ANTIBODIES; VACCINE VECTOR; CLEAVAGE SITE; IMMUNIZATION
AB Newcastle disease virus (NDV) belongs to serotype 1 of the avian paramyxoviruses (APMV-1) and causes severe disease in chickens. Current live attenuated NDV vaccines are not fully satisfactory. An alternative is to use a viral vector vaccine that infects chickens but does not cause disease. APMV serotype 3 infects a wide variety of avian species but does not cause any apparent disease in chickens. In this study, we constructed a reverse-genetics system for recovery of infectious APMV-3 strain Netherlands from cloned cDNAs. Two recombinant viruses, rAPMV3-F and rAPMV3-HN, were generated expressing the NDV fusion (F) and hemagglutinin-neuraminidase (HN) proteins, respectively, from added genes. These viruses were used to immunize 2-week-old chickens by the oculonasal route in order to evaluate the contribution of each protein to the induction of NDV-specific neutralizing antibodies and protective immunity. Each virus induced high titers of NDV-specific hemagglutination inhibition and serum neutralizing antibodies, but the response to F protein was greater. Protective immunity was evaluated by challenging the immunized birds 21 days later with virulent NDV via the oculonasal, intramuscular, or intravenous route. With oculonasal or intramuscular challenge, all three recombinant viruses (rAPMV3, rAPMV3-F, and rAPMV3-HN) were protective, while all unvaccinated birds succumbed to death. These results indicated that rAPMV3 alone can provide cross-protection against NDV challenge. However, with intravenous challenge, birds immunized with rAPMV3 were not protected, whereas birds immunized with rAPMV3-F alone or in combination with rAPMV3-HN were completely protected, and birds immunized with rAPMV3-HN alone were partially protected. These results indicate that the NDV F and HN proteins are independent neutralization and protective antigens, but the contribution by F is greater. rAMPV3 represents an avirulent vaccine vector that can be used against NDV and other poultry pathogens.
C1 [Kumar, Sachin; Nayak, Baibaswata; 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 NIAID [N01A060009]; NIAID, NIH
FX This research was supported by NIAID contract no. N01A060009 (85%
   support) and the NIAID, NIH Intramural Research Program (15% support).
NR 69
TC 25
Z9 27
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUL
PY 2011
VL 85
IS 13
BP 6521
EP 6534
DI 10.1128/JVI.00367-11
PG 14
WC Virology
SC Virology
GA 775CG
UT WOS:000291434300040
PM 21525340
ER

PT J
AU Hansman, GS
   Biertumpfel, C
   Georgiev, I
   McLellan, JS
   Chen, L
   Zhou, TQ
   Katayama, K
   Kwong, PD
AF Hansman, Grant S.
   Biertuempfel, Christian
   Georgiev, Ivelin
   McLellan, Jason S.
   Chen, Lei
   Zhou, Tongqing
   Katayama, Kazuhiko
   Kwong, Peter D.
TI Crystal Structures of GII.10 and GII.12 Norovirus Protruding Domains in
   Complex with Histo-Blood Group Antigens Reveal Details for a Potential
   Site of Vulnerability
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NORWALK VIRUS-INFECTION; DIFFRACTION DATA; SIALIC-ACID; BINDING;
   GASTROENTERITIS; SUSCEPTIBILITY; IDENTIFICATION; STRAIN; HEMAGGLUTININ;
   CONSERVATION
AB Noroviruses are the dominant cause of outbreaks of gastroenteritis worldwide, and interactions with human histo-blood group antigens (HBGAs) are thought to play a critical role in their entry mechanism. Structures of noroviruses from genogroups GI and GII in complex with HBGAs, however, reveal different modes of interaction. To gain insight into norovirus recognition of HBGAs, we determined crystal structures of norovirus protruding domains from two rarely detected GII genotypes, GII.10 and GII.12, alone and in complex with a panel of HBGAs, and analyzed structure-function implications related to conservation of the HBGA binding pocket. The GII.10- and GII.12-apo structures as well as the previously solved GII.4-apo structure resembled each other more closely than the GI.1-derived structure, and all three GII structures showed similar modes of HBGA recognition. The primary GII norovirus-HBGA interaction involved six hydrogen bonds between a terminal alpha fucose1-2 of the HBGAs and a dimeric capsid interface, which was composed of elements from two protruding subdomains. Norovirus interactions with other saccharide units of the HBGAs were variable and involved fewer hydrogen bonds. Sequence analysis revealed a site of GII norovirus sequence conservation to reside under the critical alpha fucose1-2 and to be one of the few patches of conserved residues on the outer virion-capsid surface. The site was smaller than that involved in full HBGA recognition, a consequence of variable recognition of peripheral saccharides. Despite this evasion tactic, the HBGA site of viral vulnerability may provide a viable target for small molecule- and antibody-mediated neutralization of GII norovirus.
C1 [Kwong, Peter D.] NIAID, Struct Biol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Hansman, Grant S.; Katayama, Kazuhiko] Natl Inst Infect Dis, Dept Virol 2, Tokyo 2080011, Japan.
RP Kwong, PD (reprint author), NIAID, Struct Biol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40,Room 4508, Bethesda, MD 20892 USA.
EM pdkwong@nih.gov
RI McLellan, Jason/A-6874-2010; Hansman, Grant/K-7983-2013; Zhou,
   Tongqing/A-6880-2010
OI Biertumpfel, Christian/0000-0002-7528-6547; Hansman,
   Grant/0000-0001-8735-4618; Zhou, Tongqing/0000-0002-3935-4637
FU National Institutes of Health (United States); Japan Health Science
   Foundation; Ministry of Health, Labor, and Welfare of Japan; U.S.
   Department of Energy, Basic Energy Sciences, Office of Science
   [W-31-109-Eng-38]
FX Support for this work was provided by the Intramural Research Program of
   the National Institutes of Health (United States), by a grant from The
   Japan Health Science Foundation, and by grants from the Ministry of
   Health, Labor, and Welfare of Japan. Use of sector 22 (Southeast Region
   Collaborative Access Team) at the Advanced Photon Source was supported
   by the U.S. Department of Energy, Basic Energy Sciences, Office of
   Science, under contract W-31-109-Eng-38.
NR 48
TC 59
Z9 63
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUL
PY 2011
VL 85
IS 13
BP 6687
EP 6701
DI 10.1128/JVI.00246-11
PG 15
WC Virology
SC Virology
GA 775CG
UT WOS:000291434300055
PM 21525337
ER

PT J
AU Shen, M
   Zheng, TZ
   Lan, Q
   Zhang, YW
   Hosgood, HD
   Zahm, SH
   Holford, TR
   Leaderer, B
   Yeager, M
   Yuenger, J
   Chanock, S
   Rothman, N
AF Shen, Min
   Zheng, Tongzhang
   Lan, Qing
   Zhang, Yawei
   Hosgood, H. Dean, III
   Zahm, Shelia H.
   Holford, Theodore R.
   Leaderer, Brian
   Yeager, Meredith
   Yuenger, Jeff
   Chanock, Stephen
   Rothman, Nathaniel
TI Polymorphisms in integrin genes and lymphoma risk
SO LEUKEMIA RESEARCH
LA English
DT Article
DE Lymphoma; Integrin; Innate immunity; Single nucleotide polymorphism
ID IMMUNITY
AB Immune deficiency is one of the best characterized and strongest known risk factors for non-Hodgkin lymphoma (NHL). We studied the association between single nucleotide polymorphisms (SNPs) in integrin genes that are important components in human innate immunity and the risk of NHL in a population-based case-control study of women in Connecticut, USA. A total of 373 tag SNPs in 33 gene regions were included in the analysis of 448 cases and 525 controls. The ADAM19 rs11466782 SNP was associated with an increased risk of lymphoma (OR, 1.73; 95% CI, 1.28-2.35; P(additive) = 0.0004), and the ICAM3 rs2304240 (OR, 0.67; 95% CI, 0.52-0.86; P(additive) = 0.002) and the PTGDR rs708486 SNPs (OR, 0.75; 95% CI, 0.63-0.90; P(additive) = 0.002) were associated with reduced risk of lymphoma. Two gene regions (ADAM19 (P = 0.009) and ICAM3 (P = 0.009)) displayed global associations with lymphoma risk at the P < 0.01 level. While our results suggest that genetic polymorphisms in integrin genes may play a role in the genesis of lymphoma in women, they should be viewed as exploratory until they are replicated in additional populations. Published by Elsevier Ltd.
C1 [Shen, Min; Lan, Qing; Hosgood, H. Dean, III; Zahm, Shelia H.; Yeager, Meredith; Yuenger, Jeff; Chanock, Stephen; Rothman, Nathaniel] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
   [Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Leaderer, Brian] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
RP Hosgood, HD (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, MSC 7240,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM hosgoodd@mail.nih.gov
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
   NIH [CA62006]
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 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.
   Support for this study was also provided by the NIH grant CA62006 (T.Z.)
NR 8
TC 5
Z9 5
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2126
J9 LEUKEMIA RES
JI Leuk. Res.
PD JUL
PY 2011
VL 35
IS 7
BP 968
EP 970
DI 10.1016/j.leukres.2010.12.012
PG 3
WC Oncology; Hematology
SC Oncology; Hematology
GA 775OS
UT WOS:000291470800040
PM 21239057
ER

PT J
AU Kashaw, SK
   Kashaw, V
   Mishra, P
   Jain, NK
   Stables, JP
AF Kashaw, Sushil K.
   Kashaw, Varsha
   Mishra, Pradeep
   Jain, N. K.
   Stables, J. P.
TI Design, synthesis, and potential CNS activity of some new bioactive
   1-(4-substituted-phenyl)-3-(4-oxo-2-methyl-4H-quinazolin-3-yl)-urea
SO MEDICINAL CHEMISTRY RESEARCH
LA English
DT Article
DE 4(3H)-quinazolinone; Anticonvulsant; Sedative-hypnotic
ID DEPRESSANT ACTIVITY; ANTICONVULSANT ACTIVITIES; QUINAZOLINE-4(3H)-ONES;
   SEMICARBAZONES
AB Twelve new 1-(4-substituted-phenyl)-3-(4-oxo-2-methyl-4H-quinazolin-3-yl)-urea were synthesized and screened for anticonvulsant, CNS depressant, and sedative-hypnotic activity. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight 2,3-Disubstituted-quinazolin-4(3H)-one were examined in the maximal electroshock-induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Spectroscopic data and elemental analysis were consistent with the newly synthesized compounds. The neurotoxicity was assessed using the rotorod method. M3, M4, and M10 were found to be active in both MES screen and scPTZ screen at 0.5 h. All except M11 showed more than 44% decrease in locomotor activity after 1 h of compound administration via actophotometer screen. CNS-depressant activity screened with the help of the forced swim method resulted into some potent compounds. Except for M6 and M11 other tested compounds were found to exhibit potent CNS depressants activity as indicated by increased immobility time. It can be concluded that newly synthesized compounds possessed sedative-hypnotic and CNS depressant activities.
C1 [Kashaw, Sushil K.; Kashaw, Varsha; Mishra, Pradeep; Jain, N. K.] Dr Hari Singh Gour Vishwavidyalaya, Dept Pharmaceut Sci, Pharmaceut Chem Div, Sagar, India.
   [Stables, J. P.] NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA.
RP Kashaw, SK (reprint author), Dr Hari Singh Gour Vishwavidyalaya, Dept Pharmaceut Sci, Pharmaceut Chem Div, Sagar, India.
EM sushilkashaw@gmail.com
NR 19
TC 0
Z9 0
U1 0
U2 0
PU BIRKHAUSER BOSTON INC
PI CAMBRIDGE
PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 USA
SN 1054-2523
J9 MED CHEM RES
JI Med. Chem. Res.
PD JUL
PY 2011
VL 20
IS 6
BP 738
EP 745
DI 10.1007/s00044-010-9362-x
PG 8
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 775WN
UT WOS:000291494300010
ER

PT J
AU Lin, NW
   Li, XG
   Cui, KR
   Chepelev, I
   Tie, F
   Liu, B
   Li, GY
   Harte, P
   Zhao, KJ
   Huang, SM
   Zhou, L
AF Lin, Nianwei
   Li, Xingguo
   Cui, Kairong
   Chepelev, Iouri
   Tie, Feng
   Liu, Bo
   Li, Guangyao
   Harte, Peter
   Zhao, Keji
   Huang, Suming
   Zhou, Lei
TI A Barrier-Only Boundary Element Delimits the Formation of Facultative
   Heterochromatin in Drosophila melanogaster and Vertebrates
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID POLYCOMB RESPONSE ELEMENT; CCAAT DISPLACEMENT PROTEIN; ENHANCER-BLOCKING
   ACTIVITY; CENTRAL-NERVOUS-SYSTEM; NEUROBLAST APOPTOSIS; NEURAL
   PROLIFERATION; DNA METHYLATION; GENE-EXPRESSION; FAB-7 BOUNDARY; CUT
   REPEAT
AB Formation of facultative heterochromatin at specific genomic loci is fundamentally important in defining cellular properties such as differentiation potential and responsiveness to developmental, physiological, and environmental stimuli. By the nature of their formation, heterochromatin and repressive histone marks propagate until the chain reaction is broken. While certain active promoters can block propagation of heterochromatin, there are also specialized DNA elements, referred to as chromatin barriers, that serve to demarcate the boundary of facultative heterochromatin formation. In this study, we identified a chromatin barrier that specifically limits the formation of repressive chromatin to a distal enhancer region so that repressive histone modifications cannot reach the promoter and promoter-proximal enhancer regions of reaper. Unlike all of the known boundary elements identified for Drosophila melanogaster, this IRER (irradiation-responsive enhancer region) left barrier (ILB) does not exhibit enhancer-blocking activity. Not only has the ILB been conserved in different Drosophila species, it can also function as an effective chromatin barrier in vertebrate cells. This suggests that the mechanism by which it functions to spatially restrict the formation of repressive chromatin marked by trimethylated H3K27 has also been conserved widely during evolution.
C1 [Lin, Nianwei; Liu, Bo; Li, Guangyao; Zhou, Lei] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
   [Lin, Nianwei; Liu, Bo; Li, Guangyao; Zhou, Lei] Univ Florida, UF Shands Canc Ctr, Gainesville, FL 32610 USA.
   [Li, Xingguo; Huang, Suming] Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
   [Cui, Kairong; Chepelev, Iouri; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
   [Tie, Feng; Harte, Peter] Case Western Reserve Univ, Dept Genet, Sch Med, Cleveland, OH 44106 USA.
RP Zhou, L (reprint author), Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA.
EM leizhou@ufl.edu
RI Lin, Nianwei/I-4919-2012; Lin, Nianwei/I-4653-2013; Li,
   Guangyao/I-8241-2015; Liu, Bo/K-1268-2016
OI Lin, Nianwei/0000-0002-0811-8797; Li, Guangyao/0000-0003-0029-3854; 
FU NICHD;  [CA095542];  [HL091929];  [HL090589]
FX We are very grateful to Paul Schedl at Princeton University for
   providing us the pCfhl vector and transgenic lines carrying pCfhl and
   pCfhl-Fab7_1.2k. The H3K27me3 and H3K9me3 antibodies used by the Zhou
   group were kindly provided by Thomas Jenuwein at the Max Planck
   Institute of Immunobiology. The 2B10 (Cut) antibody developed by Gerry
   Rubin was obtained from the Developmental Studies Hybridoma Bank,
   developed under the auspices of the NICHD and maintained by the
   University of Iowa.; This work was supported by grants CA095542 (L.Z.)
   and HL091929 and HL090589 (S.H.).
NR 55
TC 8
Z9 8
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD JUL
PY 2011
VL 31
IS 13
BP 2729
EP 2741
DI 10.1128/MCB.05165-11
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 775BK
UT WOS:000291431400016
PM 21518956
ER

PT J
AU Malicet, C
   Rochman, M
   Postnikov, Y
   Bustin, M
AF Malicet, Cedric
   Rochman, Mark
   Postnikov, Yuri
   Bustin, Michael
TI Distinct Properties of Human HMGN5 Reveal a Rapidly Evolving but
   Functionally Conserved Nucleosome Binding Protein
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID GROUP CHROMOSOMAL-PROTEINS; HISTONE H1; LINKER HISTONE;
   CHROMATIN-STRUCTURE; LIVING CELLS; FRAP ANALYSIS; DNA-DAMAGE; MOBILITY;
   HMG-17; ACTIVATION
AB The HMGN family is a family of nucleosome-binding architectural proteins that affect the structure and function of chromatin in vertebrates. We report that the HMGN5 variant, encoded by a gene located on chromosome X, is a rapidly evolving protein with an acidic C-terminal domain that differs among vertebrate species. We found that the intranuclear organization and nucleosome interactions of human HMGN5 are distinct from those of mouse HMGN5 and that the C-terminal region of the protein is the main determinant of the chromatin interaction properties. Despite their apparent differences, both mouse and human HMGN5 proteins interact with histone H1, reduce its chromatin residence time, and can induce large-scale chromatin decompaction in living cells. Analysis of HMGN5 mutants suggests that distinct domains in HMGN5 affect specific steps in the interaction of H1 with chromatin. Elevated levels of either human or mouse HMGN5 affect the transcription of numerous genes, most in a variant-specific manner. Our study identifies HMGN5 as a rapidly evolving vertebrate nuclear protein with species-specific properties. HMGN5 has a highly disordered structure, binds dynamically to nucleosome core particles, modulates the binding of H1 to chromatin, reduces the compaction of the chromatin fiber, and affects transcription.
C1 [Malicet, Cedric; Rochman, Mark; Postnikov, Yuri; Bustin, Michael] NCI, Prot Sect, Lab Metab, 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 [N01-CO-12400]
FX This project was supported by the Center for Cancer Research intramural
   program of the NCI, NIH, under contract number N01-CO-12400.
NR 43
TC 10
Z9 10
U1 0
U2 2
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 JUL
PY 2011
VL 31
IS 13
BP 2742
EP 2755
DI 10.1128/MCB.05216-11
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 775BK
UT WOS:000291431400017
PM 21518955
ER

PT J
AU Kim, JS
   Xu, XH
   Li, HF
   Solomon, D
   Lane, WS
   Jin, T
   Waldman, T
AF Kim, Jung-Sik
   Xu, Xuehua
   Li, Huifang
   Solomon, David
   Lane, William S.
   Jin, Tian
   Waldman, Todd
TI Mechanistic Analysis of a DNA Damage-Induced, PTEN-Dependent Size
   Checkpoint in Human Cells
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID TUMOR-SUPPRESSOR PTEN; HUMAN CANCER-CELLS; LHERMITTE-DUCLOS-DISEASE;
   OVARIAN CARCINOMAS; SIGNALING PATHWAY; MUTATION ANALYSIS; ORGAN GROWTH;
   G(1) ARREST; SOMA SIZE; IN-VIVO
AB Following DNA damage, human cells undergo arrests in the G(1) and G(2) phases of the cell cycle and a simultaneous arrest in cell size. We previously demonstrated that the cell size arrest can be uncoupled from the cell cycle arrest by mutational inactivation of the PTEN tumor suppressor gene. Here we show that the cell size checkpoint is inducible by DNA-damaging chemotherapeutic agents as well as by ionizing radiation and is effectively regulated by PTEN but not by its oncogenic counterpart, PIK3CA. Mutational analysis of PTEN and pharmacological inhibition of Akt revealed that modulation of Akt phosphorylation is unnecessary for cell size checkpoint control. To discover putative PTEN regulators and/or effectors involved in size checkpoint control, we employed a novel endogenous epitope tagging (EET) approach, which revealed that endogenous PTEN interacts at the membrane with an actin-remodeling complex that includes actin, gelsolin, and EPLIN. Pharmacological inhibition of actin remodeling in PTEN(+/+) cells recapitulated the lack of size checkpoint control seen in PTEN(-/-) cells. Taken together, these results provide further support for the existence of a DNA damage-inducible size checkpoint that is regulated by a major tumor suppressor, and they provide a novel Akt-independent mechanism by which PTEN controls cell size.
C1 [Kim, Jung-Sik; Li, Huifang; Solomon, David; Waldman, Todd] Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA.
   [Solomon, David] Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Tumor Biol Training Program, Washington, DC 20057 USA.
   [Xu, Xuehua; Jin, Tian] NIAID, Chemotaxis Signal Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
   [Lane, William S.] Harvard Univ, Mass Spectrometry & Prote Resource Lab, FAS Ctr Syst Biol, Cambridge, MA 02138 USA.
RP Waldman, T (reprint author), Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Dept Oncol, 3970 Reservoir Rd NW,NRB E304, Washington, DC 20057 USA.
EM waldmant@georgetown.edu
FU National Institutes of Health [CA115699, CA143282]; American Cancer
   Society [RPG MGO-112078]; Lombardi Comprehensive Cancer Center [P30
   CA051008]; NIH [T32 CA009686]
FX This work was supported by National Institutes of Health grants CA115699
   and CA143282 to T. W., American Cancer Society grant RPG MGO-112078 to
   T. W., and the Lombardi Comprehensive Cancer Center Support grant P30
   CA051008. D. S. was supported, in part, by the NIH training grant T32
   CA009686.
NR 57
TC 17
Z9 17
U1 0
U2 1
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 JUL
PY 2011
VL 31
IS 13
BP 2756
EP 2771
DI 10.1128/MCB.01323-10
PG 16
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 775BK
UT WOS:000291431400018
PM 21536651
ER

PT J
AU Walsh, SB
   Xu, JM
   Xu, H
   Kurundkar, AR
   Maheshwari, A
   Grizzle, WE
   Timares, L
   Huang, CC
   Kopelovich, L
   Elmets, CA
   Athar, M
AF Walsh, Stephanie B.
   Xu, Jianmin
   Xu, Hui
   Kurundkar, Ashish R.
   Maheshwari, Akhil
   Grizzle, William E.
   Timares, Laura
   Huang, Conway C.
   Kopelovich, Levy
   Elmets, Craig A.
   Athar, Mohammad
TI Cyclosporine A Mediates Pathogenesis of Aggressive Cutaneous Squamous
   Cell Carcinoma by Augmenting Epithelial-Mesenchymal Transition: Role of
   TGF beta Signaling Pathway
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE nuclear factor of activated T-cells; carcinogenesis; tumor progression;
   skin carcinogenesis; immune suppression; cyclosporine A; TGF beta; EMT
ID ORGAN TRANSPLANT RECIPIENTS; LONG-TERM IMMUNOSUPPRESSION; SKIN-CANCER;
   KERATINOCYTES; GROWTH; MANAGEMENT; MECHANISM; APOPTOSIS; RISK; MICE
AB Organ transplant recipients (OTRs) develop multiple aggressive and metastatic non-melanoma skin cancers (NMSCs). Yet, the underlying mechanism remains elusive. Employing a variety of immune-compromised murine models, immunoblotting, immunohistochemical and immunofluorescence techniques, we show that human squamous xenograft tumors in nude mice grow faster and become significantly larger in size following treatment with the immunosuppressive drug, cyclosporine A (CsA). Re-injected tumor cells isolated from CsA-treated xenografts continued to form larger tumors in nude mice than those from vehicle-controls and retained the CsA-signatures of calcineurin signaling inhibition. Similar results were obtained when these tumors were grown in SCID-beige mice or in immuno-competent mice inoculated with syngeinic tumor cells. Consistently, tumors in the CsA group manifested enhanced cellular proliferation and decreased apoptosis. Tumors in CsA-treated animals also showed an augmented epithelial-mesenchymal transition (EMT) characterized by an increased expression of fibronectin, alpha-SMA, vimentin, N-cadherin, MMP-9/-2, snail and twist with a concomitant decrease in E-cadherin. CsA-treated xenograft tumors manifested increased TGF beta 1 expression and TGF beta-dependent signaling characterized by increased nuclear p-Smad 2/3. Our data demonstrate that CsA alters the phenotype of skin SCCs to an invasive and aggressive tumor-type by enhancing expression of proteins regulating EMT acting through the TGFb1 signaling pathway providing at least one unique mechanism by which multiple aggressive and metastatic NMSCs develop in OTRs. Mol. Carcinog. (C) 2011 Wiley-Liss, Inc.
C1 [Walsh, Stephanie B.; Xu, Jianmin; Xu, Hui; Timares, Laura; Huang, Conway C.; Elmets, Craig A.; Athar, Mohammad] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA.
   [Walsh, Stephanie B.; Xu, Jianmin; Xu, Hui; Timares, Laura; Huang, Conway C.; Elmets, Craig A.; Athar, Mohammad] Univ Alabama, Skin Dis Res Ctr, Birmingham, AL 35294 USA.
   [Kurundkar, Ashish R.; Maheshwari, Akhil] Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA.
   [Grizzle, William E.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA.
   [Kopelovich, Levy] NCI, Canc Prevent Div, EPN, Bethesda, MD 20892 USA.
RP Athar, M (reprint author), Univ Alabama, Dept Dermatol, Volker Hall,Room 509,1670 Univ Blvd, Birmingham, AL 35294 USA.
FU NIH [R01 ES015323, NO1-CN-43300, P30 AR050948, R21 ES017494,
   T32AR053458]
FX This work was supported in part by NIH grants R01 ES015323,
   NO1-CN-43300, P30 AR050948, R21 ES017494, and T32AR053458.
NR 34
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U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0899-1987
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD JUL
PY 2011
VL 50
IS 7
BP 516
EP 527
DI 10.1002/mc.20744
PG 12
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 777HQ
UT WOS:000291606900004
PM 21308804
ER

PT J
AU Kiely, M
   Thornberry, JS
   Bhaskar, B
   Rodan, MF
AF Kiely, Michele
   Thornberry, Jutta S.
   Bhaskar, Brinda
   Rodan, Margaret F.
TI Patterns of alcohol consumption among pregnant African-American women in
   Washington, DC, USA
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE prenatal alcohol consumption; risk assessment; binge drinking
ID IDENTIFICATION TEST AUDIT; RISK-DRINKING; SCREENING QUESTIONNAIRES;
   EXPOSED PREGNANCIES; SPECTRUM DISORDERS; CHILDBEARING AGE;
   BINGE-DRINKING; BIRTH-WEIGHT; CHILDREN; BEHAVIOR
AB P>Kiely M, Thornberry JS, Bhaskar B, Rodan MF. Patterns of alcohol consumption among pregnant African-American women in Washington, DC, USA. Paediatric and Perinatal Epidemiology 2011; 25: 328-339.
   The objective of this paper is to describe the patterns and associated behaviours related to alcohol consumption among a selected sample of pregnant women seeking prenatal care in inner city Washington DC. Women receiving prenatal care at one of nine sites completed an anonymous alcohol-screening questionnaire. Questions concerned the amount, type and pattern of alcohol consumption. Women were categorised as at no, low, moderate or high risk for alcohol consumption during pregnancy. For comparisons of risk levels of drinking, bivariate associations were examined using Fisher's exact test. Odds ratios (ORs) and 95% confidence intervals (CIs) were also computed. Although 31% of current/recent drinkers stated that they continued to drink during pregnancy, responses to quantity/frequency questions revealed that 42% continued to do so. Women who were at high compared with moderate risk acknowledged that others were worried about their consumption [OR = 4.0, 95% CI 1.5, 10.6], that they drank upon rising [OR = 6.7, 95% CI 1.8, 26.9], had a need to reduce drinking [OR = 3.2, 95% CI 1.3, 8.1] and in the past 5 years had had fractures [OR = 4.2, 95% CI 1.0, 17.8] or a road traffic injury [OR = 3.4, 95% CI 1.0, 12.2]. Women in the high/moderate compared with low-risk group were more likely to have been injured in a fight or assault [OR = 2.7, 95% CI 1.3, 5.6]. This study validated the usefulness of our questionnaire in identifying women who were at risk for alcohol consumption during pregnancy across a range of consumption levels. Using our screening tool, women were willing to disclose their drinking habits. This low-cost method identifies women appropriate for targeting of interventions.
C1 [Kiely, Michele] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Collaborat Studies Unit, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA.
   [Thornberry, Jutta S.] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
   [Rodan, Margaret F.] George Mason Univ, Sch Nursing, Fairfax, VA 22030 USA.
   [Bhaskar, Brinda] Novartis Healthcare Pvt Ltd, Hyderabad, Andhra Pradesh, India.
RP Kiely, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Collaborat Studies Unit, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,Room 7B-05, Bethesda, MD 20892 USA.
EM kielym@nih.gov
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); Office of
   Research on Minority Health (ORMH); Office of Research on Women's Health
   (ORWH); National Institute of Child Health and Human Development
   (NICHD), National Institutes of Health (NIH) [U18-HD30447, U18-HD30458,
   U18-HD30450, U18-HD30445, U18-HD31919, U18-HD30454, U18-HD31206]
FX This work was supported by the National Institute on Alcohol Abuse and
   Alcoholism (NIAAA), the Office of Research on Minority Health (ORMH),
   the Office of Research on Women's Health (ORWH) and grants (U18-HD30447,
   U18-HD30458, U18-HD30450, U18-HD30445, U18-HD31919, U18-HD30454, and
   U18-HD31206) from the National Institute of Child Health and Human
   Development (NICHD), National Institutes of Health (NIH).
NR 45
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U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD JUL
PY 2011
VL 25
IS 4
BP 328
EP 339
DI 10.1111/j.1365-3016.2010.01179.x
PG 12
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
   Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
   Pediatrics
GA 774OI
UT WOS:000291395500004
PM 21649675
ER

PT J
AU Hintz, SR
   Stevenson, DK
   Yao, Q
   Wong, RJ
   Das, A
   Van Meurs, KP
   Morris, BH
   Tyson, JE
   Oh, W
   Poole, WK
   Phelps, DL
   McDavid, GE
   Grisby, C
   Higgins, RD
AF Hintz, Susan R.
   Stevenson, David K.
   Yao, Qing
   Wong, Ronald J.
   Das, Abhik
   Van Meurs, Krisa P.
   Morris, Brenda H.
   Tyson, Jon E.
   Oh, William
   Poole, W. Kenneth
   Phelps, Dale L.
   McDavid, Georgia E.
   Grisby, Cathy
   Higgins, Rosemary D.
CA Eunice Kennedy Shriver Natl Inst C
TI Is phototherapy exposure associated with better or worse outcomes in
   501-to 1000-g-birth-weight infants?
SO ACTA PAEDIATRICA
LA English
DT Article
DE Extremely low birth weight infants; mortality; neurodevelopmental
   outcome; phototherapy
ID LOW-BIRTH-WEIGHT; PATENT DUCTUS-ARTERIOSUS; NEURODEVELOPMENTAL OUTCOMES;
   UNBOUND BILIRUBIN; PRETERM INFANTS; HYPERBILIRUBINEMIA; MORTALITY
AB Aim:
   To compare risk-adjusted outcomes at 18- to 22-month-corrected age for extremely low birth weight (ELBW) infants who never received phototherapy (NoPTx) to those who received any phototherapy (PTx) in the NICHD Neonatal Research Network randomized trial of Aggressive vs. Conservative Phototherapy.
   Methods:
   Outcomes at 18 to 22-month-corrected age included death, neurodevelopmental impairment (NDI) and Bayley Scales Mental Developmental Index (MDI). Regression models evaluated the independent association of PTx with adverse outcomes controlling for centre and other potentially confounding variables.
   Results:
   Of 1972 infants, 216 were NoPTx and 1756 were PTx. For the entire 501- to 1000-g-BW cohort, PTx was not independently associated with death or NDI (OR 0.85, 95% CI: 0.60-1.20), death or adverse neurodevelopmental endpoints. However, among infants 501-750 g BW, the rate of significant developmental impairment with MDI < 50 was significantly higher for NoPTx (29%) than PTx (12%) (p = 0.004).
   Conclusions:
   Phototherapy did not appear to be independently associated with death or NDI for the overall ELBW group. Whether PTx increases mortality could not be excluded because of bias from deaths before reaching conservative treatment threshold. The higher rate of MDI < 50 in the 501- to 750-g-BW NoPTx group is concerning and consistent with NRN Trial results.
C1 [Hintz, Susan R.; Stevenson, David K.; Wong, Ronald J.; Van Meurs, Krisa P.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
   [Yao, Qing; Poole, W. Kenneth] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
   [Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
   [Morris, Brenda H.; Tyson, Jon E.; McDavid, Georgia E.] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX USA.
   [Oh, William] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
   [Phelps, Dale L.] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
   [Grisby, Cathy] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA.
   [Higgins, Rosemary D.] NICHHD, Eunice Kennedy Shriver Natl Inst, NIH, Bethesda, MD 20892 USA.
RP Hintz, SR (reprint author), Stanford Univ, Lucile Packard Childrens Hosp, Ctr Comprehens Fetal Hlth, Div Neonatal & Dev Med,Sch Med, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA.
EM srhintz@stanford.edu
FU NCRR NIH HHS [M01 RR016587, KL2 RR024149, M01 RR006022, M01 RR007122,
   M01 RR008084, UL1 RR024139, UL1 RR024148, UL1 RR024160]; NICHD NIH HHS
   [U10 HD021364, U10 HD021373, U10 HD021385, U10 HD021397, U10 HD027851,
   U10 HD027853, U10 HD027856, U10 HD027871, U10 HD027880, U10 HD027904,
   U10 HD034216, U10 HD036790, U10 HD040461, U10 HD040492, U10 HD040498,
   U10 HD040521, U10 HD040689]
NR 25
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U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0803-5253
J9 ACTA PAEDIATR
JI Acta Paediatr.
PD JUL
PY 2011
VL 100
IS 7
BP 960
EP 965
DI 10.1111/j.1651-2227.2011.02175.x
PG 6
WC Pediatrics
SC Pediatrics
GA 772HE
UT WOS:000291224200021
PM 21272067
ER

PT J
AU Mueller, GA
   Gosavi, RA
   Pomes, A
   Wunschmann, S
   Moon, AF
   London, RE
   Pedersen, LC
AF Mueller, G. A.
   Gosavi, R. A.
   Pomes, A.
   Wuenschmann, S.
   Moon, A. F.
   London, R. E.
   Pedersen, L. C.
TI Ara h 2: crystal structure and IgE binding distinguish two
   subpopulations of peanut allergic patients by epitope diversity
SO ALLERGY
LA English
DT Article
DE allergy; Ara h 2; immunotherapy; peanut; structure
ID WORM ALPHA-AMYLASE; ANGSTROM RESOLUTION; PROTEINS; INHIBITOR; SEVERITY;
   FOOD; CHILDREN; ARA-H-2; WHEAT
AB P>Background:
   Peanut allergy affects 1% of the population and causes the most fatal food-related anaphylactic reactions. The protein Ara h 2 is the most potent peanut allergen recognized by 80-90% of peanut allergic patients.
   Methods:
   The crystal structure of the major peanut allergen Ara h 2 was determined for the first time at 2.7 A resolution using a customized maltose-binding protein (MBP)-fusion system. IgE antibody binding to the MBP fusion construct vs the natural allergen was compared by ELISA using sera from peanut allergic patients.
   Results:
   The structure of Ara h 2 is a five-helix bundle held together by four disulfide bonds and related to the prolamin protein superfamily. The fold is most similar to other amylase and trypsin inhibitors. The MBP-Ara h 2 fusion construct was positively recognized by IgE from 76% of allergic patients (25/33). Two populations of patients could be identified. Subpopulation 1 (n = 14) showed an excellent correlation of IgE antibody binding to natural vs recombinant Ara h 2. Subpopulation 2 (n = 15) showed significantly reduced IgE binding to the MBP fusion protein. Interestingly, about 20% of the IgE binding in subpopulation 2 could be recovered by increasing the distance between MBP and Ara h 2 in a second construct.
   Discussion:
   The reduced IgE binding to the MBP-Ara h 2 of subpopulation 2 indicates that the MBP molecule protects an immunodominant epitope region near the first helix of Ara h 2. Residues involved in the epitope(s) are suggested by the crystal structure. The MBP-Ara h 2 fusion constructs will be useful to further elucidate the relevance of certain epitopes to peanut allergy.
C1 [Mueller, G. A.; Gosavi, R. A.; Moon, A. F.; London, R. E.; Pedersen, L. C.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC USA.
   [Pomes, A.; Wuenschmann, S.] INDOOR Biotechnol Inc, Charlottesville, VA USA.
RP Mueller, GA (reprint author), 111 TW Alexander Dr,MD-MR01, Res Triangle Pk, NC 27709 USA.
EM mueller3@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences; National
   Institute of Allergy and Infectious Diseases [R01AI077653]; U S
   Department of Energy, Office of Science, Office of Basic Energy Sciences
   [W-31-109-Eng-38]
FX We are grateful to Dr Robert Petrovich in the Protein Expression Core
   Facility for use of the CD spectrometer and Dr Jason Williams in the
   Protein Microcharacterization Facility for mass spectrometric analysis.
   We thank Dr Michael Fessler and Dr Donald Cook for a critical reading of
   the manuscript. This research was supported in part by the Intramural
   Research Program of the NIH, National Institute of Environmental Health
   Sciences. AP and SW were funded in part by grant R01AI077653 from the
   National Institute of Allergy and Infectious Diseases. The content is
   solely the responsibility of the authors and does not necessarily
   represent the official views of the National Institute of Allergy And
   Infectious Diseases or the National Institutes of Health. X-ray
   diffraction data were collected at Southeast Regional Collaborative
   Access Team (SER-CAT) 22-ID (or 22-BM) beamline at the Advanced Photon
   Source, Argonne National Laboratory. Use of the Advanced Photon Source
   was supported by the U S Department of Energy, Office of Science, Office
   of Basic Energy Sciences, under Contract No. W-31-109-Eng-38.
NR 38
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U2 13
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-4538
J9 ALLERGY
JI Allergy
PD JUL
PY 2011
VL 66
IS 7
BP 878
EP 885
DI 10.1111/j.1398-9995.2010.02532.x
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 772FP
UT WOS:000291220000010
PM 21255036
ER

PT J
AU Huerta-Yepez, S
   Baay-Guzman, GJ
   Bebenek, IG
   Hernandez-Pando, R
   Vega, MI
   Chi, L
   Riedl, M
   Diaz-Sanchez, D
   Kleerup, E
   Tashkin, DP
   Gonzalez, FJ
   Bonavida, B
   Zeidler, M
   Hankinson, O
AF Huerta-Yepez, S.
   Baay-Guzman, G. J.
   Bebenek, I. G.
   Hernandez-Pando, R.
   Vega, M. I.
   Chi, L.
   Riedl, M.
   Diaz-Sanchez, D.
   Kleerup, E.
   Tashkin, D. P.
   Gonzalez, F. J.
   Bonavida, B.
   Zeidler, M.
   Hankinson, O.
TI Hypoxia Inducible Factor promotes murine allergic airway inflammation
   and is increased in asthma and rhinitis
SO ALLERGY
LA English
DT Article
DE allergic airway inflammation; asthma; hypoxia-inducible factor; rhinitis
ID ARYL-HYDROCARBON RECEPTOR; NUCLEAR TRANSLOCATOR PROTEIN; ENDOTHELIAL
   GROWTH-FACTOR; ARNT-DEFICIENT MICE; PROLYL 4-HYDROXYLASE;
   GENE-EXPRESSION; FACTOR 1-ALPHA; AH RECEPTOR; ANGIOGENESIS; HIF-1-ALPHA
AB P>Background:
   New therapies are necessary to address inadequate asthma control in many patients. This study sets out to investigate whether hypoxia-inducible factor (HIF) is essential for development of allergic airway inflammation (AAI) and therefore a potential novel target for asthma treatment.
   Methods:
   Mice conditionally knocked out for HIF-1 beta were examined for their ability to mount an allergic inflammatory response in the lung after intratracheal exposure to ovalbumin. The effects of treating wild-type mice with either ethyl-3,4-dihydroxybenzoate (EDHB) or 2-methoxyestradiol (2ME), which upregulate and downregulate HIF, respectively, were determined. HIF-1 alpha levels were also measured in endobronchial biopsies and bronchial fluid of patients with asthma and nasal fluid of patients with rhinitis after challenge.
   Results:
   Deletion of HIF-1 beta resulted in diminished AAI and diminished production of ovalbumin-specific IgE and IgG(1). EDHB enhanced the inflammatory response, which was muted upon simultaneous inhibition of vascular endothelial growth factor (VEGF). EDHB and 2ME antagonized each other with regard to their effects on airway inflammation and mucus production. The levels of HIF-1 alpha and VEGF increased in lung tissue and bronchial fluid of patients with asthma and in the nasal fluid of patients with rhinitis after challenge.
   Conclusions:
   Our results support the notion that HIF is directly involved in the development of AAI. Most importantly, we demonstrate for the first time that HIF-1 alpha is increased after challenge in patients with asthma and rhinitis. Therefore, we propose that HIF may be a potential therapeutic target for asthma and possibly for other inflammatory diseases.
C1 [Huerta-Yepez, S.; Baay-Guzman, G. J.] Hosp Infantil Mexico Dr Federico Gomez, Unidad Invest Enfermedades Oncol, Mexico City, DF, Mexico.
   [Bebenek, I. G.; Chi, L.; Hankinson, O.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
   [Hernandez-Pando, R.] Natl Inst Med Sci & Nutr, Dept Pathol, Expt Pathol Sect, Salvador Zubiran, Mexico.
   [Vega, M. I.] IMSS, Hosp Oncol CMN Siglo XXI, Unidad Invest Med Enfermedades Oncol, Mexico City, DF, Mexico.
   [Riedl, M.; Zeidler, M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Clin Immunol & Allergy, Los Angeles, CA 90095 USA.
   [Diaz-Sanchez, D.] US EPA, Clin Res Branch, Human Studies Div, Natl Hlth & Environm Effects Res Lab, Chapel Hill, NC USA.
   [Tashkin, D. P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
   [Gonzalez, F. J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Bonavida, B.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA.
   [Zeidler, M.] WLA VA Med Ctr, Div Pulm Crit Care & Sleep Med, Los Angeles, CA USA.
RP Hankinson, O (reprint author), UCLA Pathol & Lab Med, Box 951732,10833 Le Conte Ave,13-244 Factor Bldg, Los Angeles, CA 90095 USA.
EM ohank@mednet.ucla.edu
FU University of California Institute for Mexico and the United States (UC
   MEXUS-CONACYT); Mexico Federal Funds [HIM/2008/034]; National Institutes
   of Health [R01 CA28868, R01 HL080343]; National Cancer Institute; US
   Environmental Protection Agency; Universidad Nacional Autonoma de Mexico
   (UNAM); Consejo Nacional de Ciencia y Tecnologia, Mexico
   [CONACyT-195431]
FX Supported by a Collaborative Research Grant from the University of
   California Institute for Mexico and the United States (UC MEXUS-CONACYT)
   (S.H.Y and O.H), Mexico Federal Funds Grant HIM/2008/034 (S.H.-Y., G.
   B.-G.), National Institutes of Health grants R01 CA28868 (O.H.) and R01
   HL080343 (E. K. and M.Z.), and the National Cancer Institute Intramural
   Research Program (F.J.G.), and the US Environmental Protection Agency
   (D. D-S.). We thank Kelly Joiner and Stephen Hop for helping prepare the
   manuscript for submission and Xiaomeng Wu for technical assistance. We
   thank Programa de Doctorado en Ciencias Biomedicas, Facultad de Medicina
   from the Universidad Nacional Autonoma de Mexico (UNAM), Doctoral
   scholarship degree grant (G.J. B-G) CONACyT-195431 from Consejo Nacional
   de Ciencia y Tecnologia, Mexico.
NR 34
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U1 1
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0105-4538
J9 ALLERGY
JI Allergy
PD JUL
PY 2011
VL 66
IS 7
BP 909
EP 918
DI 10.1111/j.1398-9995.2011.02594.x
PG 10
WC Allergy; Immunology
SC Allergy; Immunology
GA 772FP
UT WOS:000291220000014
PM 21517900
ER

PT J
AU Botello-Harbaum, M
   Haynie, DL
   Murray, KW
   Iannotti, RJ
AF Botello-Harbaum, M.
   Haynie, D. L.
   Murray, K. W.
   Iannotti, R. J.
TI Cigarette smoking status and recurrent subjective health complaints
   among US school-aged adolescents
SO CHILD CARE HEALTH AND DEVELOPMENT
LA English
DT Article
DE adolescents; cigarette smoking; HBSC; positive health; psychological
   complaints; subjective well-being
ID FAMILY AFFLUENCE SCALE; YOUNG ADOLESCENTS; DEPRESSIVE SYMPTOMS; SOMATIC
   COMPLAINTS; SUBSTANCE-USE; FOLLOW-UP; PREDICTORS; HEADACHES; CHILDREN;
   RISK
AB Background Subjective health complaints are common among adolescents. There is evidence that girls are more likely to register complaints than boys. This study examines gender differences in the relationship between daily smoking and recurrent subjective health complaints in school-aged adolescents in the USA.
   Methods A cross-sectional design with a multistage probability sample was used to survey 13 339 middle and high school students (grades 6 through 10) with the US 2001-2002 Health Behavior in School-Aged Children Survey.
   Results Recurrent subjective health complaints were higher for adolescents who smoke daily and experiment with cigarettes than for those who never smoke. In logistic regression analyses, the odds of daily smoking increased twofold for both boys and girls who report recurrent irritability/bad temper. For girls, the odds of daily smoking were higher among those who reported recurrent headache, stomachache and backache compared with never smokers. For boys only recurrent backache and feeling dizzy were associated with increased odds of daily smoking.
   Conclusions The relationship between recurrent subjective health complaints and daily smoking provides new insights into both conditions for school-aged adolescents. Findings from this study suggest different patterns of association between daily smoking and recurrent subjective health complaints occur for girls and boys. Further studies are needed to explore causes and treatment of daily smoking and recurrent health complaints among school-aged children.
C1 [Botello-Harbaum, M.] EMMES Corp, Rockville, MD 20580 USA.
   [Haynie, D. L.; Iannotti, R. J.] NICHD Eunice Kennedy Shriver Natl Inst Child Hlth, Rockville, MD USA.
   [Murray, K. W.] Johns Hopkins Univ, Dept Gen Pediat & Adolescent Med, Baltimore, MD USA.
RP Botello-Harbaum, M (reprint author), EMMES Corp, 401 N Washington St,Suite 700, Rockville, MD 20580 USA.
EM mbotello-harbaum@emmes.com
OI Haynie, Denise/0000-0002-8270-6079
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development; Maternal and Child Health Bureau of the Health Resources
   and Services Administration
FX The 2001 HBSC is an international study carried out in collaboration
   with WHO/EURO. The international co-ordinator of the 2001-2002 study was
   Candace Currie, University of Edinburgh, Scotland; and the data bank
   manager was Oddrun Samdal, University of Bergen, Norway. A complete list
   of the participating researchers can be found on the HBSC website
   (http://www.HBSC.org). Work on this manuscript 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
   with one author (Dr Ronald J. Iannotti) as principal investigator of the
   US HBSC.
NR 40
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U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0305-1862
J9 CHILD CARE HLTH DEV
JI Child Care Health Dev.
PD JUL
PY 2011
VL 37
IS 4
BP 551
EP 558
DI 10.1111/j.1365-2214.2010.01147.x
PG 8
WC Psychology, Developmental; Pediatrics
SC Psychology; Pediatrics
GA 773ML
UT WOS:000291311300011
PM 20825423
ER

PT J
AU Young-Wolff, KC
   Enoch, MA
   Prescott, CA
AF Young-Wolff, Kelly C.
   Enoch, Mary-Anne
   Prescott, Carol A.
TI The influence of gene-environment interactions on alcohol consumption
   and alcohol use disorders: A comprehensive review
SO CLINICAL PSYCHOLOGY REVIEW
LA English
DT Review
DE Gene-environment interactions; Alcohol; Drinking; Adoption; Twin;
   Genotype
ID SEROTONIN TRANSPORTER GENE; CROSS-FOSTERING ANALYSIS; STRESSFUL LIFE
   EVENTS; ANTISOCIAL PERSONALITY-DISORDER; ADOLESCENT DRINKING BEHAVIOR;
   SUBSTANCE-USE DISORDERS; MAO-A GENE; MONOAMINE-OXIDASE; CRHR1 GENE;
   EPIDEMIOLOGIC SURVEY
AB Since 2005, a rapidly expanding literature has evaluated whether environmental factors such as socio-cultural context and adversity interact with genetic influences on drinking behaviors. This article critically reviews empirical research on alcohol-related genotype-environment interactions (GxE) and provides a contextual framework for understanding how genetic factors combine with (or are shaped by) environmental factors to influence the development of drinking behaviors and alcohol use disorders. Collectively, evidence from twin, adoption, and molecular genetic studies indicates that the degree of importance of genetic influences on risk for drinking outcomes can vary in different populations and under different environmental circumstances. However, methodological limitations and lack of consistent replications in this literature make it difficult to draw firm conclusions regarding the nature and effect size of alcohol-related GxE. On the basis of this review, we describe several methodological challenges as they relate to current research on GxE in drinking behaviors and provide recommendations to aid future research. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Young-Wolff, Kelly C.; Prescott, Carol A.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA.
   [Enoch, Mary-Anne] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA.
RP Young-Wolff, KC (reprint author), Univ So Calif, Dept Psychol, SGM 501,3620 So McClintock Ave, Los Angeles, CA 90089 USA.
EM kellyyw@gmail.com
FU NIA NIH HHS [R37 AG007137]; NIAAA NIH HHS [F31 AA018611, F31
   AA018611-02]
NR 147
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U1 7
U2 24
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0272-7358
J9 CLIN PSYCHOL REV
JI Clin. Psychol. Rev.
PD JUL
PY 2011
VL 31
IS 5
BP 800
EP 816
DI 10.1016/j.cpr.2011.03.005
PG 17
WC Psychology, Clinical
SC Psychology
GA 771VM
UT WOS:000291188800009
PM 21530476
ER

PT J
AU Williams, RC
   Muller, YL
   Hanson, RL
   Knowler, WC
   Mason, CC
   Bian, L
   Ossowski, V
   Wiedrich, K
   Chen, YF
   Marcovina, S
   Hahnke, J
   Nelson, RG
   Baier, LJ
   Bogardus, C
AF Williams, R. C.
   Muller, Y. L.
   Hanson, R. L.
   Knowler, W. C.
   Mason, C. C.
   Bian, L.
   Ossowski, V.
   Wiedrich, K.
   Chen, Y. F.
   Marcovina, S.
   Hahnke, J.
   Nelson, R. G.
   Baier, L. J.
   Bogardus, C.
TI HLA-DRB1 reduces the risk of type 2 diabetes mellitus by increased
   insulin secretion
SO DIABETOLOGIA
LA English
DT Article
DE HLA-DRB1; Insulin secretion; mRNA expression; Single-nucleotide
   polymorphism; Type 2 diabetes
ID GLUTAMIC-ACID DECARBOXYLASE; RIVER-INDIAN-COMMUNITY; X-RAY
   ABSORPTIOMETRY; PIMA-INDIANS; GENETIC-CHARACTERISTICS; SUSCEPTIBILITY
   LOCI; HLA; ASSOCIATION; AUTOIMMUNE; RESISTANCE
AB We sought to identify the physiological implications of genetic variation at the HLA-DRB1 region in full-heritage Pima Indians in Arizona.
   Single-nucleotide polymorphisms from the HLA region on chromosome 6p were tested for association with skeletal muscle mRNA expression of HLA-DRB1 and HLA-DRA, and with type 2 diabetes mellitus and prediabetic traits.
   The A allele at rs9268852, which tags HLA-DRB1*02(1602), was associated both with higher HLA-DRB1 mRNA expression (n = 133, p = 4.27 x 10(-14)) and decreased risk of type 2 diabetes (n = 3,265, OR 0.723, p = 0.002). Among persons with normal glucose tolerance (n = 266) this allele was associated with a higher mean acute insulin response during an intravenous glucose tolerance test (p = 0.005), higher mean 30 min insulin concentration during an oral glucose tolerance test (p = 0.017) and higher body fat percentage (p = 0.010). The polymorphism was not associated with HLA-DRA mRNA expression or insulin sensitivity.
   HLA-DRB1*02 is protective for type 2 diabetes, probably by enhancing self tolerance, thereby protecting against the autoimmune-mediated reduction of insulin secretion.
C1 [Williams, R. C.; Muller, Y. L.; Hanson, R. L.; Knowler, W. C.; Mason, C. C.; Bian, L.; Ossowski, V.; Wiedrich, K.; Hahnke, J.; Nelson, R. G.; Baier, L. J.; Bogardus, C.] NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA.
   [Chen, Y. F.] Tzu Chi Univ, Hualien, Taiwan.
   [Marcovina, S.] NW Lipid Metab & Diabet Res Labs, Seattle, WA USA.
RP Williams, RC (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
EM williamsr@mail.nih.gov
RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015
OI Hanson, Robert/0000-0002-4252-7068
FU Blood Systems Foundation [BSF45-3, BSF45-4]; Blood Systems, Scottsdale,
   AZ, USA; NIDDK; American Diabetes Association [7-04-DCS-02, 7-06-MN-06]
FX We thank the research volunteers for their assistance and the staff of
   the Phoenix Epidemiology and Clinical Research Branch, NIDDK, for
   conducting the examinations. This research was partially supported by
   grants BSF45-3 and BSF45-4 from Blood Systems Foundation, Blood Systems,
   Scottsdale, AZ, USA, by the Intramural Research Program of the NIDDK,
   and grants 7-04-DCS-02 and 7-06-MN-06 to C. Bogardus from the American
   Diabetes Association.
NR 50
TC 9
Z9 10
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
EI 1432-0428
J9 DIABETOLOGIA
JI Diabetologia
PD JUL
PY 2011
VL 54
IS 7
BP 1684
EP 1692
DI 10.1007/s00125-011-2122-8
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 774MZ
UT WOS:000291392000014
PM 21484216
ER

PT J
AU Lindeblad, M
   Kapetanovic, IM
   Kabirov, KK
   Dinger, N
   Mankovskaya, I
   Morrisey, R
   Martin-Jimenez, T
   Lyubimov, A
AF Lindeblad, Matthew
   Kapetanovic, Izet M.
   Kabirov, Kasim K.
   Dinger, Nancy
   Mankovskaya, Irina
   Morrisey, Robert
   Martin-Jimenez, Tomas
   Lyubimov, Alexander
TI Assessment of oral toxicity and safety of 9-cis-UAB30, a potential
   chemopreventive agent, in rat and dog studies
SO DRUG AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE 9-cis-UAB30; chemoprevention; toxicity; oral; rat; Beagle dog; rexinoid
ID TRANS-RETINOIC ACID; LIVER TOXICITY; TELOMERASE; VITAMIN; 9CUAB30; CELLS
AB 9-cis-UAB30 is a potential chemopreventative agent that has been shown to be effective on many different types of tumors. The safety and toxicity of 9-cis-UAB30 had not been previously established. These studies were conducted to evaluate the potential toxicity and pharmacokinetics in a rodent and a nonrodent species for the purpose of investigational new drug submission. Oral gavage administration of 9-cis-UAB30 at the doses 0, 3, 15, and 100 mg/kg/day to CD (R) rats for 28 days showed a dose-dependent (although not dose-proportional) increase in plasma drug levels in week 4. The liver was the target organ for toxicity of 9-cis-UAB30. Hepatomegaly along with increases in serum aspartate-aminotransferase and alkaline-phosphatase levels were seen in rats. Moderate hypoalbuminemia and hyperglobulinemia resulted in a decreased albumin/globulin ratio. Histopathology revealed hepatocellular change consistent with hepatic glycogen deposition. Toxicity studies in dogs did not show treatment-related toxicity at doses as high as 100 mg/kg/day (highest dose tested) administered by capsules for 28 days. No effects on the central nervous system (functional observational battery in rats) or cardiovascular function (safety pharmacology study in telemeterized dogs) were seen. The no observed adverse effect level (NOAEL) in the rat studies was 3 mg/kg/day; however, the adverse effects seen in rats receiving 15 mg/kg/day (the least observed adverse effect level) was a slight, but statistically significant, elevation in fibrinogen and decrease in prothrombin time, which may be a sign of some tendency for increased blood coagulation. The NOAEL in the dog study was at least 100 mg/kg/day.
C1 [Lindeblad, Matthew; Kabirov, Kasim K.; Dinger, Nancy; Mankovskaya, Irina; Lyubimov, Alexander] Univ Illinois, Toxicol Res Lab, Dept Pharmacol, Chicago, IL 60612 USA.
   [Kapetanovic, Izet M.; Lyubimov, Alexander] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
   [Morrisey, Robert] Charles River Co, Pathol Associates Int, Chicago Div, Chicago, IL USA.
   [Martin-Jimenez, Tomas] Univ Tennessee, Coll Vet Med, Knoxville, TN USA.
RP Lyubimov, A (reprint author), Univ Illinois, Toxicol Res Lab, Dept Pharmacol, 808 S Wood St, Chicago, IL 60612 USA.
EM lyubimov@uic.edu
FU NCI [N01-CN 43306]
FX This work was supported by the NCI Contract No. N01-CN 43306.
NR 13
TC 6
Z9 6
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0148-0545
J9 DRUG CHEM TOXICOL
JI Drug Chem. Toxicol.
PD JUL
PY 2011
VL 34
IS 3
BP 300
EP 310
DI 10.3109/01480545.2010.536771
PG 11
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy; Toxicology
SC Chemistry; Pharmacology & Pharmacy; Toxicology
GA 774AQ
UT WOS:000291354100011
PM 21649485
ER

PT J
AU Wacholder, S
AF Wacholder, Sholom
TI On Standards of Evidence
SO EPIDEMIOLOGY
LA English
DT Editorial Material
ID EPIDEMIOLOGY; ASSOCIATION; PROBABILITY; ENVIRONMENT; FALSE
C1 NCI, Biostat Branch, DCEG, Bethesda, MD 20892 USA.
RP Wacholder, S (reprint author), NCI, Biostat Branch, DCEG, EPS 8046, Bethesda, MD 20892 USA.
EM wacholds@exchange.nih.gov
NR 12
TC 3
Z9 3
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD JUL
PY 2011
VL 22
IS 4
BP 464
EP 466
DI 10.1097/EDE.0b013e31821d127d
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 772RJ
UT WOS:000291252100004
PM 21642772
ER

PT J
AU Sorlie, PD
AF Sorlie, Paul D.
TI When Implausible Findings Emanate From High-quality Studies
SO EPIDEMIOLOGY
LA English
DT Editorial Material
C1 NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP Sorlie, PD (reprint author), NHLBI, Div Cardiovasc Sci, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM sorliep@mail.nih.gov
NR 6
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD JUL
PY 2011
VL 22
IS 4
BP 542
EP 543
DI 10.1097/EDE.0b013e31821d111e
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 772RJ
UT WOS:000291252100016
PM 21642776
ER

PT J
AU Metcalf, CJE
   Bjornstad, ON
   Ferrari, MJ
   Klepac, P
   Bharti, N
   Lopez-Gatell, H
   Grenfell, BT
AF Metcalf, C. J. E.
   Bjornstad, O. N.
   Ferrari, M. J.
   Klepac, P.
   Bharti, N.
   Lopez-Gatell, H.
   Grenfell, B. T.
TI The epidemiology of rubella in Mexico: seasonality, stochasticity and
   regional variation
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Article
DE Analysis of data; epidemiology; rubella; statistics
ID CONGENITAL-RUBELLA; DEVELOPING-COUNTRIES; QUANTITATIVE INVESTIGATIONS;
   SYNDROME CRS; MEASLES; VACCINATION; DYNAMICS; MODEL; TRANSMISSION;
   ATTRACTORS
AB The factors underlying the temporal dynamics of rubella outside of Europe and North America are not well known. Here we used 20 years of incidence reports from Mexico to identify variation in seasonal forcing and magnitude of transmission across the country and to explore determinants of inter-annual variability in epidemic magnitude in rubella. We found considerable regional variation in both magnitude of transmission and amplitude of seasonal variation in transmission. Several lines of evidence pointed to stochastic dynamics as an important driver of multi-annual cycles. Since average age of infection increased with the relative importance of stochastic dynamics, this conclusion has implications for the burden of congenital rubella syndrome. We discuss factors underlying regional variation, and implications of the importance of stochasticity for vaccination implementation.
C1 [Metcalf, C. J. E.; Klepac, P.; Bharti, N.; Grenfell, B. T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
   [Metcalf, C. J. E.; Bjornstad, O. N.; Ferrari, M. J.; Klepac, P.; Bharti, N.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
   [Bjornstad, O. N.; Grenfell, B. T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Metcalf, CJE (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Eno Hall, Princeton, NJ 08544 USA.
EM cmetcalf@princeton.edu
RI Bjornstad, Ottar/I-4518-2012
FU NIH [R01 GM083983-01]; Bill and Melinda Gates Foundation; Science &
   Technology Directorate, Department of Homeland Security; Fogarty
   International Center, National Institutes of Health
FX We thank the staff of Direccion General de Epidemiologia and the Mexican
   National Surveillance System for their efforts in conducting
   surveillance activities and providing the rubella data used in this
   study. This work was funded by the Bill and Melinda Gates Foundation and
   grant NIH R01 GM083983-01 (C.J.E.M., B.T.G., O.N.B, M.J.F.), and the
   RAPIDD program of the Science & Technology Directorate, Department of
   Homeland Security and the Fogarty International Center, National
   Institutes of Health (B.T.G., O.N.B, M.J.F.).
NR 33
TC 17
Z9 17
U1 1
U2 15
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0950-2688
J9 EPIDEMIOL INFECT
JI Epidemiol. Infect.
PD JUL
PY 2011
VL 139
IS 7
BP 1029
EP 1038
DI 10.1017/S0950268810002165
PG 10
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 770UY
UT WOS:000291115200008
PM 20843389
ER

PT J
AU Asher, KP
   Gupta, GN
   Boris, RS
   Pinto, PA
   Linehan, WM
   Bratslavsky, G
AF Asher, Kevin P.
   Gupta, Gopal N.
   Boris, Ronald S.
   Pinto, Peter A.
   Linehan, W. Marston
   Bratslavsky, Gennady
TI Robot-Assisted Laparoscopic Partial Adrenalectomy for Pheochromocytoma:
   The National Cancer Institute Technique
SO EUROPEAN UROLOGY
LA English
DT Article
DE Adrenalectomy; Laparoscopy; Partial adrenalectomy; Pheochromocytoma;
   Robotic surgery
ID ALDOSTERONE-PRODUCING ADENOMAS; HIPPEL-LINDAU-DISEASE; SPARING-SURGERY;
   HEREDITARY PHEOCHROMOCYTOMA; FOLLOW-UP; NEOPLASIA; OUTCOMES
AB Background: Partial adrenalectomy has recently been advocated to preserve unaffected adrenal tissue during resection of pheochromocytoma.
   Objective: To describe a robot-assisted laparoscopic partial adrenalectomy (RALPA) technique and to report on early functional and oncologic outcomes.
   Design, setting, and participants: From 2007 to 2010, 15 RALPA were performed on 12 consecutive patients with pheochromocytoma. Follow-up data of > 1 yr are available on 11 procedures. Median follow-up for the entire cohort was 17.3 mo (range: 6-45).
   Surgical procedure: Positioning and port placement is designed for adequate reach and visualization of the upper retroperitoneum. The plane between the adrenal cortex and pheochromocytoma pseudocapsule is identified visually and with laparoscopic ultrasound. The tumor is dissected away from normal adrenal cortex, preserving normal adrenal tissue.
   Measurements: Preoperative, perioperative, pathologic, and functional outcomes data were analyzed.
   Results and limitations: Fourteen of 15 cases were completed robotically. Among 15 procedures, 4 were performed on a solitary adrenal gland. Four cases required resection of multiple tumors (up to six) with two performed in a solitary gland. The mean age of the patients was 30 yr, and the mean body mass index was 27. The mean operative time was 163 min, the median estimated blood loss was 161 ml, and the median tumor size was 2.7 cm (range: 1.3-5.5). There was one conversion to an open procedure in a patient requiring reoperation on a solitary adrenal gland. One patient who underwent RALPA on a solitary adrenal gland required postoperative steroid supplementation at last follow-up. At a median follow-up of 17.3 mo (range: 6-45), there were no recurrences or metastatic events. Study limitations include small sample size and short follow-up.
   Conclusions: RALPA for the treatment of pheochromocytoma is feasible and safe and provides encouraging functional and oncologic outcomes, even in patients with a solitary adrenal lesion or multiple ipsilateral lesions. Published by Elsevier B.V. on behalf of European Association of Urology.
C1 [Asher, Kevin P.; Gupta, Gopal N.; Boris, Ronald S.; Pinto, Peter A.; Linehan, W. Marston; Bratslavsky, Gennady] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10 Room 1-5940, Bethesda, MD 20892 USA.
EM bratslag@mail.nih.gov
FU Intramural NIH HHS [Z01 BC011023-01]; NCI NIH HHS [Z01 BC011028-01, Z01
   BC011038-01, Z01 BC011089-01, Z01 BC011023-01]
NR 24
TC 19
Z9 20
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
J9 EUR UROL
JI Eur. Urol.
PD JUL
PY 2011
VL 60
IS 1
BP 118
EP 124
DI 10.1016/j.eururo.2011.03.046
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 772BS
UT WOS:000291205700026
PM 21507561
ER

PT J
AU Nasonkin, IO
   Lazo, K
   Hambright, D
   Brooks, M
   Fariss, R
   Swaroop, A
AF Nasonkin, Igor O.
   Lazo, Kevin
   Hambright, Dustin
   Brooks, Matthew
   Fariss, Robert
   Swaroop, Anand
TI Distinct Nuclear Localization Patterns of DNA Methyltransferases in
   Developing and Mature Mammalian Retina
SO JOURNAL OF COMPARATIVE NEUROLOGY
LA English
DT Article
DE epigenetics; methylation; development; neurogenesis; photoreceptor; gene
   regulation; vision
ID CELL-FATE DETERMINATION; DE-NOVO METHYLATION; EPIGENETIC REGULATION;
   STEM-CELLS; GENE-EXPRESSION; PHOTORECEPTOR DEVELOPMENT; NEURONAL
   PROGENITORS; ROD PHOTORECEPTORS; NEURAL PROGENITORS; HEMATOPOIETIC STEM
AB DNA methyltransferases-DNMT1, DNMT3a, and DNMT3b-produce methylation patterns that dynamically regulate chromatin remodeling and gene expression. The vertebrate retina provides an ideal model to elucidate molecular control of neurogenesis as all neuronal cell types and Muller glia are generated in a conserved order from common pools of progenitor cells. As a prelude to exploring epigenetic regulation of mammalian retinal development, we investigated the expression of Dnmt1, Dnmt3a, and Dnmt3b in the mouse retina from embryonic day (E) 10.5 to 10 months of age. High levels of transcripts for all three Dnmt genes were observed in early stages of retinal differentiation, with significantly reduced expression after birth. Although DNMT1 protein is abundant in retinal progenitors at E10.5, it becomes restricted to postmitotic cells by E15.5. Most cells in the postnatal retina show nuclear immunostaining of DNMT1; however, the photoreceptors exhibit distinctive patterns. In rods, weak expression of DNMT1 is detected in perinuclear region and in the nucleus, whereas a strong nuclear labeling is evident in cones. DNMT3a and DNMT3b show a discrete pattern in developing retina with high expression at E11.5, little or no immunostaining by E15.5, and then postnatal expression overlapping with DNMT1 in early born neurons (ganglion, amacrine and horizontal cells, and cones). Robust nuclear localization of DNMTs in cones compared to rods suggests a potential role of DNA methylation in differential remodeling of chromatin in these two specialized neurons. Our studies indicate that DNA methyltransferases contribute to the establishment and maturation of cell fates during retinal development. J. Comp. Neurol. 519:1914-1930, 2011.
C1 [Nasonkin, Igor O.; Lazo, Kevin; Hambright, Dustin; Brooks, Matthew; Swaroop, Anand] NEI, N NRL, NIH, Bethesda, MD 20892 USA.
RP Swaroop, A (reprint author), NEI, N NRL, NIH, MSC 0610,6 Ctr Dr, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
RI feng, jian/G-9313-2011; 
OI Swaroop, Anand/0000-0002-1975-1141
FU National Eye Institute, National Institutes of Health
FX Intramural Program of the National Eye Institute, National Institutes of
   Health.
NR 100
TC 20
Z9 22
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9967
J9 J COMP NEUROL
JI J. Comp. Neurol.
PD JUL 1
PY 2011
VL 519
IS 10
BP 1914
EP 1930
DI 10.1002/cne.22613
PG 17
WC Neurosciences; Zoology
SC Neurosciences & Neurology; Zoology
GA 770TK
UT WOS:000291111200005
PM 21452232
ER

PT J
AU Galarza-Munoz, G
   Soto-Morales, SI
   Holmgren, M
   Rosenthal, JJC
AF Galarza-Munoz, Gaddiel
   Soto-Morales, Sonia I.
   Holmgren, Miguel
   Rosenthal, Joshua J. C.
TI Physiological adaptation of an Antarctic Na+/K+-ATPase to the cold
SO JOURNAL OF EXPERIMENTAL BIOLOGY
LA English
DT Article
DE Antarctica; ion channels; ion transporters; Na+/K+-ATPase; octopus;
   temperature adaptation
ID SODIUM-POTASSIUM PUMP; CURRENT-VOLTAGE RELATIONSHIP; CYTOSOLIC
   MALATE-DEHYDROGENASES; DIFFERENT THERMAL ENVIRONMENTS; PIG VENTRICULAR
   MYOCYTES; NA/K PUMP; TEMPERATURE ADAPTATION; XENOPUS-OOCYTES; MOLECULAR
   ACTIVITY; HOMEOVISCOUS ADAPTATION
AB Because enzymatic activity is strongly suppressed by the cold, polar poikilotherms face significant adaptive challenges. For example, at 0 degrees C the catalytic activity of a typical enzyme from a temperate organism is reduced by more than 90%. Enzymes embedded in the plasma membrane, such as the Na+/K+-ATPase, may be even more susceptible to the cold because of thermal effects on the lipid bilayer. Accordingly, adaptive changes in response to the cold may include adjustments to the enzyme or the surrounding lipid environment, or synergistic changes to both. To assess the contribution of the enzyme itself, we cloned orthologous Na+/K+-ATPase alpha-subunits from an Antarctic (Pareledone sp.; -1.8 degrees C) and a temperate octopus (Octopus bimaculatus; similar to 18 degrees C), and compared their turnover rates and temperature sensitivities in a heterologous expression system. The primary sequences of the two pumps were found to be highly similar (97% identity), with most differences being conservative changes involving hydrophobic residues. The physiology of the pumps was studied using an electrophysiological approach in intact Xenopus oocytes. The voltage dependence of the pumps was equivalent. However, at room temperature the maximum turnover rate of the Antarctic pump was found to be 25% higher than that of the temperate pump. In addition, the Antarctic pump exhibited a lower temperature sensitivity, leading to significantly higher relative activity at lower temperatures. Orthologous Na+/K+ pumps were then isolated from two tropical and two Arctic octopus. The temperature sensitivities of these pumps closely matched those of the temperate and Antarctic pumps, respectively. Thus, reduced thermal sensitivity appears to be a common mechanism driving cold adaptation in the Na+/K+-ATPase.
C1 [Holmgren, Miguel] Natl Inst Neurol Disorders & Stroke, Mol Neurophysiol Sect, NIH, Bethesda, MD 20892 USA.
   [Galarza-Munoz, Gaddiel; Soto-Morales, Sonia I.; Rosenthal, Joshua J. C.] Univ Puerto Rico, Inst Neurobiol, San Juan, PR 00901 USA.
   [Rosenthal, Joshua J. C.] Univ Puerto Rico, Dept Biochem, San Juan, PR 00901 USA.
RP Holmgren, M (reprint author), Natl Inst Neurol Disorders & Stroke, Mol Neurophysiol Sect, NIH, Bethesda, MD 20892 USA.
EM holmgren@ninds.nih.gov; rosenthal.joshua@gmail.com
FU NSF [IBN-0344070, 0206200]; NIH (NINDS); RCMI [G12 RR 03051]; NIH [2 U54
   NS039405-06, 1R01NS64259, S06GM08102]; NCRR [P20 RR16470]; University of
   Puerto Rico Biology Department
FX We would like to thank Dr Chris DeVries for kindly providing samples of
   Pareledone sp. from McMurdo Station, Antarctica. We also thank the
   Section on Instrumentation of the National Institute of Mental Health
   for technical assistance. This work was directly supported by NSF
   IBN-0344070, NIH 2 U54 NS039405-06, NIH 1R01NS64259 and the Intramural
   Research Program of the NIH (NINDS). Part of the work was conducted in
   the Molecular Biology Core Facility at the Institute of Neurobiology,
   which is supported by RCMI grant no. G12 RR 03051. Some DNA sequencing
   was performed at the Sequencing and Genotyping facility, University of
   Puerto Rico-Rio Piedras, which is supported in part by NCRR-AABRE grant
   no. P20 RR16470, NIH-SCORE grant no. S06GM08102, University of Puerto
   Rico Biology Department, and NSF-CREST grant no. 0206200. Deposited in
   PMC for release after 12 months.
NR 86
TC 13
Z9 13
U1 3
U2 21
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
   CAMBS, ENGLAND
SN 0022-0949
J9 J EXP BIOL
JI J. Exp. Biol.
PD JUL
PY 2011
VL 214
IS 13
BP 2164
EP 2174
DI 10.1242/jeb.048744
PG 11
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 774LC
UT WOS:000291386300012
PM 21653810
ER

PT J
AU Kelly, PJ
   Goudar, SS
   Chakraborty, H
   Moore, J
   Derman, R
   Kodkany, B
   Bellad, M
   Naik, VA
   Angolkar, M
   Bloch, M
AF Kelly, Patricia J.
   Goudar, Shivaprasad S.
   Chakraborty, Hrishikesh
   Moore, Janet
   Derman, Richard
   Kodkany, Bhala
   Bellad, Mrutyunjaya
   Naik, Vijjaya A.
   Angolkar, Mubashir
   Bloch, Michele
TI Pregnant women and children's exposure to tobacco and solid fuel smoke
   in southwestern India
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Women's health; second-hand smoke; solid fuel smoke; environmental
   risks; child health
ID INDOOR AIR-POLLUTION
AB Methods. aEuro integral We conducted a survey of exposure to second-hand smoke (SHS) and solid fuel smoke (SFS) among 736 pregnant women. Odds ratios (OR) and 95%% confidence intervals (CI) were computed using logistic regression models to assess the relationship between demographic variables and exposure to SHS and to SFS.
   Results. aEuro integral While few respondents smoked cigarettes, 19.9%% of women and 27.8%% of children were frequently or always exposed to SHS, and 43.5%% were at high and 46.7%% at medium risk for SFE. Low educational levels and illiteracy were associated with exposure.
   Conclusions. aEuro integral Smoke exposure is a serious health risk for many poor women and children in India.
C1 [Kelly, Patricia J.] Univ Missouri, Sch Nursing, Kansas City, MO 64108 USA.
   [Goudar, Shivaprasad S.; Kodkany, Bhala; Bellad, Mrutyunjaya; Naik, Vijjaya A.; Angolkar, Mubashir] Jawaharlal Nehru Med Coll, Women & Childrens Hlth Res Unit, Belgaum, India.
   [Chakraborty, Hrishikesh; Moore, Janet] Res Triangle Inst, Res Triangle Pk, NC 27709 USA.
   [Derman, Richard] Christiana Care Hlth Syst, Wilmington, DE USA.
   [Bloch, Michele] NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA.
RP Kelly, PJ (reprint author), Univ Missouri, Sch Nursing, 2464 Charlotte St, Kansas City, MO 64108 USA.
EM kellypj@umkc.edu
OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053
FU National Institute of Health Child Health and Human Development as part
   of the Global Network for Health [UO1-HD042372, UO1 HD040636]; National
   Cancer Institute; Bill and Melinda Gates Foundation; US Department of
   Health and Human Services' Office on Women's Health
FX Support for this project was provided by National Institute of Health
   Child Health and Human Development as part of the Global Network for
   Health, grant numbers UO1-HD042372, and UO1 HD040636, the National
   Cancer Institute, The Bill and Melinda Gates Foundation, and the US
   Department of Health and Human Services' Office on Women's Health.
NR 10
TC 1
Z9 1
U1 1
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD JUL
PY 2011
VL 24
IS 7
BP 973
EP 977
DI 10.3109/14767058.2010.537411
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 772FY
UT WOS:000291220900021
PM 21158490
ER

PT J
AU Ping, YF
   Yao, XH
   Jiang, JY
   Zhao, LT
   Yu, SC
   Jiang, T
   Lin, MCM
   Chen, JH
   Wang, B
   Zhang, R
   Cui, YH
   Qian, C
   Wang, JM
   Bian, XW
AF Ping, Yi-fang
   Yao, Xiao-hong
   Jiang, Jian-yong
   Zhao, Lin-tao
   Yu, Shi-cang
   Jiang, Tao
   Lin, Marie C. M.
   Chen, Jian-hong
   Wang, Bin
   Zhang, Rong
   Cui, You-hong
   Qian, Cheng
   Wang, Ji Ming
   Bian, Xiu-wu
TI The chemokine CXCL12 and its receptor CXCR4 promote glioma stem
   cell-mediated VEGF production and tumour angiogenesis via PI3K/AKT
   signalling
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE glioma; cancer stem cells; angiogenesis; CXCR4; cell signalling
ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; MALIGNANT
   HUMAN GLIOMAS; BREAST-CANCER CELLS; IN-VITRO; GLIOBLASTOMA; EXPRESSION;
   ACTIVATION; AKT; IDENTIFICATION
AB Chemokines and their receptors are actively involved in inflammation, immune responses, and cancer development. Here we report the detection of CD133(+) glioma stem-like cells (GSCs) co-expressing a chemokine receptor CXCR4 in human primary glioma tissues. These GSCs were located in areas adjacent to tumour vascular capillaries, suggesting an association between GSCs and tumour angiogenesis. To test this hypothesis, we isolated CD133(+) GSCs from surgical specimens of human primary gliomas and glioma cell lines. As compared to CD133(-) cells, CD133(+) GSCs expressed significantly higher levels of CXCR4 mRNA and protein, and migrated more efficiently in response to the CXCR4 ligand CXCL12. In addition, CXCL12 induced vascular endothelial growth factor (VEGF) production by CD133(+) GSCs via activation of the PI3K/AKT signalling pathway. Furthermore, knocking down of CXCR4 using RNA interference or inhibition of CXCR4 function by an antagonist AMD3100 not only reduced VEGF production by CD133(+) GSCs in vitro, but also attenuated the growth and angiogenesis of tumour xenografts in vivo formed by CD133(+) GSCs in SCID mice. These results indicate that CXCL12 and its receptor CXCR4 promote GSC-initiated glioma growth and angiogenesis by stimulating VEGF production. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
C1 [Ping, Yi-fang; Yao, Xiao-hong; Jiang, Jian-yong; Zhao, Lin-tao; Yu, Shi-cang; Lin, Marie C. M.; Chen, Jian-hong; Wang, Bin; Zhang, Rong; Cui, You-hong; Qian, Cheng; Bian, Xiu-wu] Third Mil Med Univ, Inst Pathol, Southwest Hosp, Chongqing 400038, Peoples R China.
   [Ping, Yi-fang; Yao, Xiao-hong; Jiang, Jian-yong; Zhao, Lin-tao; Yu, Shi-cang; Lin, Marie C. M.; Chen, Jian-hong; Wang, Bin; Zhang, Rong; Cui, You-hong; Qian, Cheng; Bian, Xiu-wu] Third Mil Med Univ, SW Canc Ctr, Southwest Hosp, Chongqing 400038, Peoples R China.
   [Jiang, Tao] Beijing Capital Med Univ, Dept Neurosurg, Tiantan Hosp, Beijing 100050, Peoples R China.
   [Lin, Marie C. M.] Chinese Univ Hong Kong, Brain Tumour Ctr, Div Neurosurg, PWH, Shatin, Hong Kong, Peoples R China.
   [Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Bian, XW (reprint author), Third Mil Med Univ, Inst Pathol, Southwest Hosp, Chongqing 400038, Peoples R China.
EM bianxiuwu@263.net
RI Bian, Xiuwu/F-1569-2011; Jiang, Tao/N-8142-2014; Bian,
   Xiu-wu/D-4736-2017
OI Bian, Xiu-wu/0000-0003-4383-0197
FU National Basic Research Programme of China (973 Programme)
   [2010CB529403]; National Natural Science Foundation of China (NSFC)
   [30725035, 30930103, 81001127]
FX We thank Dr Shideng Bao of Stem Cell Biology and Regenerative Medicine,
   Cleveland Clinic Lerner Research Institute, for his critical review, and
   Mrs Wei Sun and Miss Li-ting Wang (Central Laboratory, Third Military
   Medical University, Chongqing, China) for technical assistance in laser
   confocal scanning microscopy. This project was supported by grants from
   the National Basic Research Programme of China (973 Programme, No
   2010CB529403) and the National Natural Science Foundation of China
   (NSFC, Nos 30725035, 30930103, and 81001127).
NR 54
TC 98
Z9 111
U1 6
U2 29
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3417
J9 J PATHOL
JI J. Pathol.
PD JUL
PY 2011
VL 224
IS 3
BP 344
EP 354
DI 10.1002/path.2908
PG 11
WC Oncology; Pathology
SC Oncology; Pathology
GA 774MB
UT WOS:000291389500008
PM 21618540
ER

PT J
AU Bhaumik, P
   Horimoto, Y
   Xiao, HG
   Miura, T
   Hidaka, K
   Kiso, Y
   Wlodawer, A
   Yada, RY
   Gustchina, A
AF Bhaumik, Prasenjit
   Horimoto, Yasumi
   Xiao, Huogen
   Miura, Takuya
   Hidaka, Koushi
   Kiso, Yoshiaki
   Wlodawer, Alexander
   Yada, Rickey Y.
   Gustchina, Alla
TI Crystal structures of the free and inhibited forms of plasmepsin I (PMI)
   from Plasmodium falciparum
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE Malaria; Plasmepsin; Aspartic protease; Crystal structure; Enzyme
   inhibition
ID HIV-1 PROTEASE INHIBITOR; HISTO-ASPARTIC PROTEASE; HYDROXYMETHYLCARBONYL
   ISOSTERE; ENZYMATIC CHARACTERIZATION; MACROMOLECULAR STRUCTURES;
   MAXIMUM-LIKELIHOOD; DIGESTIVE VACUOLE; ESCHERICHIA-COLI; EXPRESSION;
   DESIGN
AB Plasmepsin I (PM!) is one of the four vacuolar pepsin-like proteases responsible for hemoglobin degradation by the malarial parasite Plasmodium falciparum, and the only one with no crystal structure reported to date. Due to substantial functional redundancy of these enzymes, lack of inhibition of even a single plasmepsin can defeat efforts in creating effective antiparasitic agents. We have now solved crystal structures of the recombinant PMI as apoenzyme and in complex with the potent peptidic inhibitor, KNI-10006. at the resolution of 2.4 and 3.1 angstrom, respectively. The apoenzyme crystallized in the orthorhombic space group P2(1)2(1)2(1) with two molecules in the asymmetric unit and the structure has been refined to the final R-factor of 20.7%. The KNI-10006 bound enzyme crystallized in the tetragonal space, group P4(3) with four molecules in the asymmetric unit and the structure has been refined to the final R-factor of 21.1%. In the PMI-KNI-10006 complex, the inhibitors were bound identically to all four enzyme molecules, with the opposite directionality of the main chain of KNI-10006 relative to the direction of the enzyme substrates. Such a mode of binding of inhibitors containing an allophenylnorstatine-dimethylthioproline insert in the P1-P1' positions, previously reported in a complex with PMIV, demonstrates the importance of satisfying the requirements for the proper positioning of the functional groups in the mechanism-based inhibitors towards the catalytic machinery of aspartic proteases, as opposed to binding driven solely by the specificity of the individual enzymes. A comparison of the structure of the PMI-KNI-10006 complex with the structures of other vacuolar plasmepsins identified the important differences between them and may help in the design of specific inhibitors targeting the individual enzymes. Published by Elsevier Inc.
C1 [Bhaumik, Prasenjit; Wlodawer, Alexander; Gustchina, Alla] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
   [Horimoto, Yasumi; Xiao, Huogen; Yada, Rickey Y.] Univ Guelph, Dept Food Sci, Guelph, ON N1G 2W1, Canada.
   [Miura, Takuya; Hidaka, Koushi; Kiso, Yoshiaki] Kyoto Pharmaceut Univ, Dept Med Chem, Yamashina Ku, Kyoto 6078412, Japan.
   [Miura, Takuya; Hidaka, Koushi; Kiso, Yoshiaki] Kyoto Pharmaceut Univ, Ctr Frontier Res Med Sci, Yamashina Ku, Kyoto 6078412, Japan.
RP Gustchina, A (reprint author), NCI, Prot Struct Sect, Macromol Crystallog Lab, Bldg 539,Rm 143, Frederick, MD 21702 USA.
EM gustchia@mail.nih.gov
RI Yada, Rickey/A-8289-2013
FU US Department of Energy, Office of Science, Office of Basic Energy
   Sciences [W-31-109-Eng-38]; NIH, National Cancer Institute, Center for
   Cancer Research; Natural Sciences and Engineering Research Council of
   Canada; Canada Research Chairs Program
FX We would like to thank Drs. Sergei Pletnev and Zbyszek Dauter for their
   help in data collection. Diffraction data were collected at the
   Southeast Regional Collaborative Access Team (SER-CAT) beamline 22-ID,
   located at the Advanced Photon Source, Argonne National Laboratory. Use
   of the Advanced Photon Source was supported by the US Department of
   Energy, Office of Science, Office of Basic Energy Sciences, under
   Contract No. W-31-109-Eng-38. This project was supported in part by the
   Intramural Research Program of the NIH, National Cancer Institute,
   Center for Cancer Research. Financial support from the Natural Sciences
   and Engineering Research Council of Canada and the Canada Research
   Chairs Program is also gratefully acknowledged.
NR 65
TC 20
Z9 20
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD JUL
PY 2011
VL 175
IS 1
BP 73
EP 84
DI 10.1016/j.jsb.2011.04.009
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 774FX
UT WOS:000291371800008
PM 21521654
ER

PT J
AU Kosmidis, S
   Botella, JA
   Mandilaras, K
   Schneuwly, S
   Skoulakis, EMC
   Rouault, TA
   Missirlis, F
AF Kosmidis, Stylianos
   Botella, Jose A.
   Mandilaras, Konstantinos
   Schneuwly, Stephan
   Skoulakis, Efthimios M. C.
   Rouault, Tracey A.
   Missirlis, Fanis
TI Ferritin overexpression in Drosophila glia leads to iron deposition in
   the optic lobes and late-onset behavioral defects
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE Optic lamina; Inclusions; Metals; Circadian clock; Restless legs;
   Hyperferritinemia
ID RESTLESS LEGS SYNDROME; KINASE-ASSOCIATED NEURODEGENERATION;
   DOPAMINERGIC NEURON LOSS; OXIDATIVE STRESS; PARKINSONS-DISEASE;
   MITOCHONDRIAL-FUNCTION; RETINAL DEGENERATION; RESPONSIVE ELEMENT;
   FRIEDREICHS-ATAXIA; ALPHA-SYNUCLEIN
AB Cellular and organismal iron storage depends on the function of the ferritin protein complex in insects and mammals alike. In the central nervous system of insects, the distribution and relevance of ferritin remain unclear, though ferritin has been implicated in Drosophila models of Alzheimers' and Parkinsons' disease and in Aluminum-induced neurodegeneration. Here we show that transgene-derived expression of ferritin subunits in glial cells of Drosophila melanogaster causes a late-onset behavioral decline, characterized by loss of circadian rhythms in constant darkness and impairment of elicited locomotor responses. Anatomical analysis of the affected brains revealed crystalline inclusions of iron-loaded ferritin in a subpopulation of glial cells but not significant neurodegeneration. Although transgene-induced glial ferritin expression was well tolerated throughout development and in young flies, it turned disadvantageous at older age. The flies we characterize in this report contribute to the study of ferritin in the Drosophila brain and can be used to assess the contribution of glial iron metabolism in neurodegenerative models of disease. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Mandilaras, Konstantinos; Missirlis, Fanis] Queen Mary Univ London, Sch Biol & Chem Sci, London E1 4NS, England.
   [Kosmidis, Stylianos; Skoulakis, Efthimios M. C.] BSRC Alexander Fleming, Inst Cellular & Dev Biol, Vari 16672, Greece.
   [Botella, Jose A.; Schneuwly, Stephan] Univ Regensburg, Inst Zool, D-93040 Regensburg, Germany.
   [Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, Bethesda, MD 20892 USA.
RP Missirlis, F (reprint author), Queen Mary Univ London, Sch Biol & Chem Sci, Mile End Rd, London E1 4NS, England.
EM f.missirlis@qmul.ac.uk
RI Missirlis, Fanis/C-1137-2011
OI Missirlis, Fanis/0000-0003-0467-8444
FU Marie Curie International Reintegration Grant "DrosoFela"; Greek General
   Secretariat of Research and Technology; National Institute of Child
   Health and Human Development
FX We thank Manos Mavrakis, Anuja Mehta, Boris Dunkov and Ralf Stanewsky
   for their critical comments on earlier drafts of the manuscript and
   funding from the Marie Curie International Reintegration Grant
   "DrosoFela" (F.M.), the EPAN-YB13 grant from the Greek General
   Secretariat of Research and Technology (S.K.) and the intramural program
   of the National Institute of Child Health and Human Development (F.M.
   and T.A.R.).
NR 80
TC 12
Z9 13
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 0969-9961
J9 NEUROBIOL DIS
JI Neurobiol. Dis.
PD JUL
PY 2011
VL 43
IS 1
SI SI
BP 213
EP 219
DI 10.1016/j.nbd.2011.03.013
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 771RZ
UT WOS:000291179700024
PM 21440626
ER

PT J
AU Weinrich, M
   Stuart, M
AF Weinrich, Michael
   Stuart, Mary
TI Coverage Policy for Neurorehabilitation: An International Perspective
SO NEUROREHABILITATION AND NEURAL REPAIR
LA English
DT Article
DE neurologic rehabilitation; insurance; coverage; health policy
ID TRAUMATIC BRAIN-INJURY; SPINAL-CORD-INJURY; HEALTH-CARE REFORM;
   SUB-SAHARAN AFRICA; STROKE REHABILITATION; INPATIENT REHABILITATION;
   MEDICAL REHABILITATION; UNITED-STATES; MANAGED CARE; INSURANCE
AB Background. Coverage policy ultimately determines the delivery of services. This article summarizes the authors' effort to ascertain the extent of publically available information on coverage for neurorehabilitation services internationally. Objective. Present available data on neurorehabilitation coverage and examine the needs for further research in this area. Methods. Review of published literature, review of government Web sites, survey of World Federation of NeuroRehabilitation (WFNR) program chairs, and attendees of the 2010 World Congress of NeuroRehabilitation. Results. A wide variation in coverage was found internationally. Data are not routinely accessible. Conclusions. Informed policy requires current data. There is an opportunity for the WFNR to provide leadership in policy for neurorehabilitation services by assembling and maintaining current data on coverage policy internationally.
C1 [Weinrich, Michael] NIH, Natl Ctr Med Rehabil Res, Eunice Kennedy Shriver Inst Child Hlth & Human De, Rockville, MD 20852 USA.
   [Stuart, Mary] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA.
RP Weinrich, M (reprint author), NIH, Natl Ctr Med Rehabil Res, Eunice Kennedy Shriver Inst Child Hlth & Human De, Rockville, MD 20852 USA.
EM weinricm@mail.nih.gov
NR 69
TC 1
Z9 1
U1 1
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1545-9683
EI 1552-6844
J9 NEUROREHAB NEURAL RE
JI Neurorehabil. Neural Repair
PD JUL-AUG
PY 2011
VL 25
IS 6
BP 531
EP 539
DI 10.1177/1545968310397207
PG 9
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 774KL
UT WOS:000291384200005
PM 21427275
ER

PT J
AU Blair, A
   Thomas, K
   Coble, J
   Sandler, DP
   Hines, CJ
   Lynch, CF
   Knott, C
   Purdue, MP
   Zahm, SH
   Alavanja, MCR
   Dosemeci, M
   Kamel, F
   Hoppin, JA
   Freeman, LB
   Lubin, JH
AF Blair, Aaron
   Thomas, Kent
   Coble, Joseph
   Sandler, Dale P.
   Hines, Cynthia J.
   Lynch, Charles F.
   Knott, Charles
   Purdue, Mark P.
   Zahm, Shelia Hoar
   Alavanja, Michael C. R.
   Dosemeci, Mustafa
   Kamel, Freya
   Hoppin, Jane A.
   Freeman, Laura Beane
   Lubin, Jay H.
TI Impact of pesticide exposure misclassification on estimates of relative
   risks in the Agricultural Health Study
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID FARM APPLICATORS; CANCER INCIDENCE; RELIABILITY; DISEASE; CHLORPYRIFOS;
   INFORMATION; COHORT; WOMEN
AB Background The Agricultural Health Study (AHS) is a prospective study of licensed pesticide applicators and their spouses in Iowa and North Carolina. We evaluate the impact of occupational pesticide exposure misclassification on relative risks using data from the cohort and the AHS Pesticide Exposure Study (AHS/PES).
   Methods We assessed the impact of exposure misclassification on relative risks using the range of correlation coefficients observed between measured post-application urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) and a chlorpyrifos metabolite and exposure estimates based on an algorithm from 83 AHS pesticide applications.
   Results Correlations between urinary levels of 2,4-D and a chlorpyrifos metabolite and algorithm estimated intensity scores were about 0.4 for 2,4-D (n=64), 0.8 for liquid chlorpyrifos (n=4) and 0.6 for granular chlorpyrifos (n=12). Correlations of urinary levels with kilograms of active ingredient used, duration of application, or number of acres treated were lower and ranged from -0.36 to 0.19. These findings indicate that a priori expert-derived algorithm scores were more closely related to measured urinary levels than individual exposure determinants evaluated here. Estimates of potential bias in relative risks based on the correlations from the AHS/PES indicate that non-differential misclassification of exposure using the algorithm would bias estimates towards the null, but less than that from individual exposure determinants.
   Conclusions Although correlations between algorithm scores and urinary levels were quite good (ie, correlations between 0.4 and 0.8), exposure misclassification would still bias relative risk estimates in the AHS towards the null and diminish study power.
C1 [Blair, Aaron; Purdue, Mark P.; Zahm, Shelia Hoar; Alavanja, Michael C. R.; Dosemeci, Mustafa; Freeman, Laura Beane; Lubin, Jay H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Thomas, Kent] US EPA, Natl Exposure Res Lab, Res Triangle Pk, NC 27711 USA.
   [Sandler, Dale P.; Kamel, Freya; Hoppin, Jane A.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
   [Hines, Cynthia J.] NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA.
   [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
   [Knott, Charles] Battelle Inc, Ctr Publ Hlth Res, Res Triangle Pk, NC USA.
   [Knott, Charles] Battelle Inc, Ctr Evaluat, Res Triangle Pk, NC USA.
RP Blair, A (reprint author), NCI, Div Canc Epidemiol & Genet, Execut Plaza S,Room 8008, Bethesda, MD 20892 USA.
EM blaira@mail.nih.gov
RI Zahm, Shelia/B-5025-2015; Purdue, Mark/C-9228-2016; Beane Freeman,
   Laura/C-4468-2015; 
OI Purdue, Mark/0000-0003-1177-3108; Beane Freeman,
   Laura/0000-0003-1294-4124; Kamel, Freya/0000-0001-5052-6615; Sandler,
   Dale/0000-0002-6776-0018
FU NIH (Division of Cancer Epidemiology and Genetics, National Cancer
   Institute) [Z01CP010119]; NIH (National Institute of Environmental
   Health Sciences) [Z01-ES049030-1]; U.S. Environmental Protection Agency
   [68-D99-011, 68-D99-012, DW-75-93912801-0]
FX This research was partially supported by the Intramural Research Program
   of the NIH (Division of Cancer Epidemiology and Genetics, National
   Cancer Institute (Z01CP010119) and the National Institute of
   Environmental Health Sciences (Z01-ES049030-1)). This work has been
   funded in part by the U.S. Environmental Protection Agency under
   Contracts 68-D99-011 and 68-D99-012, and through Interagency Agreement
   DW-75-93912801-0.
NR 34
TC 16
Z9 16
U1 1
U2 15
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 JUL
PY 2011
VL 68
IS 7
BP 537
EP 541
DI 10.1136/oem.2010.059469
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 773KY
UT WOS:000291307400012
PM 21257983
ER

PT J
AU Lombaert, IMA
   Knox, SM
   Hoffman, MP
AF Lombaert, I. M. A.
   Knox, S. M.
   Hoffman, M. P.
TI Salivary gland progenitor cell biology provides a rationale for
   therapeutic salivary gland regeneration
SO ORAL DISEASES
LA English
DT Review
DE salivary gland; regeneration; progenitor cells; stem cells
ID STEM-CELLS; RADIATION-DAMAGE
AB An irreversible loss of salivary gland function often occurs in humans after removal of salivary tumors, after therapeutic radiation of head and neck tumors, as a result of Sjogren's syndrome and in genetic syndromes affecting gland development. The permanent loss of gland function impairs the oral health of these patients and broadly affects their quality of life. The regeneration of functional salivary gland tissue is thus an important therapeutic goal for the field of regenerative medicine and will likely involve stem/progenitor cell biology and/or tissue engineering approaches. Recent reports demonstrate how both innervation of the salivary gland epithelium and certain growth factors influence progenitor cell growth during mouse salivary gland development. These advances in our understanding suggest that developmental mechanisms of mouse salivary gland development may provide a paradigm for postnatal regeneration of both mice and human salivary glands. Herein, we will discuss the developmental mechanisms that influence progenitor cell biology and the implications for salivary gland regeneration.
C1 [Lombaert, I. M. A.; Knox, S. M.; Hoffman, M. P.] NIDCR, Matrix & Morphogenesis Unit, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Hoffman, MP (reprint author), NIDCR, Matrix & Morphogenesis Unit, Lab Cell & Dev Biol, NIH, Bldg 30 Rm 430,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA.
EM mhoffman@mail.nih.gov
OI Knox, Sarah/0000-0002-7567-083X
FU Intramural NIH HHS [ZIA DE000707-08, ZIA DE000722-04, Z99 DE999999]
NR 23
TC 33
Z9 35
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
EI 1601-0825
J9 ORAL DIS
JI Oral Dis.
PD JUL
PY 2011
VL 17
IS 5
BP 445
EP 449
DI 10.1111/j.1601-0825.2010.01783.x
PG 5
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 772GY
UT WOS:000291223500001
PM 21223454
ER

PT J
AU Perez, P
   Adriaansen, J
   Goldsmith, CM
   Zheng, C
   Baum, BJ
AF Perez, P.
   Adriaansen, J.
   Goldsmith, C. M.
   Zheng, C.
   Baum, B. J.
TI Transgenic alpha-1-antitrypsin secreted into the bloodstream from
   salivary glands is biologically active
SO ORAL DISEASES
LA English
DT Article
DE human alpha-1-antitrypsin; bioactivity; gene therapy; secretion;
   salivary glands
ID MEDIATED GENE-TRANSFER; SUBMANDIBULAR-GLANDS; ADENOVIRAL VECTOR;
   SYSTEMIC DELIVERY; SERINE PROTEINASE; SJOGRENS-SYNDROME; MURINE MODEL;
   ALPHA(1)-ANTITRYPSIN; THERAPEUTICS; DEFICIENCY
AB Objectives:
   Salivary glands are potentially a valuable target for gene therapeutics. Herein, we examined the expression and biochemical activity of human alpha-1-antitrypsin (hA1AT) produced in rodent submandibular glands after gene transfer.
   Methods:
   A serotype 5 adenoviral vector (Ad.hA1AT) was constructed and first characterized by dose response and time course studies using SMIE cells in vitro. hA1AT expression was analysed by ELISA and the biologic activity determined by the inhibition of human neutrophil elastase (hNE) and formation of hA1AT-hNE complexes. Ad.hA1AT was administered to submandibular glands of rats and mice. The levels and activity of hA1AT were analysed in saliva, serum and gland extracts. Treatment with endoglycosidase H and Peptide N-Glycosidase F was used to assess N-linked glycosylation.
   Results:
   Transgenic hA1AT, expressed in submandibular glands following Ad.hA1AT administration, was secreted into the bloodstream, N-glycosylated and biochemically active.
   Conclusion:
   After in vivo gene transfer, rodent salivary glands can produce a non-hormonal, transgenic, secretory glycoprotein exhibiting complex and conformation-dependent biologic activity.
C1 [Perez, P.; Adriaansen, J.; Goldsmith, C. M.; Zheng, C.; Baum, B. J.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Perez, P (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1A01,10 Ctr Dr, Bethesda, MD 20892 USA.
EM perezriverosp@mail.nih.gov
FU Division of Intramural Research of the National Institute of Dental and
   Craniofacial Research
FX The Division of Intramural Research of the National Institute of Dental
   and Craniofacial Research supported this research.
NR 32
TC 5
Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1354-523X
EI 1601-0825
J9 ORAL DIS
JI Oral Dis.
PD JUL
PY 2011
VL 17
IS 5
BP 476
EP 483
DI 10.1111/j.1601-0825.2010.01775.x
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 772GY
UT WOS:000291223500005
PM 21122036
ER

PT J
AU Proschan, MA
   Shaw, PA
AF Proschan, Michael A.
   Shaw, Pamela A.
TI Asymptotics of Bonferroni for dependent normal test statistics
SO STATISTICS & PROBABILITY LETTERS
LA English
DT Article
DE Bonferroni; Extreme value theory; Familywise error rate; Genome wide
   association; Multiple comparisons
ID MAXIMUM TERM; SEQUENCES
AB The Bonferroni adjustment is sometimes used to control the familywise error rate (FWE) when the number of comparisons is huge. In genome wide association studies, researchers compare cases to controls with respect to thousands of single nucleotide polymorphisms. It has been claimed that the Bonferroni adjustment is only slightly conservative if the comparisons are nearly independent. We show that the veracity of this claim depends on how one defines "nearly". Specifically, if the test statistics' pairwise correlations converge to 0 as the number of tests tend to infinity, the conservatism of the Bonferroni procedure depends on their rate of convergence. The type I error rate of Bonferroni can tend to 0 or 1 - exp(-alpha) approximate to alpha, depending on that rate. We show using elementary probability theory what happens to the distribution of the number of errors when using Bonferroni, as the number of dependent normal test statistics gets large. We also use the limiting behavior of Bonferroni to shed light on properties of other commonly used test statistics. Published by Elsevier B.V.
C1 [Proschan, Michael A.; Shaw, Pamela A.] NIAID, Bethesda, MD 20892 USA.
RP Proschan, MA (reprint author), NIAID, 6700B Rockledge Dr,MSC 7630, Bethesda, MD 20892 USA.
EM proscham@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 18
TC 3
Z9 3
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-7152
EI 1879-2103
J9 STAT PROBABIL LETT
JI Stat. Probab. Lett.
PD JUL
PY 2011
VL 81
IS 7
SI SI
BP 739
EP 748
DI 10.1016/j.spl.2010.11.013
PG 10
WC Statistics & Probability
SC Mathematics
GA 771QG
UT WOS:000291175200005
PM 24882910
ER

PT J
AU Simon, R
   Simon, NR
AF Simon, Richard
   Simon, Noah Robin
TI Using randomization tests to preserve type I error with response
   adaptive and covariate adaptive randomization
SO STATISTICS & PROBABILITY LETTERS
LA English
DT Article
DE Response adaptive randomization; Adaptive stratification; Clinical
   trials
ID CONTROLLED CLINICAL-TRIAL; PLAY-WINNER RULE; TREATMENT ASSIGNMENT;
   DESIGN
AB We demonstrate that clinical trials using response adaptive randomized treatment assignment rules are subject to substantial bias if there are time trends in unknown prognostic factors and standard methods of analysis are used. We develop a general class of randomization tests based on generating the null distribution of a general test statistic by repeating the adaptive randomized treatment assignment rule holding fixed the sequence of outcome values and covariate vectors actually observed in the trial. We develop broad conditions on the adaptive randomization method and the stochastic mechanism by which outcomes and covariate vectors are sampled that ensure that the type I error is controlled at the level of the randomization test. These conditions ensure that the use of the randomization test protects the type terror against time trends that are independent of the treatment assignments. Under some conditions in which the prognosis of future patients is determined by knowledge of the current randomization weights, the type I error is not strictly protected. We show that response adaptive randomization can result in substantial reduction in statistical power when the type I error is preserved. Our results also ensure that type I error is controlled at the level of the randomization test for adaptive stratification designs used for balancing covariates. Published by Elsevier B.V.
C1 [Simon, Richard] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
   [Simon, Noah Robin] Stanford Univ, Dept Stat, Stanford, CA 94305 USA.
RP Simon, R (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rsimon@nih.gov; nsimon@stanford.edu
FU Intramural NIH HHS [Z99 CA999999]
NR 15
TC 10
Z9 10
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-7152
EI 1879-2103
J9 STAT PROBABIL LETT
JI Stat. Probab. Lett.
PD JUL
PY 2011
VL 81
IS 7
SI SI
BP 767
EP 772
DI 10.1016/j.spl.2010.12.018
PG 6
WC Statistics & Probability
SC Mathematics
GA 771QG
UT WOS:000291175200008
PM 21769160
ER

PT J
AU Pfeiffer, RM
   Petracci, E
AF Pfeiffer, R. M.
   Petracci, E.
TI Variance computations for functionals of absolute risk estimates
SO STATISTICS & PROBABILITY LETTERS
LA English
DT Article
DE Absolute risk; Functional delta method; Bootstrap
ID ATTRIBUTABLE RISK
AB We present a simple influence function based approach for computing the variances of estimates of absolute risk and functions of absolute risk. We apply this approach to criteria that assess the impact of changes in the risk factor distribution on absolute risk for an individual and at the population level. As an illustration we use an absolute risk prediction model for breast cancer that includes modifiable risk factors in addition to standard breast cancer risk factors. Influence function based variance estimates for absolute risk and the criteria are compared to bootstrap variance estimates. Published by Elsevier B.V.
C1 [Pfeiffer, R. M.] NCI, Biostat Branch, DCEG, Bethesda, MD 20892 USA.
   [Petracci, E.] Univ Bologna, Dept Stat, I-40126 Bologna, Italy.
RP Pfeiffer, RM (reprint author), NCI, Biostat Branch, DCEG, 6120 Execut Blvd,EPS-8030, Bethesda, MD 20892 USA.
EM pfeiffer@mail.nih.gov; elisabetta.petracci2@unibo.it
RI Pfeiffer, Ruth /F-4748-2011; Petracci, Elisabetta/K-1520-2016
OI Petracci, Elisabetta/0000-0001-9456-3514
FU Intramural NIH HHS [Z01 CP010181-06, ZIA CP010181-08]
NR 10
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-7152
J9 STAT PROBABIL LETT
JI Stat. Probab. Lett.
PD JUL
PY 2011
VL 81
IS 7
SI SI
BP 807
EP 812
DI 10.1016/j.spl.2011.02.002
PG 6
WC Statistics & Probability
SC Mathematics
GA 771QG
UT WOS:000291175200013
PM 21643476
ER

PT J
AU Wang, LL
   Li, QZ
   Li, ZH
   Zheng, G
AF Wang, Linglu
   Li, Qizhai
   Li, Zhaohai
   Zheng, Gang
TI Bayes factors in the presence of population stratification
SO STATISTICS & PROBABILITY LETTERS
LA English
DT Article
DE Approximate Bayes factor; Clustering; Genome-wide association studies;
   Odds ratio; Population stratification
ID GENOME-WIDE ASSOCIATION; GENETIC ASSOCIATION; SUBSTRUCTURE
AB Hidden population stratification (PS) is a main concern in the analysis of case-control genetic association studies. All methods to correct for hidden PS have been focused on classical hypothesis testing, and cannot be directly applied to Bayesian analysis. In this paper, to study the impact and the correction of hidden PS on Bayes factor (BF), we use a simple approximation of BF in terms of the maximum likelihood estimates of the odds ratio (OR) and its asymptotic variance. One advantage is that the commonly used principal components analysis method with a large panel of null markers scanned from existing genome-wide association studies can be directly employed to correct for hidden PS in estimating the OR and its asymptotic variance, through which a correction to BF for hidden PS can be achieved. Using simulations, we examine the impact of ignoring hidden PS on BF and show that the proposed method yields an appropriate correction in Bayesian analysis. Published by Elsevier B.V.
C1 [Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
   [Wang, Linglu; Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
   [Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China.
RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM zhengg@nhlbi.nih.gov
FU National Young Science Foundation of China [10901155]
FX Q. Li is partially supported by the National Young Science Foundation of
   China, No. 10901155. We would like to thank reviewers, AE and the Guest
   Editor for their helpful comments and encouragement. In particular, the
   AE provided us many critical suggestions, which substantially improved
   our presentation.
NR 13
TC 1
Z9 1
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-7152
EI 1879-2103
J9 STAT PROBABIL LETT
JI Stat. Probab. Lett.
PD JUL
PY 2011
VL 81
IS 7
SI SI
BP 836
EP 841
DI 10.1016/j.spl.2011.02.020
PG 6
WC Statistics & Probability
SC Mathematics
GA 771QG
UT WOS:000291175200017
ER

PT J
AU Wiener, L
   Battles, H
   Mamalian, C
   Zadeh, S
AF Wiener, Lori
   Battles, Haven
   Mamalian, Cynthia
   Zadeh, Sima
TI ShopTalk: a pilot study of the feasibility and utility of a therapeutic
   board game for youth living with cancer
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Pediatric cancer; Adolescent cancer; Psychosocial adjustment; Game
AB ShopTalk is a therapeutic game, created to help youth living with cancer talk about their illness in a non-threatening way. The aim of this study is to learn how the game is being used in clinical settings and to gather information regarding the usefulness of ShopTalk in establishing a therapeutic relationship and in assessing key psychosocial issues in the child's life.
   ShopTalk was distributed at a social work pediatric oncology conference and to 70 sites. Game holders were asked to complete a survey regarding their clinical experience using ShopTalk.
   Responses came from 110 professionals. ShopTalk has been found to be as an effective tool in identifying coping skills and psychological adjustment, as well as issues related to family relationships, depression/sadness, stress, prognosis, peer relationships, and self-esteem. Respondents found ShopTalk useful from diagnosis to end of life. Qualitative feedback suggested therapeutic value along with discomfort with specific questions.
   ShopTalk appears to be a beneficial therapeutic tool in building rapport and identifying and discussing difficult issues with medically ill children. Areas for future versions of the game and research exploring patient/therapist outcomes are discussed.
C1 [Wiener, Lori] NCI, NIH, Pediat Clin, Bethesda, MD 20892 USA.
   [Wiener, Lori; Battles, Haven; Zadeh, Sima] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
   [Mamalian, Cynthia] Mamalian Consulting, Bethesda, MD USA.
RP Wiener, L (reprint author), NCI, NIH, Pediat Clin, 10 Ctr Dr,Room 1-6466, Bethesda, MD 20892 USA.
EM wienerl@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute; National Cancer
   Institute, National Institutes of Health
FX This research was supported by the Center for Cancer Research, National
   Cancer Institute. Funding for the production of ShopTalk was obtained
   from the Philip Pizzo Gift Fund at the National Cancer Institute,
   National Institutes of Health. We would like to thank the hundreds of
   children treated at the National Cancer Institute from 1999 to 2009 who
   provided invaluable insights that helped in the development of this
   game. We would also like to acknowledge Crystal Mackall, MD, for her
   unyielding support of psychosocial interventions for children living
   with cancer that led to the manufacturing of ShopTalk, along with Brie
   Kohrt, MA for her assistance with the training video and data collection
   and Nia Billings, MA, for her help with the data coding for the
   manuscript preparation.
NR 15
TC 9
Z9 9
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD JUL
PY 2011
VL 19
IS 7
BP 1049
EP 1054
DI 10.1007/s00520-011-1130-z
PG 6
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA 774BU
UT WOS:000291357100024
PM 21451945
ER

PT J
AU Huang, JH
   Hu, KN
   Decker, B
AF Huang, Jen-How
   Hu, Kan-Nian
   Decker, Berryinne
TI Organic Arsenic in the Soil Environment: Speciation, Occurrence,
   Transformation, and Adsorption Behavior
SO WATER AIR AND SOIL POLLUTION
LA English
DT Review
DE Organic arsenic; Soil; Speciation; Transformation; Adsorption
ID CHEMICAL WARFARE AGENTS; MONOMETHYLARSONOUS ACID; ORGANOARSENIC
   COMPOUNDS; SURFACE COMPLEXATION; CONTAMINATED SOILS; PLANTS;
   ACCUMULATION; EVOLUTION; WATER; BIOTRANSFORMATION
AB An attempt is made to describe the fate and behavior of organic arsenic (As) compounds in the soil environment, based on an extensive literature researches. The objective of this review is to provide an overview on the state of knowledge to date about the occurrence and potential transformation of organic As, including methylation, degradation, and hydration, in soils and their uptake and accumulation in plants and animals. Accordingly, the biogeochemical cycle of organic As in the soil environment is proposed.
C1 [Huang, Jen-How] Swiss Fed Inst Technol Zurich, Inst Biogeochem & Pollutant Dynam, CH-8092 Zurich, Switzerland.
   [Hu, Kan-Nian] NIDDKD, Lab Chem Phys, NIH, Bethesda, MD 20892 USA.
   [Decker, Berryinne] Case Western Reserve Univ, Dept Chem Engn, Cleveland, OH 44106 USA.
RP Huang, JH (reprint author), Swiss Fed Inst Technol Zurich, Inst Biogeochem & Pollutant Dynam, CH-8092 Zurich, Switzerland.
EM jenhow.huang@env.ethz.ch
FU Swiss National Science Foundation [PZ00P2_122212]; National Institute of
   Diabetes and Digestive and Kidney Diseases of the National Institutes of
   Health
FX Financial support of JHH comes from Swiss National Science Foundation
   Ambizione fellowship (PZ00P2_122212). KNH is supported by a fellowship
   from the Intramural Research Program of the National Institute of
   Diabetes and Digestive and Kidney Diseases of the National Institutes of
   Health.
NR 72
TC 28
Z9 28
U1 12
U2 107
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0049-6979
J9 WATER AIR SOIL POLL
JI Water Air Soil Pollut.
PD JUL
PY 2011
VL 219
IS 1-4
BP 401
EP 415
DI 10.1007/s11270-010-0716-2
PG 15
WC Environmental Sciences; Meteorology & Atmospheric Sciences; Water
   Resources
SC Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences;
   Water Resources
GA 772QM
UT WOS:000291249700034
ER

PT J
AU Yan, YJ
   Chen, K
   Yang, M
   Sun, XL
   Liu, SL
   Chen, XY
AF Yan, Yongjun
   Chen, Kai
   Yang, Min
   Sun, Xilin
   Liu, Shuanglong
   Chen, Xiaoyuan
TI A new F-18-labeled BBN-RGD peptide heterodimer with a symmetric linker
   for prostate cancer imaging
SO AMINO ACIDS
LA English
DT Article
DE Integrin alpha v beta 3; Gastrin-releasing peptide receptor; BBN-RGD
   heterodimer; PET; 18F
ID INTEGRIN ALPHA(V)BETA(3) EXPRESSION; NEUROENDOCRINE DIFFERENTIATION;
   BOMBESIN HETERODIMER; TUMOR ANGIOGENESIS; RECEPTOR; MICROPET;
   ADENOCARCINOMA; PET; ANALOGS
AB A peptide heterodimer comprises two different receptor-targeting peptide ligands. Molecular imaging probes based on dual-receptor targeting peptide heterodimers exhibit improved tumor targeting efficacy for multi-receptor expressing tumors compared with their parent single-receptor targeting peptide monomers. Previously we have developed bombesin (BBN)-RGD (Arg-Gly-Asp) peptide heterodimers, in which BBN and RGD are covalently connected with an asymmetric glutamate linker (J Med Chem 52:425-432, 2009). Although F-18-labeled heterodimers showed significantly better microPET imaging quality than F-18-labeled RGD and BBN monomers in a PC-3 xenograft model which co-expresses gastrin-releasing peptide receptor (GRPR) and integrin alpha v beta 3, tedious heterodimer synthesis due to the asymmetric nature of glutamate linker restricts their clinical applications. In this study, we report the use of a symmetric linker AEADP [AEADP = 3,3'-(2-aminoethylazanediyl)dipropanoic acid] for the synthesis of BBN-RGD peptide heterodimer. The F-18-labeled heterodimer (F-18-FB-AEADP-BBN-RGD) showed comparable microPET imaging results with glutamate linked BBN-RGD heterodimers, indicating that the replacement of glutamate linker with AEADP linker did not affect the biological activities of BBN-RGD heterodimer. The heterodimer synthesis is rather easy and straightforward. Because tumors often co-express multiple receptors, the use of a symmetric linker provides a general method of fast assembly of various peptide heterodimers for imaging multi-receptor expressing tumors.
C1 [Yan, Yongjun; Yang, Min; Sun, Xilin; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA.
   [Yan, Yongjun; Chen, Kai; Liu, Shuanglong; Chen, Xiaoyuan] Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA.
   [Yan, Yongjun; Chen, Kai; Liu, Shuanglong; Chen, Xiaoyuan] Stanford Univ, Sch Med, Bio X Program, Stanford, CA 94305 USA.
   [Yang, Min] Jiangsu Inst Nucl Med, Key Lab Nucl Med, Wuxi 214063, Peoples R China.
   [Sun, Xilin] Harbin Med Coll, Affiliated Hosp 4, Dept Med Imaging & Nucl Med, Harbin 150001, Peoples R China.
RP Chen, XY (reprint author), NIBIB, LOMIN, NIH, 31 Ctr Dr,Suite 1C14, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
FU National Cancer Institute (NCI) [R01 CA119053, P50 CA114747, U54
   CA119367]; National Institute of Biomedical Imaging and Bioengineering
   (NIBIB), National Institutes of Health (NIH)
FX This work was supported in part by the National Cancer Institute (NCI)
   grants R01 CA119053, P50 CA114747, and U54 CA119367) and the Intramural
   Research Program of the National Institute of Biomedical Imaging and
   Bioengineering (NIBIB), National Institutes of Health (NIH).
NR 33
TC 23
Z9 27
U1 2
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-4451
J9 AMINO ACIDS
JI Amino Acids
PD JUL
PY 2011
VL 41
IS 2
BP 439
EP 447
DI 10.1007/s00726-010-0762-5
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 769QT
UT WOS:000291034000018
PM 20936525
ER

PT J
AU Bland, DC
   Zampieri, C
   Damiano, DL
AF Bland, Daniel C.
   Zampieri, Cris
   Damiano, Diane L.
TI Effectiveness of physical therapy for improving gait and balance in
   individuals with traumatic brain injury: A systematic review
SO BRAIN INJURY
LA English
DT Review
DE Traumatic brain injury; rehabilitation; therapy
ID RANDOMIZED CONTROLLED-TRIAL; INPATIENT REHABILITATION;
   ELECTRICAL-STIMULATION; EXERCISE PROGRAMS; RECOVERY; DEFICITS; MODERATE;
   DESIGN; SCALE
AB Primary objective: The purpose of this review was to investigate the efficacy or effectiveness of non-aerobic exercise interventions to improve balance and gait in functionally mild-to-moderate individuals with TBI (those who demonstrate the ability or capacity to ambulate) and to provide evidence-based guidelines for clinical practice.
   Methods: The authors searched eight databases for papers including exercise interventions to improve gait and balance post-TBI. Twenty papers fully met inclusion criteria. The quality of studies was determined by the Physiotherapy Evidence Database (PEDro) scale and strength by Sackett's Levels of Evidence.
   Results: This study found limited evidence of the positive effects of balance, gait or the combination of both interventions in TBI rehabilitation. Most studies included small sample sizes with heterogeneous groups and the interventions were variable and lacked standardization. The outcome measures were variable and low in quality.
   Conclusions: The state of evidence for gait and balance interventions in patients with mild-to-moderate TBI is surprisingly poor. Greater consideration and conformity in the choice of outcome measures and attention in the design and standardization treatment approaches are essential in future research to advance practice.
C1 [Bland, Daniel C.; Zampieri, Cris; Damiano, Diane L.] NIH, Funct & Appl Biomechan Sect, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
   [Bland, Daniel C.] Duke Univ, Sch Med, Durham, NC USA.
RP Damiano, DL (reprint author), NIH, Funct & Appl Biomechan Sect, Dept Rehabil Med, Ctr Clin, Bldg 10,Room 1-1469, Bethesda, MD 20892 USA.
EM damianod@cc.nih.gov
RI Damiano, Diane/B-3338-2010
OI Damiano, Diane/0000-0002-2770-5356
FU NIH; Pfizer Inc; NIH, Clinical Center, Rehabilitation Medicine
   Department; center for neuroscience and regenerative medicine (CNRM)
FX This research year was made possible through the Clinical Research
   Training Program, a public-private partnership supported jointly by the
   NIH and Pfizer Inc (via a grant to the Foundation for NIH from Pfizer
   Inc). This research was also supported by the Intramural Research
   Program of the NIH, Clinical Center, Rehabilitation Medicine Department.
   This research was also supported by the center for neuroscience and
   regenerative medicine (CNRM). Dr Damiano and Dr Zampieri are employed by
   the NIH. The authors report no conflicts of interest. The authors alone
   are responsible for the content and writing of the paper.
NR 46
TC 19
Z9 19
U1 7
U2 34
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0269-9052
J9 BRAIN INJURY
JI Brain Inj.
PD JUL
PY 2011
VL 25
IS 7-8
BP 664
EP 679
DI 10.3109/02699052.2011.576306
PG 16
WC Neurosciences; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 769RJ
UT WOS:000291035600003
PM 21561297
ER

PT J
AU Hofmann, JN
   Torner, A
   Chow, WH
   Ye, WM
   Purdue, MP
   Duberg, AS
AF Hofmann, Jonathan N.
   Torner, Anna
   Chow, Wong-Ho
   Ye, Weimin
   Purdue, Mark P.
   Duberg, Ann-Sofi
TI Risk of kidney cancer and chronic kidney disease in relation to
   hepatitis C virus infection: a nationwide register-based cohort study in
   Sweden
SO EUROPEAN JOURNAL OF CANCER PREVENTION
LA English
DT Article
DE cancer registry; chronic hepatitis C virus infection; chronic kidney
   disease; kidney cancer; renal cell carcinoma
ID GENDER-DIFFERENCES; RENAL-DISEASE; CARCINOMA; LYMPHOMA
AB Chronic hepatitis C virus (HCV) infection is an established cause of liver cancer, and recent studies have suggested a link with kidney cancer. The aim of this study was to evaluate risk of kidney cancer in relation to HCV infection in a nationwide registry-based study of Swedish residents diagnosed with HCV between 1990 and 2006. A total of 43 000 individuals with chronic HCV infection were included, and the mean follow-up time was 9.3 years. Observed kidney cancer incidence and mortality in the cohort were compared with expected values based on the age-adjusted and sex-adjusted rates in the general population. Risk of hospitalization for other chronic kidney disease was also evaluated using Cox proportional hazards regression. No association between HCV infection and risk of kidney cancer was observed [standardized incidence ratio with 1-year lag = 1.2; 95% confidence interval (CI): 0.8-1.7]. Risk of hospitalization for noncancer kidney disease was significantly elevated in the HCV cohort, with significantly stronger associations observed among women than among men [hazard ratio = 5.8 (95% CI: 4.2-7.9) and 3.9 (95% CI: 3.2-4.8) for women and men, respectively]. Results of this study do not support the hypothesis that chronic HCV infection confers an increased risk of kidney cancer. However, we did find an association between HCV infection and chronic kidney disease, particularly among women. Given inconsistent findings in the literature, it is premature to consider HCV infection to be a risk factor for kidney cancer. European Journal of Cancer Prevention 20:326-330 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Hofmann, Jonathan N.; Chow, Wong-Ho; Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Torner, Anna] Swedish Inst Infect Dis Control, Dept Epidemiol, Solna, Sweden.
   [Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
   [Duberg, Ann-Sofi] Orebro Univ Hosp, Dept Infect Dis, Orebro, Sweden.
RP Hofmann, JN (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8109,MSC 7240, Bethesda, MD 20892 USA.
EM hofmannjn@mail.nih.gov
RI Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
FU National Institutes of Health, National Cancer Institute, Division of
   Cancer Epidemiology and Genetics; Research Committee of Orebro County
   Council [2007/4077, OLL-91961]
FX This research was supported in part by the Intramural Research Program
   of the National Institutes of Health, National Cancer Institute,
   Division of Cancer Epidemiology and Genetics, and the Research Committee
   of Orebro County Council (Grants 2007/4077 and OLL-91961).
NR 21
TC 13
Z9 13
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-8278
J9 EUR J CANCER PREV
JI Eur. J. Cancer Prev.
PD JUL
PY 2011
VL 20
IS 4
BP 326
EP 330
DI 10.1097/CEJ.0b013e32834572fa
PG 5
WC Oncology
SC Oncology
GA 769PK
UT WOS:000291029600011
PM 21386707
ER

PT J
AU Simon, SL
AF Simon, Steven L.
TI ORGAN-SPECIFIC EXTERNAL DOSE COEFFICIENTS AND PROTECTIVE APRON
   TRANSMISSION FACTORS FOR HISTORICAL DOSE RECONSTRUCTION FOR MEDICAL
   PERSONNEL
SO HEALTH PHYSICS
LA English
DT Article
DE diagnostic radiology; dose, external; exposure, occupational; medical
   radiation
ID US RADIOLOGIC TECHNOLOGISTS; MONTE-CARLO CALCULATIONS; ADULT VOXEL
   PHANTOM; RADIATION PROTECTION; DIAGNOSTIC-RADIOLOGY; EQUIVALENT;
   DOSIMETRY; BACKSCATTER
AB While radiation absorbed dose (Gy) to the skin or other organs is sometimes estimated for patients from diagnostic radiologic examinations or therapeutic procedures, rarely is occupationally-received radiation absorbed dose to individual organs/tissues estimated for medical personnel; e. g., radiologic technologists or radiologists. Generally, for medical personnel, equivalent or effective radiation doses are estimated for compliance purposes. In the very few cases when organ doses to medical personnel are reconstructed, the data is usually for the purpose of epidemiologic studies; e. g., a study of historical doses and risks to a cohort of about 110,000 radiologic technologists presently underway at the U. S. National Cancer Institute. While ICRP and ICRU have published organ-specific external dose conversion coefficients (DCCs) (i.e., absorbed dose to organs and tissues per unit air kerma and dose equivalent per unit air kerma), those factors have been published primarily for mono-energetic photons at selected energies. This presents two related problems for historical dose reconstruction, both of which are addressed here. It is necessary to derive conversion factor values for (1) continuous distributions of energy typical of diagnostic medical x-rays (bremsstrahlung radiation), and (2) energies of particular radioisotopes used in medical procedures, neither of which are presented in published tables. For derivation of DCCs for bremsstrahlung radiation, combinations of x-ray tube potentials and filtrations were derived for different time periods based on a review of relevant literature. Three peak tube potentials (70 kV, 80 kV, and 90 kV) with four different amounts of beam filtration were determined to be applicable for historic dose reconstruction. The probabilities of these machine settings were assigned to each of the four time periods (earlier than 1949, 1949-1954, 1955-1968, and after 1968). Continuous functions were fit to each set of discrete values of the ICRP/ICRU mono-energetic DCCs and the functions integrated over the air-kerma weighted photon fluence of the 12 defined x-ray spectra. The air kerma-weighted DCCs in this work were developed specifically for an irradiation geometry of anterior to posterior (AP) and for the following tissues: thyroid, breast, ovary, lens of eye, lung, colon, testes, heart, skin (anterior side only), red bone marrow (RBM), and brain. In addition, a series of functional relationships to predict D-T K-a(-1) values for RBM dependent on body mass index [BMI (kg m(-2)) equivalent to weight per height(2)] and average photon energy were derived from a published analysis. Factors to account for attenuation of radiation by protective lead aprons were also developed. Because lead protective aprons often worn by radiology personnel not only reduce the intensity of x-ray exposure but also appreciably harden the transmitted fluence of bremsstrahlung x-rays, DCCs were separately calculated for organs possibly protected by lead aprons by considering three cases: no apron, 0.25 mm Pb apron, and 0.5 mm Pb apron. For estimation of organ doses from conducting procedures with radioisotopes, continuous functions of the reported mono-energetic values were developed, and DCCs were derived by estimation of the function at relevant energies. By considering the temporal changes in primary exposure-related parameters (e. g.
   , energy distribution), the derived DCCs and transmission factors presented here allow for more realistic historical dose reconstructions for medical personnl when monitoring badge readings are the primary data on which estimation of an individual's organ doses are based. Health Phys. 101(1):13-27; 2011
C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM ssimon@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
FX The author appreciates the assistance of Stephen M. Seltzer of the
   National Institute of Standards and Technology (NIST) for review and
   correction of the method for the air kerma weighting and of Robert
   Weinstock for discussions on mathematical issues. This research was
   supported by the Intramural Research Program of the National Cancer
   Institute, National Institutes of Health.
NR 37
TC 7
Z9 7
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD JUL
PY 2011
VL 101
IS 1
BP 13
EP 27
DI 10.1097/HP.0b013e318204a60a
PG 15
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
   Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
   Medical Imaging
GA 769NF
UT WOS:000291021500002
PM 21617389
ER

PT J
AU Furl, N
   Garrido, L
   Dolan, RJ
   Driver, J
   Duchaine, B
AF Furl, Nicholas
   Garrido, Lucia
   Dolan, Raymond J.
   Driver, Jon
   Duchaine, Bradley
TI Fusiform Gyrus Face Selectivity Relates to Individual Differences in
   Facial Recognition Ability
SO JOURNAL OF COGNITIVE NEUROSCIENCE
LA English
DT Article
ID SUPERIOR TEMPORAL SULCUS; HUMAN VISUAL-CORTEX; CONGENITAL PROSOPAGNOSIA;
   FMRI-ADAPTATION; DEVELOPMENTAL PROSOPAGNOSICS; DISTINCT REPRESENTATIONS;
   ACQUIRED PROSOPAGNOSIA; DETAILED EXPLORATION; UNFAMILIAR FACES; NEURAL
   BASIS
AB Regions of the occipital and temporal lobes, including a region in the fusiform gyrus (FG), have been proposed to constitute a "core" visual representation system for faces, in part because they show face selectivity and face repetition suppression. But recent fMRI studies of developmental prosopagnosics (DPs) raise questions about whether these measures relate to face processing skills. Although DPs manifest deficient face processing, most studies to date have not shown unequivocal reductions of functional responses in the proposed core regions. We scanned 15 DPs and 15 non-DP control participants with fMRI while employing factor analysis to derive behavioral components related to face identification or other processes. Repetition suppression specific to facial identities in FG or to expression in FG and STS did not show compelling relationships with face identification ability. However, we identified robust relationships between face selectivity and face identification ability in FG across our sample for several convergent measures, including voxel-wise statistical parametric mapping, peak face selectivity in individually defined "fusiform face areas" (FFAs), and anatomical extents (cluster sizes) of those FFAs. None of these measures showed associations with behavioral expression or object recognition ability. As a group, DPs had reduced face-selective responses in bilateral FFA when compared with non-DPs. Individual DPs were also more likely than non-DPs to lack expected face-selective activity in core regions. These findings associate individual differences in face processing ability with selectivity in core face processing regions. This confirms that face selectivity can provide a valid marker for neural mechanisms that contribute to face identification ability.
C1 [Furl, Nicholas; Garrido, Lucia; Dolan, Raymond J.; Driver, Jon; Duchaine, Bradley] UCL, London WC1E 6BT, England.
RP Furl, N (reprint author), NIH, Bldg 49,1B80,49 Convent Dr, Bethesda, MD 20892 USA.
EM furlno@mail.nih.gov
OI furl, nicholas/0000-0003-2488-1343; Garrido, Lucia/0000-0002-1955-6506;
   Dolan, Ray/0000-0001-9356-761X
FU Portuguese Foundation for Science and Technology [SFRH/BD/22580/2005];
   Economic and Social Research Council [RES-061-23-0400]; The Wellcome
   Trust
FX The authors are grateful to their colleagues at the University College
   London, namely, Laura Germine and Raka Tavashmi for assistance with
   behavioral measurement and/or fMRI data collection, Bogdan Draganski and
   Ferath Kherif for advice and support, and John Stevens for clinical
   evaluation of the participants. This work was supported by the
   Portuguese Foundation for Science and Technology (grant no.
   SFRH/BD/22580/2005 to L. G.), the Economic and Social Research Council
   (grant no. RES-061-23-0400 to B. D.), and The Wellcome Trust (R. J. D.
   and J. D.). J. D. is a Royal Society Research Professor. Editorial
   assistance for the manuscript was provided by the National Institutes of
   Health Fellows Editorial Board.
NR 47
TC 69
Z9 71
U1 1
U2 19
PU MIT PRESS
PI CAMBRIDGE
PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA
SN 0898-929X
J9 J COGNITIVE NEUROSCI
JI J. Cogn. Neurosci.
PD JUL
PY 2011
VL 23
IS 7
BP 1723
EP 1740
DI 10.1162/jocn.2010.21545
PG 18
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 762JR
UT WOS:000290473000012
PM 20617881
ER

PT J
AU Fancher, RM
   Zhang, HJ
   Sleczka, B
   Derbin, G
   Rockar, R
   Marathe, P
AF Fancher, R. Marcus
   Zhang, Hongjian
   Sleczka, Bogdan
   Derbin, George
   Rockar, Richard
   Marathe, Punit
TI Development of a Canine Model to Enable the Preclinical Assessment of
   Ph-dependent Absorption of Test Compounds
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE dog; pH effect; absorption; pentagastrin; famotidine
ID GASTRIC RESIDENCE TIME; BEAGLE DOGS; IN-VITRO; DRUG ABSORPTION; ORAL
   ABSORPTION; DOSAGE FORMS; DISSOLUTION MEDIA; INTRAGASTRIC PH; SOLUBLE
   DRUGS; WEAK BASES
AB A preclinical canine model capable of predicting a compound's potential for pH-dependent absorption in humans was developed. This involved the surgical insertion of a gastrostomy feeding tube into the stomach of a beagle dog. The tube was sutured in position to allow frequent withdrawal of gastric fluid for pH measurement. Therefore, it was possible to measure pH in the stomach and assess the effect of gastric pH-modifying agents on the absorption of various test compounds. Fasted gastric pH in the dog showed considerable inter- and intra-animal variability. Pretreatment of pentagastrin (6 mu g/kg intramuscularly) 20 min prior to test compound administration was determined to be adequate for simulating fasting stomach pH in humans. Pretreatment with famotidine [40 mg orally] 1 h prior to test compound administration was determined to be adequate for simulating human gastric pH when acid-reducing agents are coadministered. Pentagastrin and famotidine pretreatments were used to test two discovery compounds and distinct differences in their potential for pH-dependent absorption were observed. The model described herein can be used preclinically to screen out compounds, differentiate compounds, and support the assessment of various formulation-and prodrug-based strategies to mitigate the pH effect. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 2979-2988, 2011
C1 [Fancher, R. Marcus; Zhang, Hongjian; Sleczka, Bogdan; Marathe, Punit] Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08540 USA.
   [Derbin, George] Bristol Myers Squibb Pharmaceut Res Inst, New Brunswick, NJ 08903 USA.
   [Rockar, Richard] NIH Anim Ctr, NIH, Dickerson, MD 20842 USA.
RP Marathe, P (reprint author), Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08540 USA.
EM punit.marathe@bms.com
NR 49
TC 12
Z9 12
U1 6
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3549
J9 J PHARM SCI-US
JI J. Pharm. Sci.
PD JUL
PY 2011
VL 100
IS 7
BP 2979
EP 2988
DI 10.1002/jps.22486
PG 10
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
   Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA 765RE
UT WOS:000290725500042
PM 21254068
ER

PT J
AU Borodovsky, M
   Przytycka, TM
   Rajasekaran, S
   Zelikovsky, A
AF Borodovsky, Mark
   Przytycka, Teresa M.
   Rajasekaran, Sanguthevar
   Zelikovsky, Alexander
TI Guest Editors' Introduction to the Special Section on Bioinformatics
   Research and Applications
SO IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
LA English
DT Editorial Material
C1 [Borodovsky, Mark] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA.
   [Borodovsky, Mark] Georgia Inst Technol, Sch Computat Sci & Engn, Atlanta, GA 30332 USA.
   [Borodovsky, Mark] Emory Univ, Atlanta, GA 30332 USA.
   [Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
   [Rajasekaran, Sanguthevar] Univ Connecticut, Dept Comp Sci & Engn, Storrs, CT 06269 USA.
   [Zelikovsky, Alexander] Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA.
RP Borodovsky, M (reprint author), Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA.
EM borodovsky@gatech.edu; przytyck@mail.nih.gov; rajasek@engr.uconn.edu;
   alexz@cs.gsu.edu
RI Zelikovsky, Alexander/A-9049-2008
OI Zelikovsky, Alexander/0000-0003-4424-4691
NR 0
TC 0
Z9 0
U1 0
U2 0
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
SN 1545-5963
J9 IEEE ACM T COMPUT BI
JI IEEE-ACM Trans. Comput. Biol. Bioinform.
PD JUL-AUG
PY 2011
VL 8
IS 4
BP 865
EP 866
PG 2
WC Biochemical Research Methods; Computer Science, Interdisciplinary
   Applications; Mathematics, Interdisciplinary Applications; Statistics &
   Probability
SC Biochemistry & Molecular Biology; Computer Science; Mathematics
GA 762CD
UT WOS:000290449000001
PM 21812137
ER

PT J
AU Zhang, P
   Li, HQ
   Wang, HH
   Wong, STC
   Zhou, XB
AF Zhang, Peng
   Li, Houqiang
   Wang, Honghui
   Wong, Stephen T. C.
   Zhou, Xiaobo
TI Peak Tree: A New Tool for Multiscale Hierarchical Representation and
   Peak Detection of Mass Spectrometry Data
SO IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
LA English
DT Article
DE Mass spectrometry; peak identification; peak tree; scale-space
   filtering; wavelets; feature selection
ID WAVELET TRANSFORM; SPECTRA; QUANTIFICATION; CLASSIFICATION;
   OPTIMIZATION; BIOMARKERS; SELECTION; ALIGNMENT; COLONY; TIME
AB Peak detection is one of the most important steps in mass spectrometry (MS) analysis. However, the detection result is greatly affected by severe spectrum variations. Unfortunately, most current peak detection methods are neither flexible enough to revise false detection results nor robust enough to resist spectrum variations. To improve flexibility, we introduce peak tree to represent the peak information in MS spectra. Each tree node is a peak judgment on a range of scales, and each tree decomposition, as a set of nodes, is a candidate peak detection result. To improve robustness, we combine peak detection and common peak alignment into a closed-loop framework, which finds the optimal decomposition via both peak intensity and common peak information. The common peak information is derived and loopily refined from the density clustering of the latest peak detection result. Finally, we present an improved ant colony optimization biomarker selection method to build a whole MS analysis system. Experiment shows that our peak detection method can better resist spectrum variations and provide higher sensitivity and lower false detection rates than conventional methods. The benefits from our peak-tree-based system for MS disease analysis are also proved on real SELDI data.
C1 [Zhang, Peng; Li, Houqiang] Univ Sci & Technol China, Dept Elect Engn & Informat Sci, Hefei 230027, Anhui, Peoples R China.
   [Wang, Honghui] NIH, Ctr Clin, Bethesda, MD 20892 USA.
   [Wong, Stephen T. C.; Zhou, Xiaobo] Methodist Hosp, Res Inst, Weill Cornell Med Coll, Dept Radiol & Bioinformat Core, Houston, TX 77030 USA.
RP Li, HQ (reprint author), Univ Sci & Technol China, Dept Elect Engn & Informat Sci, POB 4, Hefei 230027, Anhui, Peoples R China.
EM charmp@mail.ustc.edu.cn; lihq@ustc.edu.cn; hwang2@cc.nih.gov;
   STWong@tmhs.org; XZhou@tmhs.org
RI Li, Houqiang Li/B-6259-2013
FU Program for New Century Excellent Talents in University (NCET);
   MOE-Microsoft Key Laboratory of Multimedia Computing and Communication
   [07122804]; TMHRI; NIH [R01 LM008696, R01 LM009161, R01 AG028928]
FX The work of Dr. Li and Mr. Zhang is supported by Program for New Century
   Excellent Talents in University (NCET) and open fund of MOE-Microsoft
   Key Laboratory of Multimedia Computing and Communication under contract
   No. 07122804. Dr. Zhou is partially funded by TMHRI scholarship award.
   He and Dr. Wong are also partially funded by NIH R01 LM008696, R01
   LM009161, and R01 AG028928 Grants. The authors thank the anonymous
   reviewers for the very detailed comments, which have greatly helped them
   to improve their manuscript. The demonstration Matlab code on peak
   detection is accessible at http://staff.ustc.edu.cn/similar to
   lihq/peaktree. Houqiang Li is the corresponding author of this paper.
NR 32
TC 5
Z9 5
U1 1
U2 8
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
SN 1545-5963
J9 IEEE ACM T COMPUT BI
JI IEEE-ACM Trans. Comput. Biol. Bioinform.
PD JUL-AUG
PY 2011
VL 8
IS 4
BP 1054
EP 1066
DI 10.1109/TCBB.2009.56
PG 13
WC Biochemical Research Methods; Computer Science, Interdisciplinary
   Applications; Mathematics, Interdisciplinary Applications; Statistics &
   Probability
SC Biochemistry & Molecular Biology; Computer Science; Mathematics
GA 762CD
UT WOS:000290449000017
PM 21566254
ER

PT J
AU Raafat, A
   Goldhar, AS
   Klauzinska, M
   Xu, KL
   Amirjazil, I
   Mccurdy, D
   Lashin, K
   Salomon, D
   Vonderhaar, BK
   Egan, S
   Callahan, R
AF Raafat, Ahmed
   Goldhar, Anita S.
   Klauzinska, Malgorzata
   Xu, Keli
   Amirjazil, Idean
   Mccurdy, David
   Lashin, Karim
   Salomon, David
   Vonderhaar, Barbara K.
   Egan, Sean
   Callahan, Robert
TI Expression of Notch Receptors, Ligands, and Target Genes During
   Development of the Mouse Mammary Gland
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID ESTROGEN-RESPONSIVE ELEMENT; TRUNCATED INT3 GENE; HUMAN BREAST-CANCER;
   SIGNALING PATHWAY; CELL-FATE; BINDING-SITES; CROSS-TALK;
   DIFFERENTIATION; TUMORIGENESIS; EPITHELIUM
AB Notch genes play a critical role in mammary gland growth, development and tumorigenesis. In the present study, we have quantitatively determined the levels and mRNA expression patterns of the Notch receptor genes, their ligands and target genes in the postnatal mouse mammary gland. The steady state levels of Notch3 mRNA are the highest among receptor genes, Jagged1 and DII3 mRNA levels are the highest among ligand genes and Hey2 mRNA levels are highest among expressed Hes/Hey target genes analyzed during different stages of postnatal mammary gland development. Using an immunohistochemical approach with antibodies specific for each Notch receptor, we show that Notch proteins are temporally regulated in mammary epithelial cells during normal mammary gland development in the FVB/N mouse. The loss of ovarian hormones is associated with changes in the levels of Notch receptor mRNAs (Notch2 higher and Notch3 lower) and ligand mRNAs (DII1 and DII4 are higher, whereas DII3 and Jagged1 are lower) in the mammary gland of ovariectomized mice compared to intact mice. These data define expression of the Notch ligand/receptor system throughout development of the mouse mammary gland and help set the stage for genetic analysis of Notch in this context. J. Cell. Physiol. J. Cell. Physiol. 226: 1940-1952, 2011. (C) 2010 Wiley-Liss, Inc.
C1 [Raafat, Ahmed; Goldhar, Anita S.; Klauzinska, Malgorzata; Amirjazil, Idean; Mccurdy, David; Lashin, Karim; Salomon, David; Vonderhaar, Barbara K.; Callahan, Robert] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA.
   [Xu, Keli; Egan, Sean] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 1L7, Canada.
RP Callahan, R (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, 37 Convent Dr,Bldg 37,Rm 1118A, Bethesda, MD 20892 USA.
EM rc54d@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; Genome
   Canada through the Ontario Genomics Institute
FX This research was supported by the Intramural Research Program of the
   NIH, National Cancer Institute, Center for Cancer Research. S. E. Egan's
   lab has been supported by funds from Genome Canada through the Ontario
   Genomics Institute.
NR 59
TC 21
Z9 22
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9541
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD JUL
PY 2011
VL 226
IS 7
BP 1940
EP 1952
DI 10.1002/jcp.22526
PG 13
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 762ZB
UT WOS:000290519900028
PM 21506125
ER

PT J
AU Kuan, CT
   Wakiya, K
   Keir, ST
   Li, JJ
   Herndon, JE
   Pastan, I
   Bigner, DD
AF Kuan, Chien-Tsun
   Wakiya, Kenji
   Keir, Stephen T.
   Li, Jianjun
   Herndon, James E., II
   Pastan, Ira
   Bigner, Darell D.
TI Affinity-matured anti-glycoprotein NMB recombinant immunotoxins
   targeting malignant gliomas and melanomas
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE GPNMB; phage display; recombinant immunotoxin; single-chain Fv; yeast
   display
ID GROWTH-FACTOR RECEPTOR; SINGLE-CHAIN FV; PHAGE DISPLAY; IN-VITRO;
   MONOCLONAL-ANTIBODIES; ANTI-CD22 IMMUNOTOXIN; SOMATIC HYPERMUTATION;
   CELL-LINES; EXOTOXIN-A; MATURATION
AB Glycoprotein NMB (GPNMB), a transmembrane glycoprotein highly expressed in high-grade gliomas (HGGs), is an attractive target in cancer immunotherapy. We isolated a GPNMB-specific scFv clone, G49, from a human synthetic phage-display library. To obtain mutant single-chain variable-fragment antibodies (scFvs) with improved affinity and immunotoxins with increased activity, we subjected G49 to in vitro affinity maturation by a complementarity-determining-region (CDR) random-mutagenesis technique. Using light-chain CDR3 mutagenesis, cell-based panning by phage display, subsequent heavy-chain CDR1 mutagenesis, and flow-cytometric selection by yeast-surface display, we generated the mutant scFv clone 902V, with an overall 11-fold increase in affinity for GPNMB. Clone 902V was further randomized throughout the whole scFv by error-prone PCR, and one mutant, F6V, was selected by yeast-surface display. F6V scFv, differing from 902V by one amino-acid change in the light-chain CDR2, exhibited an affinity for GPNMB of 0.30 nM. The F6V mutant scFv clone was fused with a truncated form of Pseudomonas exotoxin A to form the immunotoxin F6V-PE38. F6V-PE38 demonstrated significant protein-synthesis-inhibition activity on GPNMB-expressing glioma and malignant melanoma cells (IC(50) = 0.5 ng/ ml [8 pM]), a 60-fold improvement over G49 activity, but no cytotoxicity on GPNMB-negative cells. Furthermore, F6V-PE38 exhibited significant antitumor activity against subcutaneous malignant glioma xenografts in two nude-mouse models and a melanoma neoplastic meningitis model in athymic rats. These GPNMB-specific scFv antibodies and immunotoxins hold promise as reagents in targeted therapy for HGGs and other GPNMB-expressing malignancies.
C1 [Kuan, Chien-Tsun; Wakiya, Kenji; Li, Jianjun; Bigner, Darell D.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA.
   [Kuan, Chien-Tsun; Wakiya, Kenji; Keir, Stephen T.; Li, Jianjun; Herndon, James E., II; Bigner, Darell D.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA.
   [Keir, Stephen T.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
   [Herndon, James E., II] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
   [Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kuan, CT (reprint author), Duke Univ, Med Ctr, Dept Pathol, Res Dr,Box 3156, Durham, NC 27710 USA.
EM kuan@duke.edu
FU National Institutes of Health [MO1 RR30]; NINDS [5P50 NS020023]; NCI [CA
   5P50 108786, R37 CA011898]; Finding Cures for Glioma
FX Grant sponsor: National Institutes of Health; Grant numbers: MO1 RR30
   (General Clinical Research Centers Program, National Center for Research
   Resources), 5P50 NS020023 (NINDS), CA 5P50 108786 (NCI SPORE), R37
   CA011898 (NCI Merit Award), Intramural Research Program; Grant sponsor:
   Finding Cures for Glioma
NR 45
TC 16
Z9 17
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 1
PY 2011
VL 129
IS 1
BP 111
EP 121
DI 10.1002/ijc.25645
PG 11
WC Oncology
SC Oncology
GA 756BS
UT WOS:000289987300011
PM 20824708
ER

PT J
AU Kilfoy, BA
   Zhang, YW
   Park, Y
   Holford, TR
   Schatzkin, A
   Hollenbeck, A
   Ward, MH
AF Kilfoy, Briseis A.
   Zhang, Yawei
   Park, Yikyung
   Holford, Theodore R.
   Schatzkin, Arthur
   Hollenbeck, Albert
   Ward, Mary H.
TI Dietary nitrate and nitrite and the risk of thyroid cancer in the
   NIH-AARP Diet and Health Study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE thyroid; cancer; nitrate; nitrite; NIH-AARP
ID RETIRED-PERSONS DIET; N-NITROSO COMPOUNDS; DRINKING-WATER; ENVIRONMENTAL
   CHEMICALS; AMERICAN-ASSOCIATION; NATIONAL-INSTITUTES; UNITED-STATES;
   COHORT; FOOD; GENDER
AB During the past several decades, an increasing incidence of thyroid cancer has been observed worldwide. Nitrate inhibits iodide uptake by the thyroid, potentially disrupting thyroid function. An increased risk of thyroid cancer associated with nitrate intake was recently reported in a cohort study of older women in Iowa. We evaluated dietary nitrate and nitrite intake and thyroid cancer risk overall and for subtypes in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, a large prospective cohort of 490,194 men and women, ages 50-71 years in 1995-1996. Dietary intakes were assessed using a 124-item food frequency questionnaire. During an average of 7 years of follow-up we identified 370 incident thyroid cancer cases (170 men, 200 women) with complete dietary information. Among men, increasing nitrate intake was positively associated with thyroid cancer risk (relative risk [RR] for the highest quintile versus lowest quintile RR = 2.28, 95% confidence interval [CI]: 1.29-4.041; p-trend < 0.001); however, we observed no trend with intake among women (p-trend = 0.61). Nitrite intake was not associated with risk of thyroid cancer for either men or women. We evaluated risk for the two main types of thyroid cancer. We found positive associations for nitrate intake and both papillary (RR = 2.10; 95% CI: 1.09-4.05; p-trend = 0.05) and follicular thyroid cancer (RR = 3.42; 95% CI: 1.03-11.4; p-trend = 0.01) among men. Nitrite intake was associated with increased risk of follicular thyroid cancer (RR = 2.74; 95%CI: 0.86-8.77; p-trend = 0.04) among men. Our results support a role of nitrate in thyroid cancer risk and suggest that further studies to investigate these exposures are warranted.
C1 [Kilfoy, Briseis A.; Zhang, Yawei; Holford, Theodore R.] Yale Univ, Sch Epidemiol & Publ Hlth, New Haven, CT USA.
   [Kilfoy, Briseis A.; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA.
   [Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA.
   [Hollenbeck, Albert] AARP, Washington, DC USA.
RP Kilfoy, BA (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv,EPS, Room 8111,6120 Execut Blvd, Bethesda, MD 20852 USA.
EM kilfoyb@mail.nih.gov
RI Aschebrook-Kilfoy, Briseis/A-2537-2012; 
OI Park, Yikyung/0000-0002-6281-489X
FU National Institutes of Health [TU2CA105666]; National Cancer Institute
   (NCI); National Cancer Institute, National Institutes of Health,
   Department of Health and Human Service
FX Grant sponsor: National Institutes of Health training; Grant number:
   TU2CA105666; Grant sponsor: Intramural Research Program of the National
   Cancer Institute (NCI); Dr. Kilfoy was supported by National Institutes
   of Health training grant TU2CA105666. This research was supported [in
   part] by the Intramural Research Program of the National Cancer
   Institute, National Institutes of Health, Department of Health and Human
   Service. The investigators are indebted to all participants for
   providing the data and for their commitment to the NIH-AARP Diet and
   Health Study. The authors also thank Dr. Bernard T. Nolan of the U.S.
   Geological Survey for providing the national dataset of estimated
   nitrate levels in groundwater used for drinking water supplies and Matt
   Airola of Westat Inc. for the Geographic Information System analysis.
NR 45
TC 35
Z9 35
U1 2
U2 13
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 JUL 1
PY 2011
VL 129
IS 1
BP 160
EP 172
DI 10.1002/ijc.25650
PG 13
WC Oncology
SC Oncology
GA 756BS
UT WOS:000289987300016
PM 20824705
ER

PT J
AU Hassan, S
   Buchanan, M
   Jahan, K
   Aguilar-Mahecha, A
   Gaboury, L
   Muller, WJ
   Alsawafi, Y
   Mourskaia, AA
   Siegel, PM
   Salvucci, O
   Basik, M
AF Hassan, Saima
   Buchanan, Marguerite
   Jahan, Kaushar
   Aguilar-Mahecha, Adriana
   Gaboury, Louis
   Muller, William J.
   Alsawafi, Yaqoob
   Mourskaia, Anna A.
   Siegel, Peter M.
   Salvucci, Ombretta
   Basik, Mark
TI CXCR4 peptide antagonist inhibits primary breast tumor growth,
   metastasis and enhances the efficacy of anti-VEGF treatment or docetaxel
   in a transgenic mouse model
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE breast cancer; CXCR4; primary tumor; metastasis; therapeutic target;
   transgenic mouse
ID CHEMOKINE RECEPTOR CXCR4; CANCER METASTASIS; ENDOTHELIAL-CELLS; IN-VIVO;
   THERAPY; ANGIOGENESIS; PROGRESSION; AUTOCRINE; CTCE-9908; PATHWAY
AB CXCR4 is a chemokine receptor implicated in the homing of cancer cells to target metastatic organs, which overexpress its ligand, stromal cell-derived factor (SDF)-1. To determine the efficacy of targeting CXCR4 on primary tumor growth and metastasis, we used a peptide inhibitor of CXCR4, CTCE-9908, that was administered in a clinically relevant approach using a transgenic breast cancer mouse model. We first performed a dosing experiment of CTCE-9908 in the PyMT mouse model, testing 25, 50 and 100 mg/kg versus the scrambled peptide in groups of 8-16 mice. We then combined CTCE-9908 with docetaxel or DC101 (an anti-VEGFR2 monoclonal antibody). We found that increasing doses of CTCE-9908 alone slowed the rate of tumor growth, with a 45% inhibition of primary tumor growth at 3.5 weeks of treatment with 50 mg/kg of CTCE-9908 (p = 0.005). Expression levels of VEGF were also found to be reduced by 42% with CTCE-9908 (p = 0.01). In combination with docetaxel, CTCE-9908 administration decreased tumor volume by 38% (p = 0.02), an effect that was greater than that observed with docetaxel alone. In combination with DC101, CTCE-9908 also demonstrated an enhanced effect compared to DC101 alone, with a 37% decrease in primary tumor volume (p = 0.01) and a 75% reduction in distant metastasis (p = 0.009). In combination with docetaxel or an anti-angiogenic agent, the anti-tumor and anti-metastatic effects of CTCE-9908 were markedly enhanced, suggesting potentially new effective combinatorial therapeutic strategies in the treatment of breast cancer, which include targeting the SDF-1/CXCR4 ligand/receptor pair.
C1 [Hassan, Saima; Buchanan, Marguerite; Jahan, Kaushar; Aguilar-Mahecha, Adriana; Alsawafi, Yaqoob; Basik, Mark] McGill Univ, Dept Surg, Lady Davis Inst, Sir Mortimer B Davis Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada.
   [Gaboury, Louis] Univ Montreal, Dept Pathol, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada.
   [Muller, William J.; Mourskaia, Anna A.; Siegel, Peter M.] McGill Univ, Dept Med, Rosalind & Goodman Canc Ctr, Montreal, PQ H3T 1E2, Canada.
   [Muller, William J.; Mourskaia, Anna A.; Siegel, Peter M.] McGill Univ, Dept Biochem, Rosalind & Goodman Canc Ctr, Montreal, PQ H3T 1E2, Canada.
   [Hassan, Saima; Buchanan, Marguerite; Jahan, Kaushar; Aguilar-Mahecha, Adriana; Alsawafi, Yaqoob; Basik, Mark] McGill Univ, Dept Oncol, Lady Davis Inst, Sir Mortimer B Davis Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada.
   [Salvucci, Ombretta] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Basik, M (reprint author), McGill Univ, Dept Oncol, Lady Davis Inst, Sir Mortimer B Davis Jewish Gen Hosp, 3755 Cote Ste Catherine, Montreal, PQ H3T 1E2, Canada.
EM markbasik@gmail.com
FU Canadian Surgery Research Fund [2006]; Chemokine Therapeutics Corp;
   Chemokine Therapeutics
FX Grant sponsors: The Canadian Surgery Research Fund Operating Grant 2006,
   Chemokine Therapeutics Corp; Grant sponsor: Chemokine Therapeutics
NR 35
TC 53
Z9 55
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 1
PY 2011
VL 129
IS 1
BP 225
EP 232
DI 10.1002/ijc.25665
PG 8
WC Oncology
SC Oncology
GA 756BS
UT WOS:000289987300022
PM 20830712
ER

PT J
AU Zadeh, S
   Wiener, L
   Battles, H
   Bosk, A
   Wideman, B
   Hazra, R
   Wayne, A
   Pao, M
AF Zadeh, S.
   Wiener, L.
   Battles, H.
   Bosk, A.
   Wideman, B.
   Hazra, R.
   Wayne, A.
   Pao, M.
TI PERCEIVED BENEFIT AND BURDEN FOR YOUTH AND THEIR PARENTS FOR
   PARTICIPATION IN PSYCHOSOCIAL RESEARCH WHEN UNDERGOING TREATMENT FOR
   CANCER, NF-1, OR HIV
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
   NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2011
VL 56
IS 7
BP 1156
EP 1156
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 749CX
UT WOS:000289440800039
ER

PT J
AU Wiener, L
   Friebert, S
   Mullins, LL
   Elkin, D
   Madan-Swain, A
   Phipps, S
   Sherman-Bien, S
   Patenaude, A
   Battles, H
   Zadeh, S
   Pao, M
AF Wiener, Lori
   Friebert, Sarah
   Mullins, Larry L.
   Elkin, David
   Madan-Swain, Avi
   Phipps, Sean
   Sherman-Bien, Sandra
   Patenaude, Andrea
   Battles, Haven
   Zadeh, Sima
   Pao, Maryland
TI CHARACTERIZING LONE PARENTING: A MULTI-INSTITUTIONAL PILOT STUDY OF THE
   PERCEPTIONS OF SUPPORT AND PERCEIVED STRESS OF LONE PARENTS OF CHILDREN
   WITH CANCER
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Wiener, Lori; Battles, Haven; Zadeh, Sima] NCI, NIH, Bethesda, MD 20892 USA.
   [Mullins, Larry L.] Oklahoma State Univ, Stillwater, OK 74078 USA.
   [Elkin, David] Univ Mississippi, Med Ctr, University, MS 38677 USA.
   [Madan-Swain, Avi] Univ Alabama, Div Pediat Hematol Oncol, Childrens Hosp, Tuscaloosa, AL 35487 USA.
   [Phipps, Sean] St Jude Childrens Hosp, Memphis, TN 38105 USA.
   [Patenaude, Andrea] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Pao, Maryland] NIMH, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2011
VL 56
IS 7
BP 1157
EP 1157
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 749CX
UT WOS:000289440800043
ER

PT J
AU Wolters, P
   Martin, S
   Walker, K
   Bent, R
   Warren, K
AF Wolters, Pam
   Martin, Staci
   Walker, Katherine
   Bent, Robyn
   Warren, Kathy
TI NEUROPSYCHOLOGICAL FUNCTIONING IN CHILDREN WITH CNS TUMORS: PRELIMINARY
   RESULTS FROM BASELINE TO 6 MONTHS POST-RADIATION
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Wolters, Pam; Martin, Staci; Bent, Robyn; Warren, Kathy] NCI, POB, NIH, Bethesda, MD 20892 USA.
   [Walker, Katherine] NCI, Clin Res Directorate CMRP, SAIC Frederick Inc, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2011
VL 56
IS 7
BP 1157
EP 1157
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 749CX
UT WOS:000289440800044
ER

PT J
AU Grady, C
   Wendler, D
   Wiener, L
AF Grady, Christine
   Wendler, Dave
   Wiener, Lori
TI UNDERSTANDING WHAT ADOLESCENTS THINK ABOUT PARTICIPATING IN CLINICAL
   RESEARCH AND HOW THEIR PERCEPTIONS COMPARE TO THEIR PARENT'S PERCEPTIONS
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Wiener, Lori] Natl Canc Inst, Pediat Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2011
VL 56
IS 7
BP 1161
EP 1161
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 749CX
UT WOS:000289440800060
ER

PT J
AU Wiener, L
   Battles, H
   Zadeh, S
   Pao, M
   Osherow, J
AF Wiener, Lori
   Battles, Haven
   Zadeh, Sima
   Pao, Maryland
   Osherow, Janet
TI DEVELOPMENT AND CLINICAL USE OF AN ADVANCE PLANNING DOCUMENT FOR
   ADOLESCENTS AND YOUNG ADULTS
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Wiener, Lori; Battles, Haven; Zadeh, Sima] Natl Canc Inst, Pediat Oncol Branch, Bethesda, MD 20892 USA.
   [Pao, Maryland] NIMH, Bethesda, MD 20892 USA.
   [Osherow, Janet] Georgetown Univ Hosp, Washington, DC 20057 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2011
VL 56
IS 7
BP 1163
EP 1163
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 749CX
UT WOS:000289440800069
ER

PT J
AU O'Malley, MA
   Koonin, EV
AF O'Malley, Maureen A.
   Koonin, Eugene V.
TI How stands the Tree of Life a century and a half after The Origin?
SO BIOLOGY DIRECT
LA English
DT Review
ID HORIZONTAL GENE-TRANSFER; UNIVERSAL TREE; SPECIES TREES; GENOME TREES;
   PROKARYOTIC EVOLUTION; PHYLOGENOMIC APPROACH; ORGANISMAL PHYLOGENY;
   EUKARYOTIC EVOLUTION; RECONSTRUCTION; SYSTEMATICS
AB We examine the Tree of Life (TOL) as an evolutionary hypothesis and a heuristic. The original TOL hypothesis has failed but a new "statistical TOL hypothesis" is promising. The TOL heuristic usefully organizes data without positing fundamental evolutionary truth.
C1 [Koonin, Eugene V.] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
   [O'Malley, Maureen A.] Univ Sydney, Dept Philosophy, Sydney, NSW 2006, Australia.
RP Koonin, EV (reprint author), Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU Department of Health and Human Services (National Library of Medicine);
   Leverhulme Trust; UK's Economic and Social Research Council; Australian
   Research Council at the University of Sydney, Australia
FX EVK is supported by intramural funds of the Department of Health and
   Human Services (National Library of Medicine).; MAO acknowledges the
   Leverhulme Trust for support of the network, Questioning the Tree of
   Life. Early research for this paper was done with funding from the UK's
   Economic and Social Research Council. The writing was carried out with
   Australian Research Council Future Fellowship funding, at the University
   of Sydney, Australia.
NR 126
TC 24
Z9 24
U1 1
U2 26
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 JUN 30
PY 2011
VL 6
AR 32
DI 10.1186/1745-6150-6-32
PG 21
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 808US
UT WOS:000294006700001
PM 21714936
ER

PT J
AU Wheeler, DC
   De Roos, AJ
   Cerhan, JR
   Morton, LM
   Severson, R
   Cozen, W
   Ward, MH
AF Wheeler, David C.
   De Roos, Anneclaire J.
   Cerhan, James R.
   Morton, Lindsay M.
   Severson, Richard
   Cozen, Wendy
   Ward, Mary H.
TI Spatial-temporal analysis of non-Hodgkin lymphoma in the NCI-SEER NHL
   case-control study
SO ENVIRONMENTAL HEALTH
LA English
DT Article
ID LOCALLY WEIGHTED REGRESSION; RISK; CANCER; WASTE; CLUSTERS; EXPOSURE
AB Background: Exploring spatial-temporal patterns of disease incidence through cluster analysis identifies areas of significantly elevated or decreased risk, providing potential clues about disease risk factors. Little is known about the etiology of non-Hodgkin lymphoma (NHL), or the latency period that might be relevant for environmental exposures, and there are no published spatial-temporal cluster studies of NHL.
   Methods: We conducted a population-based case-control study of NHL in four National Cancer Institute (NCI)-Surveillance, Epidemiology, and End Results (SEER) centers: Detroit, Iowa, Los Angeles, and Seattle during 1998-2000. Using 20-year residential histories, we used generalized additive models adjusted for known risk factors to model spatially the probability that an individual had NHL and to identify clusters of elevated or decreased NHL risk. We evaluated models at five different time periods to explore the presence of clusters in a time frame of etiologic relevance.
   Results: The best model fit was for residential locations 20 years prior to diagnosis in Detroit, Iowa, and Los Angeles. We found statistically significant areas of elevated risk of NHL in three of the four study areas (Detroit, Iowa, and Los Angeles) at a lag time of 20 years. The two areas of significantly elevated risk in the Los Angeles study area were detected only at a time lag of 20 years. Clusters in Detroit and Iowa were detected at several time points.
   Conclusions: We found significant spatial clusters of NHL after allowing for disease latency and residential mobility. Our results show the importance of evaluating residential histories when studying spatial patterns of cancer.
C1 [Wheeler, David C.; Ward, Mary H.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
   [De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   [De Roos, Anneclaire J.] Univ Washington, Seattle, WA 98195 USA.
   [Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN USA.
   [Morton, Lindsay M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
   [Severson, Richard] Wayne State Univ, Dept Family Med, Detroit, MI USA.
   [Severson, Richard] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
   [Cozen, Wendy] Univ So Calif, Dept Prevent Med & Pathol, USC Keck Sch Med, Los Angeles, CA USA.
   [Cozen, Wendy] Univ So Calif, Norris Comprehens Canc Ctr, USC Keck Sch Med, Los Angeles, CA USA.
RP Wheeler, DC (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
EM dcwheels@gmail.com
RI Morton, Lindsay/B-5234-2015; 
OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X
FU National Cancer Institute [N01-PC-35139, N01 PC065064, NO1-PC-67008,
   N01-PC-71105, N01-PC67009, P01 CA17054, P30 ES07048, P30 CA014089];
   Centers for Disease Control and Prevention's National Program of Cancer
   Registries [U55/CCR921930-02]
FX We gratefully acknowledge Lonn Irish (Information Management Services,
   Inc., Silver Spring, MD) for assistance in data processing and
   preparation and Thomas M. Mack, MD, MPH (University of Southern
   California) for comments on a draft of the manuscript. This study was
   supported by the National Cancer Institute's Surveillance, Epidemiology
   and End Results Program under contracts N01-PC-35139, N01 PC065064,
   NO1-PC-67008, N01-PC-71105, N01-PC67009, P01 CA17054, P30 ES07048, P30
   CA014089, and the Centers for Disease Control and Prevention's National
   Program of Cancer Registries, under agreement #U55/CCR921930-02.
NR 47
TC 12
Z9 12
U1 1
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-069X
J9 ENVIRON HEALTH-GLOB
JI Environ. Health
PD JUN 30
PY 2011
VL 10
AR 63
DI 10.1186/1476-069X-10-63
PG 13
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health
GA 802PD
UT WOS:000293522600001
PM 21718483
ER

PT J
AU Son, YJ
   Phue, JN
   Trinh, LB
   Lee, SJ
   Shiloach, J
AF Son, Young-Jin
   Phue, Je-Nie
   Trinh, Loc B.
   Lee, Sang Jun
   Shiloach, Joseph
TI The role of Cra in regulating acetate excretion and osmotic tolerance in
   E. coli K-12 and E. coli B at high density growth
SO MICROBIAL CELL FACTORIES
LA English
DT Article
ID GLYCINE BETAINE PATHWAY; FOREIGN PROTEIN-PRODUCTION; ESCHERICHIA-COLI;
   TRANSCRIPTION LEVELS; GLUCOSE-UTILIZATION; GENES; FRUR; METABOLISM;
   FERMENTATIONS; ACCUMULATION
AB Background: E. coli B (BL21), unlike E. coli K-12 (JM109) is insensitive to glucose concentration and, therefore, grows faster and produces less acetate than E. coli K-12, especially when growing to high cell densities at high glucose concentration. By performing genomic analysis, it was demonstrated that the cause of this difference in sensitivity to the glucose concentration is the result of the differences in the central carbon metabolism activity. We hypothesized that the global transcription regulator Cra (FruR) is constitutively expressed in E. coli B and may be responsible for the different behaviour of the two strains. To investigate this possibility and better understand the function of Cra in the two strains, cra - negative E. coli B (BL21) and E. coli K-12 (JM109) were prepared and their growth behaviour and gene expression at high glucose were evaluated using microarray and real-time PCR.
   Results: The deletion of the cra gene in E. coli B (BL21) minimally affected the growth and maximal acetate accumulation, while the deletion of the same gene in E. coli K-12 (JM109) caused the cells to stop growing as soon as acetate concentration reached 6.6 g/L and the media conductivity reached 21 mS/cm. ppsA (gluconeogenesis gene), aceBA (the glyoxylate shunt genes) and poxB (the acetate producing gene) were down-regulated in both strains, while acs (acetate uptake gene) was down-regulated only in E. coli B (BL21). These transcriptional differences had little effect on acetate and pyruvate production. Additionally, it was found that the lower growth of E. coli K-12 (JM109) strain was the result of transcription inhibition of the osmoprotectant producing bet operon (betABT).
   Conclusions: The transcriptional changes caused by the deletion of cra gene did not affect the activity of the central carbon metabolism, suggesting that Cra does not act alone; rather it interacts with other pleiotropic regulators to create a network of metabolic effects. An unexpected outcome of this work is the finding that cra deletion caused transcription inhibition of the bet operon in E. coli K-12 (JM109) but did not affect this operon transcription in E. coli B (BL21). This property, together with the insensitivity to high glucose concentrations, makes this the E. coli B (BL21) strain more resistant to environmental changes.
C1 [Son, Young-Jin; Phue, Je-Nie; Trinh, Loc B.; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
   [Lee, Sang Jun] KRIBB, Ind Biotechnol & Bioenergy Res Ctr, Taejon 305806, South Korea.
RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, Bldg 14A,Room 173, Bethesda, MD 20892 USA.
EM yossi@nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health
FX Funding was provided by the intramural program of the National Institute
   of Diabetes and Digestive and Kidney Diseases, National Institutes of
   Health. The authors would like to thank Mrs. D. Livnat for critical
   review of the manuscript.
NR 31
TC 10
Z9 10
U1 1
U2 17
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2859
J9 MICROB CELL FACT
JI Microb. Cell. Fact.
PD JUN 30
PY 2011
VL 10
AR 52
DI 10.1186/1475-2859-10-52
PG 9
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 800PJ
UT WOS:000293375100001
PM 21718532
ER

PT J
AU Haney, D
   Quigley, MF
   Asher, TE
   Ambrozak, DR
   Gostick, E
   Price, DA
   Douek, DC
   Betts, MR
AF Haney, Danielle
   Quigley, Maire F.
   Asher, Tedi E.
   Ambrozak, David R.
   Gostick, Emma
   Price, David A.
   Douek, Daniel C.
   Betts, Michael R.
TI Isolation of viable antigen-specific CD8(+) T cells based on
   membrane-bound tumor necrosis factor (TNF)-alpha expression
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Cell Sorting; T cells; TNF-alpha; Viable; Functional
ID HIV-SPECIFIC CD4(+); CYTOKINE SECRETION; TNF RECEPTOR; FACTOR-ALPHA;
   LYMPHOCYTES; ASSAY; GAMMA; IDENTIFICATION; POPULATIONS; ACTIVATION
AB Current technology to isolate viable cytokine-producing antigen-specific primary human T cells is limited to bi-specific antibody capture systems, which suffer from limited sensitivity and high background. Here, we describe a novel procedure for isolating antigen-specific human T cells based on their ability to produce tumor necrosis factor (TNF)-alpha. Unlike many cytokines, TNF-alpha is initially produced in a biologically active membrane-bound form that is subsequently cleaved by TNF-alpha converting enzyme (TACE) to release the soluble form of TNF-alpha. By preventing this cleavage event, we show that TNF-alpha can be 'trapped' on the surface of the T cells from which it originates and directly labeled for viable isolation of these antigen-specific T cells. Together with other existing sorting procedures to isolate activated T cells, this new technique should permit the direct isolation of multi-functional T lymphocytes for further protein and gene expression analyses, as well as a detailed functional assessment of the potential role that TNF-alpha producing T cells play in the adaptive immune system. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Haney, Danielle; Betts, Michael R.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
   [Quigley, Maire F.; Asher, Tedi E.; Price, David A.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Ambrozak, David R.] NIAID, Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Gostick, Emma; Price, David A.] Cardiff Univ, Dept Infect Immun & Biochem, Sch Med, Cardiff CF14 4XN, S Glam, Wales.
RP Betts, MR (reprint author), Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
EM betts@mail.med.upenn.edu
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
FU Medical Research Council [G0501963]; NIAID NIH HHS [R01 AI076066-05, R01
   AI076066, R01 AI076066-02S1]
NR 38
TC 10
Z9 10
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD JUN 30
PY 2011
VL 369
IS 1-2
BP 33
EP 41
DI 10.1016/j.jim.2011.04.003
PG 9
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 793CW
UT WOS:000292799000003
PM 21501617
ER

PT J
AU Dyer, KD
   Garcia-Crespo, KE
   Killoran, KE
   Rosenberg, HF
AF Dyer, Kimberly D.
   Garcia-Crespo, Katia E.
   Killoran, Kristin E.
   Rosenberg, Helene F.
TI Antigen profiles for the quantitative assessment of eosinophils in mouse
   tissues by flow cytometry
SO JOURNAL OF IMMUNOLOGICAL METHODS
LA English
DT Article
DE Siglec F; CD11c; CD125; CD193; Eosinophil; Alveolar macrophage
ID HUMAN SIGLEC-8; MSIGLEC-F; IL-5; MICE; INFLAMMATION; ASTHMA; CELLS;
   MODEL; LUNG; DEGRANULATION
AB Much of our current understanding of eosinophil-associated pathologies has developed from the use of mouse models. While mouse eosinophils can be readily detected by flow cytometric methods, most studies do not document the efficiency of this process compared to direct counting of stained cells. Our intent was to address this knowledge gap by identifying one or more eosinophil-specific antigen profiles that yielded flow cytometric data that was statistically consistent with direct counts. We found that anti-CD193 (CCR3) and anti-CD125 (IL-5R alpha) antibodies were effective at detecting eosinophils in bone marrow of interleukin-5 transgenic mice, but these antibodies under-reported the percent positive cells. In contrast, anti-Siglec F alone or in combination with anti-CD45 can be used for the quantitative detection of eosinophils in mouse bone marrow and spleen. The antigen profile CD45(+)SiglecF(-)CD11c(-) was effective at detecting eosinophils in the lung as well as bone marrow and spleen, and the results obtained correlated with direct morphometric counts under all conditions evaluated (r(2) = 0.98-0.99). To the best of our knowledge, this is the first systematic analysis presenting definitive correlations between percent eosinophils detected by cell surface markers and direct counting of stained cells in multiple tissues and at varying degrees of eosinophilia. Published by Elsevier B.V.
C1 [Dyer, Kimberly D.; Garcia-Crespo, Katia E.; Rosenberg, Helene F.] NIAID, Eosinophil Biol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
   [Killoran, Kristin E.] NIAID, Lymphocyte Biol Unit, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Dyer, KD (reprint author), 10 Ctr Dr MSC 1883,Bldg 10 Room 11C216, Bethesda, MD 20892 USA.
EM kdyer@niaid.nih.gov
FU NIAID Division of Intramural Research [AI000941]
FX The authors thank Mr. Ricardo Dreyfuss (Medical Arts and Photography)
   for his assistance with photographing slides. This work was supported by
   NIAID Division of Intramural Research funding, project number AI000941.
NR 24
TC 23
Z9 23
U1 0
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-1759
J9 J IMMUNOL METHODS
JI J. Immunol. Methods
PD JUN 30
PY 2011
VL 369
IS 1-2
BP 91
EP 97
DI 10.1016/j.jim.2011.04.009
PG 7
WC Biochemical Research Methods; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 793CW
UT WOS:000292799000010
PM 21565196
ER

PT J
AU Bell, D
   Berchuck, A
   Birrer, M
   Chien, J
   Cramer, DW
   Dao, F
   Dhir, R
   DiSaia, P
   Gabra, H
   Glenn, P
   Godwin, AK
   Gross, J
   Hartmann, L
   Huang, M
   Huntsman, DG
   Iacocca, M
   Imielinski, M
   Kalloger, S
   Karlan, BY
   Levine, DA
   Mills, GB
   Morrison, C
   Mutch, D
   Olvera, N
   Orsulic, S
   Park, K
   Petrelli, N
   Rabeno, B
   Rader, JS
   Sikic, BI
   Smith-McCune, K
   Sood, AK
   Bowtell, D
   Penny, R
   Testa, JR
   Chang, K
   Dinh, HH
   Drummond, JA
   Fowler, G
   Gunaratne, P
   Hawes, AC
   Kovar, CL
   Lewis, LR
   Morgan, MB
   Newsham, IF
   Santibanez, J
   Reid, JG
   Trevino, LR
   Wu, YQ
   Wang, M
   Muzny, DM
   Wheeler, DA
   Gibbs, RA
   Getz, G
   Lawrence, MS
   Cibulskis, K
   Sivachenko, AY
   Sougnez, C
   Voet, D
   Wilkinson, J
   Bloom, T
   Ardlie, K
   Fennell, T
   Baldwin, J
   Gabriel, S
   Lander, ES
   Ding, L
   Fulton, RS
   Koboldt, DC
   McLellan, MD
   Wylie, T
   Walker, J
   O'Laughlin, M
   Dooling, DJ
   Fulton, L
   Abbott, R
   Dees, ND
   Zhang, Q
   Kandoth, C
   Wendl, M
   Schierding, W
   Shen, D
   Harris, CC
   Schmidt, H
   Kalicki, J
   Delehaunty, KD
   Fronick, CC
   Demeter, R
   Cook, L
   Wallis, JW
   Lin, L
   Magrini, VJ
   Hodges, JS
   Eldred, JM
   Smith, SM
   Pohl, CS
   Vandin, F
   Raphael, BJ
   Weinstock, GM
   Mardis, R
   Wilson, RK
   Meyerson, M
   Winckler, W
   Getz, G
   Verhaak, RGW
   Carter, SL
   Mermel, CH
   Saksena, G
   Nguyen, H
   Onofrio, RC
   Lawrence, MS
   Hubbard, D
   Gupta, S
   Crenshaw, A
   Ramos, AH
   Ardlie, K
   Chin, L
   Protopopov, A
   Zhang, JH
   Kim, TM
   Perna, I
   Xiao, Y
   Zhang, H
   Ren, G
   Sathiamoorthy, N
   Park, RW
   Lee, E
   Park, PJ
   Kucherlapati, R
   Absher, DM
   Waite, L
   Sherlock, G
   Brooks, JD
   Li, JZ
   Xu, J
   Myers, RM
   Laird, PW
   Cope, L
   Herman, JG
   Shen, H
   Weisenberger, DJ
   Noushmehr, H
   Pan, F
   Triche, T
   Berman, BP
   Van den Berg, DJ
   Buckley, J
   Baylin, SB
   Spellman, PT
   Purdom, E
   Neuvial, P
   Bengtsson, H
   Jakkula, LR
   Durinck, S
   Han, J
   Dorton, S
   Marr, H
   Choi, YG
   Wang, V
   Wang, NJ
   Ngai, J
   Conboy, JG
   Parvin, B
   Feiler, HS
   Speed, TP
   Gray, JW
   Levine, DA
   Socci, ND
   Liang, Y
   Taylor, BS
   Schultz, N
   Borsu, L
   Lash, AE
   Brennan, C
   Viale, A
   Sander, C
   Ladanyi, M
   Hoadley, KA
   Meng, S
   Du, Y
   Shi, Y
   Li, L
   Turman, YJ
   Zang, D
   Helms, EB
   Balu, S
   Zhou, X
   Wu, J
   Topal, MD
   Hayes, DN
   Perou, CM
   Getz, G
   Voet, D
   Saksena, G
   Zhang, JNH
   Zhang, H
   Wu, CJ
   Shukla, S
   Cibulskis, K
   Lawrence, MS
   Sivachenko, A
   Jing, R
   Park, RW
   Liu, Y
   Park, PJ
   Noble, M
   Chin, L
   Carter, H
   Kim, D
   Karchin, R
   Spellman, PT
   Purdom, E
   Neuvial, P
   Bengtsson, H
   Durinck, S
   Han, J
   Korkola, JE
   Heiser, LM
   Cho, RJ
   Hu, Z
   Parvin, B
   Speed, TP
   Gray, JW
   Schultz, N
   Cerami, E
   Taylor, BS
   Olshen, A
   Reva, B
   Antipin, Y
   Shen, R
   Mankoo, P
   Sheridan, R
   Ciriello, G
   Chang, WK
   Bernanke, JA
   Borsu, L
   Levine, DA
   Ladanyi, M
   Sander, C
   Haussler, D
   Benz, CC
   Stuart, JM
   Benz, SC
   Sanborn, JZ
   Vaske, CJ
   Zhu, J
   Szeto, C
   Scott, GK
   Yau, C
   Hoadley, KA
   Du, Y
   Balu, S
   Hayes, DN
   Perou, CM
   Wilkerson, MD
   Zhang, N
   Akbani, R
   Baggerly, KA
   Yung, WK
   Mills, GB
   Weinstein, JN
   Penny, R
   Shelton, T
   Grimm, D
   Hatfield, M
   Morris, S
   Yena, P
   Rhodes, P
   Sherman, M
   Paulauskis, J
   Millis, S
   Kahn, A
   Greene, JM
   Sfeir, R
   Jensen, MA
   Chen, J
   Whitmore, J
   Alonso, S
   Jordan, J
   Chu, A
   Zhang, JH
   Barker, A
   Compton, C
   Eley, G
   Ferguson, M
   Fielding, P
   Gerhard, DS
   Myles, R
   Schaefer, C
   Shaw, KRM
   Vaught, J
   Vockley, JB
   Good, PJ
   Guyer, MS
   Ozenberger, B
   Peterson, J
   Thomson, E
AF Bell, D.
   Berchuck, A.
   Birrer, M.
   Chien, J.
   Cramer, D. W.
   Dao, F.
   Dhir, R.
   DiSaia, P.
   Gabra, H.
   Glenn, P.
   Godwin, A. K.
   Gross, J.
   Hartmann, L.
   Huang, M.
   Huntsman, D. G.
   Iacocca, M.
   Imielinski, M.
   Kalloger, S.
   Karlan, B. Y.
   Levine, D. A.
   Mills, G. B.
   Morrison, C.
   Mutch, D.
   Olvera, N.
   Orsulic, S.
   Park, K.
   Petrelli, N.
   Rabeno, B.
   Rader, J. S.
   Sikic, B. I.
   Smith-McCune, K.
   Sood, A. K.
   Bowtell, D.
   Penny, R.
   Testa, J. R.
   Chang, K.
   Dinh, H. H.
   Drummond, J. A.
   Fowler, G.
   Gunaratne, P.
   Hawes, A. C.
   Kovar, C. L.
   Lewis, L. R.
   Morgan, M. B.
   Newsham, I. F.
   Santibanez, J.
   Reid, J. G.
   Trevino, L. R.
   Wu, Y. -Q.
   Wang, M.
   Muzny, D. M.
   Wheeler, D. A.
   Gibbs, R. A.
   Getz, G.
   Lawrence, M. S.
   Cibulskis, K.
   Sivachenko, A. Y.
   Sougnez, C.
   Voet, D.
   Wilkinson, J.
   Bloom, T.
   Ardlie, K.
   Fennell, T.
   Baldwin, J.
   Gabriel, S.
   Lander, E. S.
   Ding, L.
   Fulton, R. S.
   Koboldt, D. C.
   McLellan, M. D.
   Wylie, T.
   Walker, J.
   O'Laughlin, M.
   Dooling, D. J.
   Fulton, L.
   Abbott, R.
   Dees, N. D.
   Zhang, Q.
   Kandoth, C.
   Wendl, M.
   Schierding, W.
   Shen, D.
   Harris, C. C.
   Schmidt, H.
   Kalicki, J.
   Delehaunty, K. D.
   Fronick, C. C.
   Demeter, R.
   Cook, L.
   Wallis, J. W.
   Lin, L.
   Magrini, V. J.
   Hodges, J. S.
   Eldred, J. M.
   Smith, S. M.
   Pohl, C. S.
   Vandin, F.
   Raphael, B. J.
   Weinstock, G. M.
   Mardis, R.
   Wilson, R. K.
   Meyerson, M.
   Winckler, W.
   Getz, G.
   Verhaak, R. G. W.
   Carter, S. L.
   Mermel, C. H.
   Saksena, G.
   Nguyen, H.
   Onofrio, R. C.
   Lawrence, M. S.
   Hubbard, D.
   Gupta, S.
   Crenshaw, A.
   Ramos, A. H.
   Ardlie, K.
   Chin, L.
   Protopopov, A.
   Zhang, Juinhua
   Kim, T. M.
   Perna, I.
   Xiao, Y.
   Zhang, H.
   Ren, G.
   Sathiamoorthy, N.
   Park, R. W.
   Lee, E.
   Park, P. J.
   Kucherlapati, R.
   Absher, D. M.
   Waite, L.
   Sherlock, G.
   Brooks, J. D.
   Li, J. Z.
   Xu, J.
   Myers, R. M.
   Laird, P. W.
   Cope, L.
   Herman, J. G.
   Shen, H.
   Weisenberger, D. J.
   Noushmehr, H.
   Pan, F.
   Triche, T., Jr.
   Berman, B. P.
   Van den Berg, D. J.
   Buckley, J.
   Baylin, S. B.
   Spellman, P. T.
   Purdom, E.
   Neuvial, P.
   Bengtsson, H.
   Jakkula, L. R.
   Durinck, S.
   Han, J.
   Dorton, S.
   Marr, H.
   Choi, Y. G.
   Wang, V.
   Wang, N. J.
   Ngai, J.
   Conboy, J. G.
   Parvin, B.
   Feiler, H. S.
   Speed, T. P.
   Gray, J. W.
   Levine, D. A.
   Socci, N. D.
   Liang, Y.
   Taylor, B. S.
   Schultz, N.
   Borsu, L.
   Lash, A. E.
   Brennan, C.
   Viale, A.
   Sander, C.
   Ladanyi, M.
   Hoadley, K. A.
   Meng, S.
   Du, Y.
   Shi, Y.
   Li, L.
   Turman, Y. J.
   Zang, D.
   Helms, E. B.
   Balu, S.
   Zhou, X.
   Wu, J.
   Topal, M. D.
   Hayes, D. N.
   Perou, C. M.
   Getz, G.
   Voet, D.
   Saksena, G.
   Zhang, Junihua
   Zhang, H.
   Wu, C. J.
   Shukla, S.
   Cibulskis, K.
   Lawrence, M. S.
   Sivachenko, A.
   Jing, R.
   Park, R. W.
   Liu, Y.
   Park, P. J.
   Noble, M.
   Chin, L.
   Carter, H.
   Kim, D.
   Karchin, R.
   Spellman, P. T.
   Purdom, E.
   Neuvial, P.
   Bengtsson, H.
   Durinck, S.
   Han, J.
   Korkola, J. E.
   Heiser, L. M.
   Cho, R. J.
   Hu, Z.
   Parvin, B.
   Speed, T. P.
   Gray, J. W.
   Schultz, N.
   Cerami, E.
   Taylor, B. S.
   Olshen, A.
   Reva, B.
   Antipin, Y.
   Shen, R.
   Mankoo, P.
   Sheridan, R.
   Ciriello, G.
   Chang, W. K.
   Bernanke, J. A.
   Borsu, L.
   Levine, D. A.
   Ladanyi, M.
   Sander, C.
   Haussler, D.
   Benz, C. C.
   Stuart, J. M.
   Benz, S. C.
   Sanborn, J. Z.
   Vaske, C. J.
   Zhu, J.
   Szeto, C.
   Scott, G. K.
   Yau, C.
   Hoadley, K. A.
   Du, Y.
   Balu, S.
   Hayes, D. N.
   Perou, C. M.
   Wilkerson, M. D.
   Zhang, N.
   Akbani, R.
   Baggerly, K. A.
   Yung, W. K.
   Mills, G. B.
   Weinstein, J. N.
   Penny, R.
   Shelton, T.
   Grimm, D.
   Hatfield, M.
   Morris, S.
   Yena, P.
   Rhodes, P.
   Sherman, M.
   Paulauskis, J.
   Millis, S.
   Kahn, A.
   Greene, J. M.
   Sfeir, R.
   Jensen, M. A.
   Chen, J.
   Whitmore, J.
   Alonso, S.
   Jordan, J.
   Chu, A.
   Zhang, Jinghui
   Barker, A.
   Compton, C.
   Eley, G.
   Ferguson, M.
   Fielding, P.
   Gerhard, D. S.
   Myles, R.
   Schaefer, C.
   Shaw, K. R. Mills
   Vaught, J.
   Vockley, J. B.
   Good, P. J.
   Guyer, M. S.
   Ozenberger, B.
   Peterson, J.
   Thomson, E.
CA Canc Genome Atlas Res Network
TI Integrated genomic analyses of ovarian carcinoma
SO NATURE
LA English
DT Article
ID HIGH-THROUGHPUT ANNOTATION; GYNECOLOGIC-ONCOLOGY-GROUP; GRADE SEROUS
   CARCINOMA; BRCA MUTATION CARRIERS; CLEAR-CELL CARCINOMA; SOMATIC
   MUTATIONS; CANCER STATISTICS; DRIVER MUTATIONS; HYBRID SELECTION;
   MUTANT-CELLS
AB A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients' lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.
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   [Berchuck, A.] Duke Univ, Duke Inst Genome Sci & Policy, Med Ctr, Durham, NC 27708 USA.
   [Birrer, M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
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   [Chien, J.] Mayo Clin, Div Expt Pathol, Rochester, MN 55905 USA.
   [Cramer, D. W.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Epidemiol Ctr, Boston, MA 02115 USA.
   [Levine, D. A.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10065 USA.
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   [Gabra, H.] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Ovarian Canc Act Res Ctr, London W12 0NN, England.
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   [Hartmann, L.] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA.
   [Huang, M.] Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA.
   [Huntsman, D. G.; Kalloger, S.] British Columbia Canc Agcy, Ctr Translat & Appl Genom, Vancouver, BC V5Z 1G1, Canada.
   [Iacocca, M.; Rabeno, B.] Christiana Care Hlth Syst, Dept Pathol, Newark, DE 19718 USA.
   [Karlan, B. Y.] Univ Calif Los Angeles, Dept Obstet & Gynecol, Cedars Sinai Med Ctr, Geffen Sch Med, Los Angeles, CA 90048 USA.
   [Mills, G. B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
   Univ Texas MD Anderson Canc Ctr, Kleberg Ctr Mol Markers, Houston, TX 77030 USA.
   [Morrison, C.] Roswell Pk Canc Inst, Dept Pathol & Lab Med, Buffalo, NY 14263 USA.
   [Morrison, C.] Roswell Pk Canc Inst, Div Mol Pathol, Buffalo, NY 14263 USA.
   [Mutch, D.] Washington Univ, Div Gynecol Oncol, Dept Obstet & Gynecol, Sch Med St Louis, St Louis, MO 63110 USA.
   [Park, K.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA.
   [Petrelli, N.] Helen F Graham Canc Ctr Christina Care, Dept Surg, Newark, DE 19713 USA.
   [Rader, J. S.] Med Coll Wisconsin, Human & Mol Genet Ctr, Dept Obstet & Gynecol, Milwaukee, WI 53226 USA.
   [Sikic, B. I.] Stanford Univ, Dept Med, Div Oncol, Sch Med, Palo Alto, CA 94304 USA.
   [Sood, A. K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77230 USA.
   [Sood, A. K.] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNA, Houston, TX 77230 USA.
   [Bowtell, D.] Peter MacCallum Canc Ctr, Div Res, Melbourne, Vic 8006, Australia.
   [Penny, R.; Shelton, T.; Grimm, D.; Hatfield, M.; Morris, S.; Yena, P.; Rhodes, P.; Sherman, M.; Paulauskis, J.; Millis, S.] Internat Genom Consortium, Phoenix, AZ 85004 USA.
   [Testa, J. R.] Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19111 USA.
   [Chang, K.; Dinh, H. H.; Drummond, J. A.; Fowler, G.; Gunaratne, P.; Hawes, A. C.; Kovar, C. L.; Lewis, L. R.; Morgan, M. B.; Newsham, I. F.; Santibanez, J.; Reid, J. G.; Trevino, L. R.; Wu, Y. -Q.; Wang, M.; Muzny, D. M.; Wheeler, D. A.; Gibbs, R. A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
   [Sougnez, C.; Winckler, W.; Getz, G.] MIT, Eli & Edythe L Broad Inst, Canc Genome Project, Cambridge, MA 02142 USA.
   [Sougnez, C.; Winckler, W.; Getz, G.] MIT, Eli & Edythe L Broad Inst, Med Resequencing Project, Cambridge, MA 02142 USA.
   [Cibulskis, K.; Sougnez, C.; Wilkinson, J.; Bloom, T.; Fennell, T.; Baldwin, J.; Gabriel, S.; Winckler, W.; Getz, G.; Crenshaw, A.] Harvard Univ, Cambridge, MA 02142 USA.
   [Lander, E. S.] MIT, Dept Biol, Cambridge, MA 02142 USA.
   [Lander, E. S.] Harvard Univ, Dept Syst Biol, Boston, MA 02115 USA.
   [Ding, L.; Fulton, R. S.; Koboldt, D. C.; McLellan, M. D.; Wylie, T.; Walker, J.; O'Laughlin, M.; Dooling, D. J.; Fulton, L.; Abbott, R.; Dees, N. D.; Zhang, Q.; Kandoth, C.; Wendl, M.; Schierding, W.; Shen, D.; Harris, C. C.; Schmidt, H.; Kalicki, J.; Delehaunty, K. D.; Fronick, C. C.; Demeter, R.; Cook, L.; Wallis, J. W.; Lin, L.; Magrini, V. J.; Hodges, J. S.; Eldred, J. M.; Smith, S. M.; Pohl, C. S.; Weinstock, G. M.; Mardis, R.; Wilson, R. K.] Washington Univ, Sch Med St Louis, Genome Ctr, Dept Genet, St Louis, MO 63108 USA.
   [Vandin, F.; Raphael, B. J.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA.
   [Vandin, F.; Raphael, B. J.] Brown Univ, Ctr Computat Mol Biol, Providence, RI 02912 USA.
   [Mardis, R.; Wilson, R. K.] Washington Univ, Siteman Canc Ctr, Sch Med St Louis, St Louis, MO 63108 USA.
   [Meyerson, M.; Verhaak, R. G. W.; Carter, S. L.; Mermel, C. H.; Hubbard, D.; Ramos, A. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
   [Meyerson, M.; Hubbard, D.; Ramos, A. H.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
   [Chin, L.; Protopopov, A.; Zhang, Juinhua; Perna, I.; Xiao, Y.; Zhang, H.; Ren, G.; Zhang, Junihua; Wu, C. J.; Shukla, S.; Liu, Y.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA.
   [Chin, L.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
   [Kim, T. M.; Park, R. W.; Lee, E.; Park, P. J.; Park, R. W.] Harvard Univ, Ctr Biomed Informat, Sch Med, Boston, MA 02115 USA.
   [Sathiamoorthy, N.] Partners Ctr Personalized Genet Med, Cambridge, MA 02139 USA.
   Childrens Hosp, Informat Program, Boston, MA 02115 USA.
   [Kucherlapati, R.] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02115 USA.
   [Absher, D. M.; Waite, L.; Myers, R. M.; Speed, T. P.] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
   [Brooks, J. D.; Sander, C.] Stanford Univ, Dept Urol, Sch Med, Stanford, CA 94305 USA.
   [Li, J. Z.; Xu, J.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
   [Laird, P. W.; Shen, H.; Weisenberger, D. J.; Noushmehr, H.; Pan, F.; Triche, T., Jr.; Berman, B. P.; Van den Berg, D. J.; Buckley, J.] Univ So Calif, Epigenome Ctr, Los Angeles, CA 90089 USA.
   [Cope, L.] Johns Hopkins Univ, Biometry & Clin Trials Div, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Herman, J. G.; Baylin, S. B.] Johns Hopkins Univ, Div Canc Biol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.
   [Purdom, E.; Neuvial, P.; Bengtsson, H.] Univ Calif Berkeley, Dept Stat, Berkeley, CA 95720 USA.
   [Choi, Y. G.; Ngai, J.] Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 95720 USA.
   [Wang, V.] Univ Houston, Dept Biol & Biochem, Houston, TX 77004 USA.
   [Speed, T. P.] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia.
   [Socci, N. D.; Liang, Y.; Taylor, B. S.; Schultz, N.; Lash, A. E.; Sander, C.; Cerami, E.; Reva, B.; Antipin, Y.; Mankoo, P.; Sheridan, R.; Ciriello, G.] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.
   [Borsu, L.; Ladanyi, M.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, Dept Pathol, New York, NY 10065 USA.
   [Brennan, C.] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA.
   [Viale, A.] Mem Sloan Kettering Canc Ctr, Genom Core Lab, New York, NY 10065 USA.
   Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
   [Topal, M. D.] Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
   [Meng, S.; Du, Y.; Shi, Y.; Li, L.; Turman, Y. J.; Zang, D.; Helms, E. B.; Balu, S.; Zhou, X.; Wu, J.; Topal, M. D.; Hayes, D. N.; Wilkerson, M. D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   [Hayes, D. N.] Univ N Carolina, Dept Internal Med, Div Med Oncol, Chapel Hill, NC 27599 USA.
   [Carter, H.; Kim, D.; Karchin, R.] Johns Hopkins Univ, Dept Biomed Engn, Inst Computat Med, Baltimore, MD 21231 USA.
   [Olshen, A.; Shen, R.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA.
   Weill Cornell Grad Sch Med Sci, Dept Physiol & Biophys, New York, NY 10065 USA.
   [Bernanke, J. A.] Cornell Univ, Weill Med Coll, New York, NY 10065 USA.
   [Benz, S. C.; Sanborn, J. Z.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA.
   [Benz, S. C.; Sanborn, J. Z.] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
   Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA.
   [Benz, C. C.; Yau, C.] Buck Inst Age Res, Novato, CA 94945 USA.
   Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
   [Zhang, N.; Akbani, R.; Baggerly, K. A.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
   [Yung, W. K.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
   [Kahn, A.; Greene, J. M.; Sfeir, R.; Jensen, M. A.; Chen, J.; Whitmore, J.; Alonso, S.; Jordan, J.; Chu, A.] SRAInternational, Fairfax, VA 22033 USA.
   St Jude Childrens Res Hosp, Dept Biotechnol, Memphis, TN 38105 USA.
   [Compton, C.; Eley, G.; Fielding, P.; Gerhard, D. S.; Myles, R.; Schaefer, C.; Shaw, K. R. Mills; Vaught, J.; Vockley, J. B.] NCI, NIH, Bethesda, MD 20892 USA.
   [Ferguson, M.] MLF Consulting, Arlington, MA 02474 USA.
   [Good, P. J.; Guyer, M. S.; Ozenberger, B.; Peterson, J.; Thomson, E.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Spellman, PT (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
EM spellmap@ohsu.edu
RI sander, chris/H-1452-2011; Karchin, Rachel/A-3385-2010; Lester,
   Jenny/B-5933-2012; Meyerson, Matthew/E-7123-2012; Sherlock,
   Gavin/E-9110-2012; Laird, Peter/G-8683-2012; Weinstock,
   George/C-6314-2013; Noushmehr, Houtan/C-9692-2013; Vaske,
   Charles/D-6018-2013; Reva, Boris/B-6436-2014; Berman,
   Benjamin/D-5942-2014; Bowtell, David/H-1007-2016
OI Benz, Stephen/0000-0002-4067-0602; Triche, Tim/0000-0001-5665-946X;
   Park, Kay/0000-0001-8989-2938; Brennan, Cameron/0000-0003-4064-8891;
   Hayes, D. Neil/0000-0001-6203-7771; Kandoth, Cyriac/0000-0002-1345-3573;
   Lash, Alex/0000-0003-3787-1590; Sherlock, Gavin/0000-0002-1692-4983;
   Perou, Charles/0000-0001-9827-2247; Chien, Jeremy/0000-0003-4744-8374;
   Schultz, Nikolaus/0000-0002-0131-4904; Weinstock,
   George/0000-0002-2997-4592; Noushmehr, Houtan/0000-0003-4051-8114;
   Vaske, Charles/0000-0001-8151-6612; Reva, Boris/0000-0002-8805-389X;
   Bowtell, David/0000-0001-9089-7525
FU USA National Institutes of Health [U24CA143840, U24CA143882,
   U24CA143731, U24CA143835, U24CA143845, U24CA143858, U24CA144025,
   U24CA143866, U24CA143867, U24CA143848, U24CA143843, R21CA135877]
FX We thank J. Palchik, A. Mirick and Julia Zhang for administrative
   coordination of TCGA activities. This work was supported by the
   following grants from the USA National Institutes of Health:
   U54HG003067, U54HG003079, U54HG003273, U24CA126543, U24CA126544,
   U24CA126546, U24CA126551, U24CA126554, U24CA126561, U24CA126563,
   U24CA143840, U24CA143882, U24CA143731, U24CA143835, U24CA143845,
   U24CA143858, U24CA144025, U24CA143882, U24CA143866, U24CA143867,
   U24CA143848, U24CA143843 and R21CA135877.
NR 51
TC 1448
Z9 1467
U1 30
U2 298
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUN 30
PY 2011
VL 474
IS 7353
BP 609
EP 615
DI 10.1038/nature10166
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785CF
UT WOS:000292204300032
ER

PT J
AU Vavra, AK
   Havelka, GE
   Martinez, J
   Lee, VR
   Fu, B
   Jiang, Q
   Keefer, LK
   Kibbe, MR
AF Vavra, Ashley K.
   Havelka, George E.
   Martinez, Janet
   Lee, Vanessa R.
   Fu, Bo
   Jiang, Qun
   Keefer, Larry K.
   Kibbe, Melina R.
TI Insights into the effect of nitric oxide and its metabolites nitrite and
   nitrate at inhibiting neointimal hyperplasia
SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY
LA English
DT Article
DE Peripheral vascular disease; Neointimal hyperplasia; Nitric oxide;
   Nitrite/nitrate
ID INTIMAL HYPERPLASIA; VEIN GRAFTS; PERIVASCULAR DELIVERY;
   ENDOTHELIAL-CELLS; DIETARY NITRATE; REDUCTION; CIRCULATION; EXPRESSION;
   SYNTHASE; TISSUES
AB Objective: Periadventitial delivery of the nitric oxide (NO) donor PROLI/NO following arterial injury effectively inhibits neointimal hyperplasia. Given the short half-life of NO release from PROLI/NO, our goal was to determine if inhibition of neointimal hyperplasia by PROLI/NO was due to NO, or its metabolites nitrite and nitrate.
   Methods and results: In vitro, the NO donor DETA/NO inhibited proliferation of rat aortic vascular smooth muscle cells (RASMC), but neither nitrite nor nitrate did. In vivo, following rat carotid artery balloon injury or injury plus the molar equivalents of PROLI/NO, nitrite, or nitrate (n = 8-11/group), PROLI/NO was found to provide superior inhibition of neointimal hyperplasia (82% inhibition of intimal area, and 44% inhibition of medial area, p < 0.001). Only modest inhibition was noted with nitrite or nitrate (45% and 41% inhibition of intimal area, and 31% and 29% inhibition of medial area, respectively, p < 0.001). No effects on blood pressure were noted with any treatment groups. In vivo, only PROLI/NO inhibited cellular proliferation and increased arterial lumen area compared to injury alone (p < 0.001). However, all three treatments inhibited inflammation (p < 0.001).
   Conclusions: PROLI/NO was more effective at inhibiting neointimal hyperplasia following arterial injury than nitrite or nitrate. However, modest inhibition of neointimal hyperplasia was observed with nitrite and nitrate, likely secondary to anti-inflammatory actions. In conclusion, we have demonstrated that the efficacy of NO donors is primarily due to NO production and not its metabolites, nitrite and nitrate. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Vavra, Ashley K.; Havelka, George E.; Martinez, Janet; Lee, Vanessa R.; Fu, Bo; Jiang, Qun; Kibbe, Melina R.] Northwestern Univ, Feinberg Sch Med, Div Vasc Surg, Chicago, IL 60611 USA.
   [Vavra, Ashley K.; Havelka, George E.; Martinez, Janet; Lee, Vanessa R.; Fu, Bo; Jiang, Qun; Kibbe, Melina R.] Northwestern Univ, Feinberg Sch Med, Inst BioNanotechnol Med, Chicago, IL 60611 USA.
   [Keefer, Larry K.] NCI, Ctr Canc Res, Frederick, MD 21702 USA.
RP Kibbe, MR (reprint author), Northwestern Univ, Feinberg Sch Med, Div Vasc Surg, 676 N St Clair St,650, Chicago, IL 60611 USA.
EM mkibbe@nmh.org
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU National Institutes of Health [K08HL084203, T32 HL094293-01]; American
   Vascular Association; NIH, National Cancer Institute, Center for Cancer
   Research
FX This work was supported in part by funding from the National Institutes
   of Health (K08HL084203; M.R.K.), (T32 HL094293-01, G.E.H.), and the
   American Vascular Association (M.R.K.). It was also supported in part by
   the generosity of Mrs. Hilda Rosenbloom and Ms. Eleanor Baldwin. Lastly,
   this work was supported in part by the Intramural Research Program of
   the NIH, National Cancer Institute, Center for Cancer Research.
NR 39
TC 15
Z9 15
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1089-8603
J9 NITRIC OXIDE-BIOL CH
JI Nitric Oxide-Biol. Chem.
PD JUN 30
PY 2011
VL 25
IS 1
BP 22
EP 30
DI 10.1016/j.niox.2011.04.013
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 787YF
UT WOS:000292411900003
PM 21554972
ER

PT J
AU Lundqvist, A
   Childs, R
AF Lundqvist, Andreas
   Childs, Richard
TI Unlicensed natural born killers
SO BLOOD
LA English
DT Editorial Material
ID CELLS; ACQUISITION; EXPRESSION
C1 [Lundqvist, Andreas] NIH, Bethesda, MD 20892 USA.
   Karolinska Inst, S-10401 Stockholm, Sweden.
RP Lundqvist, A (reprint author), NIH, Bethesda, MD 20892 USA.
OI Lundqvist, Andreas/0000-0002-9709-2970
NR 7
TC 0
Z9 0
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 JUN 30
PY 2011
VL 117
IS 26
BP 6974
EP +
PG 2
WC Hematology
SC Hematology
GA 785QO
UT WOS:000292244000002
PM 21719605
ER

PT J
AU Uldrick, TS
   Polizzotto, MN
   Aleman, K
   O'Mahony, D
   Wyvill, KM
   Wang, V
   Marshall, V
   Pittaluga, S
   Steinberg, SM
   Tosato, G
   Whitby, D
   Little, RF
   Yarchoan, R
AF Uldrick, Thomas S.
   Polizzotto, Mark N.
   Aleman, Karen
   O'Mahony, Deirdre
   Wyvill, Kathleen M.
   Wang, Victoria
   Marshall, Vickie
   Pittaluga, Stefania
   Steinberg, Seth M.
   Tosato, Giovanna
   Whitby, Denise
   Little, Richard F.
   Yarchoan, Robert
TI High-dose zidovudine plus valganciclovir for Kaposi sarcoma
   herpesvirus-associated multicentric Castleman disease: a pilot study of
   virus-activated cytotoxic therapy
SO BLOOD
LA English
DT Article
ID PRIMARY EFFUSION LYMPHOMA; ANTIRETROVIRAL THERAPY; VIRAL INTERLEUKIN-6;
   GENE-EXPRESSION; CELLULAR CYTOKINES; DNA-SEQUENCES; HIV-INFECTION;
   B-CELLS; HUMAN-HERPESVIRUS-8; AIDS
AB Kaposi sarcoma herpesvirus (KSHV)associated multicentric Castleman disease (MCD) is a lymphoproliferative disorder most commonly observed in HIV-infected patients. It is characterized by KSHV-infected plasmablasts that frequently express lytic genes. Patients manifest inflammatory symptoms attributed to overproduction of KSHV viral IL-6, human IL-6, and human IL-6. There is no standard therapy and no established response criteria. We investigated an approach targeting 2 KSHV lytic genes, ORF36 and ORF21, the protein of which, respectively, phosphorylate ganciclovir and zidovudine to toxic moieties. In a pilot study, 14 HIV-infected patients with symptomatic KSHV-MCD received high-dose zidovudine (600 mg orally every 6 hours) and the oral prodrug, valganciclovir (900 mg orally every 12 hours). Responses were evaluated using new response criteria. A total of 86% of patients attained major clinical responses and 50% attained major biochemical responses. Median progression-free survival was 6 months. With 43 months of median follow-up, overall survival was 86% at 12 months and beyond. At the time of best response, the patients showed significant improvements in C-reactive protein, albumin, platelets, human IL-6, IL-10, and KSHV viral load. The most common toxicities were hematologic. These observations provide evidence that therapy designed to target cells with lytic KSHV replication has activity in KSHV-MCD. This trial was registered at www.clinicaltrials.gov as #NCT00099073. (Blood. 2011;117(26):6977-6986)
C1 [Uldrick, Thomas S.; Polizzotto, Mark N.; Aleman, Karen; O'Mahony, Deirdre; Wyvill, Kathleen M.; Wang, Victoria; Little, Richard F.; Yarchoan, Robert] NCI, HIV& AIDS Malignancy Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Marshall, Vickie; Whitby, Denise] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA.
   [Pittaluga, Stefania] NCI, Pathol Lab, Bethesda, MD USA.
   [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Bethesda, MD USA.
   [Tosato, Giovanna] NCI, Lab Cellular Oncol, Ctr Canc Res, Bethesda, MD USA.
RP Yarchoan, R (reprint author), NCI, HIV& AIDS Malignancy Branch, Ctr Canc Res, 10 Ctr Dr,Rm 6N106,MSC 1868, Bethesda, MD 20892 USA.
EM yarchoan@helix.nih.gov
FU National Institutes of Health, National Cancer Institute
   [HHSN261200800001E]
FX This work was supported in part by the Intramural Research Program of
   the National Institutes of Health, National Cancer Institute as well as
   the National Cancer Institute, National Institutes of Health (contract
   HHSN261200800001E).
NR 51
TC 50
Z9 51
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 30
PY 2011
VL 117
IS 26
BP 6977
EP 6986
DI 10.1182/blood-2010-11-317610
PG 10
WC Hematology
SC Hematology
GA 785QO
UT WOS:000292244000004
PM 21487108
ER

PT J
AU Barao, I
   Alvarez, M
   Ames, E
   Orr, MT
   Stefanski, HE
   Blazar, BR
   Lanier, LL
   Anderson, SK
   Redelman, D
   Murphy, WJ
AF Barao, Isabel
   Alvarez, Maite
   Ames, Erik
   Orr, Mark T.
   Stefanski, Heather E.
   Blazar, Bruce R.
   Lanier, Lewis L.
   Anderson, Stephen K.
   Redelman, Doug
   Murphy, William J.
TI Mouse Ly49G2(+) NK cells dominate early responses during both immune
   reconstitution and activation independently of MHC
SO BLOOD
LA English
DT Article
ID NATURAL-KILLER-CELLS; MARROW ALLOGRAFT-REJECTION; CLASS-I MOLECULES;
   COMPLEX CLASS-I; BONE-MARROW; RECEPTOR REPERTOIRE; TARGET-CELLS;
   EXPRESSION; TRANSPLANTATION; ACQUISITION
AB Natural killer (NK) cell subsets can be defined by the differential expression of inhibitory receptors for MHC class I molecules. Early after congenic HSCT, we found that Ly49G2(high) single-positive NK cells repopulated, displayed an activated phenotype, and were highly cytolytic. Over time, this subset was replaced with NK cells with a normal pattern of Ly49 expression. Treatment of mice with IL-2 also resulted in the rapid expansion of these Ly49G2(high) single-positive NK cells. Only the Ly49g (Klra7) Pro1 transcript was highly induced in both HSCT- and IL-2-treated recipients. MHC-independent expansion of the Ly49G2(+) subset was also observed after Listeria monocytogenes or mouse cytomegalovirus infection. Our data indicate that during reconstitution after HSCT and various activation stimuli, Ly49G2(+) NK cells represent the "first-responder" NK cells, which occur independently of NK-cell licensing via Ly49-MHC interactions. These data suggest that the inhibitory Ly49G2 receptor represents an activation marker on mouse NK cells under various conditions. (Blood. 2011;117(26):7032-7041)
C1 [Murphy, William J.] Univ Calif Davis, Dept Dermatol, Sch Med, CTSC IRC, Sacramento, CA 95817 USA.
   [Barao, Isabel] Univ Nevada, Dept Microbiol & Immunol, Reno, NV 89557 USA.
   [Orr, Mark T.; Lanier, Lewis L.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA.
   [Orr, Mark T.; Lanier, Lewis L.] Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA.
   [Stefanski, Heather E.; Blazar, Bruce R.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
   [Stefanski, Heather E.; Blazar, Bruce R.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
   [Anderson, Stephen K.] NCI, Frederick, MD 21701 USA.
   [Anderson, Stephen K.] SAIC Frederick Inc, Lab Expt Immunol, Canc & Inflammat Program, Frederick, MD USA.
   [Redelman, Doug] Univ Nevada, Dept Physiol, Reno, NV 89557 USA.
   [Murphy, William J.] Univ Calif Davis, Dept Internal Med, Sacramento, CA USA.
RP Murphy, WJ (reprint author), Univ Calif Davis, Dept Dermatol, Sch Med, CTSC IRC, Suite 1630,2921 Stockton Blvd, Sacramento, CA 95817 USA.
EM wmjmurphy@ucdavis.edu
RI Anderson, Stephen/B-1727-2012
OI Anderson, Stephen/0000-0002-7856-4266
FU National Institutes of Health (NIH) [R01HL089905, P20 RR016464,
   P01CA067493, A1068129]; National Cancer Institute (NCI), NIH
   [HHSN261200800001E]; NIH, NCI, Center for Cancer Research
FX This study was supported by National Institutes of Health (NIH) grants
   R01HL089905, P20 RR016464, and P01CA067493. M.T.O. is an Irvington
   Fellow of the Cancer Research Institute. L.L.L. is an American Cancer
   Society Professor and is supported by NIH grant A1068129. This project
   has been funded in whole or in part with federal funds from the National
   Cancer Institute (NCI), NIH, under contract HHSN261200800001E. This
   research was supported by the Intramural Research Program of the NIH,
   NCI, Center for Cancer Research. The content of this publication does
   not necessarily reflect the views or policies of the Department of
   Health and Human Services, nor does mention of trade names, commercial
   products, or organizations imply endorsement by the US Government.
NR 33
TC 22
Z9 22
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 30
PY 2011
VL 117
IS 26
BP 7032
EP 7041
DI 10.1182/blood-2010-11-316653
PG 10
WC Hematology
SC Hematology
GA 785QO
UT WOS:000292244000011
PM 21498673
ER

PT J
AU Shen, M
   Zhang, LP
   Lee, KM
   Vermeulen, R
   Hosgood, HD
   Li, GL
   Yin, SN
   Rothman, N
   Chanock, S
   Smith, MT
   Lan, Q
AF Shen, Min
   Zhang, Luoping
   Lee, Kyoung-Mu
   Vermeulen, Roel
   Hosgood, H. Dean
   Li, Guilan
   Yin, Songnian
   Rothman, Nathaniel
   Chanock, Stephen
   Smith, Martyn T.
   Lan, Qing
TI Polymorphisms in genes involved in innate immunity and susceptibility to
   benzene-induced hematotoxicity
SO EXPERIMENTAL AND MOLECULAR MEDICINE
LA English
DT Article
DE benzene; hematology; immunity; innate; polymorphism; single nucleotide;
   toxicity
ID REACTIVE METABOLITE; HYDROQUINONE; ASSOCIATION; FALSE
AB Benzene, a recognized hematotoxicant and carcinogen, can damage the human immune system. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and benzene hematotoxicity in a cross-sectional study of workers exposed to benzene (250 workers and 140 controls). A total of 1,236 tag SNPs in 149 gene regions of six pathways were included in the analysis. Six gene regions were significant for their association with white blood cell (WBC) counts (MBP, VCAM1, ALOX5, MPO, RAC2, and CRP) based on gene-region (P < 0.05) and SNP analyses (FOR < 0.05). VCAM1 rs3176867, ALOX5 rs7099684, and MPO rs2071409 were the three most significant SNPs. They showed similar effects on WBC subtypes, especially granulocytes, lymphocytes, and monocytes. A 3-SNP block in ALOXE3 (rs7215658, rs9892383, and rs3027208) showed a global association (omnibus P = 0.0008) with WBCs even though the three SNPs were not significant individually. Our study suggests that polymorphisms in innate immunity genes may play a role in benzene-induced hematotoxicity; however, independent replication is necessary.
C1 [Shen, Min; Lee, Kyoung-Mu; Hosgood, H. Dean; Rothman, Nathaniel; Chanock, Stephen; Lan, Qing] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
   [Zhang, Luoping; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
   [Lee, Kyoung-Mu] Korea Natl Open Univ, Dept Environm Hlth, Seoul 110791, South Korea.
   [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Julius Ctr, Univ Med Ctr Utrecht, Utrecht, Netherlands.
   [Li, Guilan; Yin, Songnian] Chinese Ctr Dis Control & Prevent, Inst Occupat Hlth & Poison Control, Beijing, Peoples R China.
RP Hosgood, HD (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
EM hosgoodd@mail.nih.gov
RI Vermeulen, Roel/F-8037-2011
OI Vermeulen, Roel/0000-0003-4082-8163
FU NIH [RO1ES06721, P42ES04705, P30ES01896]
FX This project was in part by the NIH intramural research program, and by
   NIH grants RO1ES06721, P42ES04705 and P30ES01896 (to MTS).
NR 20
TC 9
Z9 10
U1 0
U2 12
PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
PI SEOUL
PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 1226-3613
J9 EXP MOL MED
JI Exp. Mol. Med.
PD JUN 30
PY 2011
VL 43
IS 6
BP 374
EP 378
DI 10.3858/emm.2011.43.6.041
PG 5
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 785MH
UT WOS:000292232600007
PM 21540635
ER

PT J
AU Adzick, NS
   Spong, CY
   Brock, JW
AF Adzick, N. Scott
   Spong, Catherine Y.
   Brock, John W.
TI Prenatal versus Postnatal Repair of Myelomeningocele REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Adzick, N. Scott] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
   [Spong, Catherine Y.] NIH, Bethesda, MD 20892 USA.
   [Brock, John W.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
RP Adzick, NS (reprint author), Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
EM adzick@email.chop.edu
NR 4
TC 1
Z9 1
U1 1
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 30
PY 2011
VL 364
IS 26
BP 2556
EP 2556
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 785AM
UT WOS:000292199800024
ER

PT J
AU Busse, WW
   Gergen, PJ
   Calatroni, A
AF Busse, William W.
   Gergen, Peter J.
   Calatroni, Agustin
TI Anti-IgE for Asthma in Inner-City Children REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID OMALIZUMAB
C1 [Busse, William W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53715 USA.
   [Gergen, Peter J.] NIAID, Bethesda, MD 20892 USA.
   [Calatroni, Agustin] Rho Fed Syst Div, Chapel Hill, NC USA.
RP Busse, WW (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53715 USA.
EM wwb@medicine.wisc.edu
NR 3
TC 1
Z9 1
U1 1
U2 4
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 30
PY 2011
VL 364
IS 26
BP 2557
EP 2558
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 785AM
UT WOS:000292199800027
ER

PT J
AU Yu, BB
   Zhou, C
   Bandinelli, S
AF Yu, Binbing
   Zhou, Chuan
   Bandinelli, Stefania
TI Combining multiple continuous tests for the diagnosis of kidney
   impairment in the absence of a gold standard
SO STATISTICS IN MEDICINE
LA English
DT Article
DE diagnostic test; gold standard; Markov chain Monte-Carlo; sensitivity;
   specificity
ID OPERATING CHARACTERISTIC CURVES; GLOMERULAR-FILTRATION-RATE; SERUM
   CREATININE; DISEASE; CLASSIFICATION
AB Receiver operating characteristic (ROC) curves are commonly used to summarize the classification accuracy of diagnostic tests. It is not uncommon in medical practice that multiple diagnostic tests are routinely performed or multiple disease markers are available for the same individuals. When the true disease status is verified by a gold standard (GS) test, a variety of methods have been proposed to combine such potential correlated tests to increase the accuracy of disease diagnosis. In this article, we propose a method of combining multiple diagnostic tests in the absence of a GS. We assume that the test values and their classification accuracies are dependent on covariates. Simulation studies are performed to examine the performance of the combination method. The proposed method is applied to data from a population-based aging study to compare the accuracy of three screening tests for kidney function and to estimate the prevalence of moderate kidney impairment. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Yu, Binbing] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
   [Zhou, Chuan] Univ Washington, Med Ctr, Dept Pediat, Ctr Child Hlth Behav & Dev,Seattle Childrens Hosp, Seattle, WA 98195 USA.
   [Zhou, Chuan] Reg Med Ctr, Seattle, WA 98195 USA.
   [Bandinelli, Stefania] Azienda, Geriatr Unit, Sanitaria Di Firenze, Italy.
RP Yu, BB (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
EM yubi@mail.nih.gov
FU National Institute on Aging
FX The research was supported in part by the Intramural Research Program of
   the National Institute on Aging.
NR 18
TC 4
Z9 4
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD JUN 30
PY 2011
VL 30
IS 14
BP 1712
EP 1721
DI 10.1002/sim.4203
PG 10
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 777EK
UT WOS:000291598400006
PM 21432889
ER

PT J
AU Jemal, A
   Thun, M
   Yu, XQ
   Hartman, AM
   Cokkinides, V
   Center, MM
   Ross, H
   Ward, EM
AF Jemal, Ahmedin
   Thun, Michael
   Yu, Xue Q.
   Hartman, Anne M.
   Cokkinides, Vilma
   Center, Melissa M.
   Ross, Hana
   Ward, Elizabeth M.
TI Changes in smoking prevalence among U.S. adults by state and region:
   Estimates from the Tobacco Use Supplement to the Current Population
   Survey, 1992-2007
SO BMC PUBLIC HEALTH
LA English
DT Article
ID CIGARETTE-SMOKING; CONTROL PROGRAMS; UNITED-STATES; CALIFORNIA; TRENDS;
   CONSUMPTION; CESSATION
AB Background: Tobacco control policies at the state level have been a critical impetus for reduction in smoking prevalence. We examine the association between recent changes in smoking prevalence and state-specific tobacco control policies and activities in the entire U. S.
   Methods: We analyzed the 1992-93, 1998-99, and 2006-07 Tobacco Use Supplement to the Current Population Survey (TUS-CPS) by state and two indices of state tobacco control policies or activities [initial outcome index (IOI) and the strength of tobacco control (SOTC) index] measured in 1998-1999. The IOI reflects cigarette excise taxes and indoor air legislation, whereas the SOTC reflects tobacco control program resources and capacity. Pearson Correlation coefficient between the proportionate change in smoking prevalence from 1992-93 to 2006-07 and indices of tobacco control activities or programs was the main outcome measure.
   Results: Smoking prevalence decreased from 1992-93 to 2006-07 in both men and women in all states except Wyoming, where no reduction was observed among men, and only a 6.9% relative reduction among women. The percentage reductions in smoking in men and women respectively were the largest in the West (average decrease of 28.5% and 33.3%) and the smallest in the Midwest (18.6% and 20.3%), although there were notable exceptions to this pattern. The decline in smoking prevalence by state was correlated with the state's IOI in both women and men (r = -0.49, p < 0.001; r = -0.31, p = 0.03; respectively) and with state's SOTC index in women(r = -0.30, p = 0.03 0), but not men (r = -0.21, p = 0.14).
   Conclusion: State level policies on cigarette excise taxes and indoor air legislation correlate strongly with reductions in smoking prevalence since 1992. Strengthening and systematically implementing these policies could greatly accelerate further reductions in smoking.
C1 [Jemal, Ahmedin; Thun, Michael; Cokkinides, Vilma; Center, Melissa M.; Ross, Hana; Ward, Elizabeth M.] Amer Canc Soc, Atlanta, GA 30303 USA.
   [Yu, Xue Q.] NSW Canc Council, Woolloomooloo, NSW 2011, Australia.
   [Hartman, Anne M.] NCI, Rockville, MD 20852 USA.
RP Jemal, A (reprint author), Amer Canc Soc, 250 Williams St NW, Atlanta, GA 30303 USA.
EM ahmedin.jemal@cancer.org
RI Yu, Xue Qin/E-7405-2013
NR 38
TC 18
Z9 18
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2458
J9 BMC PUBLIC HEALTH
JI BMC Public Health
PD JUN 29
PY 2011
VL 11
AR 512
DI 10.1186/1471-2458-11-512
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 802HG
UT WOS:000293499300001
PM 21714876
ER

PT J
AU Park, SS
   Stranahan, AM
   Chadwick, W
   Zhou, Y
   Wang, LY
   Martin, B
   Becker, KG
   Maudsley, S
AF Park, Sung-Soo
   Stranahan, Alexis M.
   Chadwick, Wayne
   Zhou, Yu
   Wang, Liyun
   Martin, Bronwen
   Becker, Kevin G.
   Maudsley, Stuart
TI Cortical gene transcription response patterns to water maze training in
   aged mice
SO BMC NEUROSCIENCE
LA English
DT Article
ID RETROSPLENIAL CORTEX LESIONS; ENTORHINAL CORTEX; SPATIAL MEMORY;
   FUNCTIONAL NEUROANATOMY; PARAHIPPOCAMPAL REGION; MOLECULAR-MECHANISMS;
   SYNAPTIC PLASTICITY; HIPPOCAMPUS; BDNF; RAT
AB Background: The hippocampus mediates the acquisition of spatial memory, but the memory trace is eventually transferred to the cortex. We have investigated transcriptional activation of pathways related to cognitive in the cortex of the aged mouse by analyzing gene expression following water maze training.
   Results: We identified genes that were differentially responsive in aged mice with accurate spatial performance during probe trials or repeated swimming sessions, relative to home cage conditions. Effective learners exhibited significantly greater activation of several pathways, such as the mitogen-activated protein kinase and insulin receptor signaling pathways, relative to swimmers. The genes encoding activity-related cytoskeletal protein (Arc) and brain-derived neurotrophic factor (BDNF) were upregulated in proficient learners, relative to swimmers and home cage controls, while the gene encoding Rho GTPase activating protein 32 (GRIT) was downregulated. We explored the regulation of Arc, BDNF, and GRIT expression in greater morphological detail using in situ hybridization. Recall during probe trials enhanced Arc expression across multiple cortical regions involved in the cognitive component of water maze learning, while BDNF expression was more homogeneously upregulated across cortical regions involved in the associational and sensorimotor aspects of water maze training. In contrast, levels of GRIT expression were uniformly reduced across all cortical regions examined.
   Conclusions: These results suggest that cortical gene transcription is responsive to learning in aged mice that exhibit behavioral proficiency, and support a distributed hypothesis of memory storage across multiple cortical compartments.
C1 [Park, Sung-Soo; Chadwick, Wayne; Zhou, Yu; Wang, Liyun; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Baltimore, MD 21224 USA.
   [Stranahan, Alexis M.] Georgia Hlth Sci Univ, Dept Physiol, Augusta, GA 30912 USA.
   [Martin, Bronwen] NIA, Metab Unit, Baltimore, MD 21224 USA.
   [Becker, Kevin G.] NIA, Gene Express & Genom Unit, Res Resources Branch, Baltimore, MD 21224 USA.
RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, Baltimore, MD 21224 USA.
EM maudsleyst@mail.nih.gov
RI Zhou, Yu/M-7975-2014; 
OI Becker, Kevin/0000-0002-6794-6656
FU National Institute of Aging; Ford Foundation
FX This work was supported in part by the Intramural Program at the
   National Institute of Aging. A.M.S. is supported by a Ford Foundation
   postdoctoral fellowship. We are grateful to Drs. Michela Gallagher,
   Yongqing Zhang, Elin Lehrman, and Mark P. Mattson for their expertise
   and technical assistance. The authors have no actual or potential
   conflicts of interest.
NR 34
TC 10
Z9 10
U1 0
U2 4
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 JUN 29
PY 2011
VL 12
AR 63
DI 10.1186/1471-2202-12-63
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 795YY
UT WOS:000293017500001
PM 21714909
ER

PT J
AU Cao, K
   Graziotto, JJ
   Blair, CD
   Mazzulli, JR
   Erdos, MR
   Krainc, D
   Collins, FS
AF Cao, Kan
   Graziotto, John J.
   Blair, Cecilia D.
   Mazzulli, Joseph R.
   Erdos, Michael R.
   Krainc, Dimitri
   Collins, Francis S.
TI Rapamycin Reverses Cellular Phenotypes and Enhances Mutant Protein
   Clearance in Hutchinson-Gilford Progeria Syndrome Cells
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID AGGREGATE-PRONE PROTEINS; CHRONOLOGICAL LIFE-SPAN; CONJUGATION SYSTEM;
   AUTOPHAGY; LAMIN; DEGRADATION; DISEASE; TARGET; MTOR; LAMINOPATHIES
AB Hutchinson-Gilford progeria syndrome (HGPS) is a lethal genetic disorder characterized by premature aging. HGPS is most commonly caused by a de novo single-nucleotide substitution in the lamin A/C gene (LMNA) that partially activates a cryptic splice donor site in exon 11, producing an abnormal lamin A protein termed progerin. Accumulation of progerin in dividing cells adversely affects the integrity of the nuclear scaffold and leads to nuclear blebbing in cultured cells. Progerin is also produced in normal cells, increasing in abundance as senescence approaches. Here, we report the effect of rapamycin, a macrolide antibiotic that has been implicated in slowing cellular and organismal aging, on the cellular phenotypes of HGPS fibroblasts. Treatment with rapamycin abolished nuclear blebbing, delayed the onset of cellular senescence, and enhanced the degradation of progerin in HGPS cells. Rapamycin also decreased the formation of insoluble progerin aggregates and induced clearance through autophagic mechanisms in normal fibroblasts. Our findings suggest an additional mechanism for the beneficial effects of rapamycin on longevity and encourage the hypothesis that rapamycin treatment could provide clinical benefit for children with HGPS.
C1 [Graziotto, John J.; Mazzulli, Joseph R.; Krainc, Dimitri] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
   [Cao, Kan; Blair, Cecilia D.; Erdos, Michael R.; Collins, Francis S.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   [Cao, Kan] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
RP Krainc, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
EM krainc@helix.mgh.harvard.edu; francis.collins@nih.gov
FU Progeria Research Foundation; National Human Genome Research Institute; 
   [R00AG029761];  [R01NS051303]
FX This work was supported by grants R00AG029761 (K.C.) and R01NS051303
   (D.K.), The Progeria Research Foundation (J.J.G. and D.K.), and the
   intramural program of the National Human Genome Research Institute
   (F.S.C.).
NR 38
TC 93
Z9 96
U1 7
U2 39
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JUN 29
PY 2011
VL 3
IS 89
AR 89ra58
DI 10.1126/scitranslmed.3002346
PG 11
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 795NY
UT WOS:000292982100005
PM 21715679
ER

PT J
AU Matveev, V
   Bertram, R
   Sherman, A
AF Matveev, Victor
   Bertram, Richard
   Sherman, Arthur
TI Calcium cooperativity of exocytosis as a measure of Ca2+ channel domain
   overlap
SO BRAIN RESEARCH
LA English
DT Review
DE Presynaptic; Calcium cooperativity; Channel cooperativity; Current
   cooperativity; Synaptic transmission; Calcium buffer; Calcium diffusion;
   Modeling; Exocytosis; Active zone
ID SQUID GIANT SYNAPSE; TRANSMITTER RELEASE; NEUROTRANSMITTER RELEASE;
   PRESYNAPTIC CALCIUM; RIBBON SYNAPSE; NEUROMUSCULAR-JUNCTION; VESICLE
   FUSION; AFFERENT SYNAPSE; NERVE-TERMINALS; BOTULINUM TOXIN
AB The number of Ca2+ channels contributing to the exocytosis of a single neurotransmitter vesicle in a presynaptic terminal has been a question of significant interest and debate, and is important for a full understanding of localized Ca2+ signaling in general, and synaptic physiology in particular. This is usually estimated by measuring the sensitivity of the neurotransmitter release rate to changes in the synaptic Ca2+ current, which is varied using appropriate voltage-clanip protocols or via pharmacological Ca2+ channel block under the condition of constant single-channel Ca2+ current. The slope of the resulting log-log plot of transmitter release rate versus presynaptic Ca2+ current is termed Ca2+ current cooperativity of exocytosis, and provides indirect information about the underlying presynaptic morphology. In this review, we discuss the relationship between the Ca2+ current cooperativity and the average number of Ca2+ channels participating in the exocytosis of a single vesicle, termed the Ca2+ channel cooperativity. We relate these quantities to the morphology of the presynaptic active zone. We also review experimental studies of Ca2+ current cooperativity and its modulation during development in different classes of synapses. (C) 2011 Published by Elsevier B.V.
C1 [Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
   [Matveev, Victor] NJIT, 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.
RP Sherman, A (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
EM asherman@nih.gov
FU National Science Foundation [DMS-0817703, DMS-0917664]; NIH (NIDDK)
FX Supported by National Science Foundation grants DMS-0817703 (V.M.) and
   DMS-0917664 (R.B.), and the Intramural Research Program of NIH (NIDDK)
   (A.S.).
NR 88
TC 22
Z9 22
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
J9 BRAIN RES
JI Brain Res.
PD JUN 29
PY 2011
VL 1398
BP 126
EP 138
DI 10.1016/j.brainres.2011.05.011
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 788GZ
UT WOS:000292434700013
PM 21621748
ER

PT J
AU Mei, F
   Nagappan, G
   Ke, Y
   Sacktor, TC
   Lu, B
AF Mei, Fan
   Nagappan, Guhan
   Ke, Yang
   Sacktor, Todd C.
   Lu, Bai
TI BDNF Facilitates L-LTP Maintenance in the Absence of Protein Synthesis
   through PKM zeta
SO PLOS ONE
LA English
DT Article
ID LONG-TERM POTENTIATION; KINASE-M-ZETA; SYNAPTIC PLASTICITY; MEMORY;
   HIPPOCAMPUS; TRAFFICKING; EXPRESSION; INCREASES
AB Late-phase long term potentiation (L-LTP) is thought to be the cellular basis for long-term memory (LTM). While LTM as well as L-LTP is known to depend on transcription and translation, it is unclear why brain-derived neurotrophic factor (BDNF) could sustain L-LTP when protein synthesis is inhibited. The persistently active protein kinase zeta (PKM zeta) is the only molecule implicated in perpetuating L-LTP maintenance. Here, in mouse acute brain slices, we show that inhibition of PKM zeta reversed BDNF-dependent form of L-LTP. While BDNF did not alter the steady-state level of PKM zeta, BDNF together with the L-LTP inducing theta-burst stimulation (TBS) increased PKM zeta level even without protein synthesis. Finally, in the absence of de novo protein synthesis, BDNF maintained TBS-induced PKM zeta at a sufficient level. These results suggest that BDNF sustains L-LTP through PKM zeta in a protein synthesis-independent manner, revealing an unexpected link between BDNF and PKM zeta.
C1 [Mei, Fan; Ke, Yang] Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Beijing 100871, Peoples R China.
   [Mei, Fan; Nagappan, Guhan; Lu, Bai] NICHHD, Program Dev Neurobiol, Bethesda, MD 20892 USA.
   [Nagappan, Guhan; Lu, Bai] GlaxoSmithKline, R&D China, Shanghai, Peoples R China.
   [Sacktor, Todd C.] Suny Downstate Med Ctr, Dept Physiol & Pharmacol, Robert F Furchgott Ctr Neural & Behav Sci, Brooklyn, NY 11203 USA.
   [Sacktor, Todd C.] Suny Downstate Med Ctr, Dept Neurol, Brooklyn, NY 11203 USA.
RP Mei, F (reprint author), Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Beijing 100871, Peoples R China.
EM bai.b.lu@gsk.com
RI Lu, Bai/A-4018-2012; Mei, Fan/H-2665-2012; yu, yan/C-2322-2012
FU National Institutes of Child Health and Human Development; National
   Institutes of Mental Health
FX This work was supported in part by the Intramural Research Program of
   the National Institutes of Child Health and Human Development and the
   National Institutes of Mental Health. The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 32
TC 30
Z9 31
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 29
PY 2011
VL 6
IS 6
AR e21568
DI 10.1371/journal.pone.0021568
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 786FZ
UT WOS:000292290100041
PM 21747912
ER

PT J
AU Diabate, A
   Yaro, AS
   Dao, A
   Diallo, M
   Huestis, DL
   Lehmann, T
AF Diabate, Abdoulaye
   Yaro, Alpha S.
   Dao, Adama
   Diallo, Moussa
   Huestis, Diana L.
   Lehmann, Tovi
TI Spatial distribution and male mating success of Anopheles gambiae swarms
SO BMC EVOLUTIONARY BIOLOGY
LA English
DT Article
DE Anopheles gambiae; mating success; lek; scramble competition
ID FEMALE CHOICE; REPRODUCTIVE SUCCESS; SEXUAL SELECTION; MOSQUITO SWARMS;
   VECTOR MOSQUITO; MOLECULAR-FORMS; MATE CHOICE; SAO-TOME; DIPTERA;
   EVOLUTION
AB Background: Anopheles gambiae mates in flight at particular mating sites over specific landmarks known as swarm markers. The swarms are composed of males; females typically approach a swarm, and leave in copula. This mating aggregation looks like a lek, but appears to lack the component of female choice. To investigate the possible mechanisms promoting the evolution of swarming in this mosquito species, we looked at the variation in mating success between swarms and discussed the factors that structure it in light of the three major lekking models, known as the female preference model, the hotspot model, and the hotshot model.
   Results: We found substantial variation in swarm size and in mating success between swarms. A strong correlation between swarm size and mating success was observed, and consistent with the hotspot model of lek formation, the per capita mating success of individual males did not increase with swarm size. For the spatial distribution of swarms, our results revealed that some display sites were more attractive to both males and females and that females were more attracted to large swarms. While the swarm markers we recognize help us in localizing swarms, they did not account for the variation in swarm size or in the swarm mating success, suggesting that mosquitoes probably are attracted to these markers, but also perceive and respond to other aspects of the swarming site.
   Conclusions: Characterizing the mating system of a species helps understand how this species has evolved and how selective pressures operate on male and female traits. The current study looked at male mating success of An. gambiae and discussed possible factors that account for its variation. We found that swarms of An. gambiae conform to the hotspot model of lek formation. But because swarms may lack the female choice component, we propose that the An. gambiae mating system is a lek-like system that incorporates characteristics pertaining to other mating systems such as scramble mating competition.
C1 [Diabate, Abdoulaye; Huestis, Diana L.; Lehmann, Tovi] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
   [Diabate, Abdoulaye] Ctr Muraz, Inst Rech Sci Sante, Bobo Dioulasso, Burkina Faso.
   [Yaro, Alpha S.; Dao, Adama; Diallo, Moussa] Univ Bamako, Malaria Res & Training Ctr, Bamako, Mali.
RP Diabate, A (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM a_diabate@hotmail.com
OI Huestis, Diana/0000-0001-6649-4785
FU National Institutes of Allergy and Infectious Diseases; National
   Institute of Health; Multilateral Initiative on Malaria
FX We are grateful to Boaz Yuval, Nick Manoukis and several anonymous
   reviewers for useful comments and suggestions to improve the manuscript.
   This investigation was funded by the Intramural Research Program of
   National Institutes of Allergy and Infectious Diseases, National
   Institute of Health and the Multilateral Initiative on Malaria.
NR 49
TC 36
Z9 37
U1 4
U2 28
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2148
J9 BMC EVOL BIOL
JI BMC Evol. Biol.
PD JUN 28
PY 2011
VL 11
AR 184
DI 10.1186/1471-2148-11-184
PG 13
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA 799GS
UT WOS:000293274900001
PM 21711542
ER

PT J
AU Wiktorowicz, JE
   Stafford, S
   Rea, H
   Urvil, P
   Soman, K
   Kurosky, A
   Perez-Polo, JR
   Savidge, TC
AF Wiktorowicz, John E.
   Stafford, Susan
   Rea, Harriet
   Urvil, Petri
   Soman, Kizhake
   Kurosky, Alexander
   Perez-Polo, J. Regino
   Savidge, Tor C.
TI Quantification of Cysteinyl S-Nitrosylation by Fluorescence in Unbiased
   Proteomic Studies
SO BIOCHEMISTRY
LA English
DT Article
ID PROTEIN DISULFIDE-ISOMERASE; ISCHEMIC BRAIN-INJURY; BIOTIN SWITCH ASSAY;
   NITRIC-OXIDE; NEONATAL-RAT; HYPEROXIA; NITROSOGLUTATHIONE;
   RESUSCITATION; NITROSATION; PEROXYNITRITE
AB Cysteinyl S-nitrosylation has emerged as an important post-translational modification affecting protein function in health and disease. Great emphasis has been placed on global, unbiased quantification of S-nitrosylated proteins because of physiologic and oxidative stimuli. However, current strategies have been hampered by sample loss and altered protein electrophoretic mobility. Here, we describe a novel quantitative approach that uses accurate, sensitive fluorescence modification of cysteine S-nitrosylation that leaves electrophoretic mobility unaffected (SNOFlo) and introduce unique concepts for measuring changes in S-nitrosylation status relative to protein abundance. Its efficacy in defining the functional S-nitrosoproteome is demonstrated in two diverse biological applications: an in vivo rat hypoxia-ischemia/reperfusion model and antimicrobial S-nitrosoglutathione-driven transnitrosylation of an enteric microbial pathogen. The suitability of this approach for investigating endogenous S-nitrosylation is further demonstrated using Ingenuity Pathways analysis that identified nervous system and cellular development networks as the top two networks. Functional analysis of differentially S-nitrosylated proteins indicated their involvement in apoptosis, branching morphogenesis of axons, cortical neurons, and sympathetic neurites, neurogenesis, and calcium signaling. Major abundance changes were also observed for fibrillar proteins known to be stress-responsive in neurons and glia. Thus, both examples demonstrate the technique's power in confirming the widespread involvement of S-nitrosylation in hypoxia-ischemia/reperfusion injury and in antimicrobial host responses.
C1 [Wiktorowicz, John E.; Rea, Harriet; Soman, Kizhake; Kurosky, Alexander; Perez-Polo, J. Regino] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA.
   [Wiktorowicz, John E.; Stafford, Susan; Soman, Kizhake; Kurosky, Alexander] Univ Texas Med Branch, NHLBI, Prote Ctr, Galveston, TX 77555 USA.
   [Wiktorowicz, John E.; Soman, Kizhake; Kurosky, Alexander; Perez-Polo, J. Regino] Univ Texas Med Branch, Sealy Ctr Mol Med, Galveston, TX 77555 USA.
   [Urvil, Petri; Savidge, Tor C.] Univ Texas Med Branch, Dept Internal Med Gastroenterol, Galveston, TX 77555 USA.
RP Wiktorowicz, JE (reprint author), Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA.
EM jowiktor@utmb.edu
RI Soman, Kizhake/C-2028-2012
FU National Heart, Lung, and Blood Institute Proteomics Center
   [N01-HV-00245]; National Institute of Diabetes and Digestive and Kidney
   Diseases [R21-DK078032-01, 1UL1RR029876-01]; Eli and Edythe Broad
   Foundation; National Institute of Child Health and Human Development
   [PO1-HDO039833]
FX This work was supported in part by National Heart, Lung, and Blood
   Institute Proteomics Center Contract N01-HV-00245 (AK), National
   Institute of Diabetes and Digestive and Kidney Diseases Grants
   R21-DK078032-01 (T.C.S.) and 1UL1RR029876-01 (T.C.S.), the Eli and
   Edythe Broad Foundation (T.C.S.), and National Institute of Child Health
   and Human Development Grant PO1-HDO039833 (J.RP.-P.).
NR 55
TC 20
Z9 20
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 JUN 28
PY 2011
VL 50
IS 25
BP 5601
EP 5614
DI 10.1021/bi200008b
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 780YJ
UT WOS:000291897000006
PM 21615140
ER

PT J
AU Camargo, MC
   Murphy, G
   Koriyama, C
   Pfeiffer, RM
   Kim, WH
   Herrera-Goepfert, R
   Corvalan, AH
   Carrascal, E
   Abdirad, A
   Anwar, M
   Hao, Z
   Kattoor, J
   Yoshiwara-Wakabayashi, E
   Eizuru, Y
   Rabkin, CS
   Akiba, S
AF Camargo, M. C.
   Murphy, G.
   Koriyama, C.
   Pfeiffer, R. M.
   Kim, W. H.
   Herrera-Goepfert, R.
   Corvalan, A. H.
   Carrascal, E.
   Abdirad, A.
   Anwar, M.
   Hao, Z.
   Kattoor, J.
   Yoshiwara-Wakabayashi, E.
   Eizuru, Y.
   Rabkin, C. S.
   Akiba, S.
TI Determinants of Epstein-Barr virus-positive gastric cancer: an
   international pooled analysis
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE gastric cancer; EBV; prevalence; pooled analysis
ID HELICOBACTER-PYLORI; CLINICOPATHOLOGICAL FEATURES; PROTEIN EXPRESSION;
   CLINICAL-TRIALS; CARCINOMA; METAANALYSIS; LOCATION; EBV;
   ADENOCARCINOMAS; HISTOLOGY
AB BACKGROUND: Meta-analyses of the published literature indicate that about 9% of gastric cancers contain Epstein-Barr virus (EBV), with consistent and significant differences by sex and anatomic subsite. This study aimed to identify additional determinants of EBV positivity and their joint effects.
   METHODS: From 15 international populations with consistent laboratory testing for EBV, we pooled individual-level data for 5081 gastric cancer cases including information on age, sex, subsite, histologic type, diagnostic stage, geographic region, and period of diagnosis. First, we combined population-specific EBV prevalence estimates using random effects meta-analysis. We then aggregated individual-level data to estimate odds ratios of EBV positivity in relation to all variables, accounting for within-population clustering.
   RESULTS: In unadjusted analyses, EBV positivity was significantly higher in males, young subjects, non-antral subsites, diffuse-type histology, and in studies from the Americas. Multivariable analyses confirmed significant associations with histology and region. Sex interacted with age (P = 0.003) and subsite (P = 0.002) such that male predominance decreased with age for both subsites. The positivity of EBV was not significantly associated with either stage or time period.
   CONCLUSION: Aggregating individual-level data provides additional information over meta-analyses. Distinguishing histologic and geographic features as well as interactions among age, sex, and subsite further support classification of EBV-associated gastric cancer as a distinct aetiologic entity. British Journal of Cancer (2011) 105, 38-43. doi: 10.1038/bjc.2011.215 www.bjcancer.com Published online 7 June 2011 (C) 2011 Cancer Research UK
C1 [Camargo, M. C.; Murphy, G.; Pfeiffer, R. M.; Rabkin, C. S.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
   [Camargo, M. C.] Univ Illinois, Div Epidemiol & Biostat, Chicago, IL 60612 USA.
   [Koriyama, C.; Anwar, M.; Akiba, S.] Kagoshima Univ, Grad Sch Med & Dent Sci, Ctr Chron Viral Dis, Dept Epidemiol & Prevent Med, Kagoshima 8908544, Japan.
   [Kim, W. H.] Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 110799, South Korea.
   [Herrera-Goepfert, R.] Natl Canc Inst, Dept Pathol, Mexico City 14080, DF, Mexico.
   [Corvalan, A. H.] Pontificia Univ Catolica, Dept Hematol & Oncol, Santiago 133202, Chile.
   [Carrascal, E.] Univ Valle, Cali Canc Registry, Cali, Colombia.
   [Abdirad, A.] Univ Tehran Med Sci, Inst Canc, Tehran 1417613151, Iran.
   [Hao, Z.] Guangzhou Med Coll, Affiliated Hosp 2, Dept Pathol, Guagngzhou 510260, Guangdong, Peoples R China.
   [Kattoor, J.] Reg Canc Ctr, Dept Pathol, Trivandrum 695011, Kerala, India.
   [Yoshiwara-Wakabayashi, E.] Policlin Peruano Japones, Lima, Peru.
   [Eizuru, Y.] Kagoshima Univ, Grad Sch Med & Dent Sci, Ctr Chron Viral Dis, Div Oncogen & Persistent Viruses, Kagoshima 8908544, Japan.
RP Camargo, MC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM camargomc@mail.nih.gov
RI Kim, Wooho/G-3703-2011; Seoul National University,
   Pathology/B-6702-2012; Murphy, Gwen/G-7443-2015; Camargo, M.
   Constanza/R-9891-2016
FU National Cancer Institute, National Institutes of Health
FX This study was funded by the Intramural Research Program of the National
   Cancer Institute, National Institutes of Health. We thank Dr Garth
   Rauscher for his helpful comments on an earlier version of this
   manuscript. The findings and conclusions in this report are those of the
   authors and do not necessarily represent the official position of the
   United States National Cancer Institute.
NR 37
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U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD JUN 28
PY 2011
VL 105
IS 1
BP 38
EP 43
DI 10.1038/bjc.2011.215
PG 6
WC Oncology
SC Oncology
GA 784TZ
UT WOS:000292182400007
PM 21654677
ER

PT J
AU Barron, EL
   Sosnovtsev, SV
   Bok, K
   Prikhodko, V
   Sandoval-Jaime, C
   Rhodes, CR
   Hasenkrug, K
   Carmody, AB
   Ward, JM
   Perdue, K
   Green, KY
AF Barron, Elyssa L.
   Sosnovtsev, Stanislav V.
   Bok, Karin
   Prikhodko, Victor
   Sandoval-Jaime, Carlos
   Rhodes, Crystal R.
   Hasenkrug, Kim
   Carmody, Aaron B.
   Ward, Jerrold M.
   Perdue, Kathy
   Green, Kim Y.
TI Diversity of Murine Norovirus Strains Isolated from Asymptomatic Mice of
   Different Genetic Backgrounds within a Single US Research Institute
SO PLOS ONE
LA English
DT Article
ID AMINO-ACID SUBSTITUTION; MOUSE MODEL; CAPSID PROTEIN; NORWALK VIRUS;
   INFECTION; SUFFICIENT; SEQUENCE; IMMUNITY; DOMAIN; CELLS
AB Antibody prevalence studies in laboratory mice indicate that murine norovirus (MNV) infections are common, but the natural history of these viruses has not been fully established. This study examined the extent of genetic diversity of murine noroviruses isolated from healthy laboratory mice housed in multiple animal facilities within a single, large research institute-the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIAID-NIH) in Bethesda, Maryland, U. S. Ten distinct murine norovirus strains were isolated from various tissues and feces of asymptomatic wild type sentinel mice as well as asymptomatic immunodeficient (RAG 2(-/-)) mice. The NIH MNV isolates showed little cytopathic effect in permissive RAW264.7 cells in early passages, but all isolates examined could be adapted to efficient growth in cell culture by serial passage. The viruses, although closely related in genome sequence, were distinguishable from each other according to facility location, likely due to the introduction of new viruses into each facility from separate sources or vendors at different times. Our study indicates that the murine noroviruses are widespread in these animal facilities, despite rigorous guidelines for animal care and maintenance.
C1 [Barron, Elyssa L.; Sosnovtsev, Stanislav V.; Bok, Karin; Prikhodko, Victor; Sandoval-Jaime, Carlos; Rhodes, Crystal R.; Green, Kim Y.] NIAID, Infect Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   [Hasenkrug, Kim; Carmody, Aaron B.] NIAID, Retrovirus Immunol Sect, NIH, Dept Hlth & Human Serv, Hamilton, MT USA.
   [Ward, Jerrold M.; Perdue, Kathy] NIAID, Comparat Med Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Barron, EL (reprint author), NIAID, Infect Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM kgreen@niaid.nih.gov
OI Prikhodko, Victor/0000-0001-6006-9454
FU National Institute of Allergy and Infectious Diseases
FX This study was supported by the intramural research program of the
   National Institute of Allergy and Infectious Diseases. The funders had
   no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 30
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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 JUN 28
PY 2011
VL 6
IS 6
AR e21435
DI 10.1371/journal.pone.0021435
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 784FW
UT WOS:000292142800021
PM 21738664
ER

PT J
AU Firnhaber, C
   Azzoni, L
   Foulkes, AS
   Gross, R
   Yin, XF
   Van Amsterdam, D
   Schulze, D
   Glencross, DK
   Stevens, W
   Hunt, G
   Morris, L
   Fox, L
   Sanne, I
   Montaner, LJ
AF Firnhaber, Cynthia
   Azzoni, Livio
   Foulkes, Andrea S.
   Gross, Robert
   Yin, Xiangfan
   Van Amsterdam, Desiree
   Schulze, Doreen
   Glencross, Deborah K.
   Stevens, Wendy
   Hunt, Gillian
   Morris, Lynn
   Fox, Lawrence
   Sanne, Ian
   Montaner, Luis J.
TI Randomized Trial of Time-Limited Interruptions of Protease
   Inhibitor-Based Antiretroviral Therapy (ART) vs. Continuous Therapy for
   HIV-1 Infection
SO PLOS ONE
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; AFRICAN ADULTS; CELL COUNTS; ADHERENCE;
   INTERMITTENT; DETERMINANTS; PLASMA; NEVIRAPINE; INFERIOR; RISK
AB Background: The clinical outcomes of short interruptions of PI-based ART regimens remains undefined.
   Methods: A 2-arm non-inferiority trial was conducted on 53 HIV-1 infected South African participants with viral load <50 copies/ml and CD4 T cell count >450 cells/mu l on stavudine (or zidovudine), lamivudine and lopinavir/ritonavir. Subjects were randomized to a) sequential 2, 4 and 8-week ART interruptions or b) continuous ART (cART). Primary analysis was based on the proportion of CD4 count >350 cells(c)/ml over 72 weeks. Adherence, HIV-1 drug resistance, and CD4 count rise over time were analyzed as secondary endpoints.
   Results: The proportions of CD4 counts >350 cells/mu l were 82.12% for the intermittent arm and 93.73 for the cART arm; the difference of 11.95% was above the defined 10% threshold for non-inferiority (upper limit of 97.5% CI, 24.1%; 2-sided CI: -0.16, 23.1). No clinically significant differences in opportunistic infections, adverse events, adherence or viral resistance were noted; after randomization, long-term CD4 rise was observed only in the cART arm.
   Conclusion: We are unable to conclude that short PI-based ART interruptions are non-inferior to cART in retention of immune reconstitution; however, short interruptions did not lead to a greater rate of resistance mutations or adverse events than cART suggesting that this regimen may be more forgiving than NNRTIs if interruptions in therapy occur.
C1 [Firnhaber, Cynthia; Van Amsterdam, Desiree; Schulze, Doreen; Sanne, Ian] Univ Witwatersrand, Dept Med, Fac Hlth Sci, Clin HIV Res Unit, ZA-2001 Johannesburg, South Africa.
   [Azzoni, Livio; Yin, Xiangfan; Montaner, Luis J.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA.
   [Foulkes, Andrea S.] Univ Massachusetts, Div Biostat, Amherst, MA 01003 USA.
   [Gross, Robert] Univ Penn, Dept Med Infect Dis, Philadelphia, PA 19104 USA.
   [Gross, Robert] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   [Glencross, Deborah K.; Stevens, Wendy] Univ Witwatersrand, Dept Mol Med & Haematol, ZA-2001 Johannesburg, South Africa.
   [Glencross, Deborah K.; Stevens, Wendy] Univ Witwatersrand, Natl Hlth Lab Serv, ZA-2001 Johannesburg, South Africa.
   [Hunt, Gillian; Morris, Lynn] Natl Inst Communicable Dis, Johannesburg, South Africa.
   [Fox, Lawrence] NIAID, Div Aids, NIH, DHHS, Bethesda, MD 20892 USA.
RP Firnhaber, C (reprint author), Univ Witwatersrand, Dept Med, Fac Hlth Sci, Clin HIV Res Unit, ZA-2001 Johannesburg, South Africa.
EM montaner@wistar.org
OI , Lynn/0000-0003-3961-7828
FU NIH/NIAID [UO1AI51986, RO1 AI056983]; Philadelphia Foundation;
   Stengel-Miller family; Commonwealth of Pennsylvania; Pennsylvania
   Department of Health; Cancer Center Grant [P30 CA10815]
FX This work was partially supported by: NIH/NIAID grant UO1AI51986 to LJM;
   and NIH/NIAID grant RO1 AI056983 to ASF. Additional support was provided
   by The Philadelphia Foundation (Robert I. Jacobs Fund), The
   Stengel-Miller family, AIDS funds from the Commonwealth of Pennsylvania
   and from the Commonwealth Universal Research Enhancement Program,
   Pennsylvania Department of Health, as well as by a Cancer Center Grant
   (P30 CA10815). The funders had no role in study design, data collection
   and analysis, decision to publish, or preparation of the manuscript.
NR 33
TC 5
Z9 5
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 JUN 28
PY 2011
VL 6
IS 6
AR e21450
DI 10.1371/journal.pone.0021450
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 784FW
UT WOS:000292142800024
PM 21738668
ER

PT J
AU Lim, PH
   Pisat, NP
   Gadhia, N
   Pandey, A
   Donovan, FX
   Stein, L
   Salt, DE
   Eide, DJ
   MacDiarmid, CW
AF Lim, Phaik Har
   Pisat, Nilambari P.
   Gadhia, Nidhi
   Pandey, Abhinav
   Donovan, Frank X.
   Stein, Lauren
   Salt, David E.
   Eide, David J.
   MacDiarmid, Colin W.
TI Regulation of Alr1 Mg Transporter Activity by Intracellular Magnesium
SO PLOS ONE
LA English
DT Article
ID YEAST PLASMA-MEMBRANE; UBIQUITIN-PROTEIN LIGASE; ZRT1 ZINC TRANSPORTER;
   AMINO-ACID PERMEASE; SACCHAROMYCES-CEREVISIAE; ACTIN CYTOSKELETON; GENE
   ENCODES; LACZ FUSIONS; METAL-IONS; SYSTEM
AB Mg homeostasis is critical to eukaryotic cells, but the contribution of Mg transporter activity to homeostasis is not fully understood. In yeast, Mg uptake is primarily mediated by the Alr1 transporter, which also allows low affinity uptake of other divalent cations such as Ni(2+), Mn(2+), Zn(2+) and Co(2+). Using Ni(2+) uptake to assay Alr1 activity, we observed approximately ninefold more activity under Mg-deficient conditions. The mnr2 mutation, which is thought to block release of vacuolar Mg stores, was associated with increased Alr1 activity, suggesting Alr1 was regulated by intracellular Mg supply. Consistent with a previous report of the regulation of Alr1 expression by Mg supply, Mg deficiency and the mnr2 mutation both increased the accumulation of a carboxy-terminal epitope-tagged version of the Alr1 protein (Alr1-HA). However, Mg supply had little effect on ALR1 promoter activity or mRNA levels. In addition, while Mg deficiency caused a seven-fold increase in Alr1-HA accumulation, the N-terminally tagged and untagged Alr1 proteins increased less than two-fold. These observations argue that the Mg-dependent accumulation of the C-terminal epitope-tagged protein was primarily an artifact of its modification. Plasma membrane localization of YFP-tagged Alr1 was also unaffected by Mg supply, indicating that a change in Alr1 location did not explain the increased activity we observed. We conclude that variation in Alr1 protein accumulation or location does not make a substantial contribution to its regulation by Mg supply, suggesting Alr1 activity is directly regulated via as yet unknown mechanisms.
C1 [Lim, Phaik Har] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
   [Pisat, Nilambari P.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
   [Gadhia, Nidhi] Regeneron Pharmaceut Inc, Dept Pharmacol & Pharmacokinet, Tarrytown, NY 10591 USA.
   [Pandey, Abhinav] Univ Utrecht, Fac Sci, Bijvoet Ctr Biomol Res, Utrecht, Netherlands.
   [Donovan, Frank X.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Stein, Lauren] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Wauwatosa, WI USA.
   [Salt, David E.] Univ Aberdeen, Sch Biol Sci, Aberdeen, Scotland.
   [Eide, David J.; MacDiarmid, Colin W.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA.
RP Lim, PH (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
EM macdiarmid@nutrisci.wisc.edu
FU National Institutes of Health [GM056285]; University of Missouri
   Research Board
FX This work was supported by the National Institutes of Health (grant #
   GM056285 to DE) and the University of Missouri Research Board. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 87
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U1 2
U2 8
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 JUN 28
PY 2011
VL 6
IS 6
AR e20896
DI 10.1371/journal.pone.0020896
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 784FW
UT WOS:000292142800006
PM 21738593
ER

PT J
AU Meza-Carmen, V
   Pacheco-Rodriguez, G
   Kang, GS
   Kato, J
   Donati, C
   Zhang, CY
   Vichi, A
   Payne, DM
   El-Chemaly, S
   Stylianou, M
   Moss, J
   Vaughan, M
AF Meza-Carmen, Victor
   Pacheco-Rodriguez, Gustavo
   Kang, Gi Soo
   Kato, Jiro
   Donati, Chiara
   Zhang, Chun-Yi
   Vichi, Alessandro
   Payne, D. Michael
   El-Chemaly, Souheil
   Stylianou, Mario
   Moss, Joel
   Vaughan, Martha
TI Regulation of growth factor receptor degradation by ADP-ribosylation
   factor domain protein (ARD) 1
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE tyrosine receptors; ubiquitination
ID TGF-BETA RECEPTOR; EGF RECEPTOR; DOWN-REGULATION; CYTOHESIN-1;
   ENDOCYTOSIS; ACTIVATION; VESICLE; BINDING; CELLS; IDENTIFICATION
AB ADP-ribosylation factor domain protein 1 (ARD1) is a 64-kDa protein containing a functional ADP-ribosylation factor (GTP hydrolase, GTPase), GTPase-activating protein, and E3 ubiquitin ligase domains. ARD1 activation by the guanine nucleotide-exchange factor cytohesin-1 was known. GTPase and E3 ligase activities of ARD1 suggest roles in protein transport and turnover. To explore this hypothesis, we used mouse embryo fibroblasts (MEFs) from ARD1-/-mice stably transfected with plasmids for inducible expression of wild-type ARD1 protein (KO-WT), or ARD1 protein with inactivating mutations in E3 ligase domain (KO-E3), or containing persistently active GTP-bound (KO-GTP), or inactive GDP-bound (KO-GDP) GTPase domains. Inhibition of proteasomal proteases in mifepristone-induced KO-WT, KO-GDP, or KO-GTP MEFs resulted in accumulation of these ARD1 proteins, whereas KO-E3 accumulated without inhibitors. All data were consistent with the conclusion that ARD1 regulates its own steady-state levels in cells by autoubiquitination. Based on reported growth factor receptor-cytohesin interactions, EGF receptor (EGFR) was investigated in induced MEFs. Amounts of cell-surface and total EGFR were higher in KO-GDP and lower in KO-GTP than in KO-WT MEFs, with levels in both mutants greater (p = 0.001) after proteasomal inhibition. Significant differences among MEF lines in content of TGF-beta receptor III were similar to those in EGFR, albeit not as large. Differences in amounts of insulin receptor mirrored those in EGFR, but did not reach statistical significance. Overall, the capacity of ARD1 GTPase to cycle between active and inactive forms and its autoubiquitination both appear to be necessary for the appropriate turnover of EGFR and perhaps additional growth factor receptors.
C1 [Meza-Carmen, Victor; Pacheco-Rodriguez, Gustavo; Kang, Gi Soo; Kato, Jiro; Donati, Chiara; Zhang, Chun-Yi; Vichi, Alessandro; Payne, D. Michael; El-Chemaly, Souheil; Stylianou, Mario; Moss, Joel; Vaughan, Martha] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Vaughan, M (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM vaughanm@nhlbi.nih.gov
OI MEZA-CARMEN, VICTOR/0000-0003-2838-7211
FU National Institutes of Health, NHLBI
FX We thank Drs. Christian Combs and Daniela Malide from the light
   microscopy core facility National Institutes of Health, National Heart,
   Lung, and Blood Institute (NHLBI). The research was supported by the
   Intramural Research Program of the National Institutes of Health, NHLBI.
NR 37
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Z9 1
U1 1
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 28
PY 2011
VL 108
IS 26
BP 10454
EP 10459
DI 10.1073/pnas.1103867108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785SX
UT WOS:000292251000023
PM 21653881
ER

PT J
AU Lim, JC
   You, Z
   Kim, G
   Levine, RL
AF Lim, Jung Chae
   You, Zheng
   Kim, Geumsoo
   Levine, Rodney L.
TI Methionine sulfoxide reductase A is a stereospecific methionine oxidase
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID PROTEIN-BOUND METHIONINE; GLUTAMINE-SYNTHETASE; OXIDATIVE STRESS;
   NEISSERIA-MENINGITIDIS; ANTIOXIDANT DEFENSE; ESCHERICHIA-COLI;
   MECHANISM; RESIDUES; THIOLS; ENZYME
AB Methionine sulfoxide reductase A (MsrA) catalyzes the reduction of methionine sulfoxide to methionine and is specific for the S epimer of methionine sulfoxide. The enzyme participates in defense against oxidative stresses by reducing methionine sulfoxide residues in proteins back to methionine. Because oxidation of methionine residues is reversible, this covalent modification could also function as a mechanism for cellular regulation, provided there exists a stereospecific methionine oxidase. We show that MsrA itself is a stereospecific methionine oxidase, producing S-methionine sulfoxide as its product. MsrA catalyzes its own autooxidation as well as oxidation of free methionine and methionine residues in peptides and proteins. When functioning as a reductase, MsrA fully reverses the oxidations which it catalyzes.
C1 [Lim, Jung Chae; You, Zheng; Kim, Geumsoo; Levine, Rodney L.] NHLBI, Biochem Lab, Bethesda, MD 20892 USA.
RP Levine, RL (reprint author), NHLBI, Biochem Lab, Bldg 3, Bethesda, MD 20892 USA.
EM rlevine@nih.gov
RI Levine, Rodney/D-9885-2011
FU Intramural Research Division of the National Heart, Lung, and Blood
   Institute
FX This research was supported by the Intramural Research Division of the
   National Heart, Lung, and Blood Institute.
NR 44
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U1 1
U2 14
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 28
PY 2011
VL 108
IS 26
BP 10472
EP 10477
DI 10.1073/pnas.1101275108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785SX
UT WOS:000292251000026
PM 21670260
ER

PT J
AU Park, HW
   Kim, JY
   Choi, SK
   Lee, YH
   Zeng, WZ
   Kim, KH
   Muallem, S
   Lee, MG
AF Park, Hyun Woo
   Kim, Joo Young
   Choi, Soo-Kyoung
   Lee, Young-Ho
   Zeng, Weizhong
   Kim, Kyung Hwan
   Muallem, Shmuel
   Lee, Min Goo
TI Serine-threonine kinase with-no-lysine 4 (WNK4) controls blood pressure
   via transient receptor potential canonical 3 (TRPC3) in the vasculature
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID CARDIAC-HYPERTROPHY; HUMAN HYPERTENSION; TYPE-3 CHANNELS; SMOOTH-MUSCLE;
   DISEASE; COTRANSPORT; ACTIVATION; MECHANISMS; EXPRESSION; TRANSPORT
AB Mutations in the serine-threonine kinase with-no-lysine 4 (WNK4) cause pseudohypoaldosteronism type 2 (PHAII), a Mendelian form of human hypertension. WNK4 regulates diverse ion transporters in the kidney, and dysregulation of renal transporters is considered the main cause of the WNK4 mutation-associated hypertension. Another determinant of hypertension is vascular tone that is regulated by Ca(2+)-dependent blood vessel constriction. However, the role of WNK4 in vasoconstriction as part of its function to regulate blood pressure is not known. Here, we report that WNK4 is a unique modulator of blood pressure by restricting Ca(2+) influx via the transient receptor potential canonical 3 (TRPC3) channel in the vasculature. Loss of WNK4 markedly augmented TRPC3-mediated Ca(2+) influx in vascular smooth muscle cells (VSMCs) in response to a-adrenoreceptor stimulation, which is the pathological hallmark of hypertension in resistance arteries. Notably, WNK4 depletion induced hypertrophic cell growth in VSMCs and increased vasoconstriction in small mesenteric arteries via TRPC3-mediated Ca(2+) influx. In addition, WNK4 mutants harboring the Q562E PHAII-causing or the D318A kinase-inactive mutation failed to mediate TRPC3 inhibition. These results define a previously undescribed function of WNK4 and reveal a unique therapeutic target to control blood pressure in WNK4-related hypertension.
C1 [Park, Hyun Woo; Kim, Joo Young; Kim, Kyung Hwan; Lee, Min Goo] Yonsei Univ, Coll Med, Dept Pharmacol, Brain Korea Project Med Sci 21,Severance Biomed S, Seoul 120752, South Korea.
   [Choi, Soo-Kyoung; Lee, Young-Ho] Yonsei Univ, Coll Med, Dept Physiol, Seoul 120752, South Korea.
   [Zeng, Weizhong] Univ Texas SW Med Ctr Dallas, Dept Physiol, Dallas, TX 75235 USA.
   [Muallem, Shmuel] Natl Inst Dent & Craniofacial Res, Epithelial Signaling & Transport Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Lee, MG (reprint author), Yonsei Univ, Coll Med, Dept Pharmacol, Brain Korea Project Med Sci 21,Severance Biomed S, Seoul 120752, South Korea.
EM mlee@yuhs.ac
RI Lee, Min Goo/D-5635-2012
OI Lee, Min Goo/0000-0001-7436-012X
FU Korean Ministry of Education, Science, and Technology [2010-0001670,
   2010-0017752, 2007-0054658]; Yonsei University College of Medicine
FX We thank Dr. D. G. Welsh for technical advice on the reversible
   permeabilization procedure and the Yonsei-Carl Zeiss Advanced Imaging
   Center for technical assistance. This work was supported by National
   Research Foundation of Korea (NRF) Grants 2010-0001670 and 2010-0017752
   (to M. G. L.) and 2007-0054658 (to J.Y.K.), which were funded by the
   Korean Ministry of Education, Science, and Technology. M. G. L. was
   supported by the faculty research program of Yonsei University College
   of Medicine.
NR 36
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U1 0
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 28
PY 2011
VL 108
IS 26
BP 10750
EP 10755
DI 10.1073/pnas.1104271108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 785SX
UT WOS:000292251000073
PM 21670282
ER

PT J
AU Read, AF
   Day, T
   Huijben, S
AF Read, Andrew F.
   Day, Troy
   Huijben, Silvie
TI The evolution of drug resistance and the curious orthodoxy of aggressive
   chemotherapy
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE antibiotic resistance; evolutionary medicine; Plasmodium; patient
   treatment regimens; long-course chemotherapy
ID DIVERSE MALARIA INFECTIONS; PLASMODIUM-CHABAUDI INFECTIONS;
   MIXED-GENOTYPE INFECTIONS; WESTERN KENYA HIGHLANDS; ANTIMICROBIAL
   RESISTANCE; POPULATION-DYNAMICS; PYRIMETHAMINE RESISTANCE;
   CLOSTRIDIUM-DIFFICILE; ANTIBIOTIC-RESISTANCE; TRANSMISSION SUCCESS
AB The evolution of drug-resistant pathogens is a major challenge for 21st century medicine. Drug use practices vigorously advocated as resistance management tools by professional bodies, public health agencies, and medical schools represent some of humankind's largest attempts to manage evolution. It is our contention that these practices have poor theoretical and empirical justification for a broad spectrum of diseases. For instance, rapid elimination of pathogens can reduce the probability that de novo resistance mutations occur. This idea often motivates the medical orthodoxy that patients should complete drug courses even when they no longer feel sick. Yet "radical pathogen cure" maximizes the evolutionary advantage of any resistant pathogens that are present. It could promote the very evolution it is intended to retard. The guiding principle should be to impose no more selection than is absolutely necessary. We illustrate these arguments in the context of malaria; they likely apply to a wide range of infections as well as cancer and public health insecticides. Intuition is unreliable even in simple evolutionary contexts; in a social milieu where in-host competition can radically alter the fitness costs and benefits of resistance, expert opinion will be insufficient. An evidence-based approach to resistance management is required.
C1 [Read, Andrew F.; Huijben, Silvie] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA.
   [Read, Andrew F.; Huijben, Silvie] Penn State Univ, Ctr Infect Dis Dynam, Dept Entomol, University Pk, PA 16802 USA.
   [Read, Andrew F.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Day, Troy] Queens Univ, Dept Math, Kingston, ON K7L 3N6, Canada.
   [Day, Troy] Queens Univ, Dept Stat, Kingston, ON K7L 3N6, Canada.
   [Day, Troy] Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada.
RP Read, AF (reprint author), Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA.
EM a.read@psu.edu
FU National Institute of General Medical Sciences [R01GM089932]; National
   Institute of Allergy and Infectious Diseases [R01AI089819, U19AI089676];
   Wissenschaftskolleg zu Berlin
FX Our arguments benefited from discussion with V. Barclay, C. Bergstrom,
   S. Bonhoeffer, N. Colegrave, M. Ferdig, A. Griffin, J. Hansen, J.
   Juliano, M. Laufer, B. Levin, J. Lloyd Smith, M. Mackinnon, S. Meshnick,
   N. Mideo, S. Nee, R. Paul, J. de Roode, P. Schneider, F. Taddei, and A.
   Wargo, not all of whom agree with our conclusions. We thank J.
   Antonovics, A. Bell, K. Foster, M. Greischar, S. Reece, and an anonymous
   referee for comments on the manuscript and members of the Research and
   Policy in Infectious Disease Dynamics Program of the Science and
   Technology Directorate, Department of Homeland Security, and the Fogarty
   International Center, National Institutes of Health, for stimulating
   discussion. Award R01GM089932 from the National Institute of General
   Medical Sciences supported the empirical work reported here; work under
   Awards R01AI089819 and U19AI089676 from the National Institute of
   Allergy and Infectious Diseases contributed to conceptual development.
   This work greatly benefited from a Fellowship to A. F. R. at the
   Wissenschaftskolleg zu Berlin.
NR 98
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U1 2
U2 47
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 28
PY 2011
VL 108
SU 2
BP 10871
EP 10877
DI 10.1073/pnas.1100299108
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 784EE
UT WOS:000292137100012
PM 21690376
ER

PT J
AU Uldrick, TS
   Whitby, D
AF Uldrick, Thomas S.
   Whitby, Denise
TI Update on KSHV epidemiology, Kaposi Sarcoma pathogenesis, and treatment
   of Kaposi Sarcoma
SO CANCER LETTERS
LA English
DT Review
DE KSHV; Kaposis Sarcoma; Transmission; Pathogenesis; Treatment
ID PEGYLATED-LIPOSOMAL DOXORUBICIN; HUMAN-IMMUNODEFICIENCY-VIRUS;
   ENDOTHELIAL GROWTH-FACTOR; ACTIVE ANTIRETROVIRAL THERAPY;
   PROTEIN-COUPLED RECEPTOR; PRIMARY EFFUSION LYMPHOMA; MULTICENTRIC
   CASTLEMANS-DISEASE; VASCULAR-PERMEABILITY FACTOR; SOUTH-AFRICAN
   POPULATION; HUMAN-HERPESVIRUS TYPE-8
AB Much has been learned since the discovery of KSHV in 1994 about its epidemiology and pathology but much of what has been learned has yet to be translated into clinical practice. In this review, we survey the current state of knowledge on KSHV epidemiology and KS pathogenesis and highlight therapeutic opportunities in both the developed and developing world. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
C1 [Uldrick, Thomas S.] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
   [Whitby, Denise] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA.
RP Uldrick, TS (reprint author), NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
EM uldrickts@mail.nih.gov; whitbyd@mail.nih.gov
FU National Cancer Institute, National Institutes of Health [N01-CO-12400];
   National Cancer Institute
FX We thank Robert Yarchoan and Mark N. Polizzotto for helpful discussion.
   This work has been funded in part with federal funds from the National
   Cancer Institute, National Institutes of Health, under Contract
   N01-CO-12400 and by the Intramural Research Program of the National
   Cancer Institute.
NR 143
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U1 0
U2 12
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 JUN 28
PY 2011
VL 305
IS 2
SI SI
BP 150
EP 162
DI 10.1016/j.canlet.2011.02.006
PG 13
WC Oncology
SC Oncology
GA 770JB
UT WOS:000291081700007
PM 21377267
ER

PT J
AU Pichu, S
   Yalcin, EB
   Ribeiro, JMC
   King, RS
   Mather, TN
AF Pichu, Sivakamasundari
   Yalcin, Emine B.
   Ribeiro, Jose M. C.
   King, Roberta S.
   Mather, Thomas N.
TI Molecular characterization of novel sulfotransferases from the tick,
   Ixodes scapularis
SO BMC BIOCHEMISTRY
LA English
DT Article
ID SUBMANDIBULAR SALIVARY-GLANDS; TYROSYLPROTEIN SULFOTRANSFERASE;
   CAENORHABDITIS-ELEGANS; AMBLYOMMA-AMERICANUM; BOOPHILUS-MICROPLUS;
   MONOAMINE-OXIDASE; CATTLE TICK; EXPRESSION; SULFATION; CLONING
AB Background: Ixodes scapularis, commonly known as the blacklegged or deer tick, is the main vector of Lyme disease in the United States. Recent progress in transcriptome research has uncovered hundreds of different proteins expressed in the salivary glands of hard ticks, the majority of which have no known function, and include many novel protein families. We recently identified transcripts coding for two putative cytosolic sulfotransferases in these ticks which recognized phenolic monoamines as their substrates. In this current study, we characterize the genetic expression of these two cytosolic sulfotransferases throughout the tick life cycle as well as the enzymatic properties of the corresponding recombinant proteins. Interestingly, the resultant recombinant proteins showed sulfotransferase activity against both neurotransmitters dopamine and octopamine.
   Results: The two sulfotransferase genes were coded as Ixosc SULT 1 & 2 and corresponding proteins were referred as Ixosc Sult 1 and 2. Using gene-specific primers, the sulfotransferase transcripts were detected throughout the blacklegged tick life cycle, including eggs, larvae, nymphs, adult salivary glands and adult midgut. Notably, the mRNA and protein levels were altered upon feeding during both the larval and nymphal life stages. Quantitative PCR results confirm that Ixosc SULT1 was statistically increased upon blood feeding while Ixosc SULT 2 was decreased. This altered expression led us to further characterize the function of these proteins in the Ixodid tick. The sulfotransferase genes were cloned and expressed in a bacterial expression system, and purified recombinant proteins Ixosc Sult 1( R) and 2( R) showed sulfotransferase activity against neurotransmitters dopamine and octopamine as well as the common sulfotransferase substrate p-nitrophenol. Thus, dopamine-or octopamine-sulfonation may be involved in altering the biological signal for salivary secretion in I. scapularis.
   Conclusions: Collectively, these results suggest that a function of Ixosc Sult 1 and Sult 2 in Ixodid tick salivary glands may include inactivation of the salivation signal via sulfonation of dopamine or octopamine.
C1 [Pichu, Sivakamasundari; Mather, Thomas N.] Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 USA.
   [Yalcin, Emine B.; King, Roberta S.] Univ Rhode Isl, Dept Biomed & Pharmaceut Sci, Coll Pharm, Kingston, RI 02881 USA.
   [Ribeiro, Jose M. C.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Pichu, S (reprint author), Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 USA.
EM au_sudha@yahoo.com
RI King, Roberta/A-1749-2010; 
OI King, Roberta/0000-0002-3550-4255; Ribeiro, Jose/0000-0002-9107-0818
FU National Institute of Health [RO1 AI 37230, U19 AI 082642]; Division of
   Intramural Research, National Institute of Allergy and Infectious
   Diseases, NIH; URI; RI-BRIN and RI-INBRE (NIH) [P20 RR16457]
FX We are particularly grateful to Nathan Miller, Drs. Marta Gomez-Chiarri,
   Wendy M. Coy, Shahid Karim and Assem Sayedahmed for helpful technical
   discussions. This work was supported in part by National Institute of
   Health grants RO1 AI 37230 and U19 AI 082642 (TNM), a subcontract to
   USDA Special Grant 2006-34438-17306 (TNM), and by the Division of
   Intramural Research, National Institute of Allergy and Infectious
   Diseases, NIH (JMCR). Experiments were supported by the URI Proteomics
   Core facility, made available by the RI-BRIN and RI-INBRE (NIH award P20
   RR16457). Because JMCR is a government employee and this is a government
   work, the work is in the public domain in the United States.
   Notwithstanding any other agreements, the NIH reserves the right to
   provide the work to PubMedCentral for display and use by the public, and
   PubMedCentral may tag or modify the work consistent with its customary
   practices. You can establish rights outside of the U.S. subject to a
   government use license. It is contribution number 5133 of the Rhode
   Island Agricultural Experiment Station.
NR 49
TC 9
Z9 9
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2091
J9 BMC BIOCHEM
JI BMC Boichem.
PD JUN 27
PY 2011
VL 12
AR 32
DI 10.1186/1471-2091-12-32
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 803FG
UT WOS:000293566500001
PM 21708020
ER

PT J
AU Colloca, L
   Miller, FG
AF Colloca, Luana
   Miller, Franklin G.
TI Harnessing the placebo effect: the need for translational research
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE clinical practice; patient-doctor relationship; placebo theory; ethics;
   expectation; nocebo
ID TRIALS COMPARING PLACEBO; IRRITABLE-BOWEL-SYNDROME; OPEN-LABEL USE;
   CLINICAL-PRACTICE; ADVERSE EVENTS; NO TREATMENT; NOCEBO; PAIN;
   ANALGESIA; HUMANS
AB Laboratory research recently has greatly enhanced the understanding of placebo and nocebo effects by identifying specific neuromodulators and brain areas associated with them. However, little progress has been made in translating this knowledge into improved patient care. Here, we discuss the limitations in our knowledge about placebo (and nocebo) effects and the need for translational research with the aim of guiding physicians in maximizing placebo effects and minimizing nocebo effects in their routine clinical practice. We suggest some strategies for how, when and why interventions to promote beneficial placebo responses might be administered in the clinical setting.
C1 [Colloca, Luana] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
   [Colloca, Luana; Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Colloca, L (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA.
EM luana.colloca@nih.gov
OI Colloca, Luana/0000-0002-6503-4709
FU Clinical Center, NIH; National Center for Complementary and Alternative
   Medicine, International Association; EFIC-EGG
FX The opinions expressed are the views of the authors and do not
   necessarily reflect the policy of the National Institutes of Health, the
   Public Health Service, or the U.S. Department of Health and Human
   Services. This research was supported by the Intramural Research Program
   of the Clinical Center, NIH, the National Center for Complementary and
   Alternative Medicine, International Association for Study of Pain (Early
   Research Grant), and EFIC-EGG Grant.
NR 63
TC 42
Z9 45
U1 1
U2 26
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD JUN 27
PY 2011
VL 366
IS 1572
BP 1922
EP 1930
DI 10.1098/rstb.2010.0399
PG 9
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 764GM
UT WOS:000290617600017
PM 21576150
ER

PT J
AU Park, Y
   Subar, AF
   Hollenbeck, A
   Schatzkin, A
AF Park, Yikyung
   Subar, Amy F.
   Hollenbeck, Albert
   Schatzkin, Arthur
TI Dietary Fiber Intake and Mortality in the NIH-AARP Diet and Health Study
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID CORONARY-HEART-DISEASE; RETIRED-PERSONS DIET; ALL-CAUSE MORTALITY;
   C-REACTIVE PROTEIN; REDUCED RISK; CARDIOVASCULAR-DISEASE;
   AMERICAN-ASSOCIATION; LOGISTIC-REGRESSION; NATIONAL-INSTITUTES; WOMENS
   HEALTH
AB Background: Dietary fiber has been hypothesized to lower the risk of coronary heart disease, diabetes, and some cancers. However, little is known of the effect of dietary fiber intake on total death and cause-specific deaths.
   Methods: We examined dietary fiber intake in relation to total mortality and death from specific causes in the NIH (National Institutes of Health)-AARP Diet and Health Study, a prospective cohort study. Diet was assessed using a food-frequency questionnaire at baseline. Cause of death was identified using the National Death Index Plus. Cox proportional hazard models were used to estimate relative risks and 2-sided 95% confidence intervals (CIs).
   Results: During an average of 9 years of follow-up, we identified 20 126 deaths in men and 11 330 deaths in women. Dietary fiber intake was associated with a significantly lowered risk of total death in both men and women (multivariate relative risk comparing the highest with the lowest quintile, 0.78 [95% CI, 0.73-0.82; P for trend, <.001] in men and 0.78 [95% CI, 0.73-0.85; P for trend, <.001] in women). Dietary fiber intake also lowered the risk of death from cardiovascular, infectious, and respiratory diseases by 24% to 56% in men and by 34% to 59% in women. Inverse association between dietary fiber intake and cancer death was observed in men but not in women. Dietary fiber from grains, but not from other sources, was significantly inversely related to total and cause-specific death in both men and women.
   Conclusions: Dietary fiber may reduce the risk of death from cardiovascular, infectious, and respiratory diseases. Making fiber-rich food choices more often may provide significant health benefits.
C1 [Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
   [Subar, Amy F.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
   [Hollenbeck, Albert] AARP, Washington, DC USA.
RP Park, Y (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM parkyik@mail.nih.gov
OI Park, Yikyung/0000-0002-6281-489X
FU Schatzkin; National Cancer Institute, National Institutes of Health
FX Study concept and design: Park, Hollenbeck, and Schatzkin. Acquisition
   of data: Subar, Hollenbeck, and Schatzkin. Analysis and interpretation
   of data: Park and Subar. Drafting of the manuscript: Park and Subar.
   Critical revision of the manuscript for important intellectual content:
   Park, Subar, Hollenbeck, and Schatzkin. Statistical analysis: Park.
   Obtained funding: Schatzkin. Administrative, technical, and material
   support: Park and Hollenbeck. Study supervision: Park and Schatzkin.;
   The study was supported by the Intramural Research Program of the
   National Cancer Institute, National Institutes of Health.
NR 35
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U1 1
U2 20
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD JUN 27
PY 2011
VL 171
IS 12
BP 1061
EP 1068
DI 10.1001/archinternmed.2011.18
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 783WI
UT WOS:000292114400003
PM 21321288
ER

PT J
AU Butler, LM
   Kan, HD
   London, SJ
AF Butler, Lesley M.
   Kan, Haidong
   London, Stephanie J.
TI Dietary Fiber Prevents Both Morbidity and Mortality From Respiratory
   Disease
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Butler, Lesley M.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA.
   [Kan, Haidong] Fudan Univ, Sch Publ Hlth, Shanghai 200433, Peoples R China.
   [London, Stephanie J.] NIEHS, Epidemiol Branch, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Butler, LM (reprint author), Colorado State Univ, Dept Environm & Radiol Hlth Sci, 1681 Campus Delivery, Ft Collins, CO 80523 USA.
EM lesley.butler@colostate.edu
OI London, Stephanie/0000-0003-4911-5290
NR 3
TC 0
Z9 1
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD JUN 27
PY 2011
VL 171
IS 12
BP 1123
EP 1123
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 783WI
UT WOS:000292114400020
PM 21709119
ER

PT J
AU Schnabel, RB
   Benjamin, EJ
   Gudnason, V
   Heckbert, SR
AF Schnabel, Renate B.
   Benjamin, Emelia J.
   Gudnason, Vilmundur
   Heckbert, Susan R.
TI Improving the Prediction of Incident Atrial Fibrillation Reply
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
ID VARIANTS; RISK
C1 [Heckbert, Susan R.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA.
   [Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Dept Med 2, Mainz, Germany.
   [Schnabel, Renate B.; Benjamin, Emelia J.] NHLBI, Framingham Study, Framingham, MA USA.
   [Gudnason, Vilmundur] Univ Iceland, Iceland Heart Assoc, Heart Prevent Clin & Res Inst, Reykjavik, Iceland.
   [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
   [Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Mem Med Dept,Cardiol Sect,Prevent Med Dept, Boston, MA 02118 USA.
   [Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
RP Heckbert, SR (reprint author), Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, 1730 Minor Ave,Ste 1360, Seattle, WA 98101 USA.
EM heckbert@u.washington.edu
RI Gudnason, Vilmundur/K-6885-2015
OI Gudnason, Vilmundur/0000-0001-5696-0084
NR 4
TC 0
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U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD JUN 27
PY 2011
VL 171
IS 12
BP 1125
EP 1125
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 783WI
UT WOS:000292114400025
ER

PT J
AU Ishikawa, M
   Iwamoto, T
   Nakamura, T
   Doyle, A
   Fukumoto, S
   Yamada, Y
AF Ishikawa, Masaki
   Iwamoto, Tsutomu
   Nakamura, Takashi
   Doyle, Andrew
   Fukumoto, Satoshi
   Yamada, Yoshihiko
TI Pannexin 3 functions as an ER Ca2+ channel, hemichannel, and gap
   junction to promote osteoblast differentiation
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID CELL-CELL COMMUNICATION; BONE-FORMATION; KINASE-II; CHONDROCYTE
   DIFFERENTIATION; SKELETAL DEVELOPMENT; CONNEXIN FAMILY; EXPRESSION;
   GROWTH; CALMODULIN; RECEPTORS
AB The pannexin proteins represent a new gap junction family. However, the cellular functions of pannexins remain largely unknown. Here, we demonstrate that pannexin 3 (Panx3) promotes differentiation of osteoblasts and ex vivo growth of metatarsals. Panx3 expression was induced during osteogenic differentiation of C2C12 cells and primary calvarial cells, and suppression of this endogenous expression inhibited differentiation. Panx3 functioned as a unique Ca2+ channel in the endoplasmic reticulum (ER), which was activated by purinergic receptor/phosphoinositide 3-kinase (PI3K)/Akt signaling, followed by activation of calmodulin signaling for differentiation. Panx3 also formed hemichannels that allowed release of ATP into the extracellular space and activation of purinergic receptors with the subsequent activation of PI3K-Akt signaling. Panx3 also formed gap junctions and propagated Ca2+ waves between cells. Blocking the Panx3 Ca2+ channel and gap junction activities inhibited osteoblast differentiation. Thus, Panx3 appears to be a new regulator that promotes osteoblast differentiation by functioning as an ER Ca2+ channel and a hemichannel, and by forming gap junctions.
C1 [Ishikawa, Masaki; Iwamoto, Tsutomu; Nakamura, Takashi; Doyle, Andrew; Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
   [Iwamoto, Tsutomu; Nakamura, Takashi; Fukumoto, Satoshi] Tohoku Univ, Dept Pediat Dent, Grad Sch Dent, Sendai, Miyagi 9808576, Japan.
RP Yamada, Y (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM yoshi.yamada@nih.gov
RI Nakamura, Takashi/P-7796-2016
OI Nakamura, Takashi/0000-0001-9904-1037
FU National Institute of Dental and Craniofacial Research, National
   Institutes of Health; Ministry of Education, Science, and Culture of
   Japan [20791583, 20679006]; Japan Society for the Promotion of Science
FX This work was supported by the Intramural Program of the National
   Institute of Dental and Craniofacial Research, National Institutes of
   Health (to Y. Yamada), and grant-in-aids (20791583 to T. Iwamoto) and
   (20679006 to S. Fukumoto) from the Ministry of Education, Science, and
   Culture of Japan. M. Ishikawa was supported in part by a Fellowship from
   the Japan Society for the Promotion of Science.
NR 66
TC 96
Z9 97
U1 1
U2 12
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD JUN 27
PY 2011
VL 193
IS 7
BP 1257
EP 1274
DI 10.1083/jcb.201101050
PG 18
WC Cell Biology
SC Cell Biology
GA 784DS
UT WOS:000292135400012
PM 21690309
ER

PT J
AU Delorme-Walker, VD
   Peterson, JR
   Chernoff, J
   Waterman, CM
   Danuser, G
   DerMardirossian, C
   Bokoch, GM
AF Delorme-Walker, Violaine D.
   Peterson, Jeffrey R.
   Chernoff, Jonathan
   Waterman, Clare M.
   Danuser, Gaudenz
   DerMardirossian, Celine
   Bokoch, Gary M.
TI Pak1 regulates focal adhesion strength, myosin IIA distribution, and
   actin dynamics to optimize cell migration
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID FLUORESCENT SPECKLE MICROSCOPY; BREAST-CANCER CELLS; LIGHT-CHAIN KINASE;
   P21-ACTIVATED KINASE; LIVING CELLS; MATRIX ADHESIONS; LEADING-EDGE;
   HELA-CELLS; F-ACTIN; PROTRUSION
AB Cell motility requires the spatial and temporal coordination of forces in the actomyosin cytoskeleton with extracellular adhesion. The biochemical mechanism that coordinates filamentous actin (F-actin) assembly, myosin contractility, adhesion dynamics, and motility to maintain the balance between adhesion and contraction remains unknown. In this paper, we show that p21-activated kinases (Paks), downstream effectors of the small guanosine triphosphatases Rac and Cdc42, biochemically couple leading-edge actin dynamics to focal adhesion (FA) dynamics. Quantitative live cell microscopy assays revealed that the inhibition of Paks abolished F-actin flow in the lamella, displaced myosin IIA from the cell edge, and decreased FA turnover. We show that, by controlling the dynamics of these three systems, Paks regulate the protrusive activity and migration of epithelial cells. Furthermore, we found that expressing Pak1 was sufficient to overcome the inhibitory effects of excess adhesion strength on cell motility. These findings establish Paks as critical molecules coordinating cytoskeletal systems for efficient cell migration.
C1 [Delorme-Walker, Violaine D.; DerMardirossian, Celine; Bokoch, Gary M.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
   [Delorme-Walker, Violaine D.; DerMardirossian, Celine; Bokoch, Gary M.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA.
   [Peterson, Jeffrey R.; Chernoff, Jonathan] Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA.
   [Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
   [Danuser, Gaudenz] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
RP DerMardirossian, C (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
EM dmceline@scripps.edu
RI Chernoff, Jonathan/I-7631-2014; DerMardirossian, Celine/P-1020-2015; 
OI Chernoff, Jonathan/0000-0002-4803-7836; Waterman,
   Clare/0000-0001-6142-6775
FU [GM44428];  [GM39434];  [CA117884];  [DOD W81XWH-06-1-0213];  [GM071868]
FX This work was supported by grants GM44428 and GM39434 (to G.M. Bokoch
   and C. DerMardirossian), CA117884 and DOD W81XWH-06-1-0213 (to J.
   Chernoff), and GM071868 (to G. Danuser). V. D. Delorme-Walker is a
   fellow of the American Heart Association (Western States Affiliate).
NR 51
TC 51
Z9 53
U1 0
U2 17
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0021-9525
J9 J CELL BIOL
JI J. Cell Biol.
PD JUN 27
PY 2011
VL 193
IS 7
BP 1289
EP 1303
DI 10.1083/jcb.201010059
PG 15
WC Cell Biology
SC Cell Biology
GA 784DS
UT WOS:000292135400014
PM 21708980
ER

PT J
AU Venkatesan, A
   Uzasci, L
   Chen, ZH
   Rajbhandari, L
   Anderson, C
   Lee, MH
   Bianchet, MA
   Cotter, R
   Song, HJ
   Nath, A
AF Venkatesan, Arun
   Uzasci, Lerna
   Chen, Zhaohui
   Rajbhandari, Labchan
   Anderson, Carol
   Lee, Myoung-Hwa
   Bianchet, Mario A.
   Cotter, Robert
   Song, Hongjun
   Nath, Avindra
TI Impairment of adult hippocampal neural progenitor proliferation by
   methamphetamine: role for nitrotyrosination
SO MOLECULAR BRAIN
LA English
DT Article
ID PROTEIN-TYROSINE NITRATION; INDUCED DOPAMINERGIC NEUROTOXICITY; ZINC
   SUPEROXIDE-DISMUTASE; NITRIC-OXIDE; PYRUVATE-KINASE; DENTATE GYRUS;
   CELL-PROLIFERATION; SPATIAL MEMORY; STATISTICAL-MODEL; OXIDATIVE STRESS
AB Methamphetamine (METH) abuse has reached epidemic proportions, and it has become increasingly recognized that abusers suffer from a wide range of neurocognitive deficits. Much previous work has focused on the deleterious effects of METH on mature neurons, but little is known about the effects of METH on neural progenitor cells (NPCs). It is now well established that new neurons are continuously generated from NPCs in the adult hippocampus, and accumulating evidence suggests important roles for these neurons in hippocampal-dependent cognitive functions. In a rat hippocampal NPC culture system, we find that METH results in a dose-dependent reduction of NPC proliferation, and higher concentrations of METH impair NPC survival. NPC differentiation, however, is not affected by METH, suggesting cell-stage specificity of the effects of METH. We demonstrate that the effects of METH on NPCs are, in part, mediated through oxidative and nitrosative stress. Further, we identify seventeen NPC proteins that are post-translationally modified via 3-nitrotyrosination in response to METH, using mass spectrometric approaches. One such protein was pyruvate kinase isoform M2 (PKM2), an important mediator of cellular energetics and proliferation. We identify sites of PKM2 that undergo nitrotyrosination, and demonstrate that nitration of the protein impairs its activity. Thus, METH abuse may result in impaired adult hippocampal neurogenesis, and effects on NPCs may be mediated by protein nitration. Our study has implications for the development of novel therapeutic approaches for METH-abusing individuals with neurologic dysfunction and may be applicable to other neurodegenerative diseases in which hippocampal neurogenesis is impaired.
C1 [Venkatesan, Arun; Rajbhandari, Labchan; Anderson, Carol; Lee, Myoung-Hwa; Song, Hongjun; Nath, Avindra] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21287 USA.
   [Uzasci, Lerna; Chen, Zhaohui; Cotter, Robert] Johns Hopkins Univ, Middle Atlantic Mass Spectrometry Lab, Sch Med, Baltimore, MD 21287 USA.
   [Song, Hongjun] Johns Hopkins Univ, Inst Cell Engn, Sch Med, Baltimore, MD 21287 USA.
   [Song, Hongjun; Nath, Avindra] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Sch Med, Baltimore, MD 21287 USA.
   [Anderson, Carol; Lee, Myoung-Hwa; Nath, Avindra] NIH, Sect Infect Nervous Syst, Bethesda, MD 20892 USA.
RP Venkatesan, A (reprint author), Johns Hopkins Univ, Dept Neurol, Sch Med, 600 N Wolfe St, Baltimore, MD 21287 USA.
EM avenkat2@jhmi.edu
RI Bianchet, Mario/K-2131-2015
OI Bianchet, Mario/0000-0001-9032-7549
FU NIH [K08DA022946, R01DA024593, AG024984, NS047344]; Howard Hughes
   Medical Institute
FX This work was supported by NIH (K08DA022946) and Howard Hughes Medical
   Institute to A. V., NIH R01DA024593 to A.N., and NIH (AG024984,
   NS047344) to H.S.
NR 72
TC 13
Z9 13
U1 1
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-6606
J9 MOL BRAIN
JI Mol. Brain
PD JUN 27
PY 2011
VL 4
AR 28
DI 10.1186/1756-6606-4-28
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 007XJ
UT WOS:000308921400001
PM 21708025
ER

PT J
AU Chadwick, W
   Mitchell, N
   Caroll, J
   Zhou, Y
   Park, SS
   Wang, LY
   Becker, KG
   Zhang, YQ
   Lehrmann, E
   Wood, WH
   Martin, B
   Maudsley, S
AF Chadwick, Wayne
   Mitchell, Nick
   Caroll, Jenna
   Zhou, Yu
   Park, Sung-Soo
   Wang, Liyun
   Becker, Kevin G.
   Zhang, Yongqing
   Lehrmann, Elin
   Wood, William H., III
   Martin, Bronwen
   Maudsley, Stuart
TI Amitriptyline-Mediated Cognitive Enhancement in Aged 3xTg Alzheimer's
   Disease Mice Is Associated with Neurogenesis and Neurotrophic Activity
SO PLOS ONE
LA English
DT Article
ID NERVE GROWTH-FACTOR; COMMON MECHANISM; A-BETA; BRAIN; HIPPOCAMPAL;
   OLIGOMERS; MOUSE; TAU; ANGIOGENESIS; PATHOGENESIS
AB Approximately 35 million people worldwide suffer from Alzheimer's disease (AD). Existing therapeutics, while moderately effective, are currently unable to stem the widespread rise in AD prevalence. AD is associated with an increase in amyloid beta (A beta) oligomers and hyperphosphorylated tau, along with cognitive impairment and neurodegeneration. Several antidepressants have shown promise in improving cognition and alleviating oxidative stress in AD but have failed as long-term therapeutics. In this study, amitriptyline, an FDA-approved tricyclic antidepressant, was administered orally to aged and cognitively impaired transgenic AD mice (3xTgAD). After amitriptyline treatment, cognitive behavior testing demonstrated that there was a significant improvement in both long-and short-term memory retention. Amitriptyline treatment also caused a significant potentiation of non-toxic A beta monomer with a concomitant decrease in cytotoxic dimer A beta load, compared to vehicle-treated 3xTgAD controls. In addition, amitriptyline administration caused a significant increase in dentate gyrus neurogenesis as well as increases in expression of neurosynaptic marker proteins. Amitriptyline treatment resulted in increases in hippocampal brain-derived neurotrophic factor protein as well as increased tyrosine phosphorylation of its cognate receptor (TrkB). These results indicate that amitriptyline has significant beneficial actions in aged and damaged AD brains and that it shows promise as a tolerable novel therapeutic for the treatment of AD.
C1 [Chadwick, Wayne; Zhou, Yu; Park, Sung-Soo; Wang, Liyun; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA.
   [Mitchell, Nick] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
   [Caroll, Jenna] Univ Penn, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA.
   [Becker, Kevin G.; Zhang, Yongqing; Lehrmann, Elin; Wood, William H., III] NIA, Genom Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
   [Martin, Bronwen] NIA, Metab Unit, NIH, Baltimore, MD 21224 USA.
RP Chadwick, W (reprint author), NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA.
EM maudsleyst@mail.nih.gov
RI Zhou, Yu/M-7975-2014
FU National Institutes of Health
FX This work was carried out in-part by funding from the Intramural
   Research Program of the National Institutes of Health. The funders had
   no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript. No additional external
   funding received for this study.
NR 50
TC 39
Z9 39
U1 0
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 JUN 27
PY 2011
VL 6
IS 6
AR e21660
DI 10.1371/journal.pone.0021660
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 783OD
UT WOS:000292092600069
PM 21738757
ER

PT J
AU Chadwick, W
   Boyle, JP
   Zhou, Y
   Wang, LY
   Park, SS
   Martin, B
   Wang, R
   Becker, KG
   Wood, WH
   Zhang, YQ
   Peers, C
   Maudsley, S
AF Chadwick, Wayne
   Boyle, John P.
   Zhou, Yu
   Wang, Liyun
   Park, Sung-Soo
   Martin, Bronwen
   Wang, Rui
   Becker, Kevin G.
   Wood, William H., III
   Zhang, Yongqing
   Peers, Chris
   Maudsley, Stuart
TI Multiple Oxygen Tension Environments Reveal Diverse Patterns of
   Transcriptional Regulation in Primary Astrocytes
SO PLOS ONE
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; GROWTH-FACTOR RECEPTOR; DIETARY ENERGY-INTAKE;
   EXPRESSION PATTERNS; ALZHEIMERS-DISEASE; ENDOTHELIAL-CELLS;
   MOLECULAR-CLONING; OXIDATIVE STRESS; RAT-BRAIN; IN-VITRO
AB The central nervous system normally functions at O-2 levels which would be regarded as hypoxic by most other tissues. However, most in vitro studies of neurons and astrocytes are conducted under hyperoxic conditions without consideration of O-2-dependent cellular adaptation. We analyzed the reactivity of astrocytes to 1, 4 and 9% O-2 tensions compared to the cell culture standard of 20% O-2, to investigate their ability to sense and translate this O-2 information to transcriptional activity. Variance of ambient O-2 tension for rat astrocytes resulted in profound changes in ribosomal activity, cytoskeletal and energy-regulatory mechanisms and cytokine-related signaling. Clustering of transcriptional regulation patterns revealed four distinct response pattern groups that directionally pivoted around the 4% O-2 tension, or demonstrated coherent ascending/decreasing gene expression patterns in response to diverse oxygen tensions. Immune response and cell cycle/cancer-related signaling pathway transcriptomic subsets were significantly activated with increasing hypoxia, whilst hemostatic and cardiovascular signaling mechanisms were attenuated with increasing hypoxia. Our data indicate that variant O-2 tensions induce specific and physiologically-focused transcript regulation patterns that may underpin important physiological mechanisms that connect higher neurological activity to astrocytic function and ambient oxygen environments. These strongly defined patterns demonstrate a strong bias for physiological transcript programs to pivot around the 4% O-2 tension, while uni-modal programs that do not, appear more related to pathological actions. The functional interaction of these transcriptional 'programs' may serve to regulate the dynamic vascular responsivity of the central nervous system during periods of stress or heightened activity.
C1 [Chadwick, Wayne; Zhou, Yu; Wang, Liyun; Park, Sung-Soo; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA.
   [Boyle, John P.; Peers, Chris] Univ Leeds, Inst Cardiovasc Res, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England.
   [Martin, Bronwen; Wang, Rui] NIA, Metab Unit, NIH, Baltimore, MD 21224 USA.
   [Becker, Kevin G.; Wood, William H., III; Zhang, Yongqing] NIA, Gene Express & Genom Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA.
RP Chadwick, W (reprint author), NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA.
EM c.s.peers@leeds.ac.uk; maudsleyst@mail.nih.gov
RI Zhou, Yu/M-7975-2014; Boyle, John/N-4868-2016; 
OI Becker, Kevin/0000-0002-6794-6656
FU National Institute on Aging/National Institutes of Health; Alzheimer's
   Research Trust (ART/PG) [2006/1]; The Alzheimer's Society; Medical
   Research Council
FX This work was carried out by funding from the Intramural Research
   Program of the National Institute on Aging/National Institutes of
   Health, the Alzheimer's Research Trust (ART/PG 2006/1), The Alzheimer's
   Society and the Medical Research Council. The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 74
TC 13
Z9 13
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 27
PY 2011
VL 6
IS 6
AR e21638
DI 10.1371/journal.pone.0021638
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 783OD
UT WOS:000292092600067
PM 21738745
ER

PT J
AU Meissner, K
   Kohls, N
   Colloca, L
AF Meissner, Karin
   Kohls, Niko
   Colloca, Luana
TI Introduction to placebo effects in medicine: mechanisms and clinical
   implications
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Editorial Material
DE placebo; nocebo; neurobiology; psychological mechanisms; randomized
   controlled trials; clinical practice
ID CHOLECYSTOKININ ANTAGONIST PROGLUMIDE; RANDOMIZED CONTROLLED-TRIALS;
   DISPOSITIONAL OPTIMISM; PARKINSONS-DISEASE; ANALGESIC RESPONSE; POWERFUL
   PLACEBO; OPIOID SYSTEMS; PAIN; ACUPUNCTURE; NALOXONE
AB The field of placebo research has made considerable progress in the last years and it has become a major focus of interest. We know now that the placebo effect is a real neurobiological phenomenon and that the brain's 'inner pharmacy' is a critical determinant for the occurrence of psychobiological and behavioural changes relevant to healing processes and well-being. However, harnessing the advantages of placebo effects in healthcare is still a challenge. The first part of the theme issue summarizes and discusses the various kinds of placebo mechanisms across medical fields, thereby not only focusing on two main explanatory models-expectation and conditioning theory-but also taking into account empathy and social learning, emotion and motivation, spirituality and the healing ritual. The second part of the issue focuses on questions related to transferring knowledge from placebo research into clinical practice and discusses implications for the design and interpretation of clinical trials, for the therapeutic settings in daily patient care, and for future translational placebo research.
C1 [Meissner, Karin] Univ Munich, Inst Med Psychol, D-80336 Munich, Germany.
   [Meissner, Karin] Tech Univ Munich, Klinikum Rechts Isar, Inst Gen Practice, D-81776 Munich, Germany.
   [Kohls, Niko] Univ Munich, Human Sci Ctr, Generat Res Program, D-83646 Bad Tolz, Germany.
   [Kohls, Niko] Peter Schilffarth Inst Sociotechnol PSI, D-83646 Bad Tolz, Germany.
   [Kohls, Niko] Samueli Inst, Brain Mind & Healing Program, Alexandria, VA 22314 USA.
   [Colloca, Luana] NIH, Natl Ctr Alternat & Complementary Med, Bethesda, MD 20892 USA.
   [Colloca, Luana] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Meissner, K (reprint author), Univ Munich, Inst Med Psychol, Goethestr 31, D-80336 Munich, Germany.
EM karin.meissner@med.lmu.de
OI Colloca, Luana/0000-0002-6503-4709
NR 64
TC 19
Z9 22
U1 3
U2 23
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
EI 1471-2970
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD JUN 27
PY 2011
VL 366
IS 1572
BP 1783
EP 1789
DI 10.1098/rstb.2010.0414
PG 7
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 764GM
UT WOS:000290617600002
PM 21576135
ER

PT J
AU Colloca, L
   Miller, FG
AF Colloca, Luana
   Miller, Franklin G.
TI How placebo responses are formed: a learning perspective
SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Review
DE conditioning; expectation; evolution; nocebo; social learning; verbal
   suggestion
ID IRRITABLE-BOWEL-SYNDROME; SYNDROME IBS PATIENTS; PARKINSONS-DISEASE;
   ASTHMATIC SUBJECTS; AIRWAY REACTIVITY; DOPAMINE RELEASE; NOCEBO
   RESPONSES; EXPECTANCY; ANALGESIA; MECHANISMS
AB Despite growing scientific interest in the placebo effect and increasing understanding of neurobiological mechanisms, theoretical conceptualization of the placebo effect remains poorly developed. Substantial mechanistic research on this phenomenon has proceeded with little guidance by any systematic theoretical paradigm. This review seeks to present a theoretical perspective on the formation of placebo responses. We focus on information processing, and argue that different kinds of learning along with individuals' genetic make-up evolved as the proximate cause for triggering behavioural and neural mechanisms that enable the formation of individual expectations and placebo responses. Conceptualizing the placebo effect in terms of learning offers the opportunity for facilitating scientific investigation with a significant impact on medical care.
C1 [Colloca, Luana] NIH, NCCAM, Bethesda, MD 20892 USA.
   [Colloca, Luana; Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Colloca, L (reprint author), NIH, NCCAM, Bldg 10, Bethesda, MD 20892 USA.
EM luana.colloca@nih.gov
OI Colloca, Luana/0000-0002-6503-4709
FU Clinical Center, NIH; National Center for Complementary and Alternative
   Medicine (NCCAM); International Association
FX This research is supported by the Intramural Research Program of the
   Clinical Center, NIH, the National Center for Complementary and
   Alternative Medicine (NCCAM), and the International Association for
   Study of Pain (IASP, Early Research Grant).
NR 83
TC 56
Z9 58
U1 6
U2 30
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8436
J9 PHILOS T R SOC B
JI Philos. Trans. R. Soc. B-Biol. Sci.
PD JUN 27
PY 2011
VL 366
IS 1572
BP 1859
EP 1869
DI 10.1098/rstb.2010.0398
PG 11
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 764GM
UT WOS:000290617600010
PM 21576143
ER

PT J
AU Cockrell, AS
   van Praag, H
   Santistevan, N
   Ma, H
   Kafri, T
AF Cockrell, Adam S.
   van Praag, Henriette
   Santistevan, Nicholas
   Ma, Hong
   Kafri, Tal
TI The HIV-1 Rev/RRE system is required for HIV-1 5 ' UTR cis elements to
   augment encapsidation of heterologous RNA into HIV-1 viral particles
SO RETROVIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; HIGH-TITER;
   LENTIVIRAL VECTORS; NUCLEAR EXPORT; PACKAGING SIGNALS; GENE-THERAPY;
   GENOMIC RNA; CELL-LINE; REV
AB Background: The process of HIV-1 genomic RNA (gRNA) encapsidation is governed by a number of viral encoded components, most notably the Gag protein and gRNA cis elements in the canonical packaging signal (psi). Also implicated in encapsidation are cis determinants in the R, U5, and PBS (primer binding site) from the 5' untranslated region (UTR). Although conventionally associated with nuclear export of HIV-1 RNA, there is a burgeoning role for the Rev/RRE in the encapsidation process. Pleiotropic effects exhibited by these cis and trans viral components may confound the ability to examine their independent, and combined, impact on encapsidation of RNA into HIV-1 viral particles in their innate viral context. We systematically reconstructed the HIV-1 packaging system in the context of a heterologous murine leukemia virus (MLV) vector RNA to elucidate a mechanism in which the Rev/RRE system is central to achieving efficient and specific encapsidation into HIV-1 viral particles.
   Results: We show for the first time that the Rev/RRE system can augment RNA encapsidation independent of all cis elements from the 5' UTR (R, U5, PBS, and psi). Incorporation of all the 5' UTR cis elements did not enhance RNA encapsidation in the absence of the Rev/RRE system. In fact, we demonstrate that the Rev/RRE system is required for specific and efficient encapsidation commonly associated with the canonical packaging signal. The mechanism of Rev/RRE-mediated encapsidation is not a general phenomenon, since the combination of the Rev/RRE system and 5' UTR cis elements did not enhance encapsidation into MLV-derived viral particles. Lastly, we show that heterologous MLV RNAs conform to transduction properties commonly associated with HIV-1 viral particles, including in vivo transduction of non-dividing cells (i.e. mouse neurons); however, the cDNA forms are episomes predominantly in the 1-LTR circle form.
   Conclusions: Premised on encapsidation of a heterologous RNA into HIV-1 viral particles, our findings define a functional HIV-1 packaging system as comprising the 5' UTR cis elements, Gag, and the Rev/RRE system, in which the Rev/RRE system is required to make the RNA amenable to the ensuing interaction between Gag and the canonical packaging signal for subsequent encapsidation.
C1 [Cockrell, Adam S.; Ma, Hong; Kafri, Tal] Univ N Carolina, Sch Med, Gene Therapy Ctr, Chapel Hill, NC 27515 USA.
   [van Praag, Henriette; Santistevan, Nicholas] NIA, Neuroplast & Behav Unit, Baltimore, MD 21224 USA.
RP Kafri, T (reprint author), Univ N Carolina, Sch Med, Gene Therapy Ctr, Chapel Hill, NC 27515 USA.
EM kafri@med.unc.edu
RI van Praag, Henriette/F-3939-2015; Santistevan, Nicholas/L-3233-2015
OI van Praag, Henriette/0000-0002-5727-434X; Santistevan,
   Nicholas/0000-0002-4657-6860
FU NIH, National Institute on Aging; University of North Carolina (UNC)
   Center for AIDS Research; NIH [2-R01-DK058702, 5-PO1-HL066973]
FX The following reagents were obtained from NIH AIDS Research and
   Reference Reagent Program: HIV-1 p24 monoclonal antibody, p24 polyclonal
   antibody, and Etravirine. We thank Linda Kitabayashi for assistance in
   preparing confocal microscopy images. We thank Christopher Baum for
   providing us with the Gag/Pol-4XCTE helper/packaging construct. We thank
   Dawn Bowles for comprehensive review of the manuscript. This research
   was supported, in part, by the Intramural Research Program of the NIH,
   National Institute on Aging (N.S., H.vP.). The study was primarily
   supported by the University of North Carolina (UNC) Center for AIDS
   Research graduate student training grant (to A.C.) and by the NIH grants
   2-R01-DK058702 (to T.K.) and 5-PO1-HL066973 (to T.K.).
NR 42
TC 11
Z9 11
U1 0
U2 2
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 JUN 24
PY 2011
VL 8
AR 51
DI 10.1186/1742-4690-8-51
PG 17
WC Virology
SC Virology
GA 789NH
UT WOS:000292521700001
PM 21702950
ER

PT J
AU ZeRuth, GT
   Yang, XP
   Jetten, AM
AF ZeRuth, Gary T.
   Yang, Xiao-Ping
   Jetten, Anton M.
TI Modulation of the Transactivation Function and Stability of Kruppel-like
   Zinc Finger Protein Gli-similar 3 (Glis3) by Suppressor of Fused
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INSULIN GENE-TRANSCRIPTION; NEONATAL DIABETES-MELLITUS; BETA-CELL
   FUNCTION; NEGATIVE REGULATOR; PRIMARY CILIA; SUFU; LOCI; MICE;
   ASSOCIATION; DEGRADATION
AB Glis3 is a member of the Glis subfamily of Kruppel-like zinc finger transcription factors. Recently, Glis3 has been linked to both type I and type II diabetes and shown to positively regulate insulin gene expression. In this study, we have identified a region within the N terminus of Glis3 that shares high levels of homology with the Cubitus interruptus (Ci)/Gli family of proteins. We demonstrated that Glis3 interacts with Suppressor of Fused (SUFU), which involves a VYGHF motif located within this conserved region. We further showed that SUFU is able to inhibit the activation of the insulin promoter by Glis3 but not the activation by a Glis3 mutant deficient in its ability to bind SUFU, suggesting that the inhibitory effect is dependent on the interaction between the two proteins. Exogenous SUFU did not affect the nuclear localization of Glis3; however, Glis3 promoted the nuclear accumulation of SUFU. Additionally, we demonstrated that SUFU stabilizes Glis3 in part by antagonizing the Glis3 association with a Cullin 3-based E3 ubiquitin ligase that promotes the ubiquitination and degradation of Glis3. This is the first reported instance of Glis3 interacting with SUFU and suggests a novel role for SUFU in the modulation of Glis3 signaling. Given the critical role of Glis3 in pancreatic beta-cell generation and maintenance, the elevated Glis3 expression in several cancers, and the established role of SUFU as a tumor suppressor, these data provide further insight into Glis3 regulation and its function in development and disease.
C1 [ZeRuth, Gary T.; Yang, Xiao-Ping; Jetten, Anton M.] NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Jetten, AM (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM jetten@niehs.nih.gov
OI Jetten, Anton/0000-0003-0954-4445
FU National Institutes of Health, NIEHS [Z01-ES-100485]
FX This work was supported, in whole or in part, by National Institutes of
   Health Grant Z01-ES-100485 from the Intramural Research Program of the
   NIEHS.
NR 50
TC 6
Z9 6
U1 1
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 JUN 24
PY 2011
VL 286
IS 25
BP 22077
EP 22089
DI 10.1074/jbc.M111.224964
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 778QP
UT WOS:000291719900014
PM 21543335
ER

PT J
AU Iwaki, S
   Lu, YB
   Xie, ZH
   Druey, KM
AF Iwaki, Shoko
   Lu, Yunbiao
   Xie, Zhihui
   Druey, Kirk M.
TI p53 Negatively Regulates RGS13 Protein Expression in Immune Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MAST-CELLS; GENE-EXPRESSION; TRANSCRIPTION; RESPONSIVENESS; RESPONSES;
   LYMPHOMA
AB RGS13, a member of the regulator of G protein signaling (RGS) family, inhibits G protein-coupled receptor signaling in B cells and mast cells (MCs) and suppresses IgE-antigen-induced MC degranulation and anaphylaxis. Although RGS13 expression is induced by immune receptor and chemokine receptor stimulation, the molecular regulation of RGS13 transcription is unknown. Here, we investigated the role of two p53 response elements (REs) in the regulation of RGS13 promoter activity and expression. We found that a 1000-bp DNA fragment upstream of the ATG translation start site (TSS) had promoter activity in reporter gene assays, and deletion or mutation of a p53-binding motif nearest the TSS abolished promoter activity. Notably, p53 bound to both REs in the RGS13 promoter in vivo as assessed by chromatin immunoprecipitation, suggesting that the p53 RE most distal to the TSS is physiologically inactive. We detected reduced RGS13 expression in MCs exogenously expressing p53 or treated with doxorubicin, which induces genotoxic stress and leads to p53 accumulation. RNA silencing of p53 up-regulated RGS13 expression in B lymphocytes, and bone marrow-derived MCs from p53(-/-) mice had increased RGS13 expression. Finally, p53-depleted B cells with increased RGS13 expression had reduced Ca(2+) mobilization in response to sphingosine 1-phosphate. These studies indicate that p53 may modulate immune responses through suppression of RGS13 transcription in MCs and B cells.
C1 [Iwaki, Shoko; Lu, Yunbiao; Xie, Zhihui; Druey, Kirk M.] NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Druey, KM (reprint author), NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Room 11N242,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kdruey@niaid.nih.gov
FU National Institutes of Health, NIAID [AI000939-06 LAD]
FX This work was supported, in whole or in part, by National Institutes of
   Health Intramural Research Program Grant AI000939-06 LAD from NIAID.
NR 28
TC 1
Z9 1
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 JUN 24
PY 2011
VL 286
IS 25
BP 22219
EP 22226
DI 10.1074/jbc.M111.228924
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 778QP
UT WOS:000291719900029
PM 21531726
ER

PT J
AU Manzano, M
   Reichert, ED
   Polo, S
   Falgout, B
   Kasprzak, W
   Shapiro, BA
   Padmanabhan, R
AF Manzano, Mark
   Reichert, Erin D.
   Polo, Stephanie
   Falgout, Barry
   Kasprzak, Wojciech
   Shapiro, Bruce A.
   Padmanabhan, Radhakrishnan
TI Identification of Cis-Acting Elements in the 3 '-Untranslated Region of
   the Dengue Virus Type 2 RNA That Modulate Translation and Replication
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID WEST-NILE-VIRUS; PARALLEL GENETIC ALGORITHM; SECONDARY
   STRUCTURE-ANALYSIS; CAP-DEPENDENT TRANSLATION; 3 UNTRANSLATED REGION;
   STEM-LOOP STRUCTURE; DE-NOVO SYNTHESIS; CYCLIZATION SEQUENCES; VIRAL
   REPLICATION; FLAVIVIRUS RNA
AB Using the massively parallel genetic algorithm for RNA folding, we show that the core region of the 3'-untranslated region of the dengue virus (DENV) RNA can form two dumbbell structures (5' - and 3' -DBs) of unequal frequencies of occurrence. These structures have the propensity to form two potential pseudoknots between identical five-nucleotide terminal loops 1 and 2 (TL1 and TL2) and their complementary pseudoknot motifs, PK2 and PK1. Mutagenesis using a DENV2 replicon RNA encoding the Renilla luciferase reporter indicated that all four motifs and the conserved sequence 2 (CS2) element within the 3' -DB are important for replication. However, for translation, mutation of TL1 alone does not have any effect; TL2 mutation has only a modest effect in translation, but translation is reduced by similar to 60% in the TL1/TL2 double mutant, indicating that TL1 exhibits a cooperative synergy with TL2 in translation. Despite the variable contributions of individual TL and PK motifs in translation, WT levels are achieved when the complementarity between TL1/PK2 and TL2/PK1 is maintained even under conditions of inhibition of the translation initiation factor 4E function mediated by LY294002 via a noncanonical pathway. Taken together, our results indicate that the cis-acting RNA elements in the core region of DENV2 RNA that include two DB structures are required not only for RNA replication but also for optimal translation.
C1 [Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, NIH, Ft Detrick, MD 21702 USA.
   [Manzano, Mark; Reichert, Erin D.; Padmanabhan, Radhakrishnan] Georgetown Univ Sch Med, Dept Microbiol & Immunol, Washington, DC 20057 USA.
   [Polo, Stephanie; Falgout, Barry] US FDA, Ctr Biol Evaluat & Review, Bethesda, MD 20892 USA.
   [Kasprzak, Wojciech] SAIC Frederick Inc, Basic Sci Program, Frederick, MD USA.
RP Shapiro, BA (reprint author), NCI, Ctr Canc Res Nanobiol Program, NIH, Ft Detrick, MD 21702 USA.
EM shapirbr@mail.nih.gov; rp55@georgetown.edu
FU National Institutes of Health (NIH) [AI 57705, AI 70791]; NCI, NIH
   [NO1-CO-12400, HHSN261200800001E]; NCI, NIH, Center for Cancer Research
FX This work was supported, in whole or in part, by National Institutes of
   Health (NIH) Grants AI 57705 and AI 70791 (to R. P.); by NCI, NIH,
   Contracts NO1-CO-12400 and HHSN261200800001E (to W. K.); and by the
   Intramural Research Program of the NCI, NIH, Center for Cancer Research.
   This work constitutes a partial fulfillment of the requirements for the
   degree of Doctor of Philosophy at Georgetown University School of
   Medicine for E. R. and M. M.
NR 88
TC 34
Z9 35
U1 0
U2 8
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 JUN 24
PY 2011
VL 286
IS 25
BP 22521
EP 22534
DI 10.1074/jbc.M111.234302
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 778QP
UT WOS:000291719900060
PM 21515677
ER

PT J
AU Kleinau, G
   Mueller, S
   Jaeschke, H
   Grzesik, P
   Neumann, S
   Diehl, A
   Paschke, R
   Krause, G
AF Kleinau, Gunnar
   Mueller, Sandra
   Jaeschke, Holger
   Grzesik, Paul
   Neumann, Susanne
   Diehl, Anne
   Paschke, Ralf
   Krause, Gerd
TI Defining Structural and Functional Dimensions of the Extracellular
   Thyrotropin Receptor Region
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LUTEINIZING-HORMONE-RECEPTOR; THYROID-STIMULATING HORMONE; LEUCINE-RICH
   DOMAIN; HUMAN TSH RECEPTOR; HINGE REGION; CONSTITUTIVE ACTIVITY;
   TRANSMEMBRANE DOMAIN; INVERSE AGONIST; GONADOTROPIN RECEPTORS;
   SIGNAL-TRANSDUCTION
AB The extracellular region of the thyrotropin receptor (TSHR) can be subdivided into the leucine-rich repeat domain (LRRD) and the hinge region. Both the LRRD and the hinge region interact with thyrotropin (TSH) or autoantibodies. Structural data for the TSHR LRRD were previously determined by crystallization (amino acids Glu(30)-Thr(257), 10 repeats), but the structure of the hinge region is still undefined. Of note, the amino acid sequence (Trp(258)-Tyr(279)) following the crystallized LRRD comprises a pattern typical for leucine-rich repeats with conserved hydrophobic side chains stabilizing the repeat fold. Moreover, functional data for amino acids between the LRRD and the transmembrane domain were fragmentary. We therefore investigated systematically these TSHR regions by mutagenesis to reveal insights into their functional contribution and potential structural features. We found that mutations of conserved hydrophobic residues between Thr(257) and Tyr(279) cause TSHR misfold, which supports a structural fold of this peptide, probably as an additional leucine-rich repeat. Furthermore, we identified several new mutations of hydrophilic amino acids in the entire hinge region leading to partial TSHR inactivation, indicating that these positions are important for intramolecular signal transduction. In summary, we provide new information regarding the structural features and functionalities of extracellular TSHR regions. Based on these insights and in context with previous results, we suggest an extracellular activation mechanism that supports an intramolecular agonistic unit as a central switch for activating effects at the extracellular region toward the serpentine domain.
C1 [Kleinau, Gunnar; Grzesik, Paul; Diehl, Anne; Krause, Gerd] Leibniz Inst Mol Pharmacol, Dept Biol Struct, D-13125 Berlin, Germany.
   [Kleinau, Gunnar] Charite, Inst Expt Pediat Endocrinol, D-13353 Berlin, Germany.
   [Mueller, Sandra; Jaeschke, Holger; Paschke, Ralf] Univ Leipzig, Dept Internal Med Neurol & Dermatol, D-04103 Leipzig, Germany.
   [Neumann, Susanne] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
RP Krause, G (reprint author), Leibniz Inst Mol Pharmacol, Dept Biol Struct, D-13125 Berlin, Germany.
EM gkrause@FMP-Berlin.de
FU National Institutes of Health, NIDDK; Medical Faculty, University of
   Leipzig [NBL Formel.1-108]; Deutsche Forschungsgemeinschaft [KL2334/2-1,
   KR1273/1-2,3, Pa 423/15-1,2]
FX This work was supported, in whole or in part, by the National Institutes
   of Health, NIDDK, Intramural Research Program. This work was also
   supported by Medical Faculty, University of Leipzig, Grant NBL
   Formel.1-108 and by Deutsche Forschungsgemeinschaft Grants KL2334/2-1,
   KR1273/1-2,3, and Pa 423/15-1,2.
NR 62
TC 13
Z9 13
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 24
PY 2011
VL 286
IS 25
BP 22622
EP 22631
DI 10.1074/jbc.M110.211193
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 778QP
UT WOS:000291719900069
PM 21525003
ER

PT J
AU Northrup, DL
   Zhao, KJ
AF Northrup, Daniel L.
   Zhao, Keji
TI Application of ChIP-Seq and Related Techniques to the Study of Immune
   Function
SO IMMUNITY
LA English
DT Review
ID REGULATORY T-CELLS; TISSUE-SPECIFIC ENHANCERS; CYTOKINE GENE-EXPRESSION;
   EMBRYONIC STEM-CELLS; LOCUS-CONTROL REGION; TRANSCRIPTION FACTORS; DNA
   METHYLATION; HUMAN GENOME; CHROMATIN-STRUCTURE; STAT3-DEPENDENT MANNER
AB Behaviors observed at the cellular level such as development and acquisition of effector functions by immune cells result from transcriptional changes. The biochemical mediators of transcription are sequence-specific transcription factors (TFs), chromatin modifying enzymes, and chromatin, the complex of DNA and histone proteins. Covalent modification of DNA and histones, also termed epigenetic modification, influences the accessibility of target sequences for transcription factors on chromatin and the expression of linked genes required for immune functions. Genome-wide techniques such as ChIP-Seq have described the entire "cistrome" of transcription factors involved in specific developmental steps of B and T cells and started to define specific immune responses in terms of the binding profiles of critical effectors and epigenetic modification patterns. Current data suggest that both promoters and enhancers are prepared for action at different stages of activation by epigenetic modification through distinct transcription factors in different cells.
C1 [Northrup, Daniel L.; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Northrup, DL (reprint author), NHLBI, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM northrupd@nhlbi.nih.gov; zhaok@nhlbi.nih.gov
FU Division of Intramural Research, National Heart, Lung and Blood
   Institute
FX The Division of Intramural Research, National Heart, Lung and Blood
   Institute supported the research in the authors' laboratory.
NR 109
TC 36
Z9 36
U1 0
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JUN 24
PY 2011
VL 34
IS 6
BP 830
EP 842
DI 10.1016/j.immuni.2011.06.002
PG 13
WC Immunology
SC Immunology
GA 787AT
UT WOS:000292349700005
PM 21703538
ER

PT J
AU Decker, KB
   Chen, Q
   Hsieh, ML
   Boucher, P
   Stibitz, S
   Hinton, DM
AF Decker, Kimberly B.
   Chen, Qing
   Hsieh, Meng-Lun
   Boucher, Philip
   Stibitz, Scott
   Hinton, Deborah M.
TI Different Requirements for sigma Region 4 in BvgA Activation of the
   Bordetella pertussis Promoters P-fim3 and P-fhaB
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE BvgA; fim; sigma; polymerase; promoter
ID COLI RNA-POLYMERASE; BACTERIAL TRANSCRIPTION INITIATION; AMP RECEPTOR
   PROTEIN; AMINO-ACID CONTACTS; C-TERMINAL DOMAIN; ESCHERICHIA-COLI;
   DNA-BINDING; CRYSTAL-STRUCTURE; ALPHA-SUBUNITS; ABORTIVE INITIATION
AB Bordetella pertussis BvgA is a global response regulator that activates virulence genes, including adhesin-encoding fim3 and fhaB. At the fhaB promoter, P-fhaB, a BvgA binding site lies immediately upstream of the -35 promoter element recognized by Region 4 of the sigma subunit of RNA polymerase (RNAP). We demonstrate that sigma Region 4 is required for BvgA activation of P-fhaB, a hallmark of Class II activation. In contrast, the promoter-proximal BvgA binding site at P-fim3 includes the -35 region, which is composed of a tract of cytosines that lacks specific sequence information. We demonstrate that sigma Region 4 is not required for BvgA activation at P-fim3. Nonetheless, Region 4 mutations that impair its typical interactions with core and with the -35 DNA affect P-fim3 transcription. Hydroxyl radical cleavage using RNAP with sigma D581C-FeBABE positions Region 4 near the -35 region of P-fim3; cleavage using RNAP with alpha 276C-FeBABE or alpha 302C-FeBABE also positions an alpha subunit C-terminal domain within the -35 region, on a different helical face from the promoter-proximal BvgA similar to P dimer. Our results suggest that the -35 region of P-fim3 accommodates a BvgA similar to P dimer, an alpha subunit C-terminal domain, and sigma Region 4. Molecular modeling suggests how BvgA, sigma Region 4, and alpha might coexist within this DNA in a conformation that suggests a novel mechanism of activation. Published by Elsevier Ltd.
C1 [Decker, Kimberly B.; Hsieh, Meng-Lun; Hinton, Deborah M.] NIDDK, Gene Express & Regulat Sect, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Chen, Qing; Boucher, Philip; Stibitz, Scott] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Hinton, DM (reprint author), NIDDK, Gene Express & Regulat Sect, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA.
EM dhinton@helix.nih.gov
FU National Institutes of Health, National Institute of Diabetes and
   Digestive and Kidney Diseases
FX We are grateful to C. Meares for the Cys(-)rpoD plasmid, to D. Lewis and
   S. Adhya for pDL934, to S. Dove and A. Hochschild for pBR alpha -
   sigma<SUP>HYb4</SUP>, to T. James for the molecular modeling, and to L.
   Knipling for the construction of pET sigma<SUP>fl</SUP>CF and pET
   sigma<SUP>Hyb4</SUP> and purification of sigma<SUP>HYb4</SUP>. We also
   thank R. Bonocora, L. Knipling, T. James, A. Boulanger-Castaing, S. Jha,
   and C. Jones for helpful discussions. K. Decker is a graduate student in
   the Graduate Partnership Program, Johns Hopkins University-National
   Institutes of Health. This research was supported in part by the
   Intramural Research Program of the National Institutes of Health,
   National Institute of Diabetes and Digestive and Kidney Diseases.
NR 97
TC 10
Z9 10
U1 2
U2 2
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 JUN 24
PY 2011
VL 409
IS 5
BP 692
EP 709
DI 10.1016/j.jmb.2011.04.017
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 781EL
UT WOS:000291913300002
PM 21536048
ER

PT J
AU McLellan, JS
   Correia, BE
   Chen, M
   Yang, YP
   Graham, BS
   Schief, WR
   Kwong, PD
AF McLellan, Jason S.
   Correia, Bruno E.
   Chen, Man
   Yang, Yongping
   Graham, Barney S.
   Schief, William R.
   Kwong, Peter D.
TI Design and Characterization of Epitope-Scaffold Immunogens That Present
   the Motavizumab Epitope from Respiratory Syncytial Virus
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE palivizumab; Synagis (R); structure-based vaccine design; X-ray
   structure
ID FUSION GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; STRUCTURAL BASIS; PROTEIN;
   INFECTION; VACCINE; NEUTRALIZATION; PALIVIZUMAB; EFFICIENT; SOFTWARE
AB Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, but an effective vaccine has not yet been developed. An ideal vaccine would elicit protective antibodies while avoiding virus-specific T-cell responses, which have been implicated in vaccine-enhanced disease with previous RSV vaccines. We propose that heterologous proteins designed to present RSV-neutralizing antibody epitopes and to elicit cognate antibodies have the potential to fulfill these vaccine requirements, as they can be fashioned to be free of viral T-cell epitopes. Here we present the design and characterization of three epitope-scaffolds that present the epitope of motavizumab, a potent neutralizing antibody that binds to a helix loop helix motif in the RSV fusion glycoprotein. Two of the epitope-scaffolds could be purified, and one epitope-scaffold based on a Staphylococcus aureus protein A domain bound motavizumab with kinetic and thermodynamic properties consistent with the free epitope-scaffold being stabilized in a conformation that closely resembled the motavizumab-bound state. This epitope-scaffold was well folded as assessed by circular dichroism and isothermal titration calorimetry, and its crystal structure (determined in complex with motavizumab to 1.9 angstrom resolution) was similar to the computationally designed model, with all hydrogen-bond interactions critical for binding to motavizumab preserved. Immunization of mice with this epitope-scaffold failed to elicit neutralizing antibodies but did elicit sera with F binding activity. The elicitation of F binding antibodies suggests that some of the design criteria for eliciting protective antibodies without virus-specific T-cell responses are being met, but additional optimization of these novel immunogens is required. Published by Elsevier Ltd.
C1 [McLellan, Jason S.; Chen, Man; Yang, Yongping; Graham, Barney S.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   [Correia, Bruno E.; Schief, William R.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
   [Correia, Bruno E.] Inst Gulbenkian Ciencias, PhD Program Computat Biol, Oeiras, Portugal.
RP McLellan, JS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mclellanja@mail.nih.gov
RI McLellan, Jason/A-6874-2010
FU National Institutes of Health (National Institute of Allergy and
   Infectious Diseases); Portuguese Fundacao para a Ciencia e a Tecnologia
   [SFRH/BD/32958/2006]; US Department of Energy, Basic Energy Sciences,
   Office of Science [W-31-109-Eng-38]
FX The authors would like to thank the staff at SER-CAT for help with X-ray
   diffraction data collection and the members of the Structural Biology
   Section and Structural Bioinformatics Section at the Vaccine Research
   Center for insightful comments and discussions. Support for this work
   was provided by the Intramural Research Program of the National
   Institutes of Health (National Institute of Allergy and Infectious
   Diseases). B.E.C. was supported by a fellowship from the Portuguese
   Fundacao para a Ciencia e a Tecnologia (SFRH/BD/32958/2006). Use of
   sector 22 (SER-CAT) at the Advanced Photon Source was supported by the
   US Department of Energy, Basic Energy Sciences, Office of Science, under
   contract number W-31-109-Eng-38.
NR 32
TC 45
Z9 47
U1 6
U2 21
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 JUN 24
PY 2011
VL 409
IS 5
BP 853
EP 866
DI 10.1016/j.jmb.2011.04.044
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 781EL
UT WOS:000291913300013
PM 21549714
ER

PT J
AU Wang, QY
   Liu, YF
   Soetandyo, N
   Baek, K
   Hegde, R
   Ye, YH
AF Wang, Qiuyan
   Liu, Yanfen
   Soetandyo, Nia
   Baek, Kheewoong
   Hegde, Ramanujan
   Ye, Yihong
TI A Ubiquitin Ligase-Associated Chaperone Holdase Maintains Polypeptides
   in Soluble States for Proteasome Degradation
SO MOLECULAR CELL
LA English
DT Article
ID RETICULUM-ASSOCIATED DEGRADATION; I HEAVY-CHAINS; ENDOPLASMIC-RETICULUM;
   MEMBRANE-PROTEIN; MOLECULAR CHAPERONES; RETRO-TRANSLOCATION; MISFOLDED
   PROTEINS; QUALITY-CONTROL; ER LUMEN; GP78
AB Endoplasmic reticulum-associated degradation (ERAD) employs membrane-bound ubiquitin ligases and the translocation-driving ATPase p97 to retrotranslocate misfolded proteins for proteasomal degradation. How retrotranslocated polypeptides bearing exposed hydrophobic motifs or transmembrane domains (TMDs) avoid aggregation before reaching the proteasome is unclear. Here we identify a ubiquitin ligase-associated multiprotein complex comprising Bag6, Ubl4A, and Trc35, which chaperones retrotranslocated polypeptides en route to the proteasome to improve ERAD efficiency. In vitro, Bag6, the central component of the complex, contains a chaperone-like activity capable of maintaining an aggregation-prone substrate in an unfolded yet soluble state. The physiological importance of this holdase activity is underscored by observations that ERAD substrates accumulate in detergent-insoluble aggregates in cells depleted of Bag6, or of Trc35, a cofactor that keeps Bag6 outside the nucleus for engagement in ERAD. Our results reveal a ubiquitin ligase-associated holdase that maintains polypeptide solubility to enhance protein quality control in mammalian cells.
C1 [Wang, Qiuyan; Liu, Yanfen; Soetandyo, Nia; Baek, Kheewoong; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Hegde, Ramanujan] NICHHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Ye, YH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM yihongy@mail.nih.gov
RI WANG, QIUYAN/C-1303-2011; 
OI Hegde, Ramanujan/0000-0001-8338-852X
FU National Institutes of Health; NIDDK
FX We thank S. Fang (University of Maryland, Baltimore, MD) for reagents,
   and Michael Krause and Martin Gellert (National Institute of Diabetes
   and Digestive and Kidney Diseases [NIDDK]) and Tom Rapoport (Harvard
   Medical School) for critical reading of the manuscript. The research is
   supported by the National Institutes of Health Intramural AIDS Targeted
   Antiviral Program (IATAP) and by the Intramural Research Program of the
   NIDDK.
NR 42
TC 86
Z9 88
U1 1
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD JUN 24
PY 2011
VL 42
IS 6
BP 758
EP 770
DI 10.1016/j.molcel.2011.05.010
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 786YK
UT WOS:000292343600007
PM 21636303
ER

PT J
AU Rigden, DJ
   Woodhead, DD
   Wong, PWH
   Galperin, MY
AF Rigden, Daniel J.
   Woodhead, Duncan D.
   Wong, Prudence W. H.
   Galperin, Michael Y.
TI New Structural and Functional Contexts of the Dx[DN]xDG Linear Motif:
   Insights into Evolution of Calcium-Binding Proteins
SO PLOS ONE
LA English
DT Article
ID BARDET-BIEDL-SYNDROME; MULTIPLE SEQUENCE ALIGNMENT; ACTIN-ASSOCIATED
   PROTEIN; EF-HAND PROTEINS; CRYSTAL-STRUCTURE; BETA-PROPELLER;
   PHOSPHOLIPASE-D; HIGH-THROUGHPUT; SITES; RECOGNITION
AB Binding of calcium ions (Ca2+) to proteins can have profound effects on their structure and function. Common roles of calcium binding include structure stabilization and regulation of activity. It is known that diverse families - EF-hands being one of at least twelve - use a Dx[DN]xDG linear motif to bind calcium in near-identical fashion. Here, four novel structural contexts for the motif are described. Existing experimental data for one of them, a thermophilic archaeal subtilisin, demonstrate for the first time a role for Dx[DN]xDG-bound calcium in protein folding. An integrin-like embedding of the motif in the blade of a beta-propeller fold - here named the calcium blade - is discovered in structures of bacterial and fungal proteins. Furthermore, sensitive database searches suggest a common origin for the calcium blade in b-propeller structures of different sizes and a pan-kingdom distribution of these proteins. Factors favouring the multiple convergent evolution of the motif appear to include its general Asp-richness, the regular spacing of the Asp residues and the fact that change of Asp into Gly and vice versa can occur though a single nucleotide change. Among the known structural contexts for the Dx[DN] xDG motif, only the calcium blade and the EF-hand are currently found intracellularly in large numbers, perhaps because the higher extracellular concentration of Ca2+ allows for easier fixing of newly evolved motifs that have acquired useful functions. The analysis presented here will inform ongoing efforts toward prediction of similar calcium-binding motifs from sequence information alone.
C1 [Rigden, Daniel J.; Woodhead, Duncan D.] Univ Liverpool, Inst Integrat Biol, Liverpool L69 3BX, Merseyside, England.
   [Wong, Prudence W. H.] Univ Liverpool, Dept Comp Sci, Liverpool, Merseyside, England.
   [Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Rigden, DJ (reprint author), Univ Liverpool, Inst Integrat Biol, Liverpool L69 3BX, Merseyside, England.
EM drigden@liv.ac.uk
RI Galperin, Michael/B-5859-2013; 
OI Galperin, Michael/0000-0002-2265-5572; Rigden,
   Daniel/0000-0002-7565-8937; Wong, Prudence W.H./0000-0001-7935-7245
FU Biotechnology and Biological Sciences Research Council; National
   Institutes of Health at the National Library of Medicine
FX Biotechnology and Biological Sciences Research Council studentship
   (DDW); National Institutes of Health Intramural Research Program at the
   National Library of Medicine (MYG). The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 92
TC 24
Z9 26
U1 0
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 24
PY 2011
VL 6
IS 6
AR e21507
DI 10.1371/journal.pone.0021507
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782UF
UT WOS:000292036900046
PM 21720552
ER

PT J
AU Cerritelli, SM
   Chon, HG
   Crouch, RJ
AF Cerritelli, Susana M.
   Chon, Hyongi
   Crouch, Robert J.
TI A New Twist for Topoisomerase
SO SCIENCE
LA English
DT Editorial Material
ID RIBONUCLEOTIDE INCORPORATION; TRANSCRIPTION ELONGATION; GENOME
   STABILITY; DNA; INSTABILITY; REPAIR
C1 [Cerritelli, Susana M.; Chon, Hyongi; Crouch, Robert J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Dev, NIH, Bethesda, MD 20892 USA.
RP Cerritelli, SM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Dev, NIH, Bethesda, MD 20892 USA.
EM crouchr@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 15
TC 4
Z9 4
U1 1
U2 2
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUN 24
PY 2011
VL 332
IS 6037
BP 1510
EP 1511
DI 10.1126/science.1208450
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782EE
UT WOS:000291990000029
PM 21700860
ER

PT J
AU Kim, N
   Huang, SYN
   Williams, JS
   Li, YC
   Clark, AB
   Cho, JE
   Kunkel, TA
   Pommier, Y
   Jinks-Robertson, S
AF Kim, Nayun
   Huang, Shar-yin N.
   Williams, Jessica S.
   Li, Yue C.
   Clark, Alan B.
   Cho, Jang-Eun
   Kunkel, Thomas A.
   Pommier, Yves
   Jinks-Robertson, Sue
TI Mutagenic Processing of Ribonucleotides in DNA by Yeast Topoisomerase I
SO SCIENCE
LA English
DT Article
ID MISMATCH REPAIR PROTEINS; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION;
   CAMPTOTHECIN; INSTABILITY; ANTICANCER; SEQUENCE; H2
AB The ribonuclease (RNase) H class of enzymes degrades the RNA component of RNA:DNA hybrids and is important in nucleic acid metabolism. RNase H2 is specialized to remove single ribonucleotides [ribonucleoside monophosphates (rNMPs)] from duplex DNA, and its absence in budding yeast has been associated with the accumulation of deletions within short tandem repeats. Here, we demonstrate that rNMP-associated deletion formation requires the activity of Top1, a topoisomerase that relaxes supercoils by reversibly nicking duplex DNA. The reported studies extend the role of Top1 to include the processing of rNMPs in genomic DNA into irreversible single-strand breaks, an activity that can have distinct mutagenic consequences and may be relevant to human disease.
C1 [Kim, Nayun; Li, Yue C.; Cho, Jang-Eun; Jinks-Robertson, Sue] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
   [Huang, Shar-yin N.; Pommier, Yves] NCI, Lab Mol Pharmacol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Williams, Jessica S.; Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Lab Mol Genet, NIH, Res Triangle Pk, NC 27709 USA.
   [Williams, Jessica S.; Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Jinks-Robertson, S (reprint author), Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
EM sue.robertson@duke.edu
FU NIH [R01 GM38464, R01 GM93197]; Center for Cancer Research, National
   Cancer Institute, NIH; Division of Intramural Research of the NIH,
   National Institute of Environmental Health Sciences [Z01 ES065070, Z01
   ES065089]
FX S.J.-R. was supported by NIH grants R01 GM38464 and R01 GM93197; Y.P.
   was supported by the Intramural Program, Center for Cancer Research,
   National Cancer Institute, NIH; and T.A.K. was supported by Projects Z01
   ES065070 and Z01 ES065089 from the Division of Intramural Research of
   the NIH, National Institute of Environmental Health Sciences.
NR 17
TC 122
Z9 123
U1 1
U2 8
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUN 24
PY 2011
VL 332
IS 6037
BP 1561
EP 1564
DI 10.1126/science.1205016
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782EE
UT WOS:000291990000046
PM 21700875
ER

PT J
AU Maruoka, H
   Jayasekara, MPS
   Barrett, MO
   Franklin, DA
   de Castro, S
   Kim, N
   Costanzi, S
   Harden, TK
   Jacobson, KA
AF Maruoka, Hiroshi
   Jayasekara, M. P. Suresh
   Barrett, Matthew O.
   Franklin, Derek A.
   de Castro, Sonia
   Kim, Nathaniel
   Costanzi, Stefano
   Harden, T. Kendall
   Jacobson, Kenneth A.
TI Pyrimidine Nucleotides with 4-Alkyloxyimino and Terminal Tetraphosphate
   delta-Ester Modifications as Selective Agonists of the P2Y(4) Receptor
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; URACIL NUCLEOTIDES; EXTRACELLULAR LOOPS;
   LIGAND RECOGNITION; MUTAGENESIS; ANTAGONISTS; ANALOGS; 5'-TRIPHOSPHATE;
   PHARMACOLOGY; ARCHITECTURE
AB P2Y(2) and P2Y(4) receptors are G protein-coupled receptors, activated by UTP and dinudeoside tetraphosphates, which are difficult to distinguish pharmacologically for lack of potent and selective ligands. We structurally varied phosphate and uracil moieties in analogues of pyrimidine nucleoside 5'-triphosphates and 5'-tetraphosphate esters. P2Y(4) receptor potency in phospholipase C stimulation in transfected 1321N1 human astrocytoma cells was enhanced in N-4-alkyloxycytidine derivatives. OH groups on a terminal delta-glucose phosphoester of uridine 5'-tetraphosphate were inverted or substituted with H or F to probe H-bonding effects. N-4-(Phenylpropoxy)-CTP 16 (MRS4062), Up(4)-[1]3'-deoxy-3'-fluoroglucose 34 (MRS2927), and N-4-(phenylethoxy)-CTP 15 exhibit >= 10-fold selectivity for human P2Y(4) over P2Y(2) and P2Y(6) receptors (EC50 values 23, 62, and 73 nM, respectively). delta-3-Chlorophenyl phosphoester 21 of Up(4) activated P2Y(2) but not P2Y(4) receptor. Selected nucleotides tested for chemical and enzymatic stability were much more stable than UTP. Agonist docking at CXCR4-based P2Y(2) and P2Y(4) receptor models indicated greater steric tolerance of N-4-phenylpropoxy group at P2Y(4). Thus, distal structural changes modulate potency, selectivity, and stability of extended uridine tetraphosphate derivatives, and we report the first P2Y(4) receptor-selective agonists.
C1 [Maruoka, Hiroshi; Jayasekara, M. P. Suresh; de Castro, Sonia; Kim, Nathaniel; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
   [Barrett, Matthew O.; Franklin, Derek A.; Harden, T. Kendall] Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA.
   [Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI de castro, sonia/E-7303-2012; Jacobson, Kenneth/A-1530-2009; Costanzi,
   Stefano/G-8990-2013; 
OI de castro, sonia/0000-0002-3838-6856; Jacobson,
   Kenneth/0000-0001-8104-1493; Costanzi, Stefano/0000-0003-3183-7332
FU NIGMS [GM38213]; NIDDK, National Institutes of Health; Pharma Co., Ltd.;
   Ministerio de Educacion y Ciencia (Spain)
FX X-ray determination was performed by Dr. Yoshiaki Oyama, Asubio
   Pharmaceuticals (Osaka, Japan). Mass spectral measurements were
   performed by Dr. Noel Whittaker (NIDDK). We thank Dr. Francesca
   Deflorian (NIDDK) and Dr. Andrei A. Ivanov (Emory University) for
   helpful discussions. This research was supported in part by NIGMS
   research grant GM38213 and by the Intramural Research Program of NIDDK,
   National Institutes of Health. H.M. thanks Asubio Pharma Co., Ltd. for
   financial support. S.d.C. thanks Ministerio de Educacion y Ciencia
   (Spain) for financial support.
NR 45
TC 29
Z9 30
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD JUN 23
PY 2011
VL 54
IS 12
BP 4018
EP 4033
DI 10.1021/jm101591j
PG 16
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 778MS
UT WOS:000291709100003
PM 21528910
ER

PT J
AU Kumar, V
   Kumar, S
   Hassan, M
   Wu, HL
   Thimmulappa, RK
   Kumar, A
   Sharma, SK
   Parmar, VS
   Biswal, S
   Malhotra, SV
AF Kumar, Vineet
   Kumar, Sarvesh
   Hassan, Mohammad
   Wu, Hailong
   Thimmulappa, Rajesh K.
   Kumar, Amit
   Sharma, Sunil K.
   Parmar, Virinder S.
   Biswal, Shyam
   Malhotra, Sanjay V.
TI Novel Chalcone Derivatives as Potent Nrf2 Activators in Mice and Human
   Lung Epithelial Cells
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID ANTIOXIDANT RESPONSE ELEMENT; CANCER CHEMOPREVENTIVE AGENTS;
   TRANSCRIPTION FACTOR NRF2; NITRIC-OXIDE PRODUCTION; FACTOR-KAPPA-B;
   SIGNALING PATHWAY; GENE-EXPRESSION; ANTIINFLAMMATORY ACTIVITY;
   ENDOTHELIAL-CELLS; MOLECULAR TARGET
AB Nrf2-mediated activation of antioxidant response element is a central part of molecular mechanisms governing the protective function of phase II detoxification and antioxidant enzymes against carcinogenesis, oxidative stress, and inflammation. Nrf2 is sequestered in the cytoplasm by its repressor, Keap1. We have designed and synthesized novel chalcone derivatives as Nrf2 activators. The potency of these compounds was measured by the expression of Nrf2 dependent antioxidant genes GCLM, NQO1, and HO1 in human lung epithelial cells, while the cytotoxicity was analyzed using MTT assay. In vivo potency of identified lead compounds to activate Nrf2 was evaluated using a mouse model. Our studies showed 2-trifluoromethyl-2'-methoxychalone (2b) to be a potent activator of Nrf2, both in vitro and in mice. Additional experiments showed that the activation of Nrf2 by this compound is independent of reactive oxygen species or redox changes. We have discussed a quantitative structure-activity relationship and proposed a possible mechanism of Nrf2, activation.
C1 [Kumar, Sarvesh; Wu, Hailong; Thimmulappa, Rajesh K.; Biswal, Shyam] Johns Hopkins Univ, Dept Environm Hlth Sci, Johns Hopkins Sch Publ Hlth, Baltimore, MD 21205 USA.
   [Kumar, Vineet; Hassan, Mohammad; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Kumar, Amit; Sharma, Sunil K.; Parmar, Virinder S.] Univ Delhi, Dept Chem, Bioorgan Lab, Delhi 110007, India.
RP Biswal, S (reprint author), Johns Hopkins Univ, Dept Environm Hlth Sci, Johns Hopkins Sch Publ Hlth, Baltimore, MD 21205 USA.
EM sbiswal@jhsph.edu; malhotrasa@mail.nih.gov
FU NCI, National Institutes of Health [HSN261200800001E]; National
   Institutes of Health [HL081205, 1U01HL105569]; National Heart, Lung, and
   Blood Institute Specialized Centers [P50HL084945]; Flight Attendant
   Medical Research Institute; National Cancer Institute [5P50CA058184,
   5R01CA140492]; National Institute on Environmental Health Sciences
   [P50ES015903, P01 ES018176, ES03819]; University of Delhi; Department of
   Scientific and Industrial Research (DSIR, New Delhi)
FX V.K., M.H., and S.V.M. thank the National Cancer Institute (NCI)
   Developmental Therapeutics Program. This project has been funded in
   whole or in part with funds from the NCI, National Institutes of Health,
   Grant HSN261200800001E. This work was also supported by National
   Institutes of Health Grant HL081205 (S.B.), National Heart, Lung, and
   Blood Institute Specialized Centers of Clinically Oriented Research
   Grant P50HL084945, the Flight Attendant Medical Research Institute (S.B.
   and R.K.T.), National Cancer Institute Grants 5P50CA058184 and
   5R01CA140492, NIH Phase 2 grant 1U01HL105569, and National Institute on
   Environmental Health Sciences Grants P50ES015903, P01 ES018176, and
   ES03819 (S.B.). V.S.P. and S. KS. thank the University of Delhi and the
   Department of Scientific and Industrial Research (DSIR, New Delhi) for
   financial support.
NR 83
TC 61
Z9 61
U1 4
U2 21
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD JUN 23
PY 2011
VL 54
IS 12
BP 4147
EP 4159
DI 10.1021/jm2002348
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 778MS
UT WOS:000291709100013
PM 21539383
ER

PT J
AU Lee, H
   Pastor, RW
AF Lee, Hwankyu
   Pastor, Richard W.
TI Coarse-Grained Model for PEGylated Lipids: Effect of PEGylation on the
   Size and Shape of Self-Assembled Structures
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID MOLECULAR-DYNAMICS SIMULATIONS; POLY(ETHYLENE GLYCOL);
   POLYETHYLENE-GLYCOL; FORCE-FIELD; SPHERICAL MICELLES; LIGHT-SCATTERING;
   ACTION MECHANISM; DRUG-DELIVERY; CHAIN-LENGTH; NANOPARTICLES
AB Self-assembly of polyethylene glycol (PEG)grafted lipids at different sizes and concentrations was simulated using the MARTINI coarse-grained (CG) force field. The interactions between CG PEG and CG dipalmitoylglycerophosphocholine (DPPC)-lipids were parametrized by matching densities of 19-mers of PEG and polyethylene oxide (PEO) grafted to the bilayer from all-atom simulations. Mixtures of lipids and PEG-grafted (M(w) = 550, 1250, and 2000) lipids in water self-assembled to liposomes, bicelles, and micelles at different ratios of lipids and PEGylated lipids. Average aggregate sizes decrease with increasing PEGylated-lipid concentration, in qualitative agreement with experiment. PEGylated lipids concentrate at the rims of bicelles, rather than at the planar surfaces; this also agrees with experiment, though the degree of segregation is less than that assumed in previous modeling of the experimental data. Charged lipids without PEG evenly distribute at the rim and planar surfaces of the bicelle. The average end-to-end distances of the PEG on the PEGylated lipids are comparable in liposomes, bicelles (edge or planar surface), and micelles and only slightly larger than for an isolated PEG in solution. The ability of PEGylated lipids to induce the membrane curvature by the bulky headgroup with larger PEG, and thereby modulate the phase behavior and size of lipid assemblies, arises from their relative concentration.
C1 [Lee, Hwankyu] Dankook Univ, Dept Chem Engn, Yongin 448701, South Korea.
   [Lee, Hwankyu; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Lee, H (reprint author), Dankook Univ, Dept Chem Engn, Yongin 448701, South Korea.
EM leeh@dankook.ac.kr
FU Intramural NIH HHS [ZIA HL000340-05]
NR 55
TC 56
Z9 56
U1 2
U2 81
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 JUN 23
PY 2011
VL 115
IS 24
BP 7830
EP 7837
DI 10.1021/jp2020148
PG 8
WC Chemistry, Physical
SC Chemistry
GA 778MV
UT WOS:000291709500014
PM 21618987
ER

PT J
AU Stefater, JA
   Lewkowich, I
   Rao, S
   Mariggi, G
   Carpenter, AC
   Burr, AR
   Fan, JQ
   Ajima, R
   Molkentin, JD
   Williams, BO
   Wills-Karp, M
   Pollard, JW
   Yamaguchi, T
   Ferrara, N
   Gerhardt, H
   Lang, RA
AF Stefater, James A., III
   Lewkowich, Ian
   Rao, Sujata
   Mariggi, Giovanni
   Carpenter, April C.
   Burr, Adam R.
   Fan, Jieqing
   Ajima, Rieko
   Molkentin, Jeffery D.
   Williams, Bart O.
   Wills-Karp, Marsha
   Pollard, Jeffrey W.
   Yamaguchi, Terry
   Ferrara, Napoleone
   Gerhardt, Holger
   Lang, Richard A.
TI Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in
   myeloid cells
SO NATURE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; RETINAL NEOVASCULARIZATION; MOUSE; MECHANISM;
   VASCULATURE; MACROPHAGES; TUMORIGENESIS; HETEROGENEITY; INHIBITION;
   RECEPTOR-1
AB Myeloid cells are a feature of most tissues. Here we show that during development, retinal myeloid cells (RMCs) produce Wnt ligands to regulate blood vessel branching. In the mouse retina, where angiogenesis occurs postnatally(1), somatic deletion in RMCs of the Wnt ligand transporter Wntless(2,3) results in increased angiogenesis in the deeper layers. We also show that mutation of Wnt5a and Wnt11 results in increased angiogenesis and that these ligands elicit RMC responses via a non-canonical Wnt pathway. Using cultured myeloid-like cells and RMC somatic deletion of Flt1, we show that an effector of Wnt-dependent suppression of angiogenesis by RMCs is Flt1, a naturally occurring inhibitor of vascular endothelial growth factor (VEGF)(4-6). These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching.
C1 [Stefater, James A., III; Rao, Sujata; Carpenter, April C.; Fan, Jieqing; Lang, Richard A.] Cincinnati Childrens Hosp, Visual Syst Grp, Div Pediat Ophthalmol, Med Ctr, Cincinnati, OH 45229 USA.
   [Stefater, James A., III; Rao, Sujata; Carpenter, April C.; Fan, Jieqing; Lang, Richard A.] Cincinnati Childrens Hosp, Div Dev Biol, Med Ctr, Cincinnati, OH 45229 USA.
   [Stefater, James A., III; Rao, Sujata] Univ Cincinnati, Dept Ophthalmol, Cincinnati, OH 45229 USA.
   [Lewkowich, Ian; Wills-Karp, Marsha] Cincinnati Childrens Hosp, Div Immunobiol, Med Ctr, Cincinnati, OH 45229 USA.
   [Mariggi, Giovanni; Gerhardt, Holger] Canc Res UK, Vasc Biol Lab, London Res Inst, London WC2 3PX, England.
   [Burr, Adam R.; Molkentin, Jeffery D.] Univ Cincinnati, Div Mol Cardiovasc Biol, Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA.
   [Ajima, Rieko; Yamaguchi, Terry] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA.
   [Molkentin, Jeffery D.] Univ Cincinnati, Med Ctr, Howard Hughes Med Inst, Cincinnati Childrens Hosp, Cincinnati, OH 45229 USA.
   [Williams, Bart O.] Van Andel Res Inst, Ctr Skeletal Dis Res, Grand Rapids, MI 49503 USA.
   [Pollard, Jeffrey W.] Yeshiva Univ, Albert Einstein Coll Med, Bronx, NY 10461 USA.
   [Ferrara, Napoleone] Genentech Inc, San Francisco, CA 94080 USA.
   [Gerhardt, Holger] VIB, Vasc Patterning Lab, Vesalius Res Ctr, B-3000 Louvain, Belgium.
RP Lang, RA (reprint author), Cincinnati Childrens Hosp, Visual Syst Grp, Div Pediat Ophthalmol, Med Ctr, Cincinnati, OH 45229 USA.
EM richard.lang@cchmc.org
RI Lang, Richard/E-5578-2011; Williams, Bart/A-3539-2013; Gerhardt,
   Holger/G-4610-2011; 
OI Williams, Bart/0000-0002-5261-5301; Gerhardt,
   Holger/0000-0001-9228-7472; Gerhardt, Holger/0000-0002-3030-0384
FU NIH; HHMI; Cancer Research UK
FX We thank P. Speeg for technical assistance and A. P. McMahon for the
   Wnt11 mice. This work was supported by the NIH (J.A.S., M.W-K., J.W.P.,
   J.D.M., T.Y., B.O.W., R.A.L.) by the HHMI (J.D.M.) and Cancer Research
   UK (H.G.).
NR 35
TC 109
Z9 111
U1 2
U2 29
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUN 23
PY 2011
VL 474
IS 7352
BP 511
EP 515
DI 10.1038/nature10085
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 781NJ
UT WOS:000291939700049
PM 21623369
ER

PT J
AU Fry, TJ
AF Fry, Terry J.
TI Self-enabling T cells
SO BLOOD
LA English
DT Editorial Material
ID LYMPHOCYTES; NAIVE; WT1
C1 NIH, Bethesda, MD 20892 USA.
RP Fry, TJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 9
TC 0
Z9 0
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 JUN 23
PY 2011
VL 117
IS 25
BP 6742
EP 6743
DI 10.1182/blood-2011-04-346692
PG 4
WC Hematology
SC Hematology
GA 782AM
UT WOS:000291979800003
PM 21700779
ER

PT J
AU Elf, S
   Blevins, D
   Jin, LT
   Chung, TW
   Williams, IR
   Lee, BH
   Lin, JX
   Leonard, WJ
   Taunton, J
   Khoury, HJ
   Kang, SM
AF Elf, Shannon
   Blevins, Dean
   Jin, Lingtao
   Chung, Tae-Wook
   Williams, Ifor R.
   Lee, Benjamin H.
   Lin, Jian-Xin
   Leonard, Warren J.
   Taunton, Jack
   Khoury, Hanna J.
   Kang, Sumin
TI p90RSK2 is essential for FLT3-ITD- but dispensable for BCR-ABL-induced
   myeloid leukemia
SO BLOOD
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR RECEPTOR-3; RIBOSOMAL S6
   KINASE-2; COFFIN-LOWRY-SYNDROME; HEMATOPOIETIC TRANSFORMATION;
   SIGNAL-TRANSDUCTION; LYMPHOPROLIFERATIVE DISEASE; REGULATORY
   PHOSPHORYLATION; TYROSINE PHOSPHORYLATION; RSK2 ACTIVATION
AB p90 ribosomal S6 kinase 2 (p90RSK2) is important in diverse cellular processes including gene expression, cell proliferation, and survival. We found that p90RSK2 is commonly activated in diverse leukemia cell lines expressing different leukemogenic tyrosine kinases, including BCR-ABL and FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD). Interestingly, in a murine BM transplantation (BMT) model, genetic deficiency of RSK2 did not affect the pathogenesis or disease progression of BCR-ABL-induced myeloproliferative neoplasm (PN). In contrast, FLT3-ITD induced a T-cell acute lymphoblastic leukemia in BMT mice receiving RSK2 knockout (KO) BM cells, phenotypically distinct from the myeloproliferative neoplasm induced by FLT3-ITD using wild-type BM cells. In consonance with these results, inhibition of RSK2 by an RSK inhibitor, fmk, did not effectively induce apoptosis in BCR-ABL-expressing murine Ba/F3 cells, human K562 cells or primary tissue samples from CML patients, whereas fmk treatment induced significant apoptotic cell death not only in FLT3-ITD-positive Ba/F3 cells, human Molm14 and Mv(4;11) leukemia cells, but also in primary tissue samples from AML patients. These results suggest that RSK2 is dispensable for BCR-ABL-induced myeloid leukemia, but may be required for pathogenesis and lineage determination in FLT3-ITD-induced hematopoietic transformation. RSK2 may thus represent an alternative therapeutic target in the treatment of FLT3-ITD-positive leukemia. (Blood. 2011;117(25):6885-6894)
C1 [Elf, Shannon; Blevins, Dean; Jin, Lingtao; Chung, Tae-Wook; Khoury, Hanna J.; Kang, Sumin] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Winship Canc Inst Emory, Atlanta, GA 30322 USA.
   [Lee, Benjamin H.] Novartis Inst BioMed Res, Cambridge, MA USA.
   [Lin, Jian-Xin; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
   [Taunton, Jack] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
RP Kang, SM (reprint author), Emory Univ, Sch Med, Dept Hematol & Med Oncol, Winship Canc Inst Emory, 1365-C Clifton Rd NE,C3006, Atlanta, GA 30322 USA.
EM smkang@emory.edu
RI Williams, Ifor/D-3648-2011; Jin, Lingtao/O-4316-2014
OI Williams, Ifor/0000-0002-8810-2911; 
FU American Cancer Society [RSG-11-081-01]; Leukemia & Lymphoma Society
   [LLS 3302-09]; National Institutes of Health (NIH)/National Cancer
   Institute (NCI) [P50CA128613]; Pharmacologic Sciences Training Grant
   [T32 GM008602]; NIH [GM071434]
FX This work was in part supported by American Cancer Society grant
   RSG-11-081-01 (S. K.), Leukemia & Lymphoma Society Career Development
   Program Special Fellow Award LLS 3302-09 (S. K.), National Institutes of
   Health (NIH)/National Cancer Institute (NCI) SPORE in Head and Neck
   Cancer (P50CA128613) Career Development Program Award (S. K.), and the
   Pharmacologic Sciences Training Grant T32 GM008602 (S. E.). J.T.
   acknowledges support from the NIH (GM071434).
NR 49
TC 12
Z9 13
U1 0
U2 6
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 JUN 23
PY 2011
VL 117
IS 25
BP 6885
EP 6894
DI 10.1182/blood-2010-10-315721
PG 10
WC Hematology
SC Hematology
GA 782AM
UT WOS:000291979800020
PM 21527514
ER

PT J
AU Lukasiewicz, KB
   Greenwood, TM
   Negron, VC
   Bruzek, AK
   Salisbury, JL
   Lingle, WL
AF Lukasiewicz, Kara B.
   Greenwood, Tammy M.
   Negron, Vivian C.
   Bruzek, Amy K.
   Salisbury, Jeffrey L.
   Lingle, Wilma L.
TI Control of Centrin Stability by Aurora A
SO PLOS ONE
LA English
DT Article
ID CENTROSOME DUPLICATION CYCLE; HUMAN BREAST-TUMORS; CELL-CYCLE;
   CHROMOSOMAL INSTABILITY; A OVEREXPRESSION; PROTEIN-KINASE; CANCER CELLS;
   AMPLIFICATION; PHOSPHORYLATION; IDENTIFICATION
AB Aurora A is an oncogenic serine/threonine kinase which can cause cell transformation and centrosome amplification when over-expressed. Human breast tumors show excess Aurora A and phospho-centrin in amplified centrosomes. Here, we show that Aurora A mediates the phosphorylation of and localizes with centrin at the centrosome, with both proteins reaching maximum abundance from prophase through metaphase, followed by their precipitous loss in late stages of mitosis. Overexpression of Aurora A results in excess phospho-centrin and centrosome amplification. In contrast, centrosome amplification is not seen in cells over-expressing Aurora A in the presence of a recombinant centrin mutant lacking the serine phosphorylation site at residue 170. Expression of a kinase dead Aurora A results in a decrease in mitotic index and abrogation of centrin phosphorylation. Finally, a recombinant centrin mutation that mimics centrin phosphorylation increases centrin's stability against APC/C-mediated proteasomal degradation. Taken together, these results suggest that the stability of centrin is regulated in part by Aurora A, and that excess phosphorylated centrin may promote centrosome amplification in cancer.
C1 [Lukasiewicz, Kara B.; Greenwood, Tammy M.; Salisbury, Jeffrey L.; Lingle, Wilma L.] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN USA.
   [Negron, Vivian C.; Bruzek, Amy K.; Lingle, Wilma L.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
RP Lukasiewicz, KB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cell Cycle Regulat, Program Cell Regulat & Metab, NIH, Bethesda, MD USA.
EM Salisbury@mayo.edu; lingle.wilma@mayo.edu
FU Mayo Clinic Breast Cancer SPORE NIH [CA116201]; NIH [R01 CA072836]; The
   Breast Cancer Research Foundation [FNDTBCRF-16, 17]; Mayo Foundation
FX Funding for this research was through the following grants: Mayo Clinic
   Breast Cancer SPORE NIH CA116201 (W. L. Lingle, Core Leader and James
   Ingle, PI) (http://www.nih.gov/); NIH R01 CA072836 (J.L. Salisbury, PI)
   (http://www.nih.gov/); The Breast Cancer Research Foundation
   FNDTBCRF-16, 17 (W. L. Lingle, Project Leader and J.N. Ingle, PI),
   (http://www.bcrfcure.org/); and Predoctoral Fellowship from the Mayo
   Foundation (http://www.mayo.edu/), (K. B. Lukasiewicz). The funders had
   no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 49
TC 12
Z9 12
U1 0
U2 0
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 JUN 23
PY 2011
VL 6
IS 6
AR e21291
DI 10.1371/journal.pone.0021291
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782TT
UT WOS:000292035400019
PM 21731694
ER

PT J
AU Smith, B
   Chen, ZG
   Reimers, L
   van Doorslaer, K
   Schiffman, M
   DeSalle, R
   Herrero, R
   Yu, K
   Wacholder, S
   Wang, T
   Burk, RD
AF Smith, Benjamin
   Chen, Zigui
   Reimers, Laura
   van Doorslaer, Koenraad
   Schiffman, Mark
   DeSalle, Rob
   Herrero, Rolando
   Yu, Kai
   Wacholder, Sholom
   Wang, Tao
   Burk, Robert D.
TI Sequence Imputation of HPV16 Genomes for Genetic Association Studies
SO PLOS ONE
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS TYPE-16; CERVICAL-CANCER; GENOTYPE IMPUTATION;
   HUMAN-POPULATIONS; NEOPLASIA; VARIANTS; PCR; CARCINOGENICITY;
   CLASSIFICATION; INFECTIONS
AB Background: Human Papillomavirus type 16 (HPV16) causes over half of all cervical cancer and some HPV16 variants are more oncogenic than others. The genetic basis for the extraordinary oncogenic properties of HPV16 compared to other HPVs is unknown. In addition, we neither know which nucleotides vary across and within HPV types and lineages, nor which of the single nucleotide polymorphisms (SNPs) determine oncogenicity.
   Methods: A reference set of 62 HPV16 complete genome sequences was established and used to examine patterns of evolutionary relatedness amongst variants using a pairwise identity heatmap and HPV16 phylogeny. A BLAST-based algorithm was developed to impute complete genome data from partial sequence information using the reference database. To interrogate the oncogenic risk of determined and imputed HPV16 SNPs, odds-ratios for each SNP were calculated in a case-control viral genome-wide association study (VWAS) using biopsy confirmed high-grade cervix neoplasia and self-limited HPV16 infections from Guanacaste, Costa Rica.
   Results: HPV16 variants display evolutionarily stable lineages that contain conserved diagnostic SNPs. The imputation algorithm indicated that an average of 97.5 +/- 1.03% of SNPs could be accurately imputed. The VWAS revealed specific HPV16 viral SNPs associated with variant lineages and elevated odds ratios; however, individual causal SNPs could not be distinguished with certainty due to the nature of HPV evolution.
   Conclusions: Conserved and lineage-specific SNPs can be imputed with a high degree of accuracy from limited viral polymorphic data due to the lack of recombination and the stochastic mechanism of variation accumulation in the HPV genome. However, to determine the role of novel variants or non-lineage-specific SNPs by VWAS will require direct sequence analysis. The investigation of patterns of genetic variation and the identification of diagnostic SNPs for lineages of HPV16 variants provides a valuable resource for future studies of HPV16 pathogenicity.
C1 [Smith, Benjamin; Chen, Zigui; Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
   [Chen, Zigui; van Doorslaer, Koenraad; Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
   [Reimers, Laura; Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10467 USA.
   [Schiffman, Mark; Yu, Kai; Wacholder, Sholom] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [DeSalle, Rob] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA.
   [Herrero, Rolando] Fdn INCIENSA, San Jose, Costa Rica.
   [Wang, Tao; Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
RP Smith, B (reprint author), Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
EM robert.burk@einstein.yu.edu
RI Chen, Zigui/E-8490-2017
FU Public Health Service, National Cancer Institute [CA78527]; Center
   Grants to the Einstein Cancer Research Center; Center for AIDS Research
   (CFAR); American Museum of Natural History; National Cancer Institute,
   National Institutes of Health; Department of Health and Human Services;
   National Institutes of Health [N01-CP-21081, N01-CP-33061, N01-CP-40542,
   N01-CP-50535, N01-CP-81023]
FX R.D.B. is supported in part by Public Health Service award CA78527 from
   the National Cancer Institute and uses facilities supported by Center
   Grants to the Einstein Cancer Research Center and the Center for AIDS
   Research (CFAR). R.D. thanks the Louis and Dorothy Cullman Program in
   Molecular Systematics at the American Museum of Natural History for
   support. The Guanacaste cohort (design and conduct of the study, sample
   collection, management, analysis and interpretation of the data) for the
   enrollment and follow-up phases was supported by the National Cancer
   Institute, National Institutes of Health, Department of Health and Human
   Services. National Institutes of Health (N01-CP-21081, N01-CP-33061,
   N01-CP-40542, N01-CP-50535, N01-CP-81023). The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript. However, some of the investigators are
   intramural NCI investigators, the agency funding the majority of this
   study.
NR 45
TC 34
Z9 35
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 23
PY 2011
VL 6
IS 6
AR e21375
DI 10.1371/journal.pone.0021375
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782TT
UT WOS:000292035400031
PM 21731721
ER

PT J
AU Humblet, O
   Sergeyev, O
   Altshul, L
   Korrick, SA
   Williams, PL
   Emond, C
   Birnbaum, LS
   Burns, JS
   Lee, MM
   Revich, B
   Shelepchikov, A
   Feshin, D
   Hauser, R
AF Humblet, Olivier
   Sergeyev, Oleg
   Altshul, Larisa
   Korrick, Susan A.
   Williams, Paige L.
   Emond, Claude
   Birnbaum, Linda S.
   Burns, Jane S.
   Lee, Mary M.
   Revich, Boris
   Shelepchikov, Andrey
   Feshin, Denis
   Hauser, Russ
TI Temporal trends in serum concentrations of polychlorinated dioxins,
   furans, and PCBs among adult women living in Chapaevsk, Russia: a
   longitudinal study from 2000 to 2009
SO ENVIRONMENTAL HEALTH
LA English
DT Article
ID US POPULATION; EXPOSURE; BIPHENYLS; HEALTH; POLLUTION
AB Background: The present study assessed the temporal trend in serum concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls (PCBs) among residents of a Russian town where levels of these chemicals are elevated due to prior industrial activity.
   Methods: Two serum samples were collected from eight adult women (in 2000 and 2009), and analyzed with gas chromatography-high-resolution mass spectrometry.
   Results: The average total toxic equivalency (TEQ) decreased by 30% (from 36 to 25 pg/g lipid), and the average sum of PCB congeners decreased by 19% (from 291 to 211 ng/g lipid). Total TEQs decreased for seven of the eight women, and the sum of PCBs decreased for six of eight women. During this nine year period, larger decreases in serum TEQs and PCBs were found in women with greater increases in body mass index.
   Conclusions: This study provides suggestive evidence that average serum concentrations of dioxins, furans, and PCBs are decreasing over time among residents of this town.
C1 [Humblet, Olivier; Korrick, Susan A.; Burns, Jane S.; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA.
   [Sergeyev, Oleg] Samara State Med Univ, Dept Phys Educ & Hlth, Samara, Russia.
   [Sergeyev, Oleg] Chapaevsk Med Assoc, Chapaevsk, Russia.
   [Altshul, Larisa] Environm Hlth & Engn Inc, Needham, MA USA.
   [Korrick, Susan A.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
   [Korrick, Susan A.] Harvard Univ, Sch Med, Boston, MA USA.
   [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   [Emond, Claude] Univ Montreal, Fac Med, Dept Environm & Occupat Hlth, Montreal, PQ H3C 3J7, Canada.
   [Emond, Claude] BioSimulat Consulting Inc, Newark, DE USA.
   [Birnbaum, Linda S.] NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA.
   [Lee, Mary M.] Univ Massachusetts, Sch Med, Dept Pediat, Pediat Endocrinol Div, Worcester, MA USA.
   [Lee, Mary M.] Univ Massachusetts, Sch Med, Dept Cell Biol, Pediat Endocrinol Div, Worcester, MA 01655 USA.
   [Revich, Boris] Russian Acad Sci, Inst Forecasting, Ctr Demog & Human Ecol, Moscow, Russia.
   [Shelepchikov, Andrey; Feshin, Denis] Russian Acad Sci, Inst Ecol & Evolut, Moscow, Russia.
RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA.
EM rhauser@hohp.harvard.edu
RI Sergeyev, Oleg/H-8854-2013; 
OI Sergeyev, Oleg/0000-0002-5745-3348; Lee, Mary/0000-0002-7204-4884
FU U.S. EPA [R82943701]; NIEHS [ES014370, ES00002, 5T32-ES07069-28];
   NIEHS/NHGRI [5T32ES016645-02]
FX We gratefully thank the study participants, and the staff of the
   Chapaevsk Medical Association. The research described in this article
   has been reviewed by the National Institute of Environmental Health
   Sciences, and approved for publication. Approval does not signify that
   the contents necessarily reflect the views of the Agency, nor does the
   mention of trade names or commercial products constitute endorsement or
   recommendation for use. This work was funded by U.S. EPA grant R82943701
   and NIEHS grants ES014370, ES00002, and 5T32-ES07069-28. OH was
   supported by 5T32ES016645-02 from NIEHS/NHGRI. MML is a member of the
   UMass DERC (DK32520). LA is a consultant for Environmental Health and
   Engineering, Inc. CE is an International Consultant and the President of
   BioSimulation Consulting Inc.
NR 26
TC 7
Z9 8
U1 0
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-069X
J9 ENVIRON HEALTH-GLOB
JI Environ. Health
PD JUN 22
PY 2011
VL 10
AR 62
DI 10.1186/1476-069X-10-62
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health
GA 796OD
UT WOS:000293060500001
PM 21696632
ER

PT J
AU Nagarajan, S
   Amir, D
   Grupi, A
   Goldenberg, DP
   Minton, AP
   Haas, E
AF Nagarajan, Sureshbabu
   Amir, Dan
   Grupi, Asaf
   Goldenberg, David P.
   Minton, Allen P.
   Haas, Elisha
TI Modulation of Functionally Significant Conformational Equilibria in
   Adenylate Kinase by High Concentrations of Trimethylamine Oxide
   Attributed to Volume Exclusion
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID RESONANCE ENERGY-TRANSFER; PHOSPHOGLYCERATE KINASE; PHYSIOLOGICAL
   CONSEQUENCES; PROTEIN STABILITY; ESCHERICHIA-COLI; YEAST HEXOKINASE;
   ENZYME; DOMAIN; DYNAMICS; FLUORESCENCE
AB The effect of an inert small molecule osmolyte, trimethyl amine N-oxide (TMAO), upon the conformational equilibria of Escherichia coli adenylate kinase was studied using time-resolved FRET. The relative populations of open and closed clefts between the LID and the CORE domains were measured as functions of the concentrations of the substrate ATP over the concentration range 0-18 mM and TMAO over the concentration range 0-4 M. A model was constructed according to which the enzyme exists in equilibrium among four conformational states, corresponding to combinations of open and closed conformations of the LID-CORE and AMP-CORE clefts. ATP is assumed to bind only to those conformations with the closed LID-CORE cleft, and TMAO is assumed to be differentially excluded as a hard spherical particle from each of the four conformations in accordance with calculations based upon x-ray crystallographic structures. This model was found to describe quantitatively the dependence of the fraction of the closed LID-CORE cleft upon the concentrations of both ATP and TMAO over the entire range of concentrations with just five undetermined parameters.
C1 [Nagarajan, Sureshbabu; Amir, Dan; Grupi, Asaf; Haas, Elisha] Bar Ilan Univ, Goodman Fac Life Sci, Ramat Gan, Israel.
   [Goldenberg, David P.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
   [Minton, Allen P.] NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD USA.
RP Haas, E (reprint author), Bar Ilan Univ, Goodman Fac Life Sci, Ramat Gan, Israel.
EM elisha.haas@biu.ac.il
OI Minton, Allen/0000-0001-8459-1247
FU Israel Science Foundation [ISF 1102/06]; United States-Israel Binational
   foundation [BSF 2005270]; U.S. National Science Foundation
   [MCB-0749464]; European Union [29936]; Damadian Center for Magnetic
   Resonance Research, Bar-Ilan University; Intramural Research Division of
   the National Institute of Diabetes and Digestive and Kidney Diseases
FX This work was supported by research and equipment grants from the Israel
   Science Foundation (ISF 1102/06), the United States-Israel Binational
   foundation (BSF 2005270), the U.S. National Science Foundation
   (MCB-0749464), by the Marie Curie Transfer of Knowledge grant from the
   European Union (29936), and by the Damadian Center for Magnetic
   Resonance Research, Bar-Ilan University. A.P.M.'s research is supported
   by the Intramural Research Division of the National Institute of
   Diabetes and Digestive and Kidney Diseases.
NR 54
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Z9 16
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
EI 1542-0086
J9 BIOPHYS J
JI Biophys. J.
PD JUN 22
PY 2011
VL 100
IS 12
BP 2991
EP 2999
DI 10.1016/j.bpj.2011.03.065
PG 9
WC Biophysics
SC Biophysics
GA 785JA
UT WOS:000292224100017
PM 21689533
ER

PT J
AU Chen, B
   Tycko, R
AF Chen, Bo
   Tycko, Robert
TI Simulated Self-Assembly of the HIV-1 Capsid: Protein Shape and Native
   Contacts Are Sufficient for Two-Dimensional Lattice Formation
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VITRO; CRYSTAL-STRUCTURE; INTERSUBUNIT
   INTERACTIONS; DIMERIZATION DOMAIN; TERMINAL DOMAIN; TYPE-1; DYNAMICS;
   KINETICS; POLYMORPHISM
AB We report Monte Carlo simulations of the initial stages of self-assembly of the HIV-1 capsid protein (CA), using a coarse-grained representation that mimics the CA backbone structure and intermolecular contacts observed experimentally. A simple representation of N-terminal domain/N-terminal domain and N-terminal domain/C-terminal domain interactions, coupled with the correct protein shape, is sufficient to drive formation of an ordered lattice with the correct hexagonal symmetry in two dimensions. We derive an approximate concentration/temperature phase diagram for lattice formation, and we investigate the pathway by which the lattice develops from initially separated CA dimers. Within this model, lattice formation occurs in two stages: 1), condensation of CA dimers into disordered clusters; and 2), nucleation of the lattice by the appearance of one hexamer unit within a cluster. Trimers of CA dimers are important early intermediates, and pentamers are metastable within clusters. Introduction of a preformed hexamer at the beginning of a Monte Carlo run does not directly seed lattice formation, but does facilitate the formation of large clusters. We discuss possible connections between these simulations and experimental observations concerning CA assembly within HIV-1 and in vitro.
C1 [Chen, Bo; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
RI Chen, Bo/F-3573-2015
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
   National Institutes of Health; National Institutes of Health
FX This work was supported by the Intramural Research Program of the
   National Institute of Diabetes and Digestive and Kidney Diseases of the
   National Institutes of Health, and by the National Institutes of Health
   Intramural AIDS Targeted Antiviral Program. Computational facilities of
   the Helix Systems at the National Institutes of Health were used in this
   work.
NR 66
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Z9 22
U1 1
U2 28
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD JUN 22
PY 2011
VL 100
IS 12
BP 3035
EP 3044
DI 10.1016/j.bpj.2011.05.025
PG 10
WC Biophysics
SC Biophysics
GA 785JA
UT WOS:000292224100022
PM 21689538
ER

PT J
AU Wang, PY
   Petralia, RS
   Wang, YX
   Wenthold, RJ
   Brenowitz, SD
AF Wang, Philip Y.
   Petralia, Ronald S.
   Wang, Ya-Xian
   Wenthold, Robert J.
   Brenowitz, Stephan D.
TI Functional NMDA Receptors at Axonal Growth Cones of Young Hippocampal
   Neurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID RHO GTPASES; GLUTAMATERGIC SYNAPSES; SYNAPTIC PLASTICITY; NEURITE
   OUTGROWTH; MEMBRANE-PROTEINS; EXPRESSION; MIGRATION; TRAFFICKING;
   TRANSPORT; RELEASE
AB NMDA receptors (NMDARs) are critical to the development of the nervous system, although their roles at axonal growth cones are unclear. We examined NMDAR localization and function at axonal growth cones of young hippocampal neurons. Our immunocytochemical data showed that native and transfected NMDAR subunits are expressed in axons and growth cones of young (days in vitro 3-6) hippocampal rat neurons. Moreover, immunogold electron microscopy showed that NR1 is expressed in growth cones of postnatal day 2 rat hippocampus. Local application of NMDAR agonists to growth cones of voltage-clamped neurons evoked inward currents that were blocked by bath application of an NMDAR antagonist (DL-APV), indicating that these NMDARs are functional. In addition, calcium imaging experiments indicated that NMDARs present in growth cones mediate calcium influx. Calcium transients in growth cones persisted despite pharmacological blockade of voltage-sensitive calcium channels and depletion of intracellular calcium stores. Our findings reveal the presence of functional NMDARs in axons and growth cones of young neurons, suggesting a role for these receptors in axonal guidance and synapse formation during neuronal development.
C1 [Wang, Philip Y.; Brenowitz, Stephan D.] Natl Inst Deafness & Other Commun Disorders, Sect Synapt Transmiss, NIH, Bethesda, MD 20892 USA.
   [Wang, Philip Y.; Petralia, Ronald S.; Wang, Ya-Xian; Wenthold, Robert J.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
RP Brenowitz, SD (reprint author), NIDCD, NIH, 50 South Dr,MSC 8027,Bldg 50,Room 4152, Bethesda, MD 20892 USA.
EM brenowitzs@nidcd.nih.gov
FU NIDCD
FX This work was supported by the NIDCD Intramural Research Program. We
   thank Drs. Katherine Roche, Jeff Diamond, Martin Horak, Elizabeth
   Webber, Catherine Croft Swanwick, Doris Wu, and members of the NIDCD
   Section on Synaptic Transmission and the Laboratory of Neurochemistry
   for critical reading of this manuscript. Thanks to Dr. Fang Hua for
   excellent technical assistance. Dr. Philip Wang was a PhD student in the
   NIH Graduate Partnerships Program with the University of Maryland,
   College Park, Neuroscience and Cognitive Sciences Program, during
   portions of this work. This manuscript is dedicated to the memory of our
   great friend and mentor, Dr. Robert J. Wenthold.
NR 57
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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 JUN 22
PY 2011
VL 31
IS 25
BP 9289
EP 9297
DI 10.1523/JNEUROSCI.5639-10.2011
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 782AT
UT WOS:000291980500023
PM 21697378
ER

PT J
AU Boffetta, P
   McLerran, D
   Chen, Y
   Inoue, M
   Sinha, R
   He, J
   Gupta, PC
   Tsugane, S
   Irie, F
   Tamakoshi, A
   Gao, YT
   Shu, XO
   Wang, RW
   Tsuji, I
   Kuriyama, S
   Matsuo, K
   Satoh, H
   Chen, CJ
   Yuan, JM
   Yoo, KY
   Ahsan, H
   Pan, WH
   Gu, DF
   Pednekar, MS
   Sasazuki, S
   Sairenchi, T
   Yang, G
   Xiang, YB
   Nagai, M
   Tanaka, H
   Nishino, Y
   You, SL
   Koh, WP
   Park, SK
   Shen, CY
   Thornquist, M
   Kang, D
   Rolland, B
   Feng, ZD
   Zheng, W
   Potter, JD
AF Boffetta, Paolo
   McLerran, Dale
   Chen, Yu
   Inoue, Manami
   Sinha, Rashmi
   He, Jiang
   Gupta, Prakash Chandra
   Tsugane, Shoichiro
   Irie, Fujiko
   Tamakoshi, Akiko
   Gao, Yu-Tang
   Shu, Xiao-Ou
   Wang, Renwei
   Tsuji, Ichiro
   Kuriyama, Shinichi
   Matsuo, Keitaro
   Satoh, Hiroshi
   Chen, Chien-Jen
   Yuan, Jian-Min
   Yoo, Keun-Young
   Ahsan, Habibul
   Pan, Wen-Harn
   Gu, Dongfeng
   Pednekar, Mangesh Suryakant
   Sasazuki, Shizuka
   Sairenchi, Toshimi
   Yang, Gong
   Xiang, Yong-Bing
   Nagai, Masato
   Tanaka, Hideo
   Nishino, Yoshikazu
   You, San-Lin
   Koh, Woon-Puay
   Park, Sue K.
   Shen, Chen-Yang
   Thornquist, Mark
   Kang, Daehee
   Rolland, Betsy
   Feng, Ziding
   Zheng, Wei
   Potter, John D.
TI Body Mass Index and Diabetes in Asia: A Cross-Sectional Pooled Analysis
   of 900,000 Individuals in the Asia Cohort Consortium
SO PLOS ONE
LA English
DT Article
ID CARDIOVASCULAR RISK-FACTORS; INSULIN SENSITIVITY; GLUCOSE-TOLERANCE;
   ABDOMINAL OBESITY; FAT DISTRIBUTION; CHINESE WOMEN; FETAL GROWTH;
   LIFE-STYLE; PREVALENCE; TYPE-2
AB Background: The occurrence of diabetes has greatly increased in low- and middle-income countries, particularly in Asia, as has the prevalence of overweight and obesity; in European-derived populations, overweight and obesity are established causes of diabetes. The shape of the association of overweight and obesity with diabetes risk and its overall impact have not been adequately studied in Asia.
   Methods and Findings: A pooled cross-sectional analysis was conducted to evaluate the association between baseline body mass index (BMI, measured as weight in kg divided by the square of height in m) and self-reported diabetes status in over 900,000 individuals recruited in 18 cohorts from Bangladesh, China, India, Japan, Korea, Singapore and Taiwan. Logistic regression models were fitted to calculate cohort-specific odds ratios (OR) of diabetes for categories of increasing BMI, after adjustment for potential confounding factors. OR were pooled across cohorts using a random-effects meta-analysis. The sex- and age-adjusted prevalence of diabetes was 4.3% in the overall population, ranging from 0.5% to 8.2% across participating cohorts. Using the category 22.5-24.9 Kg/m(2) as reference, the OR for diabetes spanned from 0.58 (95% confidence interval [CI] 0.31, 0.76) for BMI lower than 15.0 kg/m(2) to 2.23 (95% CI 1.86, 2.67) for BMI higher than 34.9 kg/m(2). The positive association between BMI and diabetes prevalence was present in all cohorts and in all subgroups of the study population, although the association was stronger in individuals below age 50 at baseline (p-value of interaction <0.001), in cohorts from India and Bangladesh (p<0.001), in individuals with low education (p-value 0.02), and in smokers (p-value 0.03); no differences were observed by gender, urban residence, or alcohol drinking.
   Conclusions: This study estimated the shape and the strength of the association between BMI and prevalence of diabetes in Asian populations and identified patterns of the association by age, country, and other risk factors for diabetes.
C1 [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
   [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
   [McLerran, Dale; Thornquist, Mark; Rolland, Betsy; Feng, Ziding; Potter, John D.] Fred Hutchinson Canc Res Ctr, Dept Publ Hlth Sci, Seattle, WA 98104 USA.
   [Chen, Yu] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA.
   [Inoue, Manami; Tsugane, Shoichiro; Sasazuki, Shizuka] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Epidemiol & Prevent Div, Tokyo 104, Japan.
   [Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA.
   [Gupta, Prakash Chandra; Pednekar, Mangesh Suryakant] Healis Sekhsaria Inst Publ Hlth, Navi Mumbai, India.
   [Irie, Fujiko] Ibaraki Prefectural Govt, Dept Hlth & Social Serv, Ibaraki, Japan.
   [Tamakoshi, Akiko] Aichi Med Univ, Sch Med, Dept Publ Hlth, Aichi, Japan.
   [Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
   [Shu, Xiao-Ou; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Med, Div Epidemiol, Nashville, TN USA.
   [Wang, Renwei] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA.
   [Tsuji, Ichiro; Kuriyama, Shinichi; Nagai, Masato] Tohoku Univ, Grad Sch Med, Dept Publ Hlth & Forens Med, Div Epidemiol, Sendai, Miyagi 980, Japan.
   [Matsuo, Keitaro; Tanaka, Hideo] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 464, Japan.
   [Chen, Chien-Jen; You, San-Lin] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan.
   [Chen, Chien-Jen; Pan, Wen-Harn] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan.
   [Yoo, Keun-Young; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
   [Ahsan, Habibul] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
   [Ahsan, Habibul] Univ Chicago, Dept Med & Human Genet, Chicago, IL 60637 USA.
   [Ahsan, Habibul] Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA.
   [Pan, Wen-Harn] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
   [Pan, Wen-Harn] Natl Taiwan Univ, Dept Biochem Sci & Technol, Taipei 10764, Taiwan.
   [Gu, Dongfeng] Fuwai Hosp, Beijing, Peoples R China.
   [Gu, Dongfeng] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100730, Peoples R China.
   [Gu, Dongfeng] Peking Union Med Coll, China Natl Ctr Cardiovasc Dis, Beijing 100021, Peoples R China.
   [Sairenchi, Toshimi] Dokkyo Med Univ, Sch Med, Dept Publ Hlth, Mibu, Tochigi, Japan.
   [Nishino, Yoshikazu] Miyagi Canc Ctr, Res Inst, Div Epidemiol, Sendai, Miyagi, Japan.
   [Koh, Woon-Puay] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol & Publ Hlth, Singapore 117595, Singapore.
   [Park, Sue K.] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
   [Park, Sue K.] Seoul Natl Univ, Canc Res Inst, Seoul, South Korea.
   [Park, Sue K.] Seoul Natl Univ, Inst Hlth Policy & Management, Seoul, South Korea.
   [Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taiwan Biobank, Taipei, Taiwan.
   [Shen, Chen-Yang] China Med Univ, Grad Inst Environm Sci, Taichung, Taiwan.
RP Boffetta, P (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
EM paolo.boffetta@mssm.edu; jpotter@fhcrc.org
RI Chen, Chien-Jen/C-6976-2008; Sriwisit, Sukhumaphorn/G-1405-2011;
   Tamakoshi, Akiko/D-5105-2012; Shen, CY/F-6271-2010; Kang, Dae
   Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; Park, Sue
   Kyung/J-2757-2012; Tsugane, Shocichiro/A-2424-2015; Sinha,
   Rashmi/G-7446-2015; Tanaka, Hideo/A-8145-2016; 
OI Sinha, Rashmi/0000-0002-2466-7462; Potter, John/0000-0001-5439-1500;
   Yuan, Jian-Min/0000-0002-4620-3108; Matsuo, Keitaro/0000-0003-1761-6314
FU 3-Prefecture Aichi, Ibaraki, Japan Collaborative Cohort Study (JACC);
   Japan Public Health Center-Based Study 1 (JPHC1); Japan Public Health
   Center-Based Study 2 (JPHC2); 3-Prefecture Miyagi, Miyagi, Ohsaki;
   Ministry of Health, Labour and Welfare, Japan; Ministry of Education,
   Culture, Sports, Science and Technology, Japan; China National
   Hypertension Survey Epidemiology Followup Study (CHEFS); American Heart
   Association [9750612N]; National Heart, Lung and Blood Institute [U01
   HL072507]; National Institutes for Health [R01CA0403092, R01CA144034,
   RO1 CA 82729, R37CA70867, R01CA55069, R35CA53890, R01CA80205,
   P42ES010349, R01CA102484, R01CA107431]; National Science Council and
   Department of Health, Taiwan; Department of Health, Taiwan [DOH80-27,
   DOH81-021, DOH8202-1027, DOH83-TD-015, DOH84-TD-006]; Ministry of
   Education, Science and Technology, Korea [2009-0087452]; National
   Research Foundation of Korea [2009-0087452]; International Agency for
   Research on Cancer, Lyon, France; Clinical Trials Service Unit, Oxford,
   U.K; World Health Organisation, Geneva, Switzerland
FX The cohorts participating in the pooled analysis were supported by the
   following grants: 3-Prefecture Aichi, Ibaraki, Japan Collaborative
   Cohort Study (JACC), Japan Public Health Center-Based Study 1 (JPHC1),
   Japan Public Health Center-Based Study 2 (JPHC2); 3-Prefecture Miyagi,
   Miyagi, Ohsaki: Grant in-aid for Cancer Research, Grant for the Third
   Term Comprehensive Control Research for Cancer, Grant for Health
   Services, Grant for Medical Services for Aged and Health Promotion,
   Grant for Comprehensive Research on Cardiovascular and Life-Style
   Related Diseases from the Ministry of Health, Labour and Welfare, Japan;
   Grant for the Scientific Research from the Ministry of Education,
   Culture, Sports, Science and Technology, Japan; China National
   Hypertension Survey Epidemiology Followup Study (CHEFS): American Heart
   Association (9750612N); National Heart, Lung and Blood Institute (U01
   HL072507); Chinese Academy of Medical Sciences Shanghai Cohort Study
   (SCS): National Institutes for Health (R01CA0403092, R01CA144034);
   Shanghai Men's Health Study (SMHS): National Institutes for Health (RO1
   CA 82729) Shanghai Women's Health Study (SWHS): National Institutes for
   Health (R37CA70867); The Community-Based Cancer Screening Project
   (CBCSP): National Science Council and Department of Health, Taiwan;
   Disease risk FACtor Two-township Study (CVDFACTS): Department of Health,
   Taiwan (DOH80-27, DOH81-021, DOH8202-1027, DOH83-TD-015, and
   DOH84-TD-006); The Korea Multi-center Cancer Cohort (KMCC): Ministry of
   Education, Science and Technology, Korea (2009-0087452), National
   Research Foundation of Korea (2009-0087452); The Singapore Chinese
   Health Study (SCHS): National Institutes for Health (R01CA55069,
   R35CA53890, R01CA80205, R01CA144034); Health Effects of Arsenic
   Longitudinal Study ( HEALS): National Institutes for Health
   (P42ES010349, R01CA102484, R01CA107431); The Mumbai Cohort Study (MCS):
   International Agency for Research on Cancer, Lyon, France; Clinical
   Trials Service Unit, Oxford, U.K; World Health Organisation, Geneva,
   Switzerland. The funders had no role in study design, data collection
   and analysis, decision to publish, or preparation of the manuscript.
NR 49
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PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 22
PY 2011
VL 6
IS 6
AR e19930
DI 10.1371/journal.pone.0019930
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782TF
UT WOS:000292033700006
PM 21731609
ER

PT J
AU Florea, L
   Souvorov, A
   Kalbfleisch, TS
   Salzberg, SL
AF Florea, Liliana
   Souvorov, Alexander
   Kalbfleisch, Theodore S.
   Salzberg, Steven L.
TI Genome Assembly Has a Major Impact on Gene Content: A Comparison of
   Annotation in Two Bos Taurus Assemblies
SO PLOS ONE
LA English
DT Article
ID SEQUENCE; PROGRAM; NUMBER; BLAST; TOOL
AB Gene and SNP annotation are among the first and most important steps in analyzing a genome. As the number of sequenced genomes continues to grow, a key question is: how does the quality of the assembled sequence affect the annotations? We compared the gene and SNP annotations for two different Bos taurus genome assemblies built from the same data but with significant improvements in the later assembly. The same annotation software was used for annotating both sequences. While some annotation differences are expected even between high-quality assemblies such as these, we found that a staggering 40% of the genes (>9,500) varied significantly between assemblies, due in part to the availability of new gene evidence but primarily to genome mis-assembly events and local sequence variations. For instance, although the later assembly is generally superior, 660 protein coding genes in the earlier assembly are entirely missing from the later genome's annotation, and approximately 3,600 (15%) of the genes have complex structural differences between the two assemblies. In addition, 12-20% of the predicted proteins in both assemblies have relatively large sequence differences when compared to their RefSeq models, and 6-15% of bovine dbSNP records are unrecoverable in the two assemblies. Our findings highlight the consequences of genome assembly quality on gene and SNP annotation and argue for continued improvements in any draft genome sequence. We also found that tracking a gene between different assemblies of the same genome is surprisingly difficult, due to the numerous changes, both small and large, that occur in some genes. As a side benefit, our analyses helped us identify many specific loci for improvement in the Bos taurus genome assembly.
C1 [Florea, Liliana; Salzberg, Steven L.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
   [Souvorov, Alexander] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
   [Kalbfleisch, Theodore S.] Univ Louisville, Ctr Genet & Mol Med, Louisville, KY 40292 USA.
RP Florea, L (reprint author), Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
EM florea@umiacs.umd.edu
RI Salzberg, Steven/F-6162-2011
OI Salzberg, Steven/0000-0002-8859-7432
FU National Institutes of Health [R01-LM006845, 3P20RR016481-09S1,
   1P30ES014443-01A1]; USDA National Institute of Food and Agriculture
   [2009-35205-05209]; U.S. Department of Energy [DE-EM0000197]
FX This work was supported in part by grant R01-LM006845 from the National
   Institutes of Health and by National Research Initiative Competitive
   Grant no. 2009-35205-05209 from the USDA National Institute of Food and
   Agriculture to SLS. TSK was supported in part by funding from the U.S.
   Department of Energy DE-EM0000197 and funding from the National
   Institutes of Health 3P20RR016481-09S1 and 1P30ES014443-01A1. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 25
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PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 22
PY 2011
VL 6
IS 6
AR e21400
DI 10.1371/journal.pone.0021400
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782TF
UT WOS:000292033700075
PM 21731731
ER

PT J
AU Lee, JH
   Voortman, J
   Dingemans, AMC
   Voeller, DM
   Pham, T
   Wang, YS
   Giaccone, G
AF Lee, Jih-Hsiang
   Voortman, Johannes
   Dingemans, Anne-Marie C.
   Voeller, Donna M.
   Pham, Trung
   Wang, Yisong
   Giaccone, Giuseppe
TI MicroRNA Expression and Clinical Outcome of Small Cell Lung Cancer
SO PLOS ONE
LA English
DT Article
ID PREDICTS SURVIVAL; GENE-EXPRESSION; DOWN-REGULATION; MIR-34A; CARCINOMA;
   FAMILY; CHEMORESISTANCE; CHEMOTHERAPY; APOPTOSIS; INVASION
AB The role of microRNAs in small-cell lung carcinoma (SCLC) is largely unknown. miR-34a is known as a p53 regulated tumor suppressor microRNA in many cancer types. However, its therapeutic implication has never been studied in SCLC, a cancer type with frequent dysfunction of p53. We investigated the expression of a panel of 7 microRNAs (miR-21, miR-29b, miR-34a/b/c, miR-155, and let-7a) in 31 SCLC tumors, 14 SCLC cell lines, and 26 NSCLC cell lines. We observed significantly lower miR-21, miR-29b, and miR-34a expression in SCLC cell lines than in NSCLC cell lines. The expression of the 7 microRNAs was unrelated to SCLC patients' clinical characteristics and was neither prognostic in term of overall survival or progression-free survival nor predictive of treatment response. Overexpression or downregulation of miR-34a did not influence SCLC cell viability. The expression of these 7 microRNAs also did not predict in vitro sensitivity to cisplatin or etoposide in SCLC cell lines. Overexpression or downregulation of miR-34a did not influence sensitivity to cisplatin or etoposide in SCLC cell lines. In contrast to downregulation of the miR-34a target genes cMET and Axl by overexpression of miR-34a in NSCLC cell lines, the intrinsic expression of cMET and Axl was low in SCLC cell lines and was not influenced by overexpression of miR-34a. Our results suggest that the expression of the 7 selected microRNAs are not prognostic in SCLC patients, and miR-34a is unrelated to the malignant behavior of SCLC cells and is unlikely to be a therapeutic target.
C1 [Lee, Jih-Hsiang; Voortman, Johannes; Voeller, Donna M.; Pham, Trung; Wang, Yisong; Giaccone, Giuseppe] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
   [Dingemans, Anne-Marie C.] Maastricht Univ Med Ctr, GROW Sch Oncol & Dev Biol, Dept Resp Med, Maastricht, Netherlands.
RP Lee, JH (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM giacconeg@mail.nih.gov
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU National Institutes of Health, National Cancer Institute
FX The study was funded by the National Institutes of Health, National
   Cancer Institute intramural program. No additional external funding was
   received for this study. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
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PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 22
PY 2011
VL 6
IS 6
AR e21300
DI 10.1371/journal.pone.0021300
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782TF
UT WOS:000292033700058
PM 21731696
ER

PT J
AU Liaw, H
   Lee, D
   Myung, K
AF Liaw, Hungjiun
   Lee, Deokjae
   Myung, Kyungjae
TI DNA-PK-Dependent RPA2 Hyperphosphorylation Facilitates DNA Repair and
   Suppresses Sister Chromatid Exchange
SO PLOS ONE
LA English
DT Article
ID REPLICATION PROTEIN-A; RADIATION-INDUCED PHOSPHORYLATION; S-PHASE
   CHECKPOINT; ATAXIA-TELANGIECTASIA; BINDING PROTEIN; P34 SUBUNIT;
   POLYMERASE-ETA; HUMAN-CELLS; HELA-CELLS; KINASE
AB Hyperphosphorylation of RPA2 at serine 4 and serine 8 (S4, S8) has been used as a marker for activation of the DNA damage response. What types of DNA lesions cause RPA2 hyperphosphorylation, which kinase(s) are responsible for them, and what is the biological outcome of these phosphorylations, however, have not been fully investigated. In this study we demonstrate that RPA2 hyperphosphorylation occurs primarily in response to genotoxic stresses that cause high levels of DNA double-strand breaks (DSBs) and that the DNA-dependent protein kinase complex (DNA-PK) is responsible for the modifications in vivo. Alteration of S4, S8 of RPA2 to alanines, which prevent phosphorylations at these sites, caused increased mitotic entry with concomitant increases in RAD51 foci and homologous recombination. Taken together, our results demonstrate that RPA2 hyperphosphorylation by DNA-PK in response to DSBs blocks unscheduled homologous recombination and delays mitotic entry. This pathway thus permits cells to repair DNA damage properly and increase cell viability.
C1 [Liaw, Hungjiun; Lee, Deokjae; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Liaw, H (reprint author), Natl Cheng Kung Univ, Dept Life Sci, Tainan 70101, Taiwan.
EM kmyung@mail.nih.gov
RI Liaw, Hungjiun/G-7034-2014
OI Liaw, Hungjiun/0000-0002-3481-709X
FU National Human Genome Research Institute, National Institutes of Health
   [HG012003-09]
FX This work was supported by National Human Genome Research Institute,
   National Institutes of Health (HG012003-09). The funders had no role in
   study design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
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SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 22
PY 2011
VL 6
IS 6
AR e21424
DI 10.1371/journal.pone.0021424
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782TF
UT WOS:000292033700082
PM 21731742
ER

PT J
AU Taveira-DaSilva, AM
   Hathaway, O
   Stylianou, M
   Moss, J
AF Taveira-DaSilva, Angelo M.
   Hathaway, Olanda
   Stylianou, Mario
   Moss, Joel
TI Changes in Lung Function and Chylous Effusions in Patients With
   Lymphangioleiomyomatosis Treated With Sirolimus
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; PULMONARY LYMPHANGIOLEIOMYOMATOSIS;
   GENE-PRODUCTS; MOUSE MODELS; IFN-GAMMA; RAPAMYCIN; LAM; CHYLOTHORAX;
   DISEASE; WOMEN
AB Background: Lymphangioleiomyomatosis (LAM) is a disorder that affects women and is characterized by cystic lung destruction, chylous effusions, lymphangioleiomyomas, and angiomyolipomas. It is caused by proliferation of abnormal smooth muscle-like cells. Sirolimus is a mammalian target of rapamycin inhibitor that has been reported to decrease the size of neoplastic growths in animal models of tuberous sclerosis complex and to reduce the size of angiomyolipomas and stabilize lung function in humans.
   Objective: To assess whether sirolimus therapy is associated with improvement in lung function and a decrease in the size of chylous effusions and lymphangioleiomyomas in patients with LAM.
   Design: Observational study.
   Setting: The National Institutes of Health Clinical Center.
   Patients: 19 patients with rapidly progressing LAM or chylous effusions.
   Intervention: Treatment with sirolimus.
   Measurements: Lung function and the size of chylous effusions and lymphangioleiomyomas before and during sirolimus therapy.
   Results: Over a mean of 2.5 years before beginning sirolimus therapy, the mean (+/- SE) FEV1 decreased by 2.8% +/- 0.8% predicted and diffusing capacity of the lung for carbon monoxide (DLCO) decreased by 4.8% +/- 0.9% predicted per year. In contrast, over a mean of 2.6 years of sirolimus therapy, the mean (+/- SE) FEV1 increased by 1.8% +/- 0.5% predicted and DLCO increased by 0.8% +/- 0.5% predicted per year (P < 0.001). After beginning sirolimus therapy, 12 patients with chylous effusions and 11 patients with lymphangioleiomyomas experienced almost complete resolution of these conditions. In 2 of the 12 patients, sirolimus therapy enabled discontinuation of pleural fluid drainage.
   Limitations: This was an observational study. The resolution of effusions may have affected improvements in lung function.
   Conclusion: Sirolimus therapy is associated with improvement or stabilization of lung function and reduction in the size of chylous effusions and lymphangioleiomyomas in patients with LAM.
C1 [Taveira-DaSilva, Angelo M.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
RP Taveira-DaSilva, AM (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA.
EM dasilvaa@nhlbi.nih.gov
FU NHLBI, NIH [95-H-0186]
FX Grant Support: By the Intramural Research Program, NHLBI, NIH (protocol
   95-H-0186).
NR 45
TC 64
Z9 65
U1 0
U2 3
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUN 21
PY 2011
VL 154
IS 12
BP 797
EP 805
DI 10.7326/0003-4819-154-12-201106210-00007
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 779SA
UT WOS:000291800500015
PM 21690594
ER

PT J
AU Seibert, D
   Hong, CH
   Takeuchi, F
   Olsen, C
   Hathaway, O
   Moss, J
   Darling, TN
AF Seibert, Diane
   Hong, Chien-Hui
   Takeuchi, Fumiko
   Olsen, Cara
   Hathaway, Olonda
   Moss, Joel
   Darling, Thomas N.
TI Recognition of Tuberous Sclerosis in Adult Women: Delayed Presentation
   With Life-Threatening Consequences
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID PULMONARY LYMPHANGIOLEIOMYOMATOSIS; CLINICAL CHARACTERISTICS; RENAL
   ANGIOMYOLIPOMA; CONSENSUS CONFERENCE; FORME-FRUSTE; COMPLEX; PREVALENCE;
   DIAGNOSIS; MUTATION; ASSOCIATION
AB Background: Tuberous sclerosis complex (TSC) is associated with tumor development in the brain, retina, kidney, skin, heart, and lung. Seizures, intellectual disability, and characteristic skin lesions commonly manifest in early childhood, but some findings, notably renal angiomyolipomas and pulmonary lymphangioleiomyomatosis (LAM), emerge later, placing adults with undiagnosed TSC at increased risk for morbidity and mortality.
   Objective: To describe the clinical presentation and severity of TSC in adult women.
   Design: Retrospective cohort study.
   Setting: National Institutes of Health Clinical Center, Bethesda, Maryland, 1995 to 2010.
   Patients: 79 women aged 18 years or older who were enrolled in an observational cohort study of TSC to evaluate disease manifestations.
   Measurements: History, physical examination, pulmonary function testing, chest radiography, abdominal computed tomography, high-resolution chest computed tomography, and brain magnetic resonance imaging were used to evaluate patients.
   Results: Among the 45 patients who received a diagnosis of TSC in adulthood, 21 presented with symptoms due to LAM, 19 with renal angiomyolipomas, and 10 with seizures. Of the 45 patients, 30 met clinical criteria for TSC in childhood that remained undiagnosed for a median of 21.5 years and 15 were older than 18 years before meeting the clinical criteria for TSC. Patients diagnosed in adulthood and those diagnosed in childhood had similar occurrences of pneumothorax, shortness of breath, hemoptysis, nephrectomy, and death.
   Limitation: No men were included in the study, and selection was biased toward patients having pulmonary LAM.
   Conclusion: Women who received a TSC diagnosis in adulthood had minimal morbidity during childhood but were still at risk for life-threatening pulmonary and renal manifestations.
C1 [Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA.
   NHLBI, Bethesda, MD 20892 USA.
   Kaohsiung Vet Gen Hosp, Kaohsiung, Taiwan.
RP Darling, TN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Dermatol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM mossj@nhlbi.nih.gov; tdarling@usuhs.mil
OI Darling, Thomas/0000-0002-5161-1974
FU National Institutes of Health, National Heart, Lung, and Blood
   Institute; National Cancer Institute [R01 CA100907]; Congressionally
   Directed Medical Research Programs [TS080064]
FX Grant Support: From the Intramural Research Program, National Institutes
   of Health, National Heart, Lung, and Blood Institute, and grants from
   the National Cancer Institute (R01 CA100907; Dr. Darling) and the
   Congressionally Directed Medical Research Programs (TS080064; Dr.
   Darling).
NR 43
TC 25
Z9 26
U1 0
U2 4
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUN 21
PY 2011
VL 154
IS 12
BP 806
EP 813
DI 10.7326/0003-4819-154-12-201106210-00008
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 779SA
UT WOS:000291800500016
PM 21690595
ER

PT J
AU Tu, C
   Zhou, XM
   Tarasov, SG
   Tropea, JE
   Austin, BP
   Waugh, DS
   Court, DL
   Ji, XH
AF Tu, Chao
   Zhou, Xiaomei
   Tarasov, Sergey G.
   Tropea, Joseph E.
   Austin, Brian P.
   Waugh, David S.
   Court, Donald L.
   Ji, Xinhua
TI The Era GTPase recognizes the GAUCACCUCC sequence and binds helix 45
   near the 3 ' end of 16S rRNA
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE ribosome biogenesis; cell growth regulation
ID INITIATION-FACTOR IF3; ESCHERICHIA-COLI; TRANSLATIONAL INITIATION;
   MESSENGER-RNA; SUBUNIT INTERFACE; CROSS-LINKING; KSGA;
   METHYLTRANSFERASE; PROTEIN; BIOGENESIS
AB Era, composed of a GTPase domain and a K homology domain, is essential for bacterial cell viability. It is required for the maturation of 16S rRNA and assembly of the 30S ribosomal subunit. We showed previously that the protein recognizes nine nucleotides ((1531)AUCACCUCC(1539)) near the 3' end of 16S rRNA, and that this recognition stimulates GTP-hydrolyzing activity of Era. In all three kingdoms of life, the (1530)GAUCA(1534) sequence and helix 45 (h45) (nucleotides 1506-1529) are highly conserved. It has been shown that the (1530)GA(1531) to (1530)AG(1531) double mutation severely affects the viability of bacteria. However, whether Era interacts with G1530 and/or h45 and whether such interactions (if any) contribute to the stimulation of Era's GTPase activity were not known. Here, we report two RNA structures that contain nucleotides 1506-1542 (RNA301), one in complex with Era and GDPNP (GNP), a nonhydrolysable GTP-analogue, and the other in complex with Era, GNP, and the KsgA methyltransferase. The structures show that Era recognizes 10 nucleotides, including G1530, and that Era also binds h45. Moreover, GTPase assay experiments show that G1530 does not stimulate Era's GTPase activity. Rather, A1531 and A1534 are most important for stimulation and h45 further contributes to the stimulation. Although G1530 does not contribute to the intrinsic GTPase activity of Era, its interaction with Era is important for binding and is essential for the protein to function, leading to the discovery of a new cold-sensitive phenotype of Era.
C1 [Tu, Chao; Zhou, Xiaomei; Tarasov, Sergey G.; Tropea, Joseph E.; Austin, Brian P.; Waugh, David S.; Court, Donald L.; Ji, Xinhua] NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Court, DL (reprint author), NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
EM donald.court@nih.gov; jix@mail.nih.gov
RI Ji, Xinhua/C-9664-2012
OI Ji, Xinhua/0000-0001-6942-1514
FU National Institutes of Health, National Cancer Institute, Center for
   Cancer Research
FX Data were collected at the Southeast Regional Collaborative Access Team
   (SER-CAT) of the Advanced Photon Source, Argonne National Laboratory.
   This research was supported by the Intramural Research Program of the
   National Institutes of Health, National Cancer Institute, Center for
   Cancer Research.
NR 36
TC 12
Z9 12
U1 0
U2 6
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 21
PY 2011
VL 108
IS 25
BP 10156
EP 10161
DI 10.1073/pnas.1017679108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 780LK
UT WOS:000291857500031
PM 21646538
ER

PT J
AU Rambold, AS
   Kostelecky, B
   Elia, N
   Lippincott-Schwartz, J
AF Rambold, Angelika S.
   Kostelecky, Brenda
   Elia, Natalie
   Lippincott-Schwartz, Jennifer
TI Tubular network formation protects mitochondria from autophagosomal
   degradation during nutrient starvation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE autophagy; mitofusin
ID DYNAMIN-RELATED GTPASE; MAMMALIAN-CELLS; FISSION; FUSION; DRP1;
   APOPTOSIS; MORPHOLOGY; MITOFUSIN; BAX; PHOSPHORYLATION
AB Mitochondria are highly dynamic organelles that mediate essential cell functions such as apoptosis and cell-cycle control in addition to their role as efficient ATP generators. Mitochondrial morphology changes are tightly regulated, and their shape can shift between small, fragmented units and larger networks of elongated mitochondria. We demonstrate that mitochondrial elements become significantly elongated and interconnected shortly after nutrient depletion. This mitochondrial morphological shift depends on the type of starvation, with an additive effect observed when multiple nutrients are depleted simultaneously. We further show that starvation-induced mitochondrial elongation is mediated by down-regulation of dynamin-related protein 1 (Drp1) through modulation of two Drp1 phosphorylation sites, leading to unopposed mitochondrial fusion. Finally, we establish that mitochondrial tubulation upon nutrient deprivation protects mitochondria from autophagosomal degradation, which could permit mitochondria to maximize energy production and supply autophagosomal membranes during starvation.
C1 [Rambold, Angelika S.; Kostelecky, Brenda; Elia, Natalie; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Lippincott-Schwartz, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM lippincj@mail.nih.gov
FU Deutsche Forschungsgemeinschaft
FX We thank R. Youle for contributing the Bax/BakDKO cells and the YFP-Drp1
   construct and N. Mizushima and D. C. Chan for contributing the ATG5KO
   and Mfn-deficient cell lines, respectively. We thank K. Mitra for
   helpful discussions. A. R. was supported by a postdoctoral fellowship
   from the Deutsche Forschungsgemeinschaft.
NR 47
TC 278
Z9 279
U1 5
U2 32
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 21
PY 2011
VL 108
IS 25
BP 10190
EP 10195
DI 10.1073/pnas.1107402108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 780LK
UT WOS:000291857500037
PM 21646527
ER

PT J
AU Georgea, DB
   Webb, CT
   Farnsworth, ML
   O'Shea, TJ
   Bowen, RA
   Smith, DL
   Stanley, TR
   Ellison, LE
   Rupprecht, CE
AF Georgea, Dylan B.
   Webb, Colleen T.
   Farnsworth, Matthew L.
   O'Shea, Thomas J.
   Bowen, Richard A.
   Smith, David L.
   Stanley, Thomas R.
   Ellison, Laura E.
   Rupprecht, Charles E.
TI Host and viral ecology determine bat rabies seasonality and maintenance
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE chiroptera; pathogen persistence; torpor
ID BIG BROWN BATS; EPTESICUS-FUSCUS; UNITED-STATES; DYNAMICS; COLORADO;
   PROBABILITIES; DISEASE; EPIDEMIOLOGY; SURVEILLANCE; TRANSMISSION
AB Rabies is an acute viral infection that is typically fatal. Most rabies modeling has focused on disease dynamics and control within terrestrial mammals (e. g., raccoons and foxes). As such, rabies in bats has been largely neglected until recently. Because bats have been implicated as natural reservoirs for several emerging zoonotic viruses, including SARS-like corona viruses, henipaviruses, and lyssaviruses, understanding how pathogens are maintained within a population becomes vital. Unfortunately, little is known about maintenance mechanisms for any pathogen in bat populations. We present a mathematical model parameterized with unique data from an extensive study of rabies in a Colorado population of big brown bats (Eptesicus fuscus) to elucidate general maintenance mechanisms. We propose that life history patterns of many species of temperate-zone bats, coupled with sufficiently long incubation periods, allows for rabies virus maintenance. Seasonal variability in bat mortality rates, specifically low mortality during hibernation, allows long-term bat population viability. Within viable bat populations, sufficiently long incubation periods allow enough infected individuals to enter hibernation and survive until the following year, and hence avoid an epizootic fadeout of rabies virus. We hypothesize that the slowing effects of hibernation on metabolic and viral activity maintains infected individuals and their pathogens until susceptibles from the annual birth pulse become infected and continue the cycle. This research provides a context to explore similar host ecology and viral dynamics that may explain seasonal patterns and maintenance of other bat-borne diseases.
C1 [Georgea, Dylan B.; Webb, Colleen T.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA.
   [Georgea, Dylan B.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Farnsworth, Matthew L.; Bowen, Richard A.] Colorado State Univ, Dept Biomed Sci, Ft Collins, CO 80523 USA.
   [Smith, David L.] Univ Florida, Dept Biol, Gainesville, FL 32610 USA.
   [Smith, David L.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32610 USA.
   [O'Shea, Thomas J.; Stanley, Thomas R.; Ellison, Laura E.] US Geol Survey, Ft Collins Sci Ctr, Ft Collins, CO 80526 USA.
   [Rupprecht, Charles E.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA.
RP Georgea, DB (reprint author), Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA.
EM dylangeorge@gmail.com
RI Smith, David/L-8850-2013
OI Smith, David/0000-0003-4367-3849
FU National Science Foundation [EF-0094959, DGE-0221595]; Science and
   Technology Directorate in the Department of Homeland Security; Fogarty
   International Center, National Institutes of Health; US Geological
   Survey; Department of Defense
FX We are grateful for data from the Colorado Department of Public Health
   and Environment. We thank state public health departments and diagnostic
   laboratories for collecting primary data and staff at the Center for
   Disease Control Rabies Program for data compilation. We acknowledge
   support from National Science Foundation Ecology of Infectious Disease
   Grant EF-0094959; the Research And Policy In Disease Dynamics program of
   the Science and Technology Directorate in the Department of Homeland
   Security; the Fogarty International Center, National Institutes of
   Health; and the US Geological Survey. Additional support was provided by
   National Science Foundation Integrative Graduate Education and Research
   Training Fellowship DGE-0221595 and a Department of Defense Science,
   Mathematics, and Research for Transformation (SMART) Fellowship (to
   D.B.G.).
NR 37
TC 55
Z9 55
U1 4
U2 60
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 21
PY 2011
VL 108
IS 25
BP 10208
EP 10213
DI 10.1073/pnas.1010875108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 780LK
UT WOS:000291857500040
PM 21646516
ER

PT J
AU Tadenev, ALD
   Kulaga, HM
   May-Simera, HL
   Kelley, MW
   Katsanis, N
   Reed, RR
AF Tadenev, Abigail L. D.
   Kulaga, Heather M.
   May-Simera, Helen L.
   Kelley, Matthew W.
   Katsanis, Nicholas
   Reed, Randall R.
TI Loss of Bardet-Biedl syndrome protein-8 (BBS8) perturbs olfactory
   function, protein localization, and axon targeting
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE ciliopathy; olfactory activity; protein trafficking
ID PLANAR CELL POLARITY; MOUSE MODEL; INTRAFLAGELLAR TRANSPORT; ODORANT
   RECEPTOR; SYNDROME GENES; CILIA DEFECTS; MICE; CILIOGENESIS;
   PROJECTIONS; RETINOPATHY
AB Bardet-Biedl syndrome (BBS) is a pleiotropic, heterogeneous human disease whose etiology lies primarily in dysfunctional basal bodies and/or cilia. Both BBS patients and several BBS mouse models exhibit impaired olfactory function. To explore the nature of olfactory defects in BBS, a genetic ablation of the mouse Bbs8 gene that incorporates a fluorescent reporter protein was created. The endogenous BBS8 protein and reporter are particularly abundant in olfactory sensory neurons (OSNs), and specific BBS8 antibodies reveal staining in the dendritic knob in a shell-like structure that surrounds the basal bodies. Bbs8-null mice have reduced olfactory responses to a number of odorants, and immunohistochemical analyses reveal a near-complete loss of cilia from OSNs and mislocalization of proteins normally enriched in cilia. To visualize altered protein localization in OSNs, we generated a SLP(3eGFP) knock-in mouse and imaged the apical epithelium, including dendritic knobs and proximal cilia, in ex vivo tissue preparations. Additionally, protein reagents that reflect the characteristic neuronal activity of each OSN revealed altered activity in Bbs8-null cells. In addition to previously known defects at the ciliary border, we also observed aberrant targeting of OSN axons to the olfactory bulb; axons expressing the same receptor display reduced fasciculation and project to multiple targets in the olfactory bulb. We suggest that loss of BBS8 leads to a dramatic and variable reduction in cilia, the essential signaling platform for olfaction, which alters the uniformity of responses in populations of OSNs expressing the same receptor, thereby contributing to the observed axon-targeting defects.
C1 [Tadenev, Abigail L. D.; Kulaga, Heather M.; Reed, Randall R.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Ctr Sensory Biol, Baltimore, MD 21205 USA.
   [May-Simera, Helen L.; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Lab Cochlear Dev, NIH, Bethesda, MD 20892 USA.
   [Katsanis, Nicholas] Duke Univ, Dept Cell Biol, Ctr Human Dis Modeling, Durham, NC 27710 USA.
   [Katsanis, Nicholas] Duke Univ, Dept Pediat, Durham, NC 27710 USA.
RP Reed, RR (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Ctr Sensory Biol, Baltimore, MD 21205 USA.
EM rreed@jhmi.edu
RI Katsanis, Nicholas/E-1837-2012; 
OI Katsanis, Nicholas/0000-0002-2480-0171
FU NICHD NIH HHS [R01 HD042601]; NIDCD NIH HHS [R01 DC008295]
NR 35
TC 24
Z9 24
U1 1
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 21
PY 2011
VL 108
IS 25
BP 10320
EP 10325
DI 10.1073/pnas.1016531108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 780LK
UT WOS:000291857500059
PM 21646512
ER

PT J
AU Powe, CE
   Levine, RJ
   Karumanchi, SA
AF Powe, Camille E.
   Levine, Richard J.
   Karumanchi, S. Ananth
TI Preeclampsia, a Disease of the Maternal Endothelium The Role of
   Antiangiogenic Factors and Implications for Later Cardiovascular Disease
SO CIRCULATION
LA English
DT Article
DE hypertension; preeclampsia; pregnancy; proteinuria; VEGF
ID GROWTH-FACTOR RECEPTOR; CIRCULATING ANGIOGENIC FACTORS; ELEVATED
   LIVER-ENZYMES; POSTERIOR LEUKOENCEPHALOPATHY SYNDROME; HEREDITARY
   HEMORRHAGIC TELANGIECTASIA; PREGNANCY-INDUCED HYPERTENSION; TYROSINE
   KINASE-1 EXPRESSION; VASCULAR-PERMEABILITY FACTOR; REDUCED UTERINE
   PERFUSION; NECROSIS-FACTOR-ALPHA
C1 [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Howard Hughes Med Inst, Boston, MA 02215 USA.
   [Powe, Camille E.; Karumanchi, S. Ananth] Harvard Univ, Sch Med, Boston, MA USA.
   [Levine, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Dept HHS, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
RP Karumanchi, SA (reprint author), Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Howard Hughes Med Inst, RN 370D,99 Brookline Ave, Boston, MA 02215 USA.
EM sananth@bidmc.harvard.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
   Development; Howard Hughes Medical Institute; American Heart
   Association; Burroughs Wellcome Fund
FX C.E.P. is a Howard Hughes Institute Medical Research Training Fellow. Dr
   Levine receives salary support from the intramural research program of
   the Eunice Kennedy Shriver National Institute of Child Health and Human
   Development. Dr Karumanchi is supported by the Howard Hughes Medical
   Institute, an Established Investigator award from the American Heart
   Association, and a Clinical Scientist award from the Burroughs Wellcome
   Fund.
NR 192
TC 228
Z9 244
U1 2
U2 37
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUN 21
PY 2011
VL 123
IS 24
BP 2856
EP 2869
DI 10.1161/CIRCULATIONAHA.109.853127
PG 14
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 779QM
UT WOS:000291795200019
PM 21690502
ER

PT J
AU Chowell, G
   Viboud, C
   Munayco, CV
   Gomez, J
   Simonsen, L
   Miller, MA
   Tamerius, J
   Fiestas, V
   Halsey, ES
   Laguna-Torres, VA
AF Chowell, Gerardo
   Viboud, Cecile
   Munayco, Cesar V.
   Gomez, Jorge
   Simonsen, Lone
   Miller, Mark A.
   Tamerius, James
   Fiestas, Victor
   Halsey, Eric S.
   Laguna-Torres, Victor A.
TI Spatial and Temporal Characteristics of the 2009 A/H1N1 Influenza
   Pandemic in Peru
SO PLOS ONE
LA English
DT Article
ID A H1N1 VIRUS; NEW-YORK-CITY; REPRODUCTION NUMBER; EPIDEMIC INFLUENZA;
   ABSOLUTE-HUMIDITY; TRANSMISSION; MORTALITY; WAVE; SEASONALITY; PATTERNS
AB Background: Highly refined surveillance data on the 2009 A/H1N1 influenza pandemic are crucial to quantify the spatial and temporal characteristics of the pandemic. There is little information about the spatial-temporal dynamics of pandemic influenza in South America. Here we provide a quantitative description of the age- specific morbidity pandemic patterns across administrative areas of Peru.
   Methods: We used daily cases of influenza-like-illness, tests for A/H1N1 influenza virus infections, and laboratory-confirmed A/H1N1 influenza cases reported to the epidemiological surveillance system of Peru's Ministry of Health from May 1 to December 31, 2009. We analyzed the geographic spread of the pandemic waves and their association with the winter school vacation period, demographic factors, and absolute humidity. We also estimated the reproduction number and quantified the association between the winter school vacation period and the age distribution of cases.
   Results: The national pandemic curve revealed a bimodal winter pandemic wave, with the first peak limited to school age children in the Lima metropolitan area, and the second peak more geographically widespread. The reproduction number was estimated at 1.6-2.2 for the Lima metropolitan area and 1.3-1.5 in the rest of Peru. We found a significant association between the timing of the school vacation period and changes in the age distribution of cases, while earlier pandemic onset was correlated with large population size. By contrast there was no association between pandemic dynamics and absolute humidity.
   Conclusions: Our results indicate substantial spatial variation in pandemic patterns across Peru, with two pandemic waves of varying timing and impact by age and region. Moreover, the Peru data suggest a hierarchical transmission pattern of pandemic influenza A/H1N1 driven by large population centers. The higher reproduction number of the first pandemic wave could be explained by high contact rates among school-age children, the age group most affected during this early wave.
C1 [Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Math Computat & Modeling Sci Ctr, Tempe, AZ 85069 USA.
   [Chowell, Gerardo; Viboud, Cecile; Simonsen, Lone; Miller, Mark A.] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Munayco, Cesar V.; Gomez, Jorge] Peru Minist Salud, Direcc Gen Epidemiol, Lima, Peru.
   [Simonsen, Lone] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC USA.
   [Tamerius, James] Univ Arizona, Sch Geog & Dev, Tucson, AZ USA.
   [Fiestas, Victor] Inst Nacl Salud, Lima, Peru.
   [Halsey, Eric S.; Laguna-Torres, Victor A.] USN, Med Res Unit 6, Lima, Peru.
RP Chowell, G (reprint author), Arizona State Univ, Sch Human Evolut & Social Change, Math Computat & Modeling Sci Ctr, Tempe, AZ 85069 USA.
EM gchowell@asu.edu
RI Munayco, Cesar/G-9990-2013; Chowell, Gerardo/F-5038-2012; Valle,
   Ruben/A-7512-2013; 
OI Munayco, Cesar/0000-0001-7872-8913; Chowell,
   Gerardo/0000-0003-2194-2251; FIESTAS, VICTOR/0000-0002-5554-3542;
   Simonsen, Lone/0000-0003-1535-8526
FU Office of Global Health Affairs' International Influenza Unit in the
   Office of the Secretary of the Department of Health and Human Services;
   Science & Technology Directorate, Department of Homeland Security;
   Fogarty International Center, National Institutes of Health; United
   States Department of Defense [847705AE82000AE25GB.B0016]
FX Funding for the MISMS project comes from the Office of Global Health
   Affairs' International Influenza Unit in the Office of the Secretary of
   the Department of Health and Human Services. LS acknowledge support by
   the RAPIDD program of the Science & Technology Directorate, Department
   of Homeland Security, and Fogarty International Center, National
   Institutes of Health. NAMRU-6 respiratory virus surveillance is funded
   by the United States Department of Defense Global Emerging Infections
   Systems Research Program, WORK UNIT NUMBER: 847705AE82000AE25GB.B0016.
   The funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 53
TC 22
Z9 22
U1 1
U2 9
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 JUN 21
PY 2011
VL 6
IS 6
AR e21287
DI 10.1371/journal.pone.0021287
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782CL
UT WOS:000291985100026
PM 21712984
ER

PT J
AU Nunes, B
   Viboud, C
   Machado, A
   Ringholz, C
   Rebelo-de-Andrade, H
   Nogueira, P
   Miller, M
AF Nunes, Baltazar
   Viboud, Cecile
   Machado, Ausenda
   Ringholz, Corinne
   Rebelo-de-Andrade, Helena
   Nogueira, Paulo
   Miller, Mark
TI Excess Mortality Associated with Influenza Epidemics in Portugal, 1980
   to 2004
SO PLOS ONE
LA English
DT Article
ID RESPIRATORY SYNCYTIAL-VIRUS; UNITED-STATES; HOSPITAL ADMISSIONS; IMPACT;
   VACCINATION; DISEASE; POPULATION; PNEUMONIA; SURVEILLANCE; CHILDREN
AB Background: Influenza epidemics have a substantial impact on human health, by increasing the mortality from pneumonia and influenza, respiratory and circulatory diseases, and all causes. This paper provides estimates of excess mortality rates associated with influenza virus circulation for 7 causes of death and 8 age groups in Portugal during the period of 1980-2004.
   Methodology/Principal Findings: We compiled monthly mortality time series data by age for all-cause mortality, cerebrovascular diseases, ischemic heart diseases, diseases of the respiratory system, chronic respiratory diseases, pneumonia and influenza. We also used a control outcome, deaths from injuries. Age-and cause-specific baseline mortality was modelled by the ARIMA approach; excess deaths attributable to influenza were calculated by subtracting expected deaths from observed deaths during influenza epidemic periods. Influenza was associated with a seasonal average of 24.7 all-cause excess deaths per 100,000 inhabitants, approximately 90% of which were among seniors over 65 yrs. Excess mortality was 3-6 fold higher during seasons dominated by the A(H3N2) subtype than seasons dominated by A(H1N1)/B. High excess mortality impact was also seen in children under the age of four years. Seasonal excess mortality rates from all the studied causes of death were highly correlated with each other (Pearson correlation range, 0.65 to 0.95, P<0.001) and with seasonal rates of influenza-like-illness (ILI) among seniors over 65 years (Pearson correlation rho >0.64, P<0.05). By contrast, there was no correlation with excess mortality from injuries.
   Conclusions/Significance: Our excess mortality approach is specific to influenza virus activity and produces influenza-related mortality rates for Portugal that are similar to those published for other countries. Our results indicate that all-cause excess mortality is a robust indicator of influenza burden in Portugal, and could be used to monitor the impact of influenza epidemics in this country. Additional studies are warranted to confirm these findings in other settings.
C1 [Nunes, Baltazar; Machado, Ausenda; Nogueira, Paulo] Inst Nacl Saude Dr Ricardo Jorge, Dept Epidemiol, Lisbon, Portugal.
   [Viboud, Cecile; Ringholz, Corinne; Miller, Mark] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
   [Rebelo-de-Andrade, Helena] Inst Nacl Saude Dr Ricardo Jorge, Dept Doencas Infecciosas, Lisbon, Portugal.
   [Rebelo-de-Andrade, Helena] Univ Lisbon, Fac Farm, Lisbon, Portugal.
RP Nunes, B (reprint author), Inst Nacl Saude Dr Ricardo Jorge, Dept Epidemiol, Lisbon, Portugal.
EM baltazar.nunes@insa.min-saude.pt
RI iMed.ULisboa, iMed.ULisboa/C-6292-2014; Rebelo-de-Andrade,
   Helena/E-1871-2014; iMed.ULisboa, HPI /B-4239-2014; 
OI Rebelo-de-Andrade, Helena/0000-0002-0138-0944; iMed.ULisboa, HPI
   /0000-0001-5934-0198; Nogueira, Paulo Jorge/0000-0001-8316-5035; Nunes,
   Baltazar/0000-0001-6230-7209
FU Luso-American Foundation [1-13/08]; Instituto Nacional de Saude;
   International Influenza Unit, Office of Global Health Affairs,
   Department of Health and Human Services
FX This project was initiated during a three-month visit by B. Nunes to the
   Fogarty International Center, United States National Institutes of
   Health, and supported by the Luso-American Foundation project 1-13/08
   and the Instituto Nacional de Saude Dr. Ricardo Jorge. This research was
   conducted in the context of the MISMS Study, an ongoing international
   collaborative effort to understand influenza epidemiological and
   evolutionary patterns, led by the Fogarty International Center, National
   Institutes of Health (http://www.origem.info/misms/index.php). The MISMS
   study is funded by the International Influenza Unit, Office of Global
   Health Affairs, Department of Health and Human Services. The funders had
   no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 45
TC 24
Z9 26
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 21
PY 2011
VL 6
IS 6
AR e20661
DI 10.1371/journal.pone.0020661
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782CL
UT WOS:000291985100003
PM 21713040
ER

PT J
AU Shebl, FM
   Dollard, SC
   Pfeiffer, RM
   Biryahwaho, B
   Amin, MM
   Munuo, SS
   Hladik, W
   Parsons, R
   Graubard, BI
   Mbulaiteye, SM
AF Shebl, Fatma M.
   Dollard, Sheila C.
   Pfeiffer, Ruth M.
   Biryahwaho, Benon
   Amin, Minal M.
   Munuo, Stella S.
   Hladik, Wolfgang
   Parsons, Ruth
   Graubard, Barry I.
   Mbulaiteye, Sam M.
TI Human Herpesvirus 8 Seropositivity Among Sexually Active Adults in
   Uganda
SO PLOS ONE
LA English
DT Article
ID SARCOMA-ASSOCIATED HERPESVIRUS; TO-CHILD TRANSMISSION; KAPOSIS-SARCOMA;
   RISK-FACTORS; INFECTION; SEROPREVALENCE; POPULATION; CANCER; AIDS;
   TRANSFUSION
AB Introduction: Sexual transmission of human herpesvirus 8 (HHV8) has been implicated among homosexual men, but the evidence for sexual transmission among heterosexual individuals is controversial. We investigated the role of sexual transmission of HHV8 in a nationally representative sample in Uganda, where HHV8 infection is endemic and transmitted mostly during childhood.
   Materials and Methods: The study population was a subset of participants (n = 2681) from a population-based HIV/AIDS serobehavioral survey of adults aged 15-59 years conducted in 2004/2005. High risk for sexual transmission was assessed by questionnaire and serological testing for HIV and herpes simplex virus 2. Anti-HHV8 antibodies were measured using two enzyme immunoassays targeting synthetic peptides from the K8.1 and orf65 viral genes. The current study was restricted to 2288 sexually active adults. ORs and 95% CIs for HHV8 seropositivity were estimated by fitting logistic regression models with a random intercept using MPLUS and SAS software.
   Results: The weighted prevalence of HHV8 seropositivity was 56.2%, based on 1302 seropositive individuals, and it increased significantly with age (P(trend)<0.0001). In analyses adjusting for age, sex, geography, education, and HIV status, HHV8 seropositivity was positively associated with reporting two versus one marital union (OR:1.52, 95% CI: 1.17-1.97) and each unit increase in the number of children born (OR: 1.04, 95% CI: 1.00-1.08), and was inversely associated with ever having used a condom (OR: 0.64, 95% CI: 0.45-0.89). HHV8 seropositivity was not associated with HIV (P = 0.660) or with herpes simplex virus 2 (P = 0.732) seropositivity. Other sexual variables, including lifetime number of sexual partners or having had at least one sexually transmitted disease, and socioeconomic variables were unrelated to HHV8 seropositivity.
   Conclusion: Our findings are compatible with the conclusion that sexual transmission of HHV8 in Uganda, if it occurs, is weak.
C1 [Shebl, Fatma M.; Pfeiffer, Ruth M.; Graubard, Barry I.; Mbulaiteye, Sam M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   [Dollard, Sheila C.; Amin, Minal M.] Ctr Dis Control & Prevent, Atlanta, GA USA.
   [Biryahwaho, Benon] Uganda Virus Res Inst, Entebbe, Uganda.
   [Munuo, Stella S.; Parsons, Ruth] Informat Management Serv Inc, Rockville, MD USA.
   [Hladik, Wolfgang] Ctr Dis Control & Prevent, Entebbe, Uganda.
RP Shebl, FM (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM mbulaits@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute
   (NCI); National Institutes of Health, Department of Health and Human
   Services [HHSN2612009004060P]; Support Services contract [NO2-CP-31003];
   NCI [IAA Y1CP903801]; Centers for Disease Control and Prevention [IAA
   Y1CP903801]
FX The study was supported by the Intramural Research Program of the
   Division of Cancer Epidemiology and Genetics, National Cancer Institute
   (NCI), National Institutes of Health, Department of Health and Human
   Services (contract HHSN2612009004060P and Support Services contract
   NO2-CP-31003) and with an Inter-Agency Agreement between NCI and the
   Centers for Disease Control and Prevention (IAA Y1CP903801). The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 38
TC 12
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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 JUN 21
PY 2011
VL 6
IS 6
AR e21286
DI 10.1371/journal.pone.0021286
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782CL
UT WOS:000291985100025
PM 21712983
ER

PT J
AU Baatar, D
   Patel, K
   Taub, DD
AF Baatar, Dolgor
   Patel, Kalpesh
   Taub, Dennis D.
TI The effects of ghrelin on inflammation and the immune system
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Review
DE Ghrelin; GHS-R; Inflammation; Sepsis; Proinflammatory cytokines; IL-6;
   Thymus; Aging
ID GROWTH-HORMONE SECRETAGOGUE; PROINFLAMMATORY CYTOKINE EXPRESSION;
   LEFT-VENTRICULAR DYSFUNCTION; FASTED PLASMA GHRELIN; REMOTE ORGAN
   INJURY; KAPPA-B ACTIVATION; T-CELL DEVELOPMENT; ACUTE-PANCREATITIS;
   ENDOTHELIAL-CELLS; HELICOBACTER-PYLORI
AB A number of hormones and metabolic mediators signal the brain of changes in the body's energy status and when an imbalance occurs; the brain coordinates the appropriate changes in energy intake and utilization via the control of appetite and food consumption. Under conditions of chronic inflammation and immune activation, there is often a significant loss of body mass and appetite suggesting the presence of shared ligands and signaling pathways mediating "crosstalk" between the immune and neuroendocrine systems. Ghrelin, the endogenous ligand for growth hormone secretagogue receptor (GHS-R), is produced primarily by cells in the stomach and serves as a potent circulating orexigenic hormone controlling food intake, energy expenditure, adiposity and GH secretion. The functional roles of ghrelin and other growth hormone secretagogues (GHS) within the immune system and under states of inflammatory stress and injury are only now coming to light. A number of reports over the past decade have described ghrelin to be a potent anti-inflammatory mediator both in vitro and in vivo and a promising therapeutic agent in the treatment of inflammatory diseases and injury. Moreover, ghrelin has also been shown to promote lymphocyte development in the primary lymphoid organs (bone marrow and thymus) and to ablate age-associated thymic involution. In the current report, we review the literature supporting a role for ghrelin as an anti-inflammatory agent and immunoregulatory hormone/cytokine and its potential use in the treatment of inflammatory diseases and injury. (c) 2011 Published by Elsevier Ireland Ltd.
C1 [Baatar, Dolgor; Patel, Kalpesh; Taub, Dennis D.] NIA, Clin Immunol Sect, Lab Mol Biol & Immunol, IRP,NIH,Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Taub, DD (reprint author), NIA, Clin Immunol Sect, Lab Mol Biol & Immunol, IRP,NIH,Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM Taubd@grc.nia.nih.gov
RI Patel, Kalpesh/G-6685-2012
OI Patel, Kalpesh/0000-0002-2952-6773
FU National Institute on Aging, National Institutes of Health
FX We wish to thank Ana Lustig for her assistance with this manuscript.
   This work was supported by the Intramural Research Program of the
   National Institute on Aging, National Institutes of Health.
NR 116
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U1 0
U2 16
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 JUN 20
PY 2011
VL 340
IS 1
SI SI
BP 44
EP 58
DI 10.1016/j.mce.2011.04.019
PG 15
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 793YL
UT WOS:000292860200008
PM 21565248
ER

PT J
AU Elkin, EB
   Klem, ML
   Gonzales, AM
   Ishill, NM
   Hodgson, D
   Ng, AK
   Marks, LB
   Weidhaas, J
   Freedman, GM
   Miller, RC
   Constine, LS
   Myrehaug, S
   Yahalom, J
AF Elkin, Elena B.
   Klem, Michelle L.
   Gonzales, Anne Marie
   Ishill, Nicole M.
   Hodgson, David
   Ng, Andrea K.
   Marks, Lawrence B.
   Weidhaas, Joanne
   Freedman, Gary M.
   Miller, Robert C.
   Constine, Louis S.
   Myrehaug, Sten
   Yahalom, Joachim
TI Characteristics and Outcomes of Breast Cancer in Women With and Without
   a History of Radiation for Hodgkin's Lymphoma: A Multi-Institutional,
   Matched Cohort Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID LONG-TERM SURVIVAL; FEMALE SURVIVORS; RISK-FACTORS; 2ND CANCER; DISEASE;
   CHILDHOOD; MORTALITY; AGE; CHEMOTHERAPY; RADIOTHERAPY
AB Purpose
   To compare characteristics and outcomes of breast cancer in women with and without a history of radiation therapy (RT) for Hodgkin's lymphoma (HL).
   Patients and Methods
   Women with breast cancer diagnosed from 1980 to 2006 after RT for HL were identified from eight North American hospitals and were matched three-to-one with patients with sporadic breast cancer by age, race, and year of breast cancer diagnosis. Information on patient, tumor and treatment characteristics, and clinical outcomes was abstracted from medical records.
   Results
   A total of 253 patients with breast cancer with a history of RT for HL were matched with 741 patients with sporadic breast cancer. Median time from HL to breast cancer diagnosis was 18 years. Median age at breast cancer diagnosis was 42 years. Breast cancer after RT for HL was more likely to be detected by screening, was more likely to be diagnosed at an earlier stage, and was more likely to be bilateral at diagnosis. HL survivors had an increased risk of metachronous contralateral breast cancer (adjusted hazard ratio [HR], 4.3; 95% CI, 1.7 to 11.0) and death as a result of any cause (adjusted HR, 1.9; 95% CI, 1.1 to 3.3). Breast cancer-specific mortality was also elevated, but this difference was not statistically significant (adjusted HR, 1.6; 95% CI, 0.7 to 3.4).
   Conclusion
   In women with a history of RT for HL, breast cancer is diagnosed at an earlier stage, but these women are at greater risk for bilateral disease and are more likely to die as a result of causes other than breast cancer. Our findings support close follow-up for contralateral tumors in these patients and ongoing primary care to manage comorbid conditions.
C1 [Elkin, Elena B.; Gonzales, Anne Marie; Ishill, Nicole M.; Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
   [Klem, Michelle L.] Exempla St Joseph Hosp, Denver, CO USA.
   [Hodgson, David] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
   [Ng, Andrea K.] Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Marks, Lawrence B.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA.
   [Weidhaas, Joanne] Yale Univ, New Haven, CT USA.
   [Freedman, Gary M.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
   [Miller, Robert C.] Mayo Clin, Rochester, MN USA.
   [Constine, Louis S.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
   [Myrehaug, Sten] NIH, Bethesda, MD 20892 USA.
RP Yahalom, J (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.
EM yahalomj@mskcc.org
OI Weidhaas, Joanne/0000-0002-5096-3281
FU Lymphoma Foundation; Sports Foundation Against Cancer; National Cancer
   Institute [1 K07 CA118189-01A2]; Memorial Sloan-Kettering Cancer Center
FX Supported by the Lymphoma Foundation and the Sports Foundation Against
   Cancer (J.Y.); by mentored career development award No. 1 K07
   CA118189-01A2 from the National Cancer Institute (E. B. E.); and by the
   Dr. Mortimer J. Lacher, MD, fellowship at Memorial Sloan-Kettering
   Cancer Center (M.L.K.).
NR 40
TC 26
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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 JUN 20
PY 2011
VL 29
IS 18
BP 2466
EP 2473
DI 10.1200/JCO.2010.32.4079
PG 8
WC Oncology
SC Oncology
GA 778EQ
UT WOS:000291684600020
PM 21576642
ER

PT J
AU Bjorkholm, M
   Ohm, L
   Eloranta, S
   Derolf, A
   Hultcrantz, M
   Sjoberg, J
   Andersson, T
   Hoglund, M
   Richter, J
   Landgren, O
   Kristinsson, SY
   Dickman, PW
AF Bjorkholm, Magnus
   Ohm, Lotta
   Eloranta, Sandra
   Derolf, Asa
   Hultcrantz, Malin
   Sjoberg, Jan
   Andersson, Therese
   Hoglund, Martin
   Richter, Johan
   Landgren, Ola
   Kristinsson, Sigurdur Y.
   Dickman, Paul W.
TI Success Story of Targeted Therapy in Chronic Myeloid Leukemia: A
   Population-Based Study of Patients Diagnosed in Sweden From 1973 to 2008
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CHRONIC MYELOGENOUS LEUKEMIA; SWEDISH CANCER REGISTER; RELATIVE
   SURVIVAL; CHRONIC-PHASE; INTERFERON; IMATINIB; CML; COMPLETENESS;
   HYDROXYUREA; BUSULFAN
AB Purpose
   Chronic myeloid leukemia (CML) management changed dramatically with the development of imatinib mesylate (IM), the first tyrosine kinase inhibitor targeting the BCR-ABL1 oncoprotein. In Sweden, the drug was approved in November 2001. We report relative survival (RS) of patients with CML diagnosed during a 36-year period.
   Patients and Methods
   Using data from the population-based Swedish Cancer Registry and population life tables, we estimated RS for all patients diagnosed with CML from 1973 to 2008 (n = 3,173; 1,796 males and 1,377 females; median age, 62 years). Patients were categorized into five age groups and five calendar periods, the last being 2001 to 2008. Information on use of upfront IM was collected from the Swedish CML registry.
   Results
   Relative survival improved with each calendar period, with the greatest improvement between 1994-2000 and 2001-2008. Five-year cumulative relative survival ratios (95% CIs) were 0.21 (0.17 to 0.24) for patients diagnosed 1973-1979, 0.54 (0.50 to 0.58) for 1994-2000, and 0.80 (0.75 to 0.83) for 2001-2008. This improvement was confined to patients younger than 79 years of age. Five-year RSRs for patients diagnosed from 2001 to 2008 were 0.91 (95% CI, 0.85 to 0.94) and 0.25 (95% CI, 0.10 to 0.47) for patients younger than 50 and older than 79 years, respectively. Men had inferior outcome. Upfront overall use of IM increased from 40% (2002) to 84% (2006). Only 18% of patients older than 80 years of age received IM as first-line therapy.
   Conclusion
   This large population-based study shows a major improvement in outcome of patients with CML up to 79 years of age diagnosed from 2001 to 2008, mainly caused by an increasing use of IM. The elderly still have poorer outcome, partly because of a limited use of IM. J Clin Oncol 29: 2514-2520. (C) 2011 by American Society of Clinical Oncology
C1 [Bjorkholm, Magnus; Ohm, Lotta; Derolf, Asa; Hultcrantz, Malin; Sjoberg, Jan; Kristinsson, Sigurdur Y.] Karolinska Univ Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
   [Bjorkholm, Magnus; Ohm, Lotta; Eloranta, Sandra; Derolf, Asa; Hultcrantz, Malin; Sjoberg, Jan; Andersson, Therese; Kristinsson, Sigurdur Y.; Dickman, Paul W.] Karolinska Inst, S-10401 Stockholm, Sweden.
   [Hoglund, Martin] Univ Uppsala Hosp, Uppsala, Sweden.
   [Richter, Johan] Skane Univ Hosp, Lund, Sweden.
   [Landgren, Ola] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Bjorkholm, M (reprint author), Karolinska Univ Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
EM magnus.bjorkholm@karolinska.se
RI Dickman, Paul/B-4572-2013; Kristinsson, Sigurdur /M-2910-2015;
   Andersson, Therese/E-7107-2016
OI Dickman, Paul/0000-0002-5788-3380; Kristinsson, Sigurdur
   /0000-0002-4964-7476; Andersson, Therese/0000-0001-8644-9041
FU Swedish Chronic Myeloid Leukemia Group; Novartis Sweden; Adolf H. Lundin
   Charitable Foundation; Swedish Cancer Society
FX Supported by grants from the Swedish Chronic Myeloid Leukemia Group,
   Novartis Sweden, Adolf H. Lundin Charitable Foundation, Swedish Cancer
   Society, and the regional agreement on medical training and clinical
   research between Stockholm County Council and Karolinska Institutet.
NR 27
TC 84
Z9 85
U1 0
U2 8
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 20
PY 2011
VL 29
IS 18
BP 2514
EP 2520
DI 10.1200/JCO.2011.34.7146
PG 7
WC Oncology
SC Oncology
GA 778EQ
UT WOS:000291684600027
PM 21576640
ER

PT J
AU Yang, M
   Xie, WL
   Mostaghel, E
   Nakabayashi, M
   Werner, L
   Sun, T
   Pomerantz, M
   Freedman, M
   Ross, R
   Regan, M
   Sharifi, N
   Figg, WD
   Balk, S
   Brown, M
   Taplin, ME
   Oh, WK
   Lee, GSM
   Kantoff, PW
AF Yang, Ming
   Xie, Wanling
   Mostaghel, Elahe
   Nakabayashi, Mari
   Werner, Lillian
   Sun, Tong
   Pomerantz, Mark
   Freedman, Matthew
   Ross, Robert
   Regan, Meredith
   Sharifi, Nima
   Figg, William Douglas
   Balk, Steven
   Brown, Myles
   Taplin, Mary-Ellen
   Oh, William K.
   Lee, Gwo-Shu Mary
   Kantoff, Philip W.
TI SLCO2B1 and SLCO1B3 May Determine Time to Progression for Patients
   Receiving Androgen Deprivation Therapy for Prostate Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID DIHYDROTESTOSTERONE LEVELS; ADRENAL ANDROGENS; TESTOSTERONE;
   TRANSPORTER; RECEPTOR; TISSUE; IDENTIFICATION; MECHANISMS; EFFICACY;
   BIOLOGY
AB Purpose
   Androgen deprivation therapy (ADT), an important treatment for advanced prostate cancer, is highly variable in its effectiveness. We hypothesized that genetic variants of androgen transporter genes, SLCO2B1 and SLCO1B3, may determine time to progression on ADT.
   Patients and Methods
   A cohort of 538 patients with prostate cancer treated with ADT was genotyped for SLCO2B1 and SLCO1B3 single nucleotide polymorphisms (SNP). The biologic function of a SLCO2B1 coding SNP in transporting androgen was examined through biochemical assays.
   Results
   Three SNPs in SLCO2B1 were associated with time to progression (TTP) on ADT (P < .05). The differences in median TTP for each of these polymorphisms were about 10 months. The SLCO2B1 genotype, which allows more efficient import of androgen, enhances cell growth and is associated with a shorter TTP on ADT. Patients carrying both SLCO2B1 and SLCO1B3 genotypes, which import androgens more efficiently, exhibited a median 2-year shorter TTP on ADT, demonstrating a gene-gene interaction (P-interaction = .041).
   Conclusion
   Genetic variants of SLCO2B1 and SLCO1B3 may function as pharmacogenomic determinants of resistance to ADT in prostate cancer. J Clin Oncol 29:2565-2573. (C) 2011 by American Society of Clinical Oncology
C1 [Yang, Ming; Xie, Wanling; Nakabayashi, Mari; Werner, Lillian; Sun, Tong; Pomerantz, Mark; Freedman, Matthew; Ross, Robert; Regan, Meredith; Brown, Myles; Taplin, Mary-Ellen; Lee, Gwo-Shu Mary; Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
   [Balk, Steven] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
   [Mostaghel, Elahe] Univ Washington, Seattle, WA 98195 USA.
   [Sharifi, Nima] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
   [Figg, William Douglas] NCI, NIH, Bethesda, MD 20892 USA.
   [Oh, William K.] Mt Sinai Sch Med, New York, NY USA.
RP Lee, GSM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dana 710B,44 Binney St, Boston, MA 02115 USA.
EM gwo-shu_lee@dfci.harvard.edu
RI Oh, William/B-9163-2012; Yang, Ming/G-4705-2012; Figg Sr,
   William/M-2411-2016; 
OI Oh, William/0000-0001-5113-8147; Yang, Ming/0000-0002-7722-7487; Brown,
   Myles/0000-0002-8213-1658
FU Dana-Farber/Harvard Cancer Center [2 P50 CA090381-11]; Prostate Cancer
   Foundation
FX Supported by the Dana-Farber/Harvard Cancer Center Prostate Cancer
   Specialized Program of Research Excellence Grant No. 2 P50 CA090381-11
   and a Prostate Cancer Foundation Challenge Grant.
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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 JUN 20
PY 2011
VL 29
IS 18
BP 2565
EP 2573
DI 10.1200/JCO.2010.31.2405
PG 9
WC Oncology
SC Oncology
GA 778EQ
UT WOS:000291684600034
PM 21606417
ER

PT J
AU Bear, HD
   Tang, G
   Rastogi, P
   Geyer, CE
   Robidoux, A
   Atkins, JN
   Baez, L
   Brufsky, A
   Mehta, RS
   Fehrenbacher, L
   Pajon, ER
   Senecal, FM
   Gaur, R
   Margolese, RG
   Adams, PT
   Gross, HM
   Swain, SM
   Mamounas, EP
   Costantino, JP
   Wolmark, N
AF Bear, H. D.
   Tang, G.
   Rastogi, P.
   Geyer, C. E.
   Robidoux, A.
   Atkins, J. N.
   Baez, L.
   Brufsky, A.
   Mehta, R. S.
   Fehrenbacher, L.
   Pajon, E. R.
   Senecal, F. M.
   Gaur, R.
   Margolese, R. G.
   Adams, P. T.
   Gross, H. M.
   Swain, S. M.
   Mamounas, E. P.
   Costantino, J. P.
   Wolmark, N.
TI The effect on pCR of bevacizumab and/or antimetabolites added to
   standard neoadjuvant chemotherapy: NSABP protocol B-40
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA.
   NSABBP Biostat Ctr, Pittsburgh, PA USA.
   Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
   Univ Pittsburgh, Med Ctr, Magee Womens Canc Program, Pittsburgh, PA USA.
   Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
   Allegheny Gen Hosp, Pittsburgh, PA 15212 USA.
   NSABP, Pittsfield, MA USA.
   CHUM Hotel Dieu, Montreal, PQ, Canada.
   SCCC CCOP, Winston Salem, NC USA.
   San Juan MBCCOP, San Juan, PR USA.
   Univ Calif Irvine, Irvine Sch Med, Chao Family Comprehens Canc Ctr, Orange, CA 92668 USA.
   Kaiser Permanente Calif, Vallejo, CA USA.
   Colorado Canc Res Program, Denver, CO USA.
   Northwest Med Specialties, Tacoma, WA USA.
   Kansas City CCOP, Kansas City, KS USA.
   McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada.
   Genesys Reg Med Ctr, Flint, MI USA.
   Dayton CCOP, Dayton, OH USA.
   Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
   Natl Surg Adjuvant Breast & Bowel Project, Canton, OH USA.
   Aultman Hlth Fdn, Canton, OH USA.
   Univ Pittsburgh, Grad Sch Publ Hlth, Natl Surg Adjuvant Breast & Bowel Project, Biostat Ctr, Pittsburgh, PA USA.
   Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 JUN 20
PY 2011
VL 29
IS 18
SU S
MA LBA1005
PG 1
WC Oncology
SC Oncology
GA V31EB
UT WOS:000208865800013
ER

PT J
AU Kris, MG
   Johnson, BE
   Kwiatkowski, DJ
   Iafrate, AJ
   Wistuba, II
   Aronson, SL
   Engelman, JA
   Shyr, Y
   Khuri, FR
   Rudin, CM
   Garon, EB
   Pao, W
   Schiller, JH
   Haura, EB
   Shirai, K
   Giaccone, G
   Berry, LD
   Kugler, K
   Minna, JD
   Bunn, PA
AF Kris, M. G.
   Johnson, B. E.
   Kwiatkowski, D. J.
   Iafrate, A. J.
   Wistuba, I. I.
   Aronson, S. L.
   Engelman, J. A.
   Shyr, Y.
   Khuri, F. R.
   Rudin, C. M.
   Garon, E. B.
   Pao, W.
   Schiller, J. H.
   Haura, E. B.
   Shirai, K.
   Giaccone, G.
   Berry, L. D.
   Kugler, K.
   Minna, J. D.
   Bunn, P. A.
TI Identification of driver mutations in tumor specimens from 1,000
   patients with lung adenocarcinoma: The NCI's Lung Cancer Mutation
   Consortium (LCMC)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
   Partners Hlth Canc Ctr, Boston, MA USA.
   Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
   Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
   Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
   Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
   Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
   Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
   Med Univ S Carolina, Charleston, SC 29425 USA.
   NCI, Bethesda, MD 20892 USA.
   Vanderbilt Univ, Nashville, TN 37235 USA.
   Univ Colorado, Canc Ctr Denver, Aurora, CO USA.
   Univ Colorado Denver, Ctr Canc, Aurora, CO USA.
NR 0
TC 0
Z9 0
U1 2
U2 7
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 JUN 20
PY 2011
VL 29
IS 18
SU S
MA CRA7506
PG 1
WC Oncology
SC Oncology
GA V31EB
UT WOS:000208865800005
ER

PT J
AU Larsen, EC
   Salzer, WL
   Devidas, M
   Nachman, JB
   Raetz, EA
   Loh, ML
   Heerema, NA
   Carroll, AJ
   Gastier-Foster, JM
   Borowitz, MJ
   Wood, BL
   Willman, CL
   Winick, NJ
   Hunger, S
   Carroll, WL
AF Larsen, E. C.
   Salzer, W. L.
   Devidas, M.
   Nachman, J. B.
   Raetz, E. A.
   Loh, M. L.
   Heerema, N. A.
   Carroll, A. J.
   Gastier-Foster, J. M.
   Borowitz, M. J.
   Wood, B. L.
   Willman, C. L.
   Winick, N. J.
   Hunger, S.
   Carroll, W. L.
TI Comparison of high-dose methotrexate (HD-MTX) with Capizzi methotrexate
   plus asparaginase (C-MTX/ASNase) in children and young adults with
   high-risk acute lymphoblastic leukemia (HR-ALL): A report from the
   Children's Oncology Group Study AALL0232
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Maine Childrens Canc Program, Scarborough, ME USA.
   NIH, Silver Spring, MD USA.
   Childrens Oncol Grp, Gainesville, FL USA.
   Univ Chicago, Chicago, IL 60637 USA.
   NYU, Langone Med Ctr, New York, NY USA.
   Univ Calif San Francisco, San Francisco, CA 94143 USA.
   Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
   Ohio State Univ, Arthur G James Canc Hosp, Columbus, OH 43210 USA.
   Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA.
   Univ Alabama Birmingham, Birmingham, AL USA.
   Nationwide Childrens Hosp, Columbus, OH USA.
   Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
   Univ Washington, Seattle, WA 98195 USA.
   Univ New Mexico, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA.
   UTSW, Dallas, TX USA.
   Childrens Med Ctr, Ctr Canc & Blood Disorders, Dallas, TX 75235 USA.
   Univ Colorado Denver, Hlth Sci Ctr, Aurora, CO USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
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 JUN 20
PY 2011
VL 29
IS 18
SU S
MA 3
PG 1
WC Oncology
SC Oncology
GA V31EB
UT WOS:000208865800003
PM 28023264
ER

PT J
AU Virgo, KS
   Lerro, CC
   Klabunde, CN
   Earle, C
   Ganz, PA
AF Virgo, K. S.
   Lerro, C. C.
   Klabunde, C. N.
   Earle, C.
   Ganz, P. A.
TI Barriers in providing breast and colorectal cancer survivorship care:
   Perceptions of US primary care physicians (PCPs) and medical oncologists
   (MOs)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
C1 Amer Canc Soc NHO, Atlanta, GA USA.
   NCI, Bethesda, MD 20892 USA.
   Inst Clin Evaluat Sci, Toronto, ON, Canada.
   Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
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 JUN 20
PY 2011
VL 29
IS 18
SU S
MA CRA9006
PG 1
WC Oncology
SC Oncology
GA V31EB
UT WOS:000208865800008
ER

PT J
AU Li, XH
   Johnson, KR
   Bryant, M
   Elkahloun, AG
   Amar, M
   Remaley, AT
   De Silva, R
   Hallenbeck, JM
   Quandt, JA
AF Li, Xinhui
   Johnson, Kory R.
   Bryant, Mark
   Elkahloun, Abdel G.
   Amar, Marcelo
   Remaley, Alan T.
   De Silva, Ranil
   Hallenbeck, John M.
   Quandt, Jacqueline A.
TI Intranasal Delivery of E-Selectin Reduces Atherosclerosis in ApoE-/-
   Mice
SO PLOS ONE
LA English
DT Article
ID RECEPTOR-DEFICIENT MICE; CORONARY-ARTERY-DISEASE; REGULATORY T-CELLS;
   SOLUBLE E-SELECTIN; MUCOSAL TOLERANCE; ORAL TOLERANCE; SUBARACHNOID
   HEMORRHAGE; ADHESION MOLECULES; LYMPHOID-TISSUE; CEREBROSPINAL-FLUID
AB Mucosal tolerance to E-selectin prevents stroke and protects against ischemic brain damage in experimental models of stroke studying healthy animals or spontaneously hypertensive stroke-prone rats. A reduction in inflammation and neural damage was associated with immunomodulatory or "tolerogenic" responses to E-selectin. The purpose of the current study on ApoE deficient mice is to assess the capacity of this stroke prevention innovation to influence atherosclerosis, a major underlying cause for ischemic strokes; human E-selectin is being translated as a potential clinical prevention strategy for secondary stroke. Female ApoE-/- mice received intranasal delivery of E-selectin prior to ( pre-tolerization) or simultaneously with initiation of a high-fat diet. After 7 weeks on the high-fat diet, lipid lesions in the aorta, serum triglycerides, and total cholesterol were assessed as markers of atherosclerosis development. We also assessed E-selectin-specific antibodies and cytokine responses, in addition to inflammatory responses that included macrophage infiltration of the aorta and altered gene expression profiles of aortic mRNA. Intranasal delivery of E-selectin prior to initiation of high-fat chow decreased atherosclerosis, serum total cholesterol, and expression of the leucocyte chemoattractant CCL21 that is typically upregulated in atherosclerotic lesions of ApoE-/- mice. This response was associated with the induction of E-selectin specific cells producing the immunomodulatory cytokine IL-10 and immunosuppressive antibody isotypes. Intranasal administration of E-selectin generates E-selectin specific immune responses that are immunosuppressive in nature and can ameliorate atherosclerosis, a major risk factor for ischemic stroke. These results provide additional preclinical support for the potential of induction of mucosal tolerance to E-selectin to prevent stroke.
C1 [Li, Xinhui; Hallenbeck, John M.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA.
   [Johnson, Kory R.] NINDS, Bioinformat Sect, NIH, Bethesda, MD 20892 USA.
   [Bryant, Mark] NIH, Div Vet Resources, Off Res Support, Bethesda, MD 20892 USA.
   [Elkahloun, Abdel G.] NIH, Div Intramural Res Programs, Microarray Core Facil, Bethesda, MD 20892 USA.
   [Amar, Marcelo; Remaley, Alan T.; De Silva, Ranil] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Quandt, Jacqueline A.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
RP Li, XH (reprint author), NINDS, Stroke Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM hallenbj@ninds.nih.gov; jquandt@pathology.ubc.ca
FU National Institute of Neurological Disorders and Stroke; National Heart,
   Lung and Blood Institute, NIH, Bethesda, MD
FX This research was supported by the Stroke and Neuroimmunology Branches,
   Intramural Research Program of the National Institute of Neurological
   Disorders and Stroke and also a Bench to Bedside Award from the National
   Heart, Lung and Blood Institute, NIH, Bethesda, MD. The funders had no
   role in study design, data collection and analysis, decision to publish,
   or preparation of the manuscript.
NR 61
TC 2
Z9 2
U1 2
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 20
PY 2011
VL 6
IS 6
AR e20620
DI 10.1371/journal.pone.0020620
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 782BY
UT WOS:000291983800008
PM 21701687
ER

PT J
AU Ferre, S
   Quiroz, C
   Orru, M
   Guitart, X
   Navarro, G
   Cortes, A
   Casado, V
   Canela, EI
   Lluis, C
   Franco, R
AF Ferre, Sergi
   Quiroz, Cesar
   Orru, Marco
   Guitart, Xavier
   Navarro, Gemma
   Cortes, Antonio
   Casado, Vicent
   Canela, Enric I.
   Lluis, Carme
   Franco, Rafael
TI Adenosine A(2A) receptors and A(2A) receptor heteromers as key players
   in striatal function
SO FRONTIERS IN NEUROANATOMY
LA English
DT Review
DE adenosine A(2A) receptor; striatum; receptor heteromers; dopamine
   receptors; cannabinoid receptors
ID CANNABINOID CB1 RECEPTORS; CENTRAL-NERVOUS-SYSTEM; DOPAMINE-D-2
   RECEPTORS; RAT STRIATUM; PARKINSONS-DISEASE; BASAL GANGLIA;
   GLUTAMATERGIC NEUROTRANSMISSION; CHOLINERGIC INTERNEURONS; MGLU5
   RECEPTORS; D2 DOPAMINE
AB A very significant density of adenosine A(2A) receptors (A(2A)Rs) is present in the striatum, where they are preferentially localized postsynaptically in striatopallidal medium spiny neurons (MSNs). In this localization A(2A)Rs establish reciprocal antagonistic interactions with dopamine D-2 receptors (D(2)Rs). In one type of interaction, A(2A)R and D2R are forming heteromers and, by means of an allosteric interaction, A(2A)R counteracts D2R-mediated inhibitory modulation of the effects of NMDA receptor stimulation in the striatopallidal neuron. This interaction is probably mostly responsible for the locomotor depressant and activating effects of A(2A)R agonist and antagonists, respectively. The second type of interaction involves R-2A and D2R that do not form heteromers and takes place at the level of adenylyl cyclase (AC). Due to a strong tonic effect of endogenous dopamine on striatal D2R, this interaction keeps A(2A)R from signaling through AC. However, under conditions of dopamine depletion or with blockade of D2R, A(2A)R-mediated AC activation is unleashed with an increased gene expression and activity of the striatopallidal neuron and with a consequent motor depression. This interaction is probably the main mechanism responsible for the locomotor depression induced by D2R antagonists. Finally, striatal A(2A)Rs are also localized presynaptically, in cortico-striatal glutamatergic terminals that contact the striato-nigral MSN. These presynaptic A(2A)Rs heteromerize with A(1) receptors (A(1)Rs) and their activation facilitates glutamate release. These three different types of A(2A)Rs can be pharmacologically dissected by their ability to bind ligands with different affinity and can therefore provide selective targets for drug development in different basal ganglia disorders.
C1 [Ferre, Sergi; Quiroz, Cesar; Orru, Marco; Guitart, Xavier] NIDA, Intramural Res Program, NIH, US Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
   [Navarro, Gemma; Cortes, Antonio; Casado, Vicent; Canela, Enric I.; Lluis, Carme; Franco, Rafael] Univ Barcelona, Ctr Invest Biomed Red Enfermed Neurodegenerat, Barcelona, Spain.
   [Navarro, Gemma; Cortes, Antonio; Casado, Vicent; Canela, Enric I.; Lluis, Carme; Franco, Rafael] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, Barcelona, Spain.
   [Franco, Rafael] Univ Navarra, Ctr Invest Med Aplicada, E-31080 Pamplona, Spain.
RP Ferre, S (reprint author), NIDA, Intramural Res Program, NIH, US Dept Hlth & Human Serv, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sferre@intra.nida.nih.gov
RI Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Franco,
   Rafael/C-3694-2015; Casado, Vicent/K-1660-2014; 
OI Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779;
   Franco, Rafael/0000-0003-2549-4919; Casado, Vicent/0000-0002-1764-3825
FU National Institute on Drug Abuse
FX Work supported with the intramural funds of the National Institute on
   Drug Abuse.
NR 53
TC 20
Z9 20
U1 4
U2 9
PU FRONTIERS RES FOUND
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5129
J9 FRONT NEUROANAT
JI Front. Neuroanat.
PD JUN 17
PY 2011
VL 5
AR 36
DI 10.3389/fnana.2011.00036
PG 8
WC Anatomy & Morphology; Neurosciences
SC Anatomy & Morphology; Neurosciences & Neurology
GA 886QB
UT WOS:000299867800001
PM 21731559
ER

PT J
AU Aggarwal, R
   Gupte, N
   Kass, N
   Taylor, H
   Ali, J
   Bhan, A
   Aggarwal, A
   Sisson, SD
   Kanchanaraksa, S
   McKenzie-White, J
   McGready, J
   Miotti, P
   Bollinger, RC
AF Aggarwal, Rakesh
   Gupte, Nikhil
   Kass, Nancy
   Taylor, Holly
   Ali, Joseph
   Bhan, Anant
   Aggarwal, Amita
   Sisson, Stephen D.
   Kanchanaraksa, Sukon
   McKenzie-White, Jane
   McGready, John
   Miotti, Paolo
   Bollinger, Robert C.
TI A Comparison of Online versus On-site Training in Health Research
   Methodology: A Randomized Study
SO BMC MEDICAL EDUCATION
LA English
DT Article
ID INTERNET-BASED CME; MEDICAL-EDUCATION; CAPACITY; GUIDE
AB Background: Distance learning may be useful for building health research capacity. However, evidence that it can improve knowledge and skills in health research, particularly in resource-poor settings, is limited. We compared the impact and acceptability of teaching two distinct content areas, Biostatistics and Research Ethics, through either on-line distance learning format or traditional on-site training, in a randomized study in India. Our objective was to determine whether on-line courses in Biostatistics and Research Ethics could achieve similar improvements in knowledge, as traditional on-site, classroom-based courses.
   Methods: Subjects: Volunteer Indian scientists were randomly assigned to one of two arms. Intervention: Students in Arm 1 attended a 3.5-day on-site course in Biostatistics and completed a 3.5-week on-line course in Research Ethics. Students in Arm 2 attended a 3.5-week on-line course in Biostatistics and 3.5-day on-site course in Research Ethics. For the two course formats, learning objectives, course contents and knowledge tests were identical. Main Outcome Measures: Improvement in knowledge immediately and 3-months after course completion, compared to baseline.
   Results: Baseline characteristics were similar in both arms (n = 29 each). Median knowledge score for Biostatistics increased from a baseline of 49% to 64% (p < 0.001) 3 months after the on-site course, and from 48% to 63% (p = 0.009) after the on-line course. For the on-site Research Ethics course, median score increased from 69% to 83% (p = 0.005), and for the on-line Research Ethics course from 62% to 80% (p < 0.001). Three months after the course, median gains in knowledge scores remained similar for the on-site and on-line platforms for both Biostatistics (16% vs. 12%; p = 0.59) and Research Ethics (17% vs. 13%; p = 0.14).
   Conclusion: On-line and on-site training formats led to marked and similar improvements of knowledge in Biostatistics and Research Ethics. This, combined with logistical and cost advantages of on-line training, may make on-line courses particularly useful for expanding health research capacity in resource-limited settings.
C1 [Aggarwal, Rakesh; Aggarwal, Amita] Sanjay Gandhi Postgrad Inst Med Sci, Lucknow 226014, Uttar Pradesh, India.
   [Gupte, Nikhil] BJ Med Coll, Clin Trials Unit, Pune, Maharashtra, India.
   [Kass, Nancy; Taylor, Holly; Ali, Joseph; Sisson, Stephen D.; Kanchanaraksa, Sukon; McKenzie-White, Jane; McGready, John; Bollinger, Robert C.] Johns Hopkins Univ, Baltimore, MD USA.
   [Miotti, Paolo] NIH, Off AIDS Res, Bethesda, MD 20892 USA.
RP Aggarwal, R (reprint author), Sanjay Gandhi Postgrad Inst Med Sci, Lucknow 226014, Uttar Pradesh, India.
EM aggarwal.ra@gmail.com
RI Aggarwal, Amita/A-5679-2011; 
OI Aggarwal, Rakesh/0000-0001-9689-494X
FU Fogarty International Center/USNIH [2D43 TW000010-22-AITRP]; Division of
   AIDS/NIAID/USNIH [AIU01069497]; NIH Office of AIDS Research
FX This publication has been supported, in part, by grants from the Fogarty
   International Center/USNIH (Grant#2D43 TW000010-22-AITRP) and the
   Division of AIDS/NIAID/USNIH (AIU01069497), and in part from funds
   provided through the NIH Office of AIDS Research.
NR 16
TC 16
Z9 16
U1 3
U2 20
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6920
J9 BMC MED EDUC
JI BMC Med. Educ.
PD JUN 17
PY 2011
VL 11
AR 37
DI 10.1186/1472-6920-11-37
PG 10
WC Education & Educational Research; Education, Scientific Disciplines
SC Education & Educational Research
GA 793NS
UT WOS:000292831000001
PM 21682858
ER

PT J
AU Kim, JY
   Carlson, BA
   Xu, XM
   Zeng, Y
   Chen, S
   Gladyshev, VN
   Lee, BJ
   Hatfield, DL
AF Kim, Jin Young
   Carlson, Bradley A.
   Xu, Xue-Ming
   Zeng, Yu
   Chen, Shawn
   Gladyshev, Vadim N.
   Lee, Byeong Jae
   Hatfield, Dolph L.
TI Inhibition of selenocysteine tRNA([Ser]Sec) aminoacylation provides
   evidence that aminoacylation is required for regulatory methylation of
   this tRNA
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Selenium status; Selenocysteine; Selenocysteine tRNA; Selenoproteins;
   Selenoprotein hierarchy; Um34 tRNA methylation
ID PHOSPHOSERINE TRANSFER-RNA; TRANSFER RNA<SER>SEC; MAMMALIAN-CELLS;
   EXPRESSION; SELENOPROTEINS; POPULATION; PATHWAY; LACKING; GENE; UM34
AB There are two isoforms of selenocysteine (Sec) tRNA([Ser]Sec) that differ by a single methyl group, Um34. The non-Um34 isoform supports the synthesis of a subclass of selenoproteins, designated housekeeping, while the Um34 isoform supports the expression of another subclass, designated stress-related selenoproteins. Herein, we investigated the relationship between tRNA([Ser]Sec) aminoacylation and Um34 synthesis which is the last step in the maturation of this tRNA. Mutation of the discriminator base at position 73 in ([Ser]Sec) dramatically reduced aminoacylation with serine, as did an inhibitor of seryl-tRNA synthetase, SB-217452. Although both the mutation and the inhibitor prevented Um34 synthesis, neither precluded the synthesis of any other of the known base modifications on tRNA([Ser]Sec) following microinjection and incubation of the mutant tRNA([Ser]Sec) transcript, or the wild type transcript along with inhibitor, in Xenopus oocytes. The data demonstrate that Sec tRNA([Ser]Sec) must be aminoacylated for Um34 addition. The fact that selenium is required for Um34 methylation suggests that Sec must be attached to its tRNA for Um34 methylation. This would explain why selenium is essential for the function of Um34 methylase and provides further insights into the hierarchy of selenoprotein expression. Published by Elsevier Inc.
C1 [Kim, Jin Young; Lee, Byeong Jae] Seoul Natl Univ, Inst Mol Biol & Genet, Sch Biol Sci, Lab Mol Genet & Genom, Seoul 151742, South Korea.
   [Carlson, Bradley A.; Xu, Xue-Ming; Hatfield, Dolph L.] NCI, Lab Canc Prevent, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Zeng, Yu; Chen, Shawn] Ohio Univ, Dept Biol Sci, Athens, OH 45701 USA.
   [Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.
   [Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Lee, BJ (reprint author), Seoul Natl Univ, Inst Mol Biol & Genet, Sch Biol Sci, Lab Mol Genet & Genom, Seoul 151742, South Korea.
EM imbglmg@snu.ac.kr; hatfield@mail.nih.gov
RI Chen, Shawn/K-3585-2012; Gladyshev, Vadim/A-9894-2013
FU Center for Cancer Research, National Cancer Institute, National
   Institutes of Health; Ministry of Education, Science and Technology
   [2009-0094020, 2011-0012947]; National Institutes of Health [GM061603,
   GM065204, CA080946]; American Heart Association [09BGIA2070029]; Korea
   Ministry of Education and Human Resources Development
FX This work was supported by the Intramural Research Program at the Center
   for Cancer Research, National Cancer Institute, National Institutes of
   Health (to D.L.H.); the Priority Research Centers Program and Basic
   Science Research Program through the National Research Foundation of
   Korea (NRF) funded by the Ministry of Education, Science and Technology
   (Grant Nos. 2009-0094020 and 2011-0012947 to B.J.L.); National
   Institutes of Health (Grant Nos. GM061603, GM065204 and CA080946 to
   V.N.G.), and American Heart Association (Grant No. 09BGIA2070029 to
   S.C.); JVK was supported by Brain Korea 21 Research Fellowship from the
   Korea Ministry of Education and Human Resources Development.
NR 25
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Z9 13
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUN 17
PY 2011
VL 409
IS 4
BP 814
EP 819
DI 10.1016/j.bbrc.2011.05.096
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 787ED
UT WOS:000292358500040
PM 21624347
ER

PT J
AU Sfanos, KS
   Aloia, AL
   Hicks, JL
   Esopi, DM
   Steranka, JP
   Shao, W
   Sanchez-Martinez, S
   Yegnasubramanian, S
   Burns, KH
   Rein, A
   De Marzo, AM
AF Sfanos, Karen Sandell
   Aloia, Amanda L.
   Hicks, Jessica L.
   Esopi, David M.
   Steranka, Jared P.
   Shao, Wei
   Sanchez-Martinez, Silvia
   Yegnasubramanian, Srinivasan
   Burns, Kathleen H.
   Rein, Alan
   De Marzo, Angelo M.
TI Identification of Replication Competent Murine Gammaretroviruses in
   Commonly Used Prostate Cancer Cell Lines
SO PLOS ONE
LA English
DT Article
ID HUMAN RETROVIRUS XMRV; HUMAN GENOME; VIRUS; DISEASE; MICE; CONTAMINATION
AB A newly discovered gammaretrovirus, termed XMRV, was recently reported to be present in the prostate cancer cell line CWR22Rv1. Using a combination of both immunohistochemistry with broadly-reactive murine leukemia virus (MLV) antisera and PCR, we determined if additional prostate cancer or other cell lines contain XMRV or MLV-related viruses. Our study included a total of 72 cell lines, which included 58 of the 60 human cancer cell lines used in anticancer drug screens and maintained at the NCI-Frederick (NCI-60). We have identified gammaretroviruses in two additional prostate cancer cell lines: LAPC4 and VCaP, and show that these viruses are replication competent. Viral genome sequencing identified the virus in LAPC4 and VCaP as nearly identical to another known xenotropic MLV, Bxv-1. We also identified a gammaretrovirus in the non-small-cell lung carcinoma cell line EKVX. Prostate cancer cell lines appear to have a propensity for infection with murine gammaretroviruses, and we propose that this may be in part due to cell line establishment by xenograft passage in immunocompromised mice. It is unclear if infection with these viruses is necessary for cell line establishment, or what confounding role they may play in experiments performed with these commonly used lines. Importantly, our results suggest a need for regular screening of cancer cell lines for retroviral "contamination", much like routine mycoplasma testing.
C1 [Sfanos, Karen Sandell; Hicks, Jessica L.; Burns, Kathleen H.; De Marzo, Angelo M.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
   [Aloia, Amanda L.; Sanchez-Martinez, Silvia; Rein, Alan] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
   [Esopi, David M.; Yegnasubramanian, Srinivasan; De Marzo, Angelo M.] Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA.
   [Steranka, Jared P.; Burns, Kathleen H.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA.
   [Shao, Wei] Sci Applicat Int Corp, Adv Biomed Comp Ctr, Frederick, MD USA.
   [De Marzo, Angelo M.] Johns Hopkins Univ, Sch Med, Dept Urol, Brady Urol Res Inst, Baltimore, MD 21205 USA.
RP Sfanos, KS (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
EM ksfanos@jhmi.edu
FU Prevent Cancer Foundation; NIH, National Cancer Institute, Center for
   Cancer Research; NCI-SPORE [P50CA58236]
FX K.S.S. was supported by a postdoctoral fellowship award from the Prevent
   Cancer Foundation. This research was supported in part by the Intramural
   Research Program of the NIH, National Cancer Institute, Center for
   Cancer Research. IHC studies were supported by NCI-SPORE in prostate
   cancer P50CA58236. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 25
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U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 17
PY 2011
VL 6
IS 6
AR e20874
DI 10.1371/journal.pone.0020874
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 778VR
UT WOS:000291737600025
PM 21698104
ER

PT J
AU Kasamatsu, A
   Nakao, M
   Smith, BC
   Comstock, LR
   Ono, T
   Kato, J
   Denu, JM
   Moss, J
AF Kasamatsu, Atsushi
   Nakao, Motoyuki
   Smith, Brian C.
   Comstock, Lindsay R.
   Ono, Tohru
   Kato, Jiro
   Denu, John M.
   Moss, Joel
TI Hydrolysis of O-Acetyl-ADP-ribose Isomers by ADP-ribosylhydrolase 3
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID 39-KDA POLY(ADP-RIBOSE) GLYCOHYDROLASE; NAD(+)-DEPENDENT DEACETYLASES;
   RIBOSYLARGININE HYDROLASES; TURKEY ERYTHROCYTES; SIR2 FAMILY;
   RIBOSYLTRANSFERASES; IDENTIFICATION; RIBOSYLATION; METABOLITE; PRODUCT
AB O-Acetyl-ADP-ribose (OAADPr), produced by the Sir2-catalyzed NAD(+)-dependent histone/protein deacetylase reaction, regulates diverse biological processes. Interconversion between two OAADPr isomers with acetyl attached to the C-2 '' and C-3 '' hydroxyl of ADP-ribose (ADPr) is rapid. We reported earlier that ADP-ribosylhydrolase 3 (ARH3), one of three ARH proteins sharing structural similarities, hydrolyzed OAADPr to ADPr and acetate, and poly(ADPr) to ADPr monomers. ARH1 also hydrolyzed OAADPr and poly(ADPr) as well as ADP-ribose-arginine, with arginine in alpha-anomeric linkage to C-1 '' of ADP-ribose. Because both ARH3- and ARH1-catalyzed reactions involve nucleophilic attacks at the C-1 '' position, it was perplexing that the ARH3 catalytic site would cleave OAADPr at either the 2 ''- or 3 ''-position, and we postulated the existence of a third isomer, 1 ''-OAADPr, in equilibrium with 2 ''- and 3 ''-isomers. A third isomer, consistent with 1 ''-OAADPr, was identified at pH 9.0. Further, ARH3 OAADPr hydrolase activity was greater at pH 9.0 than at neutral pH where 3 ''-OAADPr predominated. Consistent with our hypothesis, IC(50) values for ARH3 inhibition by 2 ''- and 3 ''-N-acetyl-ADPr analogs of OAADPr were significantly higher than that for ADPr. ARH1 also hydrolyzed OAADPr more rapidly at alkaline pH, but cleavage of ADP-ribose-arginine was faster at neutral pH than pH 9.0. ARH3-catalyzed hydrolysis of OAADPr in H(2) (18)O resulted in incorporation of one (18)O into ADP-ribose by mass spectrometric analysis, consistent with cleavage at the C-1 '' position. Together, these data suggest that ARH family members, ARH1 and ARH3, catalyze hydrolysis of the 1 ''-O linkage in their structurally diverse substrates.
C1 [Kasamatsu, Atsushi; Nakao, Motoyuki; Ono, Tohru; Kato, Jiro; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
   [Smith, Brian C.; Comstock, Lindsay R.; Denu, John M.] Univ Wisconsin, Dept Biomol Chem, Madison, WI 53706 USA.
RP Moss, J (reprint author), NHLBI, Cardiovasc & Pulm Branch, NIH, Rm 6D05,Bldg 10,MSC 1590, Bethesda, MD 20892 USA.
EM mossj@nhlbi.nih.gov
RI Smith, Brian/D-9949-2013
OI Smith, Brian/0000-0001-6330-2768
FU National Institutes of Health, NHLBI
FX This work was supported, in whole or in part, by the Intramural Research
   Program, National Institutes of Health, NHLBI.
NR 27
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U1 0
U2 6
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 JUN 17
PY 2011
VL 286
IS 24
BP 21110
EP 21117
DI 10.1074/jbc.M111.237636
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 775MX
UT WOS:000291464700010
PM 21498885
ER

PT J
AU Guzik-Lendrum, S
   Nagy, A
   Takagi, Y
   Houdusse, A
   Sellers, JR
AF Guzik-Lendrum, Stephanie
   Nagy, Attila
   Takagi, Yasuharu
   Houdusse, Anne
   Sellers, James R.
TI Drosophila melanogaster Myosin-18 Represents a Highly Divergent Motor
   with Actin Tethering Properties
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DICTYOSTELIUM-DISCOIDEUM MYOSIN; TUMOR-SUPPRESSOR GENE; SKELETAL-MUSCLE
   MYOSIN; KINETIC MECHANISM; ADENOSINE-TRIPHOSPHATASE; HEAVY-MEROMYOSIN;
   BINDING DOMAIN; SMOOTH-MUSCLE; IN-VITRO; ACTOMYOSIN
AB The gene encoding Drosophila myosin-18 is complex and can potentially yield six alternatively spliced mRNAs. One of the major features of this myosin is an N-terminal PDZ domain that is included in some of the predicted alternatively spliced products. To explore the biochemical properties of this protein, we engineered two minimal motor domain (MMD)-like constructs, one that contains the N-terminal PDZ (myosin-18 M-PDZ) domain and one that does not (myosin-18 M-Delta PDZ). These two constructs were expressed in the baculovirus/Sf9 system. The results suggest that Drosophila myosin-18 is highly divergent from most other myosins in the superfamily. Neither of the MMD constructs had an actin-activated MgATPase activity, nor did they even bind ATP. Both myosin-18 M-PDZ and M-Delta PDZ proteins bound to actin with K-d values of 2.61 and 1.04 mu M, respectively, but only about 50-75% of the protein bound to actin even at high actin concentrations. Unbound proteins from these actin binding assays reiterated the 60% saturation maximum, suggesting an equilibrium between actin-binding and non-actin-binding conformations of Drosophila myosin-18 in vitro. Neither the binding affinity nor the substoichiometric binding was significantly affected by ATP. Optical trapping of single molecules in three-bead assays showed short lived interactions of the myosin-18 motors with actin filaments. Combined, these data suggest that this highly divergent motor may function as an actin tethering protein.
C1 [Guzik-Lendrum, Stephanie; Nagy, Attila; Takagi, Yasuharu; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
   [Guzik-Lendrum, Stephanie] Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA.
   [Houdusse, Anne] Inst Curie CNRS, UMR144, F-75248 Paris 05, France.
RP Sellers, JR (reprint author), NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
EM sellersj@nhlbi.nih.gov
FU NHLBI
FX This work was supported, in whole or in part, by National Institutes of
   Health intramural funds from the NHLBI.
NR 55
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U1 1
U2 14
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 17
PY 2011
VL 286
IS 24
BP 21755
EP 21766
DI 10.1074/jbc.M111.218669
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 775MX
UT WOS:000291464700071
PM 21498886
ER

PT J
AU Fukuda, K
   Knight, JDR
   Piszczek, G
   Kothary, R
   Qin, J
AF Fukuda, Koichi
   Knight, James D. R.
   Piszczek, Grzegorz
   Kothary, Rashmi
   Qin, Jun
TI Biochemical, Proteomic, Structural, and Thermodynamic Characterizations
   of Integrin-linked Kinase (ILK) CROSS-VALIDATION OF THE PSEUDOKINASE
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-KINASE; CRYSTAL-STRUCTURE; CELL-ADHESION; FOCAL ADHESIONS;
   ALPHA-PARVIN; BINDING; PINCH; COMPLEXES; CANCER; CRYSTALLOGRAPHY
AB Integrin-linked kinase (ILK) is one of the few evolutionarily conserved focal adhesion proteins involved in diverse cell adhesion-dependent physiological and pathological responses. Despite more than a decade of studies and extensive literature, the kinase function of ILK is controversial. ILK contains a highly degraded kinase active site but it has been argued that ILK may be an unusual manganese (Mn)-dependent serine-threonine kinase that targets specific substrates such as glycogen synthase kinase-3 beta (GSK-3 beta). In this study, we have tackled this issue by a systematic bottom-up biochemical, proteomic, structural, and thermodynamic analysis of ILK. We show that recombinant ILK from either bacteria or mammalian cells exhibits no kinase activity on GSK-3 beta in the presence of either Mn2+ or the conventional kinase co-factor Mg2+. A comprehensive and unbiased whole cell-based kinase assay using entire mammalian CG-4 and C2C12 cell lysate did not identify any specific ILK substrates. High resolution crystallographic structure analysis further confirmed that the Mn-bound ILK adopts the same pseudo active site conformation as that of the Mg-bound ILK. More importantly, thermodynamic analysis revealed that the K220M mutation, previously thought to inactivate ILK by disrupting ATP binding, significantly impairs the structural integrity and stability of ILK, which provides a new basis for understanding how this mutation caused renal agenesis, a failure of fetal kidney development. Collectively, our data provide strong evidence that ILK lacks intrinsic kinase function. It is a bona fide pseudokinase that likely evolved from an ancestral catalytic counterpart to act as a distinct scaffold to mediate protein-protein interactions during focal adhesion assembly and many other cellular events.
C1 [Qin, Jun] Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44195 USA.
   [Knight, James D. R.; Kothary, Rashmi] Ottawa Hosp, Res Inst, Ottawa, ON K1H 8L6, Canada.
   [Knight, James D. R.; Kothary, Rashmi] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON K1H 8M5, Canada.
   [Piszczek, Grzegorz] NHLBI, Biophys Core Facil, NIH, Bethesda, MD 20892 USA.
RP Qin, J (reprint author), Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Mail Code NB20,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM qinj@ccf.org
OI Kothary, Rashmi/0000-0002-9239-7310
FU National Institute of Health; Canadian Institutes of Health Research;
   Multiple Sclerosis Society of Canada; Kirschstein-NRSA (the National
   Institutes of Health)
FX This work was supported by grants from the National Institute of Health
   (to J. Q.) and from Canadian Institutes of Health Research and the
   Multiple Sclerosis Society of Canada (to R. K.).; Supported by the
   Kirschstein-NRSA institutional research training grants (the National
   Institutes of Health).
NR 51
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U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 17
PY 2011
VL 286
IS 24
BP 21886
EP 21895
DI 10.1074/jbc.M111.240093
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 775MX
UT WOS:000291464700083
PM 21524996
ER

PT J
AU Coleman, CN
   Simon, SL
   Noska, MA
   Telfer, JL
   Bowman, T
AF Coleman, C. Norman
   Simon, Steven L.
   Noska, Michael A.
   Telfer, Jana L.
   Bowman, Thomas
TI Disaster Preparation: Lessons from Japan
SO SCIENCE
LA English
DT Letter
C1 [Coleman, C. Norman] NCI, Washington, DC 20201 USA.
   [Coleman, C. Norman] US Dept HHS, Off Preparedness & Emergency Operat, Washington, DC 20201 USA.
   [Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Noska, Michael A.] US PHS, US FDA, Silver Spring, MD 20993 USA.
   [Telfer, Jana L.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Agcy Tox Subst & Dis Registry, Atlanta, GA 30341 USA.
   [Bowman, Thomas] Ctr Dis Control & Prevent, US Publ Hlth Serv, Div Strateg Natl Stockpile, Off Publ Hlth Preparedness & Response, Atlanta, GA 30329 USA.
RP Coleman, CN (reprint author), NCI, 200 Independence Ave SW, Washington, DC 20201 USA.
EM ccoleman@mail.nih.gov
NR 0
TC 5
Z9 6
U1 0
U2 14
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUN 17
PY 2011
VL 332
IS 6036
BP 1379
EP 1379
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 778FT
UT WOS:000291689000018
PM 21680826
ER

PT J
AU Simpson, CL
   Wojciechowski, R
   Ibay, G
   Stambolian, D
   Bailey-Wilson, JE
AF Simpson, Claire L.
   Wojciechowski, Robert
   Ibay, Grace
   Stambolian, Dwight
   Bailey-Wilson, Joan E.
TI Dissecting the genetic heterogeneity of myopia susceptibility in an
   Ashkenazi Jewish population using ordered subset analysis
SO MOLECULAR VISION
LA English
DT Article
ID GENOME-WIDE SCAN; FAMILIAL HIGH MYOPIA; RHIZOMELIC CHONDRODYSPLASIA
   PUNCTATA; HIGH-GRADE MYOPIA; REFRACTIVE ERROR; OCULAR REFRACTION; EYE
   GROWTH; AFRICAN-AMERICAN; CHROMOSOME 22Q12; CONFIRMS LINKAGE
AB Purpose: Despite many years of research, most of the genetic factors contributing to myopia development remain unknown. Genetic studies have pointed to a strong inherited component, but although many candidate regions have been implicated, few genes have been positively identified.
   Methods: We have previously reported 2 genomewide linkage scans in a population of 63 highly aggregated Ashkenazi Jewish families that identified a locus on chromosome 22. Here we used ordered subset analysis (OSA), conditioned on non-parametric linkage to chromosome 22 to detect other chromosomal regions which had evidence of linkage to myopia in subsets of the families, but not the overall sample.
   Results: Strong evidence of linkage to a 19-cM linkage interval with a peak OSA nonparametric allele-sharing logarithm-of- odds (LOD) score of 3.14 on 20p12-q11.1 (Delta LOD=2.39, empirical p=0.029) was identified in a subset of 20 families that also exhibited strong evidence of linkage to chromosome 22. One other locus also presented with suggestive LOD scores > 2.0 on chromosome 11p14-q14 and one locus on chromosome 6q22-q24 had an OSA LOD score=1.76 (Delta LOD=1.65, empirical p=0.02).
   Conclusions: The chromosome 6 and 20 loci are entirely novel and appear linked in a subset of families whose myopia is known to be linked to chromosome 22. The chromosome 11 locus overlaps with the known Myopia-7 (MYP7, OMIM 609256) locus. Using ordered subset analysis allows us to find additional loci linked to myopia in subsets of families, and underlines the complex genetic heterogeneity of myopia even in highly aggregated families and genetically isolated populations such as the Ashkenazi Jews.
C1 [Simpson, Claire L.; Wojciechowski, Robert; Ibay, Grace; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA.
   [Ibay, Grace] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
   [Wojciechowski, Robert] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   [Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
RP Bailey-Wilson, JE (reprint author), NHGRI, Inherited Dis Res Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA.
EM jebw@mail.nih.gov
OI Bailey-Wilson, Joan/0000-0002-9153-2920; Wojciechowski,
   Robert/0000-0002-9593-4652
FU National Eye Institute, National Institutes of Health [R01 EY020483];
   National Human Genome Research Institute, National Institutes of Health
FX This work was supported in part R01 EY020483 from the National Eye
   Institute, National Institutes of Health and by the Intramural Program
   of the National Human Genome Research Institute, National Institutes of
   Health.
NR 70
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U1 0
U2 2
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JUN 17
PY 2011
VL 17
IS 180-82
BP 1641
EP 1651
PG 11
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 783AU
UT WOS:000292054700003
PM 21738393
ER

PT J
AU Thomas, JA
   Shatzer, TL
   Gorelick, RJ
AF Thomas, James A.
   Shatzer, Teresa L.
   Gorelick, Robert J.
TI Blocking premature reverse transcription fails to rescue the HIV-1
   nucleocapsid-mutant replication defect
SO RETROVIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACID-CHAPERONE ACTIVITY; ZINC-FINGER
   STRUCTURES; MINUS-STRAND TRANSFER; PROVIRAL DNA-SYNTHESIS; FUSION
   INHIBITOR T-20; IN-VITRO; INFECTION PROCESSES; ASSISTANCE ROLES; TYPE-1
   HIV-1
AB Background: The nucleocapsid (NC) protein of HIV-1 is critical for viral replication. Mutational analyses have demonstrated its involvement in viral assembly, genome packaging, budding, maturation, reverse transcription, and integration. We previously reported that two conservative NC mutations, His23Cys and His44Cys, cause premature reverse transcription such that mutant virions contain approximately 1,000-fold more DNA than wild-type virus, and are replication defective. In addition, both mutants show a specific defect in integration after infection.
   Results: In the present study we investigated whether blocking premature reverse transcription would relieve the infectivity defects, which we successfully performed by transfecting proviral plasmids into cells cultured in the presence of high levels of reverse transcriptase inhibitors. After subsequent removal of the inhibitors, the resulting viruses showed no significant difference in single-round infective titer compared to viruses where premature reverse transcription did occur; there was no rescue of the infectivity defects in the NC mutants upon reverse transcriptase inhibitor treatment. Surprisingly, time-course endogenous reverse transcription assays demonstrated that the kinetics for both the NC mutants were essentially identical to wild-type when premature reverse transcription was blocked. In contrast, after infection of CD4+ HeLa cells, it was observed that while the prevention of premature reverse transcription in the NC mutants resulted in lower quantities of initial reverse transcripts, the kinetics of reverse transcription were not restored to that of untreated wild-type HIV-1.
   Conclusions: Premature reverse transcription is not the cause of the replication defect but is an independent side-effect of the NC mutations.
C1 [Thomas, James A.; Shatzer, Teresa L.; Gorelick, Robert J.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Gorelick, RJ (reprint author), NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM gorelicr@mail.nih.gov
OI Thomas, James/0000-0002-2509-490X
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; SAIC-Frederick, Inc.
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 HHSN261200800001E with SAIC-Frederick, Inc. 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 78
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U1 0
U2 0
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 JUN 17
PY 2011
VL 8
AR 46
DI 10.1186/1742-4690-8-46
PG 14
WC Virology
SC Virology
GA 796TR
UT WOS:000293075800001
PM 21682883
ER

PT J
AU Gradmark, A
   Pomeroy, J
   Renstrom, F
   Steiginga, S
   Persson, M
   Wright, A
   Bluck, L
   Domellof, M
   Kahn, SE
   Mogren, I
   Franks, PW
AF Gradmark, Anna
   Pomeroy, Jeremy
   Renstrom, Frida
   Steiginga, Susanne
   Persson, Margareta
   Wright, Antony
   Bluck, Les
   Domellof, Magnus
   Kahn, Steven E.
   Mogren, Ingrid
   Franks, Paul W.
TI Physical activity, sedentary behaviors, and estimated insulin
   sensitivity and secretion in pregnant and non-pregnant women
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
DE pregnancy; physical activity; sedentary time; beta?beta?-cell response;
   insulin sensitivity
ID ENERGY-EXPENDITURE; LONGITUDINAL CHANGES; GLUCOSE-TOLERANCE; LABELED
   WATER; RESISTANCE; INTERVENTION; PREVENTION; HUMANS
AB Background: Overweight and obesity during pregnancy raise the risk of gestational diabetes and birth complications. Lifestyle factors like physical activity may decrease these risks through beneficial effects on glucose homeostasis. Here we examined physical activity patterns and their relationships with measures of glucose homeostasis in late pregnancy compared to non-pregnant women.
   Methods: Normal weight and overweight women without diabetes (N = 108; aged 25-35 years) were studied; 35 were pregnant (in gestational weeks 28-32) and 73 were non-pregnant. Insulin sensitivity and beta-cell response were estimated from an oral glucose tolerance test. Physical activity was measured during 10-days of free-living using a combined heart rate sensor and accelerometer. Total (TEE), resting (REE), and physical activity (PAEE) energy expenditure were measured using doubly-labeled water and expired gas indirect calorimetry.
   Results: Total activity was associated with reduced first-phase insulin response in both pregnant (Regression r(2) = 0.11; Spearman r = -0.47; p = 0.007) and non-pregnant women (Regression r2 = 0.11 Spearman; r = -0.36; p = 0.002). Relative to non-pregnant women, pregnant women were estimated to have secreted 67% more insulin and had 10% lower fasting glucose than non-pregnant women. Pregnant women spent 13% more time sedentary, 71% less time in moderate-to-vigorous intensity activity, had 44% lower objectively measured total activity, and 12% lower PAEE than non-pregnant women. Correlations did not differ significantly for any comparison between physical activity subcomponents and measures of insulin sensitivity or secretion.
   Conclusions: Our findings suggest that physical activity conveys similar benefits on glucose homeostasis in pregnant and non-pregnant women, despite differences in subcomponents of physical activity.
C1 [Gradmark, Anna; Pomeroy, Jeremy; Renstrom, Frida; Steiginga, Susanne; Franks, Paul W.] Umea Univ Hosp, Med Sect, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden.
   [Pomeroy, Jeremy] NIDDK, NIH, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
   [Pomeroy, Jeremy; Renstrom, Frida; Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
   [Renstrom, Frida; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
   [Steiginga, Susanne] Free Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
   [Persson, Margareta] Umea Univ Hosp, Dept Clin Sci, S-90185 Umea, Sweden.
   [Persson, Margareta] Umea Univ Hosp, Dept Nursing, S-90185 Umea, Sweden.
   [Wright, Antony; Bluck, Les] MRC Human Nutr Res, Cambridge, England.
   [Domellof, Magnus] Umea Univ Hosp, Dept Pediat, S-90185 Umea, Sweden.
   [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA.
   [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA.
   [Mogren, Ingrid] Umea Univ Hosp, Dept Clin Sci Obstet & Gynecol, S-90185 Umea, Sweden.
RP Franks, PW (reprint author), Umea Univ Hosp, Med Sect, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden.
EM paul.franks@med.lu.se
RI Domellof, Magnus/E-5307-2011; 
OI Domellof, Magnus/0000-0002-0726-7029; Steiginga,
   Susanne/0000-0002-7015-2259; Mogren, Ingrid/0000-0003-2985-1135; Franks,
   Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002
FU Torsten & Ragnar Soderbergs Foundation (via LifeGene); Fredrik; Ingrid
   Thurings Foundation, Visare Norr; Vasterbotten regional health
   authority; United States Department of Veterans Affairs; Heart-Lung
   Foundation; Swedish Diabetes Association; Swedish Heart-Lung Foundation;
   Swedish Research Council; Novo Nordisk
FX We thank the participants in this study and M. Holmgren for assistance
   in collecting data. The study was a preparatory project for the LifeGene
   Study http://www.lifegene.se and was funded by Torsten & Ragnar
   Soderbergs Foundation (via LifeGene), Fredrik and Ingrid Thurings
   Foundation, Visare Norr, and Vasterbotten regional health authority (all
   grants to PWF). SEK was supported by the United States Department of
   Veterans Affairs. FR was support by a post-doctoral stipend from the
   Heart-Lung Foundation. PWF was supported by grants from the Swedish
   Diabetes Association, the Swedish Heart-Lung Foundation, the Swedish
   Research Council, and Novo Nordisk.
NR 24
TC 21
Z9 21
U1 0
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD JUN 16
PY 2011
VL 11
AR 44
DI 10.1186/1471-2393-11-44
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 840VP
UT WOS:000296469800001
PM 21679399
ER

PT J
AU Beaudry, JT
   Fairhurst, RM
AF Beaudry, Jeanette T.
   Fairhurst, Rick M.
TI Microvascular sequestration of Plasmodium falciparum
SO BLOOD
LA English
DT Editorial Material
C1 [Beaudry, Jeanette T.; Fairhurst, Rick M.] NIAID, NIH, Bethesda, MD USA.
RP Beaudry, JT (reprint author), NIAID, NIH, Bethesda, MD USA.
NR 0
TC 4
Z9 4
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 JUN 16
PY 2011
VL 117
IS 24
BP 6410
EP 6410
DI 10.1182/blood-2010-09-305102
PG 1
WC Hematology
SC Hematology
GA 778EP
UT WOS:000291684300004
PM 21823261
ER

PT J
AU Hoechst, B
   Gamrekelashvili, J
   Manns, MP
   Greten, TF
   Korangy, F
AF Hoechst, Bastian
   Gamrekelashvili, Jaba
   Manns, Michael P.
   Greten, Tim F.
   Korangy, Firouzeh
TI Plasticity of human Th17 cells and iTregs is orchestrated by different
   subsets of myeloid cells
SO BLOOD
LA English
DT Article
ID REGULATORY T-CELLS; RETINOIC-ACID; DENDRITIC CELLS; SUPPRESSOR-CELLS;
   TGF-BETA; HEPATOCELLULAR-CARCINOMA; PERIPHERAL-BLOOD; FOXP3; LINEAGE;
   T(H)17
AB CD4(+) T helper cell differentiation is essential for mounting robust immune responses without compromising unresponsiveness toward self-tissue. Here, we show that different subsets of myeloid cells isolated from human peripheral blood modulate TGF-beta-dependent CD(4+) T-cell developmental programs ex vivo. Human CD14(+)HLA-DR(-/low) myeloid-derived suppressor cells (MDSCs) induce Foxp3(+) regulatory T cells, whereas CD14(+)HLA-DR(+) monocytes promote generation of IL-17-secreting RORc(+) Th17 cells when cocultured with naive CD4(+) T cells. More importantly, not only do these 2 subsets modulate the de novo induction of Tregs and Th17 cells from CD4(+) T cells, but MDSCs also catalyze the transdifferentiation of Foxp3(+) regulatory T cells from monocyte-induced Th17 cells. The mechanism of such Th17 plasticity is dependent on MDSC-derived TGF-beta and retinoic acid. Our results identify a previously unknown feature of the different subsets of CD14(+) myeloid cells namely their pivotal role in immune response regulation and plasticity of CD4(+) T helper cells. We propose that different subsets of myeloid cells in humans can orchestrate the differentiation of naive CD4(+) T cells into effector/regulatory T-cell subsets. The balance between these 2 subsets can impact the outcome of immune reaction from inflammation to tolerance. (Blood. 2011;117(24):6532-6541)
C1 [Greten, Tim F.; Korangy, Firouzeh] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
   [Hoechst, Bastian; Gamrekelashvili, Jaba; Manns, Michael P.; Greten, Tim F.; Korangy, Firouzeh] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30623 Hannover, Germany.
   [Hoechst, Bastian; Gamrekelashvili, Jaba; Greten, Tim F.; Korangy, Firouzeh] Twincore Ctr Expt & Clin Infect Res, Hannover, Germany.
RP Korangy, F (reprint author), NCI, Med Oncol Branch, NIH, Bldg 10-12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tim.greten@nih.gov; firouzeh.korangy@nih.gov
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
FU Helmholtz Association within the Helmholtz Alliance on Immunotherapy of
   Cancer
FX This work was supported by a grant to M. P. M. and T. F. G. from the
   Initiative and Networking Fund of the Helmholtz Association within the
   Helmholtz Alliance on Immunotherapy of Cancer.
NR 44
TC 99
Z9 111
U1 0
U2 14
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 JUN 16
PY 2011
VL 117
IS 24
BP 6532
EP 6541
DI 10.1182/blood-2010-11-317321
PG 10
WC Hematology
SC Hematology
GA 778EP
UT WOS:000291684300018
PM 21493801
ER

PT J
AU Adriani, M
   Jones, KA
   Uchiyama, T
   Kirby, MR
   Silvin, C
   Anderson, SM
   Candotti, F
AF Adriani, Marsilio
   Jones, Krysten A.
   Uchiyama, Toru
   Kirby, Martha R.
   Silvin, Christopher
   Anderson, Stacie M.
   Candotti, Fabio
TI Defective inhibition of B-cell proliferation by Wiskott-Aldrich syndrome
   protein-deficient regulatory T cells
SO BLOOD
LA English
DT Article
ID CUTTING EDGE; GRANZYME-B; IN-VITRO; WASP; HOMEOSTASIS; ACTIVATION;
   LYMPHOCYTES
AB Wiskott-Aldrich syndrome (WAS) is an inherited immunodeficiency characterized by high incidence of autoantibody-mediated autoimmune complications. Such a feature has been associated with defective suppressor activity of WAS protein-deficient, naturally occurring CD4(+)CD25(+)Foxp3(+) regulatory T cells on responder T cells. However, it remains to be established whether the altered B-cell tolerance reported in WAS patients and Was knockout (WKO) mice is secondary to abnormalities in the direct suppression of B-cell function by nTreg cells or to impaired regulation of T-helper function. Because activated nTreg cells are known to induce granzyme B-mediated B-cell killing, we decided to evaluate the regulatory capabilities of WKO nTregs on B lymphocytes. We found that preactivated WKO nTreg cells failed to effectively suppress B-cell proliferation and that such a defect was associated with reduced killing of B cells and significantly decreased degranulation of granzyme B. Altogether, these results provide additional mechanistic insights into the loss of immune tolerance in WAS. (Blood. 2011;117(24):6608-6611)
C1 [Candotti, Fabio] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
   [Jones, Krysten A.] Univ Calif San Diego, Sch Med, Dept Infect Dis, La Jolla, CA 92093 USA.
   [Uchiyama, Toru] Tohoku Univ, Sch Med, Dept Pediat, Sendai, Miyagi 980, Japan.
RP Candotti, F (reprint author), NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Bldg 49,Rm 3A04, Bethesda, MD 20892 USA.
EM fabio@mail.nih.gov
RI Adriani, Marsilio/F-2553-2013
NR 20
TC 10
Z9 10
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 16
PY 2011
VL 117
IS 24
BP 6608
EP 6611
DI 10.1182/blood-2010-12-322834
PG 4
WC Hematology
SC Hematology
GA 778EP
UT WOS:000291684300026
PM 21515824
ER

PT J
AU Arora, M
   Klein, JP
   Weisdorf, DJ
   Hassebroek, A
   Flowers, MED
   Cutler, CS
   Urbano-Ispizua, A
   Antin, JH
   Bolwell, BJ
   Boyiadzis, M
   Cahn, JY
   Cairo, MS
   Isola, L
   Jacobsohn, DA
   Jagasia, M
   Klumpp, TR
   Lee, SJ
   Petersdorf, EW
   Santarone, S
   Gale, RP
   Schouten, HC
   Spellman, S
   Wingard, JR
   Horowitz, MM
   Pavletic, SZ
AF Arora, Mukta
   Klein, John P.
   Weisdorf, Daniel J.
   Hassebroek, Anna
   Flowers, Mary E. D.
   Cutler, Corey S.
   Urbano-Ispizua, Alvaro
   Antin, Joseph H.
   Bolwell, Brian J.
   Boyiadzis, Michael
   Cahn, Jean-Yves
   Cairo, Mitchell S.
   Isola, Luis
   Jacobsohn, David A.
   Jagasia, Madan
   Klumpp, Thomas R.
   Lee, Stephanie J.
   Petersdorf, Effie W.
   Santarone, Stella
   Gale, Robert Peter
   Schouten, Harry C.
   Spellman, Stephen
   Wingard, John R.
   Horowitz, Mary M.
   Pavletic, Steven Z.
TI Chronic GVHD risk score: a Center for International Blood and Marrow
   Transplant Research analysis
SO BLOOD
LA English
DT Article
ID VERSUS-HOST-DISEASE; CHRONIC GRAFT; SURVIVAL; CLASSIFICATION; SEVERITY;
   CRITERIA
AB Several risk factors are associated with increased mortality in patients with chronic graft-versus-host disease (cGVHD), but there is considerable variability in the reported factors. Therefore, we evaluated patient, transplantation, and cGVHD characteristics to develop a risk score in 5343 patients with cGVHD. Ten variables were identified as being significant in multivariate analysis of overall survival and nonrelapse mortality (NRM): age, prior acute GVHD, time from trans-plantation to cGVHD, donor type, disease status at transplantation, GVHD prophylaxis, gender mismatch, serum bilirubin, Karnofsky score, and platelet count. These 10 variables were used to build a cGVHD risk score, and 6 risk groups (RGs) were identified. The 5-year NRM was 5% (1%-9%) in RG1, 20% (19%-23%) in RG2, 33% (29%-37%) in RG3, 43% (40%-46%) in RG4, 63% (53%-74%) in RG5, and 72% (59%-85%) in RG6. The 5-year overall survival was highest at 91% (95% confidence interval [CI]: 85%-97%) in RG1, followed by 67% (65%-69%) in RG2, 51% (46%-55%) in RG3, 40% (37%-43%) in RG4, 21% (12%-30%) in RG5, and 4% (0%-9%) in RG6 (all P < .01). This analysis demonstrates the usefulness of data from a large registry to develop risk-score categories for major transplantation outcomes. Validation of this cGVHD risk score is needed in a different population to ensure its broad applicability. (Blood. 2011;117(24):6714-6720)
C1 [Arora, Mukta; Weisdorf, Daniel J.] Univ Minnesota, Dept Hematol Oncol & Transplant, Minneapolis, MN USA.
   [Klein, John P.] Med Coll Wisconsin, Dept Biostat, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
   [Hassebroek, Anna] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
   [Flowers, Mary E. D.; Lee, Stephanie J.; Petersdorf, Effie W.; Spellman, Stephen] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   [Flowers, Mary E. D.; Lee, Stephanie J.; Petersdorf, Effie W.; Spellman, Stephen] Univ Washington, Seattle, WA 98195 USA.
   [Cutler, Corey S.; Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
   [Urbano-Ispizua, Alvaro] Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain.
   [Bolwell, Brian J.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA.
   [Boyiadzis, Michael] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
   [Cahn, Jean-Yves] CHU Grenoble, F-38043 Grenoble, France.
   [Cairo, Mitchell S.] Columbia Univ, Dept Pediat Med Pathol & Cell Biol, New York, NY USA.
   [Cairo, Mitchell S.] New York Presbyterian Morgan Stanley Childrens Ho, New York, NY USA.
   [Isola, Luis] Mt Sinai Med Ctr, Dept Bone Marrow Transplantat, New York, NY 10029 USA.
   [Jacobsohn, David A.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
   [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Dept Hematol Stem Cell Transplant, Nashville, TN USA.
   [Klumpp, Thomas R.] Temple Univ, Wynnewood, PA USA.
   [Santarone, Stella] Osped Civile, Bone Marrow Transplantat Ctr, Pescara, Italy.
   [Gale, Robert Peter] Celgene Corp, Summit, NJ USA.
   [Schouten, Harry C.] Acad Ziekenhuis, Maastricht, Netherlands.
   [Wingard, John R.] Univ Florida, Shands Canc Ctr, Gainesville, FL USA.
   [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Arora, M (reprint author), MMC 480,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM arora005@umn.edu
FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and
   Blood Institute (NHLBI) [5U01HL069294]; National Institute of Allergy
   and Infectious Diseases (NIAID); Health Resources and Services
   Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research
   [N00014-06-1-0704, N00014-08-1-0058]; AABB; Allos Inc; Amgen Inc
FX The CIBMTR is supported by Public Health Service Grant/Cooperative
   Agreement U24-CA76518 from the National Cancer Institute (NCI), the
   National Heart, Lung and Blood Institute (NHLBI), and the National
   Institute of Allergy and Infectious Diseases (NIAID); a
   Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; contract
   HHSH234200637015C with Health Resources and Services Administration
   (HRSA/DHHS); grants N00014-06-1-0704 and N00014-08-1-0058 from the
   Office of Naval Research; and grants from AABB; Allos Inc; Amgen Inc; an
   anonymous donation to the Medical College of Wisconsin; Astellas Pharma
   US Inc; Be the Match Foundation; Biogen Idec Inc; BioMarin
   Pharmaceutical Inc; Biovitrum AB; Blood Center of Wisconsin; Blue Cross
   and Blue Shield Association; Bone Marrow Foundation; Buchanan Family
   Foundation; CaridianBCT; Celgene Corporation; CellGenix GmbH; Children's
   Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and
   Consulting Services; Eisai Inc; Genentech Inc; Genzyme Corporation;
   Histogenetics Inc; HKS Medical Information Systems; Hospira Inc; Kirin
   Brewery Co Ltd; The Leukemia & Lymphoma Society; Merck & Company; The
   Medical College of Wisconsin; Millennium Pharmaceuticals Inc; Miller
   Pharmacal Group; Milliman USA Inc; Miltenyi Biotec Inc; National Marrow
   Donor Program; Nature Publishing Group; Novartis Oncology; Oncology
   Nursing Society; Osiris Therapeutics Inc; Otsuka America Pharmaceutical
   Inc; Pall Life Sciences; Pfizer Inc; Schering Corporation; Sigma-Tau
   Pharmaceuticals; Soligenix Inc; StemCyte Inc; StemSoft Software Inc;
   Sysmex America Inc; Therakos Inc; Vidacare Corporation; ViraCor
   Laboratories; ViroPharma Inc; and Wellpoint Inc.
NR 20
TC 53
Z9 56
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUN 16
PY 2011
VL 117
IS 24
BP 6714
EP 6720
DI 10.1182/blood-2010-12-323824
PG 7
WC Hematology
SC Hematology
GA 778EP
UT WOS:000291684300039
PM 21493797
ER

PT J
AU Biswas, S
   Dicks, MDJ
   Long, CA
   Remarque, EJ
   Siani, L
   Colloca, S
   Cottingham, MG
   Holder, AA
   Gilbert, SC
   Hill, AVS
   Draper, SJ
AF Biswas, Sumi
   Dicks, Matthew D. J.
   Long, Carole A.
   Remarque, Edmond J.
   Siani, Loredana
   Colloca, Stefano
   Cottingham, Matthew G.
   Holder, Anthony A.
   Gilbert, Sarah C.
   Hill, Adrian V. S.
   Draper, Simon J.
TI Transgene Optimization, Immunogenicity and In Vitro Efficacy of Viral
   Vectored Vaccines Expressing Two Alleles of Plasmodium falciparum AMA1
SO PLOS ONE
LA English
DT Article
ID APICAL MEMBRANE ANTIGEN-1; MEROZOITE SURFACE PROTEIN-1; NATURAL
   IMMUNE-RESPONSES; CYTOTOXIC T-LYMPHOCYTES; BLOOD-STAGE VACCINE; BAY
   COHORT PROJECT; MALARIA VACCINE; PROTECTIVE IMMUNITY; GROWTH-INHIBITION;
   RECOMBINANT ADENOVIRUSES
AB Background: Apical membrane antigen 1 (AMA1) is a leading candidate vaccine antigen against blood-stage malaria, although to date numerous clinical trials using mainly protein-in-adjuvant vaccines have shown limited success. Here we describe the pre-clinical development and optimization of recombinant human and simian adenoviral (AdHu5 and ChAd63) and orthopoxviral (MVA) vectors encoding transgene inserts for Plasmodium falciparum AMA1 (PfAMA1).
   Methodology/Principal Findings: AdHu5-MVA prime-boost vaccination in mice and rabbits using these vectors encoding the 3D7 allele of PfAMA1 induced cellular immune responses as well as high-titer antibodies that showed growth inhibitory activity (GIA) against the homologous but not heterologous parasite strains. In an effort to overcome the issues of PfAMA1 antigenic polymorphism and pre-existing immunity to AdHu5, a simian adenoviral (ChAd63) vector and MVA encoding two alleles of PfAMA1 were developed. This antigen, composed of the 3D7 and FVO alleles of PfAMA1 fused in tandem and with expression driven by a single promoter, was optimized for antigen secretion and transmembrane expression. These bi-allelic PfAMA1 vaccines, when administered to mice and rabbits, demonstrated comparable immunogenicity to the mono-allelic vaccines and purified serum IgG now showed GIA against the two divergent strains of P. falciparum encoded in the vaccine. CD8(+) and CD4(+) T cell responses against epitopes that were both common and unique to the two alleles of PfAMA1 were also measured in mice.
   Conclusions/Significance: Optimized transgene inserts encoding two divergent alleles of the same antigen can be successfully inserted into adeno-and pox-viral vaccine vectors. Adenovirus-MVA immunization leads to the induction of T cell responses common to both alleles, as well as functional antibody responses that are effective against both of the encoded strains of P. falciparum in vitro. These data support the further clinical development of these vaccine candidates in Phase I/IIa clinical trials.
C1 [Biswas, Sumi; Dicks, Matthew D. J.; Cottingham, Matthew G.; Gilbert, Sarah C.; Hill, Adrian V. S.; Draper, Simon J.] Univ Oxford, Jenner Inst, Oxford, England.
   [Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
   [Remarque, Edmond J.] Biomed Primate Res Ctr, Dept Parasitol, Rijswijk, Netherlands.
   [Siani, Loredana; Colloca, Stefano] Okairos AG, Rome, Italy.
   [Holder, Anthony A.] Natl Inst Med Res, Div Parasitol, London NW7 1AA, England.
RP Biswas, S (reprint author), Univ Oxford, Jenner Inst, Oxford, England.
EM sumi.biswas@ndm.ox.ac.uk
RI Cottingham, Matthew/F-1218-2011; Draper, Simon/F-1758-2011; Holder,
   Anthony/A-7554-2013; 
OI Draper, Simon/0000-0002-9415-1357; Holder, Anthony/0000-0002-8490-6058;
   Dicks, Matthew/0000-0003-1909-7095; Gilbert, Sarah/0000-0002-6823-9750
FU MalParTraining [MEST-CT-2005-020492]; PATH-MVI Malaria Vaccine
   Initiative (MVI); National Institutes of Health, National Institute of
   Allergy and Infectious Diseases; EMVDA (European Malaria Vaccine
   Development Association); UK Medical Research Council [U117532067];
   Wellcome Trust
FX SB was funded by MalParTraining, an FP6-funded Marie Curie Action under
   contract number MEST-CT-2005-020492. The GIA work was supported in part
   by the PATH-MVI Malaria Vaccine Initiative (MVI) and the Intramural
   Program of the National Institutes of Health, National Institute of
   Allergy and Infectious Diseases and in part by the EMVDA (European
   Malaria Vaccine Development Association, a European Commission
   FP6-funded consortium). AAH is funded by the UK Medical Research Council
   (U117532067). AVSH and SCG are Jenner Investigators and are funded by
   the Wellcome Trust. SJD is a Junior Research Fellow of Merton College,
   Oxford University. The funders (Okairos) had a role in study design. No
   additional external funding was received for this study.
NR 66
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 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 16
PY 2011
VL 6
IS 6
AR e20977
DI 10.1371/journal.pone.0020977
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 778UW
UT WOS:000291734100037
PM 21698193
ER

PT J
AU Vang, O
   Ahmad, N
   Baile, CA
   Baur, JA
   Brown, K
   Csiszar, A
   Das, DK
   Delmas, D
   Gottfried, C
   Lin, HY
   Ma, QY
   Mukhopadhyay, P
   Nalini, N
   Pezzuto, JM
   Richard, T
   Shukla, Y
   Surh, YJ
   Szekeres, T
   Szkudelski, T
   Walle, T
   Wu, JM
AF Vang, Ole
   Ahmad, Nihal
   Baile, Clifton A.
   Baur, Joseph A.
   Brown, Karen
   Csiszar, Anna
   Das, Dipak K.
   Delmas, Dominique
   Gottfried, Carmem
   Lin, Hung-Yun
   Ma, Qing-Yong
   Mukhopadhyay, Partha
   Nalini, Namasivayam
   Pezzuto, John M.
   Richard, Tristan
   Shukla, Yogeshwer
   Surh, Young-Joon
   Szekeres, Thomas
   Szkudelski, Tomasz
   Walle, Thomas
   Wu, Joseph M.
TI What Is New for an Old Molecule? Systematic Review and Recommendations
   on the Use of Resveratrol
SO PLOS ONE
LA English
DT Article
ID CANCER CHEMOPREVENTIVE AGENT; ACTIVATED PROTEIN-KINASE; TRAUMATIC
   BRAIN-INJURY; ABERRANT CRYPT FOCI; INDUCED DIABETIC-RATS; FATTY
   LIVER-DISEASE; KAPPA-B ACTIVATION; SPINAL-CORD-INJURY; CELLS IN-VITRO;
   RED WINE
AB Background: Resveratrol is a natural compound suggested to have beneficial health effects. However, people are consuming resveratrol for this reason without having the adequate scientific evidence for its effects in humans. Therefore, scientific valid recommendations concerning the human intake of resveratrol based on available published scientific data are necessary. Such recommendations were formulated after the Resveratrol 2010 conference, held in September 2010 in Helsingor, Denmark.
   Methodology: Literature search in databases as PubMed and ISI Web of Science in combination with manual search was used to answer the following five questions: (1)Can resveratrol be recommended in the prevention or treatment of human diseases?; (2)Are there observed "side effects" caused by the intake of resveratrol in humans?; (3)What is the relevant dose of resveratrol?; (4)What valid data are available regarding an effect in various species of experimental animals?; (5)Which relevant (overall) mechanisms of action of resveratrol have been documented?
   Conclusions/Significance: The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials. Finally, we suggest directions for future research in resveratrol regarding its mechanism of action and its safety and toxicology in human subjects.
C1 [Vang, Ole] Roskilde Univ, Dept Sci Syst & Models, Roskilde, Denmark.
   [Ahmad, Nihal] Univ Wisconsin, Dept Dermatol, Madison, WI USA.
   [Baile, Clifton A.] Univ Georgia, Dept Anim & Dairy Sci, Athens, GA 30602 USA.
   [Baur, Joseph A.] Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA.
   [Baur, Joseph A.] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
   [Brown, Karen] Univ Leicester, Dept Canc Studies & Mol Med, Bioctr, Leicester, Great Britain, England.
   [Csiszar, Anna] Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK USA.
   [Das, Dipak K.] Univ Connecticut, Sch Med, Cardiovasc Res Ctr, Farmington, CT USA.
   [Delmas, Dominique] Univ Burgundy, INSERM, U866, Dijon, France.
   [Gottfried, Carmem] Univ Fed Rio Grande do Sul, Dept Biochem, Postgrad Programme Biochem, Inst Basic Hlth Sci, Porto Alegre, RS, Brazil.
   [Lin, Hung-Yun] Ordway Res Inst, Signal Transduct Lab, Albany, NY USA.
   [Ma, Qing-Yong] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Xian 710049, Shaanxi Prov, Peoples R China.
   [Mukhopadhyay, Partha] NIH, Lab Physiol Studies, Sect Oxidat Stress Tissue Injury, Rockville, MD USA.
   [Nalini, Namasivayam] Annamalai Univ, Dept Biochem & Biotechnol, Annamalainagar 608002, Tamil Nadu, India.
   [Pezzuto, John M.] Univ Hawaii, Coll Pharm, Hilo, HI 96720 USA.
   [Richard, Tristan] Univ Bordeaux, UFR Pharmacie, Villenave Dornon, France.
   [Shukla, Yogeshwer] Indian Inst Toxicol Res, Prote Lab, Lucknow, Uttar Pradesh, India.
   [Surh, Young-Joon] Seoul Natl Univ, Coll Pharm, Seoul, South Korea.
   [Szekeres, Thomas] Med Univ Vienna, Gen Hosp Vienna, Clin Inst Med & Chem Lab Diagnost, Vienna, Austria.
   [Szkudelski, Tomasz] Agr Univ Poznan, Dept Anim Physiol & Biochem, Poznan, Poland.
   [Walle, Thomas] Med Univ S Carolina, Dept Cell & Mol Pharmacol & Expt Therapeut, Charleston, SC 29425 USA.
   [Wu, Joseph M.] New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA.
RP Vang, O (reprint author), Roskilde Univ, Dept Sci Syst & Models, Roskilde, Denmark.
EM ov@ruc.dk
RI Baur, Joseph/D-8163-2011; Shukla, Yogeshwer/B-4144-2012; MUKHOPADHYAY,
   PARTHA/G-3890-2010; 
OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Baur,
   Joseph/0000-0001-8262-6549; Vang, Ole/0000-0002-3901-8545; Richard,
   Tristan/0000-0002-5308-8697
FU European Union
FX This study was made as a part of the Resveratrol 2010 conference
   (www.resveratrol2010.com) and did not receive any specific funding from
   third parties. The conference was organized by Roskilde University,
   Danish Society for Biochemistry and Molecular Biology, The Danish
   Society of Engineers, Oresund Food with support from The European Union.
   The funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 144
TC 191
Z9 196
U1 5
U2 93
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 16
PY 2011
VL 6
IS 6
AR e19881
DI 10.1371/journal.pone.0019881
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 778UW
UT WOS:000291734100003
PM 21698226
ER

PT J
AU Ferre-D'Amare, AR
AF Ferre-D'Amare, Adrian R.
TI PROTEIN SYNTHESIS Stop the nonsense
SO NATURE
LA English
DT Editorial Material
ID PSEUDOURIDINE; TERMINATION; RIBOSOME; RNA
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
RP Ferre-D'Amare, AR (reprint author), NHLBI, NIH, Bethesda, MD 20892 USA.
EM ferrea@mail.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 8
TC 1
Z9 1
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 289
EP 290
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100028
PM 21677740
ER

PT J
AU Batista, LFZ
   Pech, M
   Zhong, FL
   Nguyen, HN
   Xie, KT
   Zaug, AJ
   Crary, SM
   Choi, J
   Sebastiano, V
   Cherry, A
   Giri, N
   Wernig, M
   Alter, BP
   Cech, TR
   Savage, SA
   Pera, RAR
   Artandi, SE
AF Batista, Luis F. Z.
   Pech, MatthewF.
   Zhong, Franklin L.
   Nguyen, Ha Nam
   Xie, Kathleen T.
   Zaug, Arthur J.
   Crary, Sharon M.
   Choi, Jinkuk
   Sebastiano, Vittorio
   Cherry, Athena
   Giri, Neelam
   Wernig, Marius
   Alter, Blanche P.
   Cech, Thomas R.
   Savage, Sharon A.
   Pera, Renee A. Reijo
   Artandi, Steven E.
TI Telomere shortening and loss of self-renewal in dyskeratosis congenita
   induced pluripotent stem cells
SO NATURE
LA English
DT Article
ID REVERSE-TRANSCRIPTASE; MOUSE; RNA; LOCALIZATION; ANTICIPATION;
   ELONGATION; GENERATION; MUTATIONS; LENGTH; LEADS
AB The differentiation of patient-derived induced pluripotent stem cells (iPSCs) to committed fates such as neurons, muscle and liver is a powerful approach for understanding key parameters of human development and disease(1-6). Whether undifferentiated iPSCs themselves can be used to probe disease mechanisms is uncertain. Dyskeratosis congenita is characterized by defective maintenance of blood, pulmonary tissue and epidermal tissues and is caused by mutations in genes controlling telomere homeostasis(7,8). Short telomeres, a hallmark of dyskeratosis congenita, impair tissue stem cell function in mouse models, indicating that a tissue stem cell defect may underlie the pathophysiology of dyskeratosis congenita(9,10). Here we show that even in the undifferentiated state, iPSCs from dyskeratosis congenita patients harbour the precise biochemical defects characteristic of each form of the disease and that the magnitude of the telomere maintenance defect in iPSCs correlates with clinical severity. In iPSCs from patients with heterozygous mutations in TERT, the telomerase reverse transcriptase, a 50% reduction in telomerase levels blunts the natural telomere elongation that accompanies reprogramming. In contrast, mutation of dyskerin (DKC1) in X-linked dyskeratosis congenita severely impairs telomerase activity by blocking telomerase assembly and disrupts telomere elongation during reprogramming. In iPSCs from a form of dyskeratosis congenita caused by mutations in TCAB1 (also known as WRAP53), telomerase catalytic activity is unperturbed, yet the ability of telomerase to lengthen telomeres is abrogated, because telomerase mislocalizes from Cajal bodies to nucleoli within the iPSCs. Extended culture of DKC1-mutant iPSCs leads to progressive telomere shortening and eventual loss of self-renewal, indicating that a similar process occurs in tissue stem cells in dyskeratosis congenita patients. These findings in iPSCs from dyskeratosis congenita patients reveal that undifferentiated iPSCs accurately recapitulate features of a human stem cell disease and may serve as a cell-culture-based system for the development of targeted therapeutics.
C1 [Batista, Luis F. Z.; Pech, MatthewF.; Zhong, Franklin L.; Choi, Jinkuk; Artandi, Steven E.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
   [Pech, MatthewF.; Zhong, Franklin L.; Choi, Jinkuk; Pera, Renee A. Reijo; Artandi, Steven E.] Stanford Univ, Sch Med, Canc Biol Program, Stanford, CA 94305 USA.
   [Nguyen, Ha Nam; Sebastiano, Vittorio; Wernig, Marius; Pera, Renee A. Reijo] Stanford Univ, Sch Med, Dept Obstet & Gynecol, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA.
   [Xie, Kathleen T.] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
   [Zaug, Arthur J.; Crary, Sharon M.; Cech, Thomas R.] Univ Colorado, Howard Hughes Med Inst, Dept Chem & Biochem, Boulder, CO 80309 USA.
   [Sebastiano, Vittorio; Cherry, Athena; Wernig, Marius] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
   [Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20852 USA.
   [Artandi, Steven E.] Stanford Univ, Sch Med, Glenn Labs Biol Aging, Stanford, CA 94305 USA.
RP Artandi, SE (reprint author), Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
EM sartandi@stanford.edu
RI Savage, Sharon/B-9747-2015; 
OI Savage, Sharon/0000-0001-6006-0740; Batista, Luis/0000-0002-7538-3240;
   Reijo Pera, Renee/0000-0002-6487-1329
FU CCR NIH HHS [RC1 HL100361-01]; Howard Hughes Medical Institute;
   Intramural NIH HHS; NCI NIH HHS [R01 CA111691, R01 CA111691-05, R01
   CA125453, R01 CA125453-05, T32 CA009302]; NHLBI NIH HHS [RC1
   HL100361-01, RC1 HL100361, U01 HL100397]; NIA NIH HHS [R01 AG033747, R01
   AG033747-02]
NR 37
TC 113
Z9 115
U1 1
U2 28
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUN 16
PY 2011
VL 474
IS 7351
BP 399
EP +
DI 10.1038/nature10084
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777TD
UT WOS:000291647100050
PM 21602826
ER

PT J
AU Xiong, W
   Koo, BN
   Morton, R
   Zhang, L
AF Xiong, W.
   Koo, B. -N.
   Morton, R.
   Zhang, L.
TI PSYCHOTROPIC AND NONPSYCHOTROPIC CANNABIS DERIVATIVES INHIBIT HUMAN
   5-HT3A RECEPTORS THROUGH A RECEPTOR DESENSITIZATION-DEPENDENT MECHANISM
SO NEUROSCIENCE
LA English
DT Article
DE cannabis; CBD; THC; 5-HT3A; desensitization; ligand-gated ion channel
ID NEUROBLASTOMA-CELLS; SEROTONIN RECEPTOR; PROTEIN; MODULATION; CHANNEL;
   CNS; ACTIVATION; KINETICS; DENSITY; NEURONS
AB Delta(9) tetrahydrocannabinol (THC) and cannabidiol (CBD) are the principal psychoactive and nonpsychoactive components of cannabis. While most THC-induced behavioral effects are thought to depend on endogenous cannabinoid 1 (CBI) receptors, the molecular targets for CBD remain unclear. Here, we report that CBD and THC inhibited the function of human 5-HT3A receptors (h5-HT(3A)Rs) expressed in HEK 293 cells. The magnitude of THC and CBD inhibition was maximal 5 min after a continuous incubation with cannabinoids. The EC50 values for CBD and THC-induced inhibition were 110 nM and 322 nM, respectively in HEK 293 cells expressing h5-HT(3A)Rs. In these cells, CBD and THC did not stimulate specific [S-35]-GTP-gamma s binding in membranes, suggesting that the inhibition by cannabinoids is unlikely mediated by a G-protein dependent mechanism. On the other hand, both CBD and THC accelerated receptor desensitization kinetics without significantly changing activation time. The extent of cannabinoid inhibition appeared to depend on receptor desensitization. Reducing receptor desensitization by nocodazole, 5-hydroxyindole and a point-mutation in the large cytoplasmic domain of the receptor significantly decreased CBD-induced inhibition. Similarly, the magnitude of THC and CBD-induced inhibition varied with the apparent desensitization rate of h5-HT(3A)Rs expressed in Xenopus oocytes. For instance, with increasing amount of h5-HT3AR cRNA injected into the oocytes, the receptor desensitization rate at steady state decreased. THC and CBD-induced inhibition was correlated with the change in the receptor desensitization rate. Thus, CBD and THC inhibit h5-HT3A receptors through a mechanism that is dependent on receptor desensitization. Published by Elsevier Ltd on behalf of IBRO.
C1 [Xiong, W.; Koo, B. -N.; Morton, R.; Zhang, L.] NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
RP Xiong, W (reprint author), NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
EM xiongw@mail.nih.gov
RI Xiong, Wei/F-8251-2011
FU National Institute on Alcohol Abuse and Alcoholism
FX The authors thank Dr. David M. Lovinger for help with critical comments.
   This work was supported by funds from the intramural program of National
   Institute on Alcohol Abuse and Alcoholism.
NR 38
TC 5
Z9 6
U1 0
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 JUN 16
PY 2011
VL 184
BP 28
EP 37
DI 10.1016/j.neuroscience.2011.03.066
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 773SU
UT WOS:000291331500003
PM 21477640
ER

PT J
AU Vardeny, O
   Uno, H
   Braunwald, E
   Rouleau, JL
   Gersh, B
   Maggioni, AP
   Domanski, M
   Pfeffer, MA
   Solomon, SD
AF Vardeny, Orly
   Uno, Hajime
   Braunwald, Eugene
   Rouleau, Jean Lucien
   Gersh, Bernard
   Maggioni, Aldo P.
   Domanski, Michael
   Pfeffer, Marc A.
   Solomon, Scott D.
CA Prevention Events ACE Inhibitor PE
TI Opposing Effects of beta Blockers and Angiotensin-Converting Enzyme
   Inhibitors on Development of New-Onset Diabetes Mellitus in Patients
   With Stable Coronary Artery Disease
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; INSULIN SENSITIVITY; ANTIHYPERTENSIVE
   TREATMENT; CARDIOVASCULAR MORBIDITY; HEART-FAILURE; HYPERTENSION;
   GLUCOSE; CARVEDILOL; PREVENTION; METOPROLOL
AB We used data from patients with stable coronary artery disease (CAD) to assess the risk of new-onset diabetes mellitus (NOD) with beta blockers and to determine whether angiotensin-converting enzyme (ACE) inhibition would modify this risk. The Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) trial randomized 8,290 patients with stable CAD to trandolapril or placebo. Presence of NOD was assessed at each study visit over a median follow-up time of 4.8 years. We examined the risk of NOD associated with beta-blocker use with Cox regression models adjusting for 25 baseline covariates and tested whether this risk was modified by randomization to the ACE inhibitor. Of 6,910 patients without diabetes mellitus at enrollment (1,179 women and 5,731 men, mean age 64 +/- 8 years), 4,147 (60%) were taking beta blockers and 733 (8.8%) developed NOD. We observed a significant interaction between beta-blocker use and randomization to ACE inhibitor with respect to NOD (p = 0.028). Participants taking beta blockers assigned to the placebo group (n = 2,090) were at increased risk for NOD adjusting for baseline covariates (hazard ratio 1.63, 95% confidence interval 1.29 to 2.05, p <0.001), and this risk was attenuated in those assigned to trandolapril (n = 2,057, hazard ratio 1.11, 95% confidence interval 0.87 to 1.42, p = 0.39). beta blocker use was associated with increased risk for NOD in patients with stable CAD, and this risk was decreased in patients treated concurrently with an ACE inhibitor. In conclusion, these data suggest that ACE inhibition may attenuate the risk for glucose abnormalities observed in patients taking beta blockers. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1705-1709)
C1 [Vardeny, Orly] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA.
   [Uno, Hajime; Braunwald, Eugene; Pfeffer, Marc A.; Solomon, Scott D.] Brigham & Womens Hosp, Boston, MA 02115 USA.
   [Rouleau, Jean Lucien] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.
   [Gersh, Bernard] Mayo Clin, Coll Med, Rochester, MN USA.
   [Maggioni, Aldo P.] ANMCO, Florence, Italy.
   [Domanski, Michael] NHLBI, Bethesda, MD 20892 USA.
RP Vardeny, O (reprint author), Univ Wisconsin, Sch Pharm, 425 N Charter St, Madison, WI 53706 USA.
EM ovardeny@pharmacy.wisc.edu
RI Solomon, Scott/I-5789-2013
FU National Institutes of Health/National Center for Research Resources,
   Bethesda, Maryland [1KL2RR025012]; National Heart, Lung, and Blood
   Institute, Bethesda, Maryland
FX Dr. Vardeny was supported by Grant 1KL2RR025012 from the National
   Institutes of Health/National Center for Research Resources, Bethesda,
   Maryland. The PEACE trial was funded by the National Heart, Lung, and
   Blood Institute, Bethesda, Maryland.
NR 30
TC 11
Z9 12
U1 1
U2 8
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUN 15
PY 2011
VL 107
IS 12
BP 1705
EP 1709
DI 10.1016/j.amjcard.2011.01.064
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 779CE
UT WOS:000291754900001
PM 21507365
ER

PT J
AU Urick, ME
   Rudd, ML
   Godwin, AK
   Sgroi, D
   Merino, M
   Bell, DW
AF Urick, Mary E.
   Rudd, Meghan L.
   Godwin, Andrew K.
   Sgroi, Dennis
   Merino, Maria
   Bell, Daphne W.
TI PIK3R1 (p85 alpha) Is Somatically Mutated at High Frequency in Primary
   Endometrial Cancer
SO CANCER RESEARCH
LA English
DT Article
ID MUTATIONS; GENES; CARCINOMA; SUBUNIT
AB Phosphoinositide 3-kinase (PI3K) is an important therapeutic target. Mutations in PIK3CA, which encodes p110 alpha, the catalytic subunit of PI3K, occur in endometrioid endometrial cancers (EEC) and nonendometrioid endometrial cancers (NEEC). The goal of this study was to determine whether PIK3R1, which encodes p85 alpha, the inhibitory subunit of PI3K, is mutated in endometrial carcinoma. We carried out exonic sequencing of PIK3R1 from 42 EECs and 66 NEECs. The pattern of PIK3R1 mutations was compared with the patterns of PIK3CA, PTEN, and KRAS mutations. The biochemical effect of seven PIK3R1 mutations was examined by stable expression in U2OS cells, followed by coimmunoprecipitation analysis of p110 alpha, and Western blotting of phospho-AKT(Ser473) (p-AKT(Ser473)). We found that PIK3R1 was somatically mutated in 43% of EECs and 12% of NEECs. The majority of mutations (93.3%) were localized to the p85 alpha-nSH2 and -iSH2 domains. Several mutations were recurrent. PIK3R1 mutations were significantly (P = 0.0015) more frequent in PIK3CA-wild type EECs (70%) than in PIK3CA mutant EECs (18%). Introduction of wild-type p85 alpha into U2OS cells reduced the level of p-AKT(Ser473) compared with the vector control. Five p85 alpha mutants, p85 alpha delH450-E451, p85 alpha delK459, p85 alpha delY463-L466, p85 alpha delR574-T576, and the p85 alpha N564D positive control, were shown to bind p110 alpha and led to increased levels of p-AKT(Ser473). The p85 alpha R348X and p85 alpha K511VfsX2 mutants did not bind p110 alpha and showed no appreciable change in p-AKT(Ser473) levels. In conclusion, our study has revealed a new mode of PI3K alteration in primary endometrial tumors and warrants future studies to determine whether PIK3R1 mutations correlate with clinical outcome to targeted therapies directed against the PI3K pathway in EEC and NEEC. Cancer Res; 71(12); 4061-7. (C)2011 AACR.
C1 [Urick, Mary E.; Rudd, Meghan L.; Bell, Daphne W.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Merino, Maria] NCI, NIH, Bethesda, MD 20892 USA.
   [Godwin, Andrew K.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
   [Sgroi, Dennis] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA.
RP Bell, DW (reprint author), NHGRI, Canc Genet Branch, NIH, Bldg 50,Room 5339,50 South Dr, Bethesda, MD 20892 USA.
EM belldaph@mail.nih.gov
FU NIH/National Human Genome Research Institute; NIH [R01 CA140323, U01
   CA113916, RO1-1CA112021-01]; Ovarian Cancer Research Fund; NCI SPORE in
   breast cancer at Massachusetts General Hospital; Avon Foundation
FX This study was funded by the Intramural Program of the NIH/National
   Human Genome Research Institute (D.W. Bell) and in part by NIH grants
   R01 CA140323 (A.K. Godwin), U01 CA113916 (A.K. Godwin), NIH
   RO1-1CA112021-01 (D.C. Sgroi), the Ovarian Cancer Research Fund (A.K.
   Godwin), the NCI SPORE in breast cancer at Massachusetts General
   Hospital (D.C. Sgroi), and the Avon Foundation (D.C. Sgroi).
NR 21
TC 78
Z9 81
U1 2
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUN 15
PY 2011
VL 71
IS 12
BP 4061
EP 4067
DI 10.1158/0008-5472.CAN-11-0549
PG 7
WC Oncology
SC Oncology
GA 777PZ
UT WOS:000291637100002
PM 21478295
ER

PT J
AU Jiang, Q
   Weiss, JM
   Back, T
   Chan, T
   Ortaldo, JR
   Guichard, S
   Wiltrout, RH
AF Jiang, Qun
   Weiss, Jonathan M.
   Back, Timothy
   Chan, Tim
   Ortaldo, John R.
   Guichard, Sylvie
   Wiltrout, Robert H.
TI mTOR Kinase Inhibitor AZD8055 Enhances the Immunotherapeutic Activity of
   an Agonist CD40 Antibody in Cancer Treatment
SO CANCER RESEARCH
LA English
DT Article
ID RENAL-CELL CARCINOMA; CD8(+) T-CELLS; MAMMALIAN TARGET; IN-VIVO;
   MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; DENDRITIC CELLS;
   NATURAL-KILLER; NK CELLS; RAPAMYCIN
AB mTOR is a central mediator of cancer cell growth, but it also directs immune cell differentiation and function. On this basis, we had explored the hypothesis that mTOR inhibition can enhance cancer immunotherapy. Here, we report that a combination of alpha CD40 agonistic antibody and the ATP-competitive mTOR kinase inhibitory drug AZD8055 elicited synergistic antitumor responses in a model of metastatic renal cell carcinoma. In contrast to the well-established mTOR inhibitor rapamycin, AZD8055 increased the infiltration, activation, and proliferation of CD8(+)T cells and natural killer cells in liver metastatic foci when combined with the CD40 agonist. AZD8055/alpha CD40-treated mice also display an increased incidence of matured macrophages and dendritic cells compared with that achieved in mice by alpha CD40 or AZD8055 treatment alone. We found that the combination treatment also increased macrophage production of TNF alpha, which played an indispensable role in activation of the observed antitumor immune response. Levels of Th1 cytokines, including interleukin 12, IFN-gamma, TNF alpha, and the Th1-associated chemokines RANTES, MIG, and IP-10 were each elevated significantly in the livers of mice treated with the combinatorial therapy versus individual treatments. Notably, the AZD8055/alpha CD40-induced antitumor response was abolished in IFN-gamma(-/-) and CD40(-/-) mice, establishing the reliance of the combination therapy on host IFN-gamma and CD40 expression. Our findings offer a preclinical proof of concept that, unlike rapamycin, the ATP-competitive mTOR kinase inhibitor AZD8055 can contribute with alpha CD40 treatment to trigger a restructuring of the tumor immune microenvironment to trigger regressions of an established metastatic cancer. Cancer Res; 71(12); 4074-84. (C)2011 AACR.
C1 [Wiltrout, Robert H.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,FCRDC, Frederick, MD 21702 USA.
   [Guichard, Sylvie] AstraZeneca, Macclesfield, Cheshire, England.
RP Wiltrout, RH (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res,FCRDC, Frederick, MD 21702 USA.
EM wiltrour@mail.nih.gov
RI Jiang, Qun/A-1358-2014
FU NIH/NCI
FX This project was funded in whole or part by the Intramural Research
   Program of NIH/NCI.
NR 49
TC 32
Z9 34
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUN 15
PY 2011
VL 71
IS 12
BP 4074
EP 4084
DI 10.1158/0008-5472.CAN-10-3968
PG 11
WC Oncology
SC Oncology
GA 777PZ
UT WOS:000291637100004
PM 21540234
ER

PT J
AU Langer, HF
   Orlova, VV
   Xie, CP
   Kaul, S
   Schneider, D
   Lonsdorf, AS
   Fahrleitner, M
   Choi, EY
   Dutoit, V
   Pellegrini, M
   Grossklaus, S
   Nawroth, PP
   Baretton, G
   Santoso, S
   Hwang, ST
   Arnold, B
   Chavakis, T
AF Langer, Harald F.
   Orlova, Valeria V.
   Xie, Changping
   Kaul, Sunil
   Schneider, Darius
   Lonsdorf, Anke S.
   Fahrleitner, Manuela
   Choi, Eun Young
   Dutoit, Vanessa
   Pellegrini, Manuela
   Grossklaus, Sylvia
   Nawroth, Peter P.
   Baretton, Gustavo
   Santoso, Sentot
   Hwang, Sam T.
   Arnold, Bernd
   Chavakis, Triantafyllos
TI A Novel Function of Junctional Adhesion Molecule-C in Mediating Melanoma
   Cell Metastasis
SO CANCER RESEARCH
LA English
DT Article
ID VASCULAR ENDOTHELIAL PERMEABILITY; JAM-C; IN-VITRO; TRANSENDOTHELIAL
   MIGRATION; CRE-RECOMBINASE; CANCER-CELLS; INTEGRIN; EXPRESSION;
   DELETION; VIVO
AB Hematogenous dissemination of melanoma is a life-threatening complication of this malignant tumor. Here, we identified junctional adhesion molecule-C (JAM-C) as a novel player in melanoma metastasis to the lung. JAM-C expression was identified in human and murine melanoma cell lines, in human malignant melanoma, as well as in metastatic melanoma including melanoma lung metastasis. JAM-C expressed on both murine B16 melanoma cells as well as on endothelial cells promoted the transendothelial migration of the melanoma cells. We generated mice with inactivation of JAM-C. JAM-C(-/-) mice as well as endothelial-specific JAM-C-deficient mice displayed significantly decreased B16 melanoma cell metastasis to the lung, whereas treatment of mice with soluble JAM-C prevented melanoma lung metastasis. Together, JAM-C represents a novel therapeutic target for melanoma metastasis. Cancer Res; 71(12); 4096-105. (C)2011 AACR.
C1 [Langer, Harald F.; Orlova, Valeria V.; Kaul, Sunil; Choi, Eun Young; Chavakis, Triantafyllos] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
   [Lonsdorf, Anke S.; Hwang, Sam T.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
   [Langer, Harald F.; Fahrleitner, Manuela] Univ Tubingen, Med Klin 3, Tubingen, Germany.
   [Orlova, Valeria V.] Leiden Univ, Med Ctr, Leiden, Netherlands.
   [Xie, Changping; Schneider, Darius; Dutoit, Vanessa; Nawroth, Peter P.; Chavakis, Triantafyllos] Univ Heidelberg, Dept Med 1, D-6900 Heidelberg, Germany.
   [Lonsdorf, Anke S.] Univ Heidelberg, Dept Dermatol, D-6900 Heidelberg, Germany.
   [Arnold, Bernd] German Canc Res Ctr, D-6900 Heidelberg, Germany.
   [Pellegrini, Manuela] Univ Roma Tor Vergata, Dept Publ Hlth & Cellular Biol, Rome, Italy.
   [Grossklaus, Sylvia; Chavakis, Triantafyllos] Univ Dresden, Dept Med, Div Vasc Inflammat Diabet & Kidney, Dresden, Germany.
   [Grossklaus, Sylvia; Chavakis, Triantafyllos] Univ Dresden, Inst Physiol, Dresden, Germany.
   [Baretton, Gustavo] Univ Dresden, Inst Pathol, Dresden, Germany.
   [Santoso, Sentot] Univ Giessen, Inst Clin Immunol & Transfus Med, D-6300 Giessen, Germany.
   [Hwang, Sam T.] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA.
RP Chavakis, T (reprint author), Univ Clin Dresden, Fetscherstr 74, D-01307 Dresden, Germany.
EM triantafyllos.chavakis@uniklinikum-dresden.de
RI Orlova, Valeria/C-6065-2014
OI Orlova, Valeria/0000-0002-1169-2802
FU NIH, National Cancer Institute; Deutsche Forschungsgemeinschaft; Center
   for Interdisciplinary Clinical Research, University of Tubingen; German
   Academy of Sciences Leopoldina; NIH/DFG
FX The work was supported by the NIH Intramural Research Program, National
   Cancer Institute (T. Chavakis) and the Deutsche Forschungsgemeinschaft
   (T. Chavakis, B. Arnold, and P.P. Nawroth). H.F. Langer was supported by
   the Center for Interdisciplinary Clinical Research, University of
   Tubingen and the German Academy of Sciences Leopoldina. A.S. Lonsdorf
   was supported by an NIH/DFG Research Career Transition Award of the NIH
   and the Deutsche Forschungsgemeinschaft.
NR 39
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U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUN 15
PY 2011
VL 71
IS 12
BP 4096
EP 4105
DI 10.1158/0008-5472.CAN-10-2794
PG 10
WC Oncology
SC Oncology
GA 777PZ
UT WOS:000291637100006
PM 21593193
ER

PT J
AU Rao, M
   Chinnasamy, N
   Hong, JA
   Zhang, YW
   Zhang, M
   Xi, SC
   Liu, F
   Marquez, VE
   Morgan, RA
   Schrump, DS
AF Rao, Mahadev
   Chinnasamy, Nachimuthu
   Hong, Julie A.
   Zhang, Yuwei
   Zhang, Mary
   Xi, Sichuan
   Liu, Fang
   Marquez, Victor E.
   Morgan, Richard A.
   Schrump, David S.
TI Inhibition of Histone Lysine Methylation Enhances Cancer-Testis Antigen
   Expression in Lung Cancer Cells: Implications for Adoptive Immunotherapy
   of Cancer
SO CANCER RESEARCH
LA English
DT Article
ID CANCER/TESTIS ANTIGEN; DNA METHYLATION; GENE-EXPRESSION; X-CHROMOSOME;
   TUMOR-CELLS; GERM-LINE; NY-ESO-1; DEMETHYLATION; LYMPHOCYTES; REPRESSION
AB Cancer-testis antigens (CTA), such as NY-ESO-1, MAGE-A1, and MAGE-A3, are immunogenic proteins encoded by genes, which are normally expressed only in male germ cells but are activated by ill-defined epigenetic mechanisms in human tumors, including lung cancers. Previously, we reported induction of these CTAs in cancer cells, but not normal cells, by DNA-demethylating agents and histone deacetylase inhibitors using clinically achievable exposure conditions. In the present study, we evaluated chromatin alterations associated with repression/activation of cancer-testis genes in lung cancer cells to further develop gene-induction regimens for cancer immunotherapy. Repression of NY-ESO-1, MAGE-A1, and MAGE-A3 coincided with DNA hypermethylation, recruitment, and binding of polycomb-group proteins, and histone heterochromatin modifications within the promoters of these genes. Derepression coincided with DNA demethylation, dissociation of polycomb proteins, and presence of euchromatin marks within the respective promoters. Short hairpin RNAs were used to inhibit several histone methyltransferases (KMT) and histone demethylases (KDM) that mediate histone methylation and repress gene expression. Knockdown of KMT6, KDM1, or KDM5B markedly enhanced deoxyazacytidine (DAC)-mediated activation of these cancer-testis genes in lung cancer cells. DZNep, a pharmacologic inhibitor of KMT6 expression, recapitulated the effects of KMT6 knockdown. Following DAC-DZNep exposure, lung cancer cells were specifically recognized and lysed by allogeneic lymphocytes expressing recombinant T-cell receptors recognizing NY-ESO-1 and MAGE-A3. Combining DNA-demethylating agents with compounds, such as DZNep, that modulate histone lysine methylation may provide a novel epigenetic strategy to augment cancer-testis gene expression as an adjunct to adoptive cancer immunotherapy. Cancer Res; 71(12); 4192-204. (C)2011 AACR.
C1 [Rao, Mahadev; Hong, Julie A.; Zhang, Yuwei; Zhang, Mary; Xi, Sichuan; Liu, Fang; Schrump, David S.] NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Chinnasamy, Nachimuthu; Morgan, Richard A.] NCI, Sect Tumor Immunol, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Marquez, Victor E.] NCI, Biol Chem Lab, Bethesda, MD 20892 USA.
RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res, 10 Ctr Dr,Rm 4-3942 MSC 1201, Bethesda, MD 20892 USA.
EM david_schrump@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 45
TC 42
Z9 44
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUN 15
PY 2011
VL 71
IS 12
BP 4192
EP 4204
DI 10.1158/0008-5472.CAN-10-2442
PG 13
WC Oncology
SC Oncology
GA 777PZ
UT WOS:000291637100015
PM 21546573
ER

PT J
AU Hoenerhoff, M
   Chu, IM
   Green, JE
AF Hoenerhoff, Mark
   Chu, Isabel M.
   Green, Jeffrey E.
TI BMI1 suffers a degrading experience
SO CELL CYCLE
LA English
DT News Item
ID SENESCENCE; ONCOGENE; CANCER; CELLS
C1 [Hoenerhoff, Mark] NIEHS, Res Triangle Pk, NC 27709 USA.
   [Chu, Isabel M.; Green, Jeffrey E.] NCI, Bethesda, MD 20892 USA.
RP Hoenerhoff, M (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA.
EM jegreen@nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JUN 15
PY 2011
VL 10
IS 12
BP 1894
EP 1895
DI 10.4161/cc.10.12.15746
PG 2
WC Cell Biology
SC Cell Biology
GA 777UT
UT WOS:000291651300010
PM 21593587
ER

PT J
AU Bates, SE
AF Bates, Susan E.
TI Prostate Cancer: Score One for Validated Targets
SO CLINICAL CANCER RESEARCH
LA English
DT Article
C1 Natl Canc Inst, CCR Focus, Bethesda, MD USA.
RP Bates, SE (reprint author), Natl Canc Inst, CCR Focus, Bethesda, MD USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 15
PY 2011
VL 17
IS 12
BP 3866
EP 3866
DI 10.1158/1078-0432.CCR-11-1175
PG 1
WC Oncology
SC Oncology
GA 777SG
UT WOS:000291644700003
PM 21680541
ER

PT J
AU Gulley, JL
   Drake, CG
AF Gulley, James L.
   Drake, Charles G.
TI Immunotherapy for Prostate Cancer: Recent Advances, Lessons Learned, and
   Areas for Further Research
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID INHIBITOR ABIRATERONE ACETATE; SIPULEUCEL-T; TUMOR-IMMUNOTHERAPY;
   ANTITUMOR-ACTIVITY; CELL INFILTRATION; CLINICAL ACTIVITY;
   IMMUNE-RESPONSE; CONCOMITANT USE; PHASE-II; VACCINE
AB A surge of interest in therapeutic cancer vaccines has arisen in the wake of recent clinical trials suggesting that such vaccines can result in statistically significant and clinically meaningful improvements in overall survival-with substantially limited side effects compared with chemotherapy-in patients with metastatic castration-resistant prostate cancer. One of these trials led to the registration of sipuleucel-T, the first therapeutic vaccine to be approved for cancer patients. In this review we highlight emerging patterns from clinical trials that suggest a need for more-appropriate patient populations (i.e., with lower tumor volume and less-aggressive disease) and endpoints (i.e., overall survival) for studies of immunotherapy alone, as well as biologically plausible explanations for these findings. We also explore the rationale for ongoing and planned studies combining therapeutic vaccines with other modalities. Finally, we attempt to put these findings into a practical clinical context and suggest fertile areas for future study. Although our discussion focuses on prostate cancer, the concepts we address most likely have broad applicability to immunotherapy for other cancers as well. Clin Cancer Res; 17(12); 3884-91. (C) 2011 AACR.
C1 [Gulley, James L.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Drake, Charles G.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA.
   [Drake, Charles G.] Johns Hopkins Univ, Dept Urol, Baltimore, MD USA.
   [Drake, Charles G.] Johns Hopkins Univ, Dept Immunol, Baltimore, MD USA.
RP Gulley, JL (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,8B09 MSC 1750, Bethesda, MD 20892 USA.
EM gulleyj@mail.nih.gov; cdrake@jhmi.edu
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU Center for Cancer Research, National Cancer Institute, National
   Institutes of Health; National Institutes of Health [R01 CA127153,
   1P50CA58236-15]; Patrick C. Walsh Fund; OneInSix Foundation; Prostate
   Cancer Foundation
FX Intramural Research Program of the Center for Cancer Research, National
   Cancer Institute, National Institutes of Health (J.L. Gulley); and
   National Institutes of Health (R01 CA127153 and 1P50CA58236-15), Patrick
   C. Walsh Fund, OneInSix Foundation, and Prostate Cancer Foundation (C.G.
   Drake). C. G. Drake is a Damon Runyon-Lilly Clinical Investigator.
NR 54
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U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 15
PY 2011
VL 17
IS 12
BP 3884
EP 3891
DI 10.1158/1078-0432.CCR-10-2656
PG 8
WC Oncology
SC Oncology
GA 777SG
UT WOS:000291644700006
PM 21680544
ER

PT J
AU Madan, RA
   Pal, SK
   Sartor, O
   Dahut, WL
AF Madan, Ravi A.
   Pal, Sumanta Kumar
   Sartor, Oliver
   Dahut, William L.
TI Overcoming Chemotherapy Resistance in Prostate Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; PAINFUL BONE METASTASES; RANDOMIZED PHASE-II;
   INTERMITTENT CHEMOTHERAPY; ANDROGEN RECEPTOR; MICROTUBULE DYNAMICS;
   INCREASED EXPRESSION; ABIRATERONE ACETATE; CLINICAL-TRIALS;
   P-GLYCOPROTEIN
AB Although treatment for prostate cancer has improved over the past several years, taxanes remain the only form of chemotherapy that improves survival in patients with metastatic castration-resistant prostate cancer (mCRPC). In addition to the promising therapeutic cancer vaccines and newly developed agents targeting androgen receptor signaling, chemotherapy-based treatments will likely continue to play a significant role in patients with mCRPC. Recently published data that showed that a second taxane (cabazitaxel) extends survival after progression on docetaxel was a significant step forward, but also highlighted the need to overcome taxane resistance in prostate cancer. Preliminary evidence suggests that several treatment strategies may improve the activity of taxanes in prostate cancer and perhaps enhance clinical outcomes. Clin Cancer Res; 17(12); 3892-902. (C) 2011 AACR.
C1 [Madan, Ravi A.] NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA.
   [Dahut, William L.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
   [Pal, Sumanta Kumar] City Hope Comprehens Canc Ctr, Dept Med Oncol & Expt Therapeut, Div Genitourinary Malignancies, Los Angeles, CA USA.
   [Sartor, Oliver] Tulane Univ, Sch Med, Dept Urol, New Orleans, LA 70112 USA.
   [Sartor, Oliver] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
RP Dahut, WL (reprint author), Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dahutw@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX The authors acknowledge the Intramural Research Program of the NIH,
   National Cancer Institute, Center for Cancer Research for their support
   of this study.; S. K. Pal, commercial research grant, GlaxoSmithKline,
   honoraria, GlaxoSmithKline, Sanofi-Aventis, Novartis, Pfizer,
   consultant, Genentech, Novartis, Allos Therapeutics; O. Sartor,
   commercial research grant, SanofiAventis, Algeta, Astra-Zeneca,
   commercial research support, Cougar, Johnson & Johnson, GlaxoSmithKline,
   honoraria, EUSA, consultant, SanofiAventis, GlaxoSmithKline,
   AstraZeneca, Algeta, Johnson and Johnson, Dendreon, Celgene, Medivation,
   Bristol-Myers Squibb, Amgen, Oncogenex, GPC-Biotech. The other authors
   declared no potential conflicts of interest.
NR 77
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U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 15
PY 2011
VL 17
IS 12
BP 3892
EP 3902
DI 10.1158/1078-0432.CCR-10-2654
PG 11
WC Oncology
SC Oncology
GA 777SG
UT WOS:000291644700007
PM 21680545
ER

PT J
AU Rosta, E
   Nowotny, M
   Yang, W
   Hummer, G
AF Rosta, Edina
   Nowotny, Marcin
   Yang, Wei
   Hummer, Gerhard
TI Catalytic Mechanism of RNA Backbone Cleavage by Ribonuclease H from
   Quantum Mechanics/Molecular Mechanics Simulations
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID SITE-DIRECTED MUTAGENESIS; FREE-ENERGY CALCULATIONS; PROTON-TRANSFER;
   RNA/DNA HYBRID; DNA-POLYMERASE; ACTIVE-SITE; METAL-ION; REVERSE
   TRANSCRIPTION; PH-DEPENDENCE; SUBSTRATE
AB We use quantum mechanics/molecular mechanics simulations to study the cleavage of the ribonucleic acid (RNA) backbone catalyzed by ribonuclease H. This protein is a prototypical member of a large family of enzymes that use two-metal catalysis to process nucleic acids. By combining Hamiltonian replica exchange with a finite-temperature string method, we calculate the free energy surface underlying the RNA-cleavage reaction and characterize its mechanism. We find that the reaction proceeds in two steps. In a first step, catalyzed primarily by magnesium ion A and its ligands, a water molecule attacks the scissile phosphate. Consistent with thiol-substitution experiments, a water proton is transferred to the downstream phosphate group. The transient phosphorane formed as a result of this nucleophilic attack decays by breaking the bond between the phosphate and the ribose oxygen. In the resulting intermediate, the dissociated but unprotonated leaving group forms an alkoxide coordinated to magnesium ion B. In a second step, the reaction is completed by protonation of the leaving group, with a neutral Asp132 as a likely proton donor. The overall reaction barrier of similar to 15 kcal mol(-1), encountered in the first step, together with the cost of protonating Asp132, is consistent with the slow measured rate of similar to 1-100/min. The two-step mechanism is also consistent with the bell-shaped pH dependence of the reaction rate. The nonmonotonic relative motion of the magnesium ions along the reaction pathway agrees with X-ray crystal structures. Proton-transfer reactions and changes in the metal ion coordination emerge as central factors in the RNA-cleavage reaction.
C1 [Rosta, Edina; Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
   [Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Nowotny, Marcin] Int Inst Mol & Cell Biol, Lab Prot Struct, PL-02109 Warsaw, Poland.
RP Hummer, G (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM Hummer@helix.nih.gov
RI Yang, Wei/D-4926-2011; Hummer, Gerhard/A-2546-2013; 
OI Yang, Wei/0000-0002-3591-2195; Hummer, Gerhard/0000-0001-7768-746X;
   Rosta, Edina/0000-0002-9823-4766
FU National Institute of Diabetes and Digestive and Kidney Diseases,
   National Institutes of Health
FX We thank Drs. Bernard Brooks, Yihan Shao, and Lee Woodcock for their
   valuable help. 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 used the computational
   resources of the Biowulf cluster.
NR 46
TC 64
Z9 64
U1 6
U2 47
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JUN 15
PY 2011
VL 133
IS 23
BP 8934
EP 8941
DI 10.1021/ja200173a
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA 777ZX
UT WOS:000291667600037
PM 21539371
ER

PT J
AU Sueyoshi, T
   Green, WD
   Vinal, K
   Woodrum, TS
   Moore, R
   Negishi, M
AF Sueyoshi, Tatsuya
   Green, William D.
   Vinal, Kellie
   Woodrum, Tyler S.
   Moore, Rick
   Negishi, Masahiko
TI Garlic Extract Diallyl Sulfide (DAS) Activates Nuclear Receptor CAR to
   Induce the Sult1e1 Gene in Mouse Liver
SO PLOS ONE
LA English
DT Article
ID CONSTITUTIVE ANDROSTANE RECEPTOR; DRUG-METABOLIZING-ENZYMES; ESTROGEN
   SULFOTRANSFERASE; ORGANOSULFUR COMPOUNDS; ENHANCER MODULE; 1E1
   EXPRESSION; CYP2B6 GENE; CANCER; MICE; RISK
AB Constituent chemicals in garlic extract are known to induce phase I and phase II enzymes in rodent livers. Here we have utilized Car(+/+) and Car(-/-) mice to demonstrate that the nuclear xenobiotic receptor CAR regulated the induction of the estrogen sulfotransferase Sult1e1 gene by diallyl sulfide (DAS) treatment in mouse liver. DAS treatment caused CAR accumulation in the nucleus, resulting in a remarkable increase of SULT1E1 mRNA (3,200 fold) and protein in the livers of Car(+/+) females but not of Car(-/-) female mice. DAS also induced other CAR-regulated genes such as Cyp2b10, Cyp3a11 and Gadd45 beta. Compared with the rapid increase of these mRNA levels, which began as early as 6 hourrs after DAS treatment, the levels of SULT1E1 mRNA began increasing after 24 hours. This slow response to DAS suggested that CAR required an additional factor to activate the Sult1e1 gene or that this activation was indirect. Despite the remarkable induction of SULT1E1, there was no decrease in the serum levels of endogenous E2 or increase of estrone sulfate while the clearance of exogenously administrated E2 was accelerated in DAS treated mice.
C1 [Sueyoshi, Tatsuya; Green, William D.; Vinal, Kellie; Woodrum, Tyler S.; Moore, Rick; Negishi, Masahiko] Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA.
RP Sueyoshi, T (reprint author), Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA.
EM sueyoshi@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences (NIEHS)
   [Zo1Es71005-01]
FX This study was supported by the Intramural Research Program of the NIH,
   National Institute of Environmental Health Sciences (NIEHS),
   Zo1Es71005-01. The funders had no role in study design, data collection
   and analysis, decision to publish, or preparation of the manuscript.
NR 47
TC 11
Z9 12
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 15
PY 2011
VL 6
IS 6
AR e21229
DI 10.1371/journal.pone.0021229
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 778TS
UT WOS:000291730000064
PM 21698271
ER

PT J
AU Yang, JH
   Baskar, S
   Kwong, KY
   Kennedy, MG
   Wiestner, A
   Rader, C
AF Yang, Jiahui
   Baskar, Sivasubramanian
   Kwong, Ka Yin
   Kennedy, Michael G.
   Wiestner, Adrian
   Rader, Christoph
TI Therapeutic Potential and Challenges of Targeting Receptor Tyrosine
   Kinase ROR1 with Monoclonal Antibodies in B-Cell Malignancies
SO PLOS ONE
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CHIMERIC RABBIT/HUMAN FAB; PHAGE DISPLAY;
   MOUSE DEVELOPMENT; EXPRESSION; GENERATION; RITUXIMAB; FAMILY;
   INFECTIONS; PHENOTYPE
AB Background: Based on its selective cell surface expression in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), receptor tyrosine kinase ROR1 has recently emerged as a promising target for therapeutic monoclonal antibodies (mAbs). To further assess the suitability of ROR1 for targeted therapy of CLL and MCL, a panel of mAbs was generated and its therapeutic utility was investigated.
   Methodology and Principal Findings: A chimeric rabbit/human Fab library was generated from immunized rabbits and selected by phage display. Chimeric rabbit/human Fab and IgG1 were investigated for their capability to bind to human and mouse ROR1, to mediate antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and internalization, and to agonize or antagonize apoptosis using primary CLL cells from untreated patients as well as MCL cell lines. A panel of mAbs demonstrated high affinity and specificity for a diverse set of epitopes that involve all three extracellular domains of ROR1, are accessible on the cell surface, and mediate internalization. The mAb with the highest affinity and slowest rate of internalization was found to be the only mAb that mediated significant, albeit weak, ADCC. None of the mAbs mediated CDC. Alone, they did not enhance or inhibit apoptosis.
   Conclusions and Significance: Owing to its relatively low cell surface density, ROR1 may be a preferred target for armed rather than naked mAbs. Provided is a panel of fully sequenced and thoroughly characterized anti-ROR1 mAbs suitable for conversion to antibody-drug conjugates, immunotoxins, chimeric antigen receptors, and other armed mAb entities for preclinical and clinical studies.
C1 [Yang, Jiahui; Baskar, Sivasubramanian; Kwong, Ka Yin; Kennedy, Michael G.; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Yang, JH (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM raderc@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
   Institutes of Health
FX This research was funded by the Intramural Research Program of the
   Center for Cancer Research, National Cancer Institute, National
   Institutes of Health. The funder had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.
NR 47
TC 29
Z9 31
U1 1
U2 6
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 JUN 15
PY 2011
VL 6
IS 6
AR e21018
DI 10.1371/journal.pone.0021018
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 778TS
UT WOS:000291730000039
PM 21698301
ER

PT J
AU McKay, GJ
   Silvestri, G
   Chakravarthy, U
   Dasari, S
   Fritsche, LG
   Weber, BH
   Keilhauer, CN
   Klein, ML
   Francis, PJ
   Klaver, CC
   Vingerling, JR
   Ho, L
   De Jong, PTDV
   Dean, M
   Sawitzke, J
   Baird, PN
   Guymer, RH
   Stambolian, D
   Orlin, A
   Seddon, JM
   Peter, I
   Wright, AF
   Hayward, C
   Lotery, AJ
   Ennis, S
   Gorin, MB
   Weeks, DE
   Kuo, CL
   Hingorani, AD
   Sofat, R
   Cipriani, V
   Swaroop, A
   Othman, M
   Kanda, A
   Chen, W
   Abecasis, GR
   Yates, JR
   Webster, AR
   Moore, AT
   Seland, JH
   Rahu, M
   Soubrane, G
   Tomazzoli, L
   Topouzis, F
   Vioque, J
   Young, IS
   Fletcher, AE
   Patterson, CC
AF McKay, Gareth J.
   Silvestri, Giuliana
   Chakravarthy, Usha
   Dasari, Shilpa
   Fritsche, Lars G.
   Weber, Bernhard H.
   Keilhauer, Claudia N.
   Klein, Michael L.
   Francis, Peter J.
   Klaver, Caroline C.
   Vingerling, Johannes R.
   Ho, Lintje
   De Jong, Paulus T. D. V.
   Dean, Michael
   Sawitzke, Julie
   Baird, Paul N.
   Guymer, Robyn H.
   Stambolian, Dwight
   Orlin, Anton
   Seddon, Johanna M.
   Peter, Inga
   Wright, Alan F.
   Hayward, Caroline
   Lotery, Andrew J.
   Ennis, Sarah
   Gorin, Michael B.
   Weeks, Daniel E.
   Kuo, Chia-Ling
   Hingorani, Aroon D.
   Sofat, Reecha
   Cipriani, Valentina
   Swaroop, Anand
   Othman, Mohammad
   Kanda, Atsuhiro
   Chen, Wei
   Abecasis, Goncalo R.
   Yates, John R.
   Webster, Andrew R.
   Moore, Anthony T.
   Seland, Johan H.
   Rahu, Mati
   Soubrane, Gisele
   Tomazzoli, Laura
   Topouzis, Fotis
   Vioque, Jesus
   Young, Ian S.
   Fletcher, Astrid E.
   Patterson, Chris C.
TI Variations in Apolipoprotein E Frequency With Age in a Pooled Analysis
   of a Large Group of Older People
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Review
DE aged; apolipoprotein E2; apolipoprotein E3; apolipoprotein E4;
   apolipoproteins E; longevity; meta-analysis; multicenter study
ID ONSET ALZHEIMERS-DISEASE; MACULAR DEGENERATION; RISK-FACTORS; E GENE; E
   POLYMORPHISM; APOE GENOTYPE; ASSOCIATION; LONGEVITY; GENDER; ALLELE
AB Variation in the apolipoprotein E gene (APOE) has been reported to be associated with longevity in humans. The authors assessed the allelic distribution of APOE isoforms epsilon 2, epsilon 3, and epsilon 4 among 10,623 participants from 15 case-control and cohort studies of age-related macular degeneration (AMD) in populations of European ancestry (study dates ranged from 1990 to 2009). The authors included only the 10,623 control subjects from these studies who were classified as having no evidence of AMD, since variation within the APOE gene has previously been associated with AMD. In an analysis stratified by study center, gender, and smoking status, there was a decreasing frequency of the APOE epsilon 4 isoform with increasing age (chi(2) for trend 14.9 (1 df); P = 0.0001), with a concomitant increase in the epsilon 3 isoform (chi(2) for trend 11.3 (1 df); P = 0.001). The association with age was strongest in epsilon 4 homozygotes; the frequency of epsilon 4 homozygosity decreased from 2.7% for participants aged 60 years or less to 0.8% for those over age 85 years, while the proportion of participants with the epsilon 3/epsilon 4 genotype decreased from 26.8% to 17.5% across the same age range. Gender had no significant effect on the isoform frequencies. This study provides strong support for an association of the APOE gene with human longevity.
C1 [McKay, Gareth J.; Young, Ian S.; Patterson, Chris C.] Queens Univ Belfast, Ctr Publ Hlth, Belfast BT12 6BA, Antrim, North Ireland.
   [Silvestri, Giuliana; Chakravarthy, Usha; Dasari, Shilpa] Queens Univ Belfast, Ctr Vision & Vasc Sci, Belfast BT12 6BA, Antrim, North Ireland.
   [Fritsche, Lars G.; Weber, Bernhard H.] Univ Regensburg, Inst Human Genet, Regensburg, Germany.
   [Keilhauer, Claudia N.] Univ Hosp Wurzburg, Dept Ophthalmol, Wurzburg, Germany.
   [Klein, Michael L.; Francis, Peter J.] Oregon Hlth & Sci Univ, Casey Eye Inst, Macular Degenerat Ctr, Portland, OR 97201 USA.
   [Vingerling, Johannes R.; Ho, Lintje] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
   [Klaver, Caroline C.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands.
   [De Jong, Paulus T. D. V.] Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Amsterdam, Netherlands.
   [De Jong, Paulus T. D. V.] Univ Amsterdam, Acad Med Ctr, Dept Ophthalmol, NL-1105 AZ Amsterdam, Netherlands.
   [Dean, Michael; Sawitzke, Julie] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA.
   [Baird, Paul N.; Guymer, Robyn H.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
   [Stambolian, Dwight; Orlin, Anton] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
   [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA.
   [Seddon, Johanna M.] Tufts Med Ctr, Boston, MA USA.
   [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
   [Wright, Alan F.; Hayward, Caroline] Western Gen Hosp, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
   [Lotery, Andrew J.] Univ Southampton, Sch Med, Clin Neurosci Div, Southampton, Hants, England.
   [Lotery, Andrew J.] Southampton Gen Hosp, Southampton Eye Unit, Southampton SO9 4XY, Hants, England.
   [Ennis, Sarah] Univ Southampton, Div Human Genet, Genet Epidemiol & Bioinformat Grp, Southampton, Hants, England.
   [Gorin, Michael B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA.
   [Gorin, Michael B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
   [Weeks, Daniel E.; Kuo, Chia-Ling] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
   [Hingorani, Aroon D.; Sofat, Reecha] UCL, Dept Med, Univ Ctr Clin Pharmacol, London, England.
   [Swaroop, Anand; Othman, Mohammad] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
   [Swaroop, Anand; Kanda, Atsuhiro] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA.
   [Chen, Wei; Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
   [Yates, John R.] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Cambridge, England.
   [Cipriani, Valentina; Yates, John R.; Webster, Andrew R.; Moore, Anthony T.] UCL, Inst Ophthalmol, London, England.
   [Cipriani, Valentina; Yates, John R.; Webster, Andrew R.; Moore, Anthony T.] Moorfields Eye Hosp, London, England.
   [Seland, Johan H.] Univ Bergen, Stavanger Univ Hosp, Eye Dept, Stavanger, Norway.
   [Rahu, Mati] Natl Inst Hlth Dev, Dept Epidemiol & Biostat, Tallinn, Estonia.
   [Soubrane, Gisele] Univ Paris 12, Clin Ophthalmol, Paris, France.
   [Tomazzoli, Laura] Univ Verona, Clin Oculist, I-37100 Verona, Italy.
   [Topouzis, Fotis] Aristotle Univ Thessaloniki, Sch Med, Dept Ophthalmol, GR-54006 Thessaloniki, Greece.
   [Vioque, Jesus] Univ Miguel Hernandez, Dept Salud Publ, Alicante, Spain.
   [Vioque, Jesus] Consorcio Invest Biomed Red Especializado Epidemi, Alicante, Spain.
   [Fletcher, Astrid E.] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England.
RP McKay, GJ (reprint author), Queens Univ Belfast, Royal Victoria Hosp, Ctr Publ Hlth, Belfast BT12 6BA, Antrim, North Ireland.
EM g.j.mckay@qub.ac.uk
RI Weeks, Daniel/B-2995-2012; Cipriani, Valentina/A-8549-2012; Dean,
   Michael/G-8172-2012; Abecasis, Goncalo/B-7840-2010; vioque,
   jesus/A-1066-2008; Klaver, Caroline/A-2013-2016; Rahu, Mati/A-9981-2008;
   Hayward, Caroline/M-8818-2016
OI Swaroop, Anand/0000-0002-1975-1141; Vioque, Jesus/0000-0002-2284-148X;
   Baird, Paul/0000-0002-1305-3502; Weeks, Daniel/0000-0001-9410-7228;
   Abecasis, Goncalo/0000-0003-1509-1825; Young, Ian/0000-0003-3890-3152;
   Cipriani, Valentina/0000-0002-0839-9955; Dean,
   Michael/0000-0003-2234-0631; Hayward, Caroline/0000-0002-9405-9550
FU Guide Dogs for the Blind Association (Reading, United Kingdom) [2008-5a,
   OR2006-02d]; United Kingdom Medical Research Council [G0000067];
   Estonian Ministry of Science and Education [SF0940026s07]; Research and
   Development Office of Northern Ireland Health Personal Social Services
   [RRG 4.5]; European Union; Deutsche Forschungsgemeinschaft [WE1259/18-1,
   WE1259/19-1]; Alcon Research Institute; Ruth and Milton Steinbach
   Foundation; Tufts University School of Medicine; Macular Degeneration
   Research Fund-Tufts Medical Center; Massachusetts Lions Eye Research
   Fund; Research to Prevent Blindness USA; Foundation Fighting Blindness;
   United Kingdom Department of Health, National Institute for Health
   Research to Moorfields Eye Hospital NHS Foundation Trust; University
   College London Institute of Ophthalmology for a Specialist Biomedical
   Research Centre for Ophthalmology; JACOM Foundation; National Health and
   Medical Research Council (Canberra, Australia); MRC [G0601354]
FX Funding was provided by the Guide Dogs for the Blind Association
   (Reading, United Kingdom) (grants 2008-5a [Giuliana Silvestri] and
   OR2006-02d [John R. Yates]); the United Kingdom Medical Research Council
   (grant G0000067 [John R. Yates]); the Estonian Ministry of Science and
   Education (grant SF0940026s07 [Mati Rahu]); the Research and Development
   Office of Northern Ireland Health Personal Social Services (grant RRG
   4.5 [Giuliana Silvestri]); EVI-GENORET, an integrated project funded
   through the European Union Research Project (grant FP6 [Usha
   Chakravarthy]); the Deutsche Forschungsgemeinschaft (grants WE1259/18-1
   and WE1259/19-1 [Bernhard H. Weber]); the Alcon Research Institute and
   the Ruth and Milton Steinbach Foundation (New York, New York) (Bernhard
   H. Weber); a Russo Grant from Tufts University School of Medicine
   (Johanna M. Seddon); the Macular Degeneration Research Fund-Tufts
   Medical Center (Johanna M. Seddon); the Massachusetts Lions Eye Research
   Fund (Johanna M. Seddon); Research to Prevent Blindness USA (Michael L.
   Klein, Peter J. Francis); the Foundation Fighting Blindness (Peter J.
   Francis); financial support from the United Kingdom Department of Health
   through an award made by the National Institute for Health Research to
   Moorfields Eye Hospital NHS Foundation Trust and University College
   London Institute of Ophthalmology for a Specialist Biomedical Research
   Centre for Ophthalmology (John R. Yates); the JACOM Foundation (Paul N.
   Baird); and a National Health and Medical Research Council (Canberra,
   Australia) Practitioner Award (Robyn H. Guymer). The Centre for Eye
   Research Australia receives operational infrastructure support from the
   Victorian government (Paul N. Baird, Robyn H. Guymer), the Macular
   Disease Society (Gareth J. McKay, Andrew J. Lotery), the T.F.C. Frost
   Charity (Andrew J. Lotery), and the British Council for the Prevention
   of Blindness (Andrew J. Lotery). Genetic analysis in the European Eye
   Study was supported by an MRC Biomarker Award (grant G0601354 [Aroon D.
   Hingorani, Astrid E. Fletcher]).
NR 38
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U1 0
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 JUN 15
PY 2011
VL 173
IS 12
BP 1357
EP 1364
DI 10.1093/aje/kwr015
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 775UK
UT WOS:000291488700002
PM 21498624
ER

PT J
AU Brasky, TM
   Till, C
   White, E
   Neuhouser, ML
   Song, XL
   Goodman, P
   Thompson, IM
   King, IB
   Albanes, D
   Kristal, AR
AF Brasky, Theodore M.
   Till, Cathee
   White, Emily
   Neuhouser, Marian L.
   Song, Xiaoling
   Goodman, Phyllis
   Thompson, Ian M.
   King, Irena B.
   Albanes, Demetrius
   Kristal, Alan R.
TI Serum Phospholipid Fatty Acids and Prostate Cancer Risk: Results From
   the Prostate Cancer Prevention Trial
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE fatty acids; histology; inflammation; phospholipids; prostatic
   neoplasms; serum
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; TRANSGENIC ADENOCARCINOMA; PLASMA
   PHOSPHOLIPIDS; BLOOD; CARCINOGENESIS; INFLAMMATION; METAANALYSIS;
   CONSUMPTION; FINASTERIDE; OMEGA-3
AB Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55-84 years, in the Prostate Cancer Prevention Trial during 1994-2003. Cases (n = 1,658) were frequency matched to controls (n 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were extracted from serum, and concentrations of omega-3, omega-6, and trans-fatty acids (TFAs) were expressed as proportions of the total. Logistic regression models estimated odds ratios and 95% confidence intervals of associations of fatty acids with prostate cancer by grade. No fatty acids were associated with low-grade prostate cancer risk. Docosahexaenoic acid was positively associated with high-grade disease (quartile 4 vs. 1: odds ratio (OR) = 2.50, 95% confidence interval (CI): 1.34, 4.65); TFA 18: 1 and TFA 18: 2 were linearly and inversely associated with risk of high-grade prostate cancer (quartile 4 vs. 1: TFA 18: 1, OR 0.55, 95% CI: 0.30, 0.98; TFA 18: 2, OR = 0.48, 95% CI: 0.27, 0.84). The study findings are contrary to those expected from the pro-and antiinflammatory effects of these fatty acids and suggest a greater complexity of effects of these nutrients with regard to prostate cancer risk.
C1 [Brasky, Theodore M.; Till, Cathee; White, Emily; Neuhouser, Marian L.; Song, Xiaoling; Goodman, Phyllis] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
   [Brasky, Theodore M.; White, Emily; Kristal, Alan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
   [Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
   [King, Irena B.] Univ New Mexico, Ctr Canc, Canc Populat Sci Res Program, Albuquerque, NM 87131 USA.
   [Albanes, Demetrius] NCI, Dept Canc Epidemiol & Genet, Washington, DC USA.
RP Brasky, TM (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA.
EM tbrasky@fhcrc.org
RI Albanes, Demetrius/B-9749-2015; 
OI Kristal, Alan/0000-0002-7329-1617
FU National Cancer Institute, National Institutes of Health [U01-CA37429,
   P01-CA108964, R01-CA63164, R25-CA94880, K05-CA154337, P30-CA054171,
   CA-054174]
FX This work is supported by the following grants and awards from the
   National Cancer Institute, National Institutes of Health: U01-CA37429
   (Prostate Cancer Prevention Trial), P01-CA108964 (Biology of the
   Prostate Cancer Prevention Trial), R01-CA63164 (Prospective Cohort Study
   of Diet and Prostate Cancer), R25-CA94880 (Cancer Prevention Training in
   Nutrition, Exercise, and Genetics), K05-CA154337 (Established
   Investigator Award in Cancer Prevention and Control), P30-CA054171
   (Cancer Therapy and Research Center Cancer Center support grant), and
   CA-054174 (Cancer Center support grant).
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U1 0
U2 16
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 15
PY 2011
VL 173
IS 12
BP 1429
EP 1439
DI 10.1093/aje/kwr027
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 775UK
UT WOS:000291488700011
PM 21518693
ER

PT J
AU Solovieff, N
   Hartley, SW
   Baldwin, CT
   Klings, ES
   Gladwin, MT
   Taylor, JG
   Kato, GJ
   Farrer, LA
   Steinberg, MH
   Sebastiani, P
AF Solovieff, Nadia
   Hartley, Stephen W.
   Baldwin, Clinton T.
   Klings, Elizabeth S.
   Gladwin, Mark T.
   Taylor, James G.
   Kato, Gregory J.
   Farrer, Lindsay A.
   Steinberg, Martin H.
   Sebastiani, Paola
TI Ancestry of African Americans with sickle cell disease
SO BLOOD CELLS MOLECULES AND DISEASES
LA English
DT Article
DE Sickle cell disease; Genetic ancestry; Admixture; Genetic association
ID HYPERTENSION; ASSOCIATION; RISK
AB The inheritance of genetic disease depends on ancestry that must be considered when interpreting genetic association studies and can provide insights when comparing traits in a population. We compared the genetic profiles of African Americans with sickle cell disease to those of Black Africans and Caucasian populations of European descent and found that they are less genetically admixed than other African Americans and have an ancestry similar to Yorubans, Mandenkas and Bantu. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Solovieff, Nadia; Hartley, Stephen W.; Farrer, Lindsay A.; Sebastiani, Paola] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
   [Baldwin, Clinton T.] Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA.
   [Klings, Elizabeth S.; Farrer, Lindsay A.; Steinberg, Martin H.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
   [Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
   [Taylor, James G.; Kato, Gregory J.] NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
RP Solovieff, N (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave,Crosstown Bldg,3rd Floor, Boston, MA 02118 USA.
EM ntimofee@bu.edu
RI Kato, Gregory/I-7615-2014; 
OI Taylor, James/0000-0002-4421-1809; Kato, Gregory/0000-0003-4465-3217;
   Steinberg, Martin/0000-0001-8800-8020; Farrer,
   Lindsay/0000-0001-5533-4225; sebastiani, paola/0000-0001-6419-1545
FU NIH [R01 HL 87681, R01 HL 068970, R01 AG09029, R01 AG025259]
FX Supported by NIH grants R01 HL 87681 and R01 HL 068970 (MHS), R01
   AG09029 and R01 AG025259 (LAF).
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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 1079-9796
EI 1096-0961
J9 BLOOD CELL MOL DIS
JI Blood Cells Mol. Dis.
PD JUN 15
PY 2011
VL 47
IS 1
BP 41
EP 45
DI 10.1016/j.bcmd.2011.04.002
PG 5
WC Hematology
SC Hematology
GA 774JB
UT WOS:000291380400006
PM 21546286
ER

PT J
AU Isakova, T
   Xie, HL
   Yang, W
   Xie, DW
   Anderson, AH
   Scialla, J
   Wahl, P
   Gutierrez, OM
   Steigerwalt, S
   He, J
   Schwartz, S
   Lo, J
   Ojo, A
   Sondheimer, J
   Hsu, CY
   Lash, J
   Leonard, M
   Kusek, JW
   Feldman, HI
   Wolf, M
AF Isakova, Tamara
   Xie, Huiliang
   Yang, Wei
   Xie, Dawei
   Anderson, Amanda Hyre
   Scialla, Julia
   Wahl, Patricia
   Gutierrez, Orlando M.
   Steigerwalt, Susan
   He, Jiang
   Schwartz, Stanley
   Lo, Joan
   Ojo, Akinlolu
   Sondheimer, James
   Hsu, Chi-yuan
   Lash, James
   Leonard, Mary
   Kusek, John W.
   Feldman, Harold I.
   Wolf, Myles
CA CRIC Study Grp
TI Fibroblast Growth Factor 23 and Risks of Mortality and End-Stage Renal
   Disease in Patients With Chronic Kidney Disease
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID VASCULAR DYSFUNCTION; PARATHYROID-HORMONE; FGF RECEPTOR; HEMODIALYSIS;
   CALCITRIOL; DEATH; FIBROBLAST-GROWTH-FACTOR-23; PROGRESSION; PHOSPHORUS;
   PREDICTION
AB Context A high level of the phosphate-regulating hormone fibroblast growth factor 23 (FGF-23) is associated with mortality in patients with end-stage renal disease, but little is known about its relationship with adverse outcomes in the much larger population of patients with earlier stages of chronic kidney disease.
   Objective To evaluate FGF-23 as a risk factor for adverse outcomes in patients with chronic kidney disease.
   Design, Setting, and Participants A prospective study of 3879 participants with chronic kidney disease stages 2 through 4 who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008.
   Main Outcome Measures All-cause mortality and end-stage renal disease.
   Results At study enrollment, the mean (SD) estimated glomerular filtration rate (GFR) was 42.8 (13.5) mL/min/1.73 m(2), and the median FGF-23 level was 145.5 RU/mL (interquartile range [IQR], 96-239 reference unit [RU]/mL). During a median follow-up of 3.5 years (IQR, 2.5-4.4 years), 266 participants died (20.3/1000 person-years) and 410 reached end-stage renal disease (33.0/1000 person-years). In adjusted analyses, higher levels of FGF-23 were independently associated with a greater risk of death (hazard ratio [HR], per SD of natural log-transformed FGF-23, 1.5; 95% confidence interval [CI], 1.3-1.7). Mortality risk increased by quartile of FGF-23: the HR was 1.3 (95% CI, 0.8-2.2) for the second quartile, 2.0 (95% CI, 1.2-3.3) for the third quartile, and 3.0 (95% CI, 1.8-5.1) for the fourth quartile. Elevated fibroblast growth factor 23 was independently associated with significantly higher risk of endstage renal disease among participants with an estimated GFR between 30 and 44 mL/min/1.73 m(2) (HR, 1.3 per SD of FGF-23 natural log-transformed FGF-23; 95% CI, 1.04-1.6) and 45 mL/min/1.73 m(2) or higher (HR, 1.7; 95% CI, 1.1-2.4), but not less than 30 mL/min/1.73 m(2).
   Conclusion Elevated FGF-23 is an independent risk factor for end-stage renal disease in patients with relatively preserved kidney function and for mortality across the spectrum of chronic kidney disease. JAMA. 2011;305(23):2432-2439 www.jama.com
C1 [Isakova, Tamara; Wahl, Patricia; Wolf, Myles] Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, Miami, FL 33136 USA.
   [Xie, Huiliang] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Div Nephrol & Hypertens, Miami, FL 33136 USA.
   [Xie, Huiliang; Yang, Wei; Anderson, Amanda Hyre; Feldman, Harold I.] Childrens Hosp Philadelphia, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
   [Leonard, Mary] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
   [Schwartz, Stanley; Feldman, Harold I.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA.
   [Scialla, Julia] Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21205 USA.
   [Gutierrez, Orlando M.] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL USA.
   [Steigerwalt, Susan] St Johns Hlth Syst, Detroit, MI USA.
   [He, Jiang] Tulane Univ, Hlth Sci Ctr, Dept Med, New Orleans, LA 70118 USA.
   [Lo, Joan] Kaiser Permanente, Oakland, CA USA.
   [Ojo, Akinlolu] Univ Michigan Hlth Syst, Dept Med, Div Nephrol, Ann Arbor, MI USA.
   [Sondheimer, James] Wayne State Univ, Sch Med, Dept Med, Div Nephrol, Detroit, MI 48201 USA.
   [Hsu, Chi-yuan] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA 94143 USA.
   [Lash, James] Univ Illinois, Dept Med, Div Nephrol, Chicago, IL USA.
   [Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD USA.
RP Wolf, M (reprint author), Univ Miami, Miller Sch Med, Dept Med, Div Nephrol & Hypertens, 1120 NW 14th St,CRB 819, Miami, FL 33136 USA.
EM mwolf2@med.miami.edu
RI Yang, Wei/A-9223-2009
OI Yang, Wei/0000-0001-8984-4389
FU National Institutes of Health [R01DK081374, K23DK087858, R01DK077128,
   UL1RR024134, UL1RR025005, M01RR16500, UL1RR024989, M01RR000042,
   UL1RR024986, UL1RR029879, RR05096, UL1RR024131]; National Institute of
   Diabetes and Digestive and Kidney Diseases [5U01DK060990, 5U01DK060984,
   5U01DK06102, 5U01DK061021, 5U01DK061028, 5U01DK60980, 5U01DK060963,
   5U01DK060902]
FX This CRIC ancillary study was supported by National Institutes of Health
   grants R01DK081374 (Dr Wolf), K23DK087858 (Dr Isakova), and R01DK077128
   (Dr Leonard). The CRIC Study is supported by cooperative agreement
   project grants 5U01DK060990, 5U01DK060984, 5U01DK06102, 5U01DK061021,
   5U01DK061028, 5U01DK60980, 5U01DK060963, and 5U01DK060902 from the
   National Institute of Diabetes and Digestive and Kidney Diseases, and by
   grants UL1RR024134, UL1RR025005, M01RR16500, UL1RR024989, M01RR000042,
   UL1RR024986, UL1RR029879, RR05096, and UL1RR024131 from the National
   Institutes of Health.
NR 32
TC 370
Z9 388
U1 1
U2 20
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 15
PY 2011
VL 305
IS 23
BP 2432
EP 2439
DI 10.1001/jama.2011.826
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 777EB
UT WOS:000291597300023
PM 21673295
ER

PT J
AU Carass, A
   Cuzzocreo, J
   Wheeler, MB
   Bazin, PL
   Resnick, SM
   Prince, JL
AF Carass, Aaron
   Cuzzocreo, Jennifer
   Wheeler, M. Bryan
   Bazin, Pierre-Louis
   Resnick, Susan M.
   Prince, Jerry L.
TI Simple paradigm for extra-cerebral tissue removal: Algorithm and
   analysis
SO NEUROIMAGE
LA English
DT Article
DE Brain extraction; Skull stripping; Watershed principle; Segmentation;
   Medical image processing
ID IMPLICIT SURFACE EVOLUTION; VOXEL-BASED MORPHOMETRY; RESONANCE BRAIN
   IMAGES; SEGMENTATION; CLASSIFICATION; RECONSTRUCTION; MRI; PET
AB Extraction of the brain i.e. cerebrum, cerebellum, and brain stem from T1-weighted structural magnetic resonance images is an important initial step in neuroimage analysis. Although automatic algorithms are available, their inconsistent handling of the cortical mantle often requires manual interaction, thereby reducing their effectiveness. This paper presents a fully automated brain extraction algorithm that incorporates elastic registration, tissue segmentation, and morphological techniques which are combined by a watershed principle, while paying special attention to the preservation of the boundary between the gray matter and the cerebrospinal fluid. The approach was evaluated by comparison to a manual rater, and compared to several other leading algorithms on a publically available data set of brain images using the Dice coefficient and containment index as performance metrics. The qualitative and quantitative impact of this initial step on subsequent cortical surface generation is also presented. Our experiments demonstrate that our approach is quantitatively better than six other leading algorithms (with statistical significance on modern T1-weighted MR data). We also validated the robustness of the algorithm on a very large data set of over one thousand subjects, and showed that it can replace an experienced manual rater as preprocessing for a cortical surface extraction algorithm with statistically insignificant differences in cortical surface position. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Carass, Aaron; Wheeler, M. Bryan; Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA.
   [Cuzzocreo, Jennifer; Bazin, Pierre-Louis] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Baltimore, MD 21218 USA.
   [Resnick, Susan M.] NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA.
RP Carass, A (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, 105 Barton Hall,3400 N Charles St, Baltimore, MD 21218 USA.
EM aaron_carass@jhu.edu
RI Prince, Jerry/A-3281-2010; 
OI Prince, Jerry/0000-0002-6553-0876; Bazin,
   Pierre-Louis/0000-0002-0141-5510; Carass, Aaron/0000-0003-4939-5085
FU National Institute of Neurological Disorders and Stroke (NINDS),
   National Institute of Health (NIH) [R01-NS37747, R01-AG016324,
   R01-NS054255]; National Institute of Biomedical Imaging and
   Bioengineering (NIBIB), National Institute of Health (NIH)
   [R21-EB009900]; NIH, National Institute on Aging
FX Funding support for this work was provided by the National Institute of
   Neurological Disorders and Stroke (NINDS), (R01-NS37747, R01-AG016324
   and R01-NS054255), and by the National Institute of Biomedical Imaging
   and Bioengineering (NIBIB) (R21-EB009900), both of which are part of the
   National Institute of Health (NIH). This research was supported in part
   by the Intramural Research Program of the NIH, National Institute on
   Aging. We are grateful to the BLSA participants and neuroimaging staff
   for their dedication to these studies. The authors gratefully
   acknowledge the help of Dr. Vitali Zagorodnov, of Nanyang Technological
   University, for providing the numerical results of his experiments,
   originally published in Sadananthan et al. (2010). The authors wish to
   thank Navid Shiee of Johns Hopkins University for his help in preparing
   this manuscript for publication. We thank the anonymous reviewers for
   their careful analysis of our paper, which helped to greatly improve
   this manuscript. The software is to be made publicly available through
   integration into the 3D Slicer (http://www.slicer.org/) software package
   distributed through NA-MIC (http://www.na-mic.org/).
NR 41
TC 59
Z9 59
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 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD JUN 15
PY 2011
VL 56
IS 4
BP 1982
EP 1992
DI 10.1016/j.neuroimage.2011.03.045
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
   Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 775KF
UT WOS:000291457500012
PM 21458576
ER

PT J
AU Murray, EA
   Wise, SP
   Drevets, WC
AF Murray, Elisabeth A.
   Wise, Steven P.
   Drevets, Wayne C.
TI Localization of Dysfunction in Major Depressive Disorder: Prefrontal
   Cortex and Amygdala
SO BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE Animal models; devaluation; emotion; frontal lobe function; mood;
   primate research; reversal; reward; self-esteem; self-reflection;
   self-valuation; self-worth
ID DEEP BRAIN-STIMULATION; TREATMENT-RESISTANT DEPRESSION; PRIMATE
   ORBITOFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; RHESUS-MONKEYS; MOOD
   DISORDERS; DECISION-MAKING; BASOLATERAL AMYGDALA; BIPOLAR DISORDER;
   NEURAL RESPONSE
AB Despite considerable effort, the localization of dysfunction in major depressive disorder (MDD) remains poorly understood. We present a hypothesis about its localization that builds on recent findings from primate neuropsychology. The hypothesis has four key components: a deficit in the valuation of "self" underlies the core disorder in MDD; the medial frontal cortex represents "self"; interactions between the amygdala and cortical representations update their valuation; and inefficiency in using positive feedback by orbital prefrontal cortex contributes to MDD.
C1 [Murray, Elisabeth A.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
   [Wise, Steven P.] Olschefskie Inst Neurobiol Knowledge, Potomac, MD USA.
   [Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK USA.
   [Drevets, Wayne C.] Univ Oklahoma, Coll Med, Tulsa, OK USA.
RP Murray, EA (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,MSC 4415,49 Convent Dr, Bethesda, MD 20892 USA.
OI Murray, Elisabeth/0000-0003-1450-1642
FU National Institute of Mental Health; Pfizer Pharmaceuticals
FX This work was supported by the Intramural Research Program of the
   National Institute of Mental Health. Dr. Drevets disclosed consulting
   fees from Pfizer Pharmaceuticals. All other authors report no biomedical
   financial interests or potential conflicts of interest.
NR 134
TC 66
Z9 68
U1 12
U2 36
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 JUN 15
PY 2011
VL 69
IS 12
BP E43
EP E54
DI 10.1016/j.biopsych.2010.09.041
PG 12
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 772QI
UT WOS:000291249200001
PM 21111403
ER

PT J
AU Dash, C
   Ahmadibeni, Y
   Hanley, MJ
   Pandhare, J
   Gotte, M
   Le Grice, SFJ
   Parang, K
AF Dash, Chandravanu
   Ahmadibeni, Yousef
   Hanley, Michael J.
   Pandhare, Jui
   Gotte, Mathias
   Le Grice, Stuart F. J.
   Parang, Keykavous
TI Inhibition of multi-drug resistant HIV-1 reverse transcriptase by
   nucleoside beta-triphosphates
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE DNA polymerase; HIV; Multi-drug resistant; Nucleoside; Reverse
   transcriptase; Solid-phase synthesis
ID CELLULAR-DNA-POLYMERASES; ANALOGS; 5'-O-(1,1-DITHIOTRIPHOSPHATES);
   5'-TRIPHOSPHATES; NUCLEOTIDES; DERIVATIVES
AB Despite the success of potent reverse transcriptase (RT) inhibitors against human immunodeficiency virus type 1 (HIV-1) in combination regimens, the development of drug resistant RTs constitutes a major hurdle for the long-term efficacy of current antiretroviral therapy. Nucleoside beta-triphosphate analogs of adenosine and nucleoside reverse transcriptase inhibitors (NRTIs) (3'-azido-2',3'-dideoxythymidine (AZT), 3'-fluoro-2',3'-dideoxythymidine (FLT), and 2',3'-didehydro-2',3'-dideoxythymidine (d4T)) were synthesized and their inhibitory activities were evaluated against wild-type and multidrug resistant HIV-1 RTs. Adenosine beta-triphosphate (1) and AZT beta-triphosphate (2) completely inhibited the DNA polymerase activity of wild type, the NRTI multi resistant, and nonnucleoside RT inhibitors (NNRTI) resistant HIV-1 RT at 10 nM, 10 and 100 mu M, respectively. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Dash, Chandravanu; Pandhare, Jui] Meharry Med Coll, Ctr AIDS Hlth Dispar Res, Dept Biochem & Canc Biol, Nashville, TN 37208 USA.
   [Ahmadibeni, Yousef] Columbus State Univ, Dept Chem, Columbus, GA 31907 USA.
   [Ahmadibeni, Yousef; Hanley, Michael J.; Parang, Keykavous] Univ Rhode Isl, Dept Biomed & Pharmaceut Sci, Kingston, RI 02881 USA.
   [Gotte, Mathias] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2T5, Canada.
   [Le Grice, Stuart F. J.] NCI, Resistance Mech Lab, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Dash, C (reprint author), Meharry Med Coll, Ctr AIDS Hlth Dispar Res, Dept Biochem & Canc Biol, Nashville, TN 37208 USA.
EM kparang@uri.edu
FU National Science Foundation [CHE 0748555]; National Center for Research
   Resources, NIH; NIH [R00DA024558, R03DA30896]; Vanderbilt-Meharry CFAR; 
   [1 P20 RR16457]
FX K.P. acknowledges the National Science Foundation, Grant Number CHE
   0748555 for the financial support and National Center for Research
   Resources, NIH, and Grant Number 1 P20 RR16457 for sponsoring the core
   facility. C. D. acknowledges NIH Grant # R00DA024558, and R03DA30896 and
   Faculty start up funds from Vanderbilt-Meharry CFAR.
NR 34
TC 3
Z9 3
U1 0
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JUN 15
PY 2011
VL 21
IS 12
BP 3519
EP 3522
DI 10.1016/j.bmcl.2011.05.005
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 771GT
UT WOS:000291145900003
PM 21605974
ER

PT J
AU Pendyala, S
   Moitra, J
   Kalari, S
   Kleeberger, SR
   Zhao, YT
   Reddy, SP
   Garcia, JGN
   Natarajan, V
AF Pendyala, Srikanth
   Moitra, Jaideep
   Kalari, Satish
   Kleeberger, Steven R.
   Zhao, Yutong
   Reddy, Sekhar P.
   Garcia, Joe G. N.
   Natarajan, Viswanathan
TI Nrf2 regulates hyperoxia-induced Nox4 expression in human lung
   endothelium: Identification of functional antioxidant response elements
   on the Nox4 promoter
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE ROS; Endothelium; ARE; Nox4; Nrf2; Free radicals
ID SMOOTH-MUSCLE-CELLS; PULMONARY EPITHELIAL-CELLS; OXYGEN SPECIES
   GENERATION; OXIDATIVE STRESS; NAD(P)H OXIDASE; NADPH OXIDASE;
   TRANSCRIPTIONAL RESPONSE; INJURY; ACTIVATION; MICE
AB Reactive oxygen species (ROS) generated by vascular endothelial and smooth muscle cells contribute to the development and progression of vascular diseases. We have recently shown that hyperoxia enhances NADPH oxidase 4 (Nox4) expression, which regulates lung endothelial cell migration and angiogenesis. Regulation of Nox4 in the vasculature is poorly understood. The objective of this study was to identify the transcriptional factor (s) involved in regulation of endothelial Nox4. We found that hyperoxia-induced Nox4 expression was markedly reduced in Nrf2(-/-) mice, compared to Nrf2(+/+) mice. Exposure of human lung microvascular endothelial cells (HLMVECs) to hyperoxia stimulated Nrf2 translocation from the cytoplasm to the nucleus and increased Nox4 expression. Knockdown of Nrf2 expression using an siRNA approach attenuated basal Nox4 expression; however, it enhanced superoxide/ROS generation under both normoxia and hyperoxia. In silico analysis revealed the presence of at least three consensus sequences for the antioxidant response element (ARE) in the promoter region of Nox4. In transient transfections, hyperoxia stimulated Nox4 promoter activity in HLMVECs, and deletion of the -438 to -458 and -619 to -636 sequences markedly reduced hyperoxia-stimulated Nox4 promoter activation. ChIP analysis revealed an enhanced recruitment of Nrf2 to the endogenous Nox4 promoter spanning these two AREs after hyperoxic insult. Collectively, these results demonstrate, for the first time, a novel role for Nrf2 in regulating hyperoxia-induced Nox4 transcription via AREs in lung endothelium. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Pendyala, Srikanth; Natarajan, Viswanathan] Univ Illinois, Dept Pharmacol, Chicago, IL 60612 USA.
   [Moitra, Jaideep] Gennova Biopharmaceut Ltd, Pune, Maharashtra, India.
   [Kalari, Satish] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
   [Kleeberger, Steven R.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA.
   [Zhao, Yutong] Univ Pittsburgh, Dept Med, Sch Med, Pittsburgh, PA 15260 USA.
   [Reddy, Sekhar P.] Johns Hopkins Sch Publ Hlth, Dept Environm Sci, Baltimore, MD 21205 USA.
   [Garcia, Joe G. N.; Natarajan, Viswanathan] Univ Illinois, Dept Med, Chicago, IL 60612 USA.
   [Garcia, Joe G. N.; Natarajan, Viswanathan] Univ Illinois, Inst Personalized Resp Med, Chicago, IL 60612 USA.
RP Natarajan, V (reprint author), Univ Illinois, Dept Pharmacol, Chicago, IL 60612 USA.
EM visnatar@uic.edu
RI Kalari, Satish/C-6967-2012
FU NIH [HL08553, HL58064, HL66109]
FX This work was supported by NIH Grants HL08553 and HL58064 to V.N. and
   HL66109 to S.P.R.
NR 33
TC 40
Z9 41
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUN 15
PY 2011
VL 50
IS 12
BP 1749
EP 1759
DI 10.1016/j.freeradbiomed.2011.03.022
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 772KQ
UT WOS:000291233200005
PM 21443946
ER

PT J
AU Li, W
   Henderson, LJ
   Major, EO
   Al-Harthi, L
AF Li, Wei
   Henderson, Lisa J.
   Major, Eugene O.
   Al-Harthi, Lena
TI IFN-gamma Mediates Enhancement of HIV Replication in Astrocytes by
   Inducing an Antagonist of the beta-Catenin Pathway (DKK1) in a STAT
   3-Dependent Manner
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; CENTRAL-NERVOUS-SYSTEM; WNT SIGNALING
   PATHWAY; ALZHEIMERS-DISEASE; INTERFERON-GAMMA; CELL FATE; INFECTION;
   ACTIVATION; EXPRESSION; SYNTHASE
AB Typically, IFN-gamma is an antiviral cytokine that inhibits the replication of many viruses, including HIV. However, in the CNS, IFN-gamma induces HIV-productive replication in astrocytes. Although astrocytes in vitro are refractory to HIV replication, recent in vivo evidence demonstrated that astrocytes are infected by HIV, and their degree of infection is correlated with proximity to activated macrophages/microglia. The ability of IFN-gamma to induce HIV replication in astrocytes suggests that the environmental milieu is critical in regulating the permissiveness of astrocytes to HIV infection. We evaluated the mechanism by which IFN-gamma relieves restricted HIV replication in astrocytes. We demonstrate that although astrocytes have robust endogenous beta-catenin signaling, a pathway that is a potent inhibitor of HIV replication, IFN-gamma diminished beta-catenin signaling in astrocytes by 40%, as evaluated by both active beta-catenin protein expression and beta-catenin-mediated T cell factor/lymphoid enhancer reporter (TOPflash) activity. Further, IFN-gamma-mediated inhibition of beta-catenin signaling was dependent on its ability to induce an antagonist of the beta-catenin signaling pathway, Dickkopf-related protein 1, in a STAT 3-dependent manner. Inhibition of STAT3 and Dickkopf-related protein 1 abrogated the ability of IFN-gamma to enhance HIV replication in astrocytes. These data demonstrated that IFN-gamma induces HIV replication in astrocytes by antagonizing the beta-catenin pathway. To our knowledge, this is the first report to point to an intricate cross-talk between IFN-gamma signaling and beta-catenin signaling that may have biologic and virologic effects on HIV outcome in the CNS, as well as on broader processes where the two pathways interface. The Journal of Immunology, 2011, 186: 6771-6778.
C1 [Li, Wei; Henderson, Lisa J.; Al-Harthi, Lena] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA.
   [Major, Eugene O.] NINDS, NIH, Bethesda, MD 20892 USA.
RP Al-Harthi, L (reprint author), Rush Univ, Med Ctr, Dept Immunol & Microbiol, 1735 W Harrison St,614 Cohn, Chicago, IL 60612 USA.
EM Lena_Al-Harthi@rush.edu
RI Li, Wei/I-8060-2014
FU National Institutes of Health [R01 NS060632, F31 NS071999]; Chicago
   Developmental Center for AIDS Research [P30 AI 082151]; National
   Institute of Allergy and Infectious Diseases; National Cancer Institute;
   National Institute of Mental Health; National Institute of Drug Abuse;
   National Institute of Child Health and Development; National Heart,
   Lung, and Blood Institute; National Center for Complementary and
   Alternative Medicine
FX This work was supported by Grants R01 NS060632 (to L.A.-H.) and F31
   NS071999 (to L.J.H.) from the National Institutes of Health. It was also
   supported by the Chicago Developmental Center for AIDS Research (P30 AI
   082151), a National Institutes of Health-funded program supported by the
   National Institute of Allergy and Infectious Diseases; the National
   Cancer Institute; the National Institute of Mental Health; the National
   Institute of Drug Abuse; the National Institute of Child Health and
   Development; the National Heart, Lung, and Blood Institute; and the
   National Center for Complementary and Alternative Medicine.
NR 42
TC 36
Z9 36
U1 1
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 JUN 15
PY 2011
VL 186
IS 12
BP 6771
EP 6778
DI 10.4049/jimmunol.1100099
PG 8
WC Immunology
SC Immunology
GA 773LV
UT WOS:000291309700017
PM 21562161
ER

PT J
AU Olivares-Zavaleta, N
   Carmody, A
   Messer, R
   Whitmire, WM
   Caldwell, HD
AF Olivares-Zavaleta, Norma
   Carmody, Aaron
   Messer, Ronald
   Whitmire, William M.
   Caldwell, Harlan D.
TI Chlamydia pneumoniae Inhibits Activated Human T Lymphocyte Proliferation
   by the Induction of Apoptotic and Pyroptotic Pathways
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID SMOOTH-MUSCLE-CELLS; CHLAMYDOPHILA-PNEUMONIAE; III SECRETION;
   ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; INFECTION; TRACHOMATIS; EXPRESSION;
   MACROPHAGES; CYTOKINE
AB Chlamydia pneumoniae is an omnipresent obligate intracellular bacterial pathogen that infects numerous host species. C. pneumoniae infections of humans are a common cause of community acquired pneumonia but have also been linked to chronic diseases such as atherosclerosis, Alzheimer's disease, and asthma. Persistent infection and immune avoidance are believed to play important roles in the pathophysiology of C. pneumoniae disease. We found that C. pneumoniae organisms inhibited activated but not nonactivated human T cell proliferation. Inhibition of proliferation was pathogen specific, heat sensitive, and multiplicity of infection dependent and required chlamydial entry but not de novo protein synthesis. Activated CD4(+) and CD8(+) T cells were equally sensitive to C. pneumoniae antiproliferative effectors. The C. pneumoniae antiproliferative effect was linked to T cell death associated with caspase 1, 8, 9, and IL-1 beta production, indicating that both apoptotic and pyroptotic cellular death pathways were activated after pathogen-T cell interactions. Collectively, these findings are consistent with the conclusion that C. pneumoniae could induce a local T cell immunosuppression and inflammatory response revealing a possible host-pathogen scenario that would support both persistence and inflammation. The Journal of Immunology, 2011, 186: 7120-7126.
C1 [Olivares-Zavaleta, Norma; Whitmire, William M.; Caldwell, Harlan D.] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
   [Carmody, Aaron] NIAID, Flow Cytometry Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
   [Messer, Ronald] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Caldwell, HD (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM hcaldwell@niaid.nih.gov
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 40
TC 18
Z9 22
U1 0
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 15
PY 2011
VL 186
IS 12
BP 7120
EP 7126
DI 10.4049/jimmunol.1100393
PG 7
WC Immunology
SC Immunology
GA 773LV
UT WOS:000291309700053
PM 21543647
ER

PT J
AU Oh, MH
   Oh, SY
   Yu, JH
   Myers, AC
   Leonard, WJ
   Liu, YJ
   Zhu, Z
   Zheng, T
AF Oh, Min-Hee
   Oh, Sun Young
   Yu, Jinho
   Myers, Allen C.
   Leonard, Warren J.
   Liu, Yong Jun
   Zhu, Zhou
   Zheng, Tao
TI IL-13 Induces Skin Fibrosis in Atopic Dermatitis by Thymic Stromal
   Lymphopoietin
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID MEDIATED ALLERGIC INFLAMMATION; PERIPHERAL-BLOOD FIBROCYTES; CD4(+)
   T-CELLS; CIRCULATING FIBROCYTES; GROWTH-FACTOR; AIRWAY INFLAMMATION;
   PULMONARY-FIBROSIS; TH2 RESPONSES; BONE-MARROW; IN-VIVO
AB Skin fibrotic remodeling is a major feature in human atopic dermatitis (AD). Inflammation and tissue fibrosis are common consequences of Th2 responses. Elevated IL-13 and thymic stromal lymphopoietin (TSLP) have been found in the AD skin lesions. Fibrocytes can be recruited to inflamed tissues to promote wound healing and fibrosis. Dermal transgenic expression of IL-13 causes an AD-like phenotype with fibrosis and increased TSLP. However, the role of TSLP in fibrotic remodeling is unknown. In this study, we investigated the role of TSLP and fibrocytes in the generation of IL-13-induced skin fibrosis. In AD lesion, cessation of IL-13 transgene expression resulted in reduced skin inflammation but with no effect on further progression of fibrosis. This was accompanied by markedly increased CD34(+)/procollagen 1(+) fibrocytes. Furthermore, fibrocytes express TSLP receptor (TSLPR), and TSLP directly promotes PBMC-derived fibrocytes to produce collagen. Neutralization of TSLP or genetic deletion of TSLPR in IL-13 transgenic mice resulted in a significant reduction in fibrocytes and in skin fibrosis. Furthermore, reduction of fibrosis by depletion of TSLP was independent of IL-13. Interestingly, the number of fibrocytes was highly increased in the skin samples of AD patients. These data indicate that the progression of skin fibrosis in IL-13-induced AD occurs via TSLP/TSLPR-dependent but IL-13-independent novel mechanisms by promoting fibrocyte functions. The Journal of Immunology, 2011, 186: 7232-7242.
C1 [Oh, Min-Hee; Oh, Sun Young; Yu, Jinho; Myers, Allen C.; Zhu, Zhou; Zheng, Tao] Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD 21224 USA.
   [Leonard, Warren J.] NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA.
   [Liu, Yong Jun] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA.
RP Zheng, T (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy & Clin Immunol, 5001 Hopkins Bayview Circle,1A-38, Baltimore, MD 21224 USA.
EM tzheng@jhmi.edu
RI Yu, Jinho/P-4293-2014
OI Yu, Jinho/0000-0002-1226-8077
FU National Institutes of Health [AI075025, HL079349]; National Heart,
   Lung, and Blood Institute/National Institutes of Health
FX This work was supported by National Institutes of Health Grants AI075025
   (to T.Z.) and HL079349 (to Z.Z.) and by the Intramural Research Program
   of the National Heart, Lung, and Blood Institute/National Institutes of
   Health (to W.J.L.).
NR 52
TC 51
Z9 53
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUN 15
PY 2011
VL 186
IS 12
BP 7232
EP 7242
DI 10.4049/jimmunol.1100504
PG 11
WC Immunology
SC Immunology
GA 773LV
UT WOS:000291309700065
PM 21576506
ER

PT J
AU Ghosh, A
   Castle, PE
AF Ghosh, Arpita
   Castle, Philip E.
TI Invited Commentary: The Importance of Prevalence in the Effectiveness of
   a (Bio)marker
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
DE biological markers; censored data; life change events; menopause;
   premenopause; survival analysis
ID HUMAN-PAPILLOMAVIRUS; CERVICAL-CANCER; ASSOCIATION; RISK
AB Metrics such as relative hazards and relative risks do not account for the prevalence of a marker over time and its relation to whether and when an outcome occurs. Uncommon markers that have good predictive values and common markers that are poorly predictive may not be (clinically) useful in predicting disease and other health outcomes. Recent work by Little et al. (Am J Epidemiol. 2011;173(12):1380-1387) highlights the development of a new method that considers both factors in predicting outcomes. Measures that incorporate both marker prevalence and predictive values and therefore are measures of "effectiveness'' may be broadly helpful in deciding which markers or exposures are useful in disease screening or should be targeted by health interventions.
C1 [Castle, Philip E.] ASCP Inst, Washington, DC 20005 USA.
   [Ghosh, Arpita] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Castle, PE (reprint author), ASCP Inst, 1225 New York Ave NW,Suite 250, Washington, DC 20005 USA.
EM philip.castle@ascp.org
NR 13
TC 2
Z9 2
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 15
PY 2011
VL 173
IS 12
BP 1388
EP 1390
DI 10.1093/aje/kwr016
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 775UK
UT WOS:000291488700005
PM 21571873
ER

PT J
AU Laughon, MM
   Langer, JC
   Bose, CL
   Smith, PB
   Ambalavanan, N
   Kennedy, KA
   Stoll, BJ
   Buchter, S
   Laptook, AR
   Ehrenkranz, RA
   Cotten, CM
   Wilson-Costello, DE
   Shankaran, S
   Van Meurs, KP
   Davis, AS
   Gantz, MG
   Finer, NN
   Yoder, BA
   Faix, RG
   Carlo, WA
   Schibler, KR
   Newman, NS
   Rich, W
   Das, A
   Higgins, RD
   Walsh, MC
AF Laughon, Matthew M.
   Langer, John C.
   Bose, Carl L.
   Smith, P. Brian
   Ambalavanan, Namasivayam
   Kennedy, Kathleen A.
   Stoll, Barbara J.
   Buchter, Susie
   Laptook, Abbot R.
   Ehrenkranz, Richard A.
   Cotten, C. Michael
   Wilson-Costello, Deanne E.
   Shankaran, Seetha
   Van Meurs, Krisa P.
   Davis, Alexis S.
   Gantz, Marie G.
   Finer, Neil N.
   Yoder, Bradley A.
   Faix, Roger G.
   Carlo, Waldemar A.
   Schibler, Kurt R.
   Newman, Nancy S.
   Rich, Wade
   Das, Abhik
   Higgins, Rosemary D.
   Walsh, Michele C.
CA Eunice Kennedy Shriver Natl Inst C
TI Prediction of Bronchopulmonary Dysplasia by Postnatal Age in Extremely
   Premature Infants
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE bronchopulmonary dysplasia; prematurity; low-birth-weight infant
ID CHRONIC LUNG-DISEASE; BIRTH-WEIGHT INFANTS; EXTREMELY PRETERM INFANTS;
   NECROTIZING ENTEROCOLITIS; RISK; IMPACT; LIFE; SURFACTANT; MORTALITY;
   OUTCOMES
AB Rationale: Benefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment.
   Objectives: To identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death.
   Methods: We assessed infants of 23-30 weeks' gestation born in 17 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and enrolled in the Neonatal Research Network Benchmarking Trial from 2000-2004.
   Measurements and Main Results: Bronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at sixpostnatal ages usinggestational age, birth weight, race and ethnicity, sex, respiratory support, and FIO 2, and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. AWeb-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at https://neonatal.rti.org.
   Conclusions: The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.
C1 [Laughon, Matthew M.; Bose, Carl L.] Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA.
   [Langer, John C.; Gantz, Marie G.] RTI Int, Stat & Epidemiol Unit, Res Triangle Pk, NC USA.
   [Smith, P. Brian; Cotten, C. Michael] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
   [Ambalavanan, Namasivayam; Carlo, Waldemar A.] Univ Alabama, Div Neonatol, Birmingham, AL USA.
   [Kennedy, Kathleen A.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA.
   [Stoll, Barbara J.; Buchter, Susie] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
   [Stoll, Barbara J.; Buchter, Susie] Childrens Healthcare Atlanta, Atlanta, GA USA.
   [Laptook, Abbot R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
   [Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
   [Wilson-Costello, Deanne E.; Newman, Nancy S.; Walsh, Michele C.] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA.
   [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
   [Van Meurs, Krisa P.; Davis, Alexis S.] Stanford Univ, Sch Med, Dept Pediat, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA.
   [Van Meurs, Krisa P.; Davis, Alexis S.] Lucile Packard Childrens Hosp, Palo Alto, CA USA.
   [Finer, Neil N.; Rich, Wade] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA.
   [Yoder, Bradley A.; Faix, Roger G.] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
   [Schibler, Kurt R.] Cincinnati Childrens Hosp Med, Med Ctr, Perinatal Inst, Cincinnati, OH USA.
   [Das, Abhik] RTI Int, Stat & Epidemiol Unit, Rockville, MD USA.
   [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Laughon, MM (reprint author), Univ N Carolina, Div Neonatal Perinatal Med, Dept Pediat, UNC Hosp, 101 Manning Dr,CB 7596,4th Floor, Chapel Hill, NC 27599 USA.
EM matt_laughon@med.unc.edu
RI Smith, Phillip/I-5565-2014; 
OI Ambalavanan, Namasivayam/0000-0003-0731-9092
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
   of Child Health and Human Development; Neonatal Research Network's
   Benchmarking Study; Surfactant Positive Airway Pressure and Pulse
   Oximetry Trial in Extremely Low Birth Weight Infants (SUPPORT)
   [NCT233324]; National Institute of Child Health and Human Development
   [1K23HD060040-01, DHHS-1R18AE000028-01]; National Institute of Child
   Health and Human Development Neonatal Research Network; Barbara Stoll;
   Waldemar Carlo; Seetha Shankaran; Michele Walsh; Krisa Van Meurs; Neil
   Finer; Rosemary Higgins; Abhik Das; Roger Faix; Michael Cotten
FX Supported by The National Institutes of Health and the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development, which
   provided grant support for the Neonatal Research Network's Benchmarking
   Study (clinical trial registered with www.clinicaltrials.gov [NCT67613]
   and Surfactant Positive Airway Pressure and Pulse Oximetry Trial in
   Extremely Low Birth Weight Infants (SUPPORT) (clinical trial registered
   with www.clinicaltrials.gov [NCT233324]). The funding agency provided
   overall oversight for study conduct. All analyses and interpretation of
   the data and the preparation, review, and approval of this manuscript
   were independent of the funding agency. Dr. Smith received support from
   the National Institute of Child Health and Human Development
   (1K23HD060040-01 and DHHS-1R18AE000028-01). Data collected at
   participating sites of the National Institute of Child Health and Human
   Development Neonatal Research Network were transmitted to RTI
   International, the data coordinating center (DCC) for the network, which
   stored, managed, and analyzed the data for this study. On behalf of the
   Neonatal Research Network, Dr. Abhik Das (DCC principal investigator),
   Mr. John Langer, and Dr. Marie Gantz (DCC statisticians) had full access
   to all the data in the study and take responsibility for the integrity
   of the data and accuracy of the data analysis.; The authors are indebted
   to their medical and nursing colleagues and the infants and their
   parents who agreed to take part in this study. Study concept and design:
   Matthew Laughon, Carl Bose, Brian Smith, Michael Cotten, Namasivayam
   Ambalavanan, Bradley Yoder, Waldemar Carlo, Kathleen Kennedy, Krisa Van
   Meurs, Richard Ehrenkranz, Marie Gantz, and Deanne Wilson-Costello.
   Acquisition of data: Barbara Stoll, Richard Ehrenkranz, Waldemar Carlo,
   Rosemary Higgins, Seetha Shankaran, Deanne Wilson-Costello, Roger Faix,
   Bradley Yoder, Krisa Van Meurs, Kurt Schibler, Susan Buchter, Neil
   Finer, Richard Ehrenkranz, Abhik Das, Marie Gantz, Nancy Newman, and
   Michael Cotten. Analysis and interpretation of data: Matthew Laughon,
   Carl Bose, P. Brian Smith, Alexis Davis, Namasivayam Ambalavanan,
   Barbara Stoll, Abbot Laptook, Bradley Yoder, Roger Faix, Waldemar Carlo,
   Rosemary Higgins, Abhik Das, Krisa Van Meurs, Kathleen Kennedy, Michael
   Cotten, and Deanne Wilson-Costello. Drafting of the manuscript: Matthew
   Laughon, Carl Bose, Waldemar Carlo, Alexis Davis, and Michael Cotten.
   Critical revision of the manuscript for important intellectual content:
   all authors. Statistical analysis: Matthew Laughon, John Langer, Michele
   Walsh, P. Brian Smith, Waldemar Carlo, Marie Gantz, and Abhik Das.
   Obtained funding: Barbara Stoll, Waldemar Carlo, Seetha Shankaran,
   Michele Walsh, Krisa Van Meurs, Waldemar Carlo, Neil Finer, Rosemary
   Higgins, Abhik Das, Roger Faix, and Michael Cotten. Administrative,
   technical, or material support: Matthew Laughon, Barbara Stoll, Richard
   Ehrenkranz, Waldemar Carlo, Rosemary Higgins, Abhik Das, Kurt Schibler,
   and Neil Finer. Study supervision: Matthew Laughon, Carl Bose, Abbot
   Laptook, Bradley Yoder, Waldemar Carlo, Rosemary Higgins, Abhik Das,
   Roger Faix, Deanne Wilson-Costello, Susan Buchter, and Michael Cotton.
NR 41
TC 81
Z9 86
U1 0
U2 6
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JUN 15
PY 2011
VL 183
IS 12
BP 1715
EP 1722
DI 10.1164/rccm.201101-0055OC
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 786KC
UT WOS:000292305600024
PM 21471086
ER

PT J
AU Kuniholm, MH
   Gao, XJ
   Xue, XN
   Kovacs, A
   Marti, D
   Thio, CL
   Peters, MG
   Greenblatt, RM
   Goedert, JJ
   Cohen, MH
   Minkoff, H
   Gange, SJ
   Anastos, K
   Fazzari, M
   Young, MA
   Strickler, HD
   Carrington, M
AF Kuniholm, Mark H.
   Gao, Xiaojiang
   Xue, Xiaonan
   Kovacs, Andrea
   Marti, Darlene
   Thio, Chloe L.
   Peters, Marion G.
   Greenblatt, Ruth M.
   Goedert, James J.
   Cohen, Mardge H.
   Minkoff, Howard
   Gange, Stephen J.
   Anastos, Kathryn
   Fazzari, Melissa
   Young, Mary A.
   Strickler, Howard D.
   Carrington, Mary
TI The Relation of HLA Genotype to Hepatitis C Viral Load and Markers of
   Liver Fibrosis in HIV-Infected and HIV-Uninfected Women
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID ACTIVE ANTIRETROVIRAL THERAPY; ANTIGEN CLASS-I; INHIBITORY RECEPTOR
   GENES; SIMPLE NONINVASIVE INDEX; INJECTION-DRUG USERS; MHC CLASS-I;
   VIRUS-INFECTION; NATURAL-HISTORY; HEPATOCELLULAR-CARCINOMA; DISEASE
   PROGRESSION
AB Methods. High-resolution HLA class I and II genotyping was conducted in a prospective cohort of 519 human immunodeficiency virus (HIV)-seropositive and 100 HIV-seronegative women with persistent HCV infection. The end points were baseline HCV viral load and 2 noninvasive indexes of liver disease, fibrosis-4 (FIB-4), and the aspartate aminotransferase to platelet ratio index (APRI), measured at baseline and prospectively.
   Results. DQB1*0301 was associated with low baseline HCV load (beta = -.4; 95% confidence interval [CI], -.6 to -.3; P < .00001), as well as with low odds of FIB-4-defined (odds ratio [OR], .5; 95% CI, .2-.9; P = .02) and APRI-defined liver fibrosis (OR, .5; 95% CI, .3-1.0; P = .06) at baseline and/or during follow-up. Most additional associations with HCV viral load also involved HLA class II alleles. Additional associations with FIB-4 and APRI primarily involved class I alleles, for example, the relation of B*1503 with APRI-defined fibrosis had an OR of 2.0 (95% CI, 1.0-3.7; P = .04).
   Conclusions. HLA genotype may influence HCV viral load and risk of liver disease, including DQB1*0301, which was associated with HCV clearance in prior studies.
C1 [Kuniholm, Mark H.; Xue, Xiaonan; Anastos, Kathryn; Fazzari, Melissa; Strickler, Howard D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
   [Gao, Xiaojiang; Marti, Darlene; Carrington, Mary] NCI Frederick, SAIC Frederick, Cancer & Inflammat Program, Expt Immunol Lab, Baltimore, MD USA.
   [Thio, Chloe L.] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
   [Gange, Stephen J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   [Goedert, James J.] NCI, NIH, Div Canc Epidemiol & Genet, Rockville, MD USA.
   [Gao, Xiaojiang; Marti, Darlene; Carrington, Mary] MIT, Ragon Inst MGH, Charlestown, MA USA.
   [Gao, Xiaojiang; Marti, Darlene; Carrington, Mary] Harvard Univ, Charlestown, MA USA.
   [Kovacs, Andrea] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA.
   [Peters, Marion G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
   [Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA USA.
   [Cohen, Mardge H.] Hlth Serv, CORE Ctr, Cook Cty Bur, Chicago, IL USA.
   [Minkoff, Howard] Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA.
   [Young, Mary A.] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA.
RP Kuniholm, MH (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave,Belfer Bldg 1308, Bronx, NY 10461 USA.
EM mark.kuniholm@einstein.yu.edu
OI Gange, Stephen/0000-0001-7842-512X
FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004,
   UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590,
   5R01AI057006, R01A1052065]; Eunice Kennedy Shriver National Institute of
   Child Health and Human Development [UO1-HD-32632]; National Cancer
   Institute (NCI) [HHSN261200800001E]; National Institute on Drug Abuse;
   National Institute on Deafness and Other Communication Disorders;
   National Center for Research Resources (UCSF-CTSI) [UL1 RR024131]; NIH,
   NCI, Center for Cancer Research; Einstein-Montefiore CFAR (NIH)
   [AI-51519]
FX Data for this study were collected by the WIHS Collaborative Study Group
   with centers (principal investigators) at New York City/Bronx Consortium
   (K. A.); Brooklyn, NY (H. M.); Washington DC, Metropolitan Consortium
   (M.A.Y.); the Connie Wofsy Study Consortium of Northern California (R.
   G.); Los Angeles County/Southern California Consortium (Alexandra
   Levine); Chicago Consortium (M. H. C.); and the Data Coordinating Center
   (S. J. G.). The WIHS is funded by the National Institute of Allergy and
   Infectious Diseases (grants UO1-AI-35004, UO1-AI-31834, UO1-AI-34994,
   UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy
   Shriver National Institute of Child Health and Human Development
   (UO1-HD-32632). The study was also funded by the National Cancer
   Institute (NCI) (contract HHSN261200800001E), the National Institute on
   Drug Abuse, the National Institute on Deafness and Other Communication
   Disorders, the National Center for Research Resources (UCSF-CTSI grant
   UL1 RR024131), and the National Institute of Allergy and Infectious
   Diseases (5R01AI057006 to H. D. S. and R01A1052065 to A. K.); and the
   Intramural Research Program of the NIH, NCI, Center for Cancer Research.
   This work was supported in part by the Einstein-Montefiore CFAR (NIH
   AI-51519).
NR 49
TC 5
Z9 5
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 15
PY 2011
VL 203
IS 12
BP 1807
EP 1814
DI 10.1093/infdis/jir192
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 770BO
UT WOS:000291062200015
PM 21606539
ER

PT J
AU Puverel, S
   Barrick, C
   Dolci, S
   Coppola, V
   Tessarollo, L
AF Puverel, Sandrine
   Barrick, Colleen
   Dolci, Susanna
   Coppola, Vincenzo
   Tessarollo, Lino
TI RanBPM is essential for mouse spermatogenesis and oogenesis
SO DEVELOPMENT
LA English
DT Article
DE Spermatogenesis; Oogenesis; Germ cell; Meiosis; Scaffold protein;
   Sterility; Prophase I; Mouse
ID PREMATURE OVARIAN FAILURE; SYNAPTONEMAL COMPLEX; ANDROGEN RECEPTOR;
   GERM-CELLS; CHROMOSOME SYNAPSIS; MEIOTIC CHROMOSOMES; BINDING-PROTEIN;
   FEMALE GERMLINE; SEQUENCE MOTIF; MALE-FERTILITY
AB RanBPM is a recently identified scaffold protein that links and modulates interactions between cell surface receptors and their intracellular signaling pathways. RanBPM has been shown to interact with a variety of functionally unrelated proteins; however, its function remains unclear. Here, we show that RanBPM is essential for normal gonad development as both male and female RanBPM(-/-) mice are sterile. In the mutant testis there was a marked decrease in spermatogonia proliferation during postnatal development. Strikingly, the first wave of spermatogenesis was totally compromised, as seminiferous tubules of homozygous mutant animals were devoid of post-meiotic germ cells. We determined that spermatogenesis was arrested around the late pachytene-diplotene stages of prophase I; surprisingly, without any obvious defect in chromosome synapsis. Interestingly, RanBPM deletion led to a remarkably quick disappearance of all germ cell types at around one month of age, suggesting that spermatogonia stem cells are also affected by the mutation. Moreover, in chimeric mice generated with RanBPM(-/-) embryonic stem cells all mutant germ cells disappeared by 3 weeks of age suggesting that RanBPM is acting in a cell-autonomous way in germ cells. RanBPM homozygous mutant females displayed a premature ovarian failure due to a depletion of the germ cell pool at the end of prophase I, as in males. Taken together, our results highlight a crucial role for RanBPM in mammalian gametogenesis in both genders.
C1 [Puverel, Sandrine; Barrick, Colleen; Coppola, Vincenzo; Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
   [Dolci, Susanna] Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, I-00133 Rome, Italy.
   [Coppola, Vincenzo] Ohio State Univ, Dept Mol Immunol Virol & Med Genet, Columbus, OH 43210 USA.
RP Tessarollo, L (reprint author), NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM tessarol@mail.nih.gov
RI Coppola, Vincenzo/E-2917-2011; dolci, susanna/B-8363-2013; 
OI Coppola, Vincenzo/0000-0001-6163-1779; dolci,
   susanna/0000-0002-6864-3673
FU NCI, Center for Cancer Research, NIH
FX We would like to thank Drs Shyam Sharan and Esta Sterneck for helpful
   discussions; Susan Reid, Eileen Southon and Donna Butcher for excellent
   technical assistance; and Dr A. F. Parlow for performing the hormone
   measurements. This research was supported by the Intramural Research
   Program of the NCI, Center for Cancer Research, NIH. Deposited in PMC
   for release after 12 months.
NR 58
TC 18
Z9 19
U1 0
U2 3
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
   CAMBS, ENGLAND
SN 0950-1991
J9 DEVELOPMENT
JI Development
PD JUN 15
PY 2011
VL 138
IS 12
BP 2511
EP 2521
DI 10.1242/dev.062505
PG 11
WC Developmental Biology
SC Developmental Biology
GA 768CP
UT WOS:000290909400012
PM 21561988
ER

PT J
AU Kempner, ES
AF Kempner, Ellis S.
TI Direct Effects of Ionizing Radiation on Macromolecules
SO JOURNAL OF POLYMER SCIENCE PART B-POLYMER PHYSICS
LA English
DT Review
DE biopolymers; ionizing radiation; radiation; radiation damage; theory
ID ENERGY-LOSS; TARGET ANALYSIS; MOLECULAR-MASS; TEMPERATURE; SENSITIVITY;
   PROTEINS; FRAGMENTATION; INACTIVATION; DEPENDENCE; PARTICLES
AB In the dry or frozen states, macromolecules are damaged directly by interactions with ionizing radiation. As crays and high-energy electrons randomly ionize orbital electrons in their path, larger molecules are more likely to suffer an interaction with these radiations. In each interaction, energy is transferred to the struck molecule, resulting in irreversibly broken covalent bonds. There is an extensive literature describing these radiation modifications in both synthetic and biopolymers. Although many different properties are measured, there emerges a similar picture of the nature of radiation damage that is common to all macromolecules. The techniques used in study of one species may be used to resolve questions raised in the other class of macromolecules. (C) 2011 Wiley Periodicals, Inc.(+) J Polym Sci Part B: Polym Phys 49: 827-831, 2011
C1 Natl Inst Arthrit Musculoskeletal & Skin Dis, NIH, Bethesda, MD 20892 USA.
RP Kempner, ES (reprint author), Natl Inst Arthrit Musculoskeletal & Skin Dis, NIH, Bethesda, MD 20892 USA.
EM eskempner@yahoo.com
FU Intramural NIH HHS [Z99 AR999999]
NR 29
TC 9
Z9 9
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-6266
J9 J POLYM SCI POL PHYS
JI J. Polym. Sci. Pt. B-Polym. Phys.
PD JUN 15
PY 2011
VL 49
IS 12
BP 827
EP 831
DI 10.1002/polb.22250
PG 5
WC Polymer Science
SC Polymer Science
GA 766DU
UT WOS:000290762000001
PM 21643521
ER

PT J
AU Geng, H
   Du, CW
   Chen, SY
   Salerno, V
   Manfredi, C
   Hsieh, P
AF Geng, Hui
   Du, Chunwei
   Chen, Siying
   Salerno, Vincenzo
   Manfredi, Candela
   Hsieh, Peggy
TI In vitro studies of DNA mismatch repair proteins
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE DNA repair; Mismatch repair; MutS; MutL
ID NUCLEAR EXTRACTS; CELLS; MECHANISM; EXCISION
AB The ability to monitor and characterize DNA mismatch repair activity in various mammalian cells is important for understanding mechanisms involved in mutagenesis and tumorigenesis. Since mismatch repair proteins recognize mismatches containing both normal and chemically altered or damaged bases, in vitro assays must accommodate a variety of mismatches in different sequence contexts. Here we describe the construction of DNA mismatch substrates containing G:T or O(6)meG:T mismatches, the purification of recombinant native human MutS alpha (MSH2-MSH6) and MutL alpha (MLH1-PMS2) proteins, and in vitro mismatch repair and excision assays that can be adapted to study mismatch repair in nuclear extracts from mismatch repair proficient and deficient cells. Published by Elsevier Inc.
C1 [Geng, Hui; Du, Chunwei; Chen, Siying; Salerno, Vincenzo; Manfredi, Candela; Hsieh, Peggy] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Hsieh, P (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 5,Room 324,5 Mem Dr,MSC 0538, Bethesda, MD 20892 USA.
EM peggyh@intra.niddk.nih.gov
FU NIDDK
FX We thank John Hays for the gift of pUC19CPDrev and Steve Matson for
   helpful discussions regarding nicking enzymes. We are grateful to Nelson
   Chan and Guo-Min Li for helpful discussions regarding excision assays.
   Funding was provided by the Intramural Research Program of NIDDK.
NR 13
TC 8
Z9 8
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 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD JUN 15
PY 2011
VL 413
IS 2
BP 179
EP 184
DI 10.1016/j.ab.2011.02.017
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 757HZ
UT WOS:000290077400013
PM 21329650
ER

PT J
AU Yang, HP
   Gierach, GL
   Danforth, KN
   Sherman, ME
   Park, Y
   Wentzensen, N
   Hollenbeck, A
   Schatzkin, A
   Brinton, LA
AF Yang, Hannah P.
   Gierach, Gretchen L.
   Danforth, Kim N.
   Sherman, Mark E.
   Park, Yikyung
   Wentzensen, Nicolas
   Hollenbeck, Albert
   Schatzkin, Arthur
   Brinton, Louise A.
TI Alcohol and endometrial cancer risk in the NIH-AARP diet and health
   study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE alcohol; endometrial cancer; prospective study
ID POSTMENOPAUSAL WOMEN; CIGARETTE-SMOKING; LIFE-STYLE;
   NATIONAL-INSTITUTES; ESTROGEN-LEVELS; HORMONE-LEVELS; CONSUMPTION;
   COHORT; METAANALYSIS; DRINKING
AB Previous investigations have provided conflicting results regarding whether alcohol consumption affects endometrial cancer risk, although in many of these studies the highest category of alcohol intake examined was limited. Further, most were unable to resolve how alcohol associations are affected by beverage type, the presence of other endometrial cancer risk factors, or tumor characteristics. To address these issues, we prospectively evaluated the association between alcohol intake and incident endometrial cancer (n = 1,491) in a cohort of 114,414 US women enrolled in the NIH-AARP Diet and Health Study. We calculated relative risks (RR) and 95% confidence intervals (CI) using Cox proportional hazards regression. After adjustment for age, body mass index (BMI), smoking and other potential confounders, the multivariable RRs (and 95% CIs) compared with nondrinkers were 0.97 (0.87-1.09) for > 0-< 12 g of alcohol/day, 1.06 (0.87-1.31) for 12-< 24 g/day and 0.93 (0.71-1.20) for >= 24 g/day (p trend 5 0.90). There was, however, some suggestion of higher risks associated with alcohol consumption among lean women (BMI, < 25) and users of menopausal hormone therapy, with significant interactions with both parameters (respective interaction p-values of 0.002 and 0.005). The relationship was also enhanced, albeit nonsignificantly so, for low grade cancers. Our results do not support that alcohol is a strong contributor to endometrial cancer risk, but slight risk increases may prevail among some users or for selected tumor characteristics.
C1 [Yang, Hannah P.; Gierach, Gretchen L.; Danforth, Kim N.; Sherman, Mark E.; Wentzensen, Nicolas; Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD USA.
   [Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD USA.
   [Hollenbeck, Albert] AARP, Washington, DC USA.
RP Yang, HP (reprint author), NCI, 6120 Execut Blvd,EPS 5102, Rockville, MD 20852 USA.
EM yanghan@mail.nih.gov
RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016; 
OI Brinton, Louise/0000-0003-3853-8562; Gierach,
   Gretchen/0000-0002-0165-5522; Park, Yikyung/0000-0002-6281-489X
FU NIH; National Cancer Institute
FX Grant sponsors: NIH (Intramural Research Program), National Cancer
   Institute; Cancer incidence data from the Atlanta metropolitan area were
   collected by the Georgia Center for Cancer Statistics, Department of
   Epidemiology, Rollins School of Public Health, Emory University. Cancer
   incidence data from California were collected by the California
   Department of Health Services, Cancer Surveillance Section. Cancer
   incidence data from the Detroit metropolitan area were collected by the
   Michigan Cancer Surveillance Program, Community Health Administration,
   State of Michigan. The Florida cancer incidence data used in this report
   were collected by the Florida Cancer Data System under contract to the
   Department of Health (DOH). The views expressed herein are solely those
   of the authors and do not necessarily reflect those of the contractor or
   DOH. Cancer incidence data from Louisiana were collected by the
   Louisiana Tumor Registry, Louisiana State University Medical Center in
   New Orleans. Cancer incidence data from New Jersey were collected by the
   New Jersey State Cancer Registry, Cancer Epidemiology Services, New
   Jersey State Department of Health and Senior Services. Cancer incidence
   data from North Carolina were collected by the North Carolina Central
   Cancer Registry. Cancer incidence data from Pennsylvania were supplied
   by the Division of Health Statistics and Research, Pennsylvania
   Department of Health, Harrisburg, Pennsylvania. The Pennsylvania
   Department of Health specifically disclaims responsibility for any
   analyses, interpretations or conclusions. Cancer incidence data from
   Arizona were collected by the Arizona Cancer Registry, Division of
   Public Health Services, Arizona Department of Health Services. Cancer
   incidence data from Texas were collected by the Texas Cancer Registry,
   Cancer Epidemiology and Surveillance Branch, Texas Department of State
   Health Services. We are indebted to the participants in the NIH-AARP
   Diet and Health Study for their outstanding cooperation. We also thank
   Mr. Sigurd Hermansen and Ms. Kerry Grace Morrissey from Westat for study
   outcomes ascertainment and management and Ms. Leslie Carroll at
   Information Management Services for data support and analysis.
NR 40
TC 5
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUN 15
PY 2011
VL 128
IS 12
BP 2953
EP 2961
DI 10.1002/ijc.25623
PG 9
WC Oncology
SC Oncology
GA 756BO
UT WOS:000289986900021
PM 20725997
ER

PT J
AU Williams, SL
   Ferrigno, L
   Maraini, G
   Rosmini, F
   Sperduto, RD
AF Williams, Sally L.
   Ferrigno, Luigina
   Maraini, Giovanni
   Rosmini, Francesco
   Sperduto, Robert D.
TI A post-trial survey to assess the impact of dissemination of results and
   unmasking on participants in a 13-year randomised controlled trial on
   age-related cataract
SO TRIALS
LA English
DT Article
ID CLINICAL-TRIAL
AB Background: The Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract was designed to assess the impact of a multivitamin-mineral supplement on age-related cataract. Trial results showed evidence of a beneficial effect of the supplement on all types of cataract combined, opposite effects on two of the three types of cataract (beneficial for nuclear opacities and harmful for posterior sub-capsular opacities) and no statistically significant effect on cortical opacities. No treatment recommendations were made. A post-trial survey was conducted on 817 surviving elderly participants to assess their satisfaction, their understanding of treatment assignment to supplement or placebo and the success of masking.
   Methods: Trial results were communicated by letter and the level of satisfaction and of understanding of the results was assessed by a questionnaire. Participants were offered the option of being unmasked: a second questionnaire was administered to this subset to assess their understanding of the randomisation process and the success of masking.
   Results: 610 participants (74.7%) responded to the survey: 94.6% thought the description of the results was "very clear" or "quite clear", 5.4% "not clear" or "do not know"; 89.8% considered the results "very interesting" or "quite interesting", 10.2% "not interesting" or "do not know"; 60.3% expressed "satisfaction", 17.2% "both satisfaction and concern", 2.6% "concern", 19.9% "indifference" or "do not know".
   480 participants (78.7%) accepted the offer to be unmasked to their treatment assignment: 395 (82.3%) recalled/understood the possibility of assignment to vitamins or placebo, 85 (17.7%) did not. 68 participants (17.2%) thought they had taken vitamins (79.4% were correct; p = 0.0006), 47 (11.9%) thought they had taken placebo (59.6% were correct; p = 0.46) and 280 (70.9%) declared they did not know.
   Conclusions: The results were made difficult to explain to study participants by the qualitatively different effect of treatment on the two most visually significant types of cataract. Although the study did not lead to a recommendation to use the dietary supplement, the vast majority of participants reported satisfaction after they received the results but almost 20% of the participants expressed some concern. Masking to treatment assignment was successful in the majority of participants.
C1 [Williams, Sally L.; Maraini, Giovanni] Univ Parma, Sez Oftalmol, I-43126 Parma, Italy.
   [Ferrigno, Luigina; Rosmini, Francesco] Ist Super Sanita, Epidemiol & Biostat Lab, I-00161 Rome, Italy.
   [Sperduto, Robert D.] NEI, Bethesda, MD 20892 USA.
RP Williams, SL (reprint author), Univ Parma, Sez Oftalmol, Via Gramsci 14, I-43126 Parma, Italy.
EM sallylouise.williams@unipr.it
NR 16
TC 1
Z9 1
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6215
J9 TRIALS
JI Trials
PD JUN 14
PY 2011
VL 12
AR 148
DI 10.1186/1745-6215-12-148
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 792FS
UT WOS:000292726600001
PM 21672204
ER

PT J
AU Martin, D
   Galisteo, R
   Molinolo, AA
   Wetzker, R
   Hirsch, E
   Gutkind, JS
AF Martin, Daniel
   Galisteo, Rebeca
   Molinolo, Alfredo A.
   Wetzker, Reinhard
   Hirsch, Emilio
   Gutkind, J. Silvio
TI PI3K gamma Mediates Kaposi's Sarcoma-Associated Herpesvirus
   vGPCR-Induced Sarcomagenesis
SO CANCER CELL
LA English
DT Article
ID PROTEIN-COUPLED RECEPTOR; 3-KINASE GAMMA; CANCER; MTOR; PI3K;
   INFLAMMATION; INHIBITION; INFECTION; PATHWAY; KSHV
AB Angioproliferative tumors induced by the Kaposi's sarcoma-associated herpesvirus (KSHV) have been successfully treated with rapamycin, which provided direct evidence of the clinical activity of mTOR inhibitors in human malignancies. However, prolonged mTOR inhibition may raise concerns in immunocompromised patients, including AIDS-Kaposi's sarcoma (KS). Here, we explored whether KSHV oncogenes deploy cell type-specific signaling pathways activating mTOR, which could be exploited to halt KS development while minimizing immune suppressive effects. We found that PI3K gamma, a PI3K isoform exhibiting restricted tissue distribution, is strictly required for signaling from the KSHV-encoded vGPCR oncogene to Akt/mTOR. Indeed, by using an endothelial-specific gene delivery system modeling KS development, we provide genetic and pharmacological evidence that PI3K gamma may represent a suitable molecular target for therapeutic intervention in KS.
C1 [Martin, Daniel; Galisteo, Rebeca; Molinolo, Alfredo A.; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
   [Wetzker, Reinhard] Univ Jena, Jena Univ Hosp, Ctr Mol Biomed, Inst Mol Cell Biol, D-07745 Jena, Germany.
   [Hirsch, Emilio] Univ Torino, Sch Med, Ctr Biotechnol, Dept Genet Biol & Biochem, I-10126 Turin, Italy.
RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
EM sg39v@nih.gov
RI Gutkind, J. Silvio/A-1053-2009; Hirsch, Emilio/F-4848-2013
OI Hirsch, Emilio/0000-0002-9073-6024
FU National Institutes of Health; National Institute of Dental and
   Craniofacial Research
FX This research was supported by a National Institutes of Health
   Intramural AIDS Targeted Antiviral Program and the National Institute of
   Dental and Craniofacial Research. We thank M. Simaan and P.
   Amornphimoltham for their help and expert advice with the fluorescence
   microscopy studies. We apologize to colleagues whose primary research
   papers may not have been cited due to space constraints.
NR 24
TC 36
Z9 39
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
J9 CANCER CELL
JI Cancer Cell
PD JUN 14
PY 2011
VL 19
IS 6
BP 805
EP 813
DI 10.1016/j.ccr.2011.05.005
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 780FI
UT WOS:000291839500013
PM 21665152
ER

PT J
AU Tarasov, SG
   Gaponenko, V
   Howard, OMZ
   Chen, YH
   Oppenheim, JJ
   Dyba, MA
   Subramaniam, S
   Lee, Y
   Michejda, C
   Tarasova, NI
AF Tarasov, Sergey G.
   Gaponenko, Vadim
   Howard, O. M. Zack
   Chen, Yuhong
   Oppenheim, Joost J.
   Dyba, Marzena A.
   Subramaniam, Sriram
   Lee, Youngshim
   Michejda, Christopher
   Tarasova, Nadya I.
TI Structural plasticity of a transmembrane peptide allows self-assembly
   into biologically active nanoparticles
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE virus-like particles; CXCL12; cancer; undruggable target
ID RECEPTOR FUNCTION; DELIVERY-SYSTEM; DESIGN; CANCER; BISIMIDAZOACRIDONES;
   NANOTECHNOLOGY; PENETRATION; TARGETS
AB Significant efforts have been devoted to the development of nanoparticular delivering systems targeting tumors. However, clinical application of nanoparticles is hampered by insufficient size homogeneity, difficulties in reproducible synthesis and manufacturing, frequent high uptake in the liver, systemic toxicity of the carriers (particularly for inorganic nanoparticles), and insufficient selectivity for tumor cells. We have found that properly modified synthetic analogs of transmembrane domains of membrane proteins can self-assemble into remarkably uniform spherical nanoparticles with innate biological activity. Self-assembly is driven by a structural transition of the peptide that adopts predominantly a beta-hairpin conformation in aqueous solutions, but folds into an alpha-helix upon spontaneous fusion of the nanoparticles with cell membrane. A 24-amino acid peptide corresponding to the second transmembrane helix of the CXCR4 forms self-assembled particles that inhibit CXCR4 function in vitro and hamper CXCR4-dependent tumor metastasis in vivo. Furthermore, such nanoparticles can encapsulate hydrophobic drugs, thus providing a delivery system with the potential for dual biological activity.
C1 [Howard, O. M. Zack; Chen, Yuhong; Oppenheim, Joost J.; Tarasova, Nadya I.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA.
   [Tarasov, Sergey G.; Dyba, Marzena A.; Michejda, Christopher] NCI, Struct Biophys Lab, Frederick, MD 21702 USA.
   [Gaponenko, Vadim; Lee, Youngshim] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA.
   [Dyba, Marzena A.] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA.
   [Subramaniam, Sriram] NCI, Cell Biol Lab, Bethesda, MD 20892 USA.
RP Tarasova, NI (reprint author), NCI, Canc & Inflammat Program, POB B, Frederick, MD 21702 USA.
EM Nadya.Tarasova@nih.gov
RI Howard, O M Zack/B-6117-2012
OI Howard, O M Zack/0000-0002-0505-7052
FU Congressionally Directed Medical Research Program [PC08116]; NIH, NCI,
   Center for Cancer Research; NCI, NIH [HHSN26120080001E]; NIH
   [R01CA135341]
FX We thank Dr. Anil Patri and Jeffrey D. Clogston (Nanotechnology
   Characterization Laboratory, SAIC, NCI-Frederick) for the help with
   measurement of Zeta potential; Stephen Lockett and Kimberly Peifley
   (Image Analysis Laboratory, Advanced Technology Program, SAIC,
   NCI-Frederick) for the help with laser scanning confocal microscopy; and
   Kunio Nagashima (SAIC, NCI-Frederick) for transmission electron
   microscopy. This work was funded by Congressionally Directed Medical
   Research Program, Prostate Cancer Research Award PC08116 (N.I.T.); by
   the Intramural Research Program of the NIH, NCI, Center for Cancer
   Research, with federal funds from the NCI, NIH, under Contract
   HHSN26120080001E; and by NIH Grant R01CA135341 (V. G.).
NR 32
TC 17
Z9 17
U1 0
U2 25
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 14
PY 2011
VL 108
IS 24
BP 9798
EP 9803
DI 10.1073/pnas.1014598108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777DD
UT WOS:000291594000019
PM 21628584
ER

PT J
AU Ferreira, FM
   Oliveira, LC
   Germino, GG
   Onuchic, JN
   Onuchic, LF
AF Ferreira, Frederico M.
   Oliveira, Leandro C.
   Germino, Gregory G.
   Onuchic, Jose N.
   Onuchic, Luiz F.
TI Macromolecular assembly of polycystin-2 intracytosolic C-terminal domain
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID PROTEIN SECONDARY STRUCTURE; RAY SOLUTION SCATTERING;
   SMALL-ANGLE-SCATTERING; STRUCTURE-BASED MODELS; KIDNEY-DISEASE;
   GLOBULAR-PROTEINS; MOLECULAR-WEIGHT; CATION CHANNEL; CA2+ CHANNELS;
   IDENTIFICATION
AB Mutations in PKD2 are responsible for approximately 15% of the autosomal dominant polycystic kidney disease cases. This gene encodes polycystin-2, a calcium-permeable cation channel whose C-terminal intracytosolic tail (PC2t) plays an important role in its interaction with a number of different proteins. In the present study, we have comprehensively evaluated the macromolecular assembly of PC2t homooligomer using a series of biophysical and biochemical analyses. Our studies, based on a new delimitation of PC2t, have revealed that it is capable of assembling as a homotetramer independently of any other portion of the molecule. Our data support this tetrameric arrangement in the presence and absence of calcium. Molecular dynamics simulations performed with a modified all-atoms structure-based model supported the PC2t tetrameric assembly, as well as how different populations are disposed in solution. The simulations demonstrated, indeed, that the best-scored structures are the ones compatible with a fourfold oligomeric state. These findings clarify the structural properties of PC2t domain and strongly support a homotetramer assembly of PC2.
C1 [Ferreira, Frederico M.; Onuchic, Luiz F.] Univ Sao Paulo, Sch Med, Div Nephrol, BR-01246903 Sao Paulo, Brazil.
   [Ferreira, Frederico M.] Univ Sao Paulo, Sch Med, Inst Heart, Immunol Lab, BR-05403900 Sao Paulo, Brazil.
   [Oliveira, Leandro C.; Onuchic, Jose N.] Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA.
   [Germino, Gregory G.] Natl Inst Diabet Digest & Kidney Dis, Bethesda, MD 20892 USA.
RP Ferreira, FM (reprint author), Univ Sao Paulo, Sch Med, Div Nephrol, BR-01246903 Sao Paulo, Brazil.
EM ferreirafm@lim12.fm.usp.br; jonuchic@ucsd.edu; lonuchic@usp.br
RI Oliveira, Leandro /F-8638-2012; Onuchic, Luiz/H-1589-2012; Ferreira,
   Frederico /A-4622-2013; 
OI Oliveira, Leandro /0000-0002-6932-6792; Germino,
   Gregory/0000-0002-3609-5588
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
   INCT-INBEQMeDI; Brazilian agency Fundacao de Amparo a Pesquisa do Estado
   de Sao Paulo (FAPESP) [2006/03098-8]; LIMs of University of Sao Paulo
   School of Medicine; Clinical Core Center [National Institutes of Health
   (NIH)] [P30 DK090868]; CNPq; National Science Foundation (NSF)
   [PHY-0822283, MCB-1051438]
FX We thank Glaucius Oliva for financial support [Conselho Nacional de
   Desenvolvimento Cientifico e Tecnologico (CNPq) INCT-INBEQMeDI] and
   access to his laboratory. We thank Hannes Fischer for valuable
   discussion and manuscript revision; Andressa P. A. Pinto for excellent
   technical support; and Paul C. Whitford for helpful suggestions on
   modeling. This work was mainly supported by Brazilian agency Fundacao de
   Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) Grant 2006/03098-8 (F.
   M. F. and L.F.O.) and LIMs of University of Sao Paulo School of
   Medicine. Additional support was provided by The Johns Hopkins
   Polycystic Kidney Disease (PKD) Research and Clinical Core Center
   [National Institutes of Health (NIH) P30 DK090868]. L.C.O. was partially
   supported by CNPq. Work in San Diego was supported in part by the Center
   for Theoretical Biological Physics sponsored by the National Science
   Foundation (NSF) Grant PHY-0822283 and NSF Grant MCB-1051438.
NR 43
TC 5
Z9 5
U1 0
U2 5
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUN 14
PY 2011
VL 108
IS 24
BP 9833
EP 9838
DI 10.1073/pnas.1106766108
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777DD
UT WOS:000291594000025
PM 21622852
ER

PT J
AU Miller, Y
   Ma, BY
   Nussinov, R
AF Miller, Yifat
   Ma, Buyong
   Nussinov, Ruth
TI Synergistic Interactions between Repeats in Tau Protein and A beta
   Amyloids May Be Responsible for Accelerated Aggregation via Polymorphic
   States
SO BIOCHEMISTRY
LA English
DT Article
ID MICROTUBULE-BINDING DOMAIN; PAIRED HELICAL FILAMENTS; TRIPLE-TRANSGENIC
   MODEL; PARTICLE MESH EWALD; ALZHEIMERS-DISEASE; MOLECULAR-DYNAMICS;
   FRONTOTEMPORAL DEMENTIA; IN-VITRO; MITOCHONDRIAL DYSFUNCTION;
   NEUROFIBRILLARY TANGLES
AB Amyloid plaques and neurofibrillary tangles simultaneously accumulate in Alzheimer's disease (AD). It is known that A beta and tau exist together in the mitochondria; however, the interactions between A beta oligomers and tau are controversial. Moreover, it is still unclear which specific domains in the tau protein can interact with A beta oligomers and what could be the effect of these interactions. Herein, we examine three different A beta-tau oligomeric complexes. These complexes present interactions of A beta with three domains in the tau protein; all contain high beta-structure propensity in their R2, R3, and R4 repeats. Our results show that, among these, A beta oligomers are likely to interact with the R2 domain to form a stable complex with better alignment in the turn region and the beta-structure domain. We therefore propose that the R2 domain can interact with soluble A beta oligomers and consequently promote aggregation. EM and AFM images and dimensions revealed highly polymorphic tau aggregates. We suggest that the polymorphic tau and A beta-tau aggregates may be largely due to repeat sequences which are prone to variable turn locations along the tau repeats.
C1 [Ma, Buyong; Nussinov, Ruth] NCI Frederick, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
   [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Ma, BY (reprint author), NCI Frederick, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA.
EM mabuyong@mail.nih.gov; ruthnu@helix.nih.gov
RI Ma, Buyong/F-9491-2011
OI Ma, Buyong/0000-0002-7383-719X
FU National Cancer Institute, National Institutes of Health
   [HHSN261200800001E]; 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 HHSN261200800001E. This research was supported (in part) by the
   Intramural Research Program of the NIH, National Cancer Institute,
   Center for Cancer Research.
NR 78
TC 45
Z9 47
U1 0
U2 26
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUN 14
PY 2011
VL 50
IS 23
BP 5172
EP 5181
DI 10.1021/bi200400u
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 773FJ
UT WOS:000291292100009
PM 21506544
ER

PT J
AU Prasad, MK
   Reed, X
   Gorkin, DU
   Cronin, JC
   McAdow, AR
   Chain, K
   Hodonsky, CJ
   Jones, EA
   Svaren, J
   Antonellis, A
   Johnson, SL
   Loftus, SK
   Pavan, WJ
   McCallion, AS
AF Prasad, Megana K.
   Reed, Xylena
   Gorkin, David U.
   Cronin, Julia C.
   McAdow, Anthony R.
   Chain, Kristopher
   Hodonsky, Chani J.
   Jones, Erin A.
   Svaren, John
   Antonellis, Anthony
   Johnson, Stephen L.
   Loftus, Stacie K.
   Pavan, William J.
   McCallion, Andrew S.
TI SOX10 directly modulates ERBB3 transcription via an intronic neural
   crest enhancer
SO BMC DEVELOPMENTAL BIOLOGY
LA English
DT Article
ID FACTOR AP-2; HIRSCHSPRUNG-DISEASE; MOUSE MODEL; MELANOCYTE DEVELOPMENT;
   CELL-LINES; EXPRESSION; ZEBRAFISH; HEREGULIN; MICE; GENE
AB Background: The ERBB3 gene is essential for the proper development of the neural crest (NC) and its derivative populations such as Schwann cells. As with all cell fate decisions, transcriptional regulatory control plays a significant role in the progressive restriction and specification of NC derived lineages during development. However, little is known about the sequences mediating transcriptional regulation of ERBB3 or the factors that bind them.
   Results: In this study we identified three transcriptional enhancers at the ERBB3 locus and evaluated their regulatory potential in vitro in NC-derived cell types and in vivo in transgenic zebrafish. One enhancer, termed ERBB3_MCS6, which lies within the first intron of ERBB3, directs the highest reporter expression in vitro and also demonstrates epigenetic marks consistent with enhancer activity. We identify a consensus SOX10 binding site within ERBB3_MCS6 and demonstrate, in vitro, its necessity and sufficiency for the activity of this enhancer. Additionally, we demonstrate that transcription from the endogenous Erbb3 locus is dependent on Sox10. Further we demonstrate in vitro that Sox10 physically interacts with that ERBB3_MCS6. Consistent with its in vitro activity, we also show that ERBB3_MCS6 drives reporter expression in NC cells and a subset of its derivative lineages in vivo in zebrafish in a manner consistent with erbb3b expression. We also demonstrate, using morpholino analysis, that Sox10 is necessary for ERBB3_MCS6 expression in vivo in zebrafish.
   Conclusions: Taken collectively, our data suggest that ERBB3 may be directly regulated by SOX10, and that this control may in part be facilitated by ERBB3_MCS6.
C1 [Prasad, Megana K.; Reed, Xylena; Gorkin, David U.; McCallion, Andrew S.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
   [Cronin, Julia C.; Loftus, Stacie K.; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
   [McAdow, Anthony R.; Chain, Kristopher; Johnson, Stephen L.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
   [Hodonsky, Chani J.; Antonellis, Anthony] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA.
   [Antonellis, Anthony] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI 48109 USA.
   [Jones, Erin A.] Univ Wisconsin, Program Cellular & Mol Biol, Madison, WI 53705 USA.
   [Svaren, John] Univ Wisconsin, Dept Comparat Biosci, Madison, WI 53705 USA.
   [McCallion, Andrew S.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA.
RP McCallion, AS (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
EM andy@jhmi.edu
OI Svaren, John/0000-0003-2963-7921
FU NIH/NIGMS; NIH/NINDS [GM071648, NS062972, NS073748]; NIGMS [GM056988];
   NIH [HD41590]
FX The authors would like to thank the Avramopoulos lab for their kind gift
   of Neuro2A cells and Seneca Bessling for her help with zebrafish
   husbandry. We would also like to thank Zachary Stine for critical
   scientific discussion and reading of the manuscript and also Grzegorz
   Burzynski for critical reading of the manuscript. Funding for this work
   comes from NIH/NIGMS and NIH/NINDS grants to ASM (GM071648 and
   NS062972), a NIGMS grant to SJ (GM056988), a NIH grant to JS (HD41590),
   a NIH/NINDS grant to AA (NS073748) and intramural NIH grants to WJP.
NR 51
TC 24
Z9 24
U1 2
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-213X
J9 BMC DEV BIOL
JI BMC Dev. Biol.
PD JUN 14
PY 2011
VL 11
AR 40
DI 10.1186/1471-213X-11-40
PG 14
WC Developmental Biology
SC Developmental Biology
GA 784EB
UT WOS:000292136700001
PM 21672228
ER

PT J
AU Kumar, A
   Cookson, MR
AF Kumar, Azad
   Cookson, Mark R.
TI Role of LRRK2 kinase dysfunction in Parkinson disease
SO EXPERT REVIEWS IN MOLECULAR MEDICINE
LA English
DT Review
ID AUTOSOMAL-DOMINANT PARKINSONISM; NORTH-AFRICAN FAMILIES; G2019S
   MUTATION; DOPAMINERGIC-NEURONS; ALPHA-SYNUCLEIN;
   LEUCINE-RICH-REPEAT-KINASE-2 LRRK2; CYTOPLASMIC LOCALIZATION;
   CAENORHABDITIS-ELEGANS; R1441C MUTATION; COMMON FOUNDER
AB Parkinson disease is a common and usually sporadic neurodegenerative disorder. However, a subset of cases are inherited and, of these, mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) are the most frequent genetic cause of disease. Here, we will discuss recent progress in understanding how LRRK2 mutations lead to disease and how this might have therapeutic implications. The effect of mutations on LRRK2 enzyme function provides clues as to which functions of the protein are important to disease. Recent work has focused on the kinase and GTP-binding domains of LRRK2, and it is assumed that these will be therapeutically important, although there is a substantial amount of work to be done to address this hypothesis.
C1 [Kumar, Azad; Cookson, Mark R.] NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, NIH, 35 Convent Dr, Bethesda, MD 20892 USA.
EM cookson@mail.nih.gov
FU NIH, National Institute on Aging
FX This research was supported by the Intramural Research Program of the
   NIH, National Institute on Aging. The authors thank the reviewers for
   their helpful and critical comments.
NR 99
TC 12
Z9 12
U1 1
U2 5
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 JUN 13
PY 2011
VL 13
AR 13
DI 10.1017/S146239941100192X
PG 12
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 777IX
UT WOS:000291610200001
PM 21676337
ER

PT J
AU Miura, K
   Perera, S
   Brockley, S
   Zhou, H
   Aebig, JA
   Moretz, SE
   Miller, LH
   Doumbo, OK
   Sagara, I
   Dicko, A
   Ellis, RD
   Long, CA
AF Miura, Kazutoyo
   Perera, Suwani
   Brockley, Sarah
   Zhou, Hong
   Aebig, Joan A.
   Moretz, Samuel E.
   Miller, Louis H.
   Doumbo, Ogobara K.
   Sagara, Issaka
   Dicko, Alassane
   Ellis, Ruth D.
   Long, Carole A.
TI Non-Apical Membrane Antigen 1 (AMA1) IgGs from Malian Children Interfere
   with Functional Activity of AMA1 IgGs as Judged by Growth Inhibition
   Assay
SO PLOS ONE
LA English
DT Article
ID MALARIA VACCINE CANDIDATE; PLASMODIUM-FALCIPARUM MALARIA; MEROZOITE
   SURFACE PROTEIN-1; RANDOMIZED CONTROLLED-TRIAL; BLOOD-STAGE VACCINE;
   ERYTHROCYTE INVASION; BLOCKING ANTIBODIES; PROTECTION; PHASE-1;
   IMMUNOGENICITY
AB Background: Apical membrane antigen 1 (AMA1) is one of the best-studied blood-stage malaria vaccine candidates. When an AMA1 vaccine was tested in a malaria naive population, it induced functionally active antibodies judged by Growth Inhibition Assay (GIA). However, the same vaccine failed to induce higher growth-inhibitory activity in adults living in a malaria endemic area. Vaccination did induce functionally active antibodies in malaria-exposed children with less than 20% inhibition in GIA at baseline, but not in children with more than that level of baseline inhibition.
   Methods: Total IgGs were purified from plasmas collected from the pediatric trial before and after immunization and pools of total IgGs were made. Another set of total IgGs was purified from U.S. adults immunized with AMA1 (US-total IgG). From these total IgGs, AMA1-specific and non-AMA1 IgGs were affinity purified and the functional activity of these IgGs was evaluated by GIA. Competition ELISA was performed with the U.S.-total IgG and non-AMA1 IgGs from malaria-exposed children.
   Results: AMA1-specific IgGs from malaria-exposed children and U.S. vaccinees showed similar growth-inhibitory activity at the same concentrations. When mixed with U. S.-total IgG, non-AMA1 IgGs from children showed an interference effect in GIA. Interestingly, the interference effect was higher with non-AMA1 IgGs from higher titer pools. The non-AMA1 IgGs did not compete with anti-AMA1 antibody in U.S.-total IgG in the competition ELISA.
   Conclusion: Children living in a malaria endemic area have a fraction of IgGs that interferes with the biological activity of anti-AMA1 antibody as judged by GIA. While the mechanism of interference is not resolved in this study, these results suggest it is not caused by direct competition between non-AMA1 IgG and AMA1 protein. This study indicates that anti-malaria IgGs induced by natural exposure may interfere with the biological effect of antibody induced by an AMA1-based vaccine in the target population.
C1 [Miura, Kazutoyo; Zhou, Hong; Moretz, Samuel E.; Miller, Louis H.; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
   [Miura, Kazutoyo; Perera, Suwani; Brockley, Sarah; Aebig, Joan A.; Miller, Louis H.; Ellis, Ruth D.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA.
   [Doumbo, Ogobara K.; Sagara, Issaka; Dicko, Alassane] Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali.
RP Miura, K (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
EM kmiura@niaid.nih.gov; clong@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases/NIH; Malaria
   Vaccine Initiative/PATH
FX This study was supported by the intramural program of the National
   Institute of Allergy and Infectious Diseases/NIH and the GIA Reference
   Center was supported by the Malaria Vaccine Initiative/PATH. The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 49
TC 6
Z9 6
U1 0
U2 0
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 JUN 13
PY 2011
VL 6
IS 6
AR e20947
DI 10.1371/journal.pone.0020947
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777ZG
UT WOS:000291663300030
PM 21695140
ER

PT J
AU Chen, M
   Nemechek, NM
   Mema, E
   Wang, J
   Weinstein, LS
AF Chen, Min
   Nemechek, Nicholas M.
   Mema, Eralda
   Wang, Jie
   Weinstein, Lee S.
TI Effects of deficiency of the G protein G(s)alpha on energy and glucose
   homeostasis
SO EUROPEAN JOURNAL OF PHARMACOLOGY
LA English
DT Review
DE G protein; Genomic imprinting; Obesity; Insulin resistance; Sympathetic
   nervous system; Melanocortin
ID XL-ALPHA-S; PSEUDOHYPOPARATHYROIDISM TYPE IB; ALBRIGHT HEREDITARY
   OSTEODYSTROPHY; CENTRAL MELANOCORTIN SYSTEM; DIET-INDUCED THERMOGENESIS;
   CENTRAL-NERVOUS-SYSTEM; HUMAN GNAS1 GENE; BODY-MASS INDEX;
   INSULIN-RESISTANCE; ADIPOSE-TISSUE
AB G(s)alpha is a ubiquitously expressed G protein alpha-subunit that couples receptors to the generation of intracellular cyclic AMP. The G(s)alpha gene GNAS is a complex gene that undergoes genomic imprinting, an epigenetic phenomenon that leads to differential expression from the two parental alleles. G(s)alpha is imprinted in a tissue-specific manner, being expressed primarily from the maternal allele in a small number of tissues. Albright hereditary osteodystrophy is a monogenic obesity disorder caused by heterozygous G(s)alpha mutations but only when the mutations are maternally inherited. Studies in mice indicate a similar parent-of-origin effect on energy and glucose metabolism, with maternal but not paternal mutations leading to obesity, reduced sympathetic nerve activity and energy expenditure, glucose intolerance and insulin resistance, with no primary effect on food intake. These effects result from G(s)alpha imprinting leading to severe G(s)alpha deficiency in one or more regions of the central nervous system, and are associated with a specific defect in melanocortins to stimulate sympathetic nerve activity and energy expenditure. Published by Elsevier B.V.
C1 [Chen, Min; Nemechek, Nicholas M.; Mema, Eralda; Wang, Jie; Weinstein, Lee S.] NIDDKD, Signal Transduct Sect, NIH, Bethesda, MD 20892 USA.
RP Chen, M (reprint author), NIDDKD, Signal Transduct Sect, NIH, Bethesda, MD 20892 USA.
EM minc@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
   National Institutes of Health, U.S. Department of Health and Human
   Services
FX This work was supported by the Intramural Research Program of the
   National Institute of Diabetes and Digestive and Kidney Diseases of the
   National Institutes of Health, U.S. Department of Health and Human
   Services.
NR 90
TC 8
Z9 9
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-2999
J9 EUR J PHARMACOL
JI Eur. J. Pharmacol.
PD JUN 11
PY 2011
VL 660
IS 1
SI SI
BP 119
EP 124
DI 10.1016/j.ejphar.2010.10.105
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 772KG
UT WOS:000291232200015
PM 21208600
ER

PT J
AU Zhou, Y
   Yi, T
   Park, SS
   Chadwick, W
   Shen, RF
   Wu, WW
   Martin, B
   Maudsley, S
AF Zhou, Yu
   Yi, Tie
   Park, Sung-Soo
   Chadwick, Wayne
   Shen, Rong-Fong
   Wu, Wells W.
   Martin, Bronwen
   Maudsley, Stuart
TI Rapid and enhanced proteolytic digestion using electric-field-oriented
   enzyme reactor
SO JOURNAL OF PROTEOMICS
LA English
DT Article
DE Enzyme reactor; Rapid digestion; Membrane proteins; Lipid rafts;
   Neurotransmission; Bioinformatics data extraction
ID SPECTROMETRY-BASED PROTEOMICS; MASS-SPECTROMETRY; MEMBRANE-PROTEINS;
   LIQUID-CHROMATOGRAPHY; SURFACES; GEL
AB We have created a novel enzyme reactor using electric field-mediated orientation and immobilization of proteolytic enzymes (trypsin/chymotrypsin) on biocompatible PVDF membranes in a continuous flow-through chamber. Using less than 5 min, this reactor in various enzyme combinations can produce enhanced rapid digestion for standardized prototypic proteins, hydrophilic proteins and hydrophobic transmembrane proteins when compared to in-solution techniques. With improved digestive efficiency, our reactor improved the overall functional analysis of lipid raft proteomes by identifying more closely functionally linked proteins and elucidated a richer set of biological processes and pathways linked to the proteins,than traditional in-solution methods. Published by Elsevier B.V.
C1 [Zhou, Yu; Park, Sung-Soo; Chadwick, Wayne; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Neurosci Lab, Biomed Res Ctr, Baltimore, MD 21224 USA.
   [Yi, Tie; Wu, Wells W.; Martin, Bronwen] NIA, Metab Unit, Lab Clin Investigat, Biomed Res Ctr, Baltimore, MD 21224 USA.
   [Shen, Rong-Fong; Wu, Wells W.] NIA, Prote Core Unit, Res Resources Branch, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, Neurosci Lab, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM maudsleyst@mail.nih.gov
RI Zhou, Yu/M-7975-2014
FU NIH, National Institute on Aging
FX This work was supported entirely by the Intramural Research Program of
   the NIH, National Institute on Aging.
NR 24
TC 15
Z9 15
U1 0
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-3919
J9 J PROTEOMICS
JI J. Proteomics
PD JUN 10
PY 2011
VL 74
IS 7
BP 1030
EP 1035
DI 10.1016/j.jprot.2011.02.007
PG 6
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 788JE
UT WOS:000292440400014
PM 21338726
ER

PT J
AU Mi, LX
   Xiao, Z
   Veenstra, TD
   Chung, FL
AF Mi, Lixin
   Xiao, Zhen
   Veenstra, Timothy D.
   Chung, Fung-Lung
TI Proteomic identification of binding targets of isothiocyanates: A
   perspective on techniques
SO JOURNAL OF PROTEOMICS
LA English
DT Review
DE Isothiocyanates; Proteomics; Mass spectrometry; Target identification;
   Covalent modification
ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; MIGRATION INHIBITORY FACTOR; HEPATIC
   PROTEIN TARGETS; PHENETHYL ISOTHIOCYANATE; CANCER CELLS; CHEMOPREVENTIVE
   AGENTS; REACTIVE METABOLITES; MASS-SPECTROMETRY; LUNG-CANCER; IN-VIVO
AB Intake of cruciferous vegetable is inversely associated with the risk of several cancer types. Isothiocyanates (ITCs) are believed to be important constituents contributing to these cancer-preventive effects. Although several mechanisms, including induction of apoptosis, have been proposed for the anti-carcinogenesis activities of ITCs, detailed upstream triggering events are still not fully understood. Identification of ITC binding targets in cellular proteins is crucial for not only mechanistic studies but also future drug screening and design. In this review, we summarize recent progress in discovery of ITC protein targets from a technical perspective. The advantages and limitations of each method are discussed to facilitate future studies on target discovery of ITCs and perhaps other compounds. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Mi, Lixin; Chung, Fung-Lung] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA.
   [Xiao, Zhen; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Mi, LX (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, 3800 Reservoir Rd,LL 128A,Box 571465, Washington, DC 20057 USA.
EM lm293@georgetown.edu
FU National Institutes of Health through the National Cancer Institute
   [CA100853]
FX This work is supported by National Institutes of Health Grant CA100853
   through the National Cancer Institute (to F.-L. C.).
NR 38
TC 7
Z9 7
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-3919
J9 J PROTEOMICS
JI J. Proteomics
PD JUN 10
PY 2011
VL 74
IS 7
BP 1036
EP 1044
DI 10.1016/j.jprot.2011.04.015
PG 9
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 788JE
UT WOS:000292440400015
PM 21555001
ER

PT J
AU Miskinyte, S
   Butler, MG
   Herve, D
   Sarret, C
   Nicolino, M
   Petralia, JD
   Bergametti, F
   Arnould, M
   Pham, VN
   Gore, AV
   Spengos, K
   Gaza, S
   Woimant, F
   Steinberg, GK
   Weinstein, BM
   Tournier-Lasserve, E
AF Miskinyte, Snaigune
   Butler, Matthew G.
   Herve, Dominique
   Sarret, Catherine
   Nicolino, Marc
   Petralia, Jacob D.
   Bergametti, Francoise
   Arnould, Minh
   Pham, Van N.
   Gore, Aniket V.
   Spengos, Konstantinos
   Gaza, Steven
   Woimant, France
   Steinberg, Gary K.
   Weinstein, Brant M.
   Tournier-Lasserve, Elisabeth
TI Loss of BRCC3 Deubiquitinating Enzyme Leads to Abnormal Angiogenesis and
   Is Associated with Syndromic Moyamoya
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID T-CELL PROLIFERATIONS; DISEASE GENE; ZEBRAFISH; EXPRESSION; COMPLEX;
   MTCP-1; LOCUS
AB Moyamoya is a cerebrovascular angiopathy characterized by a progressive stenosis of the terminal part of the intracranial carotid arteries and the compensatory development of abnormal and fragile collateral vessels, also called moyamoya vessels, leading to ischemic and hemorrhagic stroke. Moyamoya angiopathy can either be the sole manifestation of the disease (moyamoya disease) or be associated with various conditions, including neurofibromatosis, Down syndrome, TAAD (autosomal-dominant thoracic aortic aneurysm), and radiotherapy of head tumors (moyamoya syndromes). Its prevalence is ten times higher in Japan than in Europe, and an estimated 6%-12% of moyamoya disease is familial in Japan. The pathophysiological mechanisms of this condition remain obscure. Here, we report on three unrelated families affected with an X-linked moyamoya syndrome characterized by the association of a moyamoya angiopathy, short stature, and a stereotyped facial dysmorphism. Other symptoms include an hypergonadotropic hypogonadism, hypertension, dilated cardiomyopathy, premature coronary heart disease, premature hair graying, and early bilateral acquired cataract. We show that this syndromic moyamoya is caused by Xq28 deletions removing MTCP1/MTCP1NB and BRCC3. We also show that brcc3 morphant zebrafish display angiogenesis defects that are rescued by endothelium-specific expression of brcc3. Altogether, these data strongly suggest that BRCC3, a deubiquitinating enzyme that is part of the cellular BRCA1 and BRISC complexes, is an important player in angiogenesis and that BRCC3 loss-of-function mutations are associated with moyamoya angiopathy.
C1 [Miskinyte, Snaigune; Bergametti, Francoise; Arnould, Minh; Tournier-Lasserve, Elisabeth] Univ Paris 07, INSERM, UMR S 740, F-75010 Paris, France.
   [Butler, Matthew G.; Pham, Van N.; Gore, Aniket V.; Weinstein, Brant M.] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
   [Herve, Dominique; Woimant, France] Grp Hosp Lariboisiere St Louis, AP HP, Serv Neurol, Ctr Reference Malad Vasculaires Rares Cerveau & O, F-75010 Paris, France.
   [Sarret, Catherine] Hosp Civils Lyon, Hop Femme Mere Enfant, Serv Neurol Pediat, Grp Hosp Est, F-69677 Bron, France.
   [Nicolino, Marc] Univ Lyon 1, Lyon Univ Pediat Hosp, Ctr Invest Clin 201, Div Pediat Endocrinol,Hosp Civiels Lyon,INSERM U, Lyon, France.
   [Petralia, Jacob D.; Steinberg, Gary K.] Stanford Univ, Sch Med, Stanford Stroke Ctr, Dept Neurosurg, Stanford, CA 94305 USA.
   [Petralia, Jacob D.; Steinberg, Gary K.] Stanford Univ, Sch Med, Stanford Inst Neuroinnovat & Translat Neuro Sci, Stanford, CA 94305 USA.
   [Spengos, Konstantinos] Univ Athens, Sch Med, Eginit Hosp, Dept Neurol 1, Athens 11528, Greece.
   [Gaza, Steven] Hosp Univ Nord, Hop Bichat, AP HP, Plateforme Genom Constitut Grp, F-75010 Paris, France.
   [Tournier-Lasserve, Elisabeth] Hosp Lariboisiere St Louis, AP HP, Ctr Reference Malad Vasc Rares Cerveau & Oeil, Lab Genet, F-75010 Paris, France.
RP Tournier-Lasserve, E (reprint author), Univ Paris 07, INSERM, UMR S 740, 7 Denis Diderot,10 Ave Verdun, F-75010 Paris, France.
EM tournier-lasserve@univ-paris-diderot.fr
FU INSERM; Leducq Foundation; Foundation Leducq Transatlantic Network of
   Excellence; Eunice Kenndy Shriver National Institute of Child Health and
   Human Development (NICHD); Huber Family Moyamoya Fund
FX Research was supported by the INSERM and the Leducq Foundation (grant to
   E.T.L. and B.M.W.), Foundation Leducq Transatlantic Network of
   Excellence (07 CVD 02 Hemorrhagic Stroke), the intramural program of the
   Eunice Kenndy Shriver National Institute of Child Health and Human
   Development (NICHD; to B.M.W.), and the Huber Family Moyamoya Fund
   (G.K.S.).
NR 37
TC 33
Z9 34
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUN 10
PY 2011
VL 88
IS 6
BP 718
EP 728
DI 10.1016/j.ajhg.2011.04.017
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 779HK
UT WOS:000291768500004
PM 21596366
ER

PT J
AU Wright, EMMB
   Spencer, HL
   Daly, SB
   Manson, FDC
   Zeef, LAH
   Urquhart, J
   Zoppi, N
   Bonshek, R
   Tosounidis, I
   Mohan, M
   Madden, C
   Dodds, A
   Chandler, KE
   Banka, S
   Au, L
   Clayton-Smith, J
   Khan, N
   Biesecker, LG
   Wilson, M
   Rohrbach, M
   Colombi, M
   Giunta, C
   Black, GCM
AF Wright, Emma M. M. Burkitt
   Spencer, Helen L.
   Daly, Sarah B.
   Manson, Forbes D. C.
   Zeef, Leo A. H.
   Urquhart, Jill
   Zoppi, Nicoletta
   Bonshek, Richard
   Tosounidis, Ioannis
   Mohan, Meyyammai
   Madden, Colm
   Dodds, Annabel
   Chandler, Kate E.
   Banka, Siddharth
   Au, Leon
   Clayton-Smith, Jill
   Khan, Naz
   Biesecker, Leslie G.
   Wilson, Meredith
   Rohrbach, Marianne
   Colombi, Marina
   Giunta, Cecilia
   Black, Graeme C. M.
TI Mutations in PRDM5 in Brittle Cornea Syndrome Identify a Pathway
   Regulating Extracellular Matrix Development and Maintenance
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID SYNDROME TYPE-VI; KYPHOSCOLIOTIC TYPE; CROSS-LINKS; COLLAGEN; GENE;
   THICKNESS; FAMILY; ABNORMALITIES; FIBROBLASTS; INTEGRIN
AB Extreme corneal fragility and thinning, which have a high risk of catastrophic spontaneous rupture, are the cardinal features of brittle cornea syndrome (BCS), an autosomal-recessive generalized connective tissue disorder. Enucleation is frequently the only management option for this condition, resulting in blindness and psychosocial distress. Even when the cornea remains grossly intact, visual function could also be impaired by a high degree of myopia and keratoconus. Deafness is another common feature and results in combined sensory deprivation. Using autozygosity mapping, we identified mutations in PRDM5 in families with BCS. We demonstrate that regulation of expression of extracellular matrix components, particularly fibrillar collagens, by PRDM5 is a key molecular mechanism that underlies corneal fragility in BCS and controls normal corneal development and maintenance. ZNF469, encoding a zinc finger protein of hitherto undefined function, has been identified as a quantitative trait locus for central corneal thickness, and mutations in this gene have been demonstrated in Tunisian Jewish and Palestinian kindreds with BCS. We show that ZNF469 and PRDM5, two genes that when mutated cause BCS, participate in the same regulatory pathway.
C1 [Wright, Emma M. M. Burkitt; Spencer, Helen L.; Daly, Sarah B.; Manson, Forbes D. C.; Urquhart, Jill; Chandler, Kate E.; Banka, Siddharth; Clayton-Smith, Jill; Khan, Naz; Black, Graeme C. M.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester Biomed Res Ctr, Genet Med Res Grp, Manchester M13 9WL, Lancs, England.
   [Wright, Emma M. M. Burkitt; Spencer, Helen L.; Daly, Sarah B.; Manson, Forbes D. C.; Urquhart, Jill; Chandler, Kate E.; Banka, Siddharth; Clayton-Smith, Jill; Khan, Naz; Black, Graeme C. M.] St Marys Hosp, Cent Manchester Fdn Trust, Manchester M13 9WL, Lancs, England.
   [Zeef, Leo A. H.] Univ Manchester, Fac Life Sci, Manchester M13 9PL, Lancs, England.
   [Zoppi, Nicoletta; Colombi, Marina] Univ Brescia, Fac Med, Div Biol & Genet, Dept Biomed Sci & Biotechnol, I-25123 Brescia, Italy.
   [Bonshek, Richard; Au, Leon] Manchester Royal Eye Hosp, Cent Manchester Fdn Trust, Manchester M13 9WL, Lancs, England.
   [Bonshek, Richard; Tosounidis, Ioannis] Manchester Royal Infirm, Cent Manchester Fdn Trust, Natl Specialist Ophthalm Pathol Lab, Manchester M13 9WL, Lancs, England.
   [Mohan, Meyyammai] Royal Blackburn Hosp, Dept Ophthalmol, Blackburn BB2 3HH, Lancs, England.
   [Madden, Colm] Moss Side Hlth Ctr, Dept Paediat Audiol, Manchester M14 4GP, Lancs, England.
   [Dodds, Annabel] St Peters Ctr, Dept Audiol, Burnley BB11 2DL, Lancs, England.
   [Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20814 USA.
   [Biesecker, Leslie G.] Natl Inst Hlth Intramural Sequencing Ctr NISC, NIH, Rockville, MD 20892 USA.
   [Wilson, Meredith] Childrens Hosp, Dept Clin Genet, Westmead Sydney, NSW 2145, Australia.
   [Rohrbach, Marianne; Giunta, Cecilia] Univ Childrens Hosp, Div Metab, Connect Tissue Unit, CH-8032 Zurich, Switzerland.
   [Rohrbach, Marianne; Giunta, Cecilia] Childrens Res Ctr, CH-8032 Zurich, Switzerland.
RP Black, GCM (reprint author), Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester Biomed Res Ctr, Genet Med Res Grp, Manchester M13 9WL, Lancs, England.
EM graeme.black@manchester.ac.uk
RI Manson, Forbes/G-2222-2015; Urquhart, Jill/G-2282-2015; 
OI Giunta, Cecilia/0000-0002-9313-8257; Rohrbach,
   Marianne/0000-0002-4013-6012; Manson, Forbes/0000-0002-8342-660X;
   Urquhart, Jill/0000-0002-5788-5511; Colombi, Marina/0000-0002-3105-5990;
   Banka, Siddharth/0000-0002-8527-2210; Black, Graeme/0000-0001-8727-6592
FU UK National Institute for Health Research; Wellcome Trust; Fight for
   Sight; National Human Genome Research Institute of the National
   Institutes of Health
FX We thank all healthcare professionals contributing to the care of the
   families described here, particularly R.W. Paton (Royal Black-burn
   Hospital), and J. Teer of the National Human Genome Research Institute,
   for sequence coverage analysis in the ClinSeq cohort. We thank B.
   Steinmann for useful discussion and support, H. Al-Hussein for referral
   of some BCS families, and A. Schwarze and C. Burer for expert technical
   assistance. The support of the Manchester Biomedical Research Centre,
   funded by the UK National Institute for Health Research, is gratefully
   acknowledged. E.B.W. is funded by a Clinical Research Training
   Fellowship from the Wellcome Trust, and F.D.C.M. by Fight for Sight. The
   NISC comparative sequencing program and the ClinSeq study are funded by
   the National Human Genome Research Institute of the National Institutes
   of Health.
NR 26
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U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUN 10
PY 2011
VL 88
IS 6
BP 767
EP 777
DI 10.1016/j.ajhg.2011.05.007
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 779HK
UT WOS:000291768500008
ER

PT J
AU Cullinane, AR
   Curry, JA
   Carmona-Rivera, C
   Summers, CG
   Ciccone, C
   Cardillo, ND
   Dorward, H
   Hess, RA
   White, JG
   Adams, D
   Huizing, M
   Gahl, WA
AF Cullinane, Andrew R.
   Curry, James A.
   Carmona-Rivera, Carmelo
   Summers, C. Gail
   Ciccone, Carla
   Cardillo, Nicholas D.
   Dorward, Heidi
   Hess, Richard A.
   White, James G.
   Adams, David
   Huizing, Marjan
   Gahl, William A.
TI A BLOC-1 Mutation Screen Reveals that PLDN Is Mutated in
   Hermansky-Pudlak Syndrome Type 9
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID LYSOSOME-RELATED ORGANELLES; PROTEIN TRAFFICKING; COMPLEX; GENE;
   BIOGENESIS; MELANOSOMES; ENDOSOMES; DYSBINDIN; NONSENSE; PALLIDIN
AB Hermansky-Pudlak Syndrome (HPS) is an autosomal-recessive condition characterized by oculocutaneous albinism and a bleeding diathesis due to absent platelet delta granules. HPS is a genetically heterogeneous disorder of intracellular vesicle biogenesis. We first screened all our patients with HPS-like symptoms for mutations in the genes responsible for HPS-1 through HPS-6 and found no functional mutations in 38 individuals. We then examined all eight genes encoding the biogenesis of lysosome-related organelles complex-1, or BLOC-1, proteins in these individuals. This identified a homozygous nonsense mutation in PLDN in a boy with characteristic features of HPS. PLDN is mutated in the HPS mouse model pallid and encodes the protein pallidin, which interacts with the early endosomal t-SNARE syntaxin-13. We could not detect any full-length pallidin in our patient's cells despite normal mRNA expression of the mutant transcript. We could detect an alternative transcript that would skip the exon that harbored the mutation, but we demonstrate that if this transcript is translated into protein, although it correctly localizes to early endosomes, it does not interact with syntaxin-13. In our patient's melanocytes, the melanogenic protein TYRP1 showed aberrant localization, an increase in plasma-membrane trafficking, and a failure to reach melanosomes, explaining the boy's severe albinism and establishing his diagnosis as HPS-9.
C1 [Cullinane, Andrew R.; Curry, James A.; Carmona-Rivera, Carmelo; Ciccone, Carla; Cardillo, Nicholas D.; Dorward, Heidi; Hess, Richard A.; Adams, David; Huizing, Marjan; Gahl, William A.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
   [Summers, C. Gail] Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA.
   [Summers, C. Gail] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
   [White, James G.] Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA.
   [Adams, David; Gahl, William A.] NIH, Intramural Off Rare Dis Res, Off Director, Bethesda, MD 20892 USA.
RP Cullinane, AR (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
EM andrew.cullinane@nih.gov
FU National Human Genome Research Institute, National Institutes of Health,
   Bethesda, MD, USA
FX We appreciate the excellent technical assistance of Roxanne Fischer. We
   thank Thomas Markello and Hannah Carlson-Donohoe for assistance with SNP
   arrays and E. Dell'Angelica for supplying the pallidin antibody. This
   study was supported by the Intramural Research Programs of the National
   Human Genome Research Institute, National Institutes of Health,
   Bethesda, MD, USA. All authors declare no conflicts of interest.
NR 23
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUN 10
PY 2011
VL 88
IS 6
BP 778
EP 787
DI 10.1016/j.ajhg.2011.05.009
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 779HK
UT WOS:000291768500009
PM 21665000
ER

PT J
AU Chen, JJ
   Ma, ZW
   Jiao, XD
   Fariss, R
   Kantorow, WL
   Kantorow, M
   Pras, E
   Frydman, M
   Pras, E
   Riazuddin, S
   Riazuddin, SA
   Hejtmancik, JF
AF Chen, Jianjun
   Ma, Zhiwei
   Jiao, Xiaodong
   Fariss, Robert
   Kantorow, Wanda Lee
   Kantorow, Marc
   Pras, Eran
   Frydman, Moshe
   Pras, Elon
   Riazuddin, Sheikh
   Riazuddin, S. Amer
   Hejtmancik, J. Fielding
TI Mutations in FYCO1 Cause Autosomal-Recessive Congenital Cataracts
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID COMMON ELIMINATED REGION-1; NONSENSE MUTATION; MISSENSE MUTATION; GENE;
   AUTOPHAGY; DISEASE; FAMILY; CELLS; RAB7; PATHWAY
AB Congenital cataracts (CCs), responsible for about one-third of blindness in infants, are a major cause of vision loss in children worldwide. Autosomal-recessive congenital cataracts (arCC) form a clinically diverse and genetically heterogeneous group of disorders of the crystalline lens. To identify the genetic cause of arCC in consanguineous Pakistani families, we performed genome-wide linkage analysis and fine mapping and identified linkage to 3p21-p22 with a summed LOD score of 33.42. Mutations in the gene encoding FYVE and coiled-coil domain containing 1 (FTCO1), a PI(3) P-binding protein family member that is associated with the exterior of autophagosomes and mediates microtubule plus-end-directed vesicle transport, were identified in 12 Pakistani families and one Arab Israeli family in which arCC had previously been mapped to the overlapping CATC2 region. Nine different mutations were identified, including c.3755 delC (p.Ala1252AspfsX71), c.3858_3862dupGGAAT (p.Leu1288TrpfsX37), c.1045 C > T (p.Gln349X), c.2206C > T (p.Gln736X), c.2761C > T (p.Arg921X), c.2830C > T (p.Arg944X), c.3150+1 G > T, c.4127T > C (p.Leu1376Pro), and c.1546C > T (p.Gln516X). Fyco1 is expressed in the mouse embryonic and adult lens and peaks at P12d. Expressed mutant proteins p.Leu1288TrpfsX37 and p.Gln736X are truncated on immunoblots. Wild-type and p.L1376P FYCO1, the only missense mutant identified, migrate at the expected molecular mass. Both wild-type and p. Leu1376Pro FYCO1 proteins expressed in human lens epithelial cells partially colocalize to microtubules and are found adjacent to Golgi, but they primarily colocalize to autophagosomes. Thus, FYCO1 is involved in lens development and transparency in humans, and mutations in this gene are one of the most common causes of arCC in the Pakistani population.
C1 [Chen, Jianjun; Ma, Zhiwei; Jiao, Xiaodong; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
   [Kantorow, Wanda Lee; Kantorow, Marc] Florida Atlantic Univ, Dept Biomed Sci, Boca Raton, FL 33431 USA.
   [Pras, Eran] Assaf Harofeh Med Ctr, Dept Ophthalmol, IL-70300 Zerifin, Israel.
   [Pras, Eran; Frydman, Moshe; Pras, Elon] Tel Aviv Univ, Sackler Sch Med, Danek Gertner Inst Human Genet, IL-69978 Tel Aviv, Israel.
   [Riazuddin, Sheikh; Riazuddin, S. Amer] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan.
   [Riazuddin, Sheikh] Allama Iqbal Med Coll, Lahore 54550, Pakistan.
   [Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
RP Hejtmancik, JF (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
EM f3h@helix.nih.gov
FU Higher Education Commission and Ministry of Science and Technology,
   Islamabad, Pakistan; NIH [ey13022]; National Academy of Sciences; U.S.
   Department of State, Washington, DC, USA
FX The authors are thankful to all the family members for their
   participation in this study and to James Friedman for advice and
   assistance with the fluorescent localization studies. This study was
   supported in part by the Higher Education Commission and Ministry of
   Science and Technology, Islamabad, Pakistan. This work was also
   supported by the NIH grant ey13022, National Academy of Sciences, and
   the U.S. Department of State, Washington, DC, USA (Note: All findings
   and conclusions are those of the authors and do not necessarily reflect
   the views of the National Academy of Sciences or the U.S. Department of
   State).
NR 38
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U2 9
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUN 10
PY 2011
VL 88
IS 6
BP 827
EP 838
DI 10.1016/j.ajhg.2011.05.008
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 779HK
UT WOS:000291768500015
PM 21636066
ER

PT J
AU Choksi, S
   Lin, Y
   Pobezinskaya, Y
   Chen, L
   Park, C
   Morgan, M
   Li, T
   Jitkaew, S
   Cao, XM
   Kim, YS
   Kim, HS
   Levitt, P
   Shih, G
   Birre, M
   Deng, CX
   Liu, ZG
AF Choksi, Swati
   Lin, Yong
   Pobezinskaya, Yelena
   Chen, Li
   Park, Chung
   Morgan, Michael
   Li, Tao
   Jitkaew, Siriporn
   Cao, Xiumei
   Kim, You-Sun
   Kim, Hong-Sug
   Levitt, Peter
   Shih, Grace
   Birre, Michael
   Deng, Chu-Xia
   Liu, Zheng-gang
TI A HIF-1 Target, ATIA, Protects Cells from Apoptosis by Modulating the
   Mitochondrial Thioredoxin, TRX2
SO MOLECULAR CELL
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; KAPPA-B ACTIVATION; HUMAN-DISEASE; DEATH; MICE;
   LETHALITY; ISCHEMIA; OXIDASE; SIGNAL; ALPHA
AB The regulation of apoptosis is critical for controlling tissue homeostasis and preventing tumor formation and growth. Reactive oxygen species (ROS) generation plays a key role in such regulation. Here, we describe a HIF-1 target, Vasn/ATIA (anti-TNF alpha-induced apoptosis), which protects cells against TNF alpha- and hypoxia-induced apoptosis. Through the generation of ATIA knockout mice, we show that ATIA protects cells from apoptosis through regulating the function of the mitochondrial antioxidant, thioredoxin-2, and ROS generation. ATIA is highly expressed in human glioblastoma, and ATIA knockdown in glioblastoma cells renders them sensitive to hypoxia-induced apoptosis. Therefore, ATIA is not only a HIF-1 target that regulates mitochondrial redox pathways but also a potentially diagnostic marker and therapeutic target in human glioblastoma.
C1 [Choksi, Swati; Lin, Yong; Pobezinskaya, Yelena; Chen, Li; Park, Chung; Morgan, Michael; Li, Tao; Jitkaew, Siriporn; Cao, Xiumei; Kim, You-Sun; Kim, Hong-Sug; Levitt, Peter; Shih, Grace; Birre, Michael; Liu, Zheng-gang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   [Lin, Yong] Lovelace Resp Res Inst, Albuquerque, NM 87108 USA.
   [Deng, Chu-Xia] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Liu, ZG (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA.
EM zgliu@helix.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
   Institutes of Health
FX We would like to thank W.C. Yeh for TRAF2<SUP>-/-</SUP> MEFs and W. Min
   for the GST-TRX2 plasmid. We also thank K.D. Aldape for providing us
   with human glioblastoma samples. We thank A.A. Molinolo for his
   expertise in histopathology. This research was supported by the
   Intramural Research Program of Center for Cancer Research, National
   Cancer Institute, National Institutes of Health.
NR 31
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U2 2
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD JUN 10
PY 2011
VL 42
IS 5
BP 597
EP 609
DI 10.1016/j.molcel.2011.03.030
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 778AY
UT WOS:000291670600009
PM 21658601
ER

PT J
AU Ma, HX
   Zhou, ZY
   Wei, S
   Liu, ZS
   Pooley, KA
   Dunning, AM
   Svenson, U
   Roos, G
   Hosgood, HD
   Shen, M
   Wei, QY
AF Ma, Hongxia
   Zhou, Ziyuan
   Wei, Sheng
   Liu, Zhensheng
   Pooley, Karen A.
   Dunning, Alison M.
   Svenson, Ulrika
   Roos, Goran
   Hosgood, H. Dean, III
   Shen, Min
   Wei, Qingyi
TI Shortened Telomere Length Is Associated with Increased Risk of Cancer: A
   Meta-Analysis
SO PLOS ONE
LA English
DT Article
ID INCIDENT COLORECTAL-CARCINOMA; BREAST-CANCER; CIGARETTE-SMOKING;
   PREDISPOSITION FACTOR; HUMAN FIBROBLASTS; PROSTATE-CANCER;
   BLADDER-CANCER; HUMAN-DISEASE; BLOOD-CELLS; DYSFUNCTION
AB Background: Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. A series of epidemiological studies have examined the association between shortened telomeres and risk of cancers, but the findings remain conflicting.
   Methods: A dataset composed of 11,255 cases and 13,101 controls from 21 publications was included in a meta-analysis to evaluate the association between overall cancer risk or cancer-specific risk and the relative telomere length. Heterogeneity among studies and their publication bias were further assessed by the chi(2)-based Q statistic test and Egger's test, respectively.
   Results: The results showed that shorter telomeres were significantly associated with cancer risk (OR = 1.35, 95% CI = 1.14-1.60), compared with longer telomeres. In the stratified analysis by tumor type, the association remained significant in subgroups of bladder cancer (OR = 1.84, 95% CI = 1.38-2.44), lung cancer (OR = 2.39, 95% CI = 1.18-4.88), smoking-related cancers (OR = 2.25, 95% CI = 1.83-2.78), cancers in the digestive system (OR = 1.69, 95% CI = 1.53-1.87) and the urogenital system (OR = 1.73, 95% CI = 1.12-2.67). Furthermore, the results also indicated that the association between the relative telomere length and overall cancer risk was statistically significant in studies of Caucasian subjects, Asian subjects, retrospective designs, hospital-based controls and smaller sample sizes. Funnel plot and Egger's test suggested that there was no publication bias in the current meta-analysis (P = 0.532).
   Conclusions: The results of this meta-analysis suggest that the presence of shortened telomeres may be a marker for susceptibility to human cancer, but single larger, well-design prospective studies are warranted to confirm these findings.
C1 [Ma, Hongxia; Zhou, Ziyuan; Wei, Sheng; Liu, Zhensheng; Wei, Qingyi] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
   [Ma, Hongxia] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Peoples R China.
   [Pooley, Karen A.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, Cambridge, England.
   [Dunning, Alison M.] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge, England.
   [Svenson, Ulrika; Roos, Goran] Umea Univ, Dept Med Biosci Pathol, Umea, Sweden.
   [Hosgood, H. Dean, III; Shen, Min] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Ma, HX (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
EM qwei@mdanderson.org
OI Dunning, Alison Margaret/0000-0001-6651-7166
FU National Institute of Health [R01 CA131274, R01 ES011740, P30 CA016672]
FX This work was supported by National Institute of Health grants R01
   CA131274 and R01 ES011740 (Q. Wei) and P30 CA016672 (The University of
   Texas M. D. Anderson Cancer Center). The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript.
NR 72
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U1 1
U2 18
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 JUN 10
PY 2011
VL 6
IS 6
AR e20466
DI 10.1371/journal.pone.0020466
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777JU
UT WOS:000291612600010
PM 21695195
ER

PT J
AU Weinstein, SJ
   Yu, K
   Horst, RL
   Parisi, D
   Virtamo, J
   Albanes, D
AF Weinstein, Stephanie J.
   Yu, Kai
   Horst, Ronald L.
   Parisi, Dominick
   Virtamo, Jarmo
   Albanes, Demetrius
TI Serum 25-Hydroxyvitamin D and Risk of Lung Cancer in Male Smokers: A
   Nested Case-Control Study
SO PLOS ONE
LA English
DT Article
ID VITAMIN-D STATUS; SEASONAL VARIABILITY; OVARIAN-CANCER; NHANES-III;
   SURVIVAL; COHORT; POLYMORPHISMS; MORTALITY; PROSTATE; PLASMA
AB Background: A role for vitamin D in cancer risk reduction has been hypothesized, but few data exist for lung cancer. We investigated the relationship between vitamin D status, using circulating 25-hydroxyvitamin D [25(OH) D], and lung cancer risk in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish male smokers.
   Methods: Lung cancer cases (n = 500) were randomly selected based on month of blood collection, and 500 controls were matched to them based on age and blood collection date. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate-adjusted conditional logistic regression. To account for seasonal variation in 25(OH) D concentrations, season-specific and season-standardized quintiles of 25(OH) D were examined, and models were also stratified on season of blood collection (darker season = November-April and sunnier season = May-October). Predetermined, clinically-defined cutpoints for 25(OH) D and 25(OH) D as a continuous measure were also examined.
   Results: Overall, 25(OH) D was not associated with lung cancer. Risks were 1.08 (95% CI 0.67-1.75) and 0.83 (95% CI 0.53-1.31) in the highest vs. lowest season-specific and season-standardized quintiles of 25(OH) D, respectively, and 0.91 (95% CI 0.48-1.72) for the >= 75 vs. <25 nmol/L clinical categories. Inverse associations were, however, suggested for subjects with blood collections from November-April, with ORs of 0.77 (95% CI 0.41-1.45, p-trend = 0.05) and 0.65 (95% CI 0.37-1.14, p-trend = 0.07) in the highest vs. lowest season-specific and season-standardized quintiles of 25(OH) D, respectively, and 0.61 (95% CI 0.24-1.52, p-trend = 0.01) for >= 75 vs. <25 nmol/L. We also found 11% lower risk for a 10 nmol/L increase in 25(OH) D in the darker season based on the continuous measure (OR = 0.89, 95% CI 0.81-0.98, p = 0.02).
   Conclusion: In this prospective study of male smokers, circulating 25(OH) D was not associated with lung cancer risk overall, although inverse associations were suggested among those whose blood was drawn during darker months.
C1 [Weinstein, Stephanie J.; Yu, Kai; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA.
   [Parisi, Dominick] Informat Management Serv Inc, Silver Spring, MD USA.
   [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Weinstein, SJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM weinstes@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015
FU National Institutes of Health; National Cancer Institute; National
   Cancer Institute, Department of Health and Human Services [N01-CN-45165,
   N01-RC-45035, N01-RC-37004]
FX This work was supported in part by the Intramural Research Program of
   the National Institutes of Health and the National Cancer Institute.
   Additionally, this research was supported by Public Health Service
   contracts N01-CN-45165, N01-RC-45035, and N01-RC-37004 from the National
   Cancer Institute, Department of Health and Human Services. These funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript. Ronald L. Horst is an
   employee of Heartland Assays, Inc., and Dominick Parisi is an employee
   of Information Management Services, Inc. These authors played a role in
   performing the experiments and analysis of the data.
NR 40
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U1 0
U2 0
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 JUN 10
PY 2011
VL 6
IS 6
AR e20796
DI 10.1371/journal.pone.0020796
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777JU
UT WOS:000291612600028
PM 21695165
ER

PT J
AU Scheel, C
   Eaton, EN
   Li, SHJ
   Chaffer, CL
   Reinhardt, F
   Kah, KJ
   Bell, G
   Guo, W
   Rubin, J
   Richardson, AL
   Weinberg, RA
AF Scheel, Christina
   Eaton, Elinor Ng
   Li, Sophia Hsin-Jung
   Chaffer, Christine L.
   Reinhardt, Ferenc
   Kah, Kong-Jie
   Bell, George
   Guo, Wenjun
   Rubin, Jeffrey
   Richardson, Andrea L.
   Weinberg, Robert A.
TI Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem
   Cell States in the Breast
SO CELL
LA English
DT Article
ID STEM/PROGENITOR CELLS; CANCER-CELLS; IN-VITRO; TRANSITION; METASTASIS;
   PROPAGATION; EXPRESSION; PATHWAYS; DISEASE; LINES
AB The epithelial-mesenchymal transition (EMT) has been associated with the acquisition of motility, invasiveness, and self-renewal traits. During both normal development and tumor pathogenesis, this change in cell phenotype is induced by contextual signals that epithelial cells receive from their microenvironment. The signals that are responsible for inducing an EMT and maintaining the resulting cellular state have been unclear. We describe three signaling pathways, involving transforming growth factor (TGF)-beta and canonical and noncanonical Wnt signaling, that collaborate to induce activation of the EMT program and thereafter function in an autocrine fashion to maintain the resulting mesenchymal state. Downregulation of endogenously synthesized inhibitors of autocrine signals in epithelial cells enables the induction of the EMT program. Conversely, disruption of autocrine signaling by added inhibitors of these pathways inhibits migration and self-renewal in primary mammary epithelial cells and reduces tumorigenicity and metastasis by their transformed derivatives.
C1 [Scheel, Christina; Eaton, Elinor Ng; Li, Sophia Hsin-Jung; Chaffer, Christine L.; Reinhardt, Ferenc; Kah, Kong-Jie; Bell, George; Guo, Wenjun; Weinberg, Robert A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   [Li, Sophia Hsin-Jung; Kah, Kong-Jie; Weinberg, Robert A.] MIT, Dept Biol, Cambridge, MA 02139 USA.
   [Richardson, Andrea L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   [Weinberg, Robert A.] MIT Ludwig Ctr Mol Oncol, Cambridge, MA 02139 USA.
   [Rubin, Jeffrey] NCI, Bethesda, MD 20892 USA.
RP Scheel, C (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
EM scheel@wi.mit.edu; weinberg@wi.mit.edu
OI Li, Sophia Hsin-Jung/0000-0001-8972-6921
FU National Institutes of Health/National Cancer Institute [CA12515,
   DE020817]; Massachusetts Institute of Technology Ludwig Center for
   Molecular Oncology; Ludwig Fellowship for Metastasis Research; Breast
   Cancer Research Foundation; Harvard Breast Cancer SPORE; Department of
   Defense; Samuel Waxman Foundation
FX We thank Brian Bierie, Thijn Brummelkamp, Sunny Gupta, Katharina
   Leuchte, Julia Rastelli, Andreas Scheel, Scott Valastyan, and Irene
   Wuethrich for critical reading of the manuscript, members of the
   Weinberg lab for discussion, John Stingl for protocols, the Whitehead
   Microarray and Flow Cytometry Cores, and the W.M. Keck Microscopy
   Facility for technical support. This research was supported by the
   National Institutes of Health/National Cancer Institute (R.A.W.; CA12515
   and DE020817), Massachusetts Institute of Technology Ludwig Center for
   Molecular Oncology (R.A.W.), Ludwig Fellowship for Metastasis Research
   (C.S.), Breast Cancer Research Foundation (A.L.R. and R.A.W.), Harvard
   Breast Cancer SPORE (A.L.R. and R.A.W.), Department of Defense Breast
   Cancer Research Program Idea Award (R.A.W.), and Samuel Waxman
   Foundation (R.A.W.). C.S. and R.A.W. are inventors on a patent
   application in part based on findings detailed in this manuscript.
NR 29
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U1 6
U2 89
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUN 10
PY 2011
VL 145
IS 6
BP 926
EP 940
DI 10.1016/j.cell.2011.04.029
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 775LS
UT WOS:000291461600019
PM 21663795
ER

PT J
AU Jatoi, I
   Anderson, WF
   Jeong, JH
   Redmond, CK
AF Jatoi, Ismail
   Anderson, William F.
   Jeong, Jong-Hyeon
   Redmond, Carol K.
TI Breast Cancer Adjuvant Therapy: Time to Consider Its Time-Dependent
   Effects
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID ESTROGEN-RECEPTOR STATUS; HAZARD RATES; END-POINTS; RECURRENCE;
   SURVIVAL; EXPRESSION; TRIALS; CHEMOTHERAPY; MODELS
C1 [Jatoi, Ismail] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
   [Anderson, William F.] NCI, Bethesda, MD 20892 USA.
   [Jeong, Jong-Hyeon; Redmond, Carol K.] Univ Pittsburgh, Pittsburgh, PA USA.
RP Jatoi, I (reprint author), Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
OI Jeong, Jong/0000-0003-0596-2201
NR 31
TC 63
Z9 63
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 10
PY 2011
VL 29
IS 17
BP 2301
EP 2304
DI 10.1200/JCO.2010.32.3550
PG 4
WC Oncology
SC Oncology
GA 774KT
UT WOS:000291385200018
PM 21555693
ER

PT J
AU Freedman, AN
   Yu, BB
   Gail, MH
   Costantino, JP
   Graubard, BI
   Vogel, VG
   Anderson, GL
   McCaskill-Stevens, W
AF Freedman, Andrew N.
   Yu, Binbing
   Gail, Mitchell H.
   Costantino, Joseph P.
   Graubard, Barry I.
   Vogel, Victor G.
   Anderson, Garnet L.
   McCaskill-Stevens, Worta
TI Benefit/Risk Assessment for Breast Cancer Chemoprevention With
   Raloxifene or Tamoxifen for Women Age 50 Years or Older
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; SURGICAL ADJUVANT BREAST; STAR P-2 TRIAL;
   POSTMENOPAUSAL WOMEN; PREVENTION TRIAL; CLINICAL-TRIAL; BOWEL PROJECT;
   FOLLOW-UP; RISK; INTERVENTIONS
AB Purpose
   The Study of Tamoxifen and Raloxifene (STAR) demonstrated that raloxifene was as effective as tamoxifen in reducing the risk of invasive breast cancer (IBC) in postmenopausal women and had lower risks of thromboembolic events, endometrial cancer, and cataracts but had a nonstatistically significant higher risk of noninvasive breast cancer. There is a need to summarize the risks and benefits of these agents.
   Patients and Methods
   Baseline incidence rates of IBC and other health outcomes, absent raloxifene and tamoxifen, were estimated from breast cancer chemoprevention trials; the Surveillance, Epidemiology and End Results Program; and the Women's Health Initiative. Effects of raloxifene and tamoxifen were estimated from STAR and the Breast Cancer Prevention Trial. We assigned weights to health outcomes to calculate the net benefit from raloxifene compared with placebo and tamoxifen compared with placebo.
   Results
   Risks and benefits of treatment with raloxifene or tamoxifen depend on age, race, breast cancer risk, and history of hysterectomy. Over a 5-year period, postmenopausal women with an intact uterus had a better benefit/risk index for raloxifene than for tamoxifen. For postmenopausal women without a uterus, the benefit/risk ratio was similar. The benefits and risks of raloxifene and tamoxifen are described in tables that can help identify groups of women for whom the benefits outweigh the risks.
   Conclusion
   We developed a benefit/risk index to quantify benefits from chemoprevention with tamoxifen or raloxifene. This index can complement clinical evaluation in deciding whether to initiate chemoprevention and in comparing the benefits and risks of raloxifene versus tamoxifen. J Clin Oncol 29: 2327-2333. (C) 2011 by American Society of Clinical Oncology
C1 [McCaskill-Stevens, Worta] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
   NIA, Bethesda, MD 20892 USA.
   Univ Pittsburgh, Grad Sch Publ Hlth, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
   Geisinger Hlth Syst, Danville, PA USA.
   Fred Hutchinson Canc Res Ctr, Womens Hlth Initiat Clin Coordinating Ctr, Seattle, WA 98104 USA.
RP McCaskill-Stevens, W (reprint author), NCI, Canc Prevent Div, 6130 Executive Blvd,Room 2026, Bethesda, MD 20892 USA.
EM wm57h@nih.gov
FU National Heart, Lung, and Blood Institute, National Institutes of Health
   [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115,
   32118-32119, 32122, 42107-26, 42129-32, 44221]; US Department of Health
   and Human Services; National Institute on Aging; Division of Cancer
   Epidemiology and Genetics, National Cancer Institute; Public Health
   Service [U10-CA069974]
FX Supported by Contracts No. N01WH22110, 24152, 32100-2, 32105-6, 32108-9,
   32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221 from
   the National Heart, Lung, and Blood Institute, National Institutes of
   Health, US Department of Health and Human Services; by the Intramural
   Research Program of the National Institute on Aging (B.Y.), by the
   Intramural Research Program of the Division of Cancer Epidemiology and
   Genetics, National Cancer Institute (M.H.G. and B.I.G.), and by Grant
   No. U10-CA069974 from the Public Health Service (J.P.C.).
NR 27
TC 61
Z9 62
U1 1
U2 7
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 JUN 10
PY 2011
VL 29
IS 17
BP 2327
EP 2333
DI 10.1200/JCO.2010.33.0258
PG 7
WC Oncology
SC Oncology
GA 774KT
UT WOS:000291385200022
PM 21537036
ER

PT J
AU Bekaii-Saab, T
   Phelps, MA
   Li, XB
   Saji, M
   Goff, L
   Kauh, JSW
   O'Neil, BH
   Balsom, S
   Balint, C
   Liersemann, R
   Vasko, VV
   Bloomston, M
   Marsh, W
   Doyle, LA
   Ellison, G
   Grever, M
   Ringel, MD
   Villalona-Calero, MA
AF Bekaii-Saab, Tanios
   Phelps, Mitch A.
   Li, Xiaobai
   Saji, Motoyasu
   Goff, Laura
   Kauh, John Sae Wook
   O'Neil, Bert H.
   Balsom, Stephanie
   Balint, Catherine
   Liersemann, Ryan
   Vasko, Vasily V.
   Bloomston, Mark
   Marsh, William
   Doyle, L. Austin
   Ellison, Gilian
   Grever, Michael
   Ringel, Matthew D.
   Villalona-Calero, Miguel A.
TI Multi-Institutional Phase II Study of Selumetinib in Patients With
   Metastatic Biliary Cancers
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; INHIBITOR AZD6244 ARRY-142886; BRAF MUTATION
   PREDICTS; PANCREATIC-CANCER; SIGNALING PATHWAY; THYROID-CANCER; TRACT
   CANCERS; K-RAS; GROWTH; CHOLANGIOCARCINOMA
AB Purpose
   Biliary cancers (BCs) carry a poor prognosis, but targeting the RAS/RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) pathway is of significance. Selumetinib is an inhibitor of MEK1/2, so this trial was designed to determine the safety and efficacy of selumetinib in BC.
   Patients and Methods
   This was a multi-institutional phase II study of selumetinib at 100 mg given orally twice per day to patients with advanced BC. The primary end point was response rate. All patients were required to provide tissue before enrolling. The levels of phosphorylated ERK (pERK) and AKT (pAKT) were assessed by immunohistochemistry. Tumors were genotyped for the presence of BRAF- and/or RAS-activating mutations.
   Results
   Twenty-eight eligible patients with a median age of 55.6 years were enrolled. Thirty-nine percent of patients had received one prior systemic therapy. Three patients (12%) had a confirmed objective response. Another 17 patients (68%) experienced stable disease (SD), 14 of whom (56%) experienced prolonged SD (> 16 weeks). Patients gained an average nonfluid weight of 8.6 pounds. Median progression-free survival was 3.7 months (95% CI, 3.5 to 4.9) and median overall survival was 9.8 months (95% CI, 5.97 to not available). Toxicities were mild, with rash (90%) and xerostomia (54%) being most frequent. Only one patient experienced grade 4 toxicity (fatigue). All patients had tissue available for analysis. No BRAF V600E mutations were found. Two patients with short-lived SD had KRAS mutations. Absence of pERK staining was associated with lack of response.
   Conclusion
   Selumetinib displays interesting activity and acceptable tolerability in patients with metastatic BC. Our results warrant further evaluation of selumetinib in patients with metastatic BC. J Clin Oncol 29:2357-2363. (C) 2011 by American Society of Clinical Oncology
C1 [Bekaii-Saab, Tanios] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA.
   Solove Res Inst, Columbus, OH USA.
   Vanderbilt Univ, Nashville, TN USA.
   Emory Univ, Atlanta, GA 30322 USA.
   Univ N Carolina, Raleigh, NC USA.
   Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
   NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
   AstraZeneca, Macclesfield, Cheshire, England.
RP Bekaii-Saab, T (reprint author), Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, A454 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA.
EM Tanios.Bekaii-Saab@osumc.edu
RI Saji, Motoyasu/E-4007-2011; Phelps, Mitch/H-3941-2013; Bekaii-Saab,
   Tanios/E-2733-2011
OI Phelps, Mitch/0000-0002-1615-5280; 
FU National Cancer Institute, National Institutes of Health, Bethesda, MD
   [NO1-CM62207]
FX Supported by Grant No. NO1-CM62207 from the National Cancer Institute,
   National Institutes of Health, Bethesda, MD.
NR 41
TC 103
Z9 106
U1 1
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 10
PY 2011
VL 29
IS 17
BP 2357
EP 2363
DI 10.1200/JCO.2010.33.9473
PG 7
WC Oncology
SC Oncology
GA 774KT
UT WOS:000291385200026
PM 21519026
ER

PT J
AU Bjorkholm, M
   Derolf, AR
   Hultcrantz, M
   Kristinsson, SY
   Ekstrand, C
   Goldin, LR
   Andreasson, B
   Birgegard, G
   Linder, O
   Malm, C
   Markevarn, B
   Nilsson, L
   Samuelsson, J
   Granath, F
   Landgren, O
AF Bjorkholm, Magnus
   Derolf, Asa R.
   Hultcrantz, Malin
   Kristinsson, Sigurdur Y.
   Ekstrand, Charlotta
   Goldin, Lynn R.
   Andreasson, Bjorn
   Birgegard, Gunnar
   Linder, Olle
   Malm, Claes
   Markevarn, Berit
   Nilsson, Lars
   Samuelsson, Jan
   Granath, Fredrik
   Landgren, Ola
TI Treatment-Related Risk Factors for Transformation to Acute Myeloid
   Leukemia and Myelodysplastic Syndromes in Myeloproliferative Neoplasms
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID TERM-FOLLOW-UP; POLYCYTHEMIA-VERA; ESSENTIAL THROMBOCYTHEMIA;
   PROGNOSTIC-FACTORS; SINGLE-INSTITUTION; 2ND MALIGNANCIES; HYDROXYUREA;
   THERAPY; MYELOFIBROSIS; COMBINATION
AB Purpose
   Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to develop acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs). Using population-based data from Sweden, we assessed the role of MPN treatment and subsequent AML/MDS risk with special focus on the leukemogenic potential of hydroxyurea (HU).
   Methods
   On the basis of a nationwide MPN cohort (N = 11,039), we conducted a nested case-control study, including 162 patients (153 and nine with subsequent AML and MDS diagnosis, respectively) and 242 matched controls. We obtained clinical and MPN treatment data for all patients. Using logistic regression, we calculated odds ratios (ORs) as measures of AML/MDS risk.
   Results
   Forty-one (25%) of 162 patients with MPNs with AML/MDS development were never exposed to alkylating agents, radioactive phosphorous (P(32)), or HU. Compared with patients with who were not exposed to HU, the ORs for 1 to 499 g, 500 to 999 g, more than 1,000 g of HU were 1.5 (95% CI, 0.6 to 2.4), 1.4 (95% CI, 0.6 to 3.4), and 1.3 (95% CI, 0.5 to 3.3), respectively, for AML/MDS development (not significant). Patients with MPNs who received P(32) greater than 1,000 MBq and alkylators greater than 1 g had a 4.6-fold (95% CI, 2.1 to 9.8; P = .002) and 3.4-fold (95% CI, 1.1 to 10.6; P = .015) increased risk of AML/MDS, respectively. Patients receiving two or more cytoreductive treatments had a 2.9-fold (95% CI, 1.4 to 5.9) increased risk of transformation.
   Conclusion
   The risk of AML/MDS development after MPN diagnosis was significantly associated with high exposures of P(32) and alkylators but not with HU treatment. Twenty-five percent of patients with MPNs who developed AML/MDS were not exposed to cytotoxic therapy, supporting a major role for nontreatment-related factors. J Clin Oncol 29:2410-2415. (C) 2011 by American Society of Clinical Oncology
C1 [Bjorkholm, Magnus] Karolinska Univ Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
   [Bjorkholm, Magnus; Derolf, Asa R.; Hultcrantz, Malin; Kristinsson, Sigurdur Y.; Ekstrand, Charlotta; Granath, Fredrik; Landgren, Ola] Karolinska Inst, Stockholm, Sweden.
   [Bjorkholm, Magnus; Hultcrantz, Malin; Andreasson, Bjorn; Birgegard, Gunnar; Linder, Olle; Malm, Claes; Markevarn, Berit; Nilsson, Lars; Samuelsson, Jan] Swedish Chron Myeloproliferat Neoplasm Study Grp, Stockholm, Sweden.
   [Goldin, Lynn R.] NCI, NIH, Bethesda, MD 20892 USA.
RP Bjorkholm, M (reprint author), Karolinska Univ Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden.
EM magnus.bjorkholm@karolinska.se
RI Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
FU Stockholm County Council; Karolinska Institutet; Shire Pharmaceuticals;
   Adolf H. Lundin Charitable Foundation; Swedish Cancer Society; National
   Cancer Institute, National Institutes of Health, Bethesda, MD; Magnus
   Bjorkholm
FX Supported by the regional agreement on medical training and clinical
   research between Stockholm County Council and Karolinska Institutet; an
   unrestricted grant from Shire Pharmaceuticals; the Adolf H. Lundin
   Charitable Foundation; the Swedish Cancer Society; and the Intramural
   Program of the National Cancer Institute, National Institutes of Health,
   Bethesda, MD.; Funding: Magnus Bjorkholm, Shire Pharmaceuticals
NR 39
TC 78
Z9 79
U1 0
U2 4
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 JUN 10
PY 2011
VL 29
IS 17
BP 2410
EP 2415
DI 10.1200/JCO.2011.34.7542
PG 6
WC Oncology
SC Oncology
GA 774KT
UT WOS:000291385200034
PM 21537037
ER

PT J
AU Korn, EL
   Freidlin, B
   Abrams, JS
AF Korn, Edward L.
   Freidlin, Boris
   Abrams, Jeffrey S.
TI Overall Survival As the Outcome for Randomized Clinical Trials With
   Effective Subsequent Therapies
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID IXABEPILONE PLUS CAPECITABINE; BREAST-CANCER; END-POINTS; IMATINIB
   MESYLATE; TAXANE TREATMENT; ANTHRACYCLINE; CHEMOTHERAPY; TUMORS
AB We review how overall survival (OS) comparisons should be interpreted with increasing availability of effective therapies that can be given subsequently to the treatment assigned in a randomized clinical trial (RCT). We examine in detail how effective subsequent therapies influence OS comparisons under varying conditions in RCTs. A subsequent therapy given after tumor progression (or relapse) in an RCT that works better in the standard arm than the experimental arm will lead to a smaller OS difference (possibly no difference) than one would see if the subsequent therapy was not available. Subsequent treatments that are equally effective in the treatment arms would not be expected to affect the absolute OS benefit of the experimental treatment but will make the relative improvement in OS smaller. In trials in which control arm patients cross over to the experimental treatment after their condition worsens, a smaller OS difference could be observed than one would see without cross-overs. In particular, use of cross-over designs in the first definitive evaluation of a new agent in a given disease compromises the ability to assess clinical benefit. In disease settings in which there is not an intermediate end point that directly measures clinical benefit, OS should be the primary end point of an RCT. The observed difference in OS should be considered the measure of clinical benefit to the patients, regardless of subsequent therapies, provided that the subsequent therapies used in both treatment arms follow the current standard of care. J Clin Oncol 29:2439-2442. (C) 2011 by American Society of Clinical Oncology
C1 [Korn, Edward L.; Freidlin, Boris] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
   [Abrams, Jeffrey S.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Korn, EL (reprint author), NCI, Res Branch, EPN-8129, Bethesda, MD 20892 USA.
EM korne@ctep.nci.nih.gov
NR 24
TC 62
Z9 62
U1 0
U2 5
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUN 10
PY 2011
VL 29
IS 17
BP 2439
EP 2442
DI 10.1200/JCO.2011.34.6056
PG 4
WC Oncology
SC Oncology
GA 774KT
UT WOS:000291385200038
PM 21555691
ER

PT J
AU Williams, JL
   Ji, P
   Ouyang, N
   Kopelovich, L
   Rigas, B
AF Williams, Jennie L.
   Ji, Ping
   Ouyang, Nengtai
   Kopelovich, Levy
   Rigas, Basil
TI Protein nitration and nitrosylation by NO-donating aspirin in colon
   cancer cells: Relevance to its mechanism of action
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Nitric oxide-donating aspirin (NO-ASA); S-nitrosylation; NF-kappa B;
   p53; beta-Catenin; Tyrosine nitration
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; OXIDE-RELEASING ASPIRIN;
   FACTOR-KAPPA-B; NITRIC-OXIDE; COLORECTAL NEOPLASIA; TRADITIONAL NSAIDS;
   OXIDATIVE STRESS; P53; CHEMOPREVENTION; LINES
AB Nitric oxide-donating aspirin (NO-ASA) is a promising agent for cancer prevention. Although studied extensively, its molecular targets and mechanism of action are still unclear. S-nitrosylation of signaling proteins is emerging as an important regulatory mechanism by NO. Here, we examined whether S-nitrosylation of the NF-kappa B, p53, and Wnt signaling proteins by NO-ASA might explain, in part, its mechanism of action in colon cancer. NO-ASA releases significant amounts of NO detected intracellularly in HCT116 and HT-29 colon cells. Using a modified biotin switch assay we demonstrated that NO-ASA S-nitrosylates the signaling proteins p53, beta-catenin, and NF-kappa B, in colon cancer cells in a time- and concentration-dependent manner. NO-ASA suppresses NF-kappa B binding to its cognate DNA oligonucleotide, which occurs without changes in the nuclear levels of the NF-kappa B subunits p65 and p50 and is reversed by dithiothreitol that reduces -S-NO to -SH. In addition to S-nitrosylation, we documented both in vitro and in vivo widespread nitration of tyrosine residues of cellular proteins in response to NO-ASA. Our results suggest that the increased intracellular NO levels following treatment with NO-ASA modulate cell signaling by chemically modifying key protein members of signaling cascades. We speculate that S-nitrosylation and tyrosine nitration are responsible, at least in part, for the inhibitory growth effect of NO-ASA on cancer cell growth and that this may represent a general mechanism of action of NO-releasing agents. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Williams, Jennie L.; Ji, Ping; Ouyang, Nengtai; Rigas, Basil] SUNY Stony Brook, HSC, Canc Prevent Div, Stony Brook, NY 11794 USA.
   [Kopelovich, Levy] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Rigas, B (reprint author), SUNY Stony Brook, HSC, Canc Prevent Div, T17-080, Stony Brook, NY 11794 USA.
EM basil.rigas@stonybrook.edu
FU NIH [CN43302WMC08WA7, KO1 CA106604-05]
FX Grant support: NIH CN43302WMC08WA7 and KO1 CA106604-05.
NR 47
TC 12
Z9 12
U1 0
U2 3
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD JUN 10
PY 2011
VL 317
IS 10
BP 1359
EP 1367
DI 10.1016/j.yexcr.2011.03.001
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 771TY
UT WOS:000291184800005
PM 21406194
ER

PT J
AU Mannangatti, P
   Arapulisamy, O
   Shippenberg, TS
   Ramamoorthy, S
   Jayanthi, LD
AF Mannangatti, Padmanabhan
   Arapulisamy, Obulakshmi
   Shippenberg, Toni S.
   Ramamoorthy, Sammanda
   Jayanthi, Lankupalle D.
TI Cocaine Up-regulation of the Norepinephrine Transporter Requires
   Threonine 30 Phosphorylation by p38 Mitogen-activated Protein Kinase
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID DOPAMINE TRANSPORTER; EXTRACELLULAR DOPAMINE; SURFACE EXPRESSION;
   PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; SEROTONIN TRANSPORTERS; STRIA
   TERMINALIS; PHOSPHATASE 2A; BED NUCLEUS; TRAFFICKING
AB The norepinephrine (NE) transporter (NET) regulates NE signaling by rapidly clearing synaptic NE. Cocaine binds NET and modulates NE transport. These actions contribute to rewarding effects and abuse liability of cocaine. Activation of mitogen-activated protein kinase (MAPK) cascades is implicated in cocaine-induced neuroadaptations. However, the role of MAPK and the mechanisms involved in cocaine modulation of NET are not clear. Acute intra-peritoneal injections of cocaine (20 mg/kg body weight) to rats resulted in increased NE uptake by prefrontal cortex (PFC) synaptosomes with a parallel increase in the surface expression of endogenous NET. Cocaine also enhanced the immunoreactivity of phospho-p38 MAPK in the PFC synaptosomes without affecting the total p38 MAPK. In vitro cocaine (30-50 mu M) treatment of rat PFC synaptosomes increased native NET function, surface expression, and phosphorylation in a manner sensitive to p38 MAPK inhibition by PD169316. We next examined cocaine-elicited effects on wild-type human NET (hNET) expressed heterologously in human placental trophoblast cells to gain more insights into the mechanisms involved. Cocaine treatment of hNET expressing human placental trophoblast cells up-regulated the function, surface expression, and phosphorylation of hNET in a PD169316-sensitive manner. In addition, cocaine inhibited constitutive endocytosis of hNET. Mutational analysis of serine and threonine residues revealed that substitution of threonine 30, located at the amino terminus of hNET with alanine (T30A-hNET), abolished cocaine-induced up-regulation of NET function, surface expression, and phosphorylation. Furthermore, cocaine did not alter T30A-hNET endocytosis. These studies identify a novel molecular mechanism that cocaine-activated p38 MAPK-mediated phosphorylation of NET-T30 dictates surface NET availability, and hence, NE transport.
C1 [Mannangatti, Padmanabhan; Arapulisamy, Obulakshmi; Ramamoorthy, Sammanda; Jayanthi, Lankupalle D.] Med Univ S Carolina, Dept Neurosci, Div Neurosci Res, Charleston, SC 29425 USA.
   [Shippenberg, Toni S.] NIDA, Integrat Neurosci Sect, Intramural Res Program, US Dept HHS, Baltimore, MD 21224 USA.
RP Jayanthi, LD (reprint author), Med Univ S Carolina, Dept Neurosci, Div Neurosci Res, Charleston, SC 29425 USA.
EM jayanthi@musc.edu
FU National Institutes of Health [RO1-GM081054]; NIGMS, National Institute
   of Mental Health [RO1-MH62612]; National Institute on Drug Abuse
FX This work was supported, in whole or in part, by National Institutes of
   Health Grant RO1-GM081054 (to L.D.J.) from the NIGMS, National Institute
   of Mental Health Grant RO1-MH62612 (to S.R.), and the National Institute
   on Drug Abuse Intramural Research Program (to T.S.S.).
NR 57
TC 10
Z9 10
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 10
PY 2011
VL 286
IS 23
BP 20239
EP 20250
DI 10.1074/jbc.M111.226811
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 772WC
UT WOS:000291267600011
PM 21498515
ER

PT J
AU Song, CC
   Rahim, RT
   Davey, PC
   Bednar, F
   Bardi, G
   Zhang, L
   Zhang, N
   Oppenheim, JJ
   Rogers, TJ
AF Song, Changcheng
   Rahim, Rahil T.
   Davey, Penelope C.
   Bednar, Filip
   Bardi, Giuseppe
   Zhang, Lily
   Zhang, Ning
   Oppenheim, Joost J.
   Rogers, Thomas J.
TI Protein Kinase C zeta Mediates mu-Opioid Receptor-induced
   Cross-desensitization of Chemokine Receptor CCR5
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HETEROLOGOUS DESENSITIZATION; INDUCED CHEMOTAXIS; HUMAN-MONOCYTES; RAT
   ADIPOCYTES; IMMUNE-SYSTEM; PKC-ZETA; ACTIVATION; TRANSLOCATION;
   3-KINASE; CELLS
AB We have previously shown that the mu-opioid receptor (MOR) is capable of mediating cross-desensitization of several chemokine receptors including CCR5, but the biochemical mechanism of this process has not been fully elucidated. We have carried out a series of functional and biochemical studies and found that the mechanism of MOR-induced cross-desensitization of CCR5 involves the activation of PKC zeta. Inhibition of PKC zeta by its pseudosubstrate inhibitor, or its siRNA, or dominant negative mutants suppresses the cross-desensitization of CCR5. Our results further indicate that the activation of PKC zeta is mediated through a pathway involving phosphoinositol-dependent kinase-1 (PDK1). In addition, activation of MOR elevates the phosphorylation level and kinase activity of PKC zeta. The phosphorylation of PKC zeta can be suppressed by a dominant negative mutant of PDK1. We observed that following MOR activation, the interaction between PKC zeta and PDK1 is immediately increased based on the analysis of fluorescent resonance energy transfer in cells with the expression of PKC zeta-YFP and PDK1-CFP. In addition, cells expressing PKC zeta kinase motif mutants (Lys-281, Thr-410, Thr-560) fail to exhibit full MOR-induced desensitization of CCR5 activity. Taken together, we propose that upon DAMGO treatment, MOR activates PKC zeta through a PDK1-dependent signaling pathway to induce CCR5 phosphorylation and desensitization. Because CCR5 is a highly proinflammatory receptor, and a critical coreceptor for HIV-1, these results may provide a novel approach for the development of specific therapeutic agents to treat patients with certain inflammatory diseases or AIDS.
C1 [Song, Changcheng; Rahim, Rahil T.; Davey, Penelope C.; Bardi, Giuseppe; Zhang, Lily; Rogers, Thomas J.] Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Ctr Subst Abuse Res, Philadelphia, PA 19140 USA.
   [Bednar, Filip] Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA.
   [Zhang, Ning; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA.
RP Rogers, TJ (reprint author), Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Ctr Subst Abuse Res, 3307 N Broad St, Philadelphia, PA 19140 USA.
EM rogerst@temple.edu
RI Bardi, Giuseppe/B-6452-2013
FU National Institutes of Health, NIDA [DA-14230, DA-25532, P01DA-23860,
   P30DA-13429, T32DA-07237, DA-06650]
FX This work was supported, in whole or in part, by National Institutes of
   Health Grants DA-14230, DA-25532, P01DA-23860, P30DA-13429, T32DA-07237,
   and DA-06650 from NIDA.
NR 45
TC 12
Z9 12
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUN 10
PY 2011
VL 286
IS 23
BP 20354
EP 20365
DI 10.1074/jbc.M110.177303
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 772WC
UT WOS:000291267600023
PM 21454526
ER

PT J
AU David, A
   Netzer, N
   Strader, MB
   Das, SR
   Chen, CY
   Gibbs, J
   Pierre, P
   Bennink, JR
   Yewdell, JW
AF David, Alexandre
   Netzer, Nir
   Strader, Michael Brad
   Das, Suman R.
   Chen, Cai Yun
   Gibbs, James
   Pierre, Philippe
   Bennink, Jack R.
   Yewdell, Jonathan W.
TI RNA Binding Targets Aminoacyl-tRNA Synthetases to Translating Ribosomes
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROTEIN-PROTEIN INTERACTIONS; MESSENGER-RNA; ENDOPLASMIC-RETICULUM;
   MAMMALIAN-CELLS; MACROMOLECULAR ASSEMBLAGE; SUBCELLULAR-DISTRIBUTION;
   STRESS GRANULES; SHEEP LIVER; COMPLEX; PHOSPHORYLATION
AB Here, we examine tRNA-aminoacyl synthetase (ARS) localization in protein synthesis. Proteomics reveals that ten of the twenty cytosolic ARSs associate with ribosomes in sucrose gradients: phenylalanyl-RS (FRS), and the 9 ARSs that form the multi-ARS complex (MSC). Using the ribopuromycylation method (RPM) for localizing intracellular translation, we show that FRS and the MSC, and to a lesser extent other ARSs, localize to translating ribosomes, most strikingly when translation is restricted to poxvirus or alphavirus factories in infected cells. Immunoproximity fluorescence indicates close proximity between MSC and the ribosome. Stress induced-translational shutdown recruits the MSC to stress-granules, a depot for mRNA and translation components. MSC binding to mRNA provides a facile explanation for its delivery to translating ribosomes and stress granules. These findings, along with the abundance of the MSC (9 x 10(6) copies per cell, roughly equimolar with ribosomes), is consistent with the idea that MSC specificity, recently reported to vary with cellular stress (Netzer, N., Goodenbour, J. M., David, A., Dittmar, K. A., Jones, R. B., Schneider, J. R., Boone, D., Eves, E. M., Rosner, M. R., Gibbs, J. S., Embry, A., Dolan, B., Das, S., Hickman, H. D., Berglund, P., Bennink, J. R., Yewdell, J. W., and Pan, T. (2009) Nature 462, 522-526) can be modulated at the level of individual mRNAs to modify decoding of specific gene products.
C1 [Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
   [Strader, Michael Brad; Chen, Cai Yun] NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA.
   [Pierre, Philippe] Ctr Immunol Marseille Luminy, Marseille, France.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 33,33 North Dr, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
RI yewdell, jyewdell@nih.gov/A-1702-2012; Das, Suman/C-8760-2009; David,
   Alexandre/B-2447-2013; 
OI David, Alexandre/0000-0003-3365-1339; pierre,
   philippe/0000-0003-0863-8255
FU Division of Intramural Research, NIAID, National Institutes of Health
FX This work was supported, in whole or in part, by the Division of
   Intramural Research, NIAID, National Institutes of Health.
NR 50
TC 38
Z9 38
U1 0
U2 8
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 JUN 10
PY 2011
VL 286
IS 23
BP 20688
EP 20700
DI 10.1074/jbc.M110.209452
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 772WC
UT WOS:000291267600055
PM 21460219
ER

PT J
AU Shahzad-ul-Hussan, S
   Gustchina, E
   Ghirlando, R
   Clore, GM
   Bewley, CA
AF Shahzad-ul-Hussan, Syed
   Gustchina, Elena
   Ghirlando, Rodolfo
   Clore, G. Marius
   Bewley, Carole A.
TI Solution Structure of the Monovalent Lectin Microvirin in Complex with
   Man alpha(1-2)Man Provides a Basis for Anti-HIV Activity with Low
   Toxicity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID CYANOVIRIN-N; OLIGOSACCHARIDE STRUCTURES; SEDIMENTATION EQUILIBRIUM;
   MICROCYSTIS-AERUGINOSA; INACTIVATING PROTEIN; BACKBONE DYNAMICS;
   NMR-SPECTROSCOPY; VIRUS; BINDING; FUSION
AB Lectins that bind surface envelope glycoprotein gp120 of HIV with high avidity can potently inhibit viral entry. Yet properties such as multivalency that facilitate strong interactions can also cause nonspecific binding and toxicity. The cyanobacterial lectin microvirin (MVN) is unusual as it potently inhibits HIV-1 with negligible toxicity compared with cyanovirin-N (CVN), its well studied antiviral homolog. To understand the structural and mechanistic basis for these differences, we solved the solution structure of MVN free and in complex with its ligand Man alpha(1-2)Man, and we compared specificity and time windows of inhibition with CVN and Man alpha(1-2)Man-specific mAb 2G12. We show by NMR and analytical ultracentrifugation that MVN is monomeric in solution, and we demonstrate by NMR that Man alpha(1-2)Man-terminating carbohydrates interact with a single carbohydrate-binding site. Synchronized infectivity assays show that 2G12, MVN, and CVN inhibit entry with distinct kinetics. Despite shared specificity for Man alpha(12) Man termini, combinations of the inhibitors are synergistic suggesting they recognize discrete glycans and/or dynamic glycan conformations on gp120. Entry assays employing amphotropic viruses show that MVN is inactive, whereas CVN potently inhibits both. In addition to demonstrating that HIV-1 can be inhibited through monovalent interactions, given the similarity of the carbohydrate-binding site common to MVN and CVN, these data suggest that gp120 behaves as a clustered glycan epitope and that multivalent-protein interactions achievable with CVN but not MVN are required for inhibition of some viruses.
C1 [Shahzad-ul-Hussan, Syed; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
   [Gustchina, Elena; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
   [Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Bewley, CA (reprint author), 8 Ctr Dr, Bethesda, MD 20892 USA.
EM caroleb@mail.nih.gov
RI Ghirlando, Rodolfo/A-8880-2009; Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
FU National Institutes of Health (NIDDK); Intramural AIDS Targeted
   Antiviral Program of the Office of the Director
FX This work was supported, in whole or in part, by National Institutes of
   Health Intramural Research Program (NIDDK) and the Intramural AIDS
   Targeted Antiviral Program of the Office of the Director (to C. A. B.
   and G. M. C.).
NR 60
TC 31
Z9 31
U1 0
U2 9
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 JUN 10
PY 2011
VL 286
IS 23
BP 20788
EP 20796
DI 10.1074/jbc.M111.232678
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 772WC
UT WOS:000291267600064
PM 21471192
ER

PT J
AU Adler, A
   Park, YD
   Larsen, P
   Nagarajan, V
   Wollenberg, K
   Qiu, J
   Myers, TG
   Williamson, PR
AF Adler, Amos
   Park, Yoon-Dong
   Larsen, Peter
   Nagarajan, Vijayaraj
   Wollenberg, Kurt
   Qiu, Jin
   Myers, Timothy G.
   Williamson, Peter R.
TI A Novel Specificity Protein 1 (SP1)-like Gene Regulating Protein Kinase
   C-1 (Pkc1)-dependent Cell Wall Integrity and Virulence Factors in
   Cryptococcus neoformans
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GENOME-WIDE ANALYSIS; SACCHAROMYCES-CEREVISIAE; SIGNALING PATHWAY;
   CANDIDA-ALBICANS; LACCASE; CALCINEURIN; STRESS; IDENTIFICATION;
   EXPRESSION; INFECTION
AB Eukaryotic cells utilize complex signaling systems to detect their environments, responding and adapting as new conditions arise during evolution. The basidiomycete fungus Cryptococcus neoformans is a leading cause of AIDS-related death worldwide and utilizes the calcineurin and protein kinase C-1 (Pkc1) signaling pathways for host adaptation and expression of virulence. In the present studies, a C-terminal zinc finger transcription factor, homologous both to the calcineurin-responsive zinc fingers (Crz1) of ascomycetes and to the Pkc1-dependent specificity protein-1 (Sp1) transcription factors of metazoans, was identified and named SP1 because of its greater similarity to the metazoan factors. Structurally, the Cryptococcus neoformans Sp1 (Cn Sp1) protein was found to have acquired an additional zinc finger motif from that of Crz1 and showed Pkc1-dependent phosphorylation, nuclear localization, and whole genome epistatic associations under starvation conditions. Transcriptional targets of Cn Sp1 shared functional similarities with Crz1 factors, such as cell wall synthesis, but gained the regulation of processes involved in carbohydrate metabolism, including trehalose metabolism, and lost others, such as the induction of autophagy. In addition, overexpression of Cn Sp1 in a pkc1 Delta mutant showed restoration of altered phenotypes involved in virulence, including cell wall stability, nitrosative stress, and extracellular capsule production. Cn Sp1 was also found to be important for virulence of the fungus using a mouse model. In summary, these data suggest an evolutionary shift in C-terminal zinc finger proteins during fungal evolution, transforming them from calcineurin-dependent to PKC1-dependent transcription factors, helping to shape the role of fungal pathogenesis of C. neoformans.
C1 Univ Chicago, Sect Pediat Infect Dis, Dept Pediat, Chicago, IL 60637 USA.
   [Adler, Amos; Williamson, Peter R.] Univ Illinois, Infect Dis Sect, Dept Med, Coll Med, Chicago, IL 60612 USA.
   [Park, Yoon-Dong; Qiu, Jin; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
   [Nagarajan, Vijayaraj; Wollenberg, Kurt] NIAID, Bioinformat & Computat Biosciences Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
   [Myers, Timothy G.] NIAID, Genom Technol Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
   [Larsen, Peter] Argonne Natl Lab, Biosci Div, Lemont, IL 60439 USA.
RP Williamson, PR (reprint author), 9000 Rockville Pike,Bldg 10,Rm 11N234,MSC 1888, Bethesda, MD 20892 USA.
EM williamsonpr@mail.nih.gov
FU National Institutes of Health [AI45995, AI49371]; National Institutes of
   Health, NIAID
FX This work was supported, in whole or in part, by National Institutes of
   Health Grants AI45995 and AI49371 and by the Intramural Research Program
   of the National Institutes of Health, NIAID.
NR 55
TC 23
Z9 23
U1 0
U2 6
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 JUN 10
PY 2011
VL 286
IS 23
BP 20977
EP 20990
DI 10.1074/jbc.M111.230268
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 772WC
UT WOS:000291267600082
PM 21487010
ER

PT J
AU Silva, Z
   Tong, ZQ
   Cabral, MG
   Martins, C
   Castro, R
   Reis, C
   Trindade, H
   Konstantopoulos, K
   Videira, PA
AF Silva, Zelia
   Tong, ZiQiu
   Guadalupe Cabral, M.
   Martins, Catarina
   Castro, Rita
   Reis, Celso
   Trindade, Helder
   Konstantopoulos, Konstantinos
   Videira, Paula A.
TI Sialyl Lewis(x)-dependent binding of human monocyte-derived dendritic
   cells to selectins
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Monocyte-derived dendritic cells; Selectin; Adhesion; Shear flow;
   IFN-gamma
ID COLON-CARCINOMA; IFN-GAMMA; IN-VITRO; ADHESION; FLOW; MATURATION;
   PSGL-1; LIGAND; IMMUNOTHERAPY; NEUTROPHILS
AB The limited efficacy of monocyte-derived dendritic cell (mo-DC)-based vaccines is primarily attributed to the reduced mo-DC migratory capacity. One undefined aspect is the initial binding of mo-DCs to endothelial cells and vascular selectins. In this study, we investigated the role and modulation of the selectin binding determinant sialyl Lewis(x) (sLe(x)) in selectin-dependent mo-DC binding. Our data reveal that sLe(x) is required for maximal binding of mo-DCs to tumor necrosis factor (TNF)-alpha-activated endothelial cells under static conditions, as evidenced by the use of sialidase. Sialidase treatment also abrogated mo-DC cell tethering to immobilized, purified P-, L-, or E-selectin under flow. The requirement of sLe(x)-dependent binding of mo-DC to selectins was further substantiated by using sLe(x) free sugar and anti-sLe(x) antibody, which significantly suppressed mo-DC-selectin binding. P-selectin glycoprotein ligand-1 is required for mo-DC binding to both P- and L-selectin, but it is dispensable for E-selectin recognition. Interestingly, the extent of mo-DC tethering was maximal on P-selectin, followed by E- and L- selectin. Accordingly, L-selectin mediated faster mo-DC rolling than E- or P-selectin. Interferon (IFN)-gamma induces a significant increase in mo-DC surface sLe(x\) expression, which is probably due to the enhanced synthesis of C2GnT-I. These findings may contribute to improving mo-DC-based vaccination protocols. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Tong, ZiQiu; Konstantopoulos, Konstantinos] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
   [Silva, Zelia; Guadalupe Cabral, M.; Martins, Catarina; Trindade, Helder; Videira, Paula A.] Univ Nova Lisboa, CEDOC, Dept Imunol, Fac Ciencias Med, P-1200 Lisbon, Portugal.
   [Castro, Rita] Univ Lisbon, Metab & Genet Grp, Res Inst Med & Pharmaceut Sci iMed UL, Fac Farm, P-1699 Lisbon, Portugal.
   [Reis, Celso] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Oporto, Portugal.
   [Reis, Celso] Univ Porto, Fac Med, P-4100 Oporto, Portugal.
   [Konstantopoulos, Konstantinos] Johns Hopkins Univ, NCI PS OC Johns Hopkins Phys Sci Oncol Ctr, Baltimore, MD 21218 USA.
   [Konstantopoulos, Konstantinos] Johns Hopkins Univ, Inst NanoBioTechnol, Baltimore, MD 21218 USA.
RP Konstantopoulos, K (reprint author), Johns Hopkins Univ, Dept Chem & Biomol Engn, 3400 N Charles St, Baltimore, MD 21218 USA.
EM konstant@jhu.edu
RI Videira, Paula/A-5901-2013; REIS, Celso/B-9969-2008; iMed.ULisboa,
   iMed.ULisboa/C-6292-2014; Konstantopoulos, Konstantinos/A-7045-2011;
   Castro, Rita /G-7731-2011; silva, zelia/O-7243-2015; Cabral, Maria de
   Guadalupe/N-4029-2016; iMed.ULisboa, MetGen /B-5293-2014; Faculdade de
   Ciencias Medicas, Nova Medical School/K-6209-2013
OI Videira, Paula/0000-0001-5987-2485; REIS, Celso/0000-0002-0286-6639;
   Castro, Rita /0000-0002-4585-0741; silva, zelia/0000-0001-6660-426X;
   Cabral, Maria de Guadalupe/0000-0001-9016-9173; 
FU Fundacao para a Ciencia e Tecnologia, Portugal [PTDC/SAU-MII/67561/2006,
   SFRH/BPD/41168/2007]; NIH/NCI [R01 CA101135, U54 CA143868]
FX This study was supported in part by the Fundacao para a Ciencia e
   Tecnologia, Portugal - PTDC/SAU-MII/67561/2006 and SFRH/BPD/41168/2007
   (Z.S.) and the NIH/NCI R01 CA101135 and U54 CA143868 (K.K.). We thank
   Sergio Dias (CEDOC/FCM, IPO, Lisbon) for kind gift of HUVEC and Dario
   Ligeiro (CHSUL, Lisbon) for the microscopy image acquisition.
NR 31
TC 10
Z9 10
U1 1
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUN 10
PY 2011
VL 409
IS 3
BP 459
EP 464
DI 10.1016/j.bbrc.2011.05.026
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 783CQ
UT WOS:000292059500018
PM 21596017
ER

PT J
AU Kim, HJ
   Lee, CR
   Kim, M
   Peterkofsky, A
   Seok, YJ
AF Kim, Hyun-Jin
   Lee, Chang-Ro
   Kim, Miri
   Peterkofsky, Alan
   Seok, Yeong-Jae
TI Dephosphorylated NPr of the nitrogen PTS regulates lipid A biosynthesis
   by direct interaction with LpxD
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Escherichia coli; Lipid A; Nitrogen PTS; NPr; Protein-protein
   interaction
ID GLOBAL REPRESSOR MLC; ESCHERICHIA-COLI; PHOSPHOTRANSFERASE SYSTEM;
   GLUCOSE-TRANSPORTER; PROTEIN IIA(NTR); ENZYME IIA(NTR); OUTER-MEMBRANE;
   EXPRESSION; ACYLTRANSFERASE; MUTATIONS
AB Bacterial phosphoenolpyruvate-dependent phosphotransferase systems (PTS) play multiple roles in addition to sugar transport. Recent studies revealed that enzyme IIA(Ntr) of the nitrogen PTS regulates the intracellular concentration of K(+) by direct interaction with TrkA and KdpD. In this study, we show that dephosphorylated NPr of the nitrogen PTS interacts with Escherichia coli LpxD which catalyzes biosynthesis of lipid A of the lipopolysaccharide (LPS) layer. Mutations in lipid A biosynthetic genes such as IpxD are known to confer hypersensitivity to hydrophobic antibiotics such as rifampin; a ptsO (encoding NPr) deletion mutant showed increased resistance to rifampin and increased LPS biosynthesis. Taken together, our data suggest that unphosphorylated NPr decreases lipid A biosynthesis by inhibiting LpxD activity. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Kim, Hyun-Jin; Lee, Chang-Ro; Kim, Miri; Seok, Yeong-Jae] Seoul Natl Univ, Dept Biol Sci, Seoul 151742, South Korea.
   [Kim, Hyun-Jin; Lee, Chang-Ro; Kim, Miri; Seok, Yeong-Jae] Seoul Natl Univ, Inst Microbiol, Seoul 151742, South Korea.
   [Peterkofsky, Alan] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
   [Seok, Yeong-Jae] Seoul Natl Univ, Dept Biophys & Chem Biol, Seoul 151742, South Korea.
RP Seok, YJ (reprint author), Seoul Natl Univ, Dept Biol Sci, Seoul 151742, South Korea.
EM yjseok@snu.ac.kr
FU 21C Frontier Microbial Genomics and Applications Center Program
   [MG08-0201-1-0]; WCU [R31-2009-000-10032-0]; MEST [NRF 2010-0017384];
   MLTMA, Republic of Korea; NHLBI, Bethesda, MD, USA; Korean government
FX We thank Dr. C. R. Raetz for generously providing the pDC015-1 plasmid
   and Dr. R. L Levine at NIH for mass spectrometric identification of
   LpxD. This work was supported by the 21C Frontier Microbial Genomics and
   Applications Center Program (MG08-0201-1-0) the WCU program
   (R31-2009-000-10032-0) and the Korea Research Foundation Grant (NRF
   2010-0017384) from MEST, and by the Marine and Extreme Genome Research
   Center Program of the MLTMA, Republic of Korea and, in part, by the
   intramural research program of the NHLBI, Bethesda, MD, USA. H.-J. Kim
   and Miri Kim were supported by the second stage BK21 Research
   Fellowships from the Korean government.
NR 28
TC 17
Z9 18
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 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUN 10
PY 2011
VL 409
IS 3
BP 556
EP 561
DI 10.1016/j.bbrc.2011.05.044
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 783CQ
UT WOS:000292059500034
PM 21605551
ER

PT J
AU Dogan, RI
   Neveol, A
   Lu, ZY
AF Dogan, Rezarta Islamaj
   Neveol, Aurelie
   Lu, Zhiyong
TI A context-blocks model for identifying clinical relationships in patient
   records
SO BMC BIOINFORMATICS
LA English
DT Article
ID BIOMEDICAL TEXT; EXTRACTION; DOCUMENTS; KNOWLEDGE; ACQUISITION;
   PERSPECTIVE; INFORMATION; NARRATIVES
AB Background: Patient records contain valuable information regarding explanation of diagnosis, progression of disease, prescription and/or effectiveness of treatment, and more. Automatic recognition of clinically important concepts and the identification of relationships between those concepts in patient records are preliminary steps for many important applications in medical informatics, ranging from quality of care to hypothesis generation.
   Methods: In this work we describe an approach that facilitates the automatic recognition of eight relationships defined between medical problems, treatments and tests. Unlike the traditional bag-of-words representation, in this work, we represent a relationship with a scheme of five distinct context-blocks determined by the position of concepts in the text. As a preliminary step to relationship recognition, and in order to provide an end-to-end system, we also addressed the automatic extraction of medical problems, treatments and tests. Our approach combined the outcome of a statistical model for concept recognition and simple natural language processing features in a conditional random fields model. A set of 826 patient records from the 4th i2b2 challenge was used for training and evaluating the system.
   Results: Results show that our concept recognition system achieved an F-measure of 0.870 for exact span concept detection. Moreover the context-block representation of relationships was more successful (F-Measure = 0.775) at identifying relationships than bag-of-words (F-Measure = 0.402). Most importantly, the performance of the end-to-end system of relationship extraction using automatically extracted concepts (F-Measure = 0.704) was comparable to that obtained using manually annotated concepts (F-Measure = 0.711), and their difference was not statistically significant.
   Conclusions: We extracted important clinical relationships from text in an automated manner, starting with concept recognition, and ending with relationship identification. The advantage of the context-blocks representation scheme was the correct management of word position information, which may be critical in identifying certain relationships. Our results may serve as benchmark for comparison to other systems developed on i2b2 challenge data. Finally, our system may serve as a preliminary step for other discovery tasks in medical informatics.
C1 [Dogan, Rezarta Islamaj; Neveol, Aurelie; Lu, Zhiyong] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Dogan, RI (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM Rezarta.Islamaj@nih.gov
OI Islamaj Dogan, Rezarta/0000-0001-5651-1860
FU NIH, National Library of Medicine
FX This research was supported by the Intramural Research Program of the
   NIH, National Library of Medicine.
NR 32
TC 8
Z9 8
U1 1
U2 1
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 JUN 9
PY 2011
VL 12
SU 3
AR S3
DI 10.1186/1471-2105-12-S3-S3
PG 11
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
GA 940YW
UT WOS:000303930000004
ER

PT J
AU Jimeno-Yepes, A
   McInnes, BT
   Aronson, AR
AF Jimeno-Yepes, Antonio
   McInnes, Bridget T.
   Aronson, Alan R.
TI Collocation analysis for UMLS knowledge-based word sense disambiguation
SO BMC BIOINFORMATICS
LA English
DT Article
AB Background: The effectiveness of knowledge-based word sense disambiguation (WSD) approaches depends in part on the information available in the reference knowledge resource. Off the shelf, these resources are not optimized for WSD and might lack terms to model the context properly. In addition, they might include noisy terms which contribute to false positives in the disambiguation results.
   Methods: We analyzed some collocation types which could improve the performance of knowledge-based disambiguation methods. Collocations are obtained by extracting candidate collocations from MEDLINE and then assigning them to one of the senses of an ambiguous word. We performed this assignment either using semantic group profiles or a knowledge-based disambiguation method. In addition to collocations, we used second-order features from a previously implemented approach. Specifically, we measured the effect of these collocations in two knowledge-based WSD methods. The first method, AEC, uses the knowledge from the UMLS to collect examples from MEDLINE which are used to train a Naive Bayes approach. The second method, MRD, builds a profile for each candidate sense based on the UMLS and compares the profile to the context of the ambiguous word. We have used two WSD test sets which contain disambiguation cases which are mapped to UMLS concepts. The first one, the NLM WSD set, was developed manually by several domain experts and contains words with high frequency occurrence in MEDLINE. The second one, the MSH WSD set, was developed automatically using the MeSH indexing in MEDLINE. It contains a larger set of words and covers a larger number of UMLS semantic types.
   Results: The results indicate an improvement after the use of collocations, although the approaches have different performance depending on the data set. In the NLM WSD set, the improvement is larger for the MRD disambiguation method using second-order features. Assignment of collocations to a candidate sense based on UMLS semantic group profiles is more effective in the AEC method. In the MSH WSD set, the increment in performance is modest for all the methods. Collocations combined with the MRD disambiguation method have the best performance. The MRD disambiguation method and second-order features provide an insignificant change in performance. The AEC disambiguation method gives a modest improvement in performance. Assignment of collocations to a candidate sense based on knowledge-based methods has better performance.
   Conclusions: Collocations improve the performance of knowledge-based disambiguation methods, although results vary depending on the test set and method used. Generally, the AEC method is sensitive to query drift. Using AEC, just a few selected terms provide a large improvement in disambiguation performance. The MRD method handles noisy terms better but requires a larger set of terms to improve performance.
C1 [Jimeno-Yepes, Antonio; Aronson, Alan R.] Natl Lib Med, Bethesda, MD 20894 USA.
   [McInnes, Bridget T.] Univ Minnesota Twin Cities, Dept Pharmacol, Minneapolis, MN 55455 USA.
RP Jimeno-Yepes, A (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM antonio.jimeno@gmail.com
OI Jimeno Yepes, Antonio Jose/0000-0002-6581-094X
FU NIH, National Library of Medicine; National Library of Medicine
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.
   Jimeno-Yepes to the NLM Research Participation Program sponsored by the
   National Library of Medicine and administered by the Oak Ridge Institute
   for Science and Education.
NR 24
TC 2
Z9 2
U1 1
U2 3
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 JUN 9
PY 2011
VL 12
SU 3
AR S4
DI 10.1186/1471-2105-12-S3-S4
PG 12
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
GA 940YW
UT WOS:000303930000005
PM 21658291
ER

PT J
AU Wilbur, WJ
   Kim, W
AF Wilbur, W. John
   Kim, Won
TI Improving a gold standard: treating human relevance judgments of MEDLINE
   document pairs
SO BMC BIOINFORMATICS
LA English
DT Article
ID INFORMATION-SCIENCE; RETRIEVAL; PERFORMANCE; FRAMEWORK; EXPERTS
AB Given prior human judgments of the condition of an object it is possible to use these judgments to make a maximal likelihood estimate of what future human judgments of the condition of that object will be. However, if one has a reasonably large collection of similar objects and the prior human judgments of a number of judges regarding the condition of each object in the collection, then it is possible to make predictions of future human judgments for the whole collection that are superior to the simple maximal likelihood estimate for each object in isolation. This is possible because the multiple judgments over the collection allow an analysis to determine the relative value of a judge as compared with the other judges in the group and this value can be used to augment or diminish a particular judge's influence in predicting future judgments. Here we study and compare five different methods for making such improved predictions and show that each is superior to simple maximal likelihood estimates.
C1 [Wilbur, W. John; Kim, Won] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Wilbur, WJ (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM wilbur@ncbi.nlm.nih.gov
FU NIH, National Library of Medicine
FX This research was supported by the Intramural Research Program of the
   NIH, National Library of Medicine.
NR 36
TC 2
Z9 2
U1 0
U2 0
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 JUN 9
PY 2011
VL 12
SU 3
AR S5
DI 10.1186/1471-2105-12-S3-S5
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
GA 940YW
UT WOS:000303930000006
PM 21658292
ER

PT J
AU Yeganova, L
   Comeau, DC
   Wilbur, WJ
AF Yeganova, Lana
   Comeau, Donald C.
   Wilbur, W. John
TI Machine learning with naturally labeled data for identifying
   abbreviation definitions
SO BMC BIOINFORMATICS
LA English
DT Article
ID MEDLINE
AB Background: The rapid growth of biomedical literature requires accurate text analysis and text processing tools. Detecting abbreviations and identifying their definitions is an important component of such tools. Most existing approaches for the abbreviation definition identification task employ rule-based methods. While achieving high precision, rule-based methods are limited to the rules defined and fail to capture many uncommon definition patterns. Supervised learning techniques, which offer more flexibility in detecting abbreviation definitions, have also been applied to the problem. However, they require manually labeled training data.
   Methods: In this work, we develop a machine learning algorithm for abbreviation definition identification in text which makes use of what we term naturally labeled data. Positive training examples are naturally occurring potential abbreviation-definition pairs in text. Negative training examples are generated by randomly mixing potential abbreviations with unrelated potential definitions. The machine learner is trained to distinguish between these two sets of examples. Then, the learned feature weights are used to identify the abbreviation full form. This approach does not require manually labeled training data.
   Results: We evaluate the performance of our algorithm on the Ab3P, BIOADI and Medstract corpora. Our system demonstrated results that compare favourably to the existing Ab3P and BIOADI systems. We achieve an F-measure of 91.36% on Ab3P corpus, and an F-measure of 87.13% on BIOADI corpus which are superior to the results reported by Ab3P and BIOADI systems. Moreover, we outperform these systems in terms of recall, which is one of our goals.
C1 [Yeganova, Lana; Comeau, Donald C.; Wilbur, W. John] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Yeganova, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM yeganova@mail.nih.gov
FU NIH, National Library of Medicine
FX This research was supported by the Intramural Research Program of NIH,
   National Library of Medicine.
NR 15
TC 8
Z9 8
U1 0
U2 1
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 JUN 9
PY 2011
VL 12
SU 3
AR S6
DI 10.1186/1471-2105-12-S3-S6
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
GA 940YW
UT WOS:000303930000007
PM 21658293
ER

PT J
AU Zhang, XL
   Zou, J
   Le, DX
   Thoma, GR
AF Zhang, Xiaoli
   Zou, Jie
   Le, Daniel X.
   Thoma, George R.
TI A structural SVM approach for reference parsing
SO BMC BIOINFORMATICS
LA English
DT Article
ID EXTRACTION; CITATIONS; METADATA
AB Background: Automated extraction of bibliographic data, such as article titles, author names, abstracts, and references is essential to the affordable creation of large citation databases. References, typically appearing at the end of journal articles, can also provide valuable information for extracting other bibliographic data. Therefore, parsing individual reference to extract author, title, journal, year, etc. is sometimes a necessary preprocessing step in building citation-indexing systems. The regular structure in references enables us to consider reference parsing a sequence learning problem and to study structural Support Vector Machine (structural SVM), a newly developed structured learning algorithm on parsing references.
   Results: In this study, we implemented structural SVM and used two types of contextual features to compare structural SVM with conventional SVM. Both methods achieve above 98% token classification accuracy and above 95% overall chunk-level accuracy for reference parsing. We also compared SVM and structural SVM to Conditional Random Field (CRF). The experimental results show that structural SVM and CRF achieve similar accuracies at token- and chunk-levels.
   Conclusions: When only basic observation features are used for each token, structural SVM achieves higher performance compared to SVM since it utilizes the contextual label features. However, when the contextual observation features from neighboring tokens are combined, SVM performance improves greatly, and is close to that of structural SVM after adding the second order contextual observation features. The comparison of these two methods with CRF using the same set of binary features show that both structural SVM and CRF perform better than SVM, indicating their stronger sequence learning ability in reference parsing.
C1 [Zhang, Xiaoli; Zou, Jie; Le, Daniel X.; Thoma, George R.] Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA.
RP Zhang, XL (reprint author), Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM zhangxiaol@mail.nih.gov
FU National Institutes of Health (NIH); National Library of Medicine;
   Lister Hill National Center for Biomedical Communications
FX This research was supported by the Intramural Research Program of the
   National Institutes of Health (NIH), National Library of Medicine, and
   Lister Hill National Center for Biomedical Communications.
NR 22
TC 3
Z9 3
U1 0
U2 8
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 JUN 9
PY 2011
VL 12
SU 3
AR S7
DI 10.1186/1471-2105-12-S3-S7
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
GA 940YW
UT WOS:000303930000008
PM 21658294
ER

PT J
AU Jirawatnotai, S
   Hu, YD
   Michowski, W
   Elias, JE
   Becks, L
   Bienvenu, F
   Zagozdzon, A
   Goswami, T
   Wang, YYE
   Clark, AB
   Kunkel, TA
   van Harn, T
   Xia, B
   Correll, M
   Quackenbush, J
   Livingston, DM
   Gygi, SP
   Sicinski, P
AF Jirawatnotai, Siwanon
   Hu, Yiduo
   Michowski, Wojciech
   Elias, Joshua E.
   Becks, Lisa
   Bienvenu, Frederic
   Zagozdzon, Agnieszka
   Goswami, Tapasree
   Wang, Yaoyu E.
   Clark, Alan B.
   Kunkel, Thomas A.
   van Harn, Tanja
   Xia, Bing
   Correll, Mick
   Quackenbush, John
   Livingston, David M.
   Gygi, Steven P.
   Sicinski, Piotr
TI A function for cyclin D1 in DNA repair uncovered by protein interactome
   analyses in human cancers
SO NATURE
LA English
DT Article
ID HUMAN RAD51 PROTEIN; DOUBLE-STRAND BREAK; RETINOBLASTOMA-PROTEIN;
   MAMMALIAN-CELLS; IN-VITRO; DAMAGE; PHOSPHORYLATION; OVEREXPRESSION;
   RECOMBINATION; EXPRESSION
AB Cyclin D1 is a component of the core cell cycle machinery(1). Abnormally high levels of cyclin D1 are detected in many human cancer types(2). To elucidate the molecular functions of cyclin D1 in human cancers, we performed a proteomic screen for cyclin D1 protein partners in several types of human tumours. Analyses of cyclin D1 interactors revealed a network of DNA repair proteins, including RAD51, a recombinase that drives the homologous recombination process(3). We found that cyclin D1 directly binds RAD51, and that cyclin D1-RAD51 interaction is induced by radiation. Like RAD51, cyclin D1 is recruited to DNA damage sites in a BRCA2-dependent fashion. Reduction of cyclin D1 levels in human cancer cells impaired recruitment of RAD51 to damaged DNA, impeded the homologous recombination-mediated DNA repair, and increased sensitivity of cells to radiation in vitro and in vivo. This effect was seen in cancer cells lacking the retinoblastoma protein, which do not require D-cyclins for proliferation(4,5). These findings reveal an unexpected function of a core cell cycle protein in DNA repair and suggest that targeting cyclin D1 may be beneficial also in retinoblastoma-negative cancers which are currently thought to be unaffected by cyclin D1 inhibition.
C1 [Jirawatnotai, Siwanon; Hu, Yiduo; Michowski, Wojciech; Becks, Lisa; Bienvenu, Frederic; Zagozdzon, Agnieszka; van Harn, Tanja; Livingston, David M.; Sicinski, Piotr] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   [Jirawatnotai, Siwanon; Hu, Yiduo; Michowski, Wojciech; Becks, Lisa; Bienvenu, Frederic; Zagozdzon, Agnieszka; van Harn, Tanja; Livingston, David M.; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA.
   [Jirawatnotai, Siwanon] Mahidol Univ, Inst Mol Biosci, Salaya 73170, Nakhon Prathom, Thailand.
   [Elias, Joshua E.; Goswami, Tapasree; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   [Becks, Lisa] Massachusetts Coll Pharm & Hlth Sci, Dept Pharmacol, Boston, MA 02115 USA.
   [Wang, Yaoyu E.; Correll, Mick; Quackenbush, John] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02215 USA.
   [Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
   [Clark, Alan B.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
   [Xia, Bing] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Dept Radiat Oncol, New Brunswick, NJ 08903 USA.
   [Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
   [Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA.
RP Sicinski, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
EM peter_sicinski@dfci.harvard.edu
FU NIH [R01 CA083688, P01 CA080111, P01 CA109901]; Thailand Research Fund
   [MRG5280248]; Foundation for Polish Science; CCCB; Dana-Farber Strategic
   Plan Initiative; Division of Intramural Research of the NIH, NIEHS [Z01
   ES065089]
FX We thank the members of the Sicinski lab for help and advice, N. Li for
   help with initial experiments, S Panyim and Y. Geng for discussions and
   reading the manuscript, P. Nakatani for pOZ-FH-N construct, M. Jasin for
   DR-GFP system, D. Bulavin and E. Appella for anti-phospho-CDC25A
   antibodies, A. Smogorzewska for anti-FANCI antibody, A. Venkitaraman and
   M. Lee for GST-BRCA2 fragments, and DFCI Confocal and Light Microscopy
   Core Facility for assisting with confocal microscopy. This work was
   supported by R01 CA083688, P01 CA080111 and P01 CA109901 grants from NIH
   (to P.S.). S.J. is supported by The Thailand Research Fund MRG5280248,
   W.M. by Foundation for Polish Science, Y.E.W. through the CCCB and the
   Dana-Farber Strategic Plan Initiative, A.B.C. and T.A.K. by Project Z01
   ES065089 (to T.A.K.) from the Division of Intramural Research of the
   NIH, NIEHS.
NR 29
TC 130
Z9 133
U1 2
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUN 9
PY 2011
VL 474
IS 7350
BP 230
EP 234
DI 10.1038/nature10155
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 774PE
UT WOS:000291397800054
PM 21654808
ER

PT J
AU Dranovsky, A
   Picchini, AM
   Moadel, T
   Sisti, AC
   Yamada, A
   Kimura, S
   Leonardo, ED
   Hen, R
AF Dranovsky, Alex
   Picchini, Alyssa M.
   Moadel, Tiffany
   Sisti, Alexander C.
   Yamada, Atsushi
   Kimura, Shioko
   Leonardo, E. David
   Hen, Rene
TI Experience Dictates Stem Cell Fate in the Adult Hippocampus
SO NEURON
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; RAT DENTATE GYRUS; PROGENITOR CELLS; PATTERN
   SEPARATION; NEUROGENESIS; NEURONS; MICE; PROLIFERATION; DIVISION; MEMORY
AB Adult hippocampal neurogenesis has been implicated in cognitive and emotional processes, as well as in response to antidepressant treatment. However, little is known about how the adult stem cell lineage contributes to hippocampal structure and function and how this process is modulated by the animal's experience. Here we perform an indelible lineage analysis and report that neural stem cells can produce expanding and persisting populations of not only neurons, but also stem cells in the adult hippocampus. Furthermore, the ratio of stem cells to neurons depends on experiences of the animal or the location of the stem cell. Surprisingly, social isolation facilitated accumulation of stem cells, but not neurons. These results show that neural stem cells accumulate in the adult hippocampus and that the stem cell-lineage relationship is under control of anatomic and experiential niches. Our findings suggest that, in the hippocampus, fate specification may act as a form of cellular plasticity for adapting to environmental changes.
C1 [Dranovsky, Alex; Picchini, Alyssa M.; Moadel, Tiffany; Sisti, Alexander C.; Leonardo, E. David; Hen, Rene] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
   [Picchini, Alyssa M.; Hen, Rene] Columbia Univ, Dept Pharmacol, New York, NY 10032 USA.
   [Hen, Rene] Columbia Univ, Dept Neurosci, New York, NY 10032 USA.
   [Dranovsky, Alex; Picchini, Alyssa M.; Moadel, Tiffany; Sisti, Alexander C.; Leonardo, E. David; Hen, Rene] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
   [Yamada, Atsushi; Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Dranovsky, A (reprint author), Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
EM ad722@columbia.edu
FU NIH [K08MH079088, R01MH068542, NIH T32HD055165]; BRAINS [R01MH0911844];
   NARSAD; NYSTEM; NCI CCR [P50 MH66171]
FX The authors thank Matheus Araujo for technical assistance, Eric Kandel
   and Harshad Vishwasrao for sharing confocal resources, Richard Josephson
   for providing the pNerv-SXN construct, Linda Byrd for assistance with
   mice, and Frank Gonzalez. We are grateful to Chris Henderson, Fiona
   Doetsch, Ben Samuels, and Jesse Richardson-Jones for helpful discussions
   and critical reading of the manuscript. This work was supported by NIH
   K08MH079088, BRAINS R01MH0911844, and NARSAD Young Investigator Awards
   (A.D.); NIH R01MH068542 and NYSTEM (R.H.); NCI CCR Intramural Research
   Program (S.K.), P50 MH66171 (Molecular and Cellular Core) and the NYSTEM
   institutional development award; A.P. was supported by NIH T32HD055165.
   R.H. receives compensation as a consultant for Braincells, in relation
   to the generation of novel antidepressants. E.D.L. receives compensation
   as a consultant from PGxHealth.
NR 62
TC 82
Z9 85
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD JUN 9
PY 2011
VL 70
IS 5
BP 908
EP 923
DI 10.1016/j.neuron.2011.05.022
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA 780GW
UT WOS:000291843500011
PM 21658584
ER

PT J
AU Flandin, P
   Zhao, YG
   Vogt, D
   Jeong, J
   Long, J
   Potter, G
   Westphal, H
   Rubensteint, JLR
AF Flandin, Pierre
   Zhao, Yangu
   Vogt, Daniel
   Jeong, Juhee
   Long, Jason
   Potter, Gregory
   Westphal, Heiner
   Rubensteint, John L. R.
TI Lhx6 and Lhx8 Coordinately Induce Neuronal Expression of Shh that
   Controls the Generation of Interneuron Progenitors
SO NEURON
LA English
DT Article
ID MEDIAL GANGLIONIC EMINENCE; LIM-HOMEOBOX GENE; SONIC HEDGEHOG; CORTICAL
   INTERNEURONS; STRIATAL INTERNEURONS; VENTRAL TELENCEPHALON; CHOLINERGIC
   NEURONS; SPECIFICATION; FOREBRAIN; MIGRATION
AB Lhx6 and Lhx8 transcription factor coexpression in early-born MGE neurons is required to induce neuronal Shh expression. We provide evidence that these transcription factors regulate expression of a Shh enhancer in MGE neurons. Lhx6 and Lhx8 are also required to prevent Nkx2-1 expression in a subset of pallial interneurons. Shh function in early-born MGE neurons was determined by genetically eliminating Shh expression in the MGE mantle zone (MZ). This mutant had reduced SHH signaling in the overlying progenitor zone, which led to reduced Lhx6, Lhx8, and Nkx2-1 expression in the rostrodorsal MGE and a preferential reduction of late-born somatostatin(+) and parvalbumin(+) cortical interneurons. Thus, Lhx6 and Lhx8 regulate MGE development through autonomous and nonautonomous mechanisms, the latter by promoting Shh expression in MGE neurons, which in turn feeds forward to promote the developmental program of the rostrodorsal MGE.
C1 [Flandin, Pierre; Vogt, Daniel; Jeong, Juhee; Long, Jason; Potter, Gregory; Rubensteint, John L. R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA.
   [Flandin, Pierre; Vogt, Daniel; Jeong, Juhee; Long, Jason; Potter, Gregory; Rubensteint, John L. R.] Univ Calif San Francisco, Nina Ireland Lab Dev Neurobiol, San Francisco, CA 94158 USA.
   [Zhao, Yangu; Westphal, Heiner] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Mammalian Genes & Dev, Program Genom Differentiat, Bethesda, MD 20892 USA.
RP Rubensteint, JLR (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA.
EM john.rubenstein@ucsf.edu
OI Potter, Gregory/0000-0002-0585-6575; Vogt, Daniel/0000-0003-1876-5936
FU Nina Ireland; Larry L. Hillblom Foundation; March of Dimes; Weston
   Havens Foundation; NIMH [R37 MH049428, R01 MH081880]; NIDCR [K99
   DE019486-01]; Eunice Kennedy Shriver National Institute of Child Health
   and Human Development/NIH
FX This work was supported by the research grants to J.L.R.R. from Nina
   Ireland, Larry L. Hillblom Foundation, March of Dimes, Weston Havens
   Foundation, NIMH R37 MH049428 and R01 MH081880; to J.J. from NIDCR K99
   DE019486-01; and to H.W. and Y.Z. from the intramural research program
   of the Eunice Kennedy Shriver National Institute of Child Health and
   Human Development/NIH.
NR 38
TC 58
Z9 60
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD JUN 9
PY 2011
VL 70
IS 5
BP 939
EP 950
DI 10.1016/j.neuron.2011.04.020
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 780GW
UT WOS:000291843500013
PM 21658586
ER

PT J
AU Hume, JCC
   Hamilton, H
   Lee, KL
   Lehmann, T
AF Hume, Jen C. C.
   Hamilton, Howard, III
   Lee, Kevin L.
   Lehmann, Tovi
TI Susceptibility of Anopheles stephensi to Plasmodium gallinaceum: A Trait
   of the Mosquito, the Parasite, and the Environment
SO PLOS ONE
LA English
DT Article
ID AVIAN MALARIA PARASITES; COEVOLUTIONARY INTERACTIONS;
   CULICOIDES-VARIIPENNIS; WUCHERERIA-BANCROFTI; VECTOR COMPETENCE; LOCAL
   ADAPTATION; BLUETONGUE-VIRUS; GAMBIAE; HOST; TRANSMISSION
AB Background: Vector susceptibility to Plasmodium infection is treated primarily as a vector trait, although it is a composite trait expressing the joint occurrence of the parasite and the vector with genetic contributions of both. A comprehensive approach to assess the specific contribution of genetic and environmental variation on "vector susceptibility" is lacking. Here we developed and implemented a simple scheme to assess the specific contributions of the vector, the parasite, and the environment to "vector susceptibility." To the best of our knowledge this is the first study that employs such an approach.
   Methodology/Principal Findings: We conducted selection experiments on the vector (while holding the parasite "constant") and on the parasite (while holding the vector "constant") to estimate the genetic contributions of the mosquito and the parasite to the susceptibility of Anopheles stephensi to Plasmodium gallinaceum. We separately estimated the realized heritability of (i) susceptibility to parasite infection by the mosquito vector and (ii) parasite compatibility (transmissibility) with the vector while controlling the other. The heritabilities of vector and the parasite were higher for the prevalence, i. e., fraction of infected mosquitoes, than the corresponding heritabilities of parasite load, i. e., the number of oocysts per mosquito.
   Conclusions: The vector's genetics (heritability) comprised 67% of "vector susceptibility" measured by the prevalence of mosquitoes infected with P. gallinaceum oocysts, whereas the specific contribution of parasite genetics (heritability) to this trait was only 5%. Our parasite source might possess minimal genetic diversity, which could explain its low heritability (and the high value of the vector). Notably, the environment contributed 28%. These estimates are relevant only to the particular system under study, but this experimental design could be useful for other parasite-host systems. The prospects and limitations of the genetic manipulation of vector populations to render the vector resistant to the parasite are better considered on the basis of this framework.
C1 [Hume, Jen C. C.; Hamilton, Howard, III; Lee, Kevin L.; Lehmann, Tovi] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
RP Hume, JCC (reprint author), Seattle Biomed Res Inst, 4 Nickerson St, Seattle, WA 98109 USA.
EM tlehmann@niaid.nih.gov
FU NIH, NIAID
FX This study was supported by the Intramural Research Program in NIH,
   NIAID. The funders had no role in study design, data collection and
   analysis, decision to publish, or preparation of the manuscript.
NR 52
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U1 2
U2 9
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 JUN 9
PY 2011
VL 6
IS 6
AR e20156
DI 10.1371/journal.pone.0020156
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777JX
UT WOS:000291612900006
PM 21694762
ER

PT J
AU Tvermoes, BE
   Bird, GS
   Freedman, JH
AF Tvermoes, Brooke E.
   Bird, Gary S.
   Freedman, Jonathan H.
TI Cadmium Induces Transcription Independently of Intracellular Calcium
   Mobilization
SO PLOS ONE
LA English
DT Article
ID GENE-EXPRESSION; HEPG2 CELLS; METAL CARCINOGENESIS; MICROARRAY ANALYSIS;
   EPITHELIAL-CELLS; RAT HEPATOCYTES; MESANGIAL CELLS; C-FOS; APOPTOSIS;
   MECHANISMS
AB Background: Exposure to cadmium is associated with human pathologies and altered gene expression. The molecular mechanisms by which cadmium affects transcription remain unclear. It has been proposed that cadmium activates transcription by altering intracellular calcium concentration ([Ca(2+)](i)) and disrupting calcium-mediated intracellular signaling processes. This hypothesis is based on several studies that may be technically problematic; including the use of BAPTA chelators, BAPTA-based fluorescent sensors, and cytotoxic concentrations of metal.
   Methodology/Principal Finding: In the present report, the effects of cadmium on [Ca(2+)] i under non-cytotoxic and cytotoxic conditions was monitored using the protein-based calcium sensor yellow cameleon (YC3.60), which was stably expressed in HEK293 cells. In HEK293 constitutively expressing YC3.60, this calcium sensor was found to be insensitive to cadmium. Exposing HEK293::YC3.60 cells to non-cytotoxic cadmium concentrations was sufficient to induce transcription of cadmium-responsive genes but did not affect [Ca(2+)] i mobilization or increase steady-state mRNA levels of calcium-responsive genes. In contrast, exposure to cytotoxic concentrations of cadmium significantly reduced intracellular calcium stores and altered calcium-responsive gene expression.
   Conclusions/Significance: These data indicate that at low levels, cadmium induces transcription independently of intracellular calcium mobilization. The results also support a model whereby cytotoxic levels of cadmium activate calcium-responsive transcription as a general response to metal-induced intracellular damage and not via a specific mechanism. Thus, the modulation of intracellular calcium may not be a primary mechanism by which cadmium regulates transcription.
C1 [Tvermoes, Brooke E.; Freedman, Jonathan H.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
   [Bird, Gary S.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
   [Tvermoes, Brooke E.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA.
RP Tvermoes, BE (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM freedma1@niehs.nih.gov
FU NIH; NIEHS [Z01ES102045]
FX This work was supported in part by the Intramural Research Program of
   the NIH, and NIEHS (Z01ES102045). The funders had no role in study
   design, data collection and analysis, decision to publish, or
   preparation of the manuscript. No additional external funding received
   for this study.
NR 59
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U2 5
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 JUN 9
PY 2011
VL 6
IS 6
AR e20542
DI 10.1371/journal.pone.0020542
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777JX
UT WOS:000291612900014
PM 21694771
ER

PT J
AU Wohr, M
   Roullet, FI
   Hung, AY
   Sheng, M
   Crawley, JN
AF Woehr, Markus
   Roullet, Florence I.
   Hung, Albert Y.
   Sheng, Morgan
   Crawley, Jacqueline N.
TI Communication Impairments in Mice Lacking Shank1: Reduced Levels of
   Ultrasonic Vocalizations and Scent Marking Behavior
SO PLOS ONE
LA English
DT Article
ID AUTISM SPECTRUM DISORDERS; MUS-DOMESTICUS RUTTY; FEMALE HOUSE MICE;
   POSTSYNAPTIC DENSITY PROTEINS; TF/J MOUSE MODEL; DEVELOPMENTAL
   INFLUENCES; URINE MARKING; GENETIC INFLUENCES; UNUSUAL REPERTOIRE;
   SYNAPTIC PROTEINS
AB Autism is a neurodevelopmental disorder with a strong genetic component. Core symptoms are abnormal reciprocal social interactions, qualitative impairments in communication, and repetitive and stereotyped patterns of behavior with restricted interests. Candidate genes for autism include the SHANK gene family, as mutations in SHANK2 and SHANK3 have been detected in several autistic individuals. SHANK genes code for a family of scaffolding proteins located in the postsynaptic density of excitatory synapses. To test the hypothesis that a mutation in SHANK1 contributes to the symptoms of autism, we evaluated Shank1(-/-) null mutant mice for behavioral phenotypes with relevance to autism, focusing on social communication. Ultrasonic vocalizations and the deposition of scent marks appear to be two major modes of mouse communication. Our findings revealed evidence for low levels of ultrasonic vocalizations and scent marks in Shank1(-/-) mice as compared to wildtype Shank1(+/+) littermate controls. Shank1(-/-) pups emitted fewer vocalizations than Shank1(+/+) pups when isolated from mother and littermates. In adulthood, genotype affected scent marking behavior in the presence of female urinary pheromones. Adult Shank1(-/-) males deposited fewer scent marks in proximity to female urine than Shank1(+/+) males. Call emission in response to female urinary pheromones also differed between genotypes. Shank1(+/+) mice changed their calling pattern dependent on previous female interactions, while Shank1(-/-) mice were unaffected, indicating a failure of Shank1(-/-) males to learn from a social experience. The reduced levels of ultrasonic vocalizations and scent marking behavior in Shank1(-/-) mice are consistent with a phenotype relevant to social communication deficits in autism.
C1 [Woehr, Markus; Roullet, Florence I.; Crawley, Jacqueline N.] NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA.
   [Hung, Albert Y.; Sheng, Morgan] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA.
RP Wohr, M (reprint author), NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA.
EM markus.woehr@staff.uni-marburg.de; crawleyj@mail.nih.gov
FU National Institute of Mental Health; Simons Foundation
FX This work was supported by the National Institute of Mental Health
   Intramural Research Program and Simons Foundation (M. S. & A. H.). The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript.
NR 122
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U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 9
PY 2011
VL 6
IS 6
AR e20631
DI 10.1371/journal.pone.0020631
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777JX
UT WOS:000291612900018
PM 21695253
ER

PT J
AU Gerstein, HC
   Miller, ME
   Rosenberg, YD
AF Gerstein, Hertzel C.
   Miller, Michael E.
   Rosenberg, Yves D.
TI Intensive Glucose Lowering and Cardiovascular Outcomes REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Gerstein, Hertzel C.] McMaster Univ, Hamilton, ON, Canada.
   [Miller, Michael E.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
   [Rosenberg, Yves D.] NHLBI, Bethesda, MD 20892 USA.
RP Gerstein, HC (reprint author), McMaster Univ, Hamilton, ON, Canada.
EM gerstein@mcmaster.ca
RI Gerstein, Hertzel/B-1235-2013
OI Gerstein, Hertzel/0000-0001-8072-2836
NR 1
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 9
PY 2011
VL 364
IS 23
BP 2264
EP 2264
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 774NA
UT WOS:000291392100023
ER

PT J
AU Neary, NM
   King, KS
   Pacak, K
AF Neary, Nicola M.
   King, Kathryn S.
   Pacak, Karel
TI Drugs and Pheochromocytoma - Don't Be Fooled by Every Elevated
   Metanephrine
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Neary, Nicola M.; King, Kathryn S.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Neary, NM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
EM karel@mail.nih.gov
FU Intramural NIH HHS [Z01 HD008735-08]
NR 6
TC 28
Z9 29
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 9
PY 2011
VL 364
IS 23
BP 2268
EP 2270
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 774NA
UT WOS:000291392100030
PM 21651412
ER

PT J
AU Dogan, RI
   Yeganova, L
AF Dogan, Rezarta Islamaj
   Yeganova, Lana
TI Topics in machine learning for biomedical literature analysis and text
   retrieval
SO BMC BIOINFORMATICS
LA English
DT Editorial Material
C1 [Dogan, Rezarta Islamaj; Yeganova, Lana] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Yeganova, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM Yeganova@mail.nih.gov
OI Islamaj Dogan, Rezarta/0000-0001-5651-1860
NR 11
TC 0
Z9 0
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JUN 9
PY 2011
VL 12
SU 3
DI 10.1186/1471-2105-12-S3-I1
PG 3
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
GA 940YW
UT WOS:000303930000001
ER

PT J
AU Gee, ST
   Milgram, SL
   Kramer, KL
   Conlon, FL
   Moody, SA
AF Gee, Stephen T.
   Milgram, Sharon L.
   Kramer, Kenneth L.
   Conlon, Frank L.
   Moody, Sally A.
TI Yes-Associated Protein 65 (YAP) Expands Neural Progenitors and Regulates
   Pax3 Expression in the Neural Plate Border Zone
SO PLOS ONE
LA English
DT Article
ID WW DOMAIN; TRANSCRIPTION FACTOR; CRANIAL PLACODES; XENOPUS-EMBRYOS;
   GENE; INDUCTION; CREST; ENHANCER; HOMOLOG; LAEVIS
AB Yes-associated protein 65 (YAP) contains multiple protein-protein interaction domains and functions as both a transcriptional co-activator and as a scaffolding protein. Mouse embryos lacking YAP did not survive past embryonic day 8.5 and showed signs of defective yolk sac vasculogenesis, chorioallantoic fusion, and anterior-posterior (A-P) axis elongation. Given that the YAP knockout mouse defects might be due in part to nutritional deficiencies, we sought to better characterize a role for YAP during early development using embryos that develop externally. YAP morpholino (MO)mediated loss-of-function in both frog and fish resulted in incomplete epiboly at gastrulation and impaired axis formation, similar to the mouse phenotype. In frog, germ layer specific genes were expressed, but they were temporally delayed. YAP MO-mediated partial knockdown in frog allowed a shortened axis to form. YAP gain-of-function in Xenopus expanded the progenitor populations in the neural plate (sox2(+)) and neural plate border zone (pax3(+)), while inhibiting the expression of later markers of tissues derived from the neural plate border zone (neural crest, pre-placodal ectoderm, hatching gland), as well as epidermis and somitic muscle. YAP directly regulates pax3 expression via association with TEAD1 (N-TEF) at a highly conserved, previously undescribed, TEAD-binding site within the 59 regulatory region of pax3. Structure/function analyses revealed that the PDZ-binding motif of YAP contributes to the inhibition of epidermal and somitic muscle differentiation, but a complete, intact YAP protein is required for expansion of the neural plate and neural plate border zone progenitor pools. These results provide a thorough analysis of YAP mediated gene expression changes in loss-and gain-of-function experiments. Furthermore, this is the first report to use YAP structure-function analyzes to determine which portion of YAP is involved in specific gene expression changes and the first to show direct in vivo evidence of YAP's role in regulating pax3 neural crest expression.
C1 [Gee, Stephen T.] Univ N Carolina, Sch Med, Dept Cell & Dev Biol, Chapel Hill, NC 27515 USA.
   [Gee, Stephen T.; Milgram, Sharon L.; Kramer, Kenneth L.] NHLBI, NIH, Bethesda, MD 20892 USA.
   [Conlon, Frank L.] Univ N Carolina, Dept Biol, Chapel Hill, NC USA.
   [Conlon, Frank L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
   [Moody, Sally A.] George Washington Univ, Dept Anat & Regenerat Biol, Washington, DC USA.
RP Gee, ST (reprint author), Univ N Carolina, Sch Med, Dept Cell & Dev Biol, Chapel Hill, NC 27515 USA.
EM samoody@gwu.edu
OI Moody, Sally/0000-0003-4192-1087
FU NSF [IOS-0817902]; NIH; University of North Carolina at Chapel Hill; 
   [HL-65755]
FX This work was supported in part by HL-65755 (SLM), NSF IOS-0817902
   (SAM), and the NIH Intramural Research Program (NIH-IRP) (STG and SLM).
   STG was supported by the NIH-IRP and the University of North Carolina at
   Chapel Hill as a member of the NIH Graduate Partnerships Program. The
   funders had no role in study design, data collection and analysis,
   decision to publish, or preparation of the manuscript. No additional
   external funding received for this study.
NR 62
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U1 0
U2 6
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 JUN 8
PY 2011
VL 6
IS 6
AR e20309
DI 10.1371/journal.pone.0020309
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777JJ
UT WOS:000291611500015
PM 21687713
ER

PT J
AU Ishida, Y
   Oleksyk, TK
   Georgiadis, NJ
   David, VA
   Zhao, K
   Stephens, RM
   Kolokotronis, SO
   Roca, AL
AF Ishida, Yasuko
   Oleksyk, Taras K.
   Georgiadis, Nicholas J.
   David, Victor A.
   Zhao, Kai
   Stephens, Robert M.
   Kolokotronis, Sergios-Orestis
   Roca, Alfred L.
TI Reconciling Apparent Conflicts between Mitochondrial and Nuclear
   Phylogenies in African Elephants
SO PLOS ONE
LA English
DT Article
ID TETRANUCLEOTIDE MICROSATELLITE LOCI; CYTONUCLEAR GENOMIC DISSOCIATION;
   CONTROL REGION SEQUENCES; SEX-BIASED DISPERSAL; POPULATION-STRUCTURE;
   WEST-AFRICA; INBREEDING AVOIDANCE; LOXODONTA-AFRICANA; GENETIC
   DIVERSITY; FOREST ELEPHANTS
AB Conservation strategies for African elephants would be advanced by resolution of conflicting claims that they comprise one, two, three or four taxonomic groups, and by development of genetic markers that establish more incisively the provenance of confiscated ivory. We addressed these related issues by genotyping 555 elephants from across Africa with microsatellite markers, developing a method to identify those loci most effective at geographic assignment of elephants (or their ivory), and conducting novel analyses of continent-wide datasets of mitochondrial DNA. Results showed that nuclear genetic diversity was partitioned into two clusters, corresponding to African forest elephants (99.5% Cluster-1) and African savanna elephants (99.4% Cluster-2). Hybrid individuals were rare. In a comparison of basal forest "F" and savanna "S" mtDNA clade distributions to nuclear DNA partitions, forest elephant nuclear genotypes occurred only in populations in which S clade mtDNA was absent, suggesting that nuclear partitioning corresponds to the presence or absence of S clade mtDNA. We reanalyzed African elephant mtDNA sequences from 81 locales spanning the continent and discovered that S clade mtDNA was completely absent among elephants at all 30 sampled tropical forest locales. The distribution of savanna nuclear DNA and S clade mtDNA corresponded closely to range boundaries traditionally ascribed to the savanna elephant species based on habitat and morphology. Further, a reanalysis of nuclear genetic assignment results suggested that West African elephants do not comprise a distinct third species. Finally, we show that some DNA markers will be more useful than others for determining the geographic origins of illegal ivory. These findings resolve the apparent incongruence between mtDNA and nuclear genetic patterns that has confounded the taxonomy of African elephants, affirm the limitations of using mtDNA patterns to infer elephant systematics or population structure, and strongly support the existence of two elephant species in Africa.
C1 [Ishida, Yasuko; Zhao, Kai; Roca, Alfred L.] Univ Illinois, Dept Anim Sci, Urbana, IL 61801 USA.
   [Oleksyk, Taras K.] Univ Puerto Rico, Dept Biol, Mayaguez, PR USA.
   [Georgiadis, Nicholas J.] Bole & Klingenstein Fdn, Cody, WY USA.
   [David, Victor A.] NCI, Lab Genom Divers, Frederick, MD 21701 USA.
   [Stephens, Robert M.] NCI, SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD 21701 USA.
   [Kolokotronis, Sergios-Orestis] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA.
   [Roca, Alfred L.] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA.
RP Ishida, Y (reprint author), Univ Illinois, Dept Anim Sci, 328 Mumford Hall, Urbana, IL 61801 USA.
EM taras.oleksyk@upr.edu; roca@illinois.edu
RI Taras, Oleksyk/J-8805-2013; Kolokotronis, Sergios-Orestis/A-1910-2009
OI Taras, Oleksyk/0000-0002-8148-3918; Kolokotronis,
   Sergios-Orestis/0000-0003-3309-8465
FU U. S. Fish and Wildlife Service African Elephant Conservation Fund
   [AFE-0458-98210-8-G743]
FX Funding was provided by the U. S. Fish and Wildlife Service African
   Elephant Conservation Fund Grant no. AFE-0458-98210-8-G743. The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 85
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U1 5
U2 43
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 JUN 8
PY 2011
VL 6
IS 6
AR e20642
DI 10.1371/journal.pone.0020642
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777JJ
UT WOS:000291611500036
PM 21701575
ER

PT J
AU Leger, A
   Le Guiner, C
   Nickerson, ML
   Im, KM
   Ferry, N
   Moullier, P
   Snyder, RO
   Penaud-Budloo, M
AF Leger, Adrien
   Le Guiner, Caroline
   Nickerson, Michael L.
   Im, Kate Mcgee
   Ferry, Nicolas
   Moullier, Philippe
   Snyder, Richard O.
   Penaud-Budloo, Magalie
TI Adeno-Associated Viral Vector-Mediated Transgene Expression Is
   Independent of DNA Methylation in Primate Liver and Skeletal Muscle
SO PLOS ONE
LA English
DT Article
ID LONG TERMINAL REPEAT; VIRUS-DERIVED VECTORS; GENE-THERAPY VECTORS;
   TRANSCRIPTIONAL REPRESSION; INTRAMUSCULAR INJECTION; CPG METHYLATION;
   AVIAN-SARCOMA; CELLS; CHROMATIN; PROMOTER
AB Recombinant adeno-associated viral (rAAV) vectors can support long-term transgene expression in quiescent tissues. Intramuscular (IM) administration of a single-stranded AAV vector (ssAAV) in the nonhuman primate (NHP) results in a peak protein level at 2-3 months, followed by a decrease over several months before reaching a steady-state. To investigate transgene expression and vector genome persistence, we previously demonstrated that rAAV vector genomes associate with histones and form a chromatin structure in NHP skeletal muscle more than one year after injection. In the mammalian nucleus, chromatin remodeling via epigenetic modifications plays key role in transcriptional regulation. Among those, CpG hyper-methylation of promoters is a known hallmark of gene silencing. To assess the involvement of DNA methylation on the transgene expression, we injected NHP via the IM or the intravenous (IV) route with a recombinant ssAAV2/1 vector. The expression cassette contains the transgene under the transcriptional control of the constitutive Rous Sarcoma Virus promoter (RSVp). Total DNA isolated from NHP muscle and liver biopsies from 1 to 37 months post-injection was treated with sodium bisulfite and subsequently analyzed by pyrosequencing. No significant CpG methylation of the RSVp was found in rAAV virions or in vector DNA isolated from NHP transduced tissues. Direct de novo DNA methylation appears not to be involved in repressing transgene expression in NHP after gene transfer mediated by ssAAV vectors. The study presented here examines host/vector interactions and the impact on transgene expression in a clinically relevant model.
C1 [Leger, Adrien; Le Guiner, Caroline; Moullier, Philippe; Snyder, Richard O.; Penaud-Budloo, Magalie] INSERM, UMR649, Nantes, France.
   [Le Guiner, Caroline; Moullier, Philippe] Genethon, Evry, France.
   [Nickerson, Michael L.; Im, Kate Mcgee] NCI, NIH, Frederick, MD 21701 USA.
   [Ferry, Nicolas] INSERM, UMR948, Nantes, France.
   [Moullier, Philippe; Snyder, Richard O.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA.
   [Snyder, Richard O.] Univ Florida, Ctr Excellence Regenerat Hlth Biotechnol, Alachua, FL USA.
RP Leger, A (reprint author), INSERM, UMR649, Nantes, France.
EM magalie.penaud-budloo@univ-nantes.fr
OI Leger, Adrien/0000-0001-8772-6776
FU INSERM; University of Nantes; Association Francaise contre les
   Myopathies (AFM); National Institutes of Health at the National Cancer
   Institute
FX Financial support was received from the INSERM, the University of Nantes
   and the Association Francaise contre les Myopathies (AFM). This research
   was also supported in part by the Intramural Research Program of the
   National Institutes of Health at the National Cancer Institute. No
   additional external funding was received for this study. This work was
   performed under a Cooperative Agreement between INSERM, AFM,
   l'Etablissement Francais du Sang (EFS) and the University of Florida
   Center of Excellence for Regenerative Health Biotechnology. The funders
   had no role in study design, data collection and analysis, decision to
   publish, or preparation of the manuscript.
NR 53
TC 7
Z9 7
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 8
PY 2011
VL 6
IS 6
AR e20881
DI 10.1371/journal.pone.0020881
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 777JJ
UT WOS:000291611500051
PM 21687632
ER

PT J
AU Izumi, C
   Bird, JE
   Iwasa, KH
AF Izumi, Chisako
   Bird, Jonathan E.
   Iwasa, Kuni H.
TI Membrane Thickness Sensitivity of Prestin Orthologs: The Evolution of a
   Piezoelectric Protein
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID OUTER HAIR CELL; MOTOR PROTEIN; BILAYER THICKNESS; SOMATIC MOTILITY;
   LIPID-BILAYERS; ELECTROMOTILITY; CAPACITANCE; ANIONS; MODEL
AB How proteins evolve new functionality is an important question in biology; prestin (SLC26A5) is a case in point. Prestin drives outer hair cell somatic motility and amplifies mechanical vibrations in the mammalian cochlea. The motility of mammalian prestin is analogous to piezoelectricity, in which charge transfer is coupled to changes in membrane area occupied by the protein. Intriguingly, nonmammalian prestin orthologs function as anion exchangers but are apparently nonmotile. We previously found that mammalian prestin is sensitive to membrane thickness, suggesting that prestin's extended conformation has a thinner hydrophobic height in the lipid bilayer. Because prestin-based motility is a mammalian specialization, we initially hypothesized that nonmotile prestin orthologs, while functioning as anion transporters, should be much less sensitive to membrane thickness. We found the exact opposite to be true. Chicken prestin was the most sensitive to thickness changes, displaying the largest shift in voltage dependence. Platypus prestin displayed an intermediate response to membrane thickness and gerbil prestin was the least sensitive. To explain these observations, we present a theory where force production, rather than displacement, was selected for the evolution of prestin as a piezoelectric membrane motor.
C1 [Izumi, Chisako; Iwasa, Kuni H.] Natl Inst Deafness & Other Commun Disorders, Biophys Sect, NIH, Rockville, MD USA.
   [Bird, Jonathan E.] Natl Inst Deafness & Other Commun Disorders, Lab Mol Genet, NIH, Rockville, MD USA.
RP Iwasa, KH (reprint author), Natl Inst Deafness & Other Commun Disorders, Biophys Sect, NIH, Rockville, MD USA.
EM kuni.iwasa@gmail.com
OI Iwasa, Kuni/0000-0002-9397-7704; Bird, Jonathan/0000-0001-5531-8794
FU National Institute on Deafness and Other Communication Disorders,
   National Institutes of Health
FX This research was supported by the Intramural Research Program of
   National Institute on Deafness and Other Communication Disorders,
   National Institutes of Health.
NR 32
TC 4
Z9 4
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD JUN 8
PY 2011
VL 100
IS 11
BP 2614
EP 2622
DI 10.1016/j.bpj.2011.04.032
PG 9
WC Biophysics
SC Biophysics
GA 776WQ
UT WOS:000291571100010
PM 21641306
ER

PT J
AU Rowland, JH
   Mariotto, A
   Alfano, CM
   Pollack, LA
   Weir, HK
   White, A
AF Rowland, J. H.
   Mariotto, A.
   Alfano, C. M.
   Pollack, L. A.
   Weir, H. K.
   White, A.
TI Cancer Survivors-United States, 2007 (Reprinted from MMWR, vol 60, pg
   269, 2011)
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Reprint
ID PREVALENCE
C1 [Rowland, J. H.; Mariotto, A.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   [White, A.] CDC, EIS, Atlanta, GA 30333 USA.
RP Rowland, JH (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
NR 11
TC 0
Z9 0
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 8
PY 2011
VL 305
IS 22
BP 2281
EP 2282
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 773YV
UT WOS:000291349100006
ER

PT J
AU Buys, SS
   Partridge, E
   Black, A
   Johnson, CC
   Lamerato, L
   Isaacs, C
   Reding, DJ
   Greenlee, RT
   Yokochi, LA
   Kessel, B
   Crawford, ED
   Church, TR
   Andriole, GL
   Weissfeld, JL
   Fouad, MN
   Chia, D
   O'Brien, B
   Ragard, LR
   Clapp, JD
   Rathmell, JM
   Riley, TL
   Hartge, P
   Pinsky, PF
   Zhu, CS
   Izmirlian, G
   Kramer, BS
   Miller, AB
   Xu, JL
   Prorok, PC
   Gohagan, JK
   Berg, CD
AF Buys, Saundra S.
   Partridge, Edward
   Black, Amanda
   Johnson, Christine C.
   Lamerato, Lois
   Isaacs, Claudine
   Reding, Douglas J.
   Greenlee, Robert T.
   Yokochi, Lance A.
   Kessel, Bruce
   Crawford, E. David
   Church, Timothy R.
   Andriole, Gerald L.
   Weissfeld, Joel L.
   Fouad, Mona N.
   Chia, David
   O'Brien, Barbara
   Ragard, Lawrence R.
   Clapp, Jonathan D.
   Rathmell, Joshua M.
   Riley, Thomas L.
   Hartge, Patricia
   Pinsky, Paul F.
   Zhu, Claire S.
   Izmirlian, Grant
   Kramer, Barnett S.
   Miller, Anthony B.
   Xu, Jian-Lun
   Prorok, Philip C.
   Gohagan, John K.
   Berg, Christine D.
CA PLCO Project Team
TI Effect of Screening on Ovarian Cancer Mortality The Prostate, Lung,
   Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled
   Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
AB Context Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality.
   Objective To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
   Design, Setting, and Participants Randomized controlled trial of 78 216 women aged 55 to 74 years assigned to undergo either annual screening (n=39 105) or usual care (n=39 111) at 10 screening centers across the United States between November 1993 and July 2001.
   Intervention The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care. Participants were followed up for a maximum of 13 years (median [range], 12.4 years [10.9-13.0 years]) for cancer diagnoses and death until February 28, 2010.
   Main Outcome Measures Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures.
   Results Ovarian cancer was diagnosed in 212 women (5.7 per 10 000 person-years) in the intervention group and 176 (4.7 per 10 000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% confidence interval [CI], 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10 000 person-years) in the intervention group and 100 deaths (2.6 per 10 000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). Of 3285 women with false-positive results, 1080 underwent surgical follow-up; of whom, 163 women experienced at least 1 serious complication (15%). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10 000 person-years) in the intervention group and 2914 deaths (76.2 per 10 000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06).
   Conclusions Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications.
C1 [Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA.
   [Partridge, Edward; Fouad, Mona N.] Univ Alabama, Sch Med, Birmingham, AL USA.
   [Black, Amanda] NCI, Epidemiol & Biostat Program, NIH, Bethesda, MD 20892 USA.
   [Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   [Pinsky, Paul F.; Zhu, Claire S.; Izmirlian, Grant; Prorok, Philip C.; Berg, Christine D.] NCI, Early Detect Res Grp, Biometry Res Grp, Div Canc Prevent,NIH, Bethesda, MD 20892 USA.
   [Kramer, Barnett S.] NCI, Off Commun & Educ, NIH, Bethesda, MD 20892 USA.
   [Gohagan, John K.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
   [Johnson, Christine C.; Lamerato, Lois] Henry Ford Hlth Syst, Detroit, MI USA.
   [Isaacs, Claudine] Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA.
   [Reding, Douglas J.; Greenlee, Robert T.] Marshfield Clin Res Fdn, Marshfield, WI USA.
   [Yokochi, Lance A.; Kessel, Bruce] Pacific Hlth Res & Educ Inst, Honolulu, HI USA.
   Univ Colorado, Denver, CO 80202 USA.
   [Church, Timothy R.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
   [Andriole, Gerald L.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
   [Weissfeld, Joel L.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
   [Chia, David] Univ Calif Los Angeles, Immunogenet Ctr, Los Angeles, CA USA.
   [O'Brien, Barbara; Ragard, Lawrence R.] Westat Corp, Rockville, MD USA.
   [Clapp, Jonathan D.; Rathmell, Joshua M.; Riley, Thomas L.] Informat Management Serv Inc, Rockville, MD USA.
   [Miller, Anthony B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
RP Berg, CD (reprint author), Execut Plaza N,6130 Execut Blvd,MSC 7346,Room 311, Rockville, MD 20852 USA.
EM bergc@mail.nih.gov
RI Schliep, Karen/A-2803-2012; Berg , Christine/K-1047-2014; 
OI Johnson, Christine Cole/0000-0002-6864-6604; Church, Timothy
   R./0000-0003-3292-5035
FU National Cancer Institute; Division of Cancer Prevention of the National
   Cancer Institute; Division of Cancer Epidemiology and Genetics National
   Cancer Institute, National Institutes of Health, Department of Health
   and Human Services
FX The National Cancer Institute funded the Prostate, Lung, Colorectal and
   Ovarian (PLCO) Cancer Screening Trial. This research also was supported
   by contracts from the Division of Cancer Prevention of the National
   Cancer Institute and by the Intramural Research Program of the Division
   of Cancer Epidemiology and Genetics National Cancer Institute, National
   Institutes of Health, Department of Health and Human Services.
NR 22
TC 371
Z9 382
U1 3
U2 32
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 8
PY 2011
VL 305
IS 22
BP 2295
EP 2303
DI 10.1001/jama.2011.766
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 773YV
UT WOS:000291349100022
PM 21642681
ER

PT J
AU Carvajal, RD
   Antonescu, CR
   Wolchok, JD
   Chapman, PB
   Roman, RA
   Teitcher, J
   Panageas, KS
   Busam, KJ
   Chmielowski, B
   Lutzky, J
   Pavlick, AC
   Fusco, A
   Cane, L
   Takebe, N
   Vemula, S
   Bouvier, N
   Bastian, BC
   Schwartz, GK
AF Carvajal, Richard D.
   Antonescu, Cristina R.
   Wolchok, Jedd D.
   Chapman, Paul B.
   Roman, Ruth-Ann
   Teitcher, Jerrold
   Panageas, Katherine S.
   Busam, Klaus J.
   Chmielowski, Bartosz
   Lutzky, Jose
   Pavlick, Anna C.
   Fusco, Anne
   Cane, Lauren
   Takebe, Naoko
   Vemula, Swapna
   Bouvier, Nancy
   Bastian, Boris C.
   Schwartz, Gary K.
TI KIT as a Therapeutic Target in Metastatic Melanoma
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID GASTROINTESTINAL STROMAL TUMORS; COMPARATIVE GENOMIC HYBRIDIZATION;
   RECEPTOR TYROSINE KINASE; PROTOONCOGENE C-KIT; PHASE-II TRIAL; IMATINIB
   MESYLATE; CLINICAL-EFFICACY; MUTANT MELANOMA; EXPRESSION; MUTATIONS
AB Context Some melanomas arising from acral, mucosal, and chronically sun-damaged sites harbor activating mutations and amplification of the type III transmembrane receptor tyrosine kinase KIT. We explored the effects of KIT inhibition using imatinib mesylate in this molecular subset of disease.
   Objective To assess clinical effects of imatinib mesylate in patients with melanoma harboring KIT alterations.
   Design, Setting, and Patients A single-group, open-label, phase 2 trial at 1 community and 5 academic oncology centers in the United States of 295 patients with melanoma screened for the presence of KIT mutations and amplification between April 23, 2007, and April 16, 2010. A total of 51 cases with such alterations were identified and 28 of these patients were treated who had advanced unresectable melanoma arising from acral, mucosal, and chronically sun-damaged sites.
   Intervention Imatinib mesylate, 400 mg orally twice daily.
   Main Outcome Measures Radiographic response, with secondary end points including time to progression, overall survival, and correlation of molecular alterations and clinical response.
   Results Two complete responses lasting 94 (ongoing) and 95 weeks, 2 durable partial responses lasting 53 and 89 (ongoing) weeks, and 2 transient partial responses lasting 12 and 18 weeks among the 25 evaluable patients were observed. The overall durable response rate was 16% (95% confidence interval [CI], 2%-30%), with a median time to progression of 12 weeks (interquartile range [IQR], 6-18 weeks; 95% CI, 11-18 weeks), and a median overall survival of 46.3 weeks (IQR, 28 weeks-not achieved; 95% CI, 28 weeks-not achieved). Response rate was better in cases with mutations affecting recurrent hotspots or with a mutant to wild-type allelic ratio of more than 1 (40% vs 0%, P = .05), indicating positive selection for the mutated allele.
   Conclusions Among patients with advanced melanoma harboring KIT alterations, treatment with imatinib mesylate results in significant clinical responses in a subset of patients. Responses may be limited to tumors harboring KIT alterations of proven functional relevance.
C1 [Carvajal, Richard D.; Wolchok, Jedd D.; Chapman, Paul B.; Roman, Ruth-Ann; Fusco, Anne; Cane, Lauren; Schwartz, Gary K.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
   [Antonescu, Cristina R.; Busam, Klaus J.; Bastian, Boris C.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
   [Teitcher, Jerrold] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA.
   [Panageas, Katherine S.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
   [Bastian, Boris C.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
   [Chmielowski, Bartosz] Univ Calif Los Angeles, Med Ctr, Dept Med, Los Angeles, CA 90024 USA.
   [Lutzky, Jose] Mt Sinai Med Ctr, Dept Med, Miami Beach, FL 33140 USA.
   [Pavlick, Anna C.] NYU, Dept Med, Langone Med Ctr, New York, NY 10016 USA.
   [Takebe, Naoko] NCI, Div Canc Treatment, Canc Therapy Evaluat Program, Invest Drug Branch, Bethesda, MD 20892 USA.
   [Vemula, Swapna; Bouvier, Nancy; Bastian, Boris C.] Univ Calif San Francisco, Dept Dermatol, Med Ctr, San Francisco, CA 94143 USA.
   [Vemula, Swapna; Bouvier, Nancy; Bastian, Boris C.] Univ Calif San Francisco, Dept Pathol, Med Ctr, San Francisco, CA 94140 USA.
RP Carvajal, RD (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
EM carvajar@mskcc.org
OI Chmielowski, Bartosz/0000-0002-2374-3320
FU US Food and Drug Administration [R01FD003445-01]; National Institutes of
   Health [N01CM62206, P30 CA008748]; American Society of Clinical
   Oncology; American Skin Association; Live4Life Foundation
FX This study was funded by grant R01FD003445-01 from the US Food and Drug
   Administration; grants N01CM62206 and P30 CA008748 from the National
   Institutes of Health; American Society of Clinical Oncology; American
   Skin Association; and Live4Life Foundation. The Division of Cancer
   Treatment and Diagnosis at the National Cancer Institute provided the
   imatinib mesylate for this clinical trial.
NR 44
TC 299
Z9 311
U1 1
U2 17
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 8
PY 2011
VL 305
IS 22
BP 2327
EP 2334
DI 10.1001/jama.2011.746
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 773YV
UT WOS:000291349100026
PM 21642685
ER

EF