FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Eblaghie, MC
   Reedy, M
   Oliver, T
   Mishina, Y
   Hogan, BLM
AF Eblaghie, MC
   Reedy, M
   Oliver, T
   Mishina, Y
   Hogan, BLM
TI Evidence that autocrine signaling through Bmpr1a regulates the
   proliferation, survival and morphogenetic behavior of distal lung
   epithelial cells
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Bmpr1a; Alk3; Bmp4; Sftpc; conditional mutant; mouse embryo; lung;
   epithelium; proliferation; survival
ID GROWTH-FACTOR-BETA; EMBRYONIC TRACHEAL EPITHELIUM; MESENCHYME-FREE
   CULTURE; BRANCHING MORPHOGENESIS; SELF-RENEWAL; MOUSE LUNG; DEPENDENT
   MECHANISM; TISSUE INTERACTIONS; DISTINCT FUNCTIONS; PROTEIN-RECEPTOR
AB Lung development requires reciprocal epithelial/mesenchymal interactions, mediated by signaling factors such as Bmps made in both cell populations. To address the role of Bmp signaling in the epithelium, we have exploited the fact that Bmp receptor type la (Alk3) is expressed in the epithelium during branching morphogenesis. Deletion of Bmpr1a in the epithelium with an Sfipc-cre transgene leads to dramatic defects in lung development. There is reduced epithelial proliferation, extensive apoptosis, changes in cell morphology and extrusion of cells into the lumen. By E18.5, there are fewer Type II cells than normal, and the lung contains large fluid-filled spaces. If cell death is prevented by making embryos homozygous null for the proapoptotic gene, Bax, the epithelial cells that are rescued can apparently differentiate, but normal morphogenesis is not restored. To determine whether Bmps made by the epithelium can function in an autocrine manner, mesenchyme-free endoderm was cultured in Matrigel (TM) with Fgfs. Under these conditions, the mutant epithelium fails to undergo secondary budding. Abnormal development was also seen when Bmp4 was specifically deleted in the epithelium using the Sftpc-cre transgene. Our results support a model in which Burp signaling primarily regulates the proliferation, survival and morphogenetic behavior of distal lung epithelial cells. (c) 2005 Elsevier Inc. All rights reserved.
C1 Duke Univ, Ctr Med, Dept Cell Biol, Durham, NC 27710 USA.
   Natl Inst Environm Hlth Sci, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA.
RP Hogan, BLM (reprint author), Duke Univ, Ctr Eye, Dept Ophthalmol, Box 3802, Durham, NC 27710 USA.
EM b.hogan@cellbio.duke.edu
FU Intramural NIH HHS; NHLBI NIH HHS [HL080517]; NIAMS NIH HHS [AR14317]
NR 78
TC 87
Z9 89
U1 1
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD MAR 1
PY 2006
VL 291
IS 1
BP 67
EP 82
DI 10.1016//j.ydbio.2005.12.006
PG 16
WC Developmental Biology
SC Developmental Biology
GA 023LN
UT WOS:000236128300006
PM 16414041
ER

PT J
AU Mash, C
   Novak, E
   Berthier, NE
   Keen, R
AF Mash, C
   Novak, E
   Berthier, NE
   Keen, R
TI What do two-year-olds understand about hidden-object events?
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
DE reasoning; manual search; toddlers; development
ID 8-MONTH-OLD INFANTS; FIELD-THEORY; SEARCH TASK; KNOWLEDGE;
   REPRESENTATION; PERFORMANCE; LOCATION; MEMORY; DISSOCIATIONS; PERMANENCE
AB Preferential-looking studies suggest that by 2 months of age, infants may have knowledge about some object properties, such as solidity. Manual search studies of toddlers examining these same concepts, however, have failed to provide evidence for the same understanding. Investigators have recently attempted to reconcile this disparity but failed to control for the visual novelty of test outcomes. The current design corrected this problem and also tested toddlers' predictions of the object's location, The task involved the same events and apparatus that have been used in manual search tasks but used looking as the dependent measure. Children looked longer when an agent opened the correct door and found no ball than when an incorrect door was opened to reveal no ball. A 2nd experiment indicated that children's preferential-looking performance did not differ from that in manual search tasks simply because additional response time had been allowed to respond. Previous comparisons of looking versus reaching tested children's postdiction response to an object in an unexpected location, but these findings indicate that toddlers can predict where the object should be.
C1 NICHD, Sect Child & Family Res, Bethesda, MD 20892 USA.
   Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA.
RP Mash, C (reprint author), NICHD, Sect Child & Family Res, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA.
EM mashc@mail.nih.gov
FU Intramural NIH HHS; NICHD NIH HHS [HD27714]; NIMH NIH HHS [MH00332]
NR 37
TC 24
Z9 24
U1 4
U2 11
PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0012-1649
J9 DEV PSYCHOL
JI Dev. Psychol.
PD MAR
PY 2006
VL 42
IS 2
BP 263
EP 271
DI 10.1037/0012-1649.42.2.263
PG 9
WC Psychology, Developmental
SC Psychology
GA 029DF
UT WOS:000236537800005
PM 16569165
ER

PT J
AU Galambos, NL
   Barker, ET
   Krahn, HJ
AF Galambos, NL
   Barker, ET
   Krahn, HJ
TI Depression, self-esteem, and anger in emerging adulthood: Seven-year
   trajectories
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
DE depression; self-esteem; anger; emerging adults; trajectories
ID GROWTH-CURVE ANALYSIS; GENDER-DIFFERENCES; LONGITUDINAL TRAJECTORIES;
   YOUNG ADULTHOOD; LIFE-SPAN; DEVELOPMENTAL TRANSITIONS; ADOLESCENT
   DEPRESSION; FAMILY CONFLICT; SET-POINT; SYMPTOMS
AB This study used a school-based community sample (N = 920) to examine trajectories of depressive symptoms, self-esteem, and expressed anger in the critical years of emerging adulthood (ages 18-25). Using data from 5 waves, the authors discovered that multilevel models indicated that, on average, depressive symptoms and expressed anger declined, whereas self-esteem increased. Between-persons predictors of variability in trajectories included gender (gender gaps in depressive symptoms and self-esteem narrowed), parents' education, and conflict with parents (depressive symptoms and expressed anger improved fastest in participants with highly educated parents and in those with higher conflict). Across time, increases in social support and marriage were associated with increased psychological well-being, whereas longer periods of unemployment were connected with higher depression and lower self-esteem. Emerging adulthood is a time of improving psychological well-being, but individual trajectories depend on specific individual and family characteristics as well as role changes.
C1 Univ Alberta, Dept Psychol, Edmonton, AB T6G 2E9, Canada.
   NICHHD, Bethesda, MD 20892 USA.
   Univ Alberta, Dept Sociol, Edmonton, AB T6G 2M7, Canada.
RP Galambos, NL (reprint author), Univ Alberta, Dept Psychol, P-217 Biol Sci Bldg, Edmonton, AB T6G 2E9, Canada.
EM galambos@ualberta.ca
NR 82
TC 158
Z9 163
U1 11
U2 52
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0012-1649
J9 DEV PSYCHOL
JI Dev. Psychol.
PD MAR
PY 2006
VL 42
IS 2
BP 350
EP 365
DI 10.1037/0012-1649.42.2.350
PG 16
WC Psychology, Developmental
SC Psychology
GA 029DF
UT WOS:000236537800013
PM 16569173
ER

PT J
AU Sternberg, KJ
   Baradaran, LP
   Abbott, CB
   Lamb, ME
   Guterman, E
AF Sternberg, KJ
   Baradaran, LP
   Abbott, CB
   Lamb, ME
   Guterman, E
TI Type of violence, age, and gender differences in the effects of family
   violence on children's behavior problems: A mega-analysis
SO DEVELOPMENTAL REVIEW
LA English
DT Article
DE child abuse; spouse abuse; family violence; child adjustment; behavior
   problems
ID DOMESTIC VIOLENCE; DEVELOPMENTAL PSYCHOPATHOLOGY; MARITAL CONFLICT;
   YOUNG-CHILDREN; EXPOSURE; ADJUSTMENT; METAANALYSIS; ABUSE; MALTREATMENT;
   AGGRESSION
AB A mega-analytic study was designed to exploit the power of a large data set combining raw data from multiple studies (n = 1870) to examine the effects of type of family violence, age, and gender on children's behavior problems assessed using the Child Behavior Checklist (CBCL). Our findings confirmed that children who experienced multiple forms of family violence were at greater risk than children who experienced only one form of abuse, and witnesses of inter-parental violence were at similar risk as victims of violence. Age moderated the effects of family violence on externalizing behavior problems, but not on internalizing behavior problems. No main or interaction effects involving children's gender were evident. These results underscore the need to take children's age, type of violence, and type of outcome into account when examining the effects of family violence on children's behavior problems. Published by Elsevier Inc.
C1 Univ Cambridge, Fac Social & Polit Sci, Dept Social & Dev Psychol, Cambridge CB2 3RQ, England.
   NICHHD, Sect Social Emotional Dev, Bethesda, MD 20892 USA.
RP Lamb, ME (reprint author), Univ Cambridge, Fac Social & Polit Sci, Dept Social & Dev Psychol, Free Sch Lane, Cambridge CB2 3RQ, England.
EM mel37@cam.ac.uk
NR 73
TC 91
Z9 92
U1 4
U2 31
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0273-2297
J9 DEV REV
JI Dev. Rev.
PD MAR
PY 2006
VL 26
IS 1
BP 89
EP 112
DI 10.1016/j.dr.2005.12.001
PG 24
WC Psychology, Developmental
SC Psychology
GA 027UD
UT WOS:000236440200005
ER

PT J
AU Thameem, F
   Farook, VS
   Bogardus, C
   Prochazka, M
AF Thameem, F
   Farook, VS
   Bogardus, C
   Prochazka, M
TI Association of amino acid variants in the activating transcription
   factor 6 gene (ATF6) on 1q21-q23 with type 2 diabetes in Pima Indians
SO DIABETES
LA English
DT Article
ID DYSFUNCTION; MELLITUS; PROTEIN
AB Activating transcription factor 6 (ATF6) is important for protective cell response to accumulation of unfolded and misfolded proteins in endoplasmic reticulum, and disturbances of this process can contribute to beta-cell apoptosis. We analyzed the structural gene located within a region on 1q21-q23 linked with type 2 diabetes in several populations for variants in the Pima Indians. Functionally important segments of ATF6 were sequenced in 15 diabetic and 15 nondiabetic Pimas and representative single nucleotide polymorphisms (SNPs) tested for association with type 2 diabetes in 900-1,000 subjects. We identified 20 variants including three amino acid substitutions [Met(67)Val, Pro(145)Ala, and Ser(157)Pro]. Pro(145)Ala and Ser(157) Pro were in a complete linkage disequilibrium and showed a nominal association with type 2 diabetes (P = 0.05; odds ratio 2.3 [95% Cl 1.0-5.2]) and with 30-min plasma insulin during oral glucose tolerance test in 287 nondiabetic individuals (P = 0.045). Although the associations with type 2 diabetes and plasma insulin levels are marginal and their functional consequences are yet unknown, all three amino acid substitutions are located in a functionally important part of ATF6. Because these variants are not unique to the Pimas, it will be feasible to investigate their association with type 2 diabetes in other populations to better evaluate their significance for a predisposition to the disease.
C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
   Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78284 USA.
   SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA.
RP Prochazka, M (reprint author), NIDDKD, Diabet Mol Genet Sect, NIH, 445 N 5th St,Suite 210, Phoenix, AZ 85004 USA.
EM mprochazka@phx.niddk.nih.gov
FU Intramural NIH HHS
NR 9
TC 44
Z9 49
U1 0
U2 0
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD MAR
PY 2006
VL 55
IS 3
BP 839
EP 842
DI 10.2337/diabetes.55.03.06.db05-1002
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 018IL
UT WOS:000235757600036
PM 16505252
ER

PT J
AU Sosenko, JM
   Palmer, JP
   Greenbaum, CJ
   Mahon, J
   Cowie, C
   Krischer, JP
   Chase, HP
   White, NH
   Buckingham, B
   Herold, KC
   Cuthbertson, D
   Skyler, JS
AF Sosenko, JM
   Palmer, JP
   Greenbaum, CJ
   Mahon, J
   Cowie, C
   Krischer, JP
   Chase, HP
   White, NH
   Buckingham, B
   Herold, KC
   Cuthbertson, D
   Skyler, JS
CA Diabet Prevention Trial Type 1 Stu
TI Patterns of metabolic progression to type 1 diabetes in the Diabetes
   Prevention Trial-Type 1
SO DIABETES CARE
LA English
DT Article
ID ISLET-CELL ANTIBODIES; IMPAIRED GLUCOSE-TOLERANCE; INSULIN AUTOANTIBODY;
   HIGH-RISK; POSITIVE RELATIVES; IDENTICAL-TWINS; FOLLOW-UP; MELLITUS;
   CHILDREN; SECRETION
AB OBJECTIVE - There is little information regarding the pattern of metabolic deterioration before the onset of type 1 diabetes. The goal Of this Study was to utilize data from the Diabetes Prevention Trial-Type 1 (DPT-1) to obtain a picture of the metabolic progression to type I diabetes over a period of approximately 2.5 years before its diagnosis.
   RESEARCH DESIGN AND METHODS - Fifty-four DPT-1 participants (22 in the parenteral trial and 32 in the oral trial) were studied. All had oral glucose tolerance tests (OGTTs) at 6-month intervals from approximately 30 to 6 months before diagnosis. The Vast majority also had OGTTs at diagnosis. Changes in OGTT glucose and C-peptide indexes from 30 to 6 months before diagnosis were examined by calculating slopes of the indexes for each individual over that time period. Changes from 6 months before diagnosis to diagnosis were examined by paired comparisons of the OGTT metabolic indexes between the time points.
   RESULTS - Glucose levels increased gradually from 30 to 6 months before diagnosis in both the parenteral and oral groups (P < 0.001 for all indexes). Area under the curve (AUC) C-peptide (P < 0.05) and AUC C-peptide-to-AUC glucose ratio (P < 0.001) Values decreased in the oral group; peak C-peptide-to-2-h glucose ratio values decreased in both groups (P < 0.001). In participants who also had OGTTs at diagnosis, AUC C-peptide (parenteral group, P < 0.05) and peak C-peptide (oral group, P < 0.05) values decreased from the last 6 months before diagnosis; stimulated C-peptide-to-glucose ratio values decreased in both groups (P < 0.001). Conversely, fasting C-peptide levels increased in both groups (oral group, P < 0.01). Fasting C-peptide-to-fasting glucose ratio values remained constant throughout the 30-month follow-up.
   CONCLUSIONS - These data indicate that over a period of at least 2 years, glucose tolerance gradually deteriorates as stimulated C-peptide levels slowly decline in a substantial number of individuals who develop type 1 diabetes. However, fasting C-peptide levels are maintained, even at diagnosis.
C1 Univ Miami, Div Endocrinol, Miami, FL 33101 USA.
   Univ Washington, Div Endocrinol Metab, Seattle, WA 98195 USA.
   Virginia Mason Med Ctr, Benaroya Res Inst, Seattle, WA 98101 USA.
   Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada.
   NIDDK, NIH, Bethesda, MD USA.
   Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA.
   Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO 80262 USA.
   Washington Univ, Sch Med, Div Pediat Endocrinol & Metab, St Louis, MO USA.
   Stanford Univ, Div Pediat Endocrinol, Palo Alto, CA 94304 USA.
   Columbia Univ, Div Endocrinol, New York, NY USA.
RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, POB 106960 D110, Miami, FL 33101 USA.
EM jsosenko@med.miami.edu
RI Skyler, Jay/F-4211-2016
NR 35
TC 87
Z9 91
U1 0
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD MAR
PY 2006
VL 29
IS 3
BP 643
EP 649
DI 10.2337/diacare.29.03.06.dc05-1006
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 018KW
UT WOS:000235764100027
PM 16505520
ER

PT J
AU Barroso, I
   Luan, J
   Sandhu, MS
   Franks, PW
   Crowley, V
   Schafer, AJ
   O'Rahilly, S
   Wareham, NJ
AF Barroso, I
   Luan, J
   Sandhu, MS
   Franks, PW
   Crowley, V
   Schafer, AJ
   O'Rahilly, S
   Wareham, NJ
TI Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes
   and related phenotypes
SO DIABETOLOGIA
LA English
DT Article
DE association study; meta-analysis; polymorphism; PPARGC1A; type 2
   diabetes
ID RECEPTOR-GAMMA COACTIVATOR-1; TRANSCRIPTIONAL COACTIVATOR; HEPATIC
   GLUCONEOGENESIS; INSULIN-RESISTANCE; GLUCOSE-TOLERANCE; E23K VARIANT;
   PGC-1 GENE; PGC-1-ALPHA; ASSOCIATION; POLYMORPHISMS
AB Aims/hypothesis: Peroxisome proliferator-activated receptor-gamma co-activator-1 alpha (PPARGC1A) is a transcriptional co-activator with a central role in energy expenditure and glucose metabolism. Several studies have suggested that the common PPARGC1A polymorphism Gly482Ser may be associated with risk of type 2 diabetes, with conflicting results. To clarify the role of Gly482Ser in type 2 diabetes and related human metabolic phenotypes we genotyped this polymorphism in a case-control study and performed a meta-analysis of relevant published data. Materials and methods: Gly482Ser was genotyped in a type 2 diabetes case-control study (N=1,096) using MassArray technology. A literature search revealed publications that examined Gly482Ser for association with type 2 diabetes and related metabolic phenotypes. Meta-analysis of the current study and relevant published data was undertaken. Results: In the pooled meta-analysis, including data from this study and seven published reports (3,718 cases, 4,818 controls), there was evidence of between-study heterogeneity (p < 0.1). In the fixed-effects meta-analysis, the pooled odds ratio for risk of type 2 diabetes per Ser482 allele was 1.07 (95% CI 1.00-1.15, p=0.044). Elimination of one of the studies from the meta-analysis gave a summary odds ratio of 1.11 (95% CI 1.04-1.20, p=0.004), with no between-study heterogeneity (p=0.475). For quantitative metabolic traits in normoglycaemic subjects, we also found significant between-study heterogeneity. However, no significant association was observed between Gly482Ser and BMI, fasting glucose or fasting insulin. Conclusions/interpretation: This meta-analysis of data from the current and published studies supports a modest role for the Gly482Ser PPARGC1A variant in type 2 diabetes risk.
C1 Wellcome Trust Sanger Inst, Metab Dis Grp, Hinxton CB10 1SA, Cambs, England.
   MRC, Epidemiol Unit, Cambridge, England.
   Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England.
   NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
   Addenbrookes Hosp, Dept Clin Biochem, Cambridge, England.
   Addenbrookes Hosp, Dept Med, Cambridge CB2 2QQ, England.
   Incyte Genom, Cambridge, England.
RP Barroso, I (reprint author), Wellcome Trust Sanger Inst, Metab Dis Grp, Wellcome Trust Genome Campus, Hinxton CB10 1SA, Cambs, England.
EM ib1@sanger.ac.uk
OI Franks, Paul/0000-0002-0520-7604
FU Wellcome Trust
NR 26
TC 62
Z9 64
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0012-186X
J9 DIABETOLOGIA
JI Diabetologia
PD MAR
PY 2006
VL 49
IS 3
BP 501
EP 505
DI 10.1007/s00125-005-0130-2
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 014OB
UT WOS:000235488400010
PM 16435105
ER

PT J
AU Gao, ZG
   Jacobson, KA
AF Gao, ZG
   Jacobson, KA
TI Keynote review: Allosterism in membrane receptors
SO DRUG DISCOVERY TODAY
LA English
DT Review
ID PROTEIN-COUPLED RECEPTORS; EXTRACELLULAR CA2+-SENSING RECEPTOR;
   METABOTROPIC GLUTAMATE RECEPTORS; MUSCARINIC ACETYLCHOLINE-RECEPTORS;
   SOLUBLE GUANYLYL CYCLASE; NERVE GROWTH-FACTOR; ADENOSINE RECEPTORS;
   AGONIST-BINDING; BIOLOGICAL EVALUATION; DRUG DISCOVERY
AB Allosteric modulation of membrane receptors has been intensively studied in the past three decades and is now considered to be an important indirect mechanism for the control of receptor function. The allosteric site on the GABA(A) receptor is the target for the most widely prescribed sleep medicines, the benzodiazepines. Cinacalcet, an allosteric enhancer of the calcium-sensing receptor, is used to treat secondary hyperparathyroidism. Allosteric ligands might be especially valuable to control receptors for which the design of selective orthosteric agonists or antagonists has been elusive, such as muscarinic acetylcholine receptors.
C1 Natl Inst Diabet & Digest & Kidney Dis, Lab Bioorgan Chem, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA.
RP Gao, ZG (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Lab Bioorgan Chem, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA.
EM zhanguog@intra.niddk.nih.gov; kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural NIH HHS
NR 148
TC 48
Z9 50
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1359-6446
J9 DRUG DISCOV TODAY
JI Drug Discov. Today
PD MAR
PY 2006
VL 11
IS 5-6
BP 191
EP 202
DI 10.1016/S1359-6446(05)03689-5
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 024AN
UT WOS:000236167400003
PM 16580596
ER

PT J
AU Busch, MP
   Wright, DJ
   Custer, B
   Tobler, LH
   Stramer, SL
   Kleinman, SH
   Prince, HE
   Bianco, C
   Foster, G
   Petersen, LR
   Nemo, G
   Glynn, SA
AF Busch, MP
   Wright, DJ
   Custer, B
   Tobler, LH
   Stramer, SL
   Kleinman, SH
   Prince, HE
   Bianco, C
   Foster, G
   Petersen, LR
   Nemo, G
   Glynn, SA
TI West Nile virus infections projected from blood donor screening data,
   United States, 2003
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID IMMUNOGLOBULIN-M IGM; NEW-YORK; ENCEPHALITIS; EPIDEMIC; TRANSFUSION;
   PERSISTENCE; DIAGNOSIS; ANTIBODY; RNA
AB National blood donor screening for West Nile virus (WNV) RNA using minipool nucleic acid amplification testing (MP-NAT) was implemented in the United States in July 2003. We compiled national NAT yield data and performed WNV immunoglobulin M (IgM) testing in 1 WNV-epidemic region (North Dakota). State-specific MP-NAT yield, antibody seroprevalence, and the average time RNA is detectable by MP-NAT were used to estimate incident infections in 2003. WNV donor screening yielded 944 confirmed viremic donors. MP-NAT yield peaked in August with > 0.5% of donations positive for WNV RNA in 4 states. Peak IgM seroprevalence for North Dakota was 5.2% in late September. The average time viremia is detectable by MP-NAT was 6.9 days (95% confidence interval [CI] 3.0-10.7). An estimated 735,000 (95% Cl 322,000-1,147,000) infections occurred in 2003, with 256 (95% Cl 112-401) infections per neuroinvasive case. In addition to preventing transfusion-transmitted WNV infection, donor screening can serve as a tool to monitor seasonal incidence in the general population.
C1 Blood Syst Res Inst, San Francisco, CA 94118 USA.
   Univ Calif San Francisco, San Francisco, CA 94143 USA.
   WESTAT Corp, Rockville, MD 20850 USA.
   Amer Red Cross, Natl Testing & Reference Labs, Gaithersburg, MD USA.
   Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
   Focus Diagnost, Cypress, CA USA.
   Amer Blood Ctr, Washington, DC USA.
   Ctr Dis Control & Prevent, Ft Collins, CO USA.
   NHLBI, Bethesda, MD 20892 USA.
RP Busch, MP (reprint author), Blood Syst Res Inst, 270 Mason Ave, San Francisco, CA 94118 USA.
EM mbusch@bloodsystems.org
FU NHLBI NIH HHS [N01-HB-47114, N01-HB-97078, N01-HB-97079, N01-HB-97080,
   N01-HB-97081, N01-HB-97082]
NR 31
TC 73
Z9 78
U1 0
U2 3
PU CENTER DISEASE CONTROL
PI ATLANTA
PA ATLANTA, GA 30333 USA
SN 1080-6040
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD MAR
PY 2006
VL 12
IS 3
BP 395
EP 402
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 020PP
UT WOS:000235922300005
PM 16704775
ER

PT J
AU Lindsay, JR
   Nieman, LK
AF Lindsay, JR
   Nieman, LK
TI Adrenal disorders in pregnancy
SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA
LA English
DT Article
ID INDEPENDENT CUSHINGS-SYNDROME; OF-THE-LITERATURE; PRIMARY ALDOSTERONISM;
   ADDISONS-DISEASE; 21-HYDROXYLASE DEFICIENCY; PERSONAL-EXPERIENCE; LUPUS
   ANTICOAGULANT; CONSENSUS STATEMENT; GROWTH-RETARDATION; SALIVARY
   CORTISOL
AB In normal gestation, hypercortisolism and relative hyperaldosteronism are not usually clinically apparent. In contrast, adrenal disorders that do occur during pregnancy contribute to significant maternal and fetal morbidity. This article reviews the natural history, causes, diagnosis, and treatment of adrenal causes of Cushing's syndrome, adrenocortical hypofunction, primary hyperaldosteronism, and the management of adrenal pheochromocytoma in pregnancy.
C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA.
RP Nieman, LK (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bldg 10,CRC Room 1-3140, Bethesda, MD 20892 USA.
EM niemanl@mail.nih.gov
NR 99
TC 21
Z9 22
U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399 USA
SN 0889-8529
J9 ENDOCRIN METAB CLIN
JI Endocrinol. Metabol. Clin. North Amer.
PD MAR
PY 2006
VL 35
IS 1
BP 1
EP +
DI 10.1016/j.ecl.2005.09.010
PG 21
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 997YT
UT WOS:000234285600003
PM 16310640
ER

PT J
AU Liu, J
   Xie, YX
   Ducharme, DMK
   Shen, J
   Diwan, BA
   Merrick, BA
   Grissom, SF
   Tucker, CJ
   Paules, RS
   Tennant, R
   Waalkes, MP
AF Liu, J
   Xie, YX
   Ducharme, DMK
   Shen, J
   Diwan, BA
   Merrick, BA
   Grissom, SF
   Tucker, CJ
   Paules, RS
   Tennant, R
   Waalkes, MP
TI Global gene expression associated with hepatocarcinogenesis in adult
   male mice induced by in utero arsenic exposure
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE Agilent mouse oligo 22K microarray; arsenic; hepatocellular carcinoma;
   real-time RT-PCR; transplacental exposure; Western blotting
ID INDUCED MALIGNANT-TRANSFORMATION; DRINKING-WATER;
   HEPATOCELLULAR-CARCINOMA; C-MYC; INORGANIC ARSENICALS; ANIMAL-MODEL;
   LIVER-CANCER; OVEREXPRESSION; TUMORS; HYPOMETHYLATION
AB Our previous work has shown that exposure to inorganic arsenic in utero produces hepatocellular carcinoma (HCC) in adult male mice. To explore further the molecular mechanisms of transplacental arsenic hepatocarcinogenesis, we conducted a second arsenic transplacental carcinogenesis study and used a genomewide microarray to profile arsenic-induced aberrant gene expression more extensively. Briefly, pregnant C3H mice were given drinking water containing 85 ppm arsenic as sodium arsenite or unaltered water from days 8 to 18 of gestation. The incidence of HCC in adult male offspring was increased 4-fold and tumor multiplicity 3-fold after transplacental arsenic exposure. Samples of normal liver and liver tumors were taken at autopsy for genomic analysis. Arsenic exposure in utero resulted in significant alterations (p<0.001) in the expression of 2,010 genes in arsenic-exposed liver samples and in the expression of 2,540 genes in arsenic-induced HCC. Ingenuity Pathway Analysis revealed that significant alterations in gene expression occurred in a number of biological networks, and Myc plays a critical role in one of the primary networks. Real-ltime reverse transcriptase-polymerase chain reaction and Western blot analysis of selected genes/proteins showed, 90% concordance. Arsenic-altered gene expression included activation of oncogenes and HCC biomarkers, and increased expression of cell proliferation-related genes, stress proteins, and insulin-like growth factors and genes involved in cell-cell communications. Liver feminization was evidenced by increased expression of estrogen-linked genes and altered expression of genes that encode gender-related metabolic enzymes. These novel findings are in agreement with the biology and histology of arsenic-induced HCC, thereby indicating that multiple genetic events are associated with transplacental arsenic hepatocarcinogenesis.
C1 NIEHS, Inorgan Carcinogenesis Sect, NCI, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
   NIEHS, Natl Ctr Toxicogen, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
   NCI, Basic Res Program, Sci Applicat Int Corp,NIH, US Dept HHS, Frederick, MD 21701 USA.
RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, NCI, Comparat Carcinogenesis Lab, Mail Drop F0-09, Res Triangle Pk, NC 27709 USA.
EM waalkes@niehs.nih.gov
FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]
NR 52
TC 43
Z9 47
U1 2
U2 11
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 MAR
PY 2006
VL 114
IS 3
BP 404
EP 411
DI 10.1289/ehp.8534
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 018NK
UT WOS:000235771000038
PM 16507464
ER

PT J
AU Corvi, R
   Ahr, HJ
   Albertini, S
   Blakey, DH
   Clerici, L
   Coecke, S
   Douglas, GR
   Gribaldo, L
   Groten, JP
   Haase, B
   Hamernik, K
   Hartung, T
   Inoue, T
   Indans, I
   Maurici, D
   Orphanides, G
   Rembges, D
   Sansone, SA
   Snape, JR
   Toda, E
   Tong, WD
   van Delft, JH
   Weis, B
   Schechtman, LM
AF Corvi, R
   Ahr, HJ
   Albertini, S
   Blakey, DH
   Clerici, L
   Coecke, S
   Douglas, GR
   Gribaldo, L
   Groten, JP
   Haase, B
   Hamernik, K
   Hartung, T
   Inoue, T
   Indans, I
   Maurici, D
   Orphanides, G
   Rembges, D
   Sansone, SA
   Snape, JR
   Toda, E
   Tong, WD
   van Delft, JH
   Weis, B
   Schechtman, LM
TI Meeting report: Validation of toxicogenomics-based test systems:
   ECVAM-ICCVAM/NICEATM considerations for regulatory use
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE acceptance; alternatives; biomarker; predictive test; regulatory use;
   standardization; toxicogenomics; toxicology; validation
ID GENE-EXPRESSION DATABASE; MICROARRAY DATA; STANDARDS; CANCER;
   INFORMATION; REPOSITORY; TOXICOLOGY; PLATFORMS; PROFILES
AB This is the report of the first workshop "Validation of Toxicogenomics-Based Test Systems" held 11-12 December 2003 in Ispra, Italy. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and organized jointly by ECVAM, the U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). The primary aim of the workshop was for participants to discuss and define principles applicable to the validation of toxicogenomics platforms as well as validation of specific toxicologic test methods that incorporate toxicogenomics technologies. The workshop was viewed as an opportunity for initiating a dialogue between technologic experts, regulators, and the principal validation bodies and for identifying those factors to which the validation process would be applicable. It was felt that to do so now, as the technology is evolving and associated challenges are identified, would be a basis for the future validation of the technology when it reaches the appropriate stage. Because of the complexity of the issue, different aspects of the validation of toxicogenomics-based test methods were covered. The three focus areas include a) biologic validation of toxicogenomics-based test methods for regulatory decision making, b) technical and bioinformatics aspects related to validation, and c) validation issues as they relate to regulatory acceptance and use of toxicogenomics-based test methods. In this report we summarize the discussions and describe in detail the recommendations for future direction and priorities.
C1 Joint Res Ctr European Commiss, European Ctr Validat Alternat Methods, IHCP, I-21120 Ispra, Italy.
   Bayer HealthCare AG, Wuppertal, Germany.
   Hoffmann La Roche AG, Basel, Switzerland.
   Hlth Canada, Environm Hlth Canada, Ottawa, ON K1A 0L2, Canada.
   JRC, IHCP, Ispra, Italy.
   TNO, Utrecht, Netherlands.
   QIAGEN, Hilden, Germany.
   US EPA, Washington, DC 20460 USA.
   Natl Inst Hlth Sci, Tokyo 158, Japan.
   Hlth Safety Execut, London, England.
   Syngenta, Macclesfield, Cheshire, England.
   European Bioinformat Inst, European Mol Biol Lab, Cambridge, England.
   AstraZeneca, Brixham, England.
   Org Econ Cooperat & Dev, Paris, France.
   US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
   Univ Maastricht, Maastricht, Netherlands.
   NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
   US Interagcy Coordinating Comm Validat Alternat M, Res Triangle Pk, NC USA.
   US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA.
RP Corvi, R (reprint author), Joint Res Ctr European Commiss, European Ctr Validat Alternat Methods, IHCP, Via E Fermi 1, I-21120 Ispra, Italy.
EM raffaella.corvi@jrc.it
OI Sansone, Susanna-Assunta/0000-0001-5306-5690
NR 49
TC 52
Z9 57
U1 0
U2 6
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2006
VL 114
IS 3
BP 420
EP 429
DI 10.1289/ehp.8247
PG 10
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 018NK
UT WOS:000235771000040
PM 16507466
ER

PT J
AU Lawson, CC
   Grajewski, B
   Daston, GP
   Frazier, LM
   Lynch, D
   McDiarmid, M
   Murono, E
   Perreault, SD
   Robbins, WA
   Ryan, MAK
   Shelby, M
   Whelan, EA
AF Lawson, CC
   Grajewski, B
   Daston, GP
   Frazier, LM
   Lynch, D
   McDiarmid, M
   Murono, E
   Perreault, SD
   Robbins, WA
   Ryan, MAK
   Shelby, M
   Whelan, EA
TI Workgroup report: Implementing a National Occupational Reproductive
   Research Agenda - Decade one and beyond
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE communication; environmental exposure; occupational exposure;
   reproduction; research design; risk factors
ID GENE-EXPRESSION PROFILE; ESTROGEN-RECEPTOR LIGANDS; ALPHA
   BINDING-AFFINITY; 17-ALPHA-ETHYNYL ESTRADIOL; IDENTIFICATION ALGORITHM;
   ENVIRONMENTAL-IMPACT; ANDROGEN RECEPTOR; BREAST-CANCER; HUMAN GENOME;
   IN-VITRO
AB The initial goal of occupational reproductive health research is to effectively study the many toxicants, physical agents, and biomechanical and psychosocial stressors that may constitute reproductive hazards in the workplace. Although the main objective of occupational reproductive researchers and clinicians is to prevent recognized adverse reproductive outcomes, research has expanded to include a broader spectrum of chronic health outcomes potentially affected by reproductive toxicants. To aid in achieving these goals, the National Institute for Occupational Safety and Health, along with its university, federal, industry, and labor colleagues, formed the National Occupational Research Agenda (NORA) in 1996. NORA resulted in 21 research teams, including the Reproductive Health Research Team (RHRT). In this report, we describe progress made in the last decade by, the RHRT and by others in this field, including prioritizing reproductive toxicants for further study; facilitating collaboration among epidemiologists, biologists, and toxicologists; promoting quality exposure assessment in field studies and surveillance; and encouraging the design and conduct of priority occupational reproductive studies. We also describe new tools for screening reproductive toxicants and for analyzing mode of action. We recommend considering outcomes such as menopause and latent adverse effects for further study, as well as including exposures such as shift work and nanomaterials. We describe a broad domain of scholarship activities where a cohesive system of organized and aligned work activities integrates 10 years of team efforts and provides guidance for future research.
C1 NIOSH, Cincinnati, OH 45226 USA.
   Procter & Gamble Co, Cincinnati, OH USA.
   Univ Kansas, Dept Prevent Med & Publ Hlth, Wichita, KS USA.
   Univ Kansas, Dept Obstet Gynecol, Wichita, KS USA.
   Univ Maryland, Sch Med, Occupat Hlth Program, Baltimore, MD 21201 USA.
   NIOSH, Morgantown, WV USA.
   US EPA, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA.
   Univ Calif Los Angeles, Ctr Environm & Occupat Hlth, Los Angeles, CA USA.
   Dept Def Ctr Deployment Hlth Res, San Diego, CA USA.
   NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Lawson, CC (reprint author), NIOSH, 4676 Columbia Pkwy,R-15, Cincinnati, OH 45226 USA.
EM clawson@cdc.gov
NR 85
TC 13
Z9 13
U1 0
U2 6
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
   RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD MAR
PY 2006
VL 114
IS 3
BP 435
EP 441
DI 10.1289/ehp.8458
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 018NK
UT WOS:000235771000042
PM 16507468
ER

PT J
AU Schwartz, DA
AF Schwartz, DA
TI Considering a society of environmental health science
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
C1 NIEHS, Bethesda, MD 20892 USA.
RP Schwartz, DA (reprint author), NIEHS, Bethesda, MD 20892 USA.
EM david.schwartz@niehs.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
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 MAR
PY 2006
VL 114
IS 3
BP A142
EP A142
PG 1
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 018NK
UT WOS:000235771000002
PM 16507440
ER

PT J
AU Wade, PA
   Archer, TK
AF Wade, PA
   Archer, TK
TI Epigenetics: Environmental instructions for the genome
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Editorial Material
ID HISTONE MODIFICATIONS; METHYLTRANSFERASES; CLONING; CELLS
C1 NIEHS, Mol Carcinogenesis Lab, NIH, Dept Hlth & Human Serv,Eukaryotic Transcript Regu, Res Triangle Pk, NC 27709 USA.
   NIEHS, Mol Carcinogenesis Lab, NIH, Dept Hlth & Human Serv,Chromatin & Gene Express S, Res Triangle Pk, NC 27709 USA.
RP Wade, PA (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Dept Hlth & Human Serv,Eukaryotic Transcript Regu, Res Triangle Pk, NC 27709 USA.
EM archer1@niehs.nih.gov
NR 21
TC 20
Z9 20
U1 1
U2 1
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 MAR
PY 2006
VL 114
IS 3
BP A140
EP A141
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Toxicology
GA 018NK
UT WOS:000235771000001
PM 16507439
ER

PT J
AU Brinton, LA
   Lubin, JH
   Murray, MC
   Colton, T
   Hoover, RN
AF Brinton, LA
   Lubin, JH
   Murray, MC
   Colton, T
   Hoover, RN
TI Mortality rates among augmentation mammoplasty patients - An update
SO EPIDEMIOLOGY
LA English
DT Article
ID COSMETIC BREAST IMPLANTS; CANCER DIAGNOSIS; SILICONE GEL; SWEDISH WOMEN;
   DANISH WOMEN; POPULATION; SURGERY; REDUCTION; RISK; PROGNOSIS
AB Background: A large follow-up study of cosmetic breast implant patients previously suggested an overall decrease in mortality but increased risks of brain and respiratory cancers and of suicides.
   Methods: This cohort of 12,144 implant patients and 3614 patients with other types of plastic surgeries was followed for 5 additional years, enabling derivations of standardized mortality ratios (SMRs) based on population rates and relative risks (RRs) based on comparisons with the other patients.
   Results: A total of 443 implant and 221 other plastic surgery patients were identified as deceased (SMR = 0.65 [95% confidence interval (CI) = 0.6-0.7] and 0.56 [0.5-0.6], respectively). Despite evidence that implants can interfere with mammographic visualization, there was no evidence that implant patients had a higher risk of death from breast cancer as compared with either the general population or other plastic surgery patients. The previous excess risk of brain cancer deaths among implant patients was attenuated by follow-up (as the result of no additional deaths; SMR = 1.43, 0.8-2.5; RR = 2.07, 0.5-8.9). A previously observed excess risk of respiratory cancer deaths persisted in comparisons with other plastic surgery patients (RR = 1.63; 1.0-2.7), but there was no evidence of a trend of risk with follow-up time. Implant patients also showed an elevated risk of suicide (SMR = 1.63, 1.1-2.3; RR = 2.58, 0.9-7.8) and of deaths caused by motor vehicle accidents (RR = 1.73; 0.6-5.4).
   Conclusions: Although several elevations in cause-specific mortality were attenuated by additional follow-up, the excess risk of suicide among the implant patients remains of concern.
C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD USA.
   Abt Associates Inc, Chicago, IL USA.
   Boston Univ, Dept Epidemiol & Biostat, Boston, MA USA.
RP Brinton, LA (reprint author), 6120 Execut Blvd,Room 7068, Rockville, MD 20852 USA.
EM brinton@nih.gov
RI Brinton, Louise/G-7486-2015
OI Brinton, Louise/0000-0003-3853-8562
FU Intramural NIH HHS
NR 36
TC 33
Z9 33
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAR
PY 2006
VL 17
IS 2
BP 162
EP 169
DI 10.1097/01.ede.0000197056.84629.19
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 015OX
UT WOS:000235561800010
PM 16477256
ER

PT J
AU Hatch, M
   Berkowitz, G
   Janevic, T
   Sloan, R
   Lapinski, R
   James, T
   Barth, WH
AF Hatch, M
   Berkowitz, G
   Janevic, T
   Sloan, R
   Lapinski, R
   James, T
   Barth, WH
TI Race, cardiovascular reactivity, and preterm delivery among active-duty
   military women
SO EPIDEMIOLOGY
LA English
DT Article
ID HEART-RATE REACTIVITY; UNITED-STATES; PREGNANCY; STRESS; CHALLENGE;
   BIRTH; HEALTH
AB Background: Rates of preterm delivery in the United States are higher in black women compared with whites. In this study, we examined cardiovascular reactivity and risk of preterm delivery among black and white military women.
   Methods: We recruited a total of 500 black and white active-duty military women from the prenatal clinic at a large military installation, interviewing them early in pregnancy and again at 28 weeks of gestation. A subgroup of women underwent a computerized stress test to determine cardiovascular reactivity assessed as increases in heart rate and blood pressure compared with measurements taken before the stress test.
   Results: Despite a relatively low overall risk of pretenn delivery (8.2%), we found the same 2-fold racial disparity reported in other populations (hazard ratio for preterm delivery in black women vs whites = 2.30-1 95% confidence interval = 1.24-4.27). The disparity is present in all military ranks and is largest for medically indicated preterm deliveries. Among the 313 subjects who participated in the computerized stress testing, blacks exhibited more cardiac reactivity than whites. In black subjects only, a 1-mm increase in diastolic blood pressure reactivity was associated with 1.1 a day earlier delivery (-0.17 weeks). A similar trend was seen with heart rate.
   Conclusions: Autonomic dysfunction after exposure to stressors may play a role in the timing of delivery among black women.
C1 Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA.
   Columbia Univ, Dept Behav Med, New York, NY USA.
   Wilford Hall USAF Med Ctr, Div Fetal & Maternal Med, San Antonio, TX USA.
RP Hatch, M (reprint author), NCI, Div Canc Epidemiol & Genet, DHHS, NIH, 6120 Execut Blvd,EPS 7098, Rockville, MD 20852 USA.
EM hatchm@mail.nih.gov
NR 24
TC 11
Z9 11
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAR
PY 2006
VL 17
IS 2
BP 178
EP 182
DI 10.1097/01.ede.0000199528.28234.73
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 015OX
UT WOS:000235561800012
PM 16477258
ER

PT J
AU Bischoff, C
   Petersen, HC
   Graakjaer, J
   Andersen-Ranberg, K
   Vaupel, JW
   Bohr, VA
   Kolvraa, S
   Christensen, K
AF Bischoff, C
   Petersen, HC
   Graakjaer, J
   Andersen-Ranberg, K
   Vaupel, JW
   Bohr, VA
   Kolvraa, S
   Christensen, K
TI No association between telomere length and survival among the elderly
   and oldest old
SO EPIDEMIOLOGY
LA English
DT Article
ID DANISH 1905 COHORT; HUMAN FIBROBLASTS; T-CELLS; LONGEVITY; DISEASE;
   RISK; CENTENARIANS; CHROMOSOME-7; MONOSOMY-7; MORTALITY
AB Background: The consistent findings of a negative correlation between telomere length and replicative potential of cultured cells, as well as a decreasing telomere length in a number of different tissues in humans with age, have led to the suggestion that telomeres play a role in cellular aging in vivo and ultimately even in organismal aging. Furthermore, one small longitudinal study of elderly individuals has suggested that longer telomeres are associated with better survival.
   Methods: Telomere length was measured as mean terminal restriction fragment length on blood cells from 812 persons, age 73 to 101 years, who participated in population-based surveys in 1997-1998. Among the participants were 652 twins. The participants were followed up through the Danish Civil Registration system until January 2005, at which time 412 (51%) were dead.
   Results: Univariate Cox regression analyses revealed that longer telomeres were associated with better survival (hazard ratios = 0.89 [95% confidence interval = 0.76-1.04] per 1 kb in males and 0.79 [0.72-0.88] per 1 kb in females, respectively). However, including age in the analyses changed the estimates to 0.97 (0.83-1.14) and 0.93 (0.85-1.03), respectively. Intrapair comparison showed that among 175 twin pairs in which at least one died during follow up, it was the twin with the shorter telomere length who died first in 97 (55%) of the pairs (95% confidence interval = 48-63%). We could not confirm the recently reported negative correlation between telomere length and obesity or between telomere length and smoking.
   Conclusion: This longitudinal study of the elderly and oldest old does not support the hypothesis that telomere length is a predictor for remaining lifespan once age is controlled for.
C1 Univ So Denmark, Inst Publ Hlth, Epidemiol Unit, Dept Stat, DK-5000 Odense C, Denmark.
   Aarhus Univ, Inst Human Genet, DK-8000 Aarhus, Denmark.
   Univ So Denmark, Epidemiol Unit, Danish Twin Registry, Odense C, Denmark.
   NIA, Lab Mol Gerontol, NIH, Baltimore, MD USA.
   Vejle Hosp, Dept Clin Genet, Vejle, Denmark.
   Max Planck Inst Demog Res, Rostock, Germany.
RP Christensen, K (reprint author), Univ So Denmark, Inst Publ Hlth, Epidemiol Unit, Dept Stat, DK-5000 Odense C, Denmark.
EM kchristensen@health.sdu.dk
RI Christensen, Kaare/C-2360-2009; Andersen-Ranberg, Karen/P-7053-2015
OI Christensen, Kaare/0000-0002-5429-5292; Andersen-Ranberg,
   Karen/0000-0003-1970-7076
FU NIA NIH HHS [P01-AG08761]
NR 37
TC 131
Z9 139
U1 0
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
J9 EPIDEMIOLOGY
JI Epidemiology
PD MAR
PY 2006
VL 17
IS 2
BP 190
EP 194
DI 10.1097/01.ede.0000199436.55248.10
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 015OX
UT WOS:000235561800014
PM 16477260
ER

PT J
AU Theodore, WH
   Giovacchini, G
   Bonwetsch, R
   Bagic, A
   Reeves-Tyer, P
   Herscovitch, P
   Carson, RE
AF Theodore, WH
   Giovacchini, G
   Bonwetsch, R
   Bagic, A
   Reeves-Tyer, P
   Herscovitch, P
   Carson, RE
TI The effect of antiepileptic drugs on 5-HT1A-receptor binding measured by
   positron emission tomography
SO EPILEPSIA
LA English
DT Article
DE serotonin receptors; positron emission tomography; antiepileptic drug
ID TEMPORAL-LOBE EPILEPSY; 5-HT1A RECEPTOR-BINDING; HIPPOCAMPAL
   EXTRACELLULAR SEROTONIN; RAT-BRAIN; IN-VITRO; CARBAMAZEPINE;
   5-HYDROXYTRYPTAMINE; DEPRESSION; RELEASE; INVIVO
AB Purpose: To study the effect of antiepileptic drugs (AEDs) on 5-HT1A-receptor binding in patients with temporal lobe epilepsy. 5-HT1A-receptor binding, measured by positron emission tomography, is reduced in patients with temporal lobe epilepsy. Antiepileptic drugs may act on the serotonergic system, as shown in animal models, and thus affect receptor-binding measurements.
   Methods: We analyzed the effect of AEDs on 5-HT1A-receptor binding in 31 patients and 10 normal controls. Patients with structural lesions, progressive neurologic disorders, or taking other medications were excluded. None had a seizure for >= 2 days before positron emission tomography (PET). [F-18]FCWAY PET was performed on a GE Advance scanner with continuous EEG monitoring. Functional images of the distribution volume (V) were generated. Anatomic regions of interest were applied to coregistered PET images, after correction for partial-volume effect.
   Results: Patients had significantly higher [F-18]FCWAY free fraction (f(1)) than did controls. No AED effects were observed on interictal [F-18]FCWAY binding after correction for plasma free fraction. [F-18]FCWAY V/f1 reduction in epileptic foci was not affected by AEDs.
   Conclusions: 5-HT1A-receptor binding is reduced in temporal lobe epileptic foci after partial-volume correction. AED plasma free fractions should be measured when PET receptor studies are performed in patients with epilepsy.
C1 NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
   NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA.
RP Theodore, WH (reprint author), Bldg 10,Room 5N-250,9000 Rockville PIke MSC 1408, Bethesda, MD 20892 USA.
EM theodorw@ninds.nih.gov
RI Carson, Richard/H-3250-2011
OI Carson, Richard/0000-0002-9338-7966
NR 28
TC 35
Z9 36
U1 0
U2 1
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD MAR
PY 2006
VL 47
IS 3
BP 499
EP 503
DI 10.1111/j.1528-1167.2006.00458.x
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 019MP
UT WOS:000235841100006
PM 16529612
ER

PT J
AU Agodoa, L
   Norris, KC
   Shahinfar, S
   Prabhakar, KS
   Pugsley, D
AF Agodoa, Lawrence
   Norris, Keith C.
   Shahinfar, Shahnaz
   Prabhakar, Kowdle S.
   Pugsley, David
TI Renal disease in minority populations and developing nations - Foreword
SO ETHNICITY & DISEASE
LA English
DT Editorial Material
ID KIDNEY-DISEASE; DISPARITIES
C1 Charles R Drew Univ Med & Sci, Lynwood, CA 90262 USA.
   NIDDKD, Off Minority Hlth Res Coordinat, NIH, Bethesda, MD 20892 USA.
   S Shahinfar Consulting Inc, Newtown Sq, PA USA.
   Natl Kidney Fdn, Singapore, Singapore.
   Univ Adelaide, Adelaide, SA 5005, Australia.
RP Norris, KC (reprint author), Charles R Drew Univ Med & Sci, 11705 Deputy Yamamoto Pl,Suite B, Lynwood, CA 90262 USA.
EM knorris@ucla.edu
NR 5
TC 0
Z9 0
U1 0
U2 0
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
J9 ETHNIC DIS
JI Ethn. Dis.
PD SPR
PY 2006
VL 16
IS 2
SU 2
BP 1
EP 1
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 048BQ
UT WOS:000237923000001
ER

PT J
AU Weil, EJ
   Nelson, RG
AF Weil, E. Jennifer
   Nelson, Robert G.
TI Kidney disease among the indigenous peoples of Oceania
SO ETHNICITY & DISEASE
LA English
DT Article
DE kidney disease; indigenous; Oceania; diabetic nephropathy
ID STAGE RENAL-DISEASE; AUSTRALIAN ABORIGINAL COMMUNITY; CARDIOVASCULAR
   RISK-FACTORS; IMPAIRED GLUCOSE-TOLERANCE; TYPE-2 DIABETES-MELLITUS;
   PAPUA-NEW-GUINEA; BLOOD-PRESSURE; PACIFIC POPULATIONS;
   INSULIN-RESISTANCE; PIMA-INDIANS
AB The prevalence of kidney disease is increasing among the indigenous peoples of Oceania-the region of the world that includes Australia, New Zealand, Papua New Guinea, and thousands of smaller islands. The number of indigenous people with early kidney disease is hard to quantify, but risk factors, including hypertension and diabetes, are widespread. The incidence of kidney failure is known in major population centers, where dialysis treatments are available, but few data are available elsewhere in Oceania. Nevertheless, the incidence of end-stage renal disease among Aborigines, Torres Straits Islanders, Pacific Islanders and Maori is considerably higher than in the surrounding non-indigenous populations, and most of the kidney failure is attributed to diabetes. Despite the high incidence of kidney failure among indigenous people, few receive kidney transplants, and geographic and economic constraints limit the availability of dialysis treatment. Consequently, clinical management should emphasize prevention, screening, and early intervention.
C1 NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA.
RP Nelson, RG (reprint author), NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
EM rgnelson@phx.niddk.nih.gov
RI Nelson, Robert/B-1470-2012
NR 63
TC 17
Z9 17
U1 0
U2 4
PU INT SOC HYPERTENSION BLACKS-ISHIB
PI ATLANTA
PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA
SN 1049-510X
J9 ETHNIC DIS
JI Ethn. Dis.
PD SPR
PY 2006
VL 16
IS 2
SU 2
BP 24
EP 30
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 048BQ
UT WOS:000237923000008
ER

PT J
AU Arnar, DO
   Thorvaldsson, S
   Manolio, TA
   Thorgeirsson, G
   Kristjansson, K
   Hakonarson, H
   Stefansson, K
AF Arnar, DO
   Thorvaldsson, S
   Manolio, TA
   Thorgeirsson, G
   Kristjansson, K
   Hakonarson, H
   Stefansson, K
TI Familial aggregation of atrial fibrillation in Iceland
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE arrhythmia; genetics; epidemiolgy
ID MYOCARDIAL-INFARCTION; GAELIC ANCESTRY; NATURAL-HISTORY; CONFERS RISK;
   DISEASE; PREVALENCE; STROKE; MTDNA; REYKJAVIK; MUTATION
AB Aims To examine the heritability of atrial fibrillation (AF) in Icelanders, utilizing a nationwide genealogy database and population-based data on AF. AF is a disorder with a high prevalence, which has been known to cluster in families, but the heritability of the common form has not been well defined.
   Methods and results The study population included 5269 patients diagnosed since 1987 and age-sex-matched controls randomly selected from the genealogy database. Kinship coefficients (KC), expressed as genealogical index of familiality (GIF=average KCx100 000), were calculated before and after exclusion of relatives separated by one to five meiotic events. Risk ratios (RR) were calculated for first- to fifth-degree relatives. The average pairwise GIF among patients with AF was 15.9 (mean GIF for controls 13.9, 95%CI=13.3, 14.4); this declined to 15.4 (mean GIF for controls 13.6, 95%CI=13.1, 14.2) after exclusion of relatives separated by one meiosis and to 13.7 (mean GIF for controls 12.6, 95%CI=12.1, 13.2), 12.7 (mean GIF for controls 11.9, 95%CI=11.4, 12.4), and 11.3 (mean GIF for controls 10.6, 95%CI=10.1, 11.1) after exclusion of relatives within two, three, and four meioses, respectively (all P < 0.00001). RRs among relative pairs also declined incrementally, from 1.77 in first-degree relatives to 1.36, 1.18, 1.10, and 1.05 in second- through fifth-degree relatives (all P < 0.001), consistent with the declining proportion of alleles shared identically by descent. When the analysis was limited to subjects diagnosed with AF before the age of 60, first-degree relatives of the AF cases were nearly five times more likely to have AF than the general population.
   Conclusion AF shows strong evidence of heritability among unselected patients in Iceland, suggesting that there may be undiscovered genetic variants underlying the risk of the common form of AF.
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
   Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland.
   deCode Genet Inc, IS-101 Reykjavik, Iceland.
RP Hakonarson, H (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM hakonh@decode.is; kstefans@decode.is
NR 30
TC 161
Z9 162
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD MAR
PY 2006
VL 27
IS 6
BP 708
EP 712
DI 10.1093/eurheartj/ehi727
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 018NQ
UT WOS:000235771600017
PM 16428254
ER

PT J
AU Mavrakis, M
   Frescas, D
   DeLotto, R
   Lippincott-Schwartz, J
AF Mavrakis, M
   Frescas, D
   DeLotto, R
   Lippincott-Schwartz, J
TI Compartmentalization of cytoplasm and secretory organelles in the
   absence of plasma membrane boundaries within the Drosophila synctial
   blastoderm
SO EUROPEAN JOURNAL OF CELL BIOLOGY
LA English
DT Meeting Abstract
CT 29th Annual Meeting of the German Society for Cell Biology
CY MAR 29-APR 01, 2006
CL Braunschweig, GERMANY
C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0171-9335
J9 EUR J CELL BIOL
JI Eur. J. Cell Biol.
PD MAR
PY 2006
VL 85
SU 56
BP 44
EP 44
PG 1
WC Cell Biology
SC Cell Biology
GA 037DS
UT WOS:000237127500084
ER

PT J
AU Karbowski, M
   Youle, R
AF Karbowski, M
   Youle, R
TI Dynamins and endophilins: Involvement in mitochondrial outer membrane
   dynamics
SO EUROPEAN JOURNAL OF CELL BIOLOGY
LA English
DT Meeting Abstract
CT 29th Annual Meeting of the German Society for Cell Biology
CY MAR 29-APR 01, 2006
CL Braunschweig, GERMANY
C1 NINDS, Porter Neurosci Res Ctr, Surg Neurol Branch, Bethesda, MD 20892 USA.
EM youle@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0171-9335
J9 EUR J CELL BIOL
JI Eur. J. Cell Biol.
PD MAR
PY 2006
VL 85
SU 56
BP 66
EP 66
PG 1
WC Cell Biology
SC Cell Biology
GA 037DS
UT WOS:000237127500140
ER

PT J
AU Umhau, JC
   Dauphinais, KM
   Patel, SH
   Nahrwold, DA
   Hibbeln, JR
   Rawlings, RR
   George, DT
AF Umhau, JC
   Dauphinais, KM
   Patel, SH
   Nahrwold, DA
   Hibbeln, JR
   Rawlings, RR
   George, DT
TI The relationship between folate and docosahexaenoic acid in men
SO EUROPEAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE RBC folate; docosahexaenoic acid; folic acid; n-3 fatty acids;
   phosphatidylethanolamine-N-methyltransferase
ID POLYUNSATURATED FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND;
   FISH-OIL; CARDIOVASCULAR-DISEASE; RHEUMATOID-ARTHRITIS; PLASMA
   HOMOCYSTEINE; ALZHEIMER-DISEASE; BIPOLAR DISORDER; CROHNS-DISEASE
AB Objective: Docosahexaenoic acid (DHA, 22: 6n- 3), an essential omega 3 fatty acid, may protect against disorders of emotional regulation as well as cardiovascular disease. Animal studies demonstrate that dietary folate can increase tissue concentrations of DHA, although the literature, to date, includes no human studies examining the possibility that folate status may affect plasma DHA concentrations. The objective of this study is to determine if the blood concentrations of folate and DHA are correlated in humans.
   Design: Retrospective study.
   Setting: An American research hospital.
   Subjects: A total of 15 normal and 22 hostile and aggressive subjects, with a mean age of 38 years.
   Methods: Concentrations of plasma polyunsaturated essential fatty acids and red blood cell folate (RBC folate) were obtained prior to 1996, before American flour was enriched with folate.
   Results: RBC folate was significantly correlated with plasma DHA, r = 0.57, P = 0.005 in the aggressive group. Age, smoking and alcohol consumption did not alter the results. No other essential fatty acids were significantly associated with RBC folate in either group.
   Conclusions: The positive relationship between plasma DHA and RBC folate concentrations suggests that these two nutrients should be examined together in order to make the most accurate inferences about their relative contributions to disease pathogenesis. Our findings present one explanation why some conditions associated with hostility and low DHA status, such as cardiovascular disease and emotional disorders, are also associated with low folate status.
C1 NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA.
RP Umhau, JC (reprint author), NIAAA, Clin Studies Lab, NIH, 10 Ctr Dr,Bldg 10-CRC,Room 1-5330, Bethesda, MD 20892 USA.
EM Umhau@nih.gov
FU Intramural NIH HHS
NR 50
TC 27
Z9 27
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0954-3007
J9 EUR J CLIN NUTR
JI Eur. J. Clin. Nutr.
PD MAR
PY 2006
VL 60
IS 3
BP 352
EP 357
DI 10.1038/sj.ejcn.1602321
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 017BI
UT WOS:000235668700008
PM 16278690
ER

PT J
AU Chen, X
   Winkler-Pickett, RT
   Carbonetti, NH
   Ortaldo, JR
   Oppenheim, JJ
   Howard, OMZ
AF Chen, X
   Winkler-Pickett, RT
   Carbonetti, NH
   Ortaldo, JR
   Oppenheim, JJ
   Howard, OMZ
TI Pertussis toxin as an adjuvant suppresses the number and function of
   CD4(+)CD25(+) T regulatory cells
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE CD4(+)CD25(+) T regulatory cells; experimental autoimmune
   encephalomyelitis; pertussis toxin
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; BORDETELLA-PERTUSSIS;
   DENDRITIC CELLS; CYTOKINE PRODUCTION; LYMPHOCYTE-T; RESPONSES;
   ACTIVATION; IL-2; EXPRESSION; TOLERANCE
AB We observed a remarkable reduction in the frequency and immunosuppressive activity of splenic CD4(+)CD25(+) T cells in C57BL/6 mice with MOG(33-55)-induced experimental autoimmune encephalomyelitis (EAE). Our study revealed that pertussis toxin (PTx), one component of the immunogen used to induce murine EAE, was responsible for down-regulating splenic CD4(+)CD25(+) cells. Treatment of normal BALB/c mice with PTx in vivo reduced the frequency, suppressive activity and FoxP3 expression by splenic CD4(+)CD25(+) T cells. However, PTx treatment did not alter the expression of characteristic phenotypic markers (CD45RB, CD103, GITR and CTLA-4) and did not increase the expression of CD44 and CD69 by the residual splenic and lymph node CD4(+)CD25(+) T cells. This property of PTx was attributable to its ADP-ribosyltransferase activity. PTx did not inhibit suppressive activity of purified CD4(+)CD25(+) T regulatory (Treg) cells in vitro, but did so in vivo, presumably due to an indirect effect. Although the exact molecular target of PTx that reduces Treg activity remains to be defined, our data suggests that alteration of both distribution and function of splenic immunocytes should play a role. This study concludes that an underlying cause for the immunological adjuvanticity of PTx is down-regulation of Treg cell number and function.
C1 NCI, Basic Res Program, SAIC Frederick Inc, Mol Immunoregulat Lab, Frederick, MD 21702 USA.
   NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
   Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
   NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Chen, X (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Mol Immunoregulat Lab, POB B,Bldg 560,Rm 31-19, Frederick, MD 21702 USA.
EM xinc@mail.ncifcrf.gov
RI Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015
OI Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027
FU Intramural NIH HHS; NCI NIH HHS [N01 CO012400, N01-CO-012400,
   N01CO12400]
NR 39
TC 70
Z9 74
U1 1
U2 4
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD MAR
PY 2006
VL 36
IS 3
BP 671
EP 680
DI 10.1002/eji.200535353
PG 10
WC Immunology
SC Immunology
GA 028AJ
UT WOS:000236457400017
PM 16479542
ER

PT J
AU Blasi, G
   Goldberg, TE
   Weickert, T
   Das, S
   Kohn, P
   Zoltick, B
   Bertolino, A
   Callicott, JH
   Weinberger, DR
   Mattay, VS
AF Blasi, G
   Goldberg, TE
   Weickert, T
   Das, S
   Kohn, P
   Zoltick, B
   Bertolino, A
   Callicott, JH
   Weinberger, DR
   Mattay, VS
TI Brain regions underlying response inhibition and interference monitoring
   and suppression
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; PREFRONTAL CORTEX;
   FUNCTIONAL MRI; ERROR-DETECTION; ATTENTIONAL CONTROL; NEURAL MECHANISMS;
   COGNITIVE CONTROL; STROOP TASK; GO/NO-GO
AB Response inhibition and interference monitoring and suppression are two important aspects of cognitive control. Previous functional imaging studies have suggested a common network of brain regions underlying these cognitive processes; the dorsolateral prefrontal cortex (DLPFC), the ventrolateral prefrontal cortex (VLPFC), the dorsal cingulate (dACC), and the parietal cortex (PC). The relative contribution of these regions to these cognitive subprocesses, however, has not been determined. Based on previous findings supporting a role for dACC in the monitoring of conflicting information within a stimulus, we hypothesized greater activity in this cortical region during interference monitoring and suppression relative to response inhibition. On the other hand, as response inhibition is characterized by differential cognitive processes such as control implementation, top down modulation of the response, expectancy, and inhibition of behavioural response, we hypothesized increased activity in the other cortical nodes of the cognitive control network relative to interference monitoring and suppression. To this end, we conducted an event-related functional magnetic resonance imaging (fMRI) study in 57 healthy volunteers using a task preferentially involving either interference monitoring and suppression or response inhibition. Accuracy for response inhibition was lower than for interference monitoring and suppression. Imaging data showed activation in DLPFC, dACC, VLPFC, PC for both conditions. Comparisons between the two conditions indicated greater activation bilaterally in DLPFC, VLPFC and PC during response inhibition, and greater activation in the dACC during interference monitoring and suppression. These results extend previous findings by suggesting regional functional specialization within a cortical network supporting cognitive control.
C1 NIMH, CBDB, GCAP, NIH,Dept Hlth & Human Serv, Bethesda, MD 20982 USA.
   Univ Bari, Psychiat Neurosci Grp, Dept Neurol & Psychiat Sci, Bari, Italy.
   IRCCS Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy.
RP Mattay, VS (reprint author), NIMH, CBDB, GCAP, NIH,Dept Hlth & Human Serv, Bldg 10,Ctr Dr, Bethesda, MD 20982 USA.
EM vsm@mail.nih.gov
RI Bertolino, Alessandro/O-6352-2016; 
OI Bertolino, Alessandro/0000-0002-1251-1380; Callicott,
   Joseph/0000-0003-1298-3334
NR 55
TC 93
Z9 96
U1 4
U2 23
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD MAR
PY 2006
VL 23
IS 6
BP 1658
EP 1664
DI 10.1111/j.1460-9568.2006.04680.x
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 024DU
UT WOS:000236176000027
PM 16553630
ER

PT J
AU Ravasi, L
   Kiesewetter, DO
   Shimoji, K
   Lucignani, G
   Eckelman, WC
AF Ravasi, L
   Kiesewetter, DO
   Shimoji, K
   Lucignani, G
   Eckelman, WC
TI Why does the agonist [F-18]FP-TZTP bind preferentially to the M-2
   muscarinic receptor?
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE muscarinic receptor; CHO cells; PET tracer; Alzheimer's disease
ID IN-VIVO; ALZHEIMERS-DISEASE; SUBTYPE SELECTIVITY; SIGMA(1) RECEPTOR;
   RAT-BRAIN; M2; COMPETITION; INVIVO; <F-18>FP-TZTP; LOCALIZATION
AB Purpose: Preferential binding of FP-TZTP at the M-2 receptor in vivo led to investigation of [F-18]FP-TZTP as a potential PET tracer for Alzheimer's disease, in which a substantial reduction of M-2 receptors has been observed in autopsy studies. We hereby investigated in vitro the FP-TZTP behavior to further elucidate the properties of FP-TZTP that lead to its M-2 selectivity.
   Methods: Chinese hamster ovarian cells expressing the five subtypes of human muscarinic receptor as well as the wild type were harvested in culture to assess equilibrium binding. Specific binding was calculated by subtraction of non-specific binding from total binding. Internal specific binding was calculated by subtraction of external specific binding from the total specific binding. Saturation assays were also performed to calculate B-max, K-i, and IC50. In addition, equilibrium binding and dissociation kinetic studies were performed on rat brain tissue. Selected regions of interest were drawn on the digital autoradiograms and [F-18]FP-TZTP off-rates were determined by measurement of the rate of release into a buffer solution of [F-18]FP-TZTP from slide-bound cells that had been preincubated with [F-18]FP-TZTP.
   Results: At equilibrium in vitro, M-2 subtype selectivity of [F-18]FP-TZTP was not evident. We demonstrated that ATP-dependent mechanisms are not responsible for FP-TZTP M-2 selectivity. In vitro off-rate studies from rat brain tissue showed that the off-rate of FP-TZTP varied with the percentage of M-2 subtype in the tissue region.
   Conclusion: The slower dissociation kinetics of FP-TZTP from M-2 receptors compared with the four other muscarinic receptor subtypes may be a factor in its M-2 selectivity.
C1 Natl Inst Biomed Imaging & Bioengn, PET Radiochem Grp, NIH, Bethesda, MD 20892 USA.
   Univ Milan, Inst Radiol Sci, Milan, Italy.
   European Inst Oncol, Div Radiat Therapy, Unit Mol Imaging, Milan, Italy.
   NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA.
   Mol Tracer LLC, Bethesda, MD USA.
RP Kiesewetter, DO (reprint author), Natl Inst Biomed Imaging & Bioengn, PET Radiochem Grp, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM dk7k@nih.gov
RI Lucignani, Giovanni/C-6773-2008
FU Intramural NIH HHS
NR 35
TC 5
Z9 5
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 1619-7070
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD MAR
PY 2006
VL 33
IS 3
BP 292
EP 300
DI 10.1007/s00259-005-1966-x
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 022CK
UT WOS:000236032100011
PM 16333673
ER

PT J
AU Scarpa, B
   Dunson, DB
   Colombo, B
AF Scarpa, Bruno
   Dunson, David B.
   Colombo, Bernardo
TI Cervical mucus secretions on the day of intercourse: An accurate marker
   of highly fertile days
SO EUROPEAN JOURNAL OF OBSTETRICS GYNECOLOGY AND REPRODUCTIVE BIOLOGY
LA English
DT Article
DE cervical mucus; conception; fertile interval; menstrual cycle;
   ovulation; pregnancy probability; secretions
ID MENSTRUAL-CYCLE; OVULATION METHOD; CONCEPTION; PREGNANCY; PROBABILITIES;
   WINDOW; SPERM; RATES
AB Objective: To provide estimates of the probabilities of conception according to vulvar mucus observations classified by the woman on the day of intercourse.
   Study design: Prospective cohort study of 193 outwardly healthy Italian women using the Billings Ovulation Method. Outcome measures include 161 conception cycles and 2594 non-conception cycles with daily records of the type of mucus and the occurrences of sexual intercourse.
   Results: The probability of conception ranged from 0.003 for days with no noticeable secretions to 0.29 for days with most fertile-type mucus detected by the woman. The probability of most fertile type mucus by day of the menstrual cycle increased from values < 20% outside of days 10-17 to a peak of 59% on day 13.
   Conclusion: Regardless of the timing of intercourse in the menstrual cycle, the probability of conception is essentially 0 on days with no secretions. This probability increases dramatically to near 30% on days with most fertile-type mucus, an association that accurately predicts both the timing of the fertile interval and the day-specific conception probabilities across the menstrual cycle. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
   Univ Pavia, Dept Appl Stat & Econ, I-27100 Pavia, Italy.
   Univ Padua, Dept Stat, Padua, Italy.
RP Dunson, DB (reprint author), NIEHS, NIH, MD A3-03, Res Triangle Pk, NC 27709 USA.
EM dunson1@niehs.nih.gov
NR 29
TC 18
Z9 18
U1 0
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0301-2115
J9 EUR J OBSTET GYN R B
JI Eur. J. Obstet. Gynecol. Reprod. Biol.
PD MAR
PY 2006
VL 125
IS 1
BP 72
EP 78
DI 10.1016/j.ejogrb.2005.07.024
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 149YB
UT WOS:000245181700011
PM 16154254
ER

PT J
AU Insel, T
AF Insel, T
TI Social neuroscience: from genes to social behavior
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT Workshop on Neuropsychopharmacology for Young Scienctists in Europe
CY MAR 09-12, 2006
CL Nice, FRANCE
SP ECNP
ID BRAIN
C1 NIMH, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD MAR
PY 2006
VL 16
SU 1
BP S37
EP S37
DI 10.1016/S0924-977X(06)80045-3
PG 1
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 040TL
UT WOS:000237403200046
ER

PT J
AU Wargelius, H
   Fahlke, C
   Oreland, L
   Higley, JD
AF Wargelius, H
   Fahlke, C
   Oreland, L
   Higley, JD
TI Monoamine oxidase activity predicts aggressive behaviour and type II
   alcoholism in rhesus monkeys
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT Workshop on Neuropsychopharmacology for Young Scienctists in Europe
CY MAR 09-12, 2006
CL Nice, FRANCE
SP ECNP
ID PERSONALITY
C1 Uppsala Univ, Dept Neurosci Pharmacol, Uppsala, Sweden.
   Univ Gothenburg, Dept Psychol, S-40020 Gothenburg, Sweden.
   NIH, Anim Ctr, Comparat Ethol & Clin Studies Primate Unit, Poolesville, MD USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD MAR
PY 2006
VL 16
SU 1
BP S3
EP S3
DI 10.1016/S0924-977X(06)80004-0
PG 1
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 040TL
UT WOS:000237403200005
ER

PT J
AU Nyska, A
   Horowitz, M
   Anaby, D
   Sabban, A
   Leizerman, I
   Blaugrund, E
   Mayk, A
   Behar, V
AF Nyska, A
   Horowitz, M
   Anaby, D
   Sabban, A
   Leizerman, I
   Blaugrund, E
   Mayk, A
   Behar, V
TI A new method of wet scanning electron microscopy for the analysis of
   myelination in EAE mouse model of multiple sclerosis
SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE wet scanning electron microscopy; myelin; multiple sclerosis
ID PATHOGENESIS; DIAGNOSIS; TISSUES; SAMPLES; CELLS; SEM
AB Development of effective therapies for multiple sclerosis (MS) is dependent on the advancement of improved tools for evaluation of progression of this disease in animal models. We present a novel technique utilizing scanning electron microscopy (SEM) for imaging wet biological specimens thus enabling rapid and high-resolution imaging of myelin in mouse spinal cord (SC). We demonstrate the advantages of using the wet SEM technique to image myelin in a murine model of MS, experimental autoimmune encephalomyelitis (EAE) induced in the Biozzi (antibody-high) mouse, by sensitization with spinal cord homogenate (SCH) in adjuvant. Our studies show that the methodology allows easy identification of normal and pathological components with great clarity, which is then correlated with light microscopy (LM) and validated thereby. Furthermore, we demonstrate gold immunolabeling of specific epitopes. We conclude that the new technique provides a quick, accurate, and detailed structural evaluation of the SC that can be applied to advance the research of MS. (C) 2005 Elsevier GmbH. All rights reserved.
C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA.
   QuantomiX Ltd, Ness Ziona, Israel.
   Teva Ltd, Netanya, Israel.
RP Nyska, A (reprint author), Haharuv 18,POB 184, IL-23840 Timrat, Israel.
EM anyska@bezeqint.net
NR 15
TC 6
Z9 6
U1 1
U2 3
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0940-2993
J9 EXP TOXICOL PATHOL
JI Exp. Toxicol. Pathol.
PD MAR
PY 2006
VL 57
IS 4
BP 291
EP 297
DI 10.1016/j.etp.2005.11.001
PG 7
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 025AY
UT WOS:000236238900004
PM 16413765
ER

PT J
AU Leverkus, M
   Jochim, R
   Schad, S
   Brocker, EB
   Andersen, J
   Valenzuela, J
   Trautmann, A
AF Leverkus, M
   Jochim, R
   Schad, S
   Brocker, EB
   Andersen, J
   Valenzuela, J
   Trautmann, A
TI Bullous allergic hypersensitivity to bed bug bites mediated by
   immunoglobulin E against salivary nitrophorin
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung
   (ADF)
CY MAR 23-25, 2006
CL Aachen, GERMANY
SP Arbeits Gemeinsch Dermatol Forsch
C1 Univ Magdeburg, Dept Dermatol & Venerol, Lab Expt Dermatol, D-39106 Magdeburg, Germany.
   Univ Wurzburg, Dept Dermatol & Allergol, Wurzburg, Germany.
   Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA.
   NIAID, Lab Malaria & Vector Res, Vector Mol Biol Unit, NIH, Rockville, MD USA.
NR 0
TC 0
Z9 1
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2006
VL 15
IS 3
BP 191
EP 191
PG 1
WC Dermatology
SC Dermatology
GA 012WC
UT WOS:000235370600019
ER

PT J
AU Oji, V
   Aufenvenne, K
   Ahvazi, B
   Hausser, I
   Kuster, W
   Hennies, H
   Traupe, H
AF Oji, V
   Aufenvenne, K
   Ahvazi, B
   Hausser, I
   Kuster, W
   Hennies, H
   Traupe, H
TI Bathing suit ichthyosis is associated with transglutaminase 1 deficiency
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung
   (ADF)
CY MAR 23-25, 2006
CL Aachen, GERMANY
SP Arbeits Gemeinsch Dermatol Forsch
C1 Univ Munster, Dept Dermatol, D-4400 Munster, Germany.
   NIAMS, Off Sci & Technol, NIH, Bethesda, MD USA.
   NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2006
VL 15
IS 3
BP 197
EP 197
PG 1
WC Dermatology
SC Dermatology
GA 012WC
UT WOS:000235370600038
ER

PT J
AU Kostka, SL
   Dinges, S
   Knop, J
   Udey, MC
   Iwakura, Y
   von Stebut, E
AF Kostka, SL
   Dinges, S
   Knop, J
   Udey, MC
   Iwakura, Y
   von Stebut, E
TI Elucidation of the role of interleukin-17 in murine cutaneous
   leishmaniasis
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung
   (ADF)
CY MAR 23-25, 2006
CL Aachen, GERMANY
SP Arbeits Gemeinsch Dermatol Forsch
C1 Univ Mainz, Dept Dermatol, D-6500 Mainz, Germany.
   NCI, NIH, Dermatol Branch, Bethesda, MD 20892 USA.
   Univ Tokyo, Ctr Med Expt, Inst Med Sci, Tokyo, Japan.
RI Iwakura, Yoichiro/E-5457-2011
OI Iwakura, Yoichiro/0000-0002-9934-5775
NR 0
TC 0
Z9 0
U1 0
U2 1
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2006
VL 15
IS 3
BP 226
EP 227
PG 2
WC Dermatology
SC Dermatology
GA 012WC
UT WOS:000235370600134
ER

PT J
AU Molle, K
   Tada, Y
   Shibagaki, N
   Knop, J
   Udey, MC
   von Stebut, E
AF Molle, K
   Tada, Y
   Shibagaki, N
   Knop, J
   Udey, MC
   von Stebut, E
TI TAT-LACK-transduced dendritic cells induce antigen-specific CD8(+) T
   cells and efficiently vaccinate against murine cutaneous leishmaniasis
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung
   (ADF)
CY MAR 23-25, 2006
CL Aachen, GERMANY
SP Arbeits Gemeinsch Dermatol Forsch
C1 Univ Mainz, Dept Dermatol, D-6500 Mainz, Germany.
   NCI, NIH, Dermatol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2006
VL 15
IS 3
BP 226
EP 226
PG 1
WC Dermatology
SC Dermatology
GA 012WC
UT WOS:000235370600133
ER

PT J
AU Emmert, S
   Ueda, T
   Zumsteg, U
   Khan, SG
   Laspe, P
   Zachmann, K
   Leibeling, D
   Bircher, A
   Kraemer, KH
AF Emmert, S
   Ueda, T
   Zumsteg, U
   Khan, SG
   Laspe, P
   Zachmann, K
   Leibeling, D
   Bircher, A
   Kraemer, KH
TI The common R683W rather than a new fs670 -> 693ter mutation in the XPD
   gene determines the xeroderma pigmentosum phenotype in a 15-year-old boy
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung
   (ADF)
CY MAR 23-25, 2006
CL Aachen, GERMANY
SP Arbeits Gemeinsch Dermatol Forsch
C1 Univ Goettingen, Dept Dermatol, Gottingen, Germany.
   NCI, NIH, Basic Res Lab, Bethesda, MD 20892 USA.
   Univ Basel Hosp, Dept Pediatry, CH-4031 Basel, Switzerland.
   Univ Basel Hosp, Dept Dermatol, CH-4031 Basel, Switzerland.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2006
VL 15
IS 3
BP 230
EP 230
PG 1
WC Dermatology
SC Dermatology
GA 012WC
UT WOS:000235370600146
ER

PT J
AU Tormo, D
   Ferrer, A
   Steitz, J
   Speuser, P
   Gaffal, E
   Malumbres, M
   Barbacid, M
   Merlino, G
   Tuting, T
AF Tormo, D
   Ferrer, A
   Steitz, J
   Speuser, P
   Gaffal, E
   Malumbres, M
   Barbacid, M
   Merlino, G
   Tuting, T
TI Mutant CDK4 and aberrant hepatocyte growth factor signalling
   synergistically promote rapid induction of carcinogen-induced metastatic
   melanoma
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Meeting Abstract
CT 33rd Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung
   (ADF)
CY MAR 23-25, 2006
CL Aachen, GERMANY
SP Arbeits Gemeinsch Dermatol Forsch
C1 Uniklin Bonn, Bonn, Germany.
   Ctr Nacl Invest Oncol, Madrid, Spain.
   NCI, Mol Biol Lab, Bethesda, MD 20892 USA.
RI Malumbres, Marcos/E-8834-2011
OI Malumbres, Marcos/0000-0002-0829-6315
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0906-6705
J9 EXP DERMATOL
JI Exp. Dermatol.
PD MAR
PY 2006
VL 15
IS 3
BP 240
EP 241
PG 2
WC Dermatology
SC Dermatology
GA 012WC
UT WOS:000235370600181
ER

PT J
AU Robinson, MR
   Lee, SS
   Kim, H
   Kim, S
   Lutz, RJ
   Galban, C
   Bungay, PM
   Yuan, P
   Wang, NS
   Kim, J
   Csaky, KG
AF Robinson, MR
   Lee, SS
   Kim, H
   Kim, S
   Lutz, RJ
   Galban, C
   Bungay, PM
   Yuan, P
   Wang, NS
   Kim, J
   Csaky, KG
TI A rabbit model for assessing the ocular barriers to the transscleral
   delivery of triamcinolone acetonide
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE triamcinolone acetonide; conjunctival lymphatics; sclera; drug delivery;
   vitreous animal model
ID DEPOT-CORTICOSTEROID PENETRATION; HUMAN SCLERAL PERMEABILITY;
   DRUG-DELIVERY; INTRAVITREAL TRIAMCINOLONE; INTRAOCULAR PENETRATION;
   POSTERIOR SEGMENT; SUB-CONJUNCTIVAL; DIODE-LASER; INJECTION; EYE
AB Transscleral delivery of triamcinolone acetonide into the vitreous using sub-Tenon's injections may be a safer alternative to reduce the sight-threatening complications of direct intravitreal injections. However, sub-Tenon's injections have demonstrated low and poorly sustained vitreous drug levels in animal studies. To improve our understanding of the clearance mechanisms of corticosteroids, we evaluated vitreous drug levels following sub-Tenon's injection of triamcinolone acetonide in rabbits with selective elimination of conjunctival lymphatic/blood vessels and the choroid. Pigmented rabbits were given a sub-Tenon's injection of a preservative-free triamcinolone acetonide formulation of either a 10- or 20-mg dose in the superotemporal quadrant. The effect eliminating both conjunctival and choroidal clearance was evaluated by injecting the drug, followed by immediate euthanasia, effectively terminating both lymph and blood flow in the conjunctiva and choroid. To inhibit only the clearance from conjunctival lymphatics/blood vessels of a sub-Tenon's injection of triamcinolone acetonide, a group of rabbits had a 'conjunctival window' created by incising an 7 mm X 7 mm X 7 mm square through the conjunctiva to bare sclera in the superotemporal quadrant. To eliminate only the clearance of drug from the choroidal circulation, cryotherapy was performed in another group of rabbits creating a chorioretinal scar in the superotemporal quadrant. Following the sub-Tenon's drug injection, the eyes were enucleated in all groups after 3 hr and vitreous drug levels were measured with HPLC. In normal animals, a 10-mg sub-Tenon's injection showed no detectable vitreous drug levels; however, a 20-mg injection showed positive vitreous drug levels. This suggested that collectively, the transscleral clearance mechanisms inhibiting delivery into the vitreous may be saturated with a drug depot that has a higher release rate. A 10-mg sub-Tenon's drug depot was able to deliver drug into the vitreous when both the conjunctival and choroidal drug clearance was eliminated by euthanizing the animal immediately following the drug injection. in rabbits that had only a conjunctival window', selectively eliminating conjunctival drug clearance, vitreous drug levels were detected. However, in rabbits that had only cryotherapy, selectively eliminating choroidal drug clearance, vitreous drug levels were not detected suggesting that the conjunctival lymphatics/blood vessels may be an important barrier to the transscleral delivery of triamcinolone acetonide. Variability in the vitreous drug levels between rabbits in each group precluded statistical testing. In summary, the rabbit appeared to demonstrate saturable ocular barriers to transscleral delivery of triamcinolone acetonide into the vitreous following a sub-Tenon's injection. The results suggested that the conjunctival lymphatics/blood vessels may be an important barrier to the delivery of triamcinolone acetonide to the vitreous in this rabbit model. The barrier location and clearance abilities of the ocular tissues are important to consider when developing a successful transscleral drug delivery system. Animal models, retaining the dynamics of blood and lymph flow, may improve the basic understanding of the ocular barriers involved with transscleral drug transport and warrants further investigation. Published by Elsevier Ltd.
C1 NEI, NIH, Bethesda, MD USA.
   NIH, ORS, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA.
   NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA.
   Univ Maryland, Dept Chem Engn, College Pk, MD 20742 USA.
   EMMES Corp, Rockville, MD USA.
RP Robinson, MR (reprint author), NEI, NIH, 10-10N112,10 Ctr Dr MSC 1863, Bethesda, MD USA.
EM robinsonm@nei.nih.gov
RI Wang, Nam Sun/E-4253-2016
NR 62
TC 81
Z9 87
U1 4
U2 9
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
J9 EXP EYE RES
JI Exp. Eye Res.
PD MAR
PY 2006
VL 82
IS 3
BP 479
EP 487
DI 10.1016/j.exer.2005.08.007
PG 9
WC Ophthalmology
SC Ophthalmology
GA 019GQ
UT WOS:000235824000016
PM 16168412
ER

PT J
AU Chow, DK
   Glenn, CF
   Johnston, JL
   Goldberg, IG
   Wolkow, CA
AF Chow, DK
   Glenn, CF
   Johnston, JL
   Goldberg, IG
   Wolkow, CA
TI Sarcopenia in the Caenorhabditis elegans pharynx correlates with muscle
   contraction rate over lifespan
SO EXPERIMENTAL GERONTOLOGY
LA English
DT Article
DE Caenorhabditis elegans; pharynx; sarcopenia; muscle; aging; insulin;
   acetylcholine; bacteria; microbial stress
ID SKELETAL-MUSCLE; C-ELEGANS; LONGEVITY; GENETICS; SYSTEM;
   NEUROTRANSMISSION; SEROTONIN; EXERCISE; DECLINE; MUTANT
AB In muscles, sarcopenia, the loss of muscle mass, is the major cause of aging-related functional decline and frailty. Several factors are correlated with sarcopenia during aging, including contraction-related cellular injury, oxidative stress, endocrine changes and reduced regenerative potential. However the involvement of these factors has not been experimentally investigated. Here, we report that contraction-related injury may significantly promote the progression of sarcopenia in the pharynx of the nematode, Caenorhabditis elegans, a model of aging in non-regenerative tissues. Both functional and structural declines in the pharynx during aging were significantly delayed in mutants with reduced muscle contraction rates. We also examined the role of bacteria in pharynx muscle decline during aging, as previous studies reported that antimicrobial treatments could extend C. elegans lifespan. Although microbial infection may have enhanced functional decline in the pharynx during aging, it was not the sole cause of decreased pumping rates in old animals. This study identifies contraction-related injury as a factor affecting the initiation and progression of sarcopenia during aging. Further, characterization of the specific types of damage induced by muscle contraction will be helpful for understanding the underlying causes of sarcopenia. Published by Elsevier Inc.
C1 NIA, Neurosci Lab, Intramural Res Program, Gerontol Res Ctr, Baltimore, MD 21224 USA.
   NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Wolkow, CA (reprint author), NIA, Neurosci Lab, Intramural Res Program, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM wolkowca@grc.nia.nih.gov
RI Goldberg, Ilya/H-5307-2011
OI Goldberg, Ilya/0000-0001-8514-6110
FU Intramural NIH HHS [NIH0011061953, Z01 AG000320-06]
NR 32
TC 49
Z9 54
U1 1
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0531-5565
J9 EXP GERONTOL
JI Exp. Gerontol.
PD MAR
PY 2006
VL 41
IS 3
BP 252
EP 260
DI 10.1016/j.exger.2005.12.004
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 030RY
UT WOS:000236653300003
PM 16446070
ER

PT J
AU Lim, JB
   Provenzano, M
   Kwon, OH
   Bettinotti, M
   Caruccio, L
   Nagorsen, D
   Stroncek, D
AF Lim, JB
   Provenzano, M
   Kwon, OH
   Bettinotti, M
   Caruccio, L
   Nagorsen, D
   Stroncek, D
TI Identification of HLA-A33-restricted CMV pp65 epitopes as common targets
   for CD8(+) CMV-specific cytotoxic T lymphocytes
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID ALLOGENEIC MARROW TRANSPLANT; DENDRITIC CELLS; BONE-MARROW; PROTEIN
   PP65; CYTOMEGALOVIRUS DISEASE; INTERFERON-GAMMA; GENE-EXPRESSION;
   RECIPIENTS; VIRUS; INFECTION
AB Objective. To identify an immunodominant HLA-A33-restricted epitope within the CMV matrix phosphoprotein 65 (pp65) that could be used to elicit CM-specific CTLs.
   Methods. A computer algorithm was used to identify pp65 peptides that were expected to bind to HLA-A33. The peptides were screened for their ability to reactivate memory T lymphocytes from CM-seropositive HLA-A33 donors by using quantitative real-time RT-PCR. The most promising peptides were then tested for their ability to expand a CD8(+) population of HLA-33 CTLs that produced interferon-gamma (IFN-gamma) and were cytotoxic to either peptide-loaded or CMV-infected target cells.
   Results. Sixteen out of 250 peptides were selected using a computer algorithm and peptide stimulation by 8 out of the 16 induced a significant quantity, of IFN-gamma mRNA transcript from CMV-seropositive HLA-A33 peripheral blood mononuclear cells. All the eight peptides; induced consistent T-cell reactivation. One specifically, the peptide pp65(91-100) (SVNVHNPTGR), proved to be more active. T cells in vitro sensitized for 2 or 3 weeks with pp65(91-100) were cytotoxic to both HLA-A33 peptide-loaded and CNIV-infected target cells.
   Conclusions. CMV pp65(91-100) is a new HLA-A33-restricted peptide that broadens the list of antigenic determinants that can be used for CMV adoptive immunotherapy. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.
C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
   Yonsei Univ, Coll Med, Dept Lab Med, Seoul 120749, South Korea.
   Charite Univ Med Berlin, Dept Med 3, Berlin, Germany.
RP Stroncek, D (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, 10 Ctr Dr,Bldg 10,Room 1C711, Bethesda, MD 20892 USA.
EM dstroncek@cc.nih.gov
NR 37
TC 10
Z9 11
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD MAR
PY 2006
VL 34
IS 3
BP 296
EP 307
DI 10.1016/j.exphem.2005.12.006
PG 12
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 033HS
UT WOS:000236838400006
PM 16543064
ER

PT J
AU Martel, GF
   Roth, SM
   Ivey, FM
   Lemmer, JT
   Tracy, BL
   Hurlbut, DE
   Metter, EJ
   Hurley, BF
   Rogers, MA
AF Martel, GF
   Roth, SM
   Ivey, FM
   Lemmer, JT
   Tracy, BL
   Hurlbut, DE
   Metter, EJ
   Hurley, BF
   Rogers, MA
TI Age and sex affect human muscle fibre adaptations to heavy-resistance
   strength training
SO EXPERIMENTAL PHYSIOLOGY
LA English
DT Article
ID FORCE PRODUCTION CHARACTERISTICS; FAT-FREE MASS; OLDER MEN;
   HIGH-INTENSITY; ELECTROMYOGRAPHIC ACTIVITY; CONTRACTILE FUNCTION; VASTUS
   LATERALIS; CROSS-SECTIONS; WOMEN; HYPERTROPHY
AB This study assessed age and sex effects on muscle fibre adaptations to heavy-resistance strength training (ST). Twenty-two young men and women (20-30 years old) and 18 older men and women (65-75 years old) completed 9 weeks of heavy-resistance knee extension exercises with the dominant leg 3 days week(-1); the non-dominant leg served as a within-subject, untrained control. Bilateral vastus lateralis muscle biopsies were obtained before and after ST for analysis of type I, IIa and IIx muscle fibre cross-sectional area (CSA) and fibre type distribution. One-repetition maximum (1-RM) strength was also assessed before and after ST. ST resulted in increased CSA of type I, IIa and IIx muscle fibres in the trained leg of young men, type I and IIa fibres in young women, type IIa fibres in older men, and type IIx fibres in older women (all P < 0.05). Analysis of fibre type distribution revealed a significant increase in the percentage of type I fibres (P < 0.05) along with a decrease in type IIx fibres (P=0.054) after ST only in young women. There were no significant changes in muscle fibre CSA or fibre type distribution in the untrained leg for any group. All groups displayed significant increases in 1-RM (27-39%; all P < 0.01). In summary, ST led to significant increases in 1-RM and type II fibre CSA in all groups; however, age and sex influence specific muscle fibre subtype responses to ST.
C1 Univ Maryland Eastern Shore, Dept Phys Therapy, Princess Anne, MD 21853 USA.
   Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA.
   Univ Maryland, Sch Med, Div Gerontol, Baltimore, MD 21201 USA.
   Baltimore VA GRECC, Baltimore, MD USA.
   Michigan State Univ, Dept Kinesiol, E Lansing, MI 48824 USA.
   Colorado State Univ, Dept Hlth & Exercise Sci, Ft Collins, CO 80523 USA.
   NIA, Clin Res Branch, Baltimore, MD 21224 USA.
RP Martel, GF (reprint author), Univ Maryland Eastern Shore, Dept Phys Therapy, Princess Anne, MD 21853 USA.
EM gfmartel@mail.umes.edu
OI Roth, Stephen/0000-0002-7841-3695
FU NIA NIH HHS [1-AG-4-2148]
NR 35
TC 57
Z9 60
U1 3
U2 9
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0958-0670
J9 EXP PHYSIOL
JI Exp. Physiol.
PD MAR 1
PY 2006
VL 91
IS 2
BP 457
EP 464
DI 10.1113/expphysiol.2005.032771
PG 8
WC Physiology
SC Physiology
GA 019MO
UT WOS:000235841000017
PM 16407471
ER

PT J
AU Clement, PMJ
   Johansson, HE
   Wolff, EC
   Park, MH
AF Clement, PMJ
   Johansson, HE
   Wolff, EC
   Park, MH
TI Differential expression of eIF5A-1 and eIF5A-2 in human cancer cells
SO FEBS JOURNAL
LA English
DT Article
DE alternative polyadenylation; eIF5A; hypusine; post-translational
   modification; translation
ID INITIATION-FACTOR 5A; YEAST SACCHAROMYCES-CEREVISIAE; HUMAN
   DEOXYHYPUSINE SYNTHASE; HYPUSINE-CONTAINING PROTEINS; MULTIPLE
   MESSENGER-RNAS; POSTTRANSLATIONAL SYNTHESIS; OVARIAN-CANCER;
   CHICK-EMBRYO; AMINO-ACID; RAT TESTIS
AB Eukaryotic translation initiation factor 5A (eIF5A) is the only cellular protein that contains the unusual amino acid hypusine [N-epsilon-(4-amino-2-hydroxybutyl)lysine]. Vertebrates carry two genes that encode two eIF5A isoforms, eIF5A-1 and eIF5A-2, which, in humans, are 84% identical. eIF5A-1 mRNA (1.3 kb) and protein (18 kDa) are constitutively expressed in human cells. In contrast, expression of eIF5A-2 mRNA (0.7-5.6 kb) and eIF5A-2 protein (20 kDa) varies widely. Whereas eIF5A-2 mRNA was demonstrable in most cells, eIF5A-2 protein was detectable only in the colorectal and ovarian cancer-derived cell lines SW-480 and UACC-1598, which showed high overexpression of eIF5A-2 mRNA. Multiple forms of eIF5A-2 mRNA (5.6, 3.8, 1.6 and 0.7 kb) were identified as the products of one gene with various lengths of 3'-UTR, resulting from the use of different polyadenylation (AAUAAA) signals. The eIF5A-1 and eIF5A-2 precursor proteins were modified comparably in UACC-1598 cells and both were similarly stable. When eIF5A-1 and eIF5A-2 coding sequences were expressed from mammalian vectors in 293T cells, eIF5A-2 precursor was synthesized at a level comparable to that of eIF5A-1 precursor, indicating that the elements causing inefficient translation of eIF5A-2 mRNA reside outside of the open reading frame. On sucrose gradient separation of cytoplasmic RNA, only a small portion of total eIF5A-2 mRNA was associated with the polysomal fraction, compared with a much larger portion of eIF5A-1 mRNA in the polysomes. These findings suggest that the failure to detect eIF5A-2 protein even in eIF5A-2 mRNA positive cells is, at least in part, due to inefficient translation.
C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
   Childrens Hosp Oakland, Res Inst, CHORI, Oakland, CA 94609 USA.
   Univ Uppsala, Dept Cell & Mol Biol, S-75105 Uppsala, Sweden.
RP Park, MH (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Rm 211,Bldg 30, Bethesda, MD 20892 USA.
EM mhpark@nih.gov
OI Johansson, Hans/0000-0001-9495-6107
FU Intramural NIH HHS [Z01 DE000608-14]
NR 50
TC 46
Z9 53
U1 0
U2 3
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1742-464X
J9 FEBS J
JI FEBS J.
PD MAR
PY 2006
VL 273
IS 6
BP 1102
EP 1114
DI 10.1111/j.1742-4658.2006.05135.x
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 019MM
UT WOS:000235840700002
PM 16519677
ER

PT J
AU Guo, TL
   Chi, RP
   Zhang, XL
   Musgrove, DL
   Weis, C
   Germolec, DR
   White, KL
AF Guo, TL
   Chi, RP
   Zhang, XL
   Musgrove, DL
   Weis, C
   Germolec, DR
   White, KL
TI Modulation of immune response following dietary genistein exposure in
   F-0 and F-1 generations of C57BL/6 mice: Evidence of thymic regulation
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE genistein; natural killer cell activity; anti-CD3 mediated proliferation
   and phenotypic markers
ID SPRAGUE-DAWLEY RATS; ESTROGEN-RECEPTOR-ALPHA; NATURAL-KILLER-CELLS;
   PHYTOESTROGEN GENISTEIN; PHYTO-ESTROGENS; BREAST-CANCER; MOUSE THYMUS;
   EXPRESSION; IMMUNOSUPPRESSION; 17-BETA-ESTRADIOL
AB To further determine whether genistein (GEN) modulation of the immune responses was related to its endocrine-disrupting properties and time of exposure, pregnant C57BL/6 mice were exposed to GEN at 0-1250 ppm in feed starting on day 14 of gestation. The C57BL/6 offspring were exposed to GEN in utero and lactationally, and through feed after weaning until postnatal day 42. In dams, exposure to GEN increased the terminal body weight (250 and 1250 ppm), the number of splenic T cells and NK cells (250 ppm), and the activity of NK cells (250 ppm). In F-1 males, GEN increased the terminal body and spleen weights (25 and 250 ppm), the number of CD4(+)CD8(+) and CD4(-)CD8(+) thymocytes (25 ppm), and the number of splenic T cell subsets and NK cells (25 and 250 ppm). Moreover, splenic NK cell activity and atiti-CD3-mediated splenocyte proliferation were increased in all treatment groups. In F-1 females, the percentages of CD4-CD8+ and CD4(-)CD8(-) thymocytes (25 and 250 ppm), and CD4(+)CD8(-) and CD4(+)CD8(+) splenocytes (25 and 250 ppm) were increased. In contrast, the percentage and number of CD4+CD8+ thymocytes were decreased (250 ppm). Exposure to GEN decreased the percentages of splenic NK cells in all treatment groups, and decreased the activity of splenic NK cells at the 25 ppm concentration. Additionally, evaluation of CD25(+) and CD44(+) expression by thymocytes indicated that the decrease in the percentage of CD44(+)CD25(+) thymocytes was at least partially responsible for the decrease in the percentage of CD4-CD8- thymocytes in F-1 male mice. Overall, the results demonstrate that GEN can modulate the immune system in both adult and developing C57BL/6 mice in a dose-specific manner. The gender-specific effects of GEN on the immune responses in F-1 mice suggest that GEN may modulate the immune system by functioning as either an estrogen agonist or antagonist. The differential effects of GEN on thymocytes in F-1 male and female mice indicate that GEN immunomodulation might be related to its effect on thymus. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA.
   US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
   NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA.
RP Guo, TL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980613, Richmond, VA 23298 USA.
EM tlguo@hsc.vcu.edu
FU NIEHS NIH HHS [R21ES 012286, N01-ES-05454, R21 ES012286-02, R21
   ES012286-01, R21 ES012286-03]
NR 45
TC 14
Z9 15
U1 1
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-6915
J9 FOOD CHEM TOXICOL
JI Food Chem. Toxicol.
PD MAR
PY 2006
VL 44
IS 3
BP 316
EP 325
DI 10.1016/j.fct.2005.08.001
PG 10
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA 026DU
UT WOS:000236317800002
PM 16162389
ER

PT J
AU Hickman-Miller, HD
   Yewdell, JW
AF Hickman-Miller, Heather D.
   Yewdell, Jonathan W.
TI Human heterosubtypic immunity to influenza A virus: evidence from case
   studies during the 1957 pandemic
SO FUTURE VIROLOGY
LA English
DT Article
DE cross protection; heterosubtypic immunity; influenza; vaccine; virus
ID INFECTION; PROTECTION; MICE
AB Heterosubtypic immunity (HSI) to influenza A virus (IAV) occurs when some degree of protection to infection is afforded by prior infection with a different subtype of IAV (i.e., a strain with serologically non-crossreactive surface glycoproteins). The existence of HSI, although well-documented in mice, is uncertain in humans. In order to examine HSI in humans, Epstein retrieved data from the Cleveland Family Study, a study of 60 families with school-aged children. Importantly, these families were monitored for illness during 1947-1957, the end of which coincided with the Asian IAV pandemic caused by the introduction of the H2N2 strain into human populations. Culture-positive IAV infection rates were compared between adults and children. Interestingly, many more children became infected during the 1957 pandemic than adults (55 vs 17%). While previous IAV exposure during the 1 0-year study period provided protection against adult IAV infection in 1957 (only 5.6% were infected), no difference was observed in children previously infected with other subtypes of AV (with 52% infected in 1957). Serum samples taken before the pandemic did not cletectably interact with H2N2 glycoproteins, suggesting that factors other than virus-neutralizing antibodies provided HSI to adults. This re-evaluation of archived data provides an important demonstration of the possibility of HSI in humans. Improved knowledge of human HSI could lead to vaccines capable of limiting morbidity and mortality from future pandemic strains introduced into humans from animal reservoirs.
C1 NIAID, NIH, Viral Dis Lab, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), NIAID, NIH, Viral Dis Lab, 4 Ctr Dr,Room 209, Bethesda, MD 20892 USA.
EM hhmiller@niaid.nih.gov; jyewdell@mail.nih.gov
RI yewdell, jyewdell@nih.gov/A-1702-2012
NR 14
TC 0
Z9 0
U1 0
U2 3
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
   1QB, ENGLAND
SN 1746-0794
J9 FUTURE VIROL
JI Future Virol.
PD MAR
PY 2006
VL 1
IS 2
BP 161
EP 164
DI 10.2217/17460794.1.2.161
PG 4
WC Virology
SC Virology
GA 209ZC
UT WOS:000249425500008
ER

PT J
AU Tanaka, Y
   Kurbanov, F
   Mano, S
   Orito, E
   Vargas, V
   Esteban, JI
   Yuen, MF
   Lai, CL
   Kramvis, A
   Kew, MC
   Smuts, HE
   Netesov, SV
   Alter, HJ
   Mizokami, M
AF Tanaka, Y
   Kurbanov, F
   Mano, S
   Orito, E
   Vargas, V
   Esteban, JI
   Yuen, MF
   Lai, CL
   Kramvis, A
   Kew, MC
   Smuts, HE
   Netesov, SV
   Alter, HJ
   Mizokami, M
TI Molecular tracing of the global hepatitis C virus epidemic predicts
   regional patterns of hepatocellular carcinoma mortality
SO GASTROENTEROLOGY
LA English
DT Article
ID UNITED-STATES; PHYLOGENETIC ANALYSIS; LIVER-CANCER; GENOTYPE 1B; RISK
   GROUPS; HONG-KONG; B VIRUS; INFECTION; PREVALENCE; JAPAN
AB Background & Aims: Molecular evolutionary analysis based on coalescent theory can provide important insights into epidemiologic processes worldwide. This approach was combined with analyses of the hepatitis C virus (HCV) epidemiologic-historical background and HCV-related hepatocellular carcinoma (HCC) in different countries. Methods: The HCV gene sequences of :13:1 genotype 1b (HCV-1b) strains from Japan, 38 HCV-1a strains from the United States, 33 HCV-1b strains from Spain, 27 HCV-3a strains from the former Soviet Union (FSU), 47 HCV-4a strains from Egypt, 25 HCV-5a strains from South Africa, and 24 HCV-6a strains from Hong Kong isolated in this study and previous studies were analyzed. Results: The coalescent analysis indicated that a transition from constant size to rapid exponential growth (spread time) occurred in Japan in the 1920s (HCV-1b), but not until the 1940s for the same genotype in Spain and other European countries. The spread time of HCV-1a in the United States was estimated to be in the 1960s; HCV-3a in the FSU, HCV-5a in South Africa, and HCV-6a in Hong Kong in the 1960s, mid-1950s, and late 1970s, respectively. Three different linear progression curves were determined by analysis of the relationship between HCV seroprevalence and HCC mortality in different geographic regions; a steep ascent indicated the greatest progression to HCC in Japan, a near horizontal line indicated the least progression in the United States and the FSU, and an intermediate slope was observed in Europe. Conclusions: These findings strongly suggest that the initial spread time of HCV is associated with the progression dynamics of HCC in each area, irrespective of genotype.
C1 Nagoya City Univ, Grad Sch Med Sci, Dept Clin Mol Informat Med, Mizuho Ku, Nagoya, Aichi 4678601, Japan.
   Nagoya City Univ, Grad Sch Nat Sci, Nagoya, Aichi, Japan.
   Nagoya City Univ, Grad Sch Med Sci, Dept Internal Med & Mol Sci, Nagoya, Aichi 4678601, Japan.
   Hosp Gen Univ Vall Hebron, Dept Internal Med, Barcelona, Spain.
   Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China.
   Univ Witwatersrand, Dept Med, Univ Mol Hepatol Res Unit, MRC CANSA, ZA-2001 Johannesburg, South Africa.
   Univ Cape Town, Natl Hlth Lab Serv, Div Med Virol, ZA-7925 Cape Town, South Africa.
   VECTOR Koltsovo, State Res Ctr Virol & Biotechnol, Novosibirsk, Russia.
   NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Mizokami, M (reprint author), Nagoya City Univ, Grad Sch Med Sci, Dept Clin Mol Informat Med, Mizuho Ku, Nagoya, Aichi 4678601, Japan.
EM mizokami@med.nagoya-cu.ac.jp
RI Lai, Ching Lung/C-4298-2009; Netesov, Sergey/A-3751-2013; 
OI Netesov, Sergey/0000-0002-7786-2464; Kurbanov, Fuat/0000-0003-0536-3276;
   Vargas Blasco, Victor Manuel/0000-0002-7190-6948
NR 54
TC 71
Z9 74
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2006
VL 130
IS 3
BP 703
EP 714
DI 10.1053/j.gastro.2006.01.032
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 024QC
UT WOS:000236210100014
PM 16530512
ER

PT J
AU Nanda, SK
   Herion, D
   Liang, TJ
AF Nanda, SK
   Herion, D
   Liang, TJ
TI Src homology 3 domain of hepatitis C virus NS5A protein interacts with
   Bin1 and is important for apoptosis and infectivity
SO GASTROENTEROLOGY
LA English
DT Article
ID NONSTRUCTURAL 5A PROTEIN; PROGRAMMED CELL-DEATH; TUMOR-SUPPRESSOR BIN1;
   RNA REPLICATION; AMPHIPHYSIN II; ADAPTER PROTEIN; TRANSGENIC MICE; SH3
   DOMAINS; MYC; CULTURE
AB Background & Aims: HCV nonstructural protein 5A (NS5A) has been implicated in regulating cell growth and interferon response. The NS5A protein contains proline-rich regions that are highly conserved among HCV genotypes and match Src homology 3 (SH3)-binding motifs (PxxP) found in various cellular signaling molecules. Methods: We screened for HCV NS5A interacting proteins by using the yeast 2-hybrid system and studied the functional consequence of this interaction. Results: Several independent clones containing SH3 domains were isolated along with Bin1, a tumor suppressor with pro-apoptotic properties, being the most frequently identified clone. The protein-protein interaction between NS5A and Bin:1 was confirmed by in vitro binding, in vivo co-immunoprecipitation, and confocal microscopy. Deletion and mutation analyses indicated that the SH3 binding motif of HCV NS5A and SH3 domain of Bin1 are essential for interaction. Human hepatoma (HepG2) cells lacking expression of Bin1 undergo apoptosis upon infection with adeno-Bin1. Bin1-induced apoptosis was inhibited in HepG2 cells expressing wild-type NS5A but not NS5A mutant with mutations in the SH3 binding motif. Infectious HCV genome containing mutations in the SH3 binding motif was not infectious in chimpanzees. Conclusions: Our results indicate that this interaction is implicated in productive HCV infection and may contribute to the pathogenesis of hepatocellular carcinoma. In addition, the NS5A PxxP motif may represent a novel target for antiviral development.
C1 NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Liang, TJ (reprint author), Bldg 10-9B16,10 Ctr Dr, Bethesda, MD 20892 USA.
EM Jakel@intra.niddk.nih.gov
FU Intramural NIH HHS
NR 45
TC 45
Z9 48
U1 0
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2006
VL 130
IS 3
BP 794
EP 809
DI 10.1053/j.gastro.2005.12.030
PG 16
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 024QC
UT WOS:000236210100023
PM 16530520
ER

PT J
AU Yim, JJ
   Lee, HW
   Lee, HS
   Kim, YW
   Han, SK
   Shim, YS
   Holland, SM
AF Yim, JJ
   Lee, HW
   Lee, HS
   Kim, YW
   Han, SK
   Shim, YS
   Holland, SM
TI The association between microsatellite polymorphisms in intron II of the
   human Toll-like receptor 2 gene and tuberculosis among Koreans
SO GENES AND IMMUNITY
LA English
DT Article
DE Toll-like receptor 2; tuberculosis; microsatellite polymorphism
ID CELL WALL COMPONENTS; LEFT-HANDED DNA; INNATE IMMUNITY;
   MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; NRAMP1 GENE; CUTTING
   EDGE; SUSCEPTIBILITY; RECOGNITION; ACTIVATION
AB The observation that Toll-like receptor (TLR)2-deficient mice are highly susceptible to mycobacteria suggests that mutations altering TLR2 expression may impair host response to Mycobacterium tuberculosis. We evaluated the association between guanine-thymine (GT) repeat polymorphism in intron II of the TLR2 gene and the presence of tuberculosis (TB) in Koreans. The numbers of GT repeats were determined by PCR and gene scans for 176 TB patients and 196 controls. The recombinant TLR2 promoter/exonI/exonII/intronII/luciferase constructs including three representative repeats: (GT) 13, (GT) 20, and (GT) 24 were transfected into K562 cells, and luciferase activities were estimated and compared. The expression of TLR2 on CD14+ peripheral blood mononuclear cells (PBMC) from healthy volunteers were measured with flow cytometry. Genotypes with shorter GT repeats were more common among TB patients (49.4 vs 37.7%, P = 0.02). This observation was confirmed among 82 other TB patients as a validation cohort. Shorter GT repeats were associated with weaker promoter activities and lower TLR2 expression on CD14+ PBMCs. In conclusion, the development of TB disease in Koreans was associated with shorter GT repeats in intron II of the TLR2 gene. This association is correlated with lower expression of TLR2 through weaker promoter activity for genes with shorter GT repeats.
C1 NIAID, NIH, Lab Clin Infect Dis, Immunopathogenesis Sect, Bethesda, MD 20892 USA.
   Seoul Natl Univ, Coll Med, Div Pulm & Crit Care Med, Dept Internal Med, Seoul, South Korea.
   Seoul Natl Univ, Coll Med, Lung Inst, Seoul, South Korea.
RP Holland, SM (reprint author), NIAID, NIH, Lab Clin Infect Dis, Immunopathogenesis Sect, Bldg 10,CRC B3-4141,10 Ctr Dr,MSC 1684, Bethesda, MD 20892 USA.
EM smh@nih.gov
RI Yim, Jae Joon/J-2783-2012
FU Intramural NIH HHS
NR 49
TC 88
Z9 98
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1466-4879
J9 GENES IMMUN
JI Genes Immun.
PD MAR
PY 2006
VL 7
IS 2
BP 150
EP 155
DI 10.1038/sj.gene.6364274
PG 6
WC Genetics & Heredity; Immunology
SC Genetics & Heredity; Immunology
GA 017BD
UT WOS:000235668200008
PM 16437124
ER

PT J
AU Gould, TD
   Gottesman, II
AF Gould, TD
   Gottesman, II
TI Psychiatric endophenotypes and the development of valid animal models
SO GENES BRAIN AND BEHAVIOR
LA English
DT Article
DE anxiety; biological markers; bipolar disorder; construct validity;
   depression; endophenotypic; endophenotyping; genotype; intermediate
   phenotype; mania; mice; mouse; phenotype; rat; schizophrenia
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER;
   BIPOLAR DISORDER; NEUROPSYCHOLOGICAL ENDOPHENOTYPES; VAL66MET
   POLYMORPHISM; SCHIZOPHRENIA GENES; PREPULSE INHIBITION; BIOLOGICAL
   MARKERS; HUMAN-MEMORY; GENETICS
AB Endophenotypes are quantifiable components in the genes-to-behaviors pathways, distinct from psychiatric symptoms, which make genetic and biological studies of etiologies for disease categories more manageable. The endophenotype concept has emerged as a strategic tool in neuropsychiatric research. This emergence is due to many factors, including the modest reproducibility of results from studies directed toward etiologies and appreciation for the complex relationships between genes and behavior. Disease heterogeneity is often guaranteed, rather than simplified, through the current diagnostic system; inherent benefits of endophenotypes include more specific disease concepts and process definitions. Endophenotypes can be neurophysiological, biochemical, endocrine, neuroanatomical, cognitive or neuropsychological. Heritability and stability (state independence) represent key components of any useful endophenotype. Importantly, they characterize an approach that reduces the complexity of symptoms and multifaceted behaviors, resulting in units of analysis that are more amenable to being modeled in animals. We discuss the benefits of more direct interpretation of clinical endophenotypes by basic behavioral scientists. With the advent of important findings regarding the genes that predispose to psychiatric illness, we are at an important crossroads where, without anthropomorphizing, animal models may provide homologous components of psychiatric illness, rather than simply equating to similar (loosely analogized) behaviors, validators of the efficacy of current medications or models of symptoms. We conclude that there exists a need for increased collaboration between clinicians and basic scientists, the result of which should be to improve diagnosis, classification and treatment on one end and to increase the construct relevance of model organisms on the other.
C1 NIMH, Mol Pathophysiol Lab, Mood Anxiety Disorders Program, NIH,HHS, Bethesda, MD 20892 USA.
   Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA.
   Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA.
RP Gould, TD (reprint author), NIMH, Mol Pathophysiol Lab, Mood Anxiety Disorders Program, NIH,HHS, Bldg 35,Room 1C-912, Bethesda, MD 20892 USA.
EM gouldt@mail.nih.gov
RI G, I/D-8042-2011; Gottesman, Irving/B-9303-2011
FU Intramural NIH HHS
NR 80
TC 264
Z9 270
U1 4
U2 18
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1601-1848
J9 GENES BRAIN BEHAV
JI Genes Brain Behav.
PD MAR
PY 2006
VL 5
IS 2
BP 113
EP 119
DI 10.1111/j.1601-183X.2005.00186
PG 7
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 016YT
UT WOS:000235661500001
PM 16507002
ER

PT J
AU Hanaoka, R
   Katayama, S
   Dawid, IB
   Kawahara, A
AF Hanaoka, R
   Katayama, S
   Dawid, IB
   Kawahara, A
TI Characterization of the heme synthesis enzyme coproporphyrinogen oxidase
   (CPO) in zebrafish erythrogenesis
SO GENES TO CELLS
LA English
DT Article
ID ERYTHROID CELL-DIFFERENTIATION; HEREDITARY COPROPORPHYRIA;
   MOLECULAR-CLONING; ORYZIAS-LATIPES; GENE; EXPRESSION; MUTATION; MODEL;
   CDNA; HEMATOPOIESIS
AB Hemoglobin consists of heme and globin proteins and is essential for oxygen transport in all vertebrates. Although biochemical features of heme synthesis enzymes have been well characterized, the function of these enzymes in early embryogenesis is not fully understood. We found that the sixth heme synthesis enzyme, coproporphyrinogen oxidase (CPO), is predominantly expressed in the intermediate cell mass (ICM) that is a major site of zebrafish primitive hematopoiesis. Knockdown of zebrafish CPO using anti-sense morpholinos (CPO-MO) leads to a significant suppression of hemoglobin production without apparent reduction of blood cells. Injection of human CPO RNA, but not a mutant CPO RNA that is similar to a mutant responsible for a hereditary coproporphyria (HCP), restores hemoglobin production in the CPO-MO-injected embryos. Furthermore, expression of CPO in the ICM is severely suppressed in both vlad tepes/gata1 mutants and in biklf-MO-injected embryos. In contrast, over-expression of biklf and gata1 significantly induces ectopic CPO expression. The function of CPO in heme biosynthesis is apparently conserved between zebrafish and human, suggesting that CPO-MO-injected zebrafish embryos might be a useful in vivo assay system to measure the biological activity of human CPO mutations.
C1 Kyoto Univ, Lab Dev Mol Genet, Horizontal Med Res Org, Grad Sch Med,Sakyo Ku, Kyoto 6068501, Japan.
   NICHHD, Lab Mol Genet, NIH, Bethesda, MD 20892 USA.
RP Kawahara, A (reprint author), Kyoto Univ, Lab Dev Mol Genet, Horizontal Med Res Org, Grad Sch Med,Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan.
EM atsuo@hmro.med.kyoto-u.ac.jp
FU Intramural NIH HHS
NR 34
TC 12
Z9 12
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1356-9597
J9 GENES CELLS
JI Genes Cells
PD MAR
PY 2006
VL 11
IS 3
BP 293
EP 303
DI 10.1111/j.1365-2443.2006.00939.x
PG 11
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 012QZ
UT WOS:000235355500009
PM 16483317
ER

PT J
AU Tucker, DC
   Acton, RT
   Press, N
   Ruggiero, A
   Reiss, JA
   Walker, AP
   Wenzel, L
   Harrison, B
   Fadojutimi-Akinsiku, M
   Harrison, H
   Adams, P
   Crabb, JA
   Anderson, R
   Thomson, E
AF Tucker, DC
   Acton, RT
   Press, N
   Ruggiero, A
   Reiss, JA
   Walker, AP
   Wenzel, L
   Harrison, B
   Fadojutimi-Akinsiku, M
   Harrison, H
   Adams, P
   Crabb, JA
   Anderson, R
   Thomson, E
TI Predictors of belief that genetic test information about hemochromatosis
   should be shared with family members
SO GENETIC TESTING
LA English
DT Article
ID ATTITUDES; CANCER; BREAST
AB We queried 101,951 white, Hispanic, black, Asian, American Indian (i.e., American Indian or Alaska Native in the United States and North American Indian, Metis, or Inuit in Canada) and Pacific Islander ( including Native Hawaiian) adults who agreed to be genotypically and phenotypically screened for hemochromatosis as part of the Hemochromatosis and Iron Overload Screening ( HEIRS) study about their views on sharing genetic test information with family members. Multiple logistic regression ( adjusting for study site, age group, race/ethnicity, preferred language, gender, education group, income group, SF-36 General Health and Mental Health subscales, perceived benefits and limitations of genetic testing, and belief that genetic testing is a good idea) evaluated independent predictors of responding "Strongly Agree" or "Agree" versus "Disagree" or "Strongly Disagree" to the statement "Information about a person's genetic risk should be shared with family members". Agreement that genetic risk information should be shared with family members was high (93% in the overall sample of 78,952 who answered this question), but differed among racial/ethnic groups. Hispanics were significantly less likely to agree that genetic test information should be shared with family members (i.e., 88% versus 92% or more among all other ethnicities). The relationship of perceived limitations and benefits of testing, gender, and age group to the belief that information should be shared differed among racial/ethnic groups, with Spanish-preferring Hispanics being the most different from other subgroups.
C1 Univ Alabama, Birmingham, AL 35294 USA.
   Oregon Hlth Sci Univ, Kaiser Permanente Ctr Hlth Res, Portland, OR 97201 USA.
   Wake Forest Univ, Winston Salem, NC 27109 USA.
   Univ Calif Irvine, Irvine, CA USA.
   London Ontario Hlth Sci Ctr, London, ON, Canada.
   Howard Univ, Washington, DC USA.
   NHGRI, NIH, Bethesda, MD 20892 USA.
RP Tucker, DC (reprint author), Univ Alabama, 112 OB9A, Birmingham, AL 35294 USA.
EM dtucker@uab.edu
FU NCI NIH HHS [N01-CM-07003-74]; NCRR NIH HHS [M01-RR10284, M01-RR00827,
   M01-RR00032]; NHLBI NIH HHS [N01-HC05186, N01-HC05191, N01-HC05189,
   N01-HC05192, N01-HC05185, HL03679-05, N01-HC05188, N01-HC05190]
NR 15
TC 6
Z9 6
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1090-6576
J9 GENET TEST
JI Genet. Test.
PD MAR
PY 2006
VL 10
IS 1
BP 50
EP 59
DI 10.1089/gte.2006.10.50
PG 10
WC Genetics & Heredity; Medicine, Research & Experimental
SC Genetics & Heredity; Research & Experimental Medicine
GA 026OA
UT WOS:000236347300009
PM 16545004
ER

PT J
AU Cook, DN
   Whitehead, GS
   Burch, LH
   Berman, KG
   Kapadia, Z
   Wohlford-Lenane, C
   Schwartz, DA
AF Cook, DN
   Whitehead, GS
   Burch, LH
   Berman, KG
   Kapadia, Z
   Wohlford-Lenane, C
   Schwartz, DA
TI Spontaneous mutations in recombinant inbred mice: Mutant toll-like
   receptor 4 (Tlr4) in BXD29 mice
SO GENETICS
LA English
DT Article
AB Recombinant inbred (RI) mice are frequently used to identify QTL that underlie differences in measurable phenotypes between two inbred strains of mice. Here we show that one RI strain, C57BL/6J X DBA/2J (BXD29), does not develop an inflammatory response following inhalation of LPS. Approximately 25% of F-2 mice [F-1 (BXD29 X DBA/2J) X F-1] are also unresponsive to inhaled LPS, suggesting the presence Of a recessive mutation in the BXD29 strain. A genomic scan of these F-2 mice revealed that unresponsive animals, but not responsive animals, are homozygous for C57BL/6J DNA at a single locus oil chromosome 4 close to the genomic location of Tlr4. All progeny between BXD29 and gene-targeted Tlr4-deficient. mice are unresponsive to inhaled LPS, suggesting that the mutation in the BXD29 strain is allelic with Tlr4. Moreover, the intact Tlr4 receptor is not displayed on the cell surface of BXD29 macrophages. Finally, a molecular analysis of the tlr4 gene in BXD29 mice revealed that it is interrupted by a large insertion of repetitive DNA. These findings explain the unresponsiveness of BXD29 mice to LPS and suggest that data from BXD29 mice should not. be included when using BXD mice to study phenotypes affected by Tlr4 function. Our results also suggest that the frequency of such unidentified, spontaneously occurring mutations is an issue that should be considered when RI strains are Used to identify QTL.
C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
   Durham VAMC, Durham, NC 27710 USA.
RP Cook, DN (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr,Bldg 101,E244, Res Triangle Pk, NC 27709 USA.
EM cookd@niehs.nih.gov
FU NHLBI NIH HHS [HL66580, HL66611, HL66604, U01 HL066611, U01 HL066580];
   NIEHS NIH HHS [ES09607, U19 ES011375, ES11375, R01 ES007498, ES07498]
NR 8
TC 7
Z9 7
U1 0
U2 2
PU GENETICS
PI BALTIMORE
PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD MAR
PY 2006
VL 172
IS 3
BP 1751
EP 1755
DI 10.1534/genetics.105.042820
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 030XG
UT WOS:000236668100032
PM 16322526
ER

PT J
AU Kastenmayer, JP
   Ni, L
   Chu, A
   Kitchen, LE
   Au, WC
   Yang, H
   Carter, CD
   Wheeler, D
   Davis, RW
   Boeke, JD
   Snyder, MA
   Basrai, MA
AF Kastenmayer, JP
   Ni, L
   Chu, A
   Kitchen, LE
   Au, WC
   Yang, H
   Carter, CD
   Wheeler, D
   Davis, RW
   Boeke, JD
   Snyder, MA
   Basrai, MA
TI Functional genomics of genes with small open reading frames (sORFs) in
   S-cerevisiae
SO GENOME RESEARCH
LA English
DT Article
ID INTACT YEAST-CELLS; DNA-DAMAGE; CHECKPOINT GENES; ENDOPLASMIC-RETICULUM;
   SERIAL ANALYSIS; GLOBAL ANALYSIS; BUDDING YEAST; PROTEIN;
   IDENTIFICATION; COMPONENT
AB Genes with small open reading frames (sORFs; < 100 amino acids) represent an untapped Source of important biology. sORFs largely escaped analysis because they were difficult to predict computationally and less likely to be targeted by genetic screens. Thus, the Substantial number of sORFs and their potential importance have only recently become clear. To investigate sORF function, we undertook the first functional Studies of sORFs in any system, using the model eukaryote Saccharomyces cerevisiae. Based on independent experimental approaches and computational analyses, evidence exists for 299 sORFs in the S. cerevisiae genome, representing -5% of the annotated ORFs. We determined that a similar percentage of sORFs are annotated in other eukaryotes, including humans, and 184 of the S. cerevisiae sORFs exhibit similarity with ORFs in other organisms. To investigate sORF function, we constructed a collection of gene-deletion Mutants of 140 newly identified sORFs, each of which contains a strain-specific "molecular barcode," bringing the total number of sORF deletion strains to 247. Phenotypic analyses of the new gene-deletion strains identified 22 sORFs required for haploid growth, growth at high temperature, growth in the presence of a nonfermentable carbon Source, or growth in the presence of DNA damage and replication-arrest agents. We provide a collection of sORF deletion strains that can be integrated into the existing deletion collection as a resource for the yeast community for elucidating gene function. Moreover, our analyses of the S. cerevisiae sORFs establish that sORFs are conserved across eukaryotes and have important biological functions.
C1 NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20889 USA.
   Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA.
   Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA.
   Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
   Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
RP Basrai, MA (reprint author), NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20889 USA.
EM basraim@nih.gov
OI Boeke, Jef/0000-0001-5322-4946
FU Intramural NIH HHS; NHGRI NIH HHS [R01 HG002432, R01-HG02432]
NR 60
TC 96
Z9 103
U1 2
U2 13
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD MAR
PY 2006
VL 16
IS 3
BP 365
EP 373
DI 10.1101/gr.4355406
PG 9
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
GA 018CZ
UT WOS:000235742700010
PM 16510898
ER

PT J
AU Huang, R
   Wallqvist, A
   Covell, DG
AF Huang, R
   Wallqvist, A
   Covell, DG
TI Comprehensive analysis of pathway or functionally related gene
   expression in the National Cancer Institute's anticancer screen
SO GENOMICS
LA English
DT Article
DE pathway; gene expression; coregulation; cancer
ID SACCHAROMYCES-CEREVISIAE; PROTEIN INTERACTIONS; NEIGHBORING GENES;
   GENOME; COEXPRESSION; PROFILES; SCALE
AB We have analyzed the level of gene coregulation, using gene expression patterns measured across the National Cancer Institute's 60 tumor cell panels (NCI60), in the context of predefined pathways or functional categories annotated by KEGG (Kyoto Encyclopedia of Genes and Genomes), BioCarta, and GO (Gene Ontology). Statistical methods were used to evaluate the level of gene expression coherence (coordinated expression) by comparing intra- and interpathway gene-gene correlations. Our results show that gene expression in pathways, or groups of functionally related genes, has a significantly higher level of coherence than that of a randomly selected set of genes. Transcriptional-level gene regulation appears to be on a "need to be" basis, such that pathways comprising genes encoding closely interacting proteins and pathways responsible for vital cellular processes or processes that are related to growth or proliferation, specifically in cancer cells, such as those engaged in genetic information processing, cell cycle, energy metabolism, and nucleotide metabolism, tend to be more modular (lower degree of gene sharing) and to have genes significantly more coherently expressed than most signaling and regular metabolic pathways. Hierarchical clustering of pathways based on their differential gene expression in the NCI60 further revealed interesting interpathway communications or interactions indicative of a higher level of pathway regulation. The knowledge of the nature of gene expression regulation and biological pathways can be applied to understanding the mechanism by which small drug molecules interfere with biological systems. (c) 2005 Elsevier Inc. All rights reserved.
C1 NCI, Lab Computat Technol, Dev Therapeut Program, Screening Technol Branch,NIH, Frederick, MD 21702 USA.
   NCI, Sci Applicat Int Corp, NIH, Frederick, MD 21702 USA.
RP Covell, DG (reprint author), NCI, Lab Computat Technol, Dev Therapeut Program, Screening Technol Branch,NIH, Frederick, MD 21702 USA.
EM covell@ncifcrf.gov
OI wallqvist, anders/0000-0002-9775-7469
FU NCI NIH HHS [N01-CO-12400]
NR 27
TC 24
Z9 25
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 0888-7543
J9 GENOMICS
JI Genomics
PD MAR
PY 2006
VL 87
IS 3
BP 315
EP 328
DI 10.1016/j.ygeno.2005.11.011
PG 14
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 017VD
UT WOS:000235720500001
PM 16386875
ER

PT J
AU Roffman, JL
   Weiss, AP
   Goff, DC
   Rauch, SL
   Weinberger, DR
AF Roffman, JL
   Weiss, AP
   Goff, DC
   Rauch, SL
   Weinberger, DR
TI Neuroimaging-genetic paradigms: A new approach to investigate the
   pathophysiology and treatment of cognitive deficits in schizophrenia
SO HARVARD REVIEW OF PSYCHIATRY
LA English
DT Review
DE cognitive impairment; genetics; neuroimaging; schizophrenia
ID CATECHOL-O-METHYLTRANSFERASE; DORSOLATERAL PREFRONTAL CORTEX;
   CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; FACTOR VAL66MET
   POLYMORPHISM; BIPOLAR AFFECTIVE-DISORDER; VAL(108/158) MET GENOTYPE;
   NEUROTROPHIC FACTOR; WORKING-MEMORY; ALZHEIMERS-DISEASE
AB Cognitive impairment is a prominent and debilitating feature of schizophrenia. Genetic predisposition likely accounts for a large proportion of these cognitive deficits. Direct associations between candidate genes and cognitive dysfunction have been difficult to establish, however, largely due to the subtle effects of these genes on observable behavior. Neuroimaging techniques can provide a sensitive means to bridge the neurobiology of genes and behavior. Here we illustrate the use of neuroimaging-genetics paradigms to elaborate the relationship between genes and cognitive dysfunction in schizophrenia. After reviewing principles important for the selection of genes, neuroimaging techniques, and subjects, we describe how imaging-genetics investigations have helped clarify the contribution of five candidate genes (COMT, GRM3, G72, DISC1, and BDNF) to cognitive deficits in schizophrenia. The potential of this approach for improving patient care will depend on its ability to predict outcomes with greater accuracy and sensitivity than current clinical measures.
C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA.
   Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
   NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
RP Roffman, JL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,CNY 2625,Hosp E, Charlestown, MA 02129 USA.
EM jroffman@partners.org
NR 126
TC 35
Z9 35
U1 5
U2 7
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1067-3229
J9 HARVARD REV PSYCHIAT
JI Harv. Rev. Psychiatr.
PD MAR-APR
PY 2006
VL 14
IS 2
BP 78
EP 91
DI 10.1080/10673220600642945
PG 14
WC Psychiatry
SC Psychiatry
GA 039WA
UT WOS:000237337200004
PM 16603474
ER

PT J
AU Laxminarayan, R
   Over, M
   Smith, DL
AF Laxminarayan, R
   Over, M
   Smith, DL
TI Will a global subsidy of new antimalarials delay the emergence of
   resistance and save lives?
SO HEALTH AFFAIRS
LA English
DT Article
ID PLASMODIUM-FALCIPARUM MALARIA; ANTIBIOTIC-RESISTANCE; SPREAD; MODELS;
   DRUGS
AB Artemisinin-based combination treatments (ACTs) are seen as an important tool in the global effort to roll back malaria. With parasite resistance to chloroquine increasing rapidly in many parts of the world, there is greater recognition of the need for a globally coordinated strategy to ensure that artemisinins are not used as monotherapy, which has the potential to cut short their useful therapeutic life. We find that even a partial subsidy could delay the emergence of resistance and that a delay in implementing a subsidy for ACTs could facilitate the emergence of resistance and lower the economic value of ACTs.
C1 World Bank, Washington, DC 20433 USA.
   NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
EM Ramanan@rff.org
RI Smith, David/L-8850-2013
OI Smith, David/0000-0003-4367-3849
NR 16
TC 26
Z9 27
U1 0
U2 4
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD MAR-APR
PY 2006
VL 25
IS 2
BP 325
EP 336
DI 10.1377/hlthaff.25.2.325
PG 12
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 022ZK
UT WOS:000236094500004
PM 16522574
ER

PT J
AU Fuchs, VR
   Emanuel, EJ
AF Fuchs, VR
   Emanuel, EJ
TI Reform: The authors respond
SO HEALTH AFFAIRS
LA English
DT Letter
C1 Stanford Univ, Stanford, CA 94305 USA.
   NIH, Bethesda, MD 20892 USA.
RP Fuchs, VR (reprint author), Stanford Univ, Stanford, CA 94305 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD MAR-APR
PY 2006
VL 25
IS 2
BP 566
EP 566
DI 10.1377/hlthaff.25.2.566-a
PG 1
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 022ZK
UT WOS:000236094500046
ER

PT J
AU Schenck, AR
   Peacock, S
   Pignone, M
   Jackson, E
   Gunter, N
   Klabunde, CN
AF Schenck, AR
   Peacock, S
   Pignone, M
   Jackson, E
   Gunter, N
   Klabunde, CN
TI Increasing colorectal cancer testing: Translating physician
   interventions into population-based practice
SO HEALTH CARE FINANCING REVIEW
LA English
DT Article
ID PRIMARY-CARE PHYSICIANS; OCCULT BLOOD-TEST; PREVENTIVE SERVICES;
   PARTICIPATION; METAANALYSIS; DELIVERY; ADULTS; DONT
AB Colorectal cancer (CRC) screening in the Medicare population remains low despite Medicare coverage. We describe a population-based effort to increase CRC testing of Medicare enrollees in two States through promotion and distribution of office-based tools to primary care physicians and gastroenterologists. Small increases in colonoscopy test use by primary care physicians were observed, but the differences were not statistically significant. Results in one State were stronger than the other, and two components of the intervention appeared more promising than others. Use of CRC tests can be increased, but additional approaches are needed.
C1 Carolinas Ctr Med Excellence, Cary, NC 27511 USA.
   Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA.
   NCI, Bethesda, MD 20892 USA.
RP Schenck, AR (reprint author), Carolinas Ctr Med Excellence, 100 Regency Forest Dr,Suite 100, Cary, NC 27511 USA.
EM aschenck@ncqio.sdps.org
FU PHS HHS [500-02-NC03]
NR 24
TC 3
Z9 3
U1 0
U2 1
PU CENTERS FOR MEDICARE & MEDICAID SERVICES
PI BALTIMORE
PA 7500 SECURITY BOULEVARD, BALTIMORE, MD 21244-1850 USA
SN 0195-8631
J9 HEALTH CARE FINANC R
JI Health Care Finan. Rev.
PD SPR
PY 2006
VL 27
IS 3
BP 25
EP 35
PG 11
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 044XZ
UT WOS:000237708300003
PM 17290646
ER

PT J
AU Ershow, AG
   Costello, RB
AF Ershow, AG
   Costello, RB
TI Dietary guidance in heart failure: a perspective on needs for prevention
   and management
SO HEART FAILURE REVIEWS
LA English
DT Article
DE heart failure; dietary guidance; nutrition
ID SUPPLEMENTATION; INTERVENTION; HYPERTENSION; ASSOCIATION; STATEMENT;
   SODIUM; HEALTH; LIFE; CARE
AB The role that dietary factors play in preventing heart failure (HF) and in improving prognosis is increasingly recognized, indicating a need for well-grounded guidelines that can provide recommendations for daily nutrient intakes. At present, however, the state of dietary guidance is more satisfactory for persons at risk of HF (Stages A and B) than for those with a diagnosis of HF (Stages C and D). For individuals at risk of HF, a good starting point is provided by governmental and professional society guidance directed at dietary management of cardiovascular risk factors such as hypertension, hyperlipidemia, and obesity. These dietary recommendations are consonant with epidemiologic research suggesting that improving risk factor profiles likely will lower the risk of developing HF. For patients with diagnosed HF, however, little information is available to define optimal nutrient intakes and optimal food patterns. Dietary services have been shown useful in improving clinical outcomes, but nutritional management must be individualized to the patient's needs and must accommodate pharmacologic therapy, multiple co-morbidities, the possible need for nutritional supplements, repeated hospitalizations, salt and fluid retention, voluntary vs. involuntary weight loss, and other nutritional issues relevant to the aged population who comprise the majority of HF patients. Progress in the field will require well-designed clinical investigations addressing nutrient intake, nutrient metabolism, and nutritional status while mindful of the complex pathophysiology of HF.
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
   NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Ershow, AG (reprint author), NHLBI, NIH, 6701 Rockledge Dr,Room 10-194,MSC 7956, Bethesda, MD 20892 USA.
EM ErshowA@nhlbi.nih.gov; CostellB@od.nih.gov
NR 33
TC 18
Z9 20
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1382-4147
J9 HEART FAIL REV
JI Heart Fail. Rev.
PD MAR
PY 2006
VL 11
IS 1
BP 7
EP 12
DI 10.1007/s10741-006-9187-3
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 060BS
UT WOS:000238776900002
PM 16819572
ER

PT J
AU Hopenfeld, B
AF Hopenfeld, B
TI Mechanism for action potential alternans: The interplay between L-type
   calcium current and transient outward current
SO HEART RHYTHM
LA English
DT Article
DE ischemia; myocyte; electrical alternans
ID ELECTRICAL ALTERNANS; VENTRICULAR-FIBRILLATION; RESTITUTION; MYOCYTES;
   ISCHEMIA; CONTRIBUTES; DURATION; CELLS; HEART
AB BACKGROUND The ionic mechanisms underlying action potential duration alternans are not established.
   OBJECTIVES The purpose of this study was to explore the mechanisms underlying action potential alternans.
   METHODS Computer simulations were performed using a model of a single ischemic myocyte. To emulate ischemia, extracellular potassium was raised to 10 mM, L-type calcium channel conductance was decreased, and the conductivity of the transient outward current I-to was varied.
   RESULTS Alternans occurred at basic cycle lengths between 350 and 1,800 ms. The alternans resulted from the interplay of the recovery kinetics of the calcium and transient outward current inactivation gates. Depending on the diastolic interval, the transient outward current was sufficiently strong and calcium current sufficiently weak to result in the abolition of the action potential plateau and thus in an abbreviated action potential. The inactivation and recovery kinetics of the inactivation gates were such that calcium current was relatively stronger than transient outward current after an abbreviated action potential. The subsequent action potential was long because calcium current was sufficiently large to restore the action potential plateau dome after the partial repolarization caused by the transient outward current. The long-short pattern repeated indefinitely. This alternans mechanism explains how 2:1 patterns can evolve into 3:1 patterns, as observed in at least one experiment, as ischemia progresses and calcium current diminishes.
   CONCLUSION Computer simulations and basic theory suggest that the interplay between L-type calcium and transient outward currents causes at least one type of alternans.
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
RP Hopenfeld, B (reprint author), NHLBI, NIH, 10 Ctr Dr,MSC 1061, Bethesda, MD 20892 USA.
EM hopenfeldb@mail.nih.gov
FU NHLBI NIH HHS [Z01 HL 004609]
NR 19
TC 13
Z9 13
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
EI 1556-3871
J9 HEART RHYTHM
JI Heart Rhythm
PD MAR
PY 2006
VL 3
IS 3
BP 345
EP 352
DI 10.1016/j.hrthm.2005.11.016
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 018QJ
UT WOS:000235779600018
PM 16500310
ER

PT J
AU Watkins, PB
   Seeff, LB
AF Watkins, PB
   Seeff, LB
TI Drug-induced liver injury: Summary of a single topic - Clinical research
   conference
SO HEPATOLOGY
LA English
DT Review
ID SINUSOIDAL OBSTRUCTION SYNDROME; SYNDROME VENOOCCLUSIVE DISEASE;
   RESEARCH-AND-DEVELOPMENT; CAUSALITY ASSESSMENT; ACETAMINOPHEN
   HEPATOTOXICITY; MITOCHONDRIAL TOXICITY; AUTOIMMUNE HEPATITIS;
   METABOLIZING-ENZYMES; ANTIVIRAL DRUGS; UNITED-STATES
AB Idiosyncratic drug induced liver injury (DILI) remains poorly understood. It is assumed that the affected individuals possess a rare combination of genetic and non genetic factors that, if identified, would greatly improve understanding of the underlying mechanisms. This single topic conference brought together basic scientists, translational investigators, and clinicians with an interest in DILI. The goal was to define high priority areas of investigation that will soon be made possible by The Drug-Induced Liver Injury Network (DILIN). Since 2004 DILIN has been collecting clinical data, genomic DNA and some tissues from patients who have experienced bone fide DILI. The presentations spanned many different areas of DILI, and included novel data concerning mechanisms of hepatotoxicity, new "omics" approaches, and the challenges of improving causation assessment.
C1 Univ N Carolina, Chapel Hill, NC USA.
   NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Watkins, PB (reprint author), 208 Chesley Lane, Chapel Hill, NC 27514 USA.
EM pbwatkins@med.unc.edu
NR 109
TC 127
Z9 142
U1 3
U2 16
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD MAR
PY 2006
VL 43
IS 3
BP 618
EP 631
DI 10.1002/hep.21095
PG 14
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 020LP
UT WOS:000235911200029
PM 16496329
ER

PT J
AU Jeschke, U
   Kuhn, C
   Mylonas, I
   Schulze, S
   Friese, K
   Mayr, D
   Speer, R
   Briese, V
   Richter, DU
   Haase, M
   Karsten, U
AF Jeschke, U
   Kuhn, C
   Mylonas, I
   Schulze, S
   Friese, K
   Mayr, D
   Speer, R
   Briese, V
   Richter, DU
   Haase, M
   Karsten, U
TI Development and characterization of monoclonal antibodies for the
   immunohistochemical detection of glycodelin A in decidual, endometrial
   and gynaecological tumour tissues
SO HISTOPATHOLOGY
LA English
DT Article
DE decidua; endometrium; glycodelin; gynaecological cancer; monoclonal
   antibodies
ID AMNIOTIC-FLUID TRANSFERRIN; HUMAN PLACENTAL PROTEIN-14; BREAST-CANCER;
   STEROID-RECEPTORS; EARLY-PREGNANCY; OVARIAN-TUMORS; MESSENGER-RNA;
   CELLS; EXPRESSION; PP14
AB Aims: Glycodelin is a glycoprotein with a molecular weight of 28 kDa. Unusual LacdiNAc structures have been identified on glycodelin A, isolated from amniotic fluid. Three major functions of this glycoprotein have been identified. Glycodelin is an immunosuppressive molecule, a marker of morphological differentiation, and a contraceptive. Because no monoclonal antibodies for glycodelin A are commercially available, our aim was to develop and characterize three monoclonal antibodies against this glycoprotein.
   Methods and results: Glycodelin A was purified from amniotic fluid by three chromatographic steps and its purity was checked by SDS-PAGE. Antibodies were generated from immunized BALB/c mice. Three IgG1 monoclonal antibodies detecting glycodelin A were cloned. All three antibodies recognized carbohydrate structures of glycodelin A and did not cross-react with glycodelin S. They are applicable to immunohistochemistry (frozen and paraffin sections), ELISA and Western blots.
   Conclusion: The new antibodies can be used for the detection of glycodelin A in frozen and paraffin-embedded decidual and endometrial tissue. One antibody (A87-B/D2) can be used for the detection of glycodelin in endometrial and ovarian tumour tissues. Because glycodelin A is a major secretory endometrial product during the luteal phase, in early pregnancy and in gynaecological tumours, the new antibodies are, potentially, valuable tools for the study of endometrial development and tumour progression.
C1 Univ Munich, Dept Obstet & Gynaecol 1, D-80337 Munich, Germany.
   Univ Munich, Inst Pathol, D-80337 Munich, Germany.
   NIH, NCI FDA Clin Proteom Program, Bethesda, MD USA.
   Univ Rostock, Dept Obstet & Gynaecol, Fac Med, Rostock, Germany.
   Glycotope GmbH, Berlin, Germany.
RP Jeschke, U (reprint author), Univ Munich, Dept Obstet & Gynaecol 1, Maistr 11, D-80337 Munich, Germany.
EM udo.jeschke@med.uni-muenchen.de
NR 36
TC 13
Z9 13
U1 0
U2 1
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0309-0167
J9 HISTOPATHOLOGY
JI Histopathology
PD MAR
PY 2006
VL 48
IS 4
BP 394
EP 406
DI 10.1111/j.1365-2559.2006.02351.x
PG 13
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 013OY
UT WOS:000235419900007
PM 16487361
ER

PT J
AU Jones, DK
   Catani, M
   Pierpaoli, C
   Reeves, SJC
   Shergill, SS
   O'Sullivan, M
   Golesworthy, P
   McGuire, P
   Horsfield, MA
   Simmons, A
   Williams, SCR
   Howard, RJ
AF Jones, DK
   Catani, M
   Pierpaoli, C
   Reeves, SJC
   Shergill, SS
   O'Sullivan, M
   Golesworthy, P
   McGuire, P
   Horsfield, MA
   Simmons, A
   Williams, SCR
   Howard, RJ
TI Age effects on diffusion tensor magnetic resonance imaging tractography
   measures of frontal cortex connections in schizophrenia
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE MRI; fasciculi; white matter; anisotropy; mean diffusivity
ID WORKING-MEMORY DYSFUNCTION; REGIONAL WHITE-MATTER; HUMAN BRAIN; WATER
   DIFFUSION; MRI; SPECTROSCOPY; ANISOTROPY; MICROSTRUCTURE; ABNORMALITIES;
   DISCONNECTION
AB Diffusion tenser magnetic resonance imaging (DT-MRI) has previously been used to investigate white matter tracts in schizophrenia, with inconsistent results. The aim of the study was to use a novel method for tract-specific measurements of fronto-temporal fasciculi in early-onset schizophrenia. We hypothesized that by making tract-specific measurements, clear diffusion abnormalities would be revealed in specific fasciculi in schizophrenia. Measurements of diffusion anisotropy and mean diffusivity were localized within fronto-temporal fasciculi by forming 3-D reconstructions of the cingulum, uncinate, superior longitudinal, and inferior fronto-occipital fasciculi using diffusion tenser tractography. We were limited in our ability to test our hypothesis by the important and surprising finding that age affected DT-MRI-based measures in schizophrenia patients in a different way from comparison subjects, most notably in the left superior longitudinal fasciculus. The youngest schizophrenia patients that we studied had lower diffusion anisotropy than age-matched comparison subjects, but this difference diminished with increasing age. The main conclusion of this study was that direct comparisons of absolute DT-MRI-based measures between individuals with schizophrenia and comparison subjects may be problematic and misleading because of underlying age-related differences in brain maturation between groups.
C1 Inst Psychiat, Old Age Psychiat Sect, London SE5 8AF, England.
   NICHD, Sect Tissue Biophys & Biomimet, LIMB, NIH, Bethesda, MD USA.
   Univ Perugia, Inst Gerontol & Geriatr, I-06100 Perugia, Italy.
   Inst Psychiat, Sect Neuroimaging, Div Psychol Med, London SE5 8AF, England.
   St George Hosp, Sch Med, Div Clin Neurosci, London, England.
   Inst Psychiat, Dept Neurol, London SE5 8AF, England.
   Leicester Royal Infirm, Div Med Phys, Leicester, Leics, England.
RP Howard, RJ (reprint author), Inst Psychiat, Old Age Psychiat Sect, De Crespigny Pk, London SE5 8AF, England.
EM r.howard@iop.kcl.ac.uk
RI Reeves, Suzanne/B-3539-2011; Williams, Steve/D-6979-2011; Horsfield,
   Mark/C-6569-2013; O'Sullivan, Michael/A-1796-2010; Pierpaoli,
   Carlo/E-1672-2011; turton, miranda/F-4682-2011; Jones,
   Derek/D-1460-2009; Shergill, Sukhi/G-7725-2011; Howard,
   Robert/E-4890-2010; Simmons, Andrew/B-8848-2008; Catani,
   Marco/H-7801-2012
OI Williams, Steve/0000-0003-4299-1941; Horsfield,
   Mark/0000-0002-0815-6697; Jones, Derek/0000-0003-4409-8049; Simmons,
   Andrew/0000-0003-2306-5811; Catani, Marco/0000-0002-5488-6463
FU Wellcome Trust [054030/2/98]
NR 50
TC 155
Z9 159
U1 1
U2 6
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1065-9471
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD MAR
PY 2006
VL 27
IS 3
BP 230
EP 238
DI 10.1002/hbm.20179
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
   Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 018BF
UT WOS:000235737100004
PM 16082656
ER

PT J
AU Walsh, EC
   Sabeti, P
   Hutcheson, HB
   Fry, B
   Schaffner, SF
   de Bakker, PIW
   Varilly, P
   Palma, AA
   Roy, J
   Cooper, R
   Winkler, C
   Zeng, Y
   de The, G
   Lander, ES
   O'Brien, S
   Altshuler, D
AF Walsh, EC
   Sabeti, P
   Hutcheson, HB
   Fry, B
   Schaffner, SF
   de Bakker, PIW
   Varilly, P
   Palma, AA
   Roy, J
   Cooper, R
   Winkler, C
   Zeng, Y
   de The, G
   Lander, ES
   O'Brien, S
   Altshuler, D
TI Searching for signals of evolutionary selection in 168 genes related to
   immune function
SO HUMAN GENETICS
LA English
DT Article
ID GENOME SEQUENCE VARIATION; SECRETOR LOCUS FUT2; LINKAGE DISEQUILIBRIUM;
   NATURAL-SELECTION; FUSION GENE; POPULATIONS; MAP; SIGNATURES; PATTERNS;
   COMPLEX
AB Pathogens have played a substantial role in human evolution, with past infections shaping genetic variation at loci influencing immune function. We selected 168 genes known to be involved in the immune response, genotyped common single nucleotide polymorphisms across each gene in three population samples (CEPH Europeans from Utah, Han Chinese from Guangxi, and Yoruba Nigerians from Southwest Nigeria) and searched for evidence of selection based on four tests for non-neutral evolution: minor allele frequency (MAF), derived allele frequency (DAF), Fst versus heterozygosity and extended haplotype homozygosity (EHH). Six of the 168 genes show some evidence for non-neutral evolution in this initial screen, with two showing similar signals in independent data from the International HapMap Project. These analyses identify two loci involved in immune function that are candidates for having been subject to evolutionary selection, and highlight a number of analytical challenges in searching for selection in genome-wide polymorphism data.
C1 Novartis Inst Biomed Res, Cambridge, MA 02139 USA.
   MIT, Broad Inst, Cambridge, MA 02139 USA.
   NCI, Lab Gen Divers, Frederick, MD 21701 USA.
   Loyola Univ, Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA.
   Inst Viral Dis Control & Prevent, Beijing, Peoples R China.
   Inst Pasteur, Paris, France.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Walsh, EC (reprint author), Novartis Inst Biomed Res, 250 Mass Ave, Cambridge, MA 02139 USA.
EM Emily.walsh@novartis.com
RI Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011; Varilly,
   Patrick/C-8118-2013; de Bakker, Paul/B-8730-2009
OI Altshuler, David/0000-0002-7250-4107; Varilly,
   Patrick/0000-0003-4619-8174; de Bakker, Paul/0000-0001-7735-7858
FU NCI NIH HHS [N01-CO-12400]
NR 36
TC 50
Z9 51
U1 2
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD MAR
PY 2006
VL 119
IS 1-2
BP 92
EP 102
DI 10.1007/s00439-005-0090-0
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 016QM
UT WOS:000235635000010
PM 16362345
ER

PT J
AU Hahn, Y
   Lee, B
AF Hahn, Y
   Lee, B
TI Human-specific nonsense mutations identified by genome sequence
   comparisons
SO HUMAN GENETICS
LA English
DT Article
DE nonsense mutation; human; chimpanzee; molecular evolution
ID MAJOR HISTOCOMPATIBILITY COMPLEX; PAN-HOMO DIVERGENCE; CHIMPANZEE
   GENOME; FRAMESHIFT MUTATIONS; MOLECULAR EVOLUTION; PRIMATE GENOMICS;
   GENE-CLUSTER; METALLOTHIONEIN; INACTIVATION; ALIGNMENT
AB The comparative study of the human and chimpanzee genomes may shed light on the genetic ingredients for the evolution of the unique traits of humans. Here, we present a simple procedure to identify human-specific nonsense mutations that might have arisen since the human-chimpanzee divergence. The procedure involves collecting orthologous sequences in which a stop codon of the human sequence is aligned to a non-stop codon in the chimpanzee sequence and verifying that the latter is ancestral by finding homologs in other species without a stop codon. Using this procedure, we identify nine genes (CML2, FLJ14640, MT1L, NPPA, PDE3B, SERPINA13, TAP2, UIP1, and ZNF277) that would produce human-specific truncated proteins resulting in a loss or modification of the function. The premature terminations of CML2, MT1L, and SERPINA13 genes appear to abolish the original function of the encoded protein because the mutation removes a major part of the known active site in each case. The other six mutated genes are either known or presumed to produce functionally modified proteins. The mutations of five genes (CML2, FLJ14640, MT1L, NPPA, TAP2) are known or predicted to be polymorphic in humans. In these cases, the stop codon alleles are more prevalent than the ancestral allele, suggesting that the mutant alleles are approaching fixation since their emergence during the human evolution. The findings support the notion that functional modification or inactivation of genes by nonsense mutation is a part of the process of adaptive evolution and acquisition of species-specific features.
C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Lee, B (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bldg 37,MSC 4264,37 Convent Dr Room 5120A, Bethesda, MD 20892 USA.
EM bk@nih.gov
FU Intramural NIH HHS
NR 56
TC 23
Z9 24
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD MAR
PY 2006
VL 119
IS 1-2
BP 169
EP 178
DI 10.1007/s00439-005-0125-6
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 016QM
UT WOS:000235635000018
PM 16395595
ER

PT J
AU Gao, XJ
   Single, RM
   Karacki, P
   Marti, D
   O'Brien, SJ
   Carrington, M
AF Gao, XJ
   Single, RM
   Karacki, P
   Marti, D
   O'Brien, SJ
   Carrington, M
TI Diversity of MICA and linkage disequilibrium with HLA-B in two North
   American populations
SO HUMAN IMMUNOLOGY
LA English
DT Article
DE MICA polymorphism; HLA-B; linkage disequilibrium
ID EWENS SAMPLING DISTRIBUTION; GAMETIC DISEQUILIBRIUM; NULL HAPLOTYPE;
   T-CELLS; ALLELES; GENES; NKG2D
AB The MICA gene has a high degree of polymorphism. Allelic variation of MICA may influence binding of these ligands to the NK cell receptor NKG2D and may affect organ transplantation and/or disease pathogenesis. Knowledge of the population distribution of MICA alleles and their linkage disequilibrium (LD) with class I human leukocyte antigen (HLA) will enhance our understanding of the potential functional significance of the MICA polymorphism. In the present study, we characterized the MICA and HLA-B polymorphisms in two North American populations: European and African. The individual racial groups showed rather limited variation at the MICA locus, where the same set of three most common alleles, MICA*00201, *004, and *00801, account for 64 and 7196 of the allele frequency in European-Americans and African-Americans, respectively. Other common alleles (allele frequency > 5% in a population) include MICA*00901 and *010. MICA alleles showed strong linkage disequilibrium with HLA-B. Typically, a common MICA allele has strong LD with several HLA-B alleles, whereas most HLA-B alleles and their related serological groups are associated with a single MICA allele. The lack of evidence for an active diversification of the MICA gene after racial separation indicates an evolutionary history distinct from that of the classical HLA genes.
C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Basic Res Program,SAIC Frederick, Frederick, MD 21702 USA.
   Univ Vermont, Dept Math & Stat, Burlington, VT 05405 USA.
   Georgetown Univ, Sch Med, Georgetown, DC USA.
RP Carrington, M (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Basic Res Program,SAIC Frederick, POB B, Frederick, MD 21702 USA.
EM carringt@ncifcrf.gov
FU NCI NIH HHS [N01-CO12400]
NR 27
TC 35
Z9 38
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
J9 HUM IMMUNOL
JI Hum. Immunol.
PD MAR
PY 2006
VL 67
IS 3
SI SI
BP 152
EP 158
DI 10.1016/j.humimm.2006.02.009
PG 7
WC Immunology
SC Immunology
GA 049AL
UT WOS:000237987600003
PM 16698437
ER

PT J
AU Fine, LJ
   Cutler, JA
AF Fine, LJ
   Cutler, JA
TI Hypertension and the treating physician - Understanding and reducing
   therapeutic inertia
SO HYPERTENSION
LA English
DT Editorial Material
ID ISOLATED SYSTOLIC HYPERTENSION; OLDER PERSONS; UNITED-STATES; PREVENTION
C1 NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Fine, LJ (reprint author), 6701 Rockledge Dr,Rm 8138,MSC-7936, Bethesda, MD 20892 USA.
EM fine1@nhlbi.nih.gov
NR 13
TC 24
Z9 24
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD MAR
PY 2006
VL 47
IS 3
BP 319
EP 320
DI 10.1161/01.HYP.0000200692.23410.c9
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 012WT
UT WOS:000235372300002
PM 16432049
ER

PT J
AU Wang, WY
   Lee, ET
   Fabsitz, RR
   Devereux, R
   Best, L
   Welty, TK
   Howard, BV
AF Wang, WY
   Lee, ET
   Fabsitz, RR
   Devereux, R
   Best, L
   Welty, TK
   Howard, BV
TI A longitudinal study of hypertension risk factors and their relation to
   cardiovascular disease - The Strong Heart Study
SO HYPERTENSION
LA English
DT Article
DE risk factors; cardiovascular diseases
ID AMERICAN-INDIAN POPULATIONS; BLOOD-PRESSURE; ATHEROSCLEROSIS RISK;
   ALCOHOL-CONSUMPTION; MONICA PROJECT; FOLLOW-UP; PREVALENCE; HEALTH;
   MICROALBUMINURIA; DETERMINANTS
AB This study estimated hypertension incidence and explored hypertension risk factors and their association with cardiovascular disease. Data collected from 4549 American Indian participants in the 3 exams of the Strong Heart Study were used. Hypertension was defined as systolic blood pressure >= 140 mm Hg, diastolic blood pressure >= 90 mm Hg, or current use of antihypertensive medication. Generalized linear models were used to identify the risk factors for hypertension and the correlates of blood pressures. Cox proportional models with time-dependent covariates and the mixed models were used to explore the association of hypertension with cardiovascular disease. There was no sex difference in hypertension. After adjustment for other risk factors, the risks of developing hypertension among subgroups in each characterized group were as follows: prehypertensive versus normotensive, 3.21 times; macroalbuminuria and microalbuminuria versus normal, 3.47 and 1.72; diabetic versus nondiabetic, 1.56; overweight and obese versus normal weight, 1.30 and 1.51; and current alcohol drinking versus not, 1.22. Moreover, systolic blood pressure was significantly and positively associated with age, obesity, and albuminuria and negatively with smoking. After adjusting all other risk factors, those pretreated, untreated, controlled, and uncontrolled hypertensive participants had approximate to 1.74, 1.81, 2.19, and 2.77 times higher risks of developing cardiovascular disease compared with normotensive participants, respectively. In 45- to 74-year-old American Indians, the risk of developing hypertension was rising. Prehypertensive participants had 3.2/1.74 times higher risk of developing hypertension/cardiovascular disease than normotensive participants. Age, diabetes, and macro/microalbuminuria were independently significant risk factors of both hypertension and cardiovascular disease.
C1 Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK 73190 USA.
   NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA.
   Cornell Univ, Med Ctr, New York, NY 10021 USA.
   Missouri Breaks Ind Res Inc, Timber Lake, SD USA.
   Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA.
   MedStar Res Inst, Washington, DC USA.
RP Wang, WY (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, POB 26901, Oklahoma City, OK 73190 USA.
EM wenyu-wang@ouhsc.edu
FU NHLBI NIH HHS [U01-HL-41652, U01-HL-41642, UL01-HL-41654]
NR 48
TC 79
Z9 85
U1 2
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD MAR
PY 2006
VL 47
IS 3
BP 403
EP 409
DI 10.1161/01.HYP.0000200710.29498.80
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 012WT
UT WOS:000235372300023
PM 16432042
ER

PT J
AU Zhang, Y
   Lee, ET
   Devereux, RB
   Yeh, JL
   Best, LG
   Fabsitz, RR
   Howard, BV
AF Zhang, Y
   Lee, ET
   Devereux, RB
   Yeh, JL
   Best, LG
   Fabsitz, RR
   Howard, BV
TI Prehypertension, diabetes, and cardiovascular disease risk in a
   population-based sample - The Strong Heart Study
SO HYPERTENSION
LA English
DT Article
DE cardiovascular disease; cohort study; diabetes mellitus; prehypertension
ID BLOOD-PRESSURE; AMERICAN-INDIANS; HYPERTENSION; PREVENTION; CHOLESTEROL;
   MORTALITY
AB There are few data about the impact of the recently-defined category of prehypertension (systolic blood pressure 120 to 139 mm Hg or diastolic blood pressure 80 to 89 mm Hg) on cardiovascular disease incidence. It is also unknown whether this association differs between individuals with or without diabetes. A total of 2629 Strong Heart Study participants free from hypertension and cardiovascular disease at baseline examination were followed for 12 years to observe incident cardiovascular disease. Approximately 42% of the 2629 participants had diabetes. We assessed the prevalence of prehypertension and the hazard ratios of incident cardiovascular disease associated with prehypertension. Prehypertension was more prevalent in diabetic than nondiabetic participants (59.4% versus 48.2%, P < 0.001 adjusted for age). Compared with nondiabetic participants with normal blood pressure, the hazard ratios of cardiovascular disease were 3.70 (95% confidence interval: 2.66, 5.15) for those with both prehypertension and diabetes, 1.80 (1.28, 2.54) for those with prehypertension alone and 2.90 (2.03, 4.16) for those with diabetes alone. Impaired glucose tolerance or impaired fasting glucose also greatly increased the cardiovascular disease risk in prehypertensive people. Clinical investigation of more aggressive interventions, such as drug treatment for blood pressure control for prehypertensive individuals with impaired fasting glucose, impaired glucose tolerance, or diabetes is warranted.
C1 Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK 73190 USA.
   Cornell Univ, Med Ctr, New York, NY 10021 USA.
   Missouri Breaks Ind Res Inc, Timber Lake, SD USA.
   NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA.
   MedStar Res Inst, Washington, DC USA.
RP Zhang, Y (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, POB 26901, Oklahoma City, OK 73190 USA.
EM Ying-zhang4@ouhsc.edu
FU NHLBI NIH HHS [UL01-HL41654, U01-HL41642, U01-HL41652, U01-HL65520,
   U01-HL65521]
NR 20
TC 113
Z9 129
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD MAR
PY 2006
VL 47
IS 3
BP 410
EP 414
DI 10.1161/01.HYP.0000205119.19804.08
PG 5
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 012WT
UT WOS:000235372300024
PM 16446387
ER

PT J
AU Kennedy, DJ
   Vetteth, S
   Periyasamy, SM
   Kanj, M
   Fedorova, L
   Khouri, S
   Kahaleh, MB
   Xie, ZJ
   Malhotra, D
   Kolodkin, NI
   Lakatta, EG
   Fedorova, OV
   Bagrov, AY
   Shapiro, JI
AF Kennedy, DJ
   Vetteth, S
   Periyasamy, SM
   Kanj, M
   Fedorova, L
   Khouri, S
   Kahaleh, MB
   Xie, ZJ
   Malhotra, D
   Kolodkin, NI
   Lakatta, EG
   Fedorova, OV
   Bagrov, AY
   Shapiro, JI
TI Central role for the cardiotonic steroid marinobufagenin in the
   pathogenesis of experimental uremic cardiomyopathy
SO HYPERTENSION
LA English
DT Article
DE cardiomyopathy; sarcoplasmic reticulum; cardiotonic agents; fibrosis;
   renal failure; reactive oxygen species
ID LEFT-VENTRICULAR HYPERTROPHY; SIGNAL-TRANSDUCING FUNCTION; PLASMALEMMAL
   NA/K-ATPASE; CONGESTIVE-HEART-FAILURE; CARDIAC NA+/K+-ATPASE;
   CHRONIC-RENAL-FAILURE; CARDIOVASCULAR MORTALITY; RISK-FACTORS; OUABAIN;
   RAT
AB Patients with chronic renal failure develop a "uremic" cardiomyopathy characterized by diastolic dysfunction, cardiac hypertrophy, and systemic oxidant stress. Patients with chronic renal failure are also known to have increases in the circulating concentrations of the cardiotonic steroid marinobufagenin (MBG). On this background, we hypothesized that elevations in circulating MBG may be involved in the cardiomyopathy. First, we observed that administration of MBG ( 10 mu g/kg per day) for 4 weeks caused comparable increases in plasma MBG as partial nephrectomy at 4 weeks. MBG infusion caused increases in conscious blood pressure, cardiac weight, and the time constant for left ventricular relaxation similar to partial nephrectomy. Decreases in the expression of the cardiac sarcoplasmic reticulum ATPase, cardiac fibrosis, and systemic oxidant stress were observed with both MBG infusion and partial nephrectomy. Next, rats were actively immunized against a MBG-BSA conjugate or BSA control, and partial nephrectomy was subsequently performed. Immunization against MBG attenuated the cardiac hypertrophy, impairment of diastolic function, cardiac fibrosis, and systemic oxidant stress seen with partial nephrectomy without a significant effect on conscious blood pressure. These data suggest that the increased concentrations of MBG are important in the cardiac disease and oxidant stress state seen with renal failure.
C1 Med Univ Ohio, Dept Med, Toledo, OH 43614 USA.
   Med Univ Ohio, Dept Pharmacol, Toledo, OH 43614 USA.
   NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA.
RP Shapiro, JI (reprint author), Med Univ Ohio, Dept Med, 3120 Glendale Ave, Toledo, OH 43614 USA.
EM jshapiro@meduohio.edu
FU NHLBI NIH HHS [HL67963, HL63238, HL57144]
NR 41
TC 123
Z9 127
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD MAR
PY 2006
VL 47
IS 3
BP 488
EP 495
DI 10.1161/01.HYP.0000202594.82271.92
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 012WT
UT WOS:000235372300036
PM 16446397
ER

PT J
AU Munzner, T
   Johnson, C
   Moorhead, R
   Pfister, H
   Rheingans, P
   Yoo, TS
AF Munzner, T
   Johnson, C
   Moorhead, R
   Pfister, H
   Rheingans, P
   Yoo, TS
TI NIH-NSF Visualization Research Challenges report summary
SO IEEE COMPUTER GRAPHICS AND APPLICATIONS
LA English
DT Editorial Material
C1 Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
   Univ Utah, Salt Lake City, UT 84112 USA.
   Mississippi State Univ, Mississippi State, MS 39762 USA.
   Mitsubishi Elect Res Labs, Cambridge, MA USA.
   Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA.
   Natl Lib Med, Bethesda, MD 20894 USA.
RP Yoo, TS (reprint author), Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
EM tyoo@mail.nih.gov
NR 8
TC 21
Z9 21
U1 0
U2 1
PU IEEE COMPUTER SOC
PI LOS ALAMITOS
PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA
SN 0272-1716
J9 IEEE COMPUT GRAPH
JI IEEE Comput. Graph. Appl.
PD MAR-APR
PY 2006
VL 26
IS 2
BP 20
EP 24
DI 10.1109/MCG.2006.44
PG 5
WC Computer Science, Software Engineering
SC Computer Science
GA 018AU
UT WOS:000235735900004
PM 16548457
ER

PT J
AU Franaszek, M
   Summers, RM
   Pickhardt, PJ
   Choi, JR
AF Franaszek, M
   Summers, RM
   Pickhardt, PJ
   Choi, JR
TI Hybrid segmentation of colon filled with air and opacified fluid for CT
   colonography
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE colon segmentation; CT colonography; fuzzy connectedness; zero level set
ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; VIRTUAL COLONOSCOPY; COLORECTAL
   POLYPS
AB Reliable segmentation of the colon is a requirement for three-dimensional visualization programs and automatic detection of polyps on computed tomography (CT) colonography. There is an evolving clinical consensus that giving patients positive oral contrast to tag out remnants of stool and residual fluids is mandatory. The presence of positive oral contrast in the colon adds an additional challenge for colonic segmentation but ultimately is beneficial to the patient because the enhanced fluid helps reveal polyps in otherwise hidden areas. Therefore, we developed a new segmentation procedure which can handle both air- and fluid-filled parts of the colon. The procedure organizes individual air- and fluid-filled regions into a graph that enables identification and removal of undesired leakage outside the colon. In addition, the procedure provides a risk assessment of possible leakage to assist the user prior to the tedious task of visual verification. The proposed hybrid algorithm uses modified region growing, fuzzy connectedness and level set segmentation. We tested our algorithm on 160 CT coloringraphy scans containing 183 known polyps. All 183 polyps were in segmented regions. In addition, visual inspection of 24 CT colonography scans demonstrated good performance of our procedure: the reconstructed colonic wall appeared smooth even at the interface between air and fluid and there were no leaked regions.
C1 Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Natl Inst Hlth, Bethesda, MD 20892 USA.
   Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
   Natl Naval Med Res Inst, Bethesda, MD 20892 USA.
   Walter Reed Army Med Ctr, Washington, DC 20307 USA.
RP Franaszek, M (reprint author), Warren Grant Magnuson Clin Ctr, Dept Diagnost Radiol, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM mfranaszek@cc.nih.gov
FU Intramural NIH HHS
NR 26
TC 56
Z9 59
U1 0
U2 1
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA
SN 0278-0062
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD MAR
PY 2006
VL 25
IS 3
BP 358
EP 368
DI 10.1109/TMI.2005.863836
PG 11
WC Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Engineering, Electrical & Electronic; Imaging Science &
   Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
   Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 018SB
UT WOS:000235784000010
PM 16524091
ER

PT J
AU Shechter, G
   Resar, JR
   McVeigh, ER
AF Shechter, G
   Resar, JR
   McVeigh, ER
TI Displacement and velocity of the coronary arteries: Cardiac and
   respiratory motion
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE chest imaging; coronary arteries; motion; X-ray angiography
ID ANGIOGRAPHY; HEART; ARTIFACTS; DURATION; TRACKING; IMAGES; CYCLE; CT
AB This paper presents measurements of three-dimensional (3-D) displacements and velocities of the coronary arteries due to the myocardial beating motion and due to breathing. Data were acquired by reconstructing the coronary arteries and their motion from biplane angiograms in 10 patients. A parametric motion model was used to separate the cardiac and breathing motion fields. The arteries move consistently toward the left, inferior, and anterior during a cardiac contraction. The displacement and velocity of the right coronary artery during a cardiac contraction was larger than measured for the left coronary tree. Cardiac motion dominates the respiratory motion of the coronary arteries during spontaneous breathing. On inspiration, the arteries move caudally, but the motion in the left-right and anterior-posterior axes was variable. Spatial variation in respiratory displacement and velocity of the coronary arteries indicates that the breathing motion of the heart is more complex than a 3-D translation.
C1 NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA.
   Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21205 USA.
RP Philips Res USA, 345 Scarborough Rd,Briarcliff Manor, Briarcliff Manor, NY 10510 USA.
FU Intramural NIH HHS [Z01 HL004608-08]
NR 21
TC 66
Z9 66
U1 0
U2 2
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
EI 1558-254X
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD MAR
PY 2006
VL 25
IS 3
BP 369
EP 375
DI 10.1109/TMI.2005.862752
PG 7
WC Computer Science, Interdisciplinary Applications; Engineering,
   Biomedical; Engineering, Electrical & Electronic; Imaging Science &
   Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
   Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 018SB
UT WOS:000235784000011
PM 16524092
ER

PT J
AU Parchment, RE
AF Parchment, Ralph E.
TI High-fidelity In vitro modeling of clinically-defined,
   chemically-induced Organ toxicity in man using adverse effects of
   oncology drugs as ethical learning sets.
SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
LA English
DT Meeting Abstract
C1 NCI, Lab Human Toxicol & Pharmacol, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM parchmentr@email.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SOCIETY IN VITRO BIOLOGY
PI RALEIGH
PA 514 DANIELS STREET, STE 411, RALEIGH, NC 27605 USA
SN 1071-2690
J9 IN VITRO CELL DEV-AN
JI In Vitro Cell. Dev. Biol.-Anim.
PD SPR
PY 2006
VL 42
SU S
BP 5A
EP 5A
PG 1
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 106VF
UT WOS:000242129400013
ER

PT J
AU Shoemaker, RH
AF Shoemaker, Robert H.
TI The NCI 60 human tumor cell line screen: An information-rich screen
   informing on mechanisms of toxicity.
SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
LA English
DT Meeting Abstract
C1 Natl Canc Inst, Div Canc Treatment & Diag, Sreening Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA.
EM shoemaker@dtpax2.nciferf.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SOCIETY IN VITRO BIOLOGY
PI RALEIGH
PA 514 DANIELS STREET, STE 411, RALEIGH, NC 27605 USA
SN 1071-2690
J9 IN VITRO CELL DEV-AN
JI In Vitro Cell. Dev. Biol.-Anim.
PD SPR
PY 2006
VL 42
SU S
BP 5A
EP 5A
PG 1
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 106VF
UT WOS:000242129400012
ER

PT J
AU Elmore, E
   Jain, A
   Kopelovich, L
   Meyskens, FL
   Steele, VE
   Redpath, JL
AF Elmore, E.
   Jain, A.
   Kopelovich, L.
   Meyskens, F. L.
   Steele, V. E.
   Redpath, J. L.
TI Response of rosiglitazone, UAB 30, and atorvastatin in the human
   melanoma prevention assayl.
SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
LA English
DT Meeting Abstract
C1 Univ Calif Irvine, Dept Radiat Oncol, Irvine, CA 92697 USA.
   Univ Calif Irvine, Caho Family Comprehens Canc Ctr, Irvine, CA 92697 USA.
   NCI, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA.
EM eelmore@uci.edu
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SOCIETY IN VITRO BIOLOGY
PI RALEIGH
PA 514 DANIELS STREET, STE 411, RALEIGH, NC 27605 USA
SN 1071-2690
J9 IN VITRO CELL DEV-AN
JI In Vitro Cell. Dev. Biol.-Anim.
PD SPR
PY 2006
VL 42
SU S
BP 19A
EP 19A
PG 1
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 106VF
UT WOS:000242129400066
ER

PT J
AU Berman, J
AF Berman, J
TI Visceral leishmaniasis in the New World & Africa
SO INDIAN JOURNAL OF MEDICAL RESEARCH
LA English
DT Review
DE cure rate; HIV-co-infection; post-kala-azar dermal leishmaniasis;
   visceral leishmaniasis
ID AZAR DERMAL LEISHMANIASIS; PROPRIETARY SODIUM STIBOGLUCONATE; B
   CHOLESTEROL DISPERSION; ENDEMIC KALA-AZAR; NATURAL-HISTORY; NORTHEAST
   BRAZIL; SOUTHERN SUDAN; EASTERN SUDAN; FOLLOW-UP; CHAGASI
AB Visceral leishmaniasis in the New World, primarily found in northeastern Brazil, is caused by Leishmania chagasi. Compared to India, unusual features of Brazilian disease are the large number of asymptomatic infections versus symptomatic infections, and the apparent change from a zoonotic disease to a partially anthroponotic one. Visceral disease in Africa is caused by L. donovani as in India, but disease differs from that in India in being zoonotic rather than anthroponotic, and in the large numbers of patients who acquire post-kala-azar dermal leishmaniasis.
C1 Natl Ctr Complementary & Alternat Med, NIH, Bethesda, MD 20892 USA.
RP Berman, J (reprint author), Natl Ctr Complementary & Alternat Med, NIH, 6707 Democracy Blvd,Suite 401, Bethesda, MD 20892 USA.
EM Bermanjo@mail.nih.gov
NR 37
TC 33
Z9 35
U1 1
U2 2
PU INDIAN COUNCIL MEDICAL RES
PI NEW DELHI
PA PO BOX 4911 ANSARI NAGAR, NEW DELHI 110029, INDIA
SN 0971-5916
J9 INDIAN J MED RES
JI Indian J. Med. Res.
PD MAR
PY 2006
VL 123
IS 3
BP 289
EP 294
PG 6
WC Immunology; Medicine, General & Internal; Medicine, Research &
   Experimental
SC Immunology; General & Internal Medicine; Research & Experimental
   Medicine
GA 052OR
UT WOS:000238243500010
PM 16778311
ER

PT J
AU Reiman, RM
   Thompson, RW
   Feng, CG
   Hari, D
   Knight, R
   Cheever, AW
   Rosenberg, HF
   Wynn, TA
AF Reiman, RM
   Thompson, RW
   Feng, CG
   Hari, D
   Knight, R
   Cheever, AW
   Rosenberg, HF
   Wynn, TA
TI Interleukin-5 (IL-5) augments the progression of liver fibrosis by
   regulating IL-13 activity
SO INFECTION AND IMMUNITY
LA English
DT Article
ID PRIMARY BILIARY-CIRRHOSIS; MANSONI-INFECTED MICE; SCHISTOSOMA-MANSONI;
   GRANULOMA-FORMATION; EOSINOPHIL DEGRANULATION; TISSUE EOSINOPHILIA;
   HEPATIC-FIBROSIS; B-CELLS; NON-T; RESPONSES
AB Eosinophils are frequently found in increased numbers in a variety of chronic fibrotic diseases; however, their role in the development of hepatic fibrosis has not been dissected in vivo. Here, we used interleukin-5 (IL-5) knockout (KO) mice to determine whether eosinophils contribute to the progressive liver fibrosis that develops in response to chronic Schistosoma mansoni infection. Although infection intensities were similar in C57BL/6 and IL-5 KO mice, the average size of granulomas was significantly smaller in both acutely and chronically infected IL-5 KO mice. Their granulomas were also completely devoid of eosinophils. In addition, the knockout mice displayed over a 40% reduction in hepatic fibrosis by week 16 postinfection. The reduced fibrosis was associated with increased production of the antifibrotic cytokine gamma interferon. Moreover, although IL-13 production did not decrease consistently in the absence of IL-5, IL-13-triggered responses were substantially reduced in the granulomatous tissues. This was confirmed by analyzing the expression of several genes associated with alternative macrophage activation, including arginase 1, Fizz-1, and YM-1. Importantly, all of these IL-13-regulated genes have been linked with the mechanisms of wound healing and fibrosis. In addition to IL-5 polarizing the antigen-specific CD4(+) Th2 cell response, we found that granuloma eosinophils were themselves a significant source of IL-13. Thus, by producing profibrotic mediators and polarizing the Th2 response, these findings illustrate both direct and indirect roles for eosinophils and IL-5 in the pathogenesis of schistosomiasis-induced liver fibrosis. Thus, inhibiting the activity of IL-5 or eosinophils may prove effective for a variety of chronic fibrotic diseases.
C1 NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
   NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
   Biomed Res Inst, Rockville, MD 20852 USA.
RP Wynn, TA (reprint author), 50 South Dr,Rm 6154,MSC 8003, Bethesda, MD 20892 USA.
EM twynn@niaid.nih.gov
RI Wynn, Thomas/C-2797-2011
FU Intramural NIH HHS
NR 40
TC 96
Z9 106
U1 0
U2 6
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 MAR
PY 2006
VL 74
IS 3
BP 1471
EP 1479
DI 10.1128/IAI.74.3.1471-1479.2006
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 019ED
UT WOS:000235817500004
PM 16495517
ER

PT J
AU Ghany, MG
   Doo, EC
AF Ghany, MG
   Doo, EC
TI Assessment and management of chronic hepatitis B
SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA
LA English
DT Article
ID E-ANTIGEN; VIRUS-INFECTION; HBEAG SEROCONVERSION;
   HEPATOCELLULAR-CARCINOMA; PHYLOGENETIC RELATEDNESS; LAMIVUDINE THERAPY;
   ANTIVIRAL THERAPY; GENOTYPE-C; L-FMAU; REPLICATION
AB Chronic hepatitis B (CHB) is a major worldwide cause of chronic liver disease and a significant public health issue. Three predominant clinical presentations are recognized: hepatitis B e antigen (HBeAg) or typical CHB, HBeAg-negative or atypical CHB, and inactive CHB. The natural history of CHB infection in an individual may be dominated by one or a combination of these clinical presentations in a sequential fashion. These variations in clinical presentations reflect the viral-host immunology dynamics that form the basis for the development of liver disease. Therapy has been problematic in the past. There are three licensed drugs available for therapy of CHB with varied mechanisms of action. This has introduced the concept of tailored therapy for the individual patient. Many promising new agents and therapeutic approaches should become available in the near future.
C1 NIDDK, Liver Dis Sect, Bethesda, MD 20892 USA.
   NIDDK, Liver Dis Res Branch, Bethesda, MD 20892 USA.
RP Ghany, MG (reprint author), NIDDK, Liver Dis Sect, Bldg 10,Room 9B-06,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA.
EM marcg@bldg10.niddk.nih.gov
NR 60
TC 5
Z9 6
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399 USA
SN 0891-5520
J9 INFECT DIS CLIN N AM
JI Infect. Dis. Clin. North Am.
PD MAR
PY 2006
VL 20
IS 1
BP 63
EP +
DI 10.1016/j.idc.2006.01.009
PG 18
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 028WV
UT WOS:000236520400005
PM 16527649
ER

PT J
AU Yarovinsky, F
   Sher, A
AF Yarovinsky, F
   Sher, A
TI Toll-like receptor recognition of Toxoplasma gondii
SO INTERNATIONAL JOURNAL FOR PARASITOLOGY
LA English
DT Article
DE Toxoplasma gondii; apicomplexan protozoa; innate immunity; toll-like
   receptors; TLR 11; MyD88; IL-12; dendritic cells
ID DENDRITIC CELLS; INNATE IMMUNITY; ACUTE INFECTION; PARASITE;
   MACROPHAGES; RESISTANCE; INDUCTION; IL-12; RESPONSES;
   GLYCOSYLPHOSPHATIDYLINOSITOLS
AB Toxoplasma gondii potently stimulates IFN-gamma production by both the innate and adaptive immune system as part of its host adaptation. This response is known to be dependent on an Myeloid Differentiation factor 88 signaling pathway used by Toll-like receptors (TLRs), a family of proteins involved in the recognition of microbial molecular patterns. In the following review, we summarise the evidence for specific TLR function in host resistance to T gondii focusing on the recent discovery in the parasite of a profilin-like ligand that potently stimulates TLR11 and regulates the production of IL-12, a cytokine necessary for the protective IFN-gamma response. In addition, we discuss the hypothesis that TLR11 may have evolved as a general pattern recognition receptor for apicomplexan protozoa and that as highly conserved proteins associated with actin-based motility, profilins are logical ligand targets for this form of pathogen detection. Finally, we review the evidence for involvement of other TLR and TLR ligands in host resistance to T gondii and discuss how such receptors might synergise with TLR11 in the innate response to the parasite. Published by Elsevier Ltd on behalf of Australian Society for Parasitology Inc.
C1 NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Yarovinsky, F (reprint author), NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bld 50,Rm 6144,50 S Dr MSC 8003, Bethesda, MD 20892 USA.
EM fyarovinsky@niaid.nih.gov
NR 33
TC 48
Z9 50
U1 0
U2 8
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0020-7519
J9 INT J PARASITOL
JI Int. J. Parasit.
PD MAR
PY 2006
VL 36
IS 3
BP 255
EP 259
DI 10.1016/j.ijpara.2005.12.003
PG 5
WC Parasitology
SC Parasitology
GA 032PR
UT WOS:000236787300001
PM 16476433
ER

PT J
AU Abdel-Fattah, R
   Glick, A
   Rehman, I
   Maiberger, P
   Hennings, H
AF Abdel-Fattah, R
   Glick, A
   Rehman, I
   Maiberger, P
   Hennings, H
TI Methylation of the O-6-Methylguanine-DNA methyltransferase promoter
   suppresses expression in mouse skin tumors and varies with the tumor
   induction protocol
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE methylation; MGMT; skin tumors; papillomas; carcinomas
ID ETHYL-N-NITROSOUREA; TRANSGENIC MICE; O6-ALKYLGUANINE-DNA
   ALKYLTRANSFERASE; COLORECTAL TUMORIGENESIS; DNA METHYLTRANSFERASE;
   ALKYLATING-AGENTS; THYMIC LYMPHOMAS; REPAIR; GENE; HYPERMETHYLATION
AB Hypermethylation of CpG sites within the promoter region of the O-6-methylguanine-DNA methyltransferase (MGMT) gene occurs frequently in human cancer, preventing both MGMT expression and repair of alkylation damage. To assess the role of MGMT in the development of mouse skin tumors induced by initiation-promotion protocols, methylation of the MGMT promoter was examined in tumor DNA using methylation-specific PCR. To determine whether MGMT promoter methylation was affected by the tumor induction protocol, tumors were initiated by N-methyi. N'-nitro-N-nitrosoguanidine (MNNG) or 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate(TPA) or mezerein. Although the MGMT promoter was not methylated in normal skin, promoter methylation was found in 56 of 136 papillomas (41.2%) and in 19 of 37 squalmous cell carcinomas (51.4%). When methylation of the MGMT promoter was compared in the 4 treatment groups, hypermethylation was found more frequently in tumors initiated by DMBA and promoted by mezerein, a protocol associated with a high frequency of malignant conversion. Methylation was found in some tumors as early as 5 weeks after initiation, but the methylation frequency increased with time. MGMT promoter methylation reduced MGMT expression as determined by immunohistochemistry. Although MGMT promoter methylation was not generally correlated with ras mutations, the frequency of MGMT methylation was higher in MNNG-initiated, mezerein-promoted papillomas with mutations in Ha-ras compared to papillomas with Ki-ras. Methylation of the MGMT promoter, associated with reduced MGMT expression, is found in nearly half of mouse skin tumors, but varies with both the tumor initiator and tumor promoter, and may be a key step in the progression from papillomas to carcinomas. (c) 2005 Wiley-Liss, Inc.
C1 NCI, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bethesda, MD 20892 USA.
   Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA.
RP Hennings, H (reprint author), NCI, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bldg 37,Room 4054B,37 Convent Dr, Bethesda, MD 20892 USA.
EM hh20v@nih.gov
NR 28
TC 3
Z9 3
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 1
PY 2006
VL 118
IS 3
BP 527
EP 531
DI 10.1002/ijc.21316
PG 5
WC Oncology
SC Oncology
GA 000EO
UT WOS:000234443900002
PM 16094607
ER

PT J
AU Yang, XHR
   Goldstein, AM
   Chen, CJ
   Rabkin, CS
   Chen, JY
   Cheng, YJ
   Hsu, WL
   Sun, B
   Diehl, SR
   Liu, MY
   Walters, M
   Shao, W
   Ortiz-Conde, BA
   Whitby, D
   Elmore, SH
   Gulley, ML
   Hildesheim, A
AF Yang, XHR
   Goldstein, AM
   Chen, CJ
   Rabkin, CS
   Chen, JY
   Cheng, YJ
   Hsu, WL
   Sun, B
   Diehl, SR
   Liu, MY
   Walters, M
   Shao, W
   Ortiz-Conde, BA
   Whitby, D
   Elmore, SH
   Gulley, ML
   Hildesheim, A
TI Distribution of Epstein-Barr viral load in serum of individuals from
   nasopharyngeal carcinoma high-risk families in Taiwan
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE Epstein-Barr viral load; nasopharyngeal carcinoma; high-risk family;
   Epstein-Barr virus serology
ID VIRUS EBV DNA; QUANTITATIVE-ANALYSIS; CAPSID ANTIGEN; PLASMA; ANTIBODY;
   DISEASE; QUANTIFICATION; MALIGNANCIES; PATTERNS
AB The utility of EBV load as a tumor marker in nasopharyngeal carcinoma (NPC) patients suggests that it might also serve as a screening test for individuals who are at high risk for developing NPC. We previously demonstrated that unaffected individuals from high-risk families had elevated anti-EBV antibody levels compared to community controls. In this study, we measured EBV load using 2 different real-time PCR assays (targeting BamH1W and polymerase gene sequences, respectively) carried out in 2 independent research labs in serum samples from 19 untreated NPC cases, 11 healthy community controls and 100 unaffected individuals from families in which 2 or more individuals were affected with NPC. EBV genomes were detectable in 68% of NPC cases by the EBV BamH1W assay and in 74% by the EBV polymerase assay (kappa = 0.64). Patients with stage III or IV disease had significantly higher EBV load compared to those with stage I or II disease (p = 0.008). EBV DNA was detected in a single community control sample by the EBV BamH1W assay and in none of the samples by the EBV polymerase assay. Only one of 100 unaffected family members tested positive by both assays. An additional 14 were positive by only one of the 2 EBV load assays used and usually in only one of the duplicate wells tested, all with very low viral loads (3-50 copies/ml). In addition, EBV load did not correlate with EBV serology results (anti-VCA, anti-DNase, anti-EBNA-1) among these unaffected family members. In conclusion, our study suggests limited clinical utility of the EBV load test, in its current configuration, to screen individuals from high-risk families. Should a more sensitive or specific molecular assay be developed that is capable of detecting and distinguishing tumor-derived EBV genomes or gene products from true negatives, it could be evaluated as a possible screening tool for asymptomatic and early-stage NPC. (c) 2005 Wiley-Liss, Inc.
C1 NCI, DCEG, Genet Epidemiol Branch, NIH, Rockville, MD 20852 USA.
   Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan.
   Natl Taiwan Univ, Coll Med, Dept Microbiol, Taipei 10764, Taiwan.
   Westat Corp, Rockville, MD USA.
   Natl Inst Dent & Craniofacial Res, Craniofacial Epidemiol & Genet Branch, NIH, Bethesda, MD USA.
   NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA.
   Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
   Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
RP Yang, XHR (reprint author), NCI, DCEG, Genet Epidemiol Branch, NIH, Rm 7014,6120 Execut Blvd, Rockville, MD 20852 USA.
EM royang@mail.nih.gov
RI Chen, Chien-Jen/C-6976-2008
NR 33
TC 22
Z9 24
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 1
PY 2006
VL 118
IS 3
BP 780
EP 784
DI 10.1002/ijc.21396
PG 5
WC Oncology
SC Oncology
GA 000EO
UT WOS:000234443900035
PM 16106400
ER

PT J
AU Disis, ML
   Rivkin, SE
   Baron, A
   Markman, M
   Connolly, D
   Ueland, F
   Kohn, E
   Trimble, E
   Berek, JS
AF Disis, ML
   Rivkin, SE
   Baron, A
   Markman, M
   Connolly, D
   Ueland, F
   Kohn, E
   Trimble, E
   Berek, JS
TI Progress in ovarian cancer research: Proceedings of the 5th biennial
   ovarian cancer research symposium
SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
LA English
DT Review
DE cancer; ovarian; research; translational
ID GENE-EXPRESSION; RISK WOMEN; CARCINOMA; IDENTIFICATION; DIAGNOSIS;
   EVENTS; CA125; SERUM; DNA
AB Ovarian cancer remains the most lethal gynecological malignancy. The 5th Biennial Symposium overviewed the progress of ovarian cancer research over the last few years. Molecularly based technologies have allowed the identification of multiple biomarkers to aid in ovarian cancer diagnosis and treatment. Furthermore, data analysis systems evaluating the behavior of these markers have been designed. Therapeutic use of ovarian cancer protein markers has been fueled by the development of animal models that more closely simulate the pathogenesis of ovarian cancer, and multiple new therapies are being developed that may have impact against the disease. Finally, the design of clinical trials both for ovarian cancer treatment and prevention are key in advancing the science of ovarian cancer into the clinic. The need for strategies that would optimize patient participation in clinical trials is paramount.
C1 Univ Washington, Tumor Vaccine Grp, Seattle, WA 98109 USA.
   Swedish Med Ctr, Seattle, WA USA.
   Marsha Rivkin Ctr, Seattle, WA USA.
   Univ Kentucky, Lexington, KY 40506 USA.
   Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA.
   Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
   NCI, Bethesda, MD 20892 USA.
   Stanford Univ, Sch Med, Stanford Canc Ctr, Stanford, CA 94305 USA.
RP Disis, ML (reprint author), Univ Washington, Tumor Vaccine Grp, 815 Mercer St,2nd Floor, Seattle, WA 98109 USA.
EM ndisis@u.washington.edu
OI Baron, Andre/0000-0001-5901-6419
NR 20
TC 3
Z9 3
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1048-891X
J9 INT J GYNECOL CANCER
JI Int. J. Gynecol. Cancer
PD MAR-APR
PY 2006
VL 16
IS 2
BP 463
EP 469
DI 10.1111/j.1525-1438.2006.00559.x
PG 7
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 034PN
UT WOS:000236943200001
PM 16681712
ER

PT J
AU Deutsch, J
   Ma, KZ
   Rapoport, SI
AF Deutsch, J
   Ma, KZ
   Rapoport, SI
TI An accelerated mass spectrometric method for measuring myo-inositol in
   phosphatidylinositol in rat brain
SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
LA English
DT Article
DE rat brain; Folch extraction; phosphatidylinositol; myo-inositol;
   CI-GC-MS
ID LITHIUM
AB A fast and efficient chemical ionization mass spectrometric (CI-GC-MS) method for measuring myo-inositol in phosphatidylinositol (PtdIns) in rat brain has been developed. Previously, quantitation of PtdIns involved the release of the myo-inositol by two enzymatic reactions using phospholipase C and alkaline phosphatase. The hydrolytic action of these enzymes was replaced by using commercially available 48% hydrofluoric acid (HF) at 80 degrees C for 30 min. The process can be carried out on the crude Folch extract of brain phospholipids without prior thin layer chromatography (TLC) purification, thereby significantly increasing the speed of analysis. For quantification, unlabeled myo-inositol, labeled myo- and neo-inositol (internal standard) were converted to acetate derivatives and analyzed by CI-GC-MS. (c) 2005 Elsevier B.V. All rights reserved.
C1 Hebrew Univ Jerusalem, Sch Pharm, Dept Med Chem & Nat Prod, IL-91120 Jerusalem, Israel.
   NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Deutsch, J (reprint author), Hebrew Univ Jerusalem, Sch Pharm, Dept Med Chem & Nat Prod, IL-91120 Jerusalem, Israel.
EM odj@cc.huji.ac.il
NR 13
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1387-3806
J9 INT J MASS SPECTROM
JI Int. J. Mass Spectrom.
PD MAR 1
PY 2006
VL 249
BP 392
EP 395
DI 10.1016/j.ijms.2005.11.019
PG 4
WC Physics, Atomic, Molecular & Chemical; Spectroscopy
SC Physics; Spectroscopy
GA 022TO
UT WOS:000236079000047
ER

PT J
AU Sun, D
   Willingham, C
   Durrani, A
   King, P
   Cleary, K
   Wood, B
AF Sun, D
   Willingham, C
   Durrani, A
   King, P
   Cleary, K
   Wood, B
TI A novel end-effector design for robotics in image-guided needle
   procedures
SO INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY
LA English
DT Article
DE respiratory motion; bleeding; biopsy; ablation; end-effector
ID LIVER-BIOPSY
AB Background Robotic end-effectors are being developed to facilitate image-guided minimally invasive needle-based procedures, such as tumour ablation, biopsy, thoracentesis and blood sampling.
   Methods A novel mechanical end-effector was designed to address the challenges associated with any major needle-based procedure, focusing on liver biopsy and ablation. In this end-effector embodiment, the distal end of a single articulating arm can grip needles and instruments and allows a fairly high number of degrees of freedom of movement during the complex motions associated with positioning and driving needles, as well as the periodic motions associated with breathing patterns. Tightening a cable that runs through the articulations fixes the arm in a rigid state, allowing insertion of the gripped needle.
   Results A design is presented that will require electro-mechanical stimulation and remote joystick control. The associated forces of cranial-caudal motion of soft tissue organs affects design constraints. A simulation study defined the process with tissue phantoms with mechanical properties in the range of hepatic tissue and the overlying abdominal wall. The robotic arm coupled with our end-effector could be deployed in an image-guided interventional suite.
   Conclusions Such a switch-able and flexible mode for a robotic arm could overcome much of the current limitations for automated needle placements for mobile targets, and could mitigate risks from breathing or patient motion with a rigid needle gripper in place. Published in 2006 by John Wiley & Sons, Ltd.
C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA.
   Vanderbilt Univ, Dept Biomed Engn, Nashville, TN USA.
   Georgetown Univ, ISIS Ctr, Washington, DC USA.
RP Wood, B (reprint author), NIH, Dept Diagnost Radiol, Bldg 10, Bethesda, MD 20892 USA.
EM bwood@nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 9
TC 11
Z9 11
U1 3
U2 8
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1478-5951
J9 INT J MED ROBOT COMP
JI Int. J. Med. Robot. Comput. Assist. Surg.
PD MAR
PY 2006
VL 2
IS 1
BP 91
EP 97
DI 10.1002/rcs.66
PG 7
WC Surgery
SC Surgery
GA 044NG
UT WOS:000237678700014
PM 17520618
ER

PT J
AU Burke, TR
AF Burke, TR
TI Development of Grb2 SH2 domain signaling antagonists: A potential new
   class of antiproliferative agents
SO INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS
LA English
DT Article
DE Grb2; peptide mimetic; phosphotyrosyl; SH2 domain; signaling inhibitor
ID STRUCTURE-BASED DESIGN; CONSTRAINED PHOSPHOTYROSYL MIMETICS;
   PHOSPHATE-CONTAINING LIGANDS; RING-CLOSING METATHESIS; SRC HOMOLOGY-2
   DOMAIN; HIGH-AFFINITY; BINDING AFFINITY; STRUCTURAL BASIS; TYROSINE
   KINASE; TRANSDUCTION INHIBITORS
AB Aberrant Signaling through protein-tyrosine kinase (PTK)-dependent pathways is associated with several proliferative diseases. Accordingly, PTK inhibitors are being developed as new approaches for the treatment of certain cancers. Growth factor receptor bound protein 2 (Grb2) is an important downstream mediator of PTK Signaling that serves obligatory roles in many pathogenic processes. One of the primary functions of Grb2 is to bind to specific phosphotyrosyl (pTyr)-containing sequences through its Src homology 2 (SH2) domain. Agents that bind to the Grb2 SH2 domain and prevent its normal function could disrupt associated PTK Signaling and serve as alternatives to kinase-directed inhibitors. Starting from the X-ray crystal structure of a lead peptide bound to the Grb2 SH2 domain. this review will Summarize important contributions to these efforts. The presentation will be thematically arranged according to the region of peptide modified, proceeding from the N-terminus to the C-terminus, with a special section devoted to aspects of conformational constraint.
C1 Natl Canc Inst, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA.
RP Burke, TR (reprint author), Natl Canc Inst, Med Chem Lab, Canc Res Ctr, NIH, Bldg 376 Boyles St,POB B, Frederick, MD 21702 USA.
EM tburke@helix.nih.gov
RI Burke, Terrence/N-2601-2014
NR 63
TC 24
Z9 25
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 1573-3149
J9 INT J PEPT RES THER
JI Int. J. Pept. Res. Ther.
PD MAR
PY 2006
VL 12
IS 1
BP 33
EP 48
DI 10.1007/s10989-006-9014-7
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 034WE
UT WOS:000236960500004
ER

PT J
AU Krumpe, LRH
   Mori, T
AF Krumpe, LRH
   Mori, T
TI The use of phage-displayed peptide libraries to develop tumor-targeting
   drugs
SO INTERNATIONAL JOURNAL OF PEPTIDE RESEARCH AND THERAPEUTICS
LA English
DT Article
DE phage display; peptide; library; tumor; cancer; targeting; homing; drug;
   imaging, nanotechnology; biopanning; T7; M 13; lytic phage; filamentous
   phage
ID MONOCLONAL-ANTIBODIES; COMBINATORIAL LIBRARIES; HOMING PEPTIDE;
   CANCER-THERAPY; MOUSE MODEL; ZIP CODES; IN-VIVO; IDENTIFICATION;
   VASCULATURE; BINDING
AB Monoclonal antibodies have been successfully utilized as cancer-targeting therapeutics and diagnostics, but the efficacies of these treatments are limited in part by the size of the molecules and non-specific uptake by the reticuloendothelial system. Peptides are much smaller molecules that can specifically target cancer cells and as such may alleviate complications with antibody therapy. Although many endogenous and exogenous peptides have been developed into clinical therapeutics, only a subset of these consists of cancer-targeting peptides. Combinatorial biological libraries such as bacteriophage-displayed peptide libraries are a resource of potential ligands for various cancer-related molecular targets. Target-binding peptides can be affinity selected from complex mixtures of billions of displayed peptides on phage and further enriched through the biopanning process. Various cancer-specific ligands have been isolated by in vitro, in vivo, and ex vivo screening methods. As several peptides derived from phage-displayed peptide library screenings have been developed into therapeutics in current clinical trials, which validates peptide-targeting potential, the use of phage display to identify cancer-targeting therapeutics should be further exploited.
C1 Takeda Pharmaceut Co Ltd, Biomed Res Labs, Div Pharmaceut Res, Osaka 5328686, Japan.
   Sci Applicat Int Corp Frederick Inc, Basic Res Program, Frederick, MD USA.
   Natl Canc Inst, Mol Targets Dev Program, Canc Res Ctr, Frederick, MD USA.
RP Mori, T (reprint author), Takeda Pharmaceut Co Ltd, Biomed Res Labs, Div Pharmaceut Res, 2-17-85 Yodogawaku, Osaka 5328686, Japan.
EM Mori_Toshiyuki2@takeda.co.jp
NR 90
TC 48
Z9 48
U1 4
U2 19
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 1573-3149
J9 INT J PEPT RES THER
JI Int. J. Pept. Res. Ther.
PD MAR
PY 2006
VL 12
IS 1
BP 79
EP 91
DI 10.1007/s10989-005-9002-3
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 034WE
UT WOS:000236960500007
ER

PT J
AU Thayer, JF
   Hall, M
   Sollers, JJ
   Fischer, JE
AF Thayer, JF
   Hall, M
   Sollers, JJ
   Fischer, JE
TI Alcohol use, urinary cortisol, and heart rate variability in apparently
   healthy men: Evidence for impaired inhibitory control of the HPA axis in
   heavy drinkers
SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY
LA English
DT Article
DE cortisol; heart rate variability; alcohol; amygdala; prefrontal cortex
ID PREFRONTAL CORTEX; STRESS-RESPONSE; DYSREGULATION; DRINKING; BEHAVIOR;
   AMYGDALA; EMOTION; STIMULATION; ABSTINENCE; DEPRESSION
AB Alcoholism and heavy drinking are associated with a number of physiological, behavioral, affective, and cognitive problems. One Such problem involves dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, with alcoholics showing higher basal cortisol levels and reduced inhibitory feedback control. In addition, alcohol consumption is associated with decreased heart rate variability (HRV). In the present study we examined the relationships among alcohol consumption, cortisol excretion, and HRV in 542 apparently healthy men. Men in the top tertile of self-reported alcohol consumption had higher cortisol levels and lower HRV compared to men in the lower two tertiles of alcohol consumption. In addition, the inverse relationship between cortisol and HRV was greatly attenuated in the heavy drinking group even after accounting for a number of potential confounding factors. These results support prior research on the HPA axis dysregulation in alcoholics and suggest impaired inhibitory control of the HPA axis in heavy drinkers. The findings are consistent with the neurovisceral integration model, which links central and peripheral processes, and may provide a comprehensive framework for the future investigation of the complex mix of physiological, behavioral, affective, and cognitive factors which comprise the heavy drinking phenotype. (c) 2005 Published by Elsevier B.V.
C1 NIA, GRC, LPC, Baltimore, MD 21224 USA.
   Univ Pittsburgh, Pittsburgh, PA 15260 USA.
   Swiss Fed Inst Technol, Zurich, Switzerland.
RP Thayer, JF (reprint author), NIA, GRC, LPC, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM thayerj@grc.nia.nih.gov
RI Hall, Martica/D-2809-2012
OI Hall, Martica/0000-0003-0642-2098
NR 42
TC 76
Z9 78
U1 2
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-8760
J9 INT J PSYCHOPHYSIOL
JI Int. J. Psychophysiol.
PD MAR
PY 2006
VL 59
IS 3
BP 244
EP 250
DI 10.1016/j.ijpsycho.2005.10.013
PG 7
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
   Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA 025DI
UT WOS:000236245100008
PM 16325293
ER

PT J
AU Oh, DJ
   Martin, JL
   Williams, AJ
   Peck, RE
   Pokorny, C
   Russell, P
   Birk, DE
   Rhee, DJ
AF Oh, DJ
   Martin, JL
   Williams, AJ
   Peck, RE
   Pokorny, C
   Russell, P
   Birk, DE
   Rhee, DJ
TI Analysis of expression of matrix metalloproteinases and tissue
   inhibitors of metalloproteinases in human ciliary body after latanoprost
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; SMOOTH-MUSCLE-CELLS; AQUEOUS-HUMOR DYNAMICS;
   CYNOMOLGUS MONKEY EYES; HUMAN FETAL MEMBRANES; CULTURED HUMAN-CELLS;
   INTRAOCULAR-PRESSURE; EXTRACELLULAR-MATRIX; OCULAR HYPERTENSION;
   UVEOSCLERAL OUTFLOW
AB PURPOSE. To determine the effect of latanoprost on the expression of human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the ciliary body.
   METHODS. Total RNA was isolated, and qualitative RT-PCR was performed to detect the mRNA of MMPs and TIMPs in human ciliary body tissue and explant cultures of ciliary body smooth muscle (CBSM) cells. CBSM cell cultures were treated with vehicle control or latanoprost acid for 24 hours. Quantitative RT-PCR of cell cultures from five different donors was performed to determine relative changes in expression. GAPDH served as an endogenous control.
   RESULTS. The mRNA of MMP-1, -2, -3, -11, -12, -14, -15, -16, -17, -19, and -24 as well as TIMP-1 to -4 were found in ciliary body tissue and CBSM cells. MMP-9 was present after latanoprost treatment. In control CBSM cells, the relative expression of MMP mRNA was MMP-2 and -14 > MMP-24 > NIMP-1, -11, -15, -16, and -19 > MMP-3 and 17, > MMP-12. The relative expression of TIMP mRNA was TIMP-2 > TIMP- 1 > TIMP-3 > TIMP-4 Latanoprost increased MMP-3 (in three of five cultures) MMP-17 (in four of five cultures), and TIMP-3 (in all five cultures); MNIP-1, -2, -12, -14, -15, and -16 and TIMP-4 were downregulated.
   CONCLUSIONS. The transcription of the genes for MMP-3 and -17 is increased by latanoprost treatment. MMP-9 is present after latanoprost treatment and may also mediate ECM changes. TIMP-3 is upregulated and may compensate for the increase in MMPs. These coordinated changes could be expected to mediate the latanoprost-induced alteration of ECM in the ciliary body.
C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
   Wills Eye Hosp & Res Inst, Lab Mol Ophthalmol, Philadelphia, PA 19107 USA.
   NEI, Sect Aging & Ocular Dis, NIH, Bethesda, MD 20892 USA.
   Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
RP Rhee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
EM dougrhee@aol.com
RI Birk, David/I-4072-2012
OI Birk, David/0000-0002-4865-9088
FU NEI NIH HHS [EY 13997]
NR 80
TC 24
Z9 28
U1 0
U2 0
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2006
VL 47
IS 3
BP 953
EP 963
DI 10.1167/iovs.05-0516
PG 11
WC Ophthalmology
SC Ophthalmology
GA 020FR
UT WOS:000235894300027
PM 16505029
ER

PT J
AU Kukekova, AV
   Nelson, K
   Kuchtey, RW
   Lowe, JK
   Johnson, JL
   Ostrander, EA
   Aguirre, GD
   Acland, GM
AF Kukekova, AV
   Nelson, K
   Kuchtey, RW
   Lowe, JK
   Johnson, JL
   Ostrander, EA
   Aguirre, GD
   Acland, GM
TI Linkage mapping of canine rod cone dysplasia type 2 (rcd2) to CFA7, the
   canine orthologue of human 1q32
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID CYCLIC-NUCLEOTIDE-METABOLISM; RETINITIS-PIGMENTOSA; GENE-THERAPY;
   CGMP-PHOSPHODIESTERASE; ANIMAL-MODELS; INHERITED RETINOPATHY; RETINAL
   DEGENERATION; RCS RAT; GENOME; DOG
AB PURPOSE. To map the canine rcd2 retinal degeneration locus. Rod-cone dysplasia type 2 (rcd2), an early-onset autosomal recessive form of progressive retinal atrophy (PRA), is phenotypically similar to early-onset forms of retinitis pigmentosa collectively termed Leber congenital amaurosis and segregates naturally in the collie breed of dog. Multiple genes have previously been evaluated as candidates for rcd2, but all have been excluded.
   METHODS. A set of informative experimental pedigrees segregating the rcd2 phenotype was produced. A genome-wide scan of these pedigrees using a set of 241 markers was undertaken. To refine the localized homology between canine and human maps, an RH map of the identified rcd2 region was built using a 3000 cR panel. A positional candidate gene strategy was then undertaken to begin to evaluate potentially causative genes.
   RESULTs. A locus responsible for the rcd2 phenotype was mapped to CFA7 in a region corresponding to human chromosome 1, region q32.1-q32.2. Maximum linkage was observed between rcd2 and marker FH3972 (theta = 0.02; lod = 25.53), and the critical region was flanked by markers FH2226 and FH3972. As CRB1 is the closest gene on human chromosome 1q known to cause retinal degeneration, canine gene-specific markers for CRB1 were developed, and this gene was excluded as a positional candidate for rcd2.
   CONCLUSIONS. The rcd2 locus represents a novel retinal degeneration gene. It is anticipated that when identified, this gene will offer new insights into retinal developmental and degenerative processes, and new opportunities for exploring experimental therapies.
C1 Cornell Univ, Coll Vet Med, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA.
   Cole Eye Inst, Dept Ophthalmol, Cleveland, OH USA.
   Rockefeller Univ, New York, NY 10021 USA.
   NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
   Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA.
RP Acland, GM (reprint author), Cornell Univ, Coll Vet Med, James A Baker Inst Anim Hlth, Hungerford Hill Rd, Ithaca, NY 14853 USA.
EM gma2@cornell.edu
OI Johnson, Jennifer/0000-0002-3339-4419; Ostrander,
   Elaine/0000-0001-6075-9738
FU NEI NIH HHS [EY06855, EY13132, EY13729]; NIMH NIH HHS [MH069688]
NR 45
TC 9
Z9 11
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD MAR
PY 2006
VL 47
IS 3
BP 1210
EP 1215
DI 10.1167/iovs.05-0861
PG 6
WC Ophthalmology
SC Ophthalmology
GA 020FR
UT WOS:000235894300058
PM 16505060
ER

PT J
AU Anderson, SA
   Lee, KK
   Frank, JA
AF Anderson, SA
   Lee, KK
   Frank, JA
TI Gadolinium-fullerenol as a paramagnetic contrast agent for cellular
   imaging
SO INVESTIGATIVE RADIOLOGY
LA English
DT Article
DE gadolinium; fullerenes; fullerenols; cellular imaging; stem cells
ID WATER-SOLUBLE METALLOFULLERENES; MESENCHYMAL STEM-CELLS;
   MAGNETIC-RESONANCE; IN-VIVO; MULTIPLE-SCLEROSIS; MRI; TRACKING;
   RELAXIVITY; MODEL
AB Objectives: The objectives of this study were to test cell-labeling methods to achieve intracellular labeling and T1 enhancement of cells on magnetic resonance imaging using a paramagnetic Gd@C82 fullerenol contrast agent, and to determine the effect of labeling on cell viability, metabolism, and differentiation capacity.
   Materials and Methods: We tested the use of a transfection agent for labeling cells in culture with Gd@C82 fullerenol. Proliferation, viability, and differentiation assays of mesenchymal stem cell (MSC) cultures; light and electron microscopy of MSC and macrophages; and MRI of MSC, macrophage, and HeLa cervical carcinoma cell cultures in vitro and in vivo were performed to evaluate the labeled cells.
   Results: Prolamine sulfate transfection increased cell uptake oil Gd@C82 fullerenols. The label was distributed in endosomes in the cytoplasm as shown by electron microscopy. High viability was shown for all cell lines and normal differentiation capacity was shown for MSCs. T1 of labeled MSC at 7 T was reduced 71% compared with unlabeled cells.
   Conclusions: Cellular labeling with Gd@C82 is feasible and can produce T1-enbanced cells on magnetic resonance imaging. This study suggests that further investigation of Gd fullerenols for tracking studies of viable cells, including stem cells, is warranted.
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
   NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA.
RP Anderson, SA (reprint author), NHLBI, NIH, 10 Ctr Dr,Bldg 10,Room 2N240, Bethesda, MD 20892 USA.
EM andersos1@nhlbi.nih.gov
NR 22
TC 92
Z9 93
U1 0
U2 21
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-9996
J9 INVEST RADIOL
JI Invest. Radiol.
PD MAR
PY 2006
VL 41
IS 3
BP 332
EP 338
DI 10.1097/01.rli.0000192420.94038.9e
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 016PR
UT WOS:000235632800017
PM 16481917
ER

PT J
AU Keller, C
   Allan, J
   Tinkle, MB
AF Keller, C
   Allan, J
   Tinkle, MB
TI Stages of change, processes of change, and social support for exercise
   and weight gain in postpartum women
SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING
LA English
DT Article
DE exercise; physical activity; postpartum weight; social support
ID CORONARY HEART-DISEASE; PHYSICAL-ACTIVITY; AFRICAN-AMERICAN;
   TRANSTHEORETICAL MODEL; BEHAVIORAL-FACTORS; MINORITY WOMEN; HISPANIC
   WOMEN; RISK-FACTORS; PREGNANCY; ADULTS
AB Objectives: To test the extent to which social support and variables included in the Transtheoretical Model were explanatory for exercise initiation and weight maintenance in postpartum women.
   Design: A cross-sectional descriptive design.
   Setting: Data were collected in the participant's homes.
   Participants: Postpartum women who had normal pregnancies were interviewed and measured on body fat, physical activity, and psychosocial scales.
   Main Outcome Measure: (a) Stages of exercise change measure, (b) Seven Day Recall, (c) Friend and Family Support for Exercise Scale, (d) Processes of Change Questionnaire, and (e) body fat measures including body mass index and percent body fat.
   Results: Forty percent reported engaging in vigorous activity less than 1 hour daily, 55% walked less than four city blocks daily, and 52% engaged in less than 2 hours of vigorous weekend activity. Multilinear regression showed that the processes of change contributed 36% to the body mass index, and 21% of the variance in waist-thigh ratio. Of the processes of change, environmental reevaluation correlated significantly with body mass index.
   Conclusion: The impact of a woman's weight on others as well as information concerning the health effects of obesity and physical activity could enhance the initiation of exercise in the postpartum woman.
C1 Arizona State Univ, Coll Nursing, Ctr Improving Hlth Outcomes Aging, Tempe, AZ 85287 USA.
   Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA.
   NINR, NIH, Bethesda, MD 20892 USA.
RP Keller, C (reprint author), Arizona State Univ, Coll Nursing, Ctr Improving Hlth Outcomes Aging, Tempe, AZ 85287 USA.
EM Colleen.Keller@asu.edu
NR 54
TC 18
Z9 18
U1 6
U2 10
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0884-2175
J9 JOGNN-J OBST GYN NEO
JI JOGNN
PD MAR-APR
PY 2006
VL 35
IS 2
BP 232
EP 240
DI 10.1111/J.1552-6909.2006.00030.x
PG 9
WC Nursing; Obstetrics & Gynecology
SC Nursing; Obstetrics & Gynecology
GA 027CP
UT WOS:000236391600010
PM 16620249
ER

PT J
AU Wiener, LS
   Battles, HB
AF Wiener, LS
   Battles, HB
TI Untangling the web: A close look at diagnosis disclosure among
   HIV-infected adolescents
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE HIV-positive adolescents; diagnosis disclosure; posttraumatic stress
   symptoms; psychological distress
ID CHILDREN
AB As children living with human immunodeficiency virus (HIV) survive into adolescence and young adulthood, attention to the relationship of diagnosis disclosure to psychological functioning, interpersonal relationships, and HIV prevention is needed. This exploratory study describes the level of adolescents' diagnosis disclosure to family, friends, and potential sexual partners, and the relationship between disclosure and psychosocial variables. (c) 2006 Society for Adolescent Medicine. All rights reserved.
C1 NCI, NIH, Bethesda, MD 20892 USA.
RP Wiener, LS (reprint author), NCI, NIH, 9000 Rockville Pike,Bldg 10-10S255, Bethesda, MD 20892 USA.
EM wienerl@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 10
TC 41
Z9 43
U1 1
U2 4
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 MAR
PY 2006
VL 38
IS 3
BP 307
EP 309
DI 10.1016/j.jadohealth.2005.03.024
PG 3
WC Psychology, Developmental; Public, Environmental & Occupational Health;
   Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 019EA
UT WOS:000235817200023
PM 16488835
ER

PT J
AU Danshina, P
   Geyer, CB
   Dai, QS
   Goulding, EH
   Willis, WD
   McCarrey, JR
   Eddy, EM
   O'Brien, DA
AF Danshina, P
   Geyer, CB
   Dai, QS
   Goulding, EH
   Willis, WD
   McCarrey, JR
   Eddy, EM
   O'Brien, DA
TI Male fertility and sperm function are severely impaired in mice lacking
   phosphoglycerate kinase-2
SO JOURNAL OF ANDROLOGY
LA English
DT Meeting Abstract
CT 31st Annual Meeting of the American-Society-of-Andrology
CY APR 08-11, 2006
CL Chicago, IL
SP Amer Soc Androl
C1 Univ N Carolina, Sch Med, Dept Cell & Dev Biol, Labs Reprod Biol, Chapel Hill, NC USA.
   Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA.
   NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
   Univ Texas, Dept Biol, San Antonio, TX 78285 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC ANDROLOGY, INC
PI LAWRENCE
PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA
SN 0196-3635
J9 J ANDROL
JI J. Androl.
PD MAR-APR
PY 2006
SU S
MA 3
BP 35
EP 35
PG 1
WC Andrology
SC Endocrinology & Metabolism
GA 017IV
UT WOS:000235688200006
ER

PT J
AU Danshina, P
   Geyer, CB
   Dai, QS
   Goulding, EH
   Willis, WD
   McCarrey, JR
   Eddy, EM
   O'Brien, DA
AF Danshina, P
   Geyer, CB
   Dai, QS
   Goulding, EH
   Willis, WD
   McCarrey, JR
   Eddy, EM
   O'Brien, DA
TI Male fertility and sperm function are severely impaired in mice lacking
   phosphoglycerate kinase-2
SO JOURNAL OF ANDROLOGY
LA English
DT Meeting Abstract
CT 31st Annual Meeting of the American-Society-of-Andrology
CY APR 08-11, 2006
CL Chicago, IL
SP Amer Soc Androl
C1 Univ N Carolina, Sch Med, Dept Cell & Dev Biol, Labs Reprod Biol, Chapel Hill, NC USA.
   Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA.
   NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
   Univ Texas, Dept Biol, San Antonio, TX 78285 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC ANDROLOGY, INC
PI LAWRENCE
PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA
SN 0196-3635
J9 J ANDROL
JI J. Androl.
PD MAR-APR
PY 2006
SU S
MA 22
BP 44
EP 44
PG 1
WC Andrology
SC Endocrinology & Metabolism
GA 017IV
UT WOS:000235688200025
ER

PT J
AU Nakamura, N
   O'Brien, DA
   Eddy, EM
AF Nakamura, N
   O'Brien, DA
   Eddy, EM
TI Modifications of the mouse spermatogenic cell-specific type 1 hexokinase
   (HK1S) enzyme in sperm activation
SO JOURNAL OF ANDROLOGY
LA English
DT Meeting Abstract
CT 31st Annual Meeting of the American-Society-of-Andrology
CY APR 08-11, 2006
CL Chicago, IL
SP Amer Soc Androl
C1 Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA.
   Univ N Carolina, Sch Med, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC ANDROLOGY, INC
PI LAWRENCE
PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA
SN 0196-3635
J9 J ANDROL
JI J. Androl.
PD MAR-APR
PY 2006
SU S
MA 76
BP 68
EP 68
PG 1
WC Andrology
SC Endocrinology & Metabolism
GA 017IV
UT WOS:000235688200080
ER

PT J
AU El-Amin, SF
   Botchwey, E
   Tuli, R
   Kofron, MD
   Mesfin, A
   Sethuraman, S
   Tuan, RS
   Laurencin, CT
AF El-Amin, SF
   Botchwey, E
   Tuli, R
   Kofron, MD
   Mesfin, A
   Sethuraman, S
   Tuan, RS
   Laurencin, CT
TI Human osteoblast cells: isolation, characterization, and growth on
   polymers for musculoskeletal tissue engineering
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
LA English
DT Article
DE human osteoblasts; bone; tissue engineering; polymers; integrins;
   extracellular matrix
ID HUMAN-BONE CELLS; BIOERODIBLE POLYMERS; INTEGRIN EXPRESSION; POLY(LACTIC
   ACID); IMPLANT MATERIALS; DELIVERY-SYSTEMS; STEM-CELLS;
   BIOCOMPATIBILITY; DEGRADATION; CULTURE
AB We performed a detailed examination of the isolation, characterization, and growth of human osteoblast cells derived from trabecular bone. We further examined the morphology, phenotypic gene expression, mineralization, and growth of these human osteoblasts on polyester polymers used for musculoskeletal tissue engineering. Polylactic-co-glycolic acid [PLAGA (85:15, 50:50, 75:25)], and polylactic acid (L-PLA, D,L-PLA) were examined. The osteoblastic expression of key phenotypic markers osteocalcin, alkaline phosphatase, collagen, and bone sialoprotein at 4 and 8 weeks was examined. Reverse transcription-polymerase chain reaction studies revealed that trabecular-derived osteoblasts were positive for all markers evaluated with higher levels expressed over long-term culture. These cells also revealed mineralization and maturation as evidenced by energy dispersive X-ray analysis and scanning electron microscopy. Growth studies on PLAGA at 50:50, 75:25, and 85:15 ratios and PLA in the L and DL isoforms revealed that human osteoblasts actively grew, with significantly higher cell numbers attached to scaffolds composed of PLAGA 50:50 in the short term and PLAGA 85:15 in the long term compared with PLA (p < 0.05). We believe human cell adhesion among these polymeric materials may be dependent on differences in cellular integrin expression and extracellular matrix protein elaboration. (C) 2005 Wiley Periodicals, Inc.
C1 Univ Virginia, Dept Orthopaed Surg, Charlottesville, VA 22903 USA.
   Univ Virginia, Dept Chem Engn, Charlottesville, VA 22903 USA.
   NIAMSD, Cartilage Biol & Orthopaed Branch, Bethesda, MD 20892 USA.
   Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22903 USA.
RP Laurencin, CT (reprint author), Univ Virginia, Dept Orthopaed Surg, 400 Ray C Hunt Dr,Suite 330, Charlottesville, VA 22903 USA.
EM ctl3f@virginia.edu
FU NIAMS NIH HHS [AR050704]
NR 48
TC 27
Z9 32
U1 1
U2 6
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1549-3296
J9 J BIOMED MATER RES A
JI J. Biomed. Mater. Res. Part A
PD MAR 1
PY 2006
VL 76A
IS 3
BP 439
EP 449
DI 10.1002/jbm.a.30411
PG 11
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 013AY
UT WOS:000235383200001
PM 16541483
ER

PT J
AU Henrich, CJ
   Bokesch, HR
   Dean, M
   Bates, SE
   Robey, RW
   Goncharova, EI
   Wilson, JA
   McMahon, JB
AF Henrich, CJ
   Bokesch, HR
   Dean, M
   Bates, SE
   Robey, RW
   Goncharova, EI
   Wilson, JA
   McMahon, JB
TI A high-throughput cell-based assay for inhibitors of ABCG2 activity
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE ABCG2; pheophorbide a; drug resistance
ID CANCER RESISTANCE PROTEIN; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN;
   DRUG-RESISTANCE; STEM-CELLS; TRANSPORTERS; MUTATIONS; BIOAVAILABILITY;
   SPECIFICITY; MODULATION
AB ABCG2 is a member of the adenosine triphosphate (ATP)-binding cassette family of multidrug transporters associated with resistance of tumor cells to many cytotoxic agents. Evaluation of modulators of ABCG2 activity has relied on methods such as drug sensitization, biochemical characterization, and transport studies. To search for novel inhibitors of ABCG2, a fluorescent cell-based assay was developed for application in high-throughput screening. Accumulation of pheophorbide a (PhA), an ABCG2-specific substrate, forms the basis for the assay in NCI-H460/MX20 cells overexpressing wild-type ABCG2. Treatment of these cells with 10 mu M fumitremorgin C (FTC), a specific ABCG2 inhibitor, increased cell accumulation of PhA to 5.6 times control (Z'0.5). Validation included confirmation with known ABCG2 inhibitors: FTC, novobiocin, tariquidar, and quercetin. Verapamil, reported to inhibit P-glycoprotein but not ABCG2, had insignificant activity. Screening of a library of 3523 natural products identified 11 compounds with high activity (>= 50% of FTC, confirmed by reassay), including 3 flavonoids, members of a family of compounds that include ABCG2 inhibitors. One of the inhibitors detected, eupatin, was moderately potent (IC50 of 2.2 mu M) and, like FTC, restored sensitivity of resistant cells to mitoxantrone. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel inhibitors of ABCG2 activity.
C1 NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
   NCI, Mol Targets Dev Program, Frederick, MD 21702 USA.
RP Henrich, CJ (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Bldg 560,Room 32-63A, Frederick, MD 21702 USA.
EM henrichc@ncifcrf.gov
RI Dean, Michael/G-8172-2012
OI Dean, Michael/0000-0003-2234-0631
FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]
NR 36
TC 56
Z9 61
U1 0
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD MAR
PY 2006
VL 11
IS 2
BP 176
EP 183
DI 10.1177/1087057105284576
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Chemistry
GA 023SP
UT WOS:000236146800008
PM 16490770
ER

PT J
AU Freeman, HP
AF Freeman, Harold P.
TI Patient navigation: A community centered approach to reducing cancer
   mortality
SO JOURNAL OF CANCER EDUCATION
LA English
DT Article; Proceedings Paper
CT 9th Biennial Symposium on Minorities, The Medically Underserved, and
   Cancer, Intercultural Cancer Council
CY MAR 24-28, 2004
CL Washington, DC
AB Background. Profound advances in biomedical science have contributed to increased longevity and improved quality of life for many Americans. Despite this progress, a heavier burden of disease is borne by some population groups in the United States, particularly the poor and underserved. Landmark reports published since 1973 have highlighted these health disparities, explored their causal factors, and outlined strategies to reduce them. More recent research studies underscore the results of these early reports that identify social position, economic status, culture, and environment as critical determinants of who develops and survives cancer and of the quality of life of cancer survivors. Methods. The Patient Navigation Program was established in Harlem, New York, in 1990 to address the dramatic disparities in breast cancer mortality among minority women in the community. Results and Conclusions. The success of the Harlem Patient Navigation Program has provided the impetus for the development of many similar patient navigation programs across the country and for federal support for Patient Navigation research to address the critical need for effective interventions to eliminate cancer health disparities, particularly among minorities and the underserved.
C1 NCI, Ctr Reduce Canc Hlth Dispar, Rockville, MD 20852 USA.
   NIH, Bethesda, MD 20892 USA.
RP Freeman, HP (reprint author), NCI, Ctr Reduce Canc Hlth Dispar, 6116 Execut Blvd,Suite 602,MSC 8341, Rockville, MD 20852 USA.
EM dayej@od.nci.nih.gov
NR 9
TC 78
Z9 79
U1 0
U2 6
PU LAWRENCE ERLBAUM ASSOC INC
PI MAHWAH
PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA
SN 0885-8195
J9 J CANCER EDUC
JI J. Cancer Educ.
PD SPR
PY 2006
VL 21
IS 1
SU S
BP S11
EP S14
DI 10.1207/s15430154jce2101s_4
PG 4
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
   Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
   Occupational Health
GA 086QR
UT WOS:000240688600004
PM 17020496
ER

PT J
AU von Eschenbach, AC
AF von Eschenbach, Andrew C.
TI Susan Matsuko Shinagawa Cancer Control Leadership Award Luncheon,
   Keynote Speaker: A time when no one suffers or dies from cancer
SO JOURNAL OF CANCER EDUCATION
LA English
DT Article; Proceedings Paper
CT 9th Biennial Symposium on Minorities, The Medically Underserved, and
   Cancer, Intercultural Cancer Council
CY MAR 24-28, 2004
CL Washington, DC
C1 NCI, NIH, DHHS, Bethesda, MD 20892 USA.
RP von Eschenbach, AC (reprint author), NCI, NIH, DHHS, 31 Ctr Dr,Bldg 31,Room 11A48, Bethesda, MD 20892 USA.
EM hackettd@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU LAWRENCE ERLBAUM ASSOC INC
PI MAHWAH
PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA
SN 0885-8195
J9 J CANCER EDUC
JI J. Cancer Educ.
PD SPR
PY 2006
VL 21
IS 1
SU S
BP S9
EP S10
DI 10.1207/s15430154jce2101s_3
PG 2
WC Oncology; Education, Scientific Disciplines; Public, Environmental &
   Occupational Health
SC Oncology; Education & Educational Research; Public, Environmental &
   Occupational Health
GA 086QR
UT WOS:000240688600003
ER

PT J
AU Urzua, U
   Roby, KF
   Gangi, LM
   Cherry, JM
   Powell, JI
   Munroe, DJ
AF Urzua, U
   Roby, KF
   Gangi, LM
   Cherry, JM
   Powell, JI
   Munroe, DJ
TI Transcriptomic analysis of an in vitro murine model of ovarian
   carcinoma: Functional similarity to the human disease and identification
   of prospective tumoral markers and targets
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID GLUTATHIONE-S-TRANSFERASE; COLLAGEN-VI DEFICIENCY; CANCER-CELLS;
   EXTRACELLULAR-MATRIX; BREAST-CANCER; CYTOCHROME P450CYP1B1; PROGNOSTIC
   INDICATOR; JANUS KINASE-2; MOUSE MODEL; EXPRESSION
AB Ovarian cancer is an aggressive disease of poor prognostic when detected at advanced stage. it is widely accepted that the ovarian surface epithelium plays a central role in disease etiology, but little is known about disease progression at the molecular level. To identify genes involved in ovarian tumorigenesis, we carried out a genome-wide transcriptomic analysis of six spontaneously transformed mouse ovarian surface epithelial (MOSE) cell lines, an in vitro model for human ovarian carcinoma. Loess normalization followed by statistical analysis with control of multiple testing resulted in 509 differentially expressed genes using an adjusted P-value <= 0.05 as cut-off. The top 20 differentially expressed genes included 10 genes (Spp1, Cyp1b1, Btg1, Cfh, Mt1, Mt2, lgfbp5, Gstm1, Gstm2, and Esr1) implicated in various aspects of ovarian carcinomas, and other 3 genes (Gsto1, Lcn7, and Alcam) associated to breast cancer. Upon functional analysis, the majority of alterations affected genes involved in glutathione metabolism and MAPK signaling pathways. Interestingly, over 20% of the aberrantly expressed genes were related to extracellular components, suggestive of potential markers of disease progression. In addition, we identified the genes Pura, Cnn3, Arpc1b, Map4k4, Tgfb1i4, and Crsp2 correlated to in vivo tumorigenic parameters previously reported for these cells. Taken together, our findings support the utility of MOSE cells in studying ovarian cancer biology and as a source of novel diagnostic and therapeutic targets.
C1 Univ Chile, Inst Ciencias Biomed, Programa Biol Celular & Mol, Santiago, Chile.
   Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66103 USA.
   NCI, Lab Mol Technol, SAIC Frederick Inc, Frederick, MD 21701 USA.
   NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Urzua, U (reprint author), Univ Chile, Inst Ciencias Biomed, Programa Biol Celular & Mol, Independencia 1027, Santiago, Chile.
EM uurzua@med.uchile.cl
RI Urzua, Ulises/A-3982-2013; 
OI Urzua, Ulises/0000-0003-0522-5754
FU NCI NIH HHS [N01-CO-12400]
NR 84
TC 27
Z9 29
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0021-9541
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD MAR
PY 2006
VL 206
IS 3
BP 594
EP 602
DI 10.1002/jcp.20522
PG 9
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 009ZN
UT WOS:000235152400005
PM 16245302
ER

PT J
AU Schraml, FV
   Beason-Held, LL
   Fletcher, DW
   Brown, BP
AF Schraml, FV
   Beason-Held, LL
   Fletcher, DW
   Brown, BP
TI Cerebral accumulation of Tc-99m ethyl cysteinate dimer (ECD) in severe,
   transient hypothyroidism
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE depression; hypothyroidism; metabolism; imaging; radiopharmaceutical
ID POSITRON-EMISSION-TOMOGRAPHY; TREATMENT-RESISTANT DEPRESSION;
   BLOOD-FLOW; DISORDER PATIENTS; THYROID-HORMONE; MOOD DISORDERS; PANIC
   DISORDER; BRAIN ACTIVITY; HEART-RATE; METABOLISM
AB Thyroid dysfunction is a well-known contributor to psychiatric morbidity. To investigate the mechanism(s) by which thyroid hormone availability affects cerebral activity, a group of thyroidectomized individuals were studied at two points in time: when markedly hypothyroid in preparation for a thyroid cancer metastatic survey and when clinically and/or biochemically euthyroid. The analysis consisted of single photon emission computed tomography (SPECT) using a lipophilic radiopharmaceutical, technetium-99m (Tc-99m) ethyl cysteinate dimer (ECD), and measurement of mood, anxiety, and psychomotor function, at both points in time. Both increases and decreases in regional cerebral radiotracer activity were found in the hypothyroid condition relative to the euthyroid condition, and the neuropsychological assessment demonstrated significantly greater depression, anxiety, and psychomotor slowing during the hypothyroid state. Increased radiotracer activity was seen in frontal and temporal regions, posterior cingulate gyrus, thalamus, and putamen. Decreased activity was seen in the occipital cortex, and the pre- and postcentral gyri. This distribution pattern is partially consistent with findings in persons with depression and anxiety unrelated to thyroid disease, supporting the link between the symptoms observed in our subjects and their marked hypothyroidism. Finally, these results support the need to consider the effect of the thyroid state on cellular mechanisms of uptake and retention of cerebral blood flow radiopharmaceuticals when studying 'noneuthyroid' individuals.
C1 Natl Naval Med Res Inst, Dept Radiol, Bethesda, MD USA.
   Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA.
   Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA.
   Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Div Nucl Med, Baltimore, MD 21205 USA.
   NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA.
RP Schraml, FV (reprint author), Natl Naval Med Res Inst, Dept Radiol, 205 Piping Rock Dr, Silver Spring, MD 20905 USA.
EM fvschraml@bethesda.med.navy.mil
NR 64
TC 15
Z9 16
U1 2
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD MAR
PY 2006
VL 26
IS 3
BP 321
EP 329
DI 10.1038/sj.jcbfm.9600191
PG 9
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA 021IA
UT WOS:000235975700003
PM 16079789
ER

PT J
AU Nemukhin, AV
   Topol, IA
   Burt, SK
AF Nemukhin, AV
   Topol, IA
   Burt, SK
TI Electronic excitations of the chromophore from the fluorescent protein
   asFP595 in solutions
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID DENSITY-FUNCTIONAL THEORY; PROTONATION STATES; ANEMONIA-SULCATA; RED;
   GFP; ABSORPTION; RESOLUTION; MOLECULES; ENERGIES
AB We present the results of modeling spectral properties of the chromophore, 2-acetyl-4-(p-hydroxybenzylidene)-l -methyl-5-imidazolone (AHBMI), from the newly discovered fluorescent protein asFP595 in different solvents and compare computational and recent experimental data. The time-dependent density functional theory (TDDFT) method is used to estimate positions of spectral bands with large oscillator strengths for vertical transitions to excited states following geometry optimizations of chromophore coordinates in vacuo and in solutions. The performance of different TDDFT functionals in computing excitations for a simpler chromophore from the green fluorescent protein was tested at the preliminary stage. Properties of various protonation states (neutral, anionic, zwitterionic) for the cis and trans conformations of AHBMI are compared. By using the polarizable continuum model, the following solvents have been considered for AHBMI: water, ethanol, acetonitrile, and dimethyl sulfoxide. It is shown that the bands found experimentally in aqueous solution refer to the cis neutral and cis anionic (or trans zwitterionic) conformations. The computed band positions deviate from experimental ones in water by no more than 35 nm (0.23 eV). In accord with experimental studies, the band shifts in different solvents do not show correlation with the dielectric constant or dipole moment; however, the computed values of the shifts are much smaller than those measured experimentally for the ionic species.
C1 Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia.
   Russian Acad Sci, Inst Biochem Phys, Moscow 119997, Russia.
   NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
RP Nemukhin, AV (reprint author), Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia.
EM anem@lcc.chem.msu.ru
RI Nemukhin, Alexander/P-9662-2015
NR 35
TC 38
Z9 38
U1 0
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD MAR-APR
PY 2006
VL 2
IS 2
BP 292
EP 299
DI 10.1021/ct050243n
PG 8
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 022LF
UT WOS:000236056600010
PM 26626517
ER

PT J
AU Blair, RJR
   Peschardt, KS
   Budhani, S
   Mitchell, DGV
   Pine, DS
AF Blair, RJR
   Peschardt, KS
   Budhani, S
   Mitchell, DGV
   Pine, DS
TI The development of psychopathy
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Review
ID POSITRON-EMISSION-TOMOGRAPHY; MINOR PHYSICAL ANOMALIES;
   ANTISOCIAL-BEHAVIOR; CRIMINAL PSYCHOPATHS; FACIAL EXPRESSIONS;
   PERSONALITY-TRAITS; CONDUCT PROBLEMS; ORBITOFRONTAL CORTEX; COMMUNITY
   VIOLENCE; HUMAN-AGGRESSION
AB The current review focuses on the construct of psychopathy, conceptualized as a clinical entity that is fundamentally distinct from a heterogeneous collection of syndromes encompassed by the term 'conduct disorder'. We will provide an account of the development of psychopathy at multiple levels: ultimate causal (the genetic or social primary cause), molecular, neural, cognitive and behavioral. The following main claims will be made: (1) that there is a stronger genetic as opposed to social ultimate cause to this disorder. The types of social causes proposed (e.g., childhood sexual/physical abuse) should elevate emotional responsiveness, not lead to the specific form of reduced responsiveness seen in psychopathy; (2) The genetic influence leads to the emotional dysfunction that is the core of psychopathy; (3) The genetic influence at the molecular level remains unknown. However, it appears to impact the functional integrity of the amygdala and orbital/ventrolateral frontal cortex (and possibly additional systems); (4) Disruption within these two neural systems leads to impairment in the ability to form stimulus-reinforcement associations and to alter stimulus-response associations as a function of contingency change. These impairments disrupt the impact of standard socialization techniques and increase the risk for frustration-induced reactive aggression respectively.
C1 NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
   UCL, Dept Psychol, London, England.
RP Blair, RJR (reprint author), NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, Dept Hlth & Human Serv,NIH, 15K N Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA.
EM blairj@intra.nimh.nih.gov
FU Intramural NIH HHS
NR 127
TC 214
Z9 216
U1 22
U2 143
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0021-9630
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD MAR-APR
PY 2006
VL 47
IS 3-4
BP 262
EP 275
DI 10.1111/j.1469-7610.2006.01596.x
PG 14
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 014RV
UT WOS:000235498500003
PM 16492259
ER

PT J
AU Schroeder, PR
   Haugen, BR
   Pacini, F
   Reiners, C
   Schlumberger, M
   Sherman, SI
   Cooper, DS
   Schuff, KG
   Braverman, LE
   Skarulis, MC
   Davies, TF
   Mazzaferri, EL
   Daniels, GH
   Ross, DS
   Luster, M
   Samuels, MH
   Weintraub, BD
   Ridgway, EC
   Ladenson, PW
AF Schroeder, PR
   Haugen, BR
   Pacini, F
   Reiners, C
   Schlumberger, M
   Sherman, SI
   Cooper, DS
   Schuff, KG
   Braverman, LE
   Skarulis, MC
   Davies, TF
   Mazzaferri, EL
   Daniels, GH
   Ross, DS
   Luster, M
   Samuels, MH
   Weintraub, BD
   Ridgway, EC
   Ladenson, PW
TI A comparison of short-term changes in health-related quality of life in
   thyroid carcinoma patients undergoing diagnostic evaluation with
   recombinant human thyrotropin compared with thyroid hormone withdrawal
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article; Proceedings Paper
CT 87th Annual Meeting of the Endocrine-Society
CY JUN 04-07, 2005
CL San Diego, CA
SP Endocrine Soc
ID SURVEY SF-36; MEDICAL OUTCOMES; CANCER; THERAPY; DISCONTINUATION;
   HYPOTHYROIDISM; TESTS; CARE
AB Context: Thyroid carcinoma requires lifelong monitoring with serum thyroglobulin, radioactive iodine whole body scanning, and other imaging modalities. Levothyroxine (L-T(4)) withdrawal for thyroglobulin measurement and whole body scanning increases these tests' sensitivities but causes hypothyroidism. Recombinant human TSH (rhTSH) enables testing without L-T(4) withdrawal.
   Objective: Our objective was to examine the impact of short-term hypothyroidism on the health-related quality of life (HRQOL) of patients after rhTSH vs. L-T(4) withdrawal.
   Design, Setting, and Patients: In this multicenter study, the SF-36 Health Survey was administered to 228 patients at three time points: on L-T(4), after rhTSH, and after L-T(4) withdrawal.
   Interventions: Interventions included administration of rhTSH on L-T(4) and withdrawal from thyroid hormone.
   Main Outcome Measures: Mean SF-36 scores were compared during the two interventions and with the U. S. general population and patients with heart failure, depression, and migraine headache.
   Results: Patients had SF-36 scores at or above the norm for the general U. S. population in six of eight domains at baseline on L-T4 and in seven of eight domains after rhTSH. Patients' scores declined significantly in all eight domains after L-T(4) withdrawal when compared with the other two periods (P<0.0001). Patients' HRQOL scores while on L-T(4) and after rhTSH were at or above those for patients with heart failure, depression, and migraine in all eight domains. After L-T(4) withdrawal, patients' HRQOL scores were significantly below congestive heart failure, depression, and migraine headache norms in six, three, and six of the eight domains, respectively.
   Conclusions: Short-term hypothyroidism after L-T(4) withdrawal is associated with a significant decline in quality of life that is abrogated by rhTSH use.
C1 Johns Hopkins Med Inst, Div Endocrinol & Metab, Baltimore, MD 21287 USA.
   Univ Colorado, Hlth Sci Ctr, Div Endocrinol, Denver, CO 80262 USA.
   Univ Siena, Div Endocrinol & Metab, I-53100 Siena, Italy.
   Univ Wurzburg, Nukl Med Klin & Poliklin, D-97070 Wurzburg, Germany.
   Inst Gustave Roussy, Nucl Med Serv, F-94805 Villejuif, France.
   Univ Texas, MD Anderson Canc Ctr, Dept Med Specialties, Houston, TX 77030 USA.
   Sinai Hosp, Div Endocrinol, Baltimore, MD 21215 USA.
   Oregon Hlth & Sci Univ, Div Endocrinol, Portland, OR 97201 USA.
   Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA.
   NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
   CUNY Mt Sinai Sch Med, Div Endocrinol, New York, NY 10029 USA.
   Univ Florida, Shands Hosp, Div Endocrinol, Gainesville, FL 32610 USA.
   Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA.
   Trophogen Inc, Rockville, MD 20850 USA.
RP Ladenson, PW (reprint author), Johns Hopkins Med Inst, Div Endocrinol & Metab, 1830 E Monument St,Suite 333, Baltimore, MD 21287 USA.
EM ladenson@jhmi.edu
OI Sherman, Steven/0000-0002-3079-5153; Braverman,
   Lewis/0000-0003-1263-1099
FU NIDDK NIH HHS [T32DK62707]
NR 24
TC 110
Z9 114
U1 1
U2 3
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2006
VL 91
IS 3
BP 878
EP 884
DI 10.1210/jc.2005-2064
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 020DX
UT WOS:000235889700025
PM 16394083
ER

PT J
AU Denny, CC
   Emanuel, EJ
AF Denny, CC
   Emanuel, EJ
TI "Physician-assisted suicide among Oregon cancer patients": A fading
   issue
SO JOURNAL OF CLINICAL ETHICS
LA English
DT Article
ID EUTHANASIA; STATE; ACT
C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA.
EM dennycc@cc.nih.gov
NR 7
TC 1
Z9 1
U1 0
U2 3
PU UNIV PUBLISHING GROUP
PI HAGERSTOWN
PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA
SN 1046-7890
J9 J CLIN ETHIC
JI J. Clin. Ethics
PD SPR
PY 2006
VL 17
IS 1
BP 39
EP 42
PG 4
WC Ethics; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Biomedical Social Sciences
GA 035VZ
UT WOS:000237031100004
PM 16689112
ER

PT J
AU Deroo, BJ
   Korach, KS
AF Deroo, BJ
   Korach, KS
TI Estrogen receptors and human disease
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Review
ID CORONARY-ARTERY-DISEASE; POSTMENOPAUSAL HORMONE-THERAPY; ALPHA GENE
   POLYMORPHISMS; COLON-CANCER CELLS; BREAST-CANCER; PROSTATE-CANCER; HUMAN
   BONE; ER-BETA; REPLACEMENT THERAPY; BLOOD-PRESSURE
AB Estrogens influence many physiological processes in mammals, including but not limited to reproduction, cardiovascular health, bone integrity, cognition, and behavior. Given this widespread role for estrogen in human physiology, it is not surprising that estrogen is also implicated in the development or progression of numerous diseases, which include but are not limited to various types of cancer (breast, ovarian, colorectal, prostate, endometrial), osteoporosis, neurodegenerative diseases, cardiovascular disease, insulin resistance, lupus erythematosus, endometriosis, and obesity. in many of these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many therapeutic interventions. This Review will describe diseases in which estrogen, through the ER, plays a role in the development or severity of disease.
C1 Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, Res Triangle Pk, NC 27709 USA.
RP Korach, KS (reprint author), Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Receptor Biol Sect, NIH, B3-02,POB 12233, Res Triangle Pk, NC 27709 USA.
EM korach@niehs.nih.gov
OI Korach, Kenneth/0000-0002-7765-418X
FU Intramural NIH HHS
NR 126
TC 587
Z9 623
U1 16
U2 118
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 MAR
PY 2006
VL 116
IS 3
BP 561
EP 570
DI 10.1172/JCI27987
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 019RL
UT WOS:000235854300002
PM 16511588
ER

PT J
AU Scaffidi, P
   Misteli, T
AF Scaffidi, P
   Misteli, T
TI Good news in the nuclear envolpe: loss of lamin A might be a gain
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Editorial Material
ID HUTCHINSON-GILFORD-PROGERIA; PRELAMIN-A; MUSCULAR-DYSTROPHY; ZMPSTE24;
   DEFICIENCY; MUTATIONS; MICE
AB Genetic diseases often reveal the physiological roles of the affected proteins. The identification of mutations in the nuclear envelope proteins lamin A and lamin C as the cause of a diverse group of human diseases has expanded our understanding of the lamin proteins from being merely structural elements of the cell nucleus and has implicated them in novel cellular functions including signal transduction and gene expression. However, it now appears that the physiological relevance of one of the lamin proteins in organismal function has been overestimated. In this issue of the JCI, Fong et al. demonstrate that lamin A-deficient mice are phenotypically normal (see the related article beginning on page 743). The good news is these findings open the door to a new strategy for the therapeutic treatment of diseases caused by mutations in lamin A, such as muscular dystrophies and some types of premature aging syndromes.
C1 NCI, NIH, Bethesda, MD 20892 USA.
RP Misteli, T (reprint author), NCI, NIH, 41 Lib Dr,Bldg 41, Bethesda, MD 20892 USA.
EM mistelit@mail.nih.gov
NR 16
TC 10
Z9 10
U1 0
U2 0
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD MAR
PY 2006
VL 116
IS 3
BP 632
EP 634
DI 10.1172/JCI27820
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 019RL
UT WOS:000235854300012
PM 16511598
ER

PT J
AU Fong, LG
   Ng, JK
   Lammerding, J
   Vickers, TA
   Meta, M
   Cote, N
   Gavino, B
   Qiao, X
   Chang, SY
   Young, SR
   Yang, SH
   Stewart, CL
   Lee, RT
   Bennett, CF
   Bergo, MO
   Young, SG
AF Fong, LG
   Ng, JK
   Lammerding, J
   Vickers, TA
   Meta, M
   Cote, N
   Gavino, B
   Qiao, X
   Chang, SY
   Young, SR
   Yang, SH
   Stewart, CL
   Lee, RT
   Bennett, CF
   Bergo, MO
   Young, SG
TI Prelamin A and lamin A appear to be dispensable in the nuclear lamina
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID GILFORD-PROGERIA-SYNDROME; DREIFUSS MUSCULAR-DYSTROPHY; ANTISENSE
   OLIGONUCLEOTIDE; A/C GENE; ZMPSTE24-DEFICIENT MICE; DILATED
   CARDIOMYOPATHY; RESTRICTIVE DERMOPATHY; LMNA MUTATIONS; ENVELOPE;
   ZMPSTE24
AB Lamin A and lamin C, both products of Lmna, are key components of the nuclear lamina. In the mouse, a deficiency in both lamin A and lamin C leads to slow growth, muscle weakness, and death by 6 weeks of age. Fibroblasts deficient in lamins A and C contain misshapen and structurally weakened nuclei, and emerin is mislocalized away from the nuclear envelope. The physiologic rationale for the existence of the 2 different Lmna products lamin A. and lamin C is unclear, although several reports have suggested that lamin A may have particularly important functions, for example in the targeting of emerin and lamin C to the nuclear envelope. Here we report the development of lamin C-only mice (Lmna(LCO/LCO)), which produce lamin C but no lamin A or prelamin A (the precursor to lamin A). Lmna(LCO/LCO) mice were entirely healthy, and Lmna(LCO/LCO) cells displayed normal emerin targeting and exhibited only very minimal alterations in nuclear shape and nuclear deformability. Thus, at least in the mouse, prelamin A and lamin A appear to be dispensable. Nevertheless, an accumulation of farnesyl-prelamin A (as occurs with a deficiency in the prelamin A processing enzyme Zmpste24) caused dramatically misshapen nuclei and progeria-like disease phenotypes. The apparent dispensability of prelamin A suggested that lamin A-related progeroid syndromes might be treated with impunity by reducing prelamin A synthesis. Remarkably, the presence of a single Lmna(LCO) allele eliminated the nuclear shape abnormalities and progeria-like disease phenotypes in Zmpste24(-/-) mice. Moreover, treating Zmpste24(-/-) cells with a prelamin A-specific antisense oligonucleotide reduced prelamin A levels and significantly reduced the frequency of misshapen nuclei. These studies suggest a new therapeutic strategy for treating progeria and other lamin A diseases.
C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Cardiol, Los Angeles, CA USA.
   Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA.
   Brigham & Womens Hosp, Div Cardiovasc, Cambridge, MA USA.
   ISIS Pharmaceut, Carlsbad, CA 92008 USA.
   Univ Calif San Francisco, Dept Radiol, Musculoskeletal & Quantitat Res Grp, San Francisco, CA 94143 USA.
   Natl Canc Inst, Frederick, MD USA.
   Sahlgrenska Univ Hosp, Dept Internal Med, Gothenburg, Sweden.
RP Fong, LG (reprint author), 695 Charles E Young Dr S, Los Angeles, CA 90095 USA.
EM lfong@mednet.ucla.edu; sgyoung@mednet.ucla.edu
RI Lammerding, Jan/A-9498-2016
OI Lammerding, Jan/0000-0003-4335-8611
FU NCI NIH HHS [CA099506, R01 CA099506]; NHLBI NIH HHS [R01 HL082792];
   NIAID NIH HHS [AI054384, R01 AI054384]; NIAMS NIH HHS [AR050200, R01
   AR050200]; NINDS NIH HHS [R01 NS059348]
NR 43
TC 124
Z9 127
U1 0
U2 8
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 MAR
PY 2006
VL 116
IS 3
BP 743
EP 752
DI 10.1172/JCI27125
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 019RL
UT WOS:000235854300025
PM 16511604
ER

PT J
AU Xu, H
   Zhang, XJ
   Mannon, RB
   Kirk, AD
AF Xu, H
   Zhang, XJ
   Mannon, RB
   Kirk, AD
TI Platelet-derived or soluble CD154 induces vascularized allograft
   rejection independent of cell-bound CD154
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID HUMAN ENDOTHELIAL-CELLS; CD40 LIGAND; MONOCLONAL-ANTIBODY; CARDIAC
   ALLOGRAFTS; EXPRESSION; ACTIVATION; CYTOKINES; LYMPHOCYTES; ACCEPTANCE;
   COMPLEXES
AB CD154 is a cell surface molecule expressed on activated T cells that binds to CD40, an activating molecule on APCs. Its blockade has been shown to prevent allograft rejection, presumably by interrupting interactions between T cells and APCs. It is known that activated human platelets express and shed CD 154 and can induce APC activation and other immune processes in vitro. Here we show that platelet-derived CD154 is sufficient to initiate cardiac allograft rejection independent of any cellular source of this molecule. CD154-KO mice reject cardiac allografts after receiving CD154-expressing human platelets or recombinant CD154 (rCD154) trimers. Treatment with the human CD154-specific mAb 5c8 specifically prevents this induced rejection. Soluble trimers, but not platelets, induce rejection when infused temporally remote from the surgical procedure, suggesting that surgically induced platelet activation is required for CD154 release. Allograft rejection can thus be instigated by activated platelets through CD154. These data implicate platelets as a proximal component of acquired alloimmunity, providing insight into the mechanisms of allograft rejection and the physiological response to trauma in general.
C1 NIDDKD, Transplantat Branch, US Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
RP Xu, H (reprint author), NIDDKD, Transplantat Branch, US Dept Hlth & Human Serv, NIH, Room 5-5752,Bldg 10CRC,Ctr Dr, Bethesda, MD 20892 USA.
RI Kirk, Allan/B-6905-2012
FU Intramural NIH HHS
NR 32
TC 53
Z9 55
U1 0
U2 0
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD MAR
PY 2006
VL 116
IS 3
BP 769
EP 774
DI 10.1172/JC127155
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 019RL
UT WOS:000235854300028
PM 16498500
ER

PT J
AU Pfaller, MA
   Diekema, DJ
   Rex, JH
   Espinel-Ingroff, A
   Johnson, EM
   Andes, D
   Chaturvedi, V
   Ghannoum, MA
   Odds, FC
   Rinaldi, MG
   Sheehan, DJ
   Troke, P
   Walsh, TJ
   Warnock, DW
AF Pfaller, MA
   Diekema, DJ
   Rex, JH
   Espinel-Ingroff, A
   Johnson, EM
   Andes, D
   Chaturvedi, V
   Ghannoum, MA
   Odds, FC
   Rinaldi, MG
   Sheehan, DJ
   Troke, P
   Walsh, TJ
   Warnock, DW
TI Correlation of MIC with outcome for Candida species tested against
   voriconazole: Analysis and proposal for interpretive breakpoints
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID GLOBAL ANTIFUNGAL SURVEILLANCE; IN-VITRO ACTIVITIES; DISK DIFFUSION;
   FLUCONAZOLE SUSCEPTIBILITY; AMPHOTERICIN-B; BROTH MICRODILUTION;
   INVASIVE MYCOSES; TRIAZOLE; PROGRAM; PHARMACOKINETICS
AB Developing interpretive breakpoints for any given organism-drug combination requires integration of the MIC distribution, pharmacokinetic and pharmacodynamic parameters, and the relationship between the in vitro activity and outcome from both in vivo and clinical studies. Using data generated by standardized broth microdilution and disk diffusion test methods, the Antifungal Susceptibility Subcommittee of the Clinical and Laboratory Standards Institute has now proposed interpretive breakpoints for voriconazole and Candida species. The MIC distribution for voriconazole was determined using a collection of 8,702 clinical isolates. The overall MIC90 was 0.25 mu g/ml and 99% of the isolates were inhibited at <= 1 mu g/ml of voriconazole. Similar results were obtained for 1,681 Candida isolates (16 species) from the phase III clinical trials. Analysis of the available data for 249 patients from six phase III voriconazole clinical trials demonstrated a statistically significant correlation (P = 0.021) between MIC and investigator end-of-treatment assessment of outcome. Consistent with parallel pharmacodynamic analyses, these data support the following MIC breakpoints for voriconazole and Candida species: susceptible (S), <= 1 mu g/ml; susceptible dose dependent (SDD), 2 mu g/ml; and resistant (R), >= 4 mu g/ml. The corresponding disk test breakpoints are as follows: S, >= 17 mm; SDD, 14 to 16 mm; and R, <= 13 mm.
C1 Univ Iowa, Coll Med, Div Med Microbiol, Dept Pathol, Iowa City, IA 52242 USA.
   AstraZeneca, Macclesfield, Cheshire, England.
   VCU Med Ctr, Richmond, VA USA.
   HPA Ctr Infect, Bristol, Avon, England.
   Univ Wisconsin, Madison, WI USA.
   New York State Dept Hlth, Albany, NY USA.
   Case Western Reserve Univ, Cleveland, OH 44106 USA.
   Univ Aberdeen, Aberdeen, Scotland.
   Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA.
   Pfizer Inc, New York, NY USA.
   Pfizer Global Res & Dev, Sandwich, Kent, England.
   Natl Canc Inst, Bethesda, MD USA.
   Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Pfaller, MA (reprint author), Univ Iowa, Coll Med, Div Med Microbiol, Dept Pathol, C606 GH, Iowa City, IA 52242 USA.
EM michael-pfaller@uiowa.edu
OI Diekema, Daniel/0000-0003-1273-0724
NR 43
TC 193
Z9 204
U1 1
U2 4
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 MAR
PY 2006
VL 44
IS 3
BP 819
EP 826
DI 10.1128/JCM.44.3.819-826.2006
PG 8
WC Microbiology
SC Microbiology
GA 022ZP
UT WOS:000236095000022
PM 16517860
ER

PT J
AU Gelboin, HV
   Krausz, K
AF Gelboin, HV
   Krausz, K
TI Monoclonal antibodies and multifunctional cytochrome P450: Drug
   metabolism as paradigm
SO JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE monoclonal antibodies; cytochrome P450; drug discovery; drug metabolism
ID HUMAN LIVER-MICROSOMES; IN-VITRO; P450; IDENTIFICATION; SPECIFICITY;
   ENZYMES; DNA; CYTOCHROMES-P-450; INVOLVEMENT; INHIBITION
AB Monoclonal antibodies are reagents par excellence for analyzing the role of individual cytochrome P450 isoforms in multifunctional biological activities catalyzed by cytochrome P450 enzymes. The precision and utility of the monoclonal antibodies have heretofore been applied primarily to studies of human drag metabolism. The unique and precise specificity and high inhibitory activity toward individual cytochrome P450s make the monoclonal antibodies extraordinary tools for identifying and quantifying the role of each P450 isoform, in the metabolism of a drug or nondrug xenobiotic. The monoclonal antibodies identify drugs metabolized by individual,several, or polymorphic P450s. A comprehensive collection of monoclonol antibodies has been isolated to human P450s: 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C family, 2C19, 2D6, 2E1, 3A4/5, and 2J2. The monoclonol antibodies can also be used for identifying drugs and/or metabolites useful as markers for in vivo phenotyping. Clinical identification of a patient's phenotype, coupled with precise knowledge of a drug's metabolism, should lead to a reduction of adverse drug reactions and improved drug therapeutics, thereby promoting advances in drug discovery.
C1 NIH, Lab Metab, Bethesda, MD 20892 USA.
RP Gelboin, HV (reprint author), NIH, Lab Metab, Bldg 37,Room 3106, Bethesda, MD 20892 USA.
FU Intramural NIH HHS
NR 52
TC 21
Z9 22
U1 1
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0091-2700
J9 J CLIN PHARMACOL
JI J. Clin. Pharmacol.
PD MAR
PY 2006
VL 46
IS 3
BP 353
EP 372
DI 10.1177/0091270005285200
PG 20
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 016HD
UT WOS:000235610400012
PM 16490812
ER

PT J
AU Grant, BF
   Hasin, DS
   Stinson, FS
   Dawson, DA
   Goldstein, RB
   Smith, S
   Huang, B
   Saha, TD
AF Grant, BF
   Hasin, DS
   Stinson, FS
   Dawson, DA
   Goldstein, RB
   Smith, S
   Huang, B
   Saha, TD
TI The epidemiology of DSM-IV panic disorder and agoraphobia in the United
   States: Results from the National Epidemiologic Survey on Alcohol and
   Related Conditions
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
ID GENERALIZED ANXIETY DISORDER; INTERVIEW SCHEDULE AUDADIS;
   PLACEBO-CONTROLLED TRIAL; PERSONALITY-DISORDERS; PSYCHIATRIC-DISORDERS;
   LIFETIME PREVALENCE; MENTAL-DISORDERS; COMMUNITY SAMPLE; DOUBLE-BLIND;
   CLINICAL INTERVIEWERS
AB Objective: To present nationally representative data on the prevalence, correlates, and comorbidity of DSM-IV panic disorder (PAN), including the differentiation between panic with agoraphobia (PDA) and without agoraphobia (PDWA) and agoraphobia without a history of panic disorder (AG).
   Method: The data were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Prevalence, correlates, and comorbidity of PAN, PDA, and PDWA with Axis I and II disorders were determined.
   Results: Prevalences of 12-month and lifetime PAN were 2.1% and 5.1%. Rates of 12-month and lifetime PDWA were 1.6% and 4.0%, exceeding those of 12-month (0.6%) and lifetime (1.1%) PDA. Rates of 12-month and lifetime AG were extremely low, 0.05% and 0.17%. Being female, Native American, middle-aged, widowed/separated/divorced, and of low income increased risk, while being Asian, Hispanic, or black decreased risk for PAN, PDA, and PDWA. Individuals with PDA were more likely to seek treatment and had earlier ages at onset and first treatment, longer episodes, and more severe disability, impairment, panic symptomatology, and Axis I and II comorbidity than those with PDWA.
   Conclusion: PDA may be a more severe variant of PAN. Overrepresentation of PDA in treatment settings reflects increased treatment seeking and the severity of PDA relative to PDWA. The very low prevalence of AG leaves open questions about the meaning of the disorder as a distinct clinical entity as defined in the DSM-IV.
C1 NIAAA, Lab Epidemiol & Biometry, Div Clin & Biol Intramural Res, NIH, Bethesda, MD 20892 USA.
   Columbia Univ, Dept Epidemiol & Psychiat, New York, NY USA.
   New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3077,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA.
EM bgrant@willco.niaaa.nih.gov
OI Goldstein, Rise/0000-0002-9603-9473
FU NIAAA NIH HHS [K05 AA014223]; NIDA NIH HHS [R01DA018652]
NR 98
TC 143
Z9 147
U1 3
U2 26
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 240008, MEMPHIS, TN 38124 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD MAR
PY 2006
VL 67
IS 3
BP 363
EP 374
PG 13
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 031RL
UT WOS:000236721600004
PM 16649821
ER

PT J
AU Przytycka, T
   Davis, G
   Song, N
   Durand, D
AF Przytycka, T
   Davis, G
   Song, N
   Durand, D
TI Graph theoretical insights into evolution of multidomain proteins
SO JOURNAL OF COMPUTATIONAL BIOLOGY
LA English
DT Article; Proceedings Paper
CT 9th Annual International Conference on Research in Computational
   Molecular Biology (RECOMB 2005)
CY MAY 14-18, 2005
CL Cambridge, MA
SP Broad Inst MIT & Harvard, Boston Univ Ctr Adv Geonom Technol
DE multidomain proteins; protein evolution; Dollo parsimony; domain overlap
   graph; chordal graphs; Helly property
ID GENOME; SEQUENCES; FAMILIES; CLASSIFICATION; NETWORKS; KINASES
AB We study properties of multidomain proteins from a graph theoretical perspective. In particular, we demonstrate connections between properties of the domain overlap graph and certain variants of Dollo parsimony models. We apply our graph theoretical results to address several interrelated questions: do proteins acquire new domains infrequently, or often enough that the same combinations of domains will be created repeatedly through independent events? Once domain architectures are created do they persist? In other words, is the existence of ancestral proteins with domain compositions not observed in contemporary proteins unlikely? Our experimental results indicate that independent merges of domain pairs are not uncommon in large superfamilies.
C1 US Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
   Carnegie Mellon Univ, Program Computat Org & Soc, Pittsburgh, PA 15213 USA.
   Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA.
   Carnegie Mellon Univ, Dept Comp Sci, Pittsburgh, PA 15213 USA.
RP Przytycka, T (reprint author), US Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM przytyck@mail.nih.gov
FU NHGRI NIH HHS [1 K22 HG 02451-01, K22 HG002451]; NLM NIH HHS [Z01
   LM092804-02]
NR 36
TC 25
Z9 25
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1066-5277
J9 J COMPUT BIOL
JI J. Comput. Biol.
PD MAR
PY 2006
VL 13
IS 2
BP 351
EP 363
DI 10.1089/cmb.2006.13.351
PG 13
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 034TY
UT WOS:000236954700016
PM 16597245
ER

PT J
AU Yim, PJ
   Vora, AV
   Raghavan, D
   Prasad, R
   McAullife, M
   Ohman-Strickland, P
   Nosher, JL
AF Yim, PJ
   Vora, AV
   Raghavan, D
   Prasad, R
   McAullife, M
   Ohman-Strickland, P
   Nosher, JL
TI Volumetric analysis of liver metastases in computed tomography with the
   fuzzy C-means algorithm
SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
LA English
DT Article
DE volumetry; metastases; fuzzy C-means algorithm; computed tomography
ID MRI TISSUE CHARACTERIZATION; MAGNETIC-RESONANCE IMAGES; TUMOR RESPONSE;
   SOLID TUMORS; SEGMENTATION; BRAIN; MODEL
AB Tumor size is often determined from computed tomography (CT) images to assess disease progression. A study was conducted to demonstrate the advantages of the fuzzy C-means (FCM) algorithm for volumetric analysis of colorectal liver metastases in comparison with manual contouring. Intra-and interobserver variability was assessed for manual contouring and the FCM algorithm in a study involving contrast-enhanced helical CT images of 43 hypoattenuating liver lesions from 15 patients with a history of colorectal cancer. Measurement accuracy and interscan variability of the FCM and manual methods were assessed in a phantom study using paraffin pseudotumors. In the clinical imaging study, intra-and interobserver variability was reduced using the FCM algorithm as compared with manual contouring (P = 0.0070 and P = 0.0019, respectively). Accuracy of the measurement of the pseudotumor volume was improved using the FCM method as compared with the manual method (P = 0.047). Interscan variability of the pseudotumor volumes was measured using the FCM method as compared with the manual method (P = 0.04). The FCM algorithm volume was highly correlated with the manual contouring Volume (r = 0.9997). Finally, the shorter time spent in calculating tumor Volume using the FCM method versus the manual contouring method was marginally statistically significant (P = 0.080). These results suggest that the FCM algorithm has substantial advantages over manual contouring for volumetric measurement of colorectal liver metastases from CT.
C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Radiol, New Brunswick, NJ 08903 USA.
   NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
   Univ Med & Dent New Jersey, Sch Publ Hlth, Piscataway, NJ 08854 USA.
RP Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Radiol, 1 Robert Wood Johnson Pl,MEB 404, New Brunswick, NJ 08903 USA.
EM yimpj@umdnj.edu
NR 26
TC 12
Z9 13
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0363-8715
EI 1532-3145
J9 J COMPUT ASSIST TOMO
JI J. Comput. Assist. Tomogr.
PD MAR-APR
PY 2006
VL 30
IS 2
BP 212
EP 220
DI 10.1097/00004728-200603000-00008
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 028HU
UT WOS:000236478600008
PM 16628034
ER

PT J
AU Garrard, J
   Choudary, V
   Groom, H
   Dieperink, E
   Willenbring, ML
   Durfee, JM
   Ho, SB
AF Garrard, J
   Choudary, V
   Groom, H
   Dieperink, E
   Willenbring, ML
   Durfee, JM
   Ho, SB
TI Organizational change in management of hepatitis C: Evaluation of a CME
   program
SO JOURNAL OF CONTINUING EDUCATION IN THE HEALTH PROFESSIONS
LA English
DT Article
DE organizational change; integrated care model; hepatitis C;
   multispecialty education; qualitative evaluation; continuing education;
   medical
ID UNITED-STATES VETERANS; VIRUS-INFECTION; RANDOMIZED-TRIAL; PLUS
   RIBAVIRIN; MEDICAL-CARE; HEALTH-CARE; PREVALENCE; BEHAVIOR; THERAPY;
   IMPACT
AB Introduction: Effective treatment regimens exist for the hepatitis C virus (HCV): however clinicians are often resistant to evaluation or treatment of patients with alcohol or substance abuse problems. We describe a continuing medical education (CME) program for clinicians in a nationwide health care system, with emphasis on current treatment practices, multispecialty collaboration, and organizational change.
   Methods: Quantitative measures were used to assess changes in knowledge and treatment confidence, and site-specific organizational changes were qualitatively evaluated. The CME program included a preassessment of current HCV knowledge and care; a 2-day preceptor-ship; and follow-up with coaching calls at 1, 3, and 6 months. Program attendees included 54 medical and mental health providers from 28 Veterans Affairs Medical Centers.
   Results: Knowledge following the CME program increased significantly. In 93% of the sites, there were organizational changes such as HCV support group-initiated group education, in-service training, improvement in patient notification or scheduling processes, hiring of new, clinical staff, development of a business plans, and discussions about changes with administration. Of all sites, 15 (54%) changed existing antiviral treatment protocols, 18 (64%) established collaborative relationships, and almost half(13/28) established regular use of depression and alcohol use screening tools. Major barriers to change included lack of admininistration support or resources (or both) and difficulty collaborating with mental health colleagues.
   Discussion: This multifaceted CME program with follow-up coaching calls significantly increased individual knowledge and confidence scores and resulted in improved clinic processes and structures. Organizational change was facilitated by the development of an action plan. The major change agent was a nurse: the primary deterrent was an administrator.
C1 Univ Minnesota, Sch Publ Hlth, Div Hlth Serv Res & Policy, Acad Affairs & Res, Minneapolis, MN 55455 USA.
   Minneapolis Vet Affairs Med Ctr, Hepatitis C Resource Ctr, Minneapolis, MN USA.
   Univ Minnesota, Sch Publ Hlth, Div Hlth Serv Res, Minneapolis, MN USA.
   Ctr Dis Control & Prevent, Atlanta, GA USA.
   Minneapolis VA Med Ctr, Dept Psychiat, Minneapolis, MN USA.
   NIAAA, Div Treatment & Recovery Res, NIH, Rockville, MD 20852 USA.
   Minneapolis VA Med Ctr, Dept Med, Minneapolis, MN USA.
RP Garrard, J (reprint author), Univ Minnesota, Sch Publ Hlth, Div Hlth Serv Res & Policy, Acad Affairs & Res, MMC 729,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM jgarrard@umn.edu
OI Groom, Holly/0000-0003-2866-9788
NR 47
TC 4
Z9 4
U1 1
U2 4
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0894-1912
J9 J CONTIN EDUC HEALTH
JI J. Contin. Educ. Health Prof.
PD SPR
PY 2006
VL 26
IS 2
BP 145
EP 160
DI 10.1002/chp.63
PG 16
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 058WP
UT WOS:000238695600008
PM 16802308
ER

PT J
AU Willis, G
AF Willis, Gordon
TI Cognitive interviewing as a tool for improving the informed consent
   process
SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS
LA English
DT Article
DE cognitive interviewing; comprehension; informed consent
AB CONSENT MATERIALS OFTEN CONTAIN complex information, legalese, and other features that render them difficult to comprehend in such a way that consent is truly informed. I propose that researchers adapt cognitive interviewing, normally used for the pretesting of survey questionnaires, to evaluate the understandability of consent materials and the way in which subjects use this information to make decisions regarding participation. Cognitive interviewing involves the intensive probing of small samples of volunteer subjects to elucidate thought processes that otherwise remain hidden. Cognitive interviewing can be applied: (a) to further the basic science of informed consent; (b) to pretest materials for a specific study; and (c) as an embedded procedure for assessing subject thought processes in the course of obtaining consent.
C1 [Willis, Gordon] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
   [Willis, Gordon] Res Triangle Inst, Res Triangle Pk, NC 27709 USA.
RP Willis, G (reprint author), NCI, 6130 Execut Blvd,MSC 7344,EPN 4005, Bethesda, MD 20892 USA.
EM Willisg@mail.nih.gov
NR 43
TC 22
Z9 22
U1 2
U2 9
PU UNIV CALIFORNIA PRESS
PI BERKELEY
PA C/O JOURNALS DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223
   USA
SN 1556-2646
J9 J EMPIR RES HUM RES
JI J. Empir. Res. Hum. Res. Ethics
PD MAR
PY 2006
VL 1
IS 1
BP 9
EP 23
DI 10.1525/jer.2006.1.1.9
PG 15
WC Ethics; Medical Ethics
SC Social Sciences - Other Topics; Medical Ethics
GA V44MM
UT WOS:000203006800005
PM 19385864
ER

PT J
AU Odling, K
   Albertsson, C
   Russell, JT
   Martensson, LGE
AF Odling, K
   Albertsson, C
   Russell, JT
   Martensson, LGE
TI An in vivo study of exocytosis of cement proteins from barnacle Balanus
   improvisus (D.) cyprid larva
SO JOURNAL OF EXPERIMENTAL BIOLOGY
LA English
DT Article
DE barnacle cyprid; cement gland; cement secretion; exocytosis; dense core
   granules; granule swelling
ID PIECEMEAL DEGRANULATION; FUSION PORE; NEUROSECRETORY GRANULES; CELL
   SECRETION; SINUS GLAND; BETA-CELLS; VESICLES; MECHANISM; RELEASE;
   BALANOIDES
AB Barnacles, like many marine invertebrates, cause serious biofouling to marine industrial constructions and hulls of vessels as they attach themselves to such surfaces. Precise biochemical understanding of the underwater adhesion to surfaces requires a detailed characterization of the biology of the control of barnacle cement secretion and the proteins that make up the cement. In this study, we have investigated cement secretion by cyprid larvae of Balanus improvisus (D.) and the morphology of their cement glands. We studied the cement protein organization within cement granules and categorized the granules into four different types according to their size and morphology, before and after stimulation of secretion. In addition, we followed the exocytotic process of cement secretion in vivo and discovered that granules undergo a dramatic swelling during secretion. Such swelling might be due to an increased osmotic activity of granule contents, following a process of hydration. We hypothesize that this hydration is essential for exocytotic secretion and conclude that cement protein exocytosis is a more complex process than previously thought and is similar to exocytotic secretion in vertebrate systems, such as histamine secretion from mast cells and exocrine secretion in the salivary gland and the pancreas.
C1 Univ Gothenburg, Dept Zool, SE-41390 Gothenburg, Sweden.
   NICHD, Sect Cell Biol & Signal Transduct, NIH, Bethesda, MD 20892 USA.
RP Martensson, LGE (reprint author), Univ Gothenburg, Dept Zool, Medicinaregatan 18, SE-41390 Gothenburg, Sweden.
EM lena.martensson@zool.gu.se
NR 37
TC 31
Z9 31
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 MAR
PY 2006
VL 209
IS 5
BP 956
EP 964
DI 10.1242/jeb.02031
PG 9
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA 028GW
UT WOS:000236476100027
PM 16481584
ER

PT J
AU Hsia, CC
   Purcell, RH
   Farshid, M
   Lachenbruch, PA
   Yu, MYW
AF Hsia, Chu Chieh
   Purcell, Robert H.
   Farshid, Mahmood
   Lachenbruch, Peter A.
   Yu, Mei-Ying W.
TI Infectious dose of HBV in terms of copy number of DNA in human sera
SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Meeting Abstract
C1 Ctr Biol Evaluat & Res, Bethesda, MD USA.
   NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0815-9319
J9 J GASTROEN HEPATOL
JI J. Gastroenterol. Hepatol.
PD MAR
PY 2006
VL 21
SU 2
BP A102
EP A102
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 179WG
UT WOS:000247320400093
ER

PT J
AU Kakizaki, S
   Yamazaki, Y
   Horiguchi, N
   Sohara, N
   Sato, K
   Takagi, H
   Mori, M
   Negishi, M
AF Kakizaki, Satoru
   Yamazaki, Yuichi
   Horiguchi, Norio
   Sohara, Naondo
   Sato, Ken
   Takagi, Hitoshi
   Mori, Masatomo
   Negishi, Masahiko
TI Role of nuclear receptor CAR in carbon tetrachloride-induced
   hepatotoxicity
SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Meeting Abstract
C1 Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, Gunma, Japan.
   NIEHS, Pharmacogenet Sect, LRDT, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0815-9319
J9 J GASTROEN HEPATOL
JI J. Gastroenterol. Hepatol.
PD MAR
PY 2006
VL 21
SU 2
BP A208
EP A208
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 179WG
UT WOS:000247320400453
ER

PT J
AU Jensen, RT
AF Jensen, RT
TI Pancreatic neuroendocrine tumors: Overview of recent advances and
   diagnosis
SO JOURNAL OF GASTROINTESTINAL SURGERY
LA English
DT Article; Proceedings Paper
CT 46th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract
CY MAY 14-18, 2005
CL Chicago, IL
SP Soc Surg Alimentary Tract
ID ZOLLINGER-ELLISON-SYNDROME; ENDOCRINE NEOPLASIA TYPE-1; SOMATOSTATIN
   RECEPTOR SCINTIGRAPHY; METASTATIC GASTRINOMAS; SURGICAL-MANAGEMENT;
   PROGNOSTIC-FACTORS; GROWTH; SURVIVAL
C1 NIDDK, NIH, Bethesda, MD 20892 USA.
RP Jensen, RT (reprint author), NIDDK, NIH, 10 Ctr Dr,MSC 1804,Bldg 10,Room 9C-103, Bethesda, MD 20892 USA.
NR 29
TC 11
Z9 13
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1091-255X
J9 J GASTROINTEST SURG
JI J. Gastrointest. Surg.
PD MAR
PY 2006
VL 10
IS 3
BP 324
EP 326
DI 10.1016/j.gassur.2005.08.022
PG 3
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA 021UA
UT WOS:000236010200002
PM 16622982
ER

PT J
AU Inagaki, K
   Wu, XL
   Fuess, S
   Storm, TA
   Kay, MA
   Nakai, H
AF Inagaki, K
   Wu, XL
   Fuess, S
   Storm, TA
   Kay, MA
   Nakai, H
TI Analysis of vector genome integration sites in various tissues following
   systemic administration of AAV serotype 8 vector in mice
SO JOURNAL OF GENE MEDICINE
LA English
DT Meeting Abstract
CT 11th Annual Meeting of the Japan-Society-of-Gene-Therapy
CY JUL 28-30, 2005
CL JIKEI Univ Sch Med, Tokyo, JAPAN
SP Japan Soc Gene Therapy
HO JIKEI Univ Sch Med
C1 Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
   SAIC Frederick Inc, Lab Mol Technol, NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1099-498X
J9 J GENE MED
JI J. Gene. Med.
PD MAR
PY 2006
VL 8
IS 3
BP 391
EP 391
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA 039OC
UT WOS:000237314600064
ER

PT J
AU Emerson, SU
   Clemente-Casares, P
   Moiduddin, N
   Arankalle, VA
   Torian, U
   Purcell, RH
AF Emerson, SU
   Clemente-Casares, P
   Moiduddin, N
   Arankalle, VA
   Torian, U
   Purcell, RH
TI Putative neutralization epitopes and broad cross-genotype neutralization
   of Hepatitis E virus confirmed by a quantitative cell-culture assay
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID MONOCLONAL-ANTIBODIES; RECOMBINANT VACCINE; PROTEIN; ORF2; CHALLENGE;
   SEQUENCES; MACAQUES; STRAINS; SITE; DEER
AB Monolayers of Hep G2/C3A cells were inoculated with genotype 1 Hepatitis E virus (HEV) mixed with either anti-HEV or an appropriate control. After 5 or 6 days, cell monolayers were stained with anti-HEV and infected cells were identified by immunofluorescence microscopy and counted. Anti-HEV from vaccinated or infected rhesus monkeys neutralized the virus, as did mAbs that recognized epitopes on the C terminus of a recombinant vaccine protein. Antibodies were broadly cross-reactive, since convalescent serum from animals infected with any one of the four mammalian genotypes all neutralized the genotype 1 virus.
C1 NIAID, Mol Hepatitis & Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
   Natl Inst Virol, Hepatitis Div, Pune, Maharashtra, India.
RP Emerson, SU (reprint author), NIAID, Mol Hepatitis & Hepatitis Viruses Sect, Infect Dis Lab, NIH, 50 South Dr,MSC-8009, Bethesda, MD 20892 USA.
EM semerson@niaid.nih.gov
FU Intramural NIH HHS
NR 22
TC 59
Z9 72
U1 1
U2 1
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
   BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD MAR
PY 2006
VL 87
BP 697
EP 704
DI 10.1099/vir.0.81545-0
PN 3
PG 8
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 018DM
UT WOS:000235744000025
PM 16476993
ER

PT J
AU Wang, J
   Sun, R
   Wei, HM
   Dong, ZJ
   Gao, B
   Tian, ZG
AF Wang, J
   Sun, R
   Wei, HM
   Dong, ZJ
   Gao, B
   Tian, ZG
TI Poly I : C prevents T cell-mediated hepatitis via an NK-dependent
   mechanism
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE concanavalin A; polyinosinic-polycytidylic acid; NK; NKT; hepatitis
ID A-INDUCED HEPATITIS; NATURAL-KILLER-CELLS; TUMOR-NECROSIS-FACTOR;
   INDUCED LIVER-INJURY; CONCANAVALIN-A; INTRACELLULAR PATHWAYS;
   INTERFERON-GAMMA; MICE; ACTIVATION; PATHOGENESIS
AB Background/Aims: T cell immune responses play key roles in the pathogenesis of viral hepatitis, and innate immunity is known to be also activated during this process, however, the effects of innate immunity activation on T cell-mediated hepatitis remain obscure. Here we examined the effect of the activation of NK cells induced by toll-like receptor 3 (TLR3) ligand, polyinosinic-polycytidylic acid (poly I:C), on concanavalin A (Con A)-induced T cell-mediated liver injury.
   Methods: Mice received nontoxic intraperitoneal poly I:C injection before Con A intravenous administration. The liver injury was examined by measuring serum transaminase and pathology, and the function of hepatic lymphocytes was detected by FACS analysis.
   Results: Poly I:C pretreatment protected against T cell-mediated hepatitis, as evidenced by decreased mortality, hepatic necrosis, serum transaminase levels and inflammatory cytokines (IL-4, IFN-gamma). The protective effect of poly I:C was diminished in NK-depleted mice, which could be partially restored by adoptive transfer of NK cells. Administration of poly I:C caused NKT and T cell apoptosis via enhancing expression of Fas protein on these cells and expression of Fas ligand on NK cells.
   Conclusions: These findings suggest that activation of NK cells by poly I:C prevents Con A-induced T cell-hepatitis via downregulation of T/NKT cells and subsequent reduction of inflammatory cytokines. (c) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
C1 Univ Sci & Technol China, Sch Life Sci, Anhua 230027, Peoples R China.
   Shandong Univ, Sch Pharm, Shandong 250002, Peoples R China.
   Natl Inst Alcohol & Abuse & Alcholism, Lab Physiol Studies, Sect Liver Biol, NIH, Bethesda, MD 20852 USA.
RP Tian, ZG (reprint author), Univ Sci & Technol China, Sch Life Sci, 443 Huangshan Rd, Anhua 230027, Peoples R China.
EM bgao@mail.nih.gov; tzg@ustc.edu.cn
RI Tian, Zhigang/J-3512-2013
NR 43
TC 58
Z9 66
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD MAR
PY 2006
VL 44
IS 3
BP 446
EP 454
DI 10.1016/j.jhep.2005.08.015
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 019RJ
UT WOS:000235854100003
PM 16310275
ER

PT J
AU Caceres, M
   Thomas, JW
AF Caceres, M
   Thomas, JW
TI The gene of retroviral origin syncytin 1 is specific to hominoids and is
   inactive in old world monkeys
SO JOURNAL OF HEREDITY
LA English
DT Article
ID HUMAN ENDOGENOUS RETROVIRUS; GENOMIC DNA-SEQUENCES; HERV-W; TRANSPOSABLE
   ELEMENTS; PLACENTAL EXPRESSION; ENVELOPE; PRIMATES; EVOLUTION; ERVWE1;
   FAMILY
AB Syncytin 1 is one of the best known examples of recent acquisition of a new gene from an endogenous retrovirus (HERV) in the human genome and has been implicated in placental physiology. Within primates, Syncytin 1 is conserved in all hominoids but has not been characterized in Old World monkeys (OWMs). In this study, we investigated the status of Syncytin 1 in 14 hominoid and OWM species. We show that although the HERV-W provirus responsible for the origin of this gene was present in the genome of the most recent common ancestor of hominoids and OWMs, Syncytin 1 is inactive in OWMs. In addition, we were able to determine that the evolution of Syncytin 1 in hominoids involved an accumulation of amino acid changes and showed signatures of both positive and purifying selection. Our results indicate that Syncytin 1 is indeed a hominoid-specific gene and illustrate the complex and dynamic process associated with the origin of new genes.
C1 Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA.
   NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
   NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA.
RP Caceres, M (reprint author), Emory Univ, Sch Med, Dept Human Genet, 615 Michael St,Suite 301, Atlanta, GA 30322 USA.
EM mcaceres@genetics.emory.edu
RI Caceres, Mario/A-6379-2009
OI Caceres, Mario/0000-0002-7736-3251
FU NIMH NIH HHS [MH068185]
NR 39
TC 16
Z9 18
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1503
J9 J HERED
JI J. Hered.
PD MAR
PY 2006
VL 97
IS 2
BP 100
EP 106
DI 10.1093/jhered/esj011
PG 7
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA 018NX
UT WOS:000235772400002
PM 16424151
ER

PT J
AU Koh, KK
   Quon, MJ
   Han, SH
   Chung, WJ
   Kim, JA
   Shin, EK
AF Koh, KK
   Quon, MJ
   Han, SH
   Chung, WJ
   Kim, JA
   Shin, EK
TI Vascular and metabolic effects of candesartan: insights from therapeutic
   interventions
SO JOURNAL OF HYPERTENSION
LA English
DT Article; Proceedings Paper
CT International Workshop on Angitension II Receptor Blockade - Vascular
   and Organ Protective Effects
CY APR 28-30, 2005
CL Gouvieux, FRANCE
DE angiotensin II receptor blocker; endothelial function; adiponectin;
   insulin resistance; cardiovascular diseases
ID II TYPE-1 RECEPTOR; SMOOTH-MUSCLE-CELLS; PLASMINOGEN-ACTIVATOR
   INHIBITOR-1; ANGIOTENSIN-CONVERTING ENZYME; CORONARY-ARTERY-DISEASE;
   E-DEFICIENT MICE; FACTOR-KAPPA-B; HYPERTENSIVE PATIENTS; ENDOTHELIAL
   DYSFUNCTION; AT(1) RECEPTOR
AB Background Effects of angiotensin 11 type 1 receptor blockers (ARBs) to improve endothelial dysfunction may be due to mechanisms in addition to the reduction of high blood pressure per se. Endothelial dysfunction is characterized by vascular inflammation that contributes to clinically significant atherosclerosis and by an increased tendency for thrombus formation. Hypertensive patients have impaired endothelial functions that have positive predictive power with respect to future cardiovascular events.
   Objectives The present review will focus on multiple mechanisms underlying vascular and metabolic effects of ARBs that may synergize to prevent or regress atherosclerosis, onset of diabetes, and coronary heart disease.
   Conclusions Angiotensin 11 accelerates the development of atherosclerosis by activating angiotensin 11 type 1 receptors that then promote superoxide anion generation and oxidative stress, leading to activation of nuclear transcription factor and endothelial dysfunction. Activation of angiotensin 11 type 1 receptors also stimulates increased expression of plasminogen activator inhibitor type 1 and tissue factor, Endothelial dysfunction associated with the metabolic syndrome and other insulin-resistant states is characterized by impaired insulin-stimulated production of nitric oxide from the endothelium and decreased blood flow to skeletal muscle. Increasing insulin sensitivity therefore improves endothelial function, and this may be an additional mechanism whereby ARBs decrease the incidence of coronary heart disease and the onset of diabetes. Adiponectin serves to link obesity with insulin resistance. In addition, adiponectin has anti-atherogenic properties.
C1 Gachon Med Sch, Vasc Med & Atherosclerosis Unit, Div Cardiol, Gil Heart Ctr, Inchon 405760, South Korea.
   NCCAM, Diabet Unit, Clin Invest Lab, NIH, Bethesda, MD USA.
RP Koh, KK (reprint author), Gachon Med Sch, Vasc Med & Atherosclerosis Unit, Div Cardiol, Gil Heart Ctr, 1198 Kuwol Dong, Inchon 405760, South Korea.
EM kwangk@gilhospital.com
RI Quon, Michael/B-1970-2008
NR 80
TC 14
Z9 16
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0263-6352
J9 J HYPERTENS
JI J. Hypertens.
PD MAR
PY 2006
VL 24
SU 1
BP S31
EP S38
DI 10.1097/01.hjh.0000220404.38622.6a
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 043XE
UT WOS:000237635400006
PM 16601571
ER

PT J
AU Saavedra, JM
   Benicky, J
   Zhou, J
AF Saavedra, JM
   Benicky, J
   Zhou, J
TI Angiotensin II: multitasking in the brain
SO JOURNAL OF HYPERTENSION
LA English
DT Article; Proceedings Paper
CT International Workshop on Angitension II Receptor Blockade - Vascular
   and Organ Protective Effects
CY APR 28-30, 2005
CL Gouvieux, FRANCE
DE angiotensin receptor blockers; renin-angiotensin system; brain ischemia;
   stroke; brain inflammation; stress; corticotropin-releasing factor;
   vasopressin; anxiety
ID NITRIC-OXIDE SYNTHASE; SPONTANEOUSLY HYPERTENSIVE-RATS;
   CEREBRAL-BLOOD-FLOW; PARAVENTRICULAR NUCLEUS; COGNITIVE FUNCTION;
   RECEPTOR; EXPRESSION; PITUITARY; ANTAGONIST; DEPRESSION
AB In addition to controlling systemic blood pressure, angiotensin II (Ang II) has several roles in the brain, including the regulation of cerebrovascular flow and the reaction to stress. In order to clarify the central effects of Ang II and its type 1 (AT,) receptors, we reviewed the literature reporting recent research on the effects of pretreatment with the AT(1)-receptor blocker, candesartan, on experimental ischemia, cerebrovascular remodeling, and inflammation in spontaneously hypertensive rats (SHRs), and the responses to stress induced by isolation and by cold-restraint. Angiotensin II regulates the brain circulation through stimulation of AT(1)-receptors located in the cerebrovascular endothelium and central pathways. SHRs express greater numbers of endothelial AT(1)-receptors and a central sympathetic overdrive, resulting in pathological cerebrovascular growth, inflammation, decreased cerebrovascular compliance, and enhanced vulnerability to brain ischemia. Sustained central AT(1)-receptor antagonism reverses these effects. Sustained reduction of AT(1)-receptor stimulation before stress prevents the hormonal and sympathoadrenal stress responses during isolation and prevents the gastric ulceration stress response to cold-restraint indicating that increased AT(1)-receptor stimulation is essential to enhance the central sympathetic response and the formation and release of corticotropin-releasing factor (CRF) and arginine vasopressin that occur during stress. AT(1)-receptor blocking agents reverse the cortical alterations in CRF, and benzodiazepine receptors characteristic of isolation stress, effects probably related to their anti-anxiety effect in rodents. Sustained reduction of Ang II tone by AT(1)-receptor antagonism could be considered as a preventive and therapeutic approach for brain ischemia and stress-related and mood disorders. Additional preclinical studies and controlled clinical trials are necessary to confirm the efficacy of this novel therapeutic approach.
C1 NIMH, Pharmacol Sect, DIRP, NIH,DHHS, Bethesda, MD 20892 USA.
RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, DIRP, NIH,DHHS, 10 Ctr Dr,MSC 1514,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA.
EM Saavedrj@mail.nih.gov
FU Intramural NIH HHS
NR 40
TC 24
Z9 24
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0263-6352
J9 J HYPERTENS
JI J. Hypertens.
PD MAR
PY 2006
VL 24
SU 1
BP S131
EP S137
DI 10.1097/01.hjh.0000220418.09021.ee
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 043XE
UT WOS:000237635400020
PM 16601566
ER

PT J
AU Gao, N
   Schwartzberg, P
   Wilder, JA
   Blazar, BR
   Yuan, D
AF Gao, N
   Schwartzberg, P
   Wilder, JA
   Blazar, BR
   Yuan, D
TI B cell induction of IL-13 expression in NK cells: Role of CD244 and
   SLAM-associated protein
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; LINKED LYMPHOPROLIFERATIVE DISEASE; SPLENIC
   MARGINAL ZONE; IFN-GAMMA PRODUCTION; T-CELLS; MONOCLONAL-ANTIBODY;
   CUTTING EDGE; CYTOKINE EXPRESSION; INTERFERON-GAMMA; ACTIVATION
AB NK cells are an important component of the innate immune system that can also interact with B cells in a mutually productive manner. We have previously shown that activated B cells can induce NK cells to up-regulate their secretion of IFN-gamma. In this study, we show that B cells, and, particularly, marginal zone B cells, can, in addition, induce NK cells via direct cell-cell interactions to express mRNA encoding the Th2 cytokine IL-13. The induction of NK cell IL-13 mRNA expression requires the ligation of the CD244 receptor by the CD48 ligand on B cells via signaling pathways that depend upon expression of the X-linked lymphoproliferative disease gene product, SH2D1A/DSHP/SAP (SLAM-associated protein, or SAP) in NK cells. Thus, the positive signals attributed to the B cell activation of CD244 on murine NK cells appears to be more similar to the activity of CD244 on human cells. The induction of IL-13 mRNA by B cells may account for the effect of NK cells on the generation of Th2-type responses in the presence of some adjuvants.
C1 Univ Texas, SW Med Ctr, Dept Mol Pathol, Dallas, TX 75390 USA.
   NHGRI, Natl Inst Hlth, Bethesda, MD 20892 USA.
   Lovelace Resp Res Inst, Albuquerque, NM 87108 USA.
   Univ Minnesota Hosp, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA.
   Univ Minnesota Hosp, Ctr Canc, Minneapolis, MN 55455 USA.
   Ctr Canc, Minneapolis, MN 55455 USA.
RP Yuan, D (reprint author), Univ Texas, SW Med Ctr, Dept Mol Pathol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM dorothy.yuan@utsouthwestern.edu
NR 64
TC 18
Z9 18
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 1
PY 2006
VL 176
IS 5
BP 2758
EP 2764
PG 7
WC Immunology
SC Immunology
GA 059YL
UT WOS:000238768000011
PM 16493031
ER

PT J
AU Petty, HR
   Kindzelskii, AL
   Espinoza, J
   Romero, R
AF Petty, HR
   Kindzelskii, AL
   Espinoza, J
   Romero, R
TI Trophoblast contact deactivates human neutrophils
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID UNDERGOES RETROGRADE TRAFFICKING; RAT PERITONEAL-MACROPHAGES;
   PHORBOL-MYRISTATE ACETATE; COLONY-STIMULATING FACTOR; IN-VITRO;
   SUPEROXIDE PRODUCTION; SUPRAMOLECULAR COMPLEX; OXIDATIVE STRESS; CELL
   ACTIVATION; HLA-G
AB Trophoblasts are fetal epithelial cells that form an interface between mother and offspring. To evaluate their anti-inflammatory capacity, we tested the hypothesis that trophoblasts deactivate neutrophils using single-cell assays. Several biophysical (Ca2+ and NAD(P)H oscillation frequency) and physiological (oxidant production) markers of activated neutrophils revert to a nonactivated phenotype as activated cells make contact with trophoblasts. Indistinguishable results were obtained using syncytiotrophoblasts and in experiments using trophoblasts and neutrophils from the same mother to recapitulate the semiallogeneic system. These changes suggest reduced hexose monophosphate shunt (HMS) activity. We discovered that two metabolic regulatory points, glucose transport and HMS enzyme trafficking, are affected by trophoblasts. This restriction in HMS activity deactivates neutrophils, thereby limiting oxidative DNA damage within trophoblasts.
C1 Univ Michigan, Med Sch, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
   Univ Michigan, Med Sch, Dept Microbiol & Immunol, Ann Arbor, MI 48105 USA.
   Natl Inst Child Hlth & Human Dev, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA.
RP Petty, HR (reprint author), Univ Michigan, Med Sch, Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA.
EM hpetty@umich.edu
FU Intramural NIH HHS
NR 46
TC 14
Z9 14
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 1
PY 2006
VL 176
IS 5
BP 3205
EP 3214
PG 10
WC Immunology
SC Immunology
GA 059YL
UT WOS:000238768000061
PM 16493081
ER

PT J
AU Babu, S
   Blauvelt, CP
   Kumaraswami, V
   Nutman, TB
AF Babu, S
   Blauvelt, CP
   Kumaraswami, V
   Nutman, TB
TI Regulatory networks induced by live parasites impair both Th1 and Th2
   pathways in patent lymphatic filariasis: Implications for parasite
   persistence
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID BRUGIA-MALAYI; T-CELLS; TRANSCRIPTION FACTOR; IMMUNE-RESPONSE;
   HELMINTH-PARASITES; UBIQUITIN LIGASES; HOST-DEFENSE; CYTOKINE;
   INFECTIONS; EXPRESSION
AB Patent lymphatic filariasis is characterized by a profound down-regulation of immune responses with both parasite Ag-specific tolerance and bystander suppression. Although this down-regulation is confined to the Th1 arm of the immune system in response to parasite Ag, we hypothesized a more generalized suppression in response to live parasites. Indeed, when we examined the cytokine profile of a cohort of filaria-infected (n = 10) and uninfected (n = 10) individuals in response to live infective-stage larvae or microfilariae of Brugia malayi, we found significant impairment of both Th1 and Th2 cytokines characterized by diminished production of IFN-gamma, TNF-alpha, IL-4, IL-5, and IL-10 in infected patients. The molecular basis of this impaired Th1/Th2 response was examined, and we identified three major networks of immunoregulation and tolerance. First, impaired induction of T-bet and GATA-3 mRNA underlies the Th1/Th2 deficiency in infected individuals. Second, regulatory networks, as evidenced by significantly increased expression of Foxp3 (natural regulatory T cell marker) and regulatory effectors such as TGF-beta, CTLA-4, PD-1, ICOS, and indoleamine 2,3-dioxygenase play an important role in immunosuppression. Third, the compromise of effector T cell function is mediated by the enhanced induction of anergy-inducing factors cbl-b, c-cbl (cbl is abbreviation for Casitas B lymphoma), Itch, and Nedd4. Indeed, blocking CTLA-4 or neutralizing TGF-beta restored the ability to mount Th1/Th2 responses to live parasites and reversed the induction of anergy-inducing factors. Hence, we conclude that a profound impairment of live parasite-specific Th1 and Th2 immune responses occurs in lymphatic filariasis that is governed at the transcriptional level by a complex interplay of inhibitory mediators.
C1 Natl Inst Allergy & Infect Dis, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA.
   Tubercolosis Res Ctr, Madras, Tamil Nadu, India.
RP Babu, S (reprint author), Natl Inst Allergy & Infect Dis, Lab Parasit Dis, NIH, 4 Ctr Dr,Room 4-B1-05, Bethesda, MD 20892 USA.
EM sbabu@niaid.nih.gov
FU Intramural NIH HHS
NR 40
TC 131
Z9 145
U1 3
U2 16
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAR 1
PY 2006
VL 176
IS 5
BP 3248
EP 3256
PG 9
WC Immunology
SC Immunology
GA 059YL
UT WOS:000238768000066
PM 16493086
ER

PT J
AU Stauffer, JK
   Khan, T
   Salcedo, R
   Hixon, JA
   Lincoln, E
   Back, TC
   Wigginton, JM
AF Stauffer, JK
   Khan, T
   Salcedo, R
   Hixon, JA
   Lincoln, E
   Back, TC
   Wigginton, JM
TI Multicolor fluorescence-based approaches for imaging cytokine-induced
   alterations in the neovascularization, growth, metastasis, and apoptosis
   of murine neuroblastoma tumors
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE cytokine; angiogenesis; apoptosis; metastasis; fluorescence
ID IN-VIVO; CYTOCHROME-C; IL-12/PULSE IL-2; CASPASE 8; NK CELLS; DEATH;
   ANGIOGENESIS; THERAPY; PROTEIN; CANCER
AB Neuroblastoma is one of the most common solid tumors in children. The prognosis of patients with advanced neuroblastoma is poor overall despite standard therapeutic modalities and has stimulated substantial interest in the potential role for biologics such as immunotherapeutic and/or antiangiogenic agents for the treatment of neuroblastoma. To facilitate preclinical investigation of the efficacy and mechanisms of action of new biologic agents for the treatment of neuroblastoma, a comprehensive panel of disease-specific fluorescence-based model systems has been developed by our group to image the growth, neovascularization, metastasis, and apoptosis of neuroblastoma tumors. These model systems use fluorescent proteins to monitor cytokine-induced alterations in the growth and metastasis of neuroblastoma and allow for monitoring and/or quantitation of even minimal residual disease that is localized to visceral organ sites such as the liver, lung, and/or bone marrow. Further, based on the differential spectra of red fluorescent protein, green fluorescent protein (GFP), and agents such as 4'-6-diamidino-2-phenylindole (DAPI) (blue) and fluorescein isothiocyanate-dextran (green), multicolor systems have now been established by out-group that allow for combined assessment of parameters, including the macroscopic relation of tumors to their associated vasculature and, within tissue sections, simultaneous quantitation of tumor neovascularization and evaluation of therapy-induced apoptosis within the tumor and vascular endothelial compartments. Further, by engineering cells to express specific mediators of apoptosis that have been linked to GFP (ie, BID-EGFP), these systems can also be used to dissect mechanisms by which neuroblastoma cells are induced to undergo apoptosis in vitro as well as in vivo. Collectively, these model systems provide important tools for investigation of the biology of neuroblastoma tumors and evaluation of mechanisms that mediate the regression of these tumors in response to novel therapeutic agents, including cytokines such as interleukin-12.
C1 NCI, Pediat Oncol Branch, CCR, Frederick, MD 21702 USA.
   Sci Applicat Int Corp, Intramural Res Support Program, NCI, Frederick, MD USA.
RP Wigginton, JM (reprint author), NCI, Pediat Oncol Branch, CCR, Bldg 560,Room 31-93, Frederick, MD 21702 USA.
EM jw121b@nih.gov
FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]
NR 41
TC 6
Z9 7
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD MAR-APR
PY 2006
VL 29
IS 2
BP 151
EP 164
DI 10.1097/01.cji.0000190167.76663.c7
PG 14
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 018LU
UT WOS:000235766600005
PM 16531816
ER

PT J
AU Attia, P
   Powell, DJ
   Maker, AV
   Kreitman, RJ
   Pastan, I
   Rosenberg, SA
AF Attia, P
   Powell, DJ
   Maker, AV
   Kreitman, RJ
   Pastan, I
   Rosenberg, SA
TI Selective elimination of human regulatory T lymphocytes in vitro with
   the recombinant immunotoxin LMB-2
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE human; immunotoxin; LMB-2; CD25; regulatory T cell; depletion;
   Pseudomonas exotoxin
ID TOXIN FUSION PROTEIN; PSEUDOMONAS EXOTOXIN; METASTATIC MELANOMA; CELL
   LEUKEMIA; MONOCLONAL-ANTIBODY; CANCER REGRESSION; IMMUNE-RESPONSES;
   INTERLEUKIN-2; IMMUNOTHERAPY; AUTOIMMUNITY
AB CD4(+)CD25(+) T-regulatory cells (T-reg) can inhibit the proliferation and cytokine secretion of CD4(+)CD25(-) helper T cells in mice and humans. In murine tumor models, the presence of these T-reg cells can inhibit the antitumor effectiveness of T-cell transfer and active immunization approaches. We have thus initiated efforts to eliminate T-reg cells selectively from human peripheral blood mononuclear cells (PBMCs) to potentially bolster antitumor responses. LMB-2 is a recombinant immunotoxin that is a fusion of a single-chain Fv fragment of the anti-Tac anti-CD25 monoclonal antibody to a truncated form of the bacterial Pseudomonas exotoxin A. In vitro incubation of human PBMCs with LMB-2 reduced the levels of CD4(+)CD25(+) and Foxp3-expressing cells without impairing the function of the remaining lymphocytes. The short in vivo half-life of LMB-2 makes it an attractive candidate for reducing human T-reg cells in vivo before the administration of cancer vaccine or cell transfer immunotherapy approaches.
C1 NCI, Surg Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
   NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Ctr Canc Res, Room 3W-3940,10 Ctr Dr, Bethesda, MD 20892 USA.
EM sar@nih.gov
FU Intramural NIH HHS; NCI NIH HHS [Z01 SC003811-31]
NR 34
TC 48
Z9 51
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD MAR-APR
PY 2006
VL 29
IS 2
BP 208
EP 214
DI 10.1097/01.cji.0000187959.45803.0c
PG 7
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 018LU
UT WOS:000235766600010
PM 16531821
ER

PT J
AU Rosenberg, SA
   Sherry, RM
   Morton, KE
   Yang, JC
   Topalian, SL
   Royal, RE
   Kammula, US
   Restifo, NP
   Hughes, MS
   Schwarz, SL
   Ngo, LT
   Mavroukakis, SA
   White, DE
AF Rosenberg, SA
   Sherry, RM
   Morton, KE
   Yang, JC
   Topalian, SL
   Royal, RE
   Kammula, US
   Restifo, NP
   Hughes, MS
   Schwarz, SL
   Ngo, LT
   Mavroukakis, SA
   White, DE
TI Altered CD8(+) T-cell responses when immunizing with multiepitope
   peptide vaccines
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE vaccines; cancer; peptides; melanoma
ID COLONY-STIMULATING FACTOR; PHASE-I TRIAL; METASTATIC MELANOMA; REACTIVE
   CTL; ANTIGEN; IMMUNOTHERAPY; ADJUVANT; VACCINATION; LYMPHOCYTE;
   INDUCTION
AB Efforts to develop effective cancer vaccines often use combinations of immunogenic peptides to increase the applicability and effectiveness of the immunizations. The immunologic consequences of combining more than 1 self/tumor antigen in a single vaccine emulsion remain unclear, however. We performed 2 sequential clinical trials in patients at high risk for melanoma recurrence. Patients were given the highly immunogenic gp100:209-217(210M) peptide and the less immunogenic tyrosinase:368-376(370D) peptide once every 3 weeks for 4 weeks. This vaccination course was 12 weeks long, and patients were vaccinated for up to 4 courses (16 total vaccinations). In the first trial in 31 patients, the peptides were emulsified separately in incomplete Freund adjuvant and injected at 2 different sites. In the second trial in 33 patients, the peptides were emulsified together and injected at the same site. Cryopreserved lymphocytes were obtained by apheresis after each course and were evaluated for antipeptide activity using tetramer, enzyme-linked immunospot, and in vitro sensitization boost assays. When the peptides were injected at separate sites, robust specific reactivity to the native gp100:209-217 peptide was measured by each of the assays, whereas immunization with the tyrosinase:368-376(370D) peptide was far less effective. When the peptides were emulsified and injected together at the same site, immunization to the gp100:209-217(210M) epitope dropped precipitously, whereas reactivity to the tyrosinase: 368-376(370D) peptide was enhanced. These cautionary data indicate that mixing peptides in the same emulsion can alter reactivity compared with peptides injected separately by mechanisms that may include the induction of localized nonspecific inflammation or competitive binding of peptides to major histocompatibility complex molecules.
C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Clin Res Ctr, Room 3-3940, Bethesda, MD 20892 USA.
EM SAR@nih.gov
RI Restifo, Nicholas/A-5713-2008; 
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01]
NR 21
TC 26
Z9 27
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD MAR-APR
PY 2006
VL 29
IS 2
BP 224
EP 231
DI 10.1097/01.cji.0000190399.98802.10
PG 8
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 018LU
UT WOS:000235766600012
PM 16531823
ER

PT J
AU Chen, ZC
   Moayeri, M
   Zhou, YH
   Leppla, S
   Emerson, S
   Sebrell, A
   Yu, FJ
   Svitel, J
   Schuck, P
   St Claire, M
   Purcell, R
AF Chen, ZC
   Moayeri, M
   Zhou, YH
   Leppla, S
   Emerson, S
   Sebrell, A
   Yu, FJ
   Svitel, J
   Schuck, P
   St Claire, M
   Purcell, R
TI Efficient neutralization of anthrax toxin by chimpanzee monoclonal
   antibodies against protective antigen
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID BACILLUS-ANTHRACIS; RECEPTOR-BINDING; PHAGE DISPLAY; CORONAVIRUS
   INFECTION; GUINEA-PIGS; AFFINITY; PROTEIN; VIRUS; INTERNALIZATION;
   IDENTIFICATION
AB Four single-chain variable fragments (scFvs) against protective antigen (PA) and 2 scFvs against lethal factor (LF) of anthrax were isolated from a phage display library generated from immunized chimpanzees. Only 2 scFvs recognizing PA (W1 and W2) neutralized the cytotoxicity of lethal toxin in a macrophage lysis assay. Full-length immunoglobulin G (IgG) of W1 and W2 efficiently protected rats from anthrax toxin challenge. The epitope recognized by W1 and W2 was conformational and was formed by C-terminal amino acids 614 735 of PA. W1 and W2 each bound to PA with an equilibrium dissociation constant of 4 x 10(-11) mol/L to 5 x x 10(-11) mol/L, which is an affinity that is 20-100-fold higher than that for the interaction of the receptor and PA. W1 and W2 inhibited the binding of PA to the receptor, suggesting that this was the mechanism of protection. These data suggest that W1 and W2 chimpanzee monoclonal antibodies may serve as PA entry inhibitors for use in the emergency prophylaxis against and treatment of anthrax.
C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
   NIAID, Mol Hepatitis Sect, Infect Dis Lab, Bethesda, MD 20892 USA.
   NIAID, Bacterial Toxins & Therapeut Sect, Bethesda, MD 20892 USA.
   NIH, Prot Biophys Resource, Bethesda, MD 20892 USA.
   Bioqual, Rockville, MD USA.
RP Chen, ZC (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bldg 50,Rm 6533,50 S Dr, Bethesda, MD 20892 USA.
EM zchen@niaid.nih.gov
OI Schuck, Peter/0000-0002-8859-6966
FU Intramural NIH HHS; NIAID NIH HHS [N01-AO-02733]
NR 40
TC 49
Z9 50
U1 2
U2 3
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2006
VL 193
IS 5
BP 625
EP 633
DI 10.1086/500148
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 015EU
UT WOS:000235535500003
PM 16453257
ER

PT J
AU Solomon, SB
   Cui, XZ
   Gerstenberger, E
   Danner, RL
   Fitz, Y
   Banks, SM
   Natanson, C
   Eichacker, PQ
AF Solomon, SB
   Cui, XZ
   Gerstenberger, E
   Danner, RL
   Fitz, Y
   Banks, SM
   Natanson, C
   Eichacker, PQ
TI Effective dosing of lipid a analogue E5564 in rats depends on the timing
   of treatment and the route of Escherichia coli infection
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; LIPOPOLYSACCHARIDE-BINDING PROTEIN; TOLL-LIKE
   RECEPTORS; SEPTIC SHOCK; ENDOTOXIN RESPONSE; FACTOR-ALPHA; ANTIENDOTOXIN
   STRATEGIES; MONOCLONAL-ANTIBODY; RANDOMIZED-TRIAL; HOST-DEFENSE
AB Background. E5564, a competitive lipid A antagonist, inhibits endotoxin-stimulated inflammation and is under study in patients with sepsis. Methods. We tested whether clinically relevant variables, including the timing of treatment and the route of infection, influenced the effective dosing of E5564 in Escherichia coli-challenged rats.
   Results. All E5564 doses ( 0.3, 1.0, 2.0, and 3.0 mg/kg intravascular bolus followed by 10% of the bolus dose infused hourly for 24 h) administered 1 h before intravascular E. coli challenge similarly reduced the risk of death. Delaying the start of E5564 to 1 or 3 h after intravascular E. coli challenge significantly reduced the beneficial effect of the doses tested. However, increasing the dose of E5564 reversed some loss of efficacy for delayed treatment (P = .004, for increasing benefit with increasing dose at 1 h). During intrabronchial or intraperitoneal (extravascular) E. coli challenge, the pattern of effective E5564 dosing was the inverse of that for intravascular E. coli challenge (P = 0.001, for the interaction) - lower doses of E5564 were beneficial and higher doses were not (0.03, 0.3, 1.0, 2.0, and 3.0 mg/kg bolus followed by infusion) (P = .05, for decreasing benefit with increasing dose at 1 h).
   Conclusion. These findings suggest that, for maximal clinical benefit, E5564 should be given early and that dosing should be adjusted upward for intravascular infection and downward for extravascular infection.
C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Solomon, SB (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 7D43, Bethesda, MD 20892 USA.
EM ssolomon@cc.nih.gov
FU Intramural NIH HHS
NR 50
TC 19
Z9 20
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2006
VL 193
IS 5
BP 634
EP 644
DI 10.1086/500147
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 015EU
UT WOS:000235535500004
PM 16453258
ER

PT J
AU Roberts, A
   Thomas, WD
   Guarner, J
   Lamirande, EW
   Babcock, GJ
   Greenough, TC
   Vogel, L
   Hayes, N
   Sullivan, JL
   Zaki, S
   Subbarao, K
   Ambrosino, DM
AF Roberts, A
   Thomas, WD
   Guarner, J
   Lamirande, EW
   Babcock, GJ
   Greenough, TC
   Vogel, L
   Hayes, N
   Sullivan, JL
   Zaki, S
   Subbarao, K
   Ambrosino, DM
TI Therapy with a severe acute respiratory syndrome-associated
   coronavirus-neutralizing human monoclonal antibody reduces disease
   severity and viral burden in golden Syrian hamsters
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 10th International Nidovirus Symposium
CY JUN 25-30, 2005
CL Colorado Springs, CO
ID FELINE INFECTIOUS PERITONITIS; SARS CORONAVIRUS; PROTECTIVE IMMUNITY;
   CLINICAL PROGRESSION; SYNCYTIAL VIRUS; AFRICAN-GREEN; SPIKE PROTEIN;
   MICE; IMMUNIZATION; MONKEYS
AB Background. Immunotherapy with monoclonal antibodies (MAbs) offers safe interventions for the prevention of infection in patients after organ transplantation and for the treatment of cancers and autoimmune diseases. MAb 201 is a severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-specific MAb that prevents establishment of viral replication in vitro and prevents viral replication in vivo when administered prophylactically. The efficacy of MAb 201 in the treatment of SARS was evaluated in golden Syrian hamsters, an animal model that supports SARS-CoV replication to high levels and displays severe pathological changes associated with infection, including pneumonitis and pulmonary consolidation.
   Methods. Golden Syrian hamsters that were intranasally inoculated with SARS-CoV were treated with various doses of MAb 201 or an irrelevant MAb 24 h after inoculation. Two to 7 days after infection, the hamsters were killed, and their lungs were collected for evaluation of viral titers and pathological findings.
   Results. Postexposure treatment with MAb 201 can alleviate the viral burden and associated pathological findings in a golden Syrian hamster model of SARS-CoV infection. After a hamster is treated with MAb 201, its viral burden is reduced by 10(2.4)-10(3.9) 50% tissue-culture infectious doses per gram of tissue, and the severity of associated pathological findings, including interstitial pneumonitis and consolidation, is also remarkably reduced.
   Conclusions. The demonstration of successful postexposure MAb 201 therapy in an animal model that demonstrates viral replication and associated pulmonary pathological findings suggests that MAb 201 may be useful in the arsenal of tools to combat SARS.
C1 Univ Massachusetts, Massachusetts Biol Labs, Sch Med, Jamaica Plain, MA 02130 USA.
   NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
   Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA.
   Univ Massachusetts, Sch Med, Dept Mol Med, Worcester, MA USA.
   Ctr Dis Control & Prevent, Infect Dis Pathol Act, Natl Ctr Infect Dis, Atlanta, GA USA.
RP Ambrosino, DM (reprint author), Univ Massachusetts, Massachusetts Biol Labs, Sch Med, 305 South St, Jamaica Plain, MA 02130 USA.
EM donna.ambrosino@umassmed.edu
RI Guarner, Jeannette/B-8273-2013
FU NIAID NIH HHS [N01-AI65315]
NR 30
TC 47
Z9 51
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2006
VL 193
IS 5
BP 685
EP 692
DI 10.1086/500143
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 015EU
UT WOS:000235535500010
PM 16453264
ER

PT J
AU Liu, HL
   Carrington, M
   Wang, CH
   Holte, S
   Lee, J
   Greene, B
   Hladik, F
   Koelle, DM
   Wald, A
   Kurosawa, K
   Rinaldo, CR
   Celum, C
   Detels, R
   Corey, L
   McElrath, MJ
   Zhu, TF
AF Liu, HL
   Carrington, M
   Wang, CH
   Holte, S
   Lee, J
   Greene, B
   Hladik, F
   Koelle, DM
   Wald, A
   Kurosawa, K
   Rinaldo, CR
   Celum, C
   Detels, R
   Corey, L
   McElrath, MJ
   Zhu, TF
TI Repeat-region polymorphisms in the gene for the dendritic cell-specific
   intercellular adhesion molecule-3-grabbing nonintegrin related molecule:
   Effects on HIV-1 susceptibility
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 10th Conference on Retroviruses and Opportunistic Infections
CY FEB 10-14, 2003
CL BOSTON, MA
ID VIRUS TYPE-1 INFECTION; DC-SIGNR; SERONEGATIVE MEN; T-CELLS;
   ASSOCIATION; TRANSCRIPTS; PROGRESSION; ISOFORMS; PROTEIN; AIDS
AB In 1716 individuals-801 human immunodeficiency virus (HIV)-1-seropositive individuals, 217 high-risk HIV-1-seronegative individuals, and 698 general HIV-1-seronegative individuals-from a Seattle cohort and a Multicenter AIDS Cohort Study cohort, the association between HIV1 susceptibility and repeat-region polymorphisms in the gene for the dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin-related molecule (DC-SIGNR) was investigated; 16 genotypes were found in the DC-SIGNR repeat region. The DC-SIGNR homozygous 7/7 repeat was found to be associated with an increased risk of HIV-1 infection (17.5% in high-risk HIV-1-seronegative individuals vs. 28.5% in HIV-1-seropositive individuals;), whereas the DC-SIGNR heterozygous 7/5 repeat Pp. 0015 tended to be correlated with resistance to HIV-1 infection (35.5% in high-risk HIV-1-seronegative individuals vs. 27.6% in HIV-1-seropositive individuals;). These Pp. 0291 findings suggest that DC-SIGNR polymorphisms may influence susceptibility to HIV-1.
C1 Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA.
   Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
   Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA.
   Fred Hutchinson Canc Res Ctr, Program Infect Dis, Seattle, WA 98104 USA.
   Fred Hutchinson Canc Res Ctr, Program Biostat, Seattle, WA 98104 USA.
   NCI, Basic Res Program, Sci Applicat Int Corp, Lab Genom Divers, Frederick, MD 21701 USA.
   Univ Pittsburgh, Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15260 USA.
   Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
RP Zhu, TF (reprint author), Univ Washington, Sch Med, Dept Lab Med, Box 358070,1959 NE Pacific St, Seattle, WA 98195 USA.
EM tzhu@u.washington.edu
RI Zhu, Tuofu/G-6158-2010; Wang, Chunhui/F-9352-2012; Hladik,
   Florian/G-1041-2012; Wald, Anna/B-6272-2012; Koelle, David/Q-6529-2016; 
OI Hladik, Florian/0000-0002-0375-2764; Wald, Anna/0000-0003-3486-6438;
   Koelle, David/0000-0003-1255-9023; Liu, Huanliang/0000-0002-1006-6666
FU NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [AI 49109, AI 056994, AI
   35605, AI 41535, AI 45402]
NR 15
TC 41
Z9 48
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2006
VL 193
IS 5
BP 698
EP 702
DI 10.1086/499820
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 015EU
UT WOS:000235535500012
PM 16453266
ER

PT J
AU Estes, JD
   Li, QS
   Reynolds, MR
   Wietgrefe, S
   Duan, LJ
   Schacker, T
   Picker, LJ
   Watkins, DI
   Lifson, JD
   Reilly, C
   Carlis, J
   Haase, AT
AF Estes, JD
   Li, QS
   Reynolds, MR
   Wietgrefe, S
   Duan, LJ
   Schacker, T
   Picker, LJ
   Watkins, DI
   Lifson, JD
   Reilly, C
   Carlis, J
   Haase, AT
TI Premature induction of an immunosuppressive regulatory T cell response
   during acute simian immunodeficiency virus infection
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT Keystone Conference on HIV Pathogenesis
CY APR 09-15, 2005
CL Banff, CANADA
SP Ontario HIV Treatment Network
ID IMMUNOLOGICAL SELF-TOLERANCE; IN-VITRO; PERIPHERAL-BLOOD;
   AUTOIMMUNE-DISEASE; EFFECTOR FUNCTION; IMMUNE-RESPONSES; HIV-INFECTION;
   CD4(+); VIVO; SIV
AB Here we report the results of an investigation into the possibility that one mechanism responsible for the establishment of persistent human immunodeficiency virus infection is an early regulatory T (T-reg) cell response that blunts virus-specific responses. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model, we show that, indeed, viral replication and immune activation in lymphatic tissue drive a premature immunosuppressive response, with dramatic increases in the frequencies of CD4(+)CD25(+)FOXP3(+) T-reg cells, transforming growth factor-beta 1(+) cells, interleukin-10(+) cells, and indoleamine 2,3-dioxygenase(+)CD3(+) cells. When we compared SIV infection with rhesus cytomegalovirus (RhCMV) infection, we found that the frequency of T-reg cells paralleled the magnitude of immune activation during both infections but that the magnitude of immune activation and of the T-reg cell response were lower and peaked much later during RhCMV infection. Importantly, the frequency of T-reg cells inversely correlated with the magnitude of the SIV-specific cytotoxic T lymphocyte response. We conclude that an early T-reg cell response during acute SIV infection may contribute to viral persistence by prematurely limiting the antiviral immune response before infection is cleared.
C1 Univ Minnesota, Dept Microbiol, Sch Med, Minneapolis, MN 55455 USA.
   Univ Minnesota, Dept Med, Sch Med, Minneapolis, MN 55455 USA.
   Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
   Univ Minnesota, Dept Comp Sci & Engn, Inst Technol, Minneapolis, MN 55455 USA.
   Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA.
   Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI USA.
   Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Pathol, Beaverton, OR USA.
   Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Dept Mol Microbiol & Immunol, Beaverton, OR USA.
   Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
   NCI, AIDS Vaccine Program, Sci Applicat Int Corp, Frederick, MD 21701 USA.
RP Haase, AT (reprint author), Univ Minnesota, Dept Microbiol, Sch Med, MMC 196,420 Delaware St SE, Minneapolis, MN 55455 USA.
EM haase001@umn.edu
FU NCI NIH HHS [N01-CO-124000]; NCRR NIH HHS [U51 RR00169]; NIAID NIH HHS
   [AI056997, R01 AI48484, R01 AI5129, R01 AI51596, T32 AI07421]
NR 48
TC 172
Z9 180
U1 0
U2 3
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2006
VL 193
IS 5
BP 703
EP 712
DI 10.1086/500368
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 015EU
UT WOS:000235535500013
PM 16453267
ER

PT J
AU Makobongo, MO
   Keegan, B
   Long, CA
   Miller, LH
AF Makobongo, MO
   Keegan, B
   Long, CA
   Miller, LH
TI Immunization of Aotus monkeys with recombinant cysteine-rich interdomain
   region 1 alpha protects against severe disease during Plasmodium
   falciparum reinfection
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 53rd Annual Meeting of the
   American-Society-of-Tropical-Medicine-and-Hygiene
CY NOV 07-11, 2004
CL Miami Beach, FL
SP Amer Soc Trop Med & Hyg
ID NATURALLY ACQUIRED-IMMUNITY; INFECTED ERYTHROCYTES; VARIANT ANTIGEN;
   MALARIA; PARASITE; SURFACE; ANEMIA; CD36; CYTOADHERENCE; ANTIBODIES
AB Background. After continuous exposure to malarial infections in regions of Africa where malaria is hyperendemic, children attain clinical immunity. This immunity results, in part, from the acquisition of antibodies against a large repertoire of variant antigens expressed on the surface of infected erythrocytes, such as the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). We determined whether a subunit vaccine to a portion of PfEMP1 could induce protection in nonhuman primates.
   Methods. We immunized Aotus nancymai monkeys with PfEMP1 recombinant (r) cysteine-rich interdomain region 1 alpha (CIDR1 alpha) and infected them twice with P. falciparum Vietnam Oak Knoll strain, the most virulent strain of P. falciparum in Aotus monkeys-each infection expressed a different PfEMP1. Anti-PfEMP1 antibodies were analyzed by enzyme-linked immunosorbent assay against rCIDR1 alpha and by flow cytometry against infected erythrocytes.
   Results. Immunization with rCIDR1a was not protective, despite delayed patency during the first infection, but it protected monkeys against severe anemia during reinfection. Protection against anemia is associated with a more rapid increase in antibodies to PfEMP1.
   Conclusion. The findings of reduced severe disease in rCIDR1 alpha-vaccinated Aotus monkeys provide experimental support for a PfEMP1-based vaccine to protect African children against severe malarial disease. Such vaccination may function by priming for the accelerated acquisition of immunity to new PfEMP1 variants.
C1 NIAID, Malaria Vaccine Dev Branch, NIH, Twinbrook Facil 1, Rockville, MD 20852 USA.
RP Miller, LH (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, Twinbrook Facil 1, 5640 Fishers Ln, Rockville, MD 20852 USA.
EM lmiller@niaid.nih.gov
FU Intramural NIH HHS
NR 32
TC 18
Z9 19
U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 1
PY 2006
VL 193
IS 5
BP 731
EP 740
DI 10.1086/500150
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 015EU
UT WOS:000235535500016
PM 16453270
ER

PT J
AU Katz, SI
AF Katz, Stephen I.
TI Irwin Freedberg and the government
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Biographical-Item
C1 NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Katz, SI (reprint author), NIAMSD, NIH, Bldg 31-4032, Bethesda, MD 20892 USA.
EM katzs@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAR
PY 2006
VL 126
IS 3
BP 523
EP 523
DI 10.1038/sj.jid.5700177
PG 1
WC Dermatology
SC Dermatology
GA 062TW
UT WOS:000238968500008
PM 16482180
ER

PT J
AU Davidson, HM
AF Davidson, Harold M.
TI Irwin Freedberg on NIH study section
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Biographical-Item
C1 NIH, CSR, Bethesda, MD 20892 USA.
RP Davidson, HM (reprint author), NIH, CSR, 6701 Rockledge Dr,MSC 7814, Bethesda, MD 20892 USA.
EM davidsoh@csr.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAR
PY 2006
VL 126
IS 3
BP 524
EP 524
DI 10.1038/sj.jid.5700178
PG 1
WC Dermatology
SC Dermatology
GA 062TW
UT WOS:000238968500009
PM 16482181
ER

PT J
AU Diwakar, G
   Hornyak, TJ
AF Diwakar, Ganesh
   Hornyak, Thomas J.
TI Cafe-au-lait patches and senile plaques: How APPt the connection?
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Editorial Material
ID NEUROFIBROMATOSIS; VONRECKLINGHAUSEN; KERATINOCYTE; KINESIN; MACULES;
   RHO
AB Neurofibromatosis type 1 (NF1) is a genetic disease caused by mutations in the NF1 gene, which encodes the protein neurofibromin. Patients exhibit characteristic hyperpigmented patches called cafe-au-lait patches. Melanocytes of NF1 patients differ from normal human melanocytes, but no differences account completely for lesional hyperpigmentation. An association between beta-amyloid precursor protein (APP) and neurofibromin, and their localization to the melanosome, may help explain the development of cafe-au-lait patches.
C1 NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20814 USA.
RP Hornyak, TJ (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10-12N242, Bethesda, MD 20814 USA.
EM hornyakt@mail.nih.gov
FU Intramural NIH HHS
NR 18
TC 1
Z9 1
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAR
PY 2006
VL 126
IS 3
BP 547
EP 550
DI 10.1038/sj.jid.5700165
PG 4
WC Dermatology
SC Dermatology
GA 062TW
UT WOS:000238968500021
PM 16482197
ER

PT J
AU De Schepper, S
   Boucneau, JMA
   Westbroek, W
   Mommaas, M
   Onderwater, J
   Messiaen, L
   Naeyaert, JMAD
   Lambert, JLW
AF De Schepper, Sofie
   Boucneau, Joachim M. A.
   Westbroek, Wendy
   Mommaas, Mieke
   Onderwater, Jos
   Messiaen, Ludwine
   Naeyaert, Jean-Marie A. D.
   Lambert, Jo L. W.
TI Neurofibromatosis type 1 protein and amyloid precursor protein interact
   in normal human melanocytes and colocalize with melanosomes
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID AXONAL-TRANSPORT; GENE-PRODUCT; MICROTUBULES; CELLS; APP
AB The neurofibromatosis type 1 (NF1) gene product, neurofibromin, is known to interact with Ras, thereby negatively regulating its growth-promoting function. Although this is a well-established interaction, the discovery of other neurofibromin interacting partners could reveal new functional properties of this large protein. Using yeast two-hybrid analysis against a brain cDNA library, we identified a novel interaction between the amyloid precursor protein and the GTPase activating protein-related domain of neurofibromin. This interaction was further analyzed in human melanocytes and confirmed by immunoprecipitation and colocalization studies. In addition, we observed a colocalization of amyloid precursor protein and neurofibromin with melanosomes. Amyloid precursor protein has been proposed to function as a vesicle cargo receptor for the motor protein kinesin-1 in neurons. This colocalization of amyloid precursor protein and neurofibromin with melanosomes was lost in melanocytes obtained from normal skin of a NF1 patient. We suggest that a complex between amyloid precursor protein, neurofibromin, and melanosomes might be important in melanosome transport, which could shed a new light on the etiopathogenesis of pigment-cell-related manifestations in NF1.
C1 Univ Ghent, Dept Dermatol, B-9000 Ghent, Belgium.
   NHGRI, Med Genet Branch, Sect Human Biochem Genet, NIH, Bethesda, MD 20892 USA.
   Leiden Univ, Med Ctr, Dept Mol & Cell Biol, Ctr Electron Microscopy, Leiden, Netherlands.
   Univ Alabama, Dept Genet, Birmingham, AL USA.
RP De Schepper, S (reprint author), Univ Ghent, Dept Dermatol, Pintelaan 185, B-9000 Ghent, Belgium.
EM sofie.deschepper@ugent.be
NR 25
TC 16
Z9 18
U1 2
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAR
PY 2006
VL 126
IS 3
BP 653
EP 659
DI 10.1038/sj.jid.5700087
PG 7
WC Dermatology
SC Dermatology
GA 062TW
UT WOS:000238968500036
PM 16374483
ER

PT J
AU Scarpa, A
AF Scarpa, A
TI The JIM interview
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Editorial Material
C1 NIH, Ctr Sci Rev, Bethesda, MD 20892 USA.
RP Scarpa, A (reprint author), NIH, Ctr Sci Rev, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 1
U2 1
PU B C DECKER INC
PI HAMILTON
PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7,
   CANADA
SN 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2006
VL 54
IS 2
BP 47
EP 50
DI 10.2310/6650.2006.X0001
PG 4
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 021QS
UT WOS:000235999400001
PM 16472471
ER

PT J
AU Choong, NW
   Dietrich, S
   Seiwert, TY
   Tretiakova, MS
   Nallasura, V
   Davies, GC
   Lipkowitz, S
   Husain, AN
   Salgia, R
   Ma, PC
AF Choong, NW
   Dietrich, S
   Seiwert, TY
   Tretiakova, MS
   Nallasura, V
   Davies, GC
   Lipkowitz, S
   Husain, AN
   Salgia, R
   Ma, PC
TI Gefitinib response of erlotinib-refractory lung cancer with
   leptomeningeal metastasis.
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Combined Annual Meeting of the
   Central-Society-for-Clinical-Research/Midwestern-Section-of the
   American-Federation-for-Medical-Research
CY APR   28, 2006
CL Chicago, IL
SP Central Soc Clin Res, Amer Fed Med Res, Midwestern Sec
C1 Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA.
   Univ Chicago, Dept Pathol, Hematol Oncol Sect, Chicago, IL 60637 USA.
   NCI, NIH, Bethesda, MD 20892 USA.
   Case Western Reserve Univ, Case Comprehens Canc Ctr, Div Hematol Oncol, Cleveland, OH 44106 USA.
RI Nallasura, Vidya/D-8947-2011
NR 0
TC 0
Z9 0
U1 0
U2 3
PU B C DECKER INC
PI HAMILTON
PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7,
   CANADA
SN 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2006
VL 54
IS 2
MA 70
BP S355
EP S355
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 021QS
UT WOS:000235999400087
ER

PT J
AU Goldstein, DS
   Sharabi, Y
   Bentho, O
   Eisenhofer, G
AF Goldstein, DS
   Sharabi, Y
   Bentho, O
   Eisenhofer, G
TI Cardiac sympathetic denervation preceding Parkinson disease
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
CT Combined Annual Meeting of the
   Central-Society-for-Clinical-Research/Midwestern-Section-of the
   American-Federation-for-Medical-Research
CY APR   28, 2006
CL Chicago, IL
SP Central Soc Clin Res, Amer Fed Med Res, Midwestern Sec
C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU B C DECKER INC
PI HAMILTON
PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7,
   CANADA
SN 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2006
VL 54
IS 2
MA 24
BP S377
EP S377
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 021QS
UT WOS:000235999400121
ER

PT J
AU Hsu, LY
   Natanzon, A
   Kellman, P
   Hirsch, GA
   Aletras, AH
   Arai, AE
AF Hsu, LY
   Natanzon, A
   Kellman, P
   Hirsch, GA
   Aletras, AH
   Arai, AE
TI Quantitative myocardial infarction on delayed enhancement MRI. Part I:
   Animal validation of an automated feature analysis and combined
   thresholding infarct sizing algorithm
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE myocardial infarction; magnetic resonance imaging; computer algorithm;
   image processing; expert system; contrast agent; gadolinium
ID CONTRAST ENHANCEMENT; IRREVERSIBLE INJURY; AGREEMENT; IMAGES; SIZE
AB Purpose: To develop a computer algorithm to measure myocardial infarct size in gadolinium-enhanced magnetic resonance (MR) imaging and to validate this method using a canine histopathological reference.
   Materials and Methods: Delayed enhancement MR was performed in 11 dogs with myocardial infarction (MI) determined by triphenyltetrazolium chloride (TTC). Infarct size on in vivo and ex vivo images was measured by a computer algorithm based on automated feature analysis and combined thresholding (FACT). For comparison, infarct size by human manual contouring and simple intensity thresholding (based on two standard deviation [2SD] and full width at half maximum [FWHM]) were studied.
   Results: Both in vivo and ex vivo MR infarct size measured by the FACT algorithm correlated well with TTC (R = 0.95-0.97) and showed no significant bias on Bland Altman analysis (P = not significant). Despite similar cor-relations (R = 0.91-0.97), human manual contouring overestimated in vivo MR infarct size by 5.4% of the left ventricular [LV] area (equivalent to 55.1% of the MI area) vs. TTC (P < 0.001). Infarct size measured by simple intensity thresholdings was less accurate than the proposed algorithm (P < 0.001 and P = 0.007).
   Conclusion: The FACT algorithm accurately measured MI size on delayed enhancement MR imaging in vivo and ex vivo. The FACT algorithm was also more accurate than human manual contouring and simple intensity thresholding approaches.
C1 NHLBI, Cardiac Energet Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, Dept Hlth & Human Serv, NIH, 10 Ctr Dr,MSC 1061,Bldg 10,Room B1D-416, Bethesda, MD 20892 USA.
EM araia@nih.gov
OI Aletras, Anthony/0000-0002-3786-3817
NR 23
TC 91
Z9 91
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD MAR
PY 2006
VL 23
IS 3
BP 298
EP 308
DI 10.1002/jmri.20496
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 022LX
UT WOS:000236058400006
PM 16450367
ER

PT J
AU Hsu, LY
   Ingkanisorn, WP
   Kellman, P
   Aletras, AH
   Arai, AE
AF Hsu, LY
   Ingkanisorn, WP
   Kellman, P
   Aletras, AH
   Arai, AE
TI Quantitative myocardial infarction on delayed enhancement MRI. Part II:
   Clinical application of an automated feature analysis and combined
   thresholding infarct sizing algorithm
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE myocardial infarction; myocardial viability; magnetic resonance imaging;
   computer aided diagnosis; contrast agent; gadolinium
ID CARDIOVASCULAR MAGNETIC-RESONANCE; IRREVERSIBLE INJURY; SCAR
AB Purpose: To compare global and regional myocardial infarction (MI) measurements on clinical gadolinium-enhanced magnetic resonance (MR) images using human manual contouring and a computer algorithm previously validated by histopathology, and to study the degree to Which Visual assessment. and human contouring of infarct extent agreed with the computer algorithm.
   Materials and Methods: Infarct size in 20 patients was measured by human manual contouring and with an automated feature analysis and combined thresholding (FACT) computer algorithm. Short-axis slices were divided into myocardial sectors for regional analysis. Extent of infarction was also graded visually by Consensus of expert. readers and compared to human and computer contouring.
   Results: Despite good correlations (R = 0.93-0.95) between human contouring and the FACT algorithm, human contouring overestimated infarct size by 3.8% of the left. ventricle (23.8% of the MI) area (P < 0.001). Human contouring also overestimated the circumferential extent, transmural extent, and extent of infarction within a sector by 7.1%, 18.2%, and 27.9%, respectively (all P < 0.001). Both Consensus reading and human contouring overestimated infarct grades compared with the FACT algorithm (P = 0.002 and P < 0.001).
   Conclusion: Clinically relevant overestimation of MI can occur in visual interpretation and in human manual contouring, particularly with respect to extent of infarction on a regional basis.
C1 NHLBI, Cardiac Energet Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, Dept Hlth & Human Serv, NIH, 10 Ctr Dr,MSC 1061,Bldg 10,Room B1D-416, Bethesda, MD 20892 USA.
EM araia@nih.gov
OI Aletras, Anthony/0000-0002-3786-3817
NR 15
TC 55
Z9 56
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD MAR
PY 2006
VL 23
IS 3
BP 309
EP 314
DI 10.1002/jmri.20495
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 022LX
UT WOS:000236058400007
PM 16450368
ER

PT J
AU Hsu, LY
   Rhoads, KL
   Holly, JE
   Kellman, P
   Aletras, AH
   Arai, AE
AF Hsu, LY
   Rhoads, KL
   Holly, JE
   Kellman, P
   Aletras, AH
   Arai, AE
TI Quantitative myocardial perfusion analysis with a dual-bolus
   contrast-enhanced first-pass MRI technique in humans
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE magnetic resonance imaging; myocardial perfusion; myocardial blood flow;
   myocardial perfusion reserve; contrast agent; gadolinium
ID MAGNETIC-RESONANCE; BLOOD-FLOW; NONINVASIVE DETECTION; TRANSIT-TIME;
   DECONVOLUTION; RESERVE; MODEL; QUANTIFICATION; DOGS
AB Purpose: To compare fully quantitative and semiquantitative analysis of rest and stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) using a dual-bolus first-pass perfusion MRI method in humans.
   Materials and Methods: Rest and dipyridamole stress perfusion imaging was performed on 10 healthy humans by administering gadolinium contrast using a dual-bolus protocol. Ventricular and myocardial time-signal intensity curves were generated from a series of T1-weighted images and adjusted for surface-coil intensity variations. Corrected signal intensity curves were then fitted using fully quantitative model constrained deconvolution (MCD) to quantify MBF (mL/min/g) and MPR. The results were compared with semiquantitative contrast enhancement ratio (CER) and upslope index (SLP) measurements.
   Results: MBF (mL/min/g) estimated With MCD averaged 1.02 +/- 0.22 at rest and 3.39 +/- 0.59 for stress with no overlap in measures. MPR was 3.43 +/- 0.71, 1.91 +/- 0.65, and 1.16 +/- 0.19 using MCD, SLP, and CER. Both semiquantitative parameters (SLP and CER) significantly underestimated MPR (P < 0.001) and failed to completely discriminate rest and stress perfusion.
   Conclusion: Rest and stress MBF (mL/min/g) and MPR estimated by dual-bolus perfusion MRI fit within published ranges. Semiquantitative methods (SLP and CER) significantly underestimated MPR.
C1 NHLBI, Cardiac Energet Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, Dept Hlth & Human Serv, NIH, 10 Ctr Dr,MSC 1061,Bldg 10,Room B1D-416, Bethesda, MD 20892 USA.
EM araia@nih.gov
OI Aletras, Anthony/0000-0002-3786-3817
NR 21
TC 87
Z9 87
U1 2
U2 3
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD MAR
PY 2006
VL 23
IS 3
BP 315
EP 322
DI 10.1002/jmri.20502
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 022LX
UT WOS:000236058400008
PM 16463299
ER

PT J
AU Pettit, GR
   Numata, A
   Iwamoto, C
   Usami, Y
   Yamada, T
   Ohishi, H
   Cragg, GM
AF Pettit, GR
   Numata, A
   Iwamoto, C
   Usami, Y
   Yamada, T
   Ohishi, H
   Cragg, GM
TI Antineoplastic agents. 551. Isolation and structures of bauhiniastatins
   1-4 from Bauhinia purpurea
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID ANTITUMOR-ACTIVITY; PHOSPHATE; GLYCOSIDE
AB Bioassay-guided (P388 lymphocytic leukemia cell line) separation of extracts prepared from the leaves, stems, and pods of Bauhinia purpurea, and, in parallel, its roots, led to the isolation of four new dibenz[b,f]oxepins (2a, 3-5) named bauhiniastatins 1-4, as well as the known and related pacharin (1) as cancer cell growth inhibitors. The occurrence of oxepin derivatives in nature is quite rare. Bauhiniastatins 1-4 were found to exhibit significant growth inhibition against a minipanel of human cancer cell lines, and bauhiniastatin 1 (2a) was also found to inhibit the P388 cancer cell line. Structures for these new cancer cell growth inhibitors were established by spectroscopic techniques that included HRMS and 2D NMR.
C1 Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA.
   Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA.
   Osaka Univ Pharmaceut Sci, Takatsuki, Osaka 5691094, Japan.
   NCI, Div Canc Treatment & Diagnost, Nat Prod Branch, Dev Therapeut Program, Frederick, MD 21702 USA.
RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, POB 872404, Tempe, AZ 85287 USA.
EM bpettit@asu.edu
FU NCI NIH HHS [R01 CA-90441-01-05, CA44344-01A1-12]
NR 24
TC 42
Z9 42
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD MAR
PY 2006
VL 69
IS 3
BP 323
EP 327
DI 10.1021/np058075+
PG 5
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 028OK
UT WOS:000236497400004
PM 16562827
ER

PT J
AU Sakurai, Y
   Sakurai, N
   Taniguchi, M
   Nakanishi, Y
   Bastow, KF
   Wang, XH
   Cragg, GM
   Lee, KH
AF Sakurai, Y
   Sakurai, N
   Taniguchi, M
   Nakanishi, Y
   Bastow, KF
   Wang, XH
   Cragg, GM
   Lee, KH
TI Rautandiols A and B, pterocarpans and cytotoxic constituents from
   Neorautanenia mitis
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID PACHYRRHIZUS-EROSUS; ISOFLAVONE; EDULIS; NEOTENONE; AMBOENSIS;
   ROTENOIDS; CHEMISTRY; ANALOGS
AB As part of a study on potential antitumor agents from rainforest plants, two new pterocarpans, rautandiol A (1) and rautandiol B (2), together with eight known compounds, were isolated from Neorautanenia mitis. Among the compounds isolated, rotenone (3) and 12-hydroxyrotenone (4) showed significant cytotoxic activity with IC50 values of 0.008-0.010 and 0.04-0.06 mu g/mL against MCF-7 and A-549 cells, respectively.
C1 Univ N Carolina, Sch Pharm, Nat Prod Lab, Chapel Hill, NC 27599 USA.
   NCI, Dev Therapeut Program, Bethesda, MD 20892 USA.
RP Lee, KH (reprint author), Univ N Carolina, Sch Pharm, Nat Prod Lab, Chapel Hill, NC 27599 USA.
EM khlee@unc.edu
FU NCI NIH HHS [CA-17625]
NR 32
TC 16
Z9 18
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD MAR
PY 2006
VL 69
IS 3
BP 397
EP 399
DI 10.1021/np058070c
PG 3
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 028OK
UT WOS:000236497400020
PM 16562843
ER

PT J
AU Chin, YW
   Jones, WP
   Waybright, TJ
   McCloud, TG
   Rasoanaivo, P
   Cragg, GM
   Cassady, JM
   Kinghorn, AD
AF Chin, YW
   Jones, WP
   Waybright, TJ
   McCloud, TG
   Rasoanaivo, P
   Cragg, GM
   Cassady, JM
   Kinghorn, AD
TI Tropane aromatic ester alkaloids from a large-scale re-collection of
   Erythroxylum pervillei stem bark obtained in Madagascar
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID MULTIDRUG-RESISTANCE PHENOTYPE; DITERPENES; TIMBER; NOVOGRANATENSE;
   ROTUNDIFOLIUM; REVERSES; LEAVES
AB Fractionation by pH zone-refining countercurrent chromatography of an extract of the stem bark of Erythroxylum pervillei, obtained on a kilogram scale in southern Madagascar, led to the isolation and characterization of four tropane aromatic ester alkaloids as minor constituents, namely, pervilleines G (5) and H (6) and cis-pervilleines B (7) and F (8). Their structures were determined by spectroscopic data interpretation.
C1 Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA.
   SAIC Frederick Inc, Ft Detrick, MD 21702 USA.
   NCI Frederick, Ft Detrick, MD 21702 USA.
   Inst Malgache Rech Appl, Antananarivo, Madagascar.
RP Kinghorn, AD (reprint author), Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA.
EM kinghorn.4@osu.edu
OI Kinghorn, A. Douglas/0000-0002-6647-8707
FU NCI NIH HHS [U19 CA052956-15, 7U19 CA52956-15, N01-CO-12400, N01CO12400,
   U19 CA052956]
NR 23
TC 17
Z9 19
U1 2
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD MAR
PY 2006
VL 69
IS 3
BP 414
EP 417
DI 10.1021/np050366v
PG 4
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 028OK
UT WOS:000236497400025
PM 16562848
ER

PT J
AU Cragg, GM
   Newman, DJ
   Yang, SS
AF Cragg, GM
   Newman, DJ
   Yang, SS
TI Natural product extracts of plant and marine origin having antileukemia
   potential. The NCI experience
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Review
ID ANTITUMOR BICYCLIC HEXAPEPTIDE; ACYLATED TRITERPENOID SAPONINS;
   PAULLINIA-CUPANA MART; MOUSE LYMPHOMA-CELLS; SURINAM RAIN-FOREST;
   MULTIDRUG-RESISTANCE; CYTOTOXIC ACTIVITY; IN-VITRO; STEROIDAL
   GLYCOSIDES; ISOPRENYLATED XANTHONES
AB While effective treatments exist for acute lymphocytic leukemia (ALL), particularly in the case of children, and for chronic mylogenous leukemia (CML), more efficacious treatments for other forms of acute and chronic forms of the disease are still needed. The National Cancer Institute has tested over 90 000 extracts of terrestrial plants and marine plants and invertebrates in its human cancer one-dose/60-cell-line prescreen, and the results for plants and marine organisms meeting criteria established for activity against selected leukemia cell lines are presented. Taxonomic data are limited to family and genus in the case of plants, and phylum for marine organisms, and those groups of organisms exhibiting significant activity (so-called "hot" families and genera) are discussed. The "hot" terrestrial plant families Myrsinaceae and Sapindaceae have not been studied to any extent and appear to merit special attention, although leukemia cell line selectivity is also noted for other families.
C1 NCI, Natl Canc Inst, Div Canc Treatment & Diagnost, Nat Prod Branch,Dev Therapeut Program, Frederick, MD 21702 USA.
RP Newman, DJ (reprint author), NCI, Natl Canc Inst, Div Canc Treatment & Diagnost, Nat Prod Branch,Dev Therapeut Program, POB B, Frederick, MD 21702 USA.
EM dn22a@nih.gov
NR 161
TC 65
Z9 71
U1 2
U2 14
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD MAR
PY 2006
VL 69
IS 3
BP 488
EP 498
DI 10.1021/np0581216
PG 11
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 028OK
UT WOS:000236497400039
PM 16562862
ER

PT J
AU Nielsen, JA
   Maric, D
   Lau, P
   Barker, JL
   Hudson, LD
AF Nielsen, JA
   Maric, D
   Lau, P
   Barker, JL
   Hudson, LD
TI Identification of a novel oligodendrocyte cell adhesion protein using
   gene expression profiling
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 Natl Inst Neurol Disorders & Stroke, Sect Dev Genet, NIH, Bethesda, MD USA.
   Natl Inst Neurol Disorders & Stroke, Neurophysiol Lab, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 8
EP 8
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900016
ER

PT J
AU Cardona, AE
   Dutta, R
   Huang, D
   Kostenko, V
   Sasse, M
   Kidd, G
   Lee, J
   Cook, DN
   Jung, S
   Lira, SA
   Pioro, E
   Littman, DR
   Ransohoff, RM
AF Cardona, AE
   Dutta, R
   Huang, D
   Kostenko, V
   Sasse, M
   Kidd, G
   Lee, J
   Cook, DN
   Jung, S
   Lira, SA
   Pioro, E
   Littman, DR
   Ransohoff, RM
TI The control of microglial neurotoxicity by CX3CR1
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA.
   Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
   Weizmann Inst Sci, IL-76100 Rehovot, Israel.
   CUNY Mt Sinai Sch Med, New York, NY 10029 USA.
   Howard Hughes Med Inst, New York, NY USA.
   Skirball Inst Biomol Med, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 20
EP 20
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900044
ER

PT J
AU Muja, N
   Lau, P
   Hudson, LD
AF Muja, N
   Lau, P
   Hudson, LD
TI Micro RNA expression in developing oligodendrocytes
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 NINDS, NIH, Dev Genet Sect, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 33
EP 33
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900081
ER

PT J
AU Choi, SH
   Langenbach, R
   Bosetti, F
AF Choi, SH
   Langenbach, R
   Bosetti, F
TI Cyclooxygenase-1 deficient mice show decreased inflammatory markers
   after intracerebroventricular injection of lipopolysaccharide
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 NIA, NIH, Bethesda, MD 20892 USA.
   Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 41
EP 41
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900105
ER

PT J
AU Pawlosky, RJ
   Osei-Hyiaman, D
   Batkai, S
   Crutchfield, C
   King, MT
   Veech, RL
AF Pawlosky, RJ
   Osei-Hyiaman, D
   Batkai, S
   Crutchfield, C
   King, MT
   Veech, RL
TI Brain glucose metabolism changes under conditions of blood acetate
   loading in the rodent
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 NIAAAA, Lab Metab Control, Bethesda, MD USA.
   NIAAA, Lab Physiol Studies, Bethesda, MD USA.
RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 51
EP 51
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900136
ER

PT J
AU Weerth, SH
   Backlund, PS
   Hauser, J
   Yergey, AL
   Russell, JT
AF Weerth, SH
   Backlund, PS
   Hauser, J
   Yergey, AL
   Russell, JT
TI Calcium signaling protein complexes in an enriched OP cell
   membrane-preparation from rat cortices
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 NICHD, SCBST, NIH, Bethesda, MD USA.
   NICHD, LCMB, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 58
EP 58
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900157
ER

PT J
AU Ellis, CE
   Murphy, EJ
   Mitchell, DC
   Golovko, MY
   Scaglia, F
   Barcelo-Coblijn, GC
   Nussbaum, RL
AF Ellis, CE
   Murphy, EJ
   Mitchell, DC
   Golovko, MY
   Scaglia, F
   Barcelo-Coblijn, GC
   Nussbaum, RL
TI Mitochondrial lipid abnormality and electron transport chain impairment
   in mice lacking alpha-synuclein
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
   Univ N Dakota, Dept Pharmacol Physiol & Therapeut, Grand Forks, ND 58201 USA.
   NIAAA, Lab Membrane Biophys & Biochem, NIH, Bethesda, MD USA.
   Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 66
EP 66
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900176
ER

PT J
AU Blanchette-Mackie, EJ
   Comly, ME
   Dwyer, NK
   Robbins, AR
   Pentchev, PG
   Patel, SC
AF Blanchette-Mackie, EJ
   Comly, ME
   Dwyer, NK
   Robbins, AR
   Pentchev, PG
   Patel, SC
TI Apolipoprotein D (-/-) mouse fibroblasts: faulty regulation of low
   density lipoprotein metabolism
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 NIDDK, Lipid Cell Biol Sect, LCBB, NIH, Bethesda, MD USA.
   VA Connecticut Healthcare Syst, Newington, CT USA.
   New England Biomed Res Ctr, Newington, CT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 79
EP 79
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900206
ER

PT J
AU Glass, WG
   Lim, JK
   McDermott, DH
   Pletnev, A
   Cholera, R
   Gao, J
   Lekhong, S
   Yu, SF
   Frank, WA
   Pape, J
   Cheshier, RC
   Murphy, PM
AF Glass, WG
   Lim, JK
   McDermott, DH
   Pletnev, A
   Cholera, R
   Gao, J
   Lekhong, S
   Yu, SF
   Frank, WA
   Pape, J
   Cheshier, RC
   Murphy, PM
TI CCR5 saves lives: the protective role of CCR5 during West Nile virus
   infection
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 NIAID, NIH, Bethesda, MD 20892 USA.
   Arizona Dept Hlth Serv, Phoenix, AZ 85007 USA.
   Centocor Inc, Radnor, PA USA.
   Dept Publ Hlth & Environm, Denver, CO USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 94
EP 94
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900237
ER

PT J
AU Yamada, M
   Noguchi, T
   Kitamura, N
   Araya, R
   Higuchi, M
   Matsuba, Y
   Saido, TC
   Yamada, K
   Takashima, A
   Wess, J
AF Yamada, M
   Noguchi, T
   Kitamura, N
   Araya, R
   Higuchi, M
   Matsuba, Y
   Saido, TC
   Yamada, K
   Takashima, A
   Wess, J
TI Cerebrovascular abnormalities and cognitive deficits in M5 muscarinic
   acetylcholine
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 Kobe Gakuin Univ, Kobe, Hyogo 65121, Japan.
   RIKEN, BSI, Yamada Res Unit, Wako, Saitama 35101, Japan.
   RIKEN, BSI, Lab Proteolyt Neurosci, Wako, Saitama 35101, Japan.
   RIKEN, BSI, ATDG, RRC, Wako, Saitama 35101, Japan.
   RIKEN, BSI, Lab Alzheimers Dis, Wako, Saitama 35101, Japan.
   NIDDK, NIH, Bioorgan Chem Lab, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 110
EP 110
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900279
ER

PT J
AU Dwyer, NK
   Robbins, AR
   Pentchev, PG
   Patel, SC
AF Dwyer, NK
   Robbins, AR
   Pentchev, PG
   Patel, SC
TI Apolipoprotein D (-/-) mouse fibroblasts: faulty regulation of low
   density lipoprotein metabolism
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 NIDDK, Lipid Cell Biol Sect, LCBB, NIH, Bethesda, MD USA.
   VA Connecticut Healthcare Syst, Newington, CT USA.
   New England Biomed Res Ctr, Newington, CT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 114
EP 114
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900291
ER

PT J
AU Holdaway, S
   Blanchette-Mackie, EJ
   Pentchev, PG
   Patel, SC
AF Holdaway, S
   Blanchette-Mackie, EJ
   Pentchev, PG
   Patel, SC
TI Photobleaching FRET analysis reveals apoD-NPC1 interaction in
   cholesterol loaded lysosomes
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 New England Biomed Res Ctr, Newington, CT USA.
   VA Connecticut Healthcare Syst, Newington, CT USA.
   NIDDK, Lab Lipid Cell Biol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 114
EP 114
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900290
ER

PT J
AU Barcelo-Coblijn, G
   Golovko, MY
   Carr, PA
   Nussbaum, RL
   Murphy, EJ
AF Barcelo-Coblijn, G
   Golovko, MY
   Carr, PA
   Nussbaum, RL
   Murphy, EJ
TI Brain lipid composition is altered by alpha-synuclein synuclein
   deficiency
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 Univ N Dakota, Dept Pharmacol Physiol & Therapeut, Grand Forks, ND 58201 USA.
   Univ N Dakota, Dept Anat & Cell Biol, Grand Forks, ND 58201 USA.
   NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 115
EP 115
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900295
ER

PT J
AU Golovko, MY
   Faergeman, NJ
   Nussbaum, RL
   Murphy, EJ
AF Golovko, MY
   Faergeman, NJ
   Nussbaum, RL
   Murphy, EJ
TI Alpha-synuclein gene-deletion increases docosahexaenoic acid metabolism
   in brain phospholipids
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 Univ N Dakota, Dept Pharmacol Physiol & Therapeut, Grand Forks, ND 58201 USA.
   Univ So Denmark, Dept Biochem & Mol Biol, Odense, Denmark.
   NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 127
EP 127
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900326
ER

PT J
AU Fields, RD
AF Fields, RD
TI Neuronal communication beyond the synapse and with non-neuronal cells
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Society-for-Neurochemistry
CY MAR 11-15, 2006
CL Portland, OR
SP Amer Soc Neurochem
C1 NICHD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2006
VL 96
SU 1
BP 137
EP 137
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 021KU
UT WOS:000235982900351
ER

PT J
AU Shapira, NA
   Okun, MS
   Wint, D
   Foote, KD
   Byars, JA
   Bowers, D
   Springer, US
   Lang, PJ
   Greenberg, BD
   Haber, SN
   Goodman, WK
AF Shapira, NA
   Okun, MS
   Wint, D
   Foote, KD
   Byars, JA
   Bowers, D
   Springer, US
   Lang, PJ
   Greenberg, BD
   Haber, SN
   Goodman, WK
TI Panic and fear induced by deep brain stimulation
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Article
ID NORADRENERGIC MECHANISMS; SUBTHALAMIC NUCLEUS; PRIMATE; ANXIETY;
   PROJECTIONS; DISORDER; STRESS
AB Background: Mood, cognitive, and behavioural changes have been reported with deep brain stimulation (DBS) in the thalamus, globus pallidus interna, and anterior limb of the internal capsule/nucleus accumbens region.
   Objective: To investigate panic and fear resulting from DBS.
   Methods: Intraoperative DBS in the region of the right and then left anterior limb of the internal capsule and nucleus accumbens region was undertaken to treat a 52 year old man with treatment refractory obsessive-compulsive disorder (OCD). Mood, anxiety, OCD, alertness, heart rate, and subjective feelings were recorded during intraoperative test stimulation and at follow up programming sessions.
   Results: DBS at the distal (0) contact (cathode 02, anode 2+, pulse width 210 ms, rate 135 Hz, at 6 volts) elicited a panic attack (only seen at the (0) contact). The patient felt flushed, hot, fearful, and described himself as having a "panic attack." His heart rate increased from 53 to 111. The effect (present with either device) was witnessed immediately after turning the device on, and abruptly ceased in the off condition
   Conclusions: DBS of the anterior limb of the internal capsule and nucleus accumbens region caused severe "panic." This response may result from activation of limbic and autonomic networks.
C1 Univ Florida, Inst Brain, Dept Neurol, Gainesville, FL 32610 USA.
   Univ Florida, Dept Neurosurg, Gainesville, FL 32610 USA.
   Univ Florida, Dept Psychiat, Gainesville, FL 32610 USA.
   Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32610 USA.
   NIMH, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA.
   Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
   Univ Rochester, Dept Pharmacol & Physiol, Rochester, NY 14627 USA.
RP Okun, MS (reprint author), Univ Florida, Inst Brain, Dept Neurol, 100 S Newell Dr,Room L3-100, Gainesville, FL 32610 USA.
EM okun@neurology.ufl.edu
OI Okun, Michael/0000-0002-6247-9358
FU NINDS NIH HHS [R01 NS050633]
NR 17
TC 75
Z9 77
U1 0
U2 4
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD MAR
PY 2006
VL 77
IS 3
BP 410
EP 412
DI 10.1136/jnnp.2005.069906
PG 3
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA 016WK
UT WOS:000235651900033
PM 16484657
ER

PT J
AU Bisley, JW
   Goldberg, ME
AF Bisley, JW
   Goldberg, ME
TI Neural correlates of attention and distractibility in the lateral
   intraparietal area
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
ID POSTERIOR PARIETAL CORTEX; FRONTAL EYE FIELD; SELECTIVE
   VISUAL-ATTENTION; MEMORY-GUIDED SACCADE; SUPERIOR COLLICULUS; SPATIAL
   ATTENTION; SINGLE NEURONS; PREFRONTAL CORTEX; COVERT ATTENTION;
   ELECTRICAL MICROSTIMULATION
AB We examined the activity of neurons in the lateral intraparietal area ( LIP) during a task in which we measured attention in the monkey, using an advantage in contrast sensitivity as our definition of attention. The animals planned a memory-guided saccade but made or canceled it depending on the orientation of a briefly flashed probe stimulus. We measured the monkeys' contrast sensitivity by varying the contrast of the probe. Both subjects had better thresholds at the goal of the saccade than elsewhere. If a task-irrelevant distractor flashed elsewhere in the visual field, the attentional advantage transiently shifted to that site. The population response in LIP correlated with the allocation of attention; the attentional advantage lay at the location in the visual field whose representation in LIP had the greatest activity when the probe appeared. During a brief period in which there were two equally active regions in LIP, there was no attentional advantage at either location. This time, the crossing point, differed in the two animals, proving a strong correlation between the activity and behavior. The crossing point of each neuron depended on the relationship of three parameters: the visual response to the distractor, the saccade-related delay activity, and the rate of decay of the transient response to the distractor. Thus the time at which attention lingers on a distractor is set by the mechanism underlying these three biophysical properties. Finally, we showed that for a brief time LIP neurons showed a stronger response to signal canceling the planned saccade than to the confirmation signal.
C1 Columbia Univ, Coll Phys & Surg, Ctr Neurobiol & Behav, Mahoney Ctr Brain & Behav, New York, NY 10032 USA.
   NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA.
   Georgetown Univ, Sch Med, Dept Neurol, Washington, DC USA.
   New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
   Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA.
   Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
RP Bisley, JW (reprint author), Columbia Univ, Coll Phys & Surg, Ctr Neurobiol & Behav, Mahoney Ctr Brain & Behav, 1051 Riverside Dr,Unit 87,Kolb Res Annex,Rm 5-61, New York, NY 10032 USA.
EM jbisley@mednet.ucla.edu
OI Bisley, James/0000-0002-2841-0306
FU NEI NIH HHS [R01 EY014978-04, P30 EY019007, R01 EY014978, R01
   EY014978-05]; NIH HHS [DP1 OD006409]
NR 100
TC 79
Z9 79
U1 2
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD MAR
PY 2006
VL 95
IS 3
BP 1696
EP 1717
DI 10.1152/jn.00848.2005
PG 22
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 014KE
UT WOS:000235477900037
PM 16339000
ER

PT J
AU Zoghbi, SS
   Shetty, HU
   Ichise, M
   Fujita, M
   Imaizumi, M
   Liow, JS
   Shah, J
   Musachio, JL
   Pike, VW
   Innis, RB
AF Zoghbi, Sami S.
   Shetty, H. Umesha
   Ichise, Masanori
   Fujita, Masahiro
   Imaizumi, Masao
   Liow, Jeih-San
   Shah, Jay
   Musachio, John L.
   Pike, Victor W.
   Innis, Robert B.
TI PET imaging of the dopamine transporter with F-18-FECNT: A polar
   radiometabolite confounds brain radioligand measurements
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE in vivo metabolism; dopamine transporter; receptor; F-18-2
   beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-(2-fluoroethyl); nortropane
ID METABOLISM; SPECT; QUANTIFICATION; FLUOROACETATE; IOMAZENIL; ACETATE;
   BINDING; RATS
AB F-18-2 beta-Carbomethoxy-3 beta-(4-chlorophenyl)-8-(2-fluoroethyl)- nortropane (F-18-FECNT), a PET radioligand for the dopamine transporter (DAT), generates a radiometabolite that enters the rat brain. The aims of this study were to characterize this radiometabolite and to determine whether a similar phenomenon occurs in human and nonhuman primate brains by examining the stability of the apparent distribution volume in DAT-rich (striatum) and DAT-poor (cerebellum) regions of the brain. Methods: Two rats were infused with F-18-FECNT and sacrificed at 60 min. Extracts of brain and plasma were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometric (LC-MS) techniques. Two human participants and 3 rhesus monkeys were injected with F-18-FECNT and scanned kinetically, with serial arterial blood analysis. Results: At 60 min after the injection of rats, F-18-FECNT accumulated to levels about 7 times higher in the striatum than in the cortex and cerebellum. The radiometabolite was distributed at equal concentrations in all brain regions. The LC-MS techniques identified N-clealkylated FECNT as a major metabolite in the rat brain, and reverse-phase HPLC detected an equivalent amount of radiometabolite eluting with the void volume. The radiometabolite likely was F-18-fluoroacetaidehyde, the product expected from the N-clealkylation of F-18-FECNT, or its oxidation product, F-18-fluoroacetic acid. The distribution volume in the cerebellum increased up to 1.7-fold in humans between 60 and 300 min after injection and 2.0 +/- 0.1 -fold (mean +/- SD; n = 3) in nonhuman primates between 60 and 240 min after injection. Conclusion: An F-18-fluoroalkyl metabolite of F-18-FECNT origiinating in the periphery confounded the measurements of DAT in the rat brain with a reference tissue model. Its uniform distribution across brain regions suggests that it has negligible affinity for DAT (i.e., it is an inactive radiometabolite). Consistent with the rodent data, the apparent distribution volume in the cerebellum of both humans and nonhuman primates showed a continual increase at late times after injection, a result that may be attributed to entry of the radiometabolite into the brain. Thus, reference tissue modeling of F-18-FECNT will be prone to more errors than analysis with a measured arterial input function.
C1 NIH, NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
RP Zoghbi, SS (reprint author), NIH, NIMH, Mol Imaging Branch, 1 Ctr Dr,Room B3-10,MS 0135, Bethesda, MD 20892 USA.
EM zoghbis@mail.nih.gov
FU Intramural NIH HHS
NR 18
TC 106
Z9 107
U1 0
U2 9
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD MAR
PY 2006
VL 47
IS 3
BP 520
EP 527
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 213VS
UT WOS:000249695800023
PM 16513622
ER

PT J
AU Potischman, N
   Cohen, BE
   Picciano, MF
AF Potischman, N
   Cohen, BE
   Picciano, MF
TI Dietary recommendations and identified research needs for the National
   Children's Study
SO JOURNAL OF NUTRITION
LA English
DT Article
DE National Children's Study; dietary assessment; validation studies;
   maternal and child health; pregnant and lactating women
ID PREGNANCY; AVERSIONS; CRAVINGS; VALIDITY; ISSUES
AB Many years of research have resulted in a set of accepted methods for dietary assessment of adult populations in large epidemiologic studies. Yet, relatively little has been done to develop and validate dietary methods for studies of pregnant and lactating women, infants, children, and adolescents. As plans for including dietary assessment in the National Children's Study (NCS) were developed, it became clear that complex methodological issues required further study and clarification. Along with validation of existing and new instruments, research is required to identify key dietary characteristics to be assessed at various stages of childhood and adolescence and how that information can best be collected. The types of instruments used, the mode of data collection (automated vs. nonautomated instruments), the timing of data collection, and differentiation between children and parents as respondents are areas requiring further inquiry. This paper presents the research needs identified through the process followed to provide the NCS with recommendations for the collection of dietary intake data.
C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   Collaborat Consultants, Bethesda, MD 20817 USA.
   NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Potischman, N (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM potischn@mail.nih.gov
NR 12
TC 11
Z9 11
U1 1
U2 1
PU AMER SOCIETY 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 MAR
PY 2006
VL 136
IS 3
BP 686
EP 689
PG 4
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 015MO
UT WOS:000235555700020
PM 16484543
ER

PT J
AU Gail, MH
   You, WC
AF Gail, MH
   You, WC
TI A factorial trial including garlic supplements assesses effect in
   reducing precancerous gastric lesions
SO JOURNAL OF NUTRITION
LA English
DT Article; Proceedings Paper
CT Research Symposium on Significance of Garlic and Its Constituents in
   Cancer and Cardiovascular Disease
CY APR 09-11, 2005
CL Georgetown Univ, Washington, DC
HO Georgetown Univ
DE gastric cancer; Helicobacter pylori; garlic; vitamins
ID HIGH-RISK; STOMACH-CANCER; CHINESE POPULATION; SHANDONG; DIET
AB The Shandong Intervention Trial was a factorial, double-blind, placebo-controlled trial to determine whether any of 3 interventions, alone or in combination, could reduce the prevalence of precancerous gastric lesions in Linqu County, Shandong Province, China, a region with high gastric cancer mortality rates and a prevalence in adults of Helicobacter pylon of similar to 67%. The 3 interventions were one-time treatment with amoxicillin and omeprazole for Helicobacter pylori infection, and long-term administration of a garlic supplement (aged garlic extract and steam-distilled garlic oil) and a vitamin supplement (vitamins E and C and selenium). This paper describes the design and initial findings on treatment compliance, completeness of follow-up data, and eradication of Helicobacter pylori.
C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   Beijing Inst Canc Res, Beijing 100036, Peoples R China.
RP Gail, MH (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM gailm@mail.nih.gov
NR 14
TC 10
Z9 12
U1 0
U2 2
PU AMER SOCIETY 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 MAR
PY 2006
VL 136
IS 3
SU S
BP 813S
EP 815S
PG 3
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 017JE
UT WOS:000235689100024
PM 16484571
ER

PT J
AU Milner, JA
AF Milner, JA
TI Preclinical perspectives on garlic and cancer
SO JOURNAL OF NUTRITION
LA English
DT Article; Proceedings Paper
CT Research Symposium on Significance of Garlic and Its Constituents in
   Cancer and Cardiovascular Disease
CY APR 09-11, 2005
CL Georgetown Univ, Washington, DC
HO Georgetown Univ
DE garlic; allyl; sulfur; cytochromes; cell division; apoptosis; histone;
   transcriptomics
ID CELL-CYCLE ARREST; ORGANOSULFUR COMPOUNDS; DIALLYL SULFIDE;
   GENE-EXPRESSION; ALLIUM-SATIVUM; BREAST-CANCER; DNA-ADDUCTS; INHIBITION;
   RISK; PHOSPHORYLATION
AB Evidence continues to point to the anticancer properties of fresh garlic extracts, aged garlic, garlic oil, and a number of specific organosulfur compounds generated by processing garlic. These anticarcinogenic and antitumorigenic characteristics appear to arise through both dose-and temporal-related changes in a number of cellular events involved with the cancer process, including those involving drug metabolism, immunocompetence, cell cycle regulation, apoptosis, and angiogenesis. The ability of garlic and related allyl sulfur compounds to block tumors in the colon, lung, breast, and liver suggests general mechanisms that are not tissue specific. Whereas relatively few studies have compared the relative efficacy of water- and lipid-soluble allyl sulfur compounds, those that have when using chemically induced carcinogen models suggest little difference in response, whereas tumor proliferation/apoptosis is highly dependent on the species provided. A shift in sulfhydryl groups, alterations in glutathione:oxidized glutathione ratios, and resultant changes in cellular redox status may be involved in some of the phenotypic changes caused by allyl sulfur compounds. Such changes in thiols by allyl sulfurs may also account for the observed hyperphosphorylation of specific cell cycle proteins and the histone hyperacetylation that has been correlated with suppressed tumor cell proliferation. Whereas the anticarcinogenic and antitumorigenic data to date are impressive, additional studies are needed with more modest exposure to allyl sulfur compounds over prolonged periods. Likewise, additional studies are needed that incorporate transgenic and knockout models to assist in the identification of molecular targets for garlic and its associated allyl sulfur components.
C1 NCI, Div Canc Prevent, Nutrit Sci Res Grp, NIH, Rockville, MD 20854 USA.
RP Milner, JA (reprint author), NCI, Div Canc Prevent, Nutrit Sci Res Grp, NIH, Rockville, MD 20854 USA.
EM milnerj@mail.nih.gov
NR 47
TC 68
Z9 75
U1 0
U2 4
PU AMER SOCIETY 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 MAR
PY 2006
VL 136
IS 3
SU S
BP 827S
EP 831S
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 017JE
UT WOS:000235689100027
PM 16484574
ER

PT J
AU Ross, SA
   Finley, JW
   Milner, JA
AF Ross, SA
   Finley, JW
   Milner, JA
TI Allyl sulfur compounds from garlic modulate aberrant crypt formation
SO JOURNAL OF NUTRITION
LA English
DT Article; Proceedings Paper
CT Research Symposium on Significance of Garlic and Its Constituents in
   Cancer and Cardiovascular Disease
CY APR 09-11, 2005
CL Georgetown Univ, Washington, DC
HO Georgetown Univ
DE aberrant crypt foci; colorectal cancer; garlic; allyl sulfur compounds
ID POTENTIAL CHEMOPREVENTIVE AGENTS; INDUCED COLON CARCINOGENESIS; RAT
   COLON; DIALLYL SULFIDE; CANCER; FOCI; PREVENTION; EXPRESSION; TOMATO;
   ALLIUM
AB The health benefits of garlic, including inhibition of carcinogenesis, are supported by several epidemiologic and laboratory findings. Garlic's sulfur components have been reported to suppress experimentally induced tumor incidence in several organs, including the colon. Studies in humans also suggest that dietary garlic constituents reduce the risk of colorectal adenomatous polyps, which are considered precursors to colon cancer. Aberrant crypt foci (ACF) are proposed to be early preneoplastic lesions of adenoma-carcinoma in humans and chemically induced colon cancer in rodents. In preclinical studies, both water- and lipid-soluble allyl sulfur compounds arising from processed garlic inhibited ACF. The response to these allyl sulfur compounds appears to depend on several factors, including the speciation, quantity, and duration provided.
C1 NCI, Div Canc Prevent, Nutrit Sci Res Grp, US Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
   AM Todd Inc, Montgomeryville, PA 18936 USA.
RP Ross, SA (reprint author), NCI, Div Canc Prevent, Nutrit Sci Res Grp, US Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
EM rosssha@mail.nih.gov
NR 24
TC 20
Z9 20
U1 0
U2 0
PU AMER SOCIETY 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 MAR
PY 2006
VL 136
IS 3
SU S
BP 852S
EP 854S
PG 3
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 017JE
UT WOS:000235689100032
PM 16484579
ER

PT J
AU Semba, RD
   Blaum, CS
   Bartali, B
   Xue, QL
   Ricks, MO
   Guralnik, JM
   Fried, LP
AF Semba, RD
   Blaum, CS
   Bartali, B
   Xue, QL
   Ricks, MO
   Guralnik, JM
   Fried, LP
TI Denture use, malnutrition, frailty, and mortality among older women
   living in the community
SO JOURNAL OF NUTRITION HEALTH & AGING
LA English
DT Article
DE aging; carotenoids; frailty; mortality; oral health; vitamins; women
ID BONE-MINERAL DENSITY; NUTRITIONAL-STATUS; TOOTH LOSS; MASTICATORY
   PERFORMANCE; NATURAL DENTITION; NUTRIENT INTAKE; ELDERLY-PEOPLE; DENTAL
   STATUS; RISK-FACTORS; SARCOPENIA
AB Background: The relationships between denture use, malnutrition, frailty, and mortality in older women have not been well characterized. Objective: To determine whether women who use dentures and have difficulty chewing or swallowing are at hi.-her risk of malnutrition, frailty, and mortality. Design: Cross-sectional and longitudinal study of 826 women, aged 70-79, from the Women's Health and Aging Studies, two population-based longitudinal studies of community-dwelling women in Baltimore, Maryland. At enrollment, data on frailty and self-reported denture use and difficulty chewing or swallowing that limited the ability to eat was collected, and plasma vitamins A, D, E, B-6, and B-12, carotenoids, folate. and albumin were measured. Results: 63.5% of women reported using dentures, of whom 11.6% reported difficulty chewing or swallowing food. Denture users with and without difficulty chewing or swallowing and those not using dentures had, respectively, geometric mean (95% Confidence Interval [C.I]) total plasma carotenoid concentrations of 1.481 (1.302 1.684), 1.616 (1.535, 1.700), and 1.840 (1.728, 1.958) mu mol/L, respectively (P <0.0001), and 25-hydroxyvitamin D of 50.90 (44.25, 58.55), 47.46 (45.15, 50.40), and 54.0 (50.9, 56.8) nmol/L (P < 0.0001). The proportion using dentures among non-frail, pre-frail, and frail women was 58%, 66%, and 73%, respectively (P = 0.018). Women who used dentures and reported difficulty chewing or swallowing had lower five-year survival (H.R. 1.43, 95% C.I. 1.05-1.97), after adjusting for potential confounders. Conclusions: Older women living in the community who use dentures and have difficulty chewing or swallowing have a higher risk of malnutrition,, frailty, and mortality.
C1 Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
   Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
   Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
   NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Semba, RD (reprint author), 550 N Broadway,Suite 700, Baltimore, MD 21205 USA.
EM rdsemba@jhmi.edu
FU NCRR NIH HHS [RR00722]; NIA NIH HHS [N01-AG12112, R01 AG027012, R01
   AG11703-01A1, R37 AG019905]; NIAID NIH HHS [R01 AI41956]
NR 44
TC 35
Z9 37
U1 3
U2 14
PU SERDI EDITION
PI PARIS
PA 320 RUE SAINT-HONORE, PARIS, 75001, FRANCE
SN 1279-7707
J9 J NUTR HEALTH AGING
JI J. Nutr. Health Aging
PY 2006
VL 10
IS 2
BP 161
EP 167
PG 7
WC Geriatrics & Gerontology; Nutrition & Dietetics
SC Geriatrics & Gerontology; Nutrition & Dietetics
GA 035SL
UT WOS:000237021900022
PM 16554954
ER

PT J
AU Gunter, MJ
   Leitzmann, MF
AF Gunter, MJ
   Leitzmann, MF
TI Obesity and colorectal cancer: epidemiology, mechanisms and candidate
   genes
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Review
DE body size; obesity; colorectal cancer; insulin resistance; genetics
ID BODY-MASS INDEX; INSULIN-RECEPTOR SUBSTRATE-1; TUMOR-NECROSIS-FACTOR;
   C-REACTIVE PROTEIN; DIETARY GLYCEMIC LOAD; WOMEN UNITED-STATES;
   AMINO-ACID POLYMORPHISM; IGF-BINDING PROTEIN-3; GROWTH-FACTOR (IGF)-I;
   ABERRANT CRYPT FOCI
AB There is increasing evidence that dysregulation of energy homeostasis is associated with colorectal carcinogenesis. Epidemiological data have consistently demonstrated a positive relation between increased body size and colorectal malignancy, whereas mechanistic studies have sought to uncover obesity-related carcinogenic pathways. The phenomenon of "insulin resistance" or file impaired ability to normalize plasma glucose levels has formed the core of these pathways, but other mechanisms have also been advanced. Obesity-induced insulin resistance leads to elevated levels of plasma insulin, glucose and fatty acids. Exposure of the colonocyte to heightened concentrations of insulin may induce a mitogenic effect within these cells, whereas exposure to glucose and fatty acids may induce metabolic perturbations, alterations in cell signaling pathways and oxidative stress. The importance of chronic inflammation in the pathogenesis of obesity has recently been highlighted and may represent an additional mechanism linking increased adiposity to colorectal carcinogenesis. This review provides an overview of the epidemiology of body size and colorectal neoplasia and outlines current knowledge of putative mechanisms advanced to explain this relation.
   Family-based studies have shown that the propensity to become obese is heritable, but this is only manifest in conditions of excess energy intake over expenditure. Inheritance of a genetic profile that predisposes to increased body size may also be predictive of colorectal cancer. Genomewide scans, linkage studies and candidate gene investigations have highlighted more than 400 chromosomal regions that may harbor variants that predispose to increased body size. The genetics underlying the pathogenesis of obesity are likely to be complex, but variants in a range of different genes have already been associated with increased body size and insulin resistance. These include genes encoding elements of insulin signaling, adipocyte metabolism and differentiation, and regulation of energy expenditure. A number of investigators have begun to study genetic variants within these pathways in relation to colorectal neoplasia, but at present data remain limited to a handful of studies. These pathways will be discussed with particular reference to genetic polymorphisms that have been associated with obesity and insulin resistance. (c) 2006 Elsevier Inc. All rights reserved.
C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS,NIH, Rockville, MD 20852 USA.
RP Gunter, MJ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS,NIH, Rockville, MD 20852 USA.
EM gunterm@mail.nih.gov
NR 156
TC 163
Z9 168
U1 2
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD MAR
PY 2006
VL 17
IS 3
BP 145
EP 156
DI 10.1016/j.jnutbio.2005.06.011
PG 12
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 020SS
UT WOS:000235931300001
PM 16426829
ER

PT J
AU Pie, JE
   Park, JH
   Park, YH
   Ryu, YM
   Kim, KN
   Suh, SW
   Becker, KG
   Cho-Chung, YS
   Kim, MK
AF Pie, JE
   Park, JH
   Park, YH
   Ryu, YM
   Kim, KN
   Suh, SW
   Becker, KG
   Cho-Chung, YS
   Kim, MK
TI Effect of genistein on the expression of bone metabolism genes in
   ovariectomized mice using a cDNA microarray
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE osteoporosis; genistein; bone metabolism; gene profiling; cDNA
   microarray
ID RAT MODEL; BIOCHEMICAL MARKERS; BREAST-CANCER; SOY PROTEIN;
   OSTEOPOROSIS; ISOFLAVONE; PHYTOESTROGENS; RALOXIFENE; DEFICIENCY;
   TURNOVER
AB Osteoporosis associated with estrogen deficiency is defined as an abnormal decrease in bone mass leading to an increased fracture risk. Genistein (GEN), as a phytoestrogen, is a type of soybean-derived isoflavone that possesses structural similarity to estrogen. In this study, we assessed the effect of GEN in ovariectomized (OVX) mice. To determine the effect of GENT on bone metabolism, we investigated gene expression profiles using a radioactive cDNA microarray. Eight-week-old female mice were either sham operated (SHAM) or OVX. From I week after the operation, OVX mice were injected daily with intraperitoneal GEN (0.1, 0.5, 1.5 and 3.0 mg/day) or 17 beta-estradiol (E-2, 0.03 mu g/day) for 4 weeks. A cDNA microarray was used to evaluate changes in the expression of 1, 152 genes. OVX mice showed bone mineral density (BMD) loss versus SHAM mice (5.8 +/- 0.4 vs. 6.9 +/- 0.6 mg/cm(2)). However, femur BMDs were completely restored by GEN and by E-2 administration in OVX mice. Serum osteocalcin in OVX mice treated with 0.5 mg/day of GEN was 1.6-fold (44.30 +/- 5.73 ng/ml) higher than that in untreated mice. GEN treatment up-regulated 38 genes (e.g., mitogen-activated protein kinase 10) and down-regulated 18 (e.g., matrix metalloproteinase 13). Moreover, GEN was found to have a protective effect on bone loss caused by estrogen deficiency in OVX mice. The present study Suggests that GEN modulates bone metabolism-related gene expression, including calciotropic receptor, cytokines, growth factors and bone matrix proteins. (c) 2006 Elsevier Inc. All rights reserved.
C1 Korea Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 136701, South Korea.
   Anyang Univ, Coll Sci & Engn, Dept Food & Nutr, Anyang 430714, South Korea.
   Korea Univ, Dept Orthoped Surg, Seoul 136705, South Korea.
   NCI, Tumor Immunol & Biol Lab, Cellular Biochem Sect, NIH, Bethesda, MD 20892 USA.
   NIA, DNA Array Unit, NIH, Baltimore, MD 21224 USA.
RP Kim, MK (reprint author), Korea Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 136701, South Korea.
EM jerrykim@korea.ac.kr
OI Becker, Kevin/0000-0002-6794-6656
NR 33
TC 18
Z9 24
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD MAR
PY 2006
VL 17
IS 3
BP 157
EP 164
DI 10.1016/j.jnutbio.2005.06.002
PG 8
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 020SS
UT WOS:000235931300002
PM 16169203
ER

PT J
AU Zhang, YW
   Cantor, KP
   Dosemeci, M
   Lynch, CF
   Zhu, Y
   Zheng, TZ
AF Zhang, YW
   Cantor, KP
   Dosemeci, M
   Lynch, CF
   Zhu, Y
   Zheng, TZ
TI Occupational and leisure-time physical activity and risk of colon cancer
   by subsite
SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID COLORECTAL-CANCER; WOMEN; MEN; RECTUM; PREVENTION; ASPIRIN; ADENOMA;
   TURKEY; CHINA
AB Objective: Studies of physical activity and colon cancer risk by anatomic site have provided inconsistent results. Methods: We analyzed data from a population-based case-control study conducted in Iowa involving 685 colon cancer cases and 2434 control subjects. Results: Among those who reported recreational activity more than twice per week, a 30% risk reduction of colon cancer was observed for all sites with a 40% risk reduction for cancer of the right colon. Occupational physical activity was also associated with a reduced risk of colon cancer. The risk was the lowest for those with both high occupational and recreational physical activity (odds ratio, 0.5; 95% confidence interval, 0.3-0.8). Conclusions: Increased physical activity was inversely associated with colon cancer risk. The inverse associations were stronger for the right than for the left colon.
C1 Yale Univ, Sch Publ Hlth, New Haven, CT USA.
   NCI, Hormone & Reprod Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
   NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
   Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA.
RP Zheng, TZ (reprint author), 60 Coll St, New Haven, CT 06510 USA.
EM tongzhang.zheng@yale.edu
NR 35
TC 19
Z9 21
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1076-2752
J9 J OCCUP ENVIRON MED
JI J. Occup. Environ. Med.
PD MAR
PY 2006
VL 48
IS 3
BP 236
EP 243
DI 10.1097/01.jom.0000199521.72764.26
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 023ZY
UT WOS:000236165900004
PM 16531827
ER

PT J
AU Okafor, CC
   Haleem-Smith, H
   Laqueriere, P
   Manner, PA
   Tuan, RS
AF Okafor, CC
   Haleem-Smith, H
   Laqueriere, P
   Manner, PA
   Tuan, RS
TI Particulate endocytosis mediates biological responses of human
   mesenchymal stem cells to titanium wear debris
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE mesenchymal stem cells; wear debris; endocytosis; titanium; osteolysis;
   aseptic loosening; orthopedic prosthesis
ID TOTAL HIP-REPLACEMENT; IN-VITRO; PARTICLES; OSTEOBLASTS; OSTEOLYSIS;
   PROSTHESES; ARTHROPLASTY; IMPLANTS; REVISION; MARROW
AB Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteollysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis. (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   NIH, Div Bioengn & Phys Sci, Off Res Serv, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   George Washington Univ, Dept Orthopaed Surg, Washington, DC 20037 USA.
RP Tuan, RS (reprint author), Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA.
EM tuanr@mail.nih.gov
RI Laquerriere, Patrice/P-1025-2016
OI Laquerriere, Patrice/0000-0001-7637-9094
FU NIAMS NIH HHS [Z01 AR41113]
NR 34
TC 40
Z9 40
U1 2
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0736-0266
J9 J ORTHOP RES
JI J. Orthop. Res.
PD MAR
PY 2006
VL 24
IS 3
BP 461
EP 473
DI 10.1002/jor.20075
PG 13
WC Orthopedics
SC Orthopedics
GA 020OT
UT WOS:000235919900021
PM 16450379
ER

PT J
AU Sheehan, KM
   Gulmann, C
   Barrett, HL
   Eichler, GS
   Kay, EW
   Liotta, LA
   Petricoin, EF
AF Sheehan, KM
   Gulmann, C
   Barrett, HL
   Eichler, GS
   Kay, EW
   Liotta, LA
   Petricoin, EF
TI Proteomic profiling of the epithelial and stromal components of matched
   normal and colonic carcinomas using protein microarrays
SO JOURNAL OF PATHOLOGY
LA English
DT Meeting Abstract
CT 189th Meeting of the Pathological-Society-of-Great-Britain-and-Ireland
CY JAN 04-06, 2006
CL Robinson Coll, Cambridge, ENGLAND
SP Patholog Soc Great Britain Ireland
HO Robinson Coll
C1 NCI, Pathol Lab, NCI FDA Clin Proteom Program, Bethesda, MD 20892 USA.
   RCSI & Beaumont Hosp, Dept Pathol, Dublin, Ireland.
   NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
   George Mason Univ, Ctr Appl Proteom & Mol Med, Manassas, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0022-3417
J9 J PATHOL
JI J. Pathol.
PD MAR
PY 2006
VL 208
SU S
BP 14A
EP 14A
PG 1
WC Oncology; Pathology
SC Oncology; Pathology
GA 019OU
UT WOS:000235847400056
ER

PT J
AU Gulmann, C
   Sheehan, K
   Eichler, G
   Kay, E
   Liotta, L
   Petricoin, E
AF Gulmann, C
   Sheehan, K
   Eichler, G
   Kay, E
   Liotta, L
   Petricoin, E
TI Quantitative proteomic analysis shows downregulation of MAPK pathway in
   colon cancer
SO JOURNAL OF PATHOLOGY
LA English
DT Meeting Abstract
CT 189th Meeting of the Pathological-Society-of-Great-Britain-and-Ireland
CY JAN 04-06, 2006
CL Robinson Coll, Cambridge, ENGLAND
SP Patholog Soc Great Britain Ireland
HO Robinson Coll
C1 Beaumont Hosp, Dublin 9, Ireland.
   NIH, Bethesda, MD USA.
   George Mason Univ, Fairfax, VA 22030 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0022-3417
J9 J PATHOL
JI J. Pathol.
PD MAR
PY 2006
VL 208
SU S
BP 30A
EP 30A
PG 1
WC Oncology; Pathology
SC Oncology; Pathology
GA 019OU
UT WOS:000235847400117
ER

PT J
AU Robotham, DR
   Schoeller, DA
   Mercado, AB
   Mirch, MC
   Theim, KR
   Reynolds, JC
   Yanovski, JA
AF Robotham, DR
   Schoeller, DA
   Mercado, AB
   Mirch, MC
   Theim, KR
   Reynolds, JC
   Yanovski, JA
TI Estimates of body fat in children by hologic QDR-2000 and QDR-4500A
   dual-energy x-ray absorptiometers compared with deuterium dilution
SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
LA English
DT Article
DE children; body composition; fat mass; dual-energy x-ray absorptiometry;
   calibration
ID FREE MASS; PENCIL-BEAM; CRITERION METHODS; PUBERTAL CHANGES; HYDRATION;
   ADULTS; PATTERN; BONE; AGE
AB We evaluated the accuracy with which the Hologic QDR-4500A and QDR-2000 densitometers measure fat mass (FM) in 95 children. FM was derived from total body water measured by deuterium dilution (DD) in all children, by QDR-4500A in 50, and by QDR-2000 in 45 children. Compared with DD, both instruments underestimated FM (QDR-4500A: 3.35 +/- 2.5 kg, P < 0.0001; QDR-2000: 1.05 +/- 1.5 kg, P < 0.0001). Both absorptiometers showed magnitude biases relative to DD (QDR-4500: r = +0.70, P < 0.001; QDR-2000: r = -0.51, P < 0.001). We conclude that neither densitometer is equivalent to DD for estimation of children's FM. The QDR-4500A's current calibration seems to provide an even greater underestimate of FM than the QDR-2000.
C1 NICHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH,Hatfield CRC, Bethesda, MD 20892 USA.
   NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, DHHS, Bethesda, MD 20892 USA.
   Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA.
RP Yanovski, JA (reprint author), NICHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH,Hatfield CRC, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA.
EM jy15i@nih.gov
FU Intramural NIH HHS [Z99 HD999999, Z01 HD000641-12]; NICHD NIH HHS [Z01
   HD000641]
NR 22
TC 12
Z9 12
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-2116
J9 J PEDIATR GASTR NUTR
JI J. Pediatr. Gastroenterol. Nutr.
PD MAR
PY 2006
VL 42
IS 3
BP 331
EP 335
DI 10.1097/01.mpg.0000189373.31697.15
PG 5
WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
GA 018NO
UT WOS:000235771400018
PM 16540807
ER

PT J
AU Wohfahrt, JC
   Wu, TX
   Hodges, JS
   Hinrichs, JE
   Michalowicz, BS
AF Wohfahrt, Johan C.
   Wu, Tianxia
   Hodges, James S.
   Hinrichs, James E.
   Michalowicz, Bryan S.
TI No association between selected candidate gene polymorphisms and severe
   chronic periodontitis
SO JOURNAL OF PERIODONTOLOGY
LA English
DT Article
DE case-control studies; cytokines; genetics; inflammation; periodontitis;
   polymorphism; single nucleotide
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; ADHESION MOLECULE-1 ICAM-1; CHEMOKINE
   RECEPTOR CCR5; T-CELL-ACTIVATION; KAPPA-B LIGAND; HUMAN BETA-DEFENSIN-1;
   ADULT PERIODONTITIS; HAPLOTYPE BLOCKS; IL-6 GENE; POPULATION
   STRATIFICATION
AB Background: Chronic periodontitis (CP) risk is influenced by environmental and genetic factors. Using a case-control design, we tested for associations between CP and selected DNA sequence variations (single nucleotide polymorphisms [SNPs]) in or near genes coding for proteins that play a role in the pathogenesis of this disease.
   Methods: DNA was analyzed from 219 whites who were examined clinically. Cases (N = 137) were 35 years of age with eight or more teeth having >= 5 mm of proximal clinical attachment loss. Controls (N = 82) were >= 45 years of age with minimal or no proximal attachment loss or pocketing. Nine diallelic polymorphisms (gene and SNP descriptor) were studied in subjects: cytotoxic T-lymphocyte antigen-4 (CTLA-4, 49 A > G), human beta-defensin-1 (DEFBI, 692 G > A), intercellular adhesion molecule-1 (ICAM-1, 1548 A > G), Fas ligand (fasL, -844 C > T), inducible costimulator (ICOS, 3990 G > T), interleukin-6 (IL-6, -174 G > C), cysteine-cysteine chemokine receptor-5 (CCR5, 59653 C > T), osteoprotegerin (OPG, 245 T > G), and osteopontin (OPN, 707 C > T). Genotypes were determined using an automated fluorogenic 5'-nuclease, polymerase chain reaction-based assay. Gender and smoking history (pack-years) were included as covariates in logistic regression analyses.
   Results: Heavy smoking (> 10 pack-years) and male gender were significantly associated with disease (P < 0.001). For all SNPs tested, the allele frequencies and distributions of genotypes did not differ between cases and controls (P > 0.05). No unadjusted or adjusted odds ratios (comparing genotypes in cases versus controls) were significantly different than 1.0 (P > 0.05) under any additive, dominant, or recessive inheritance model.
   Conclusions: None of the SNPs tested were strongly associated with generalized severe chronic periodontitis in North American whites. A potentially more fruitful approach in future studies will be to test for associations between periodontitis and haplotype blocks constructed from either multiple SNPs in candidate gene regions or from panels of markers that span the entire genome.
C1 Univ Minnesota, Sch Dent, Dept Prevent Sci, Minneapolis, MN 55455 USA.
   Natl Inst Dent & Craniofacial Res, Bethesda, MD USA.
   Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
RP Michalowicz, BS (reprint author), Univ Minnesota, Sch Dent, Dept Prevent Sci, 17-116 Moos Tower,515 Delaware St SE, Minneapolis, MN 55455 USA.
EM micha002@umn.edu
FU NIDCR NIH HHS [DE09737]
NR 85
TC 6
Z9 7
U1 1
U2 3
PU AMER ACAD PERIODONTOLOGY
PI CHICAGO
PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA
SN 0022-3492
J9 J PERIODONTOL
JI J. Periodont.
PD MAR
PY 2006
VL 77
IS 3
BP 426
EP 436
DI 10.1902/jop.2006.050058
PG 11
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 103IJ
UT WOS:000241878600012
PM 16512757
ER

PT J
AU Weiss, A
   King, JE
   Perkins, L
AF Weiss, A
   King, JE
   Perkins, L
TI Personality and subjective well-being in orangutans (Pongo pygmaeus and
   Pongo abelii)
SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY
LA English
DT Article
DE orangutan; personality; animal; subjective well-being
ID CHIMPANZEES PAN-TROGLODYTES; MALE RHESUS MACAQUES; 5-FACTOR MODEL;
   DIMENSIONS; PERSPECTIVE; EVOLUTION; DOMINANCE; HAPPINESS; CULTURES;
   NUMBER
AB Orangutans (Pongo pygmaeus and Pongo abelii) are semisolitary apes and, among the great apes, the most distantly related to humans. Raters assessed 152 orangutans on 48 personality descriptors; 140 of these orangutans were also rated on a subjective well-being questionnaire. Principal-components analysis yielded 5 reliable personality factors: Extraversion, Dominance, Neuroticism, Agreeableness, and Intellect. The authors found no factor analogous to human Conscientiousness. Among the orangutans rated on all 48 personality descriptors and the subjective well-being questionnaire, Extraversion, Agreeableness, and low Neuroticism were related to subjective well-being. These findings suggest that analogues of human, chimpanzee, and orangutan personality domains existed in a common ape ancestor.
C1 NIA, Lab Personal & Cognit, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
   Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA.
   Zoo Atlanta, Atlanta, GA USA.
RP Weiss, A (reprint author), Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland.
EM alex.weiss@ed.ac.uk
NR 60
TC 89
Z9 90
U1 6
U2 24
PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-3514
J9 J PERS SOC PSYCHOL
JI J. Pers. Soc. Psychol.
PD MAR
PY 2006
VL 90
IS 3
BP 501
EP 511
DI 10.1037/0022-3514.90.3.501
PG 11
WC Psychology, Social
SC Psychology
GA 035ZI
UT WOS:000237039900011
PM 16594834
ER

PT J
AU Moon, C
   Krawczyk, M
   Paik, D
   Coleman, T
   Brines, M
   Juhaszova, M
   Sollott, SJ
   Lakatta, EG
   Talan, MI
AF Moon, C
   Krawczyk, M
   Paik, D
   Coleman, T
   Brines, M
   Juhaszova, M
   Sollott, SJ
   Lakatta, EG
   Talan, MI
TI Erythropoietin, modified to not stimulate red blood cell production,
   retains its cardioprotective properties
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID MITOCHONDRIAL PERMEABILITY TRANSITION; ISCHEMIA-REPERFUSION INJURY;
   MYOCARDIAL-INFARCTION; MYOCYTE APOPTOSIS; CARDIAC MYOCYTES; ACTIVATION;
   PROTECTION; ARTERY; HEART; RATS
AB Erythropoietin ( EPO), a hematopoietic cytokine, possesses strong antiapoptotic, tissue-protective properties. For clinical applications, it is desirable to separate the hematopoietic and tissue-protective properties. Recently introduced carbamylated erythropoietin ( CEPO) does not stimulate the erythropoiesis but retains the antiapoptotic and neuroprotective effects. We tested the ability of CEPO to protect cardiac tissue from toxin-induced and oxidative stress in vitro and ischemic damage in vivo and compared these effects with the effects of EPO. CEPO reduced by 50% the extent of staurosporine-induced apoptosis in isolated rats' cardiomyocytes and increased by 25% the reactive oxygen species threshold for induction of the mitochondrial permeability transition. In an experimental model of myocardial infarction induced by permanent ligation of a coronary artery in rats, similarly to EPO, a single bolus injection of 30 mu g/kg b.wt. of CEPO immediately after coronary ligation reduced apoptosis in the myocardial area at risk, examined 24 h later, by 50%. Left ventricular remodeling ( ventricular dilation) and functional decline ( fall in ejection fraction) assessed by repeated echocardiography were significantly and similarly attenuated in CEPO- and EPO-treated rats. Four weeks after coronary ligation, the myocardial infarction (MI) size in CEPO- and EPO- treated rats was half of that in untreated coronary-ligated animals. Unlike EPO, CEPO had no effect on hematocrit. The antiapoptotic cardioprotective effects of CEPO, shown by its ability to limit both post-MI left ventricular remodeling and the extent of the myocardial scar in the model of permanent coronary artery ligation in rats, demonstrate comparable potency to that of native ( nonmodified) EPO.
C1 NIA, Cardiovasc Gene Therapy Unit, Lab Cardiovasc Sci, Intramural Res Program,Gerontol Res Ctr, Baltimore, MD 21224 USA.
   Hanyang Univ, Dept Anat & Cell Biol, Seoul 133791, South Korea.
   Kenneth S Warren Inst, Ossining, NY USA.
   Warren Pharmaceut, Ossining, NY USA.
RP Talan, MI (reprint author), NIA, Cardiovasc Gene Therapy Unit, Lab Cardiovasc Sci, Intramural Res Program,Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM talanm@grc.nia.nih.gov
OI Brines, Michael/0000-0003-4151-4449
FU Intramural NIH HHS
NR 26
TC 61
Z9 68
U1 0
U2 8
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 MAR
PY 2006
VL 316
IS 3
BP 999
EP 1005
DI 10.1124/jpet.105.094854
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 014JM
UT WOS:000235476000004
PM 16306273
ER

PT J
AU Cheung, C
   Yu, AM
   Chen, CS
   Krausz, KW
   Byrd, LG
   Feigenbaum, L
   Edwards, RJ
   Waxman, DJ
   Gonzalez, FJ
AF Cheung, C
   Yu, AM
   Chen, CS
   Krausz, KW
   Byrd, LG
   Feigenbaum, L
   Edwards, RJ
   Waxman, DJ
   Gonzalez, FJ
TI Growth hormone determines sexual dimorphism of hepatic cytochrome P450
   3A4 expression in transgenic mice
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID HUMAN-LIVER; DEVELOPMENTAL EXPRESSION; MONOCLONAL-ANTIBODIES;
   DRUG-METABOLISM; GENE-EXPRESSION; MESSENGER-RNAS; RAT; CYP3A; GENDER;
   AGE
AB The impact of age and sex on the expression of hepatic cytochrome P450 3A4 (CYP3A4) was recently determined in a transgenic mouse line carrying the human CYP3A4 gene. To further investigate the physiological regulation of human CYP3A genes, a novel transgenic mouse line was generated using a bacterial artificial chromosome clone containing both CYP3A4 and CYP3A7 genes. CYP3A7 expression was observed in transgenic mouse fetal livers, whereas CYP3A4 exhibited developmental expression characterized by sexual dimorphism in postpubertal livers. Hepatic CYP3A4 protein and RNA were expressed in immature transgenic male mice and became undetectable after 6 weeks of age, whereas CYP3A4 was expressed in both immature and adult females. CYP3A4 was markedly elevated by the xenobiotic receptor activator phenobarbital in both male and female livers, demonstrating drug induction of the CYP3A4 transgene in this mouse model. Furthermore, continuous infusion of recombinant growth hormone (GH) in transgenic male mice, overriding the pulsatile male plasma GH profile, increased hepatic CYP3A4 mRNA and protein to normal female levels. Continuous GH treatment also feminized the expression of endogenous murine Cyp2b and Cyp3a44 genes. Thus, human CYP3A4 contains all of the gene regulatory sequences required for it to respond to endogenous hormonal regulators of developmental expression and sexual dimorphism, in particular GH. These findings may help elucidate the role of GH in determining the sex-dependent expression of CYP3A4 in human liver and suggest that GH therapy may alter the pharmacokinetic and pharmacodynamic properties of CYP3A4 substrates, leading to enhanced metabolism and disposition of drugs in men.
C1 NCI, Ctr Canc Res, Lab Metab, NIH, Bethesda, MD 20892 USA.
   SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Buffalo, NY 14260 USA.
   Boston Univ, Dept Biol, Div Cell & Mol Biol, Boston, MA 02215 USA.
   Sci Applicat Int Corp, NCI, Lab Anim Sci Program, Frederick, MD USA.
   Univ London Imperial Coll Sci Technol & Med, Div Med, Sect Expt Med & Toxicol, London, England.
RP Gonzalez, FJ (reprint author), NCI, Ctr Canc Res, Lab Metab, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA.
EM fjgonz@helix.nih.gov
OI Waxman, David/0000-0001-7982-9206
FU NIDDK NIH HHS [DK33765, R01 DK033765]; Wellcome Trust [064866]
NR 49
TC 55
Z9 58
U1 0
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD MAR
PY 2006
VL 316
IS 3
BP 1328
EP 1334
DI 10.1124/jpet.105.094367
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 014JM
UT WOS:000235476000043
PM 16291874
ER

PT J
AU Spiegelman, CH
   Pfeiffer, R
   Gail, M
AF Spiegelman, CH
   Pfeiffer, R
   Gail, M
TI Using chemometrics and statistics to improve proteomics biomarker
   discovery
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Editorial Material
ID OVARIAN-CANCER; SERUM PROTEOMICS
C1 Texas A&M Univ, College Stn, TX 77843 USA.
   NCI, Bethesda, MD 20892 USA.
RP Spiegelman, CH (reprint author), Texas A&M Univ, College Stn, TX 77843 USA.
RI Pfeiffer, Ruth /F-4748-2011
NR 12
TC 4
Z9 4
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
J9 J PROTEOME RES
JI J. Proteome Res.
PD MAR
PY 2006
VL 5
IS 3
BP 461
EP 462
DI 10.1021/pr0626987
PG 2
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 020GP
UT WOS:000235897000001
PM 16541529
ER

PT J
AU Wu, WW
   Wang, GH
   Baek, SJ
   Shen, RF
AF Wu, WW
   Wang, GH
   Baek, SJ
   Shen, RF
TI Comparative study of three proteomic quantitative methods, DIGE, cICAT,
   and iTRAQ, using 2D gel- or LC-MALDI TOF/TOF
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE protein quantification; DIGE; cICAT; iTRAQ; 2D gel; LC-MALDI TOF/TOF
ID MASS-SPECTROMETRIC ANALYSIS; LIQUID-CHROMATOGRAPHY; CONTAINING PEPTIDES;
   PROTEIN MIXTURES; AFFINITY TAG; ELECTROPHORESIS; QUANTIFICATION;
   TECHNOLOGY; STRATEGIES; REAGENTS
AB A comparative study on the three quantitative methods frequently used in proteomics, 2D DIGE (difference gel electrophoresis), cICAT (cleavable isotope-coded affinity tags) and iTRAQ (isobaric tags for relative and absolute quantification), was carried out. DIGE and clCAT are familiar techniques used in gel- and LC-based quantitative proteomics, respectively. iTRAQ is a new LC-based technique which is gradually gaining in popularity. A systematic comparison among these quantitative methods has not been reported. In this study, we conducted well-designed comparisons using a six-protein mixture, a reconstituted protein mixture (BSA spiked into human plasma devoid of six abundant proteins), and complex HCT-116 cell lysates as the samples. All three techniques yielded quantitative results with reasonable accuracy when the six-protein or the reconstituted protein mixture was used. In DIGE, accurate quantification was sometimes compromised due to comigration or partial comigration of proteins. The iTRAQ method is more susceptible to errors in precursor ion isolation, which could be manifested with increasing sample complexity. The quantification sensitivity of each method was estimated by the number of peptides detected for each protein. In this regard, the global-tagging iTRAQ technique was more sensitive than the cysteine-specific cICAT method, which in turn was as sensitive as, if nol more sensitive than, the DIGE technique. Protein profiling on HCT-11 16 and HCT-116 p53 -/- cell lysales displayed limited overlapping among proteins identified by the three methods, suggesting the complementary nature of these methods.
C1 NIH, NHLBI, Proteom Core Facil, Bethesda, MD 20892 USA.
   Univ Tennessee, Coll Vet Med, Dept Pathobiol, Knoxville, TN 37996 USA.
RP Shen, RF (reprint author), NIH, NHLBI, Proteom Core Facil, Bldg 10,Rm 8C213, Bethesda, MD 20892 USA.
EM shenr@nhlbi.nih.gov
OI Baek, Seung/0000-0001-7866-7778
FU Intramural NIH HHS
NR 28
TC 357
Z9 407
U1 11
U2 151
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
J9 J PROTEOME RES
JI J. Proteome Res.
PD MAR
PY 2006
VL 5
IS 3
BP 651
EP 658
DI 10.1021/pr050405o
PG 8
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 020GP
UT WOS:000235897000022
PM 16512681
ER

PT J
AU Inai, K
   Shimizu, Y
   Kawai, K
   Tokunaga, M
   Soda, M
   Mabuchi, K
   Land, CE
   Tokuokas, S
AF Inai, K
   Shimizu, Y
   Kawai, K
   Tokunaga, M
   Soda, M
   Mabuchi, K
   Land, CE
   Tokuokas, S
TI A pathology study of malignant and benign ovarian tumors among
   atomic-bomb survivors - Case series report -
SO JOURNAL OF RADIATION RESEARCH
LA English
DT Article
ID CANCER RISK; HISTOLOGIC TYPE; MORTALITY; NEOPLASMS; RADIATION; AGE
AB The present article describes the series of incident primary ovarian tumors in the Life Span Study (LSS) cohort of the Radiation Effects Research Foundation, with particular emphasis on case ascertainment and characterization of histological features of the tumors. We identified 723 ovarian tumors (260 malignant, 463 benign) in 648 individuals of about 70.000 female LSS subjects; 71 cases had more than one ovarian tumor. We histologically confirmed 601 tumors (182 malignant, 419 benign tumors). The most frequent histological type was common epithelial tumor (90.7% for malignant and 59.7% for benign tumors). The distributions of ovarian tumors by histological type were similar to those from other studies. Among malignancies, the frequency of common epithelial types relative to other tumor types increased with radiation dose (p = 0.02). Among benign tumors, the relative frequency of sex-cord stromal tumors increased with radiation dose (p = 0.04). The women with mucinous cancer had better survival than those with serous cancers (p = 0.03). Within tumor types, there was no consistent pattern of survival by radiation dose. Variations in histological types of ovarian tumors in response to radiation dose, suggested by the case series data need to be followed up by population-based incidence analysis.
C1 Hiroshima Univ, Dept Pathol, Div Med Intelligence & Informat, Program Appl Biomed,Grad Sch Biomed Sci, Hiroshima, Japan.
   Radiat Effects Res Fdn, Dept Epidemiol, Nagasaki, Japan.
   Nagasaki Gen Hlth Ctr, Dept Pathol, Nagasaki, Japan.
   NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
RP Shimizu, Y (reprint author), Hiroshima Univ, Dept Pathol, Div Med Intelligence & Informat, Program Appl Biomed,Grad Sch Biomed Sci, Hiroshima, Japan.
EM shimizu@rerf.or.jp
FU NCI NIH HHS [N01-CP-71015, N01-CP-31012]
NR 35
TC 2
Z9 2
U1 0
U2 0
PU JAPAN RADIATION RESEARCH SOC
PI CHIBA
PA C/O NAT INST RADIOLOGICAL SCI 9-1 ANAGAWA-4-CHOME INAGE-KU, CHIBA, 263,
   JAPAN
SN 0449-3060
J9 J RADIAT RES
JI J. Radiat. Res.
PD MAR
PY 2006
VL 47
IS 1
BP 49
EP 59
DI 10.1269/jrr.47.49
PG 11
WC Biology; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Radiology, Nuclear Medicine
   & Medical Imaging
GA 040SD
UT WOS:000237399800006
PM 16571918
ER

PT J
AU Li, H
   Sheng, Y
   Tang, PZ
   Tsai-Morris, CH
   Dufau, ML
AF Li, H
   Sheng, Y
   Tang, PZ
   Tsai-Morris, CH
   Dufau, ML
TI Tissue-cell- and species-specific expression of gonadotropin-regulated
   long chain acyl-CoA synthetase (GR-LACS) in gonads, adrenal and brain -
   Identification of novel forms in the brain
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE GR-LACS (gonadotropin-regulated long chain acyl-CoA synthetase); gonads;
   adrenal gland; brain
ID ARACHIDONIC-ACID; STEROIDOGENIC HORMONES; ESCHERICHIA-COLI; CLONING;
   OVARY; GENE; MECHANISMS; COENZYME; PATHWAY; ENZYME
AB Gonadotropin-regulated long chain acyl-CoA synthetase (GR-LACS) is a novel hormonally regulated fatty acyl-CoA synthetase (FACS) with activity for long-chain fatty acids. The presence of this enzyme in the Leydig cells of the mature rat testis and its mode of regulation suggest that it participates in testicular steroidogenesis. This study demonstrates that GR-LACS expression is tissue, cell and species-specific. The 79 kDa GR-LACS protein is expressed in rodent gonads and brain, and only in the mouse in the adrenal cortex. In the ovary of both species it is associated with follicles undergoing atresia. It is present in the newborn and immature testis tubules and after puberty only in the Leydig cells. A distinct GR-LACS protein species of 64 kDa that was more abundant than the 79 kDa long form was found in the rat brain. Also, a minor 73 kDa form was observed in the rat brain and mouse ovary. Two novel species resulting from alternatively splicing of the GR-LACS gene were identified in a rat brain cDNA library: a short form 1 (S1) lacking exon 8 and short form 2 (S2) lacking exons 6-8. Expression studies revealed that the sizes of the S1/S2 proteins are comparable to those of the endogenous variant species. Neither S form contains FACSs activity, Suggesting that exon 8 is essential for the enzymatic function. GR-LACS variants exhibit small but significant dominant negative effects on the FACS activity of the long form. GR-LACS variants may regulate the long form's activity in the brain. (C) 2006 Elsevier Ltd. All rights reserved.
C1 NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA.
RP Dufau, ML (reprint author), NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, NIH, Bldg 49,6A-36, Bethesda, MD 20892 USA.
EM dufaum@mail.nih.gov
NR 28
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD MAR
PY 2006
VL 98
IS 4-5
BP 207
EP 217
DI 10.1016/j.jsbmb.2005.10.005
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 028NO
UT WOS:000236494900004
ER

PT J
AU Wikoff, WR
   Conway, JF
   Tang, JH
   Lee, KK
   Gan, L
   Cheng, NQ
   Duda, RL
   Hendrix, RW
   Steven, AC
   Johnson, JE
AF Wikoff, WR
   Conway, JF
   Tang, JH
   Lee, KK
   Gan, L
   Cheng, NQ
   Duda, RL
   Hendrix, RW
   Steven, AC
   Johnson, JE
TI Time-resolved molecular dynamics of bacteriophage HK97 capsid maturation
   interpreted by electron cryo-microscopy and X-ray crystallography
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE X-ray crystallography; cryo-electron microscopy; molecular movie; HK97
   bacteriophage; capsid expansion; molecular machine; conformational
   change
ID PROTEIN STRUCTURES; VIRUS MATURATION; VISUALIZATION; SIMILARITIES;
   TRANSITION; MOLSCRIPT
AB The bacteriophage HK97 capsid is a molecular machine that exhibits large-scale conformational rearrangements of its 420 identical protein subunits during capsid maturation. Immature empty capsids, termed Prohead II, assemble in vivo in an Escherichia coli expression system. Maturation of these particles may be induced in vitro, converting them into Head II capsids that are indistinguishable in conformation from the capsid of an infectious phage particle. One method of in vitro maturation requires acidification to drive the reaction through two expansion intermediates (EI-I, EI-II) to its penultimate particle state (EI-III), which has 86% more internal volume than Prohead II. Neutralization of EI-III produces the fully mature capsid, Head II. The three expansion intermediates and the acid expansion pathway were characterized by cryo-EM analysis and 3D reconstruction. We now report that, although large-scale structural changes are involved, the electron density maps for these intermediate states are readily interpreted in terms of quasi-atomic models based on subunit structures determined by prior crystallographic analysis of Head II. Progression through the expansion intermediate states primarily represents rigid-body rotations and translations of the subunits, accompanied by refolding of two small regions, the N-terminal arm and a beta-hairpin called the E-loop. Movies made with these pseudo-atomic coordinates and the Head II X-ray coordinates illuminate various aspects of the maturation pathway in the course of which the pattern of inter-subunit interactions is sequentially transformed while the integrity of the capsid is maintained. (C) 2005 Elsevier Inc. All rights reserved.
C1 Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA.
   Inst Biol Struct, Lab Microscopie Elect Struct, F-38027 Grenoble, France.
   NIAMS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
   Univ Pittsburgh, Pittsburgh Bacteriophage Inst, Pittsburgh, PA 15260 USA.
   Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
RP Johnson, JE (reprint author), Scripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM jackj@scripps.edu
RI Gan, Lu/F-8317-2011; Conway, James/A-2296-2010
OI Gan, Lu/0000-0002-8685-4896; Conway, James/0000-0002-6581-4748
FU Intramural NIH HHS; NIAID NIH HHS [R01 AI40101]; NIGMS NIH HHS [R01
   GM47795]
NR 24
TC 39
Z9 41
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD MAR
PY 2006
VL 153
IS 3
BP 300
EP 306
DI 10.1016/j.jsb.2005.11.009
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 020XD
UT WOS:000235945600009
PM 16427314
ER

PT J
AU Dawson, DA
   Grant, BF
   Stinson, FS
   Chou, PS
AF Dawson, DA
   Grant, BF
   Stinson, FS
   Chou, PS
TI Maturing out of alcohol dependence: The impact of transitional life
   events
SO JOURNAL OF STUDIES ON ALCOHOL
LA English
DT Article
ID NATIONAL EPIDEMIOLOGIC SURVEY; USE DISORDER CRITERIA; 10-YEAR FOLLOW-UP;
   DSM-IV ALCOHOL; NATURAL RECOVERY; YOUNG ADULTHOOD; UNITED-STATES;
   SUBSTANCE USE; DRUG-USE; FUTURE-DIRECTIONS
AB Objective: The purpose of this study was to investigate the effects of transitional life events related to education, employment, and family formation on the likelihood of recovery from alcohol dependence as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), distinguishing the short- and long-term effects of these events and potential effect modification by treatment history, gender, and severity of dependence. Method: This analysis is based on data from the Wave 1 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a cross-sectional, retrospective survey of a nationally representative sample of U.S. adults 18 years of age and older. The analytic sample consisted of 4,422 individuals with prior-to-past-year (PPY) onset of DSM-IV alcohol dependence. Time-dependent proportional hazards models were used to estimate the effects of completing school, starting full-time work, getting married, becoming separated/divorced/widowed, and becoming a parent on the outcomes of nonabstinent recovery (NR; e.g., low-risk asymptomatic drinking) and abstinent recovery (AR). Results: Entry into and exit from a first marriage each increased the likelihood of NR during the first 3 years after those events occur-red (hazard rate ratio [HRR] = 1.37 and 1.76, respectively). However, individuals who were still dependent 3 or more years after those events occurred had a decreased likelihood of subsequent NR (HRR = 0.70 for both events), as did those who were still dependent 3 or more years after completing schooling (HRR = 0.54). The likelihood of AR was more than doubled in the 3 years after first becoming a parent (HRR = 2.22) but was decreased among individuals still dependent 3 or more years after starting full-time work. For the outcome of NR, all of the negative effects associated with still being dependent 3 or more years after the occurrence of key life events were more strongly negative among individuals with less severe cases of dependence. Conclusions: Transitional life events demonstrate many effects on recovery, including both direct effects consistent with role socialization and associations more reflective of selectivity than causation. Taken as a whole, these events appear to contribute to (but by no means fully explain) the high rates of recovery from alcohol dependence that have been observed even in the absence of treatment.
C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
RP Dawson, DA (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3083,5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA.
EM ddawson@mail.nih.gov
FU Intramural NIH HHS
NR 45
TC 64
Z9 64
U1 1
U2 16
PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV
PI PISCATAWAY
PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA
SN 0096-882X
J9 J STUD ALCOHOL
JI J. Stud. Alcohol
PD MAR
PY 2006
VL 67
IS 2
BP 195
EP 203
PG 9
WC Substance Abuse; Psychology
SC Substance Abuse; Psychology
GA 012DR
UT WOS:000235318900002
PM 16568565
ER

PT J
AU DeVeaugh-Geiss, J
   March, J
   Shapiro, M
   Andreason, PJ
   Emslie, G
   Ford, LM
   Greenhill, L
   Murphy, D
   Prentice, E
   Roberts, R
   Silva, S
   Swanson, JM
   Van Zwieten-Boot, B
   Vitiello, B
   Wagner, KD
   Mangum, B
AF DeVeaugh-Geiss, J
   March, J
   Shapiro, M
   Andreason, PJ
   Emslie, G
   Ford, LM
   Greenhill, L
   Murphy, D
   Prentice, E
   Roberts, R
   Silva, S
   Swanson, JM
   Van Zwieten-Boot, B
   Vitiello, B
   Wagner, KD
   Mangum, B
TI Child and adolescent psychopharmacology in the new millennium: A
   workshop for academia, industry, and government
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE pediatric psychopharmacology; pediatric depression; psychopharmacology
   trials; pediatric research equity act; best pharmaceuticals for children
   act
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PEDIATRIC PSYCHOPHARMACOLOGY;
   PSYCHOTROPIC MEDICATIONS; INDIVIDUAL SUBJECTS; CONTROLLED-TRIAL;
   CLINICAL-TRIALS; PATTERNS; PLACEBO; SAFETY; METHYLPHENIDATE
AB Objective: To give academic researchers, government officials, and industry scientists an opportunity to assess the state of pediatric psychopharmacology and identify challenges facing professionals in the field. Method: Increased federal spending and the introduction of pediatric exclusivity led to large increases in pediatric psychopharmacology research in the 1990s. Despite the increase in research, concerns exist about methods and incentives for making new medications available for use in pediatric psychiatric disorders. In recognition of these concerns, the Duke Clinical Research Institute held a roundtable in September 2004. Participants from the National Institutes of Health, regulatory agencies, academia, and the pharmaceutical industry spoke about the effects of government regulations such as the U.S. Food and Drug Administration Modernization Act and the Pediatric Research Equity Act on pediatric research from academic, clinical, and industry perspectives, and bioethical considerations of such research. Conclusions: To ensure development of new drugs for treating psychiatric disorders in children and adolescents, we must address the challenges posed by the regulatory environment governing pediatric psychopharmacology research. Strategies were identified for improving the evidence base for psychopharmacologic interventions in youth before widespread use and for more effectively defining a research agenda for the future.
C1 Duke Clin Res Inst, Durham, NC 27715 USA.
   US FDA, Rockville, MD 20857 USA.
   Univ Texas, SW Med Ctr, Dallas, TX 75230 USA.
   Johnson & Johnson Consumer Prod Inc, Titusville, NJ USA.
   New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
   Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
   Univ Calif Irvine, Irvine, CA USA.
   Committee Med Prod Human Use Med Evaluat Board, The Hague, Netherlands.
   NIMH, Bethesda, MD 20892 USA.
   Univ Texas, Med Branch, Galveston, TX 77550 USA.
RP DeVeaugh-Geiss, J (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA.
EM BRAINSTORMCNS@aol.com
NR 38
TC 21
Z9 21
U1 3
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD MAR
PY 2006
VL 45
IS 3
BP 261
EP 270
DI 10.1097/01.chi.0000194568.70912.ee
PG 10
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 017VZ
UT WOS:000235722700001
PM 16540810
ER

PT J
AU Vitiello, B
   Zuvekas, SH
   Norquist, GS
AF Vitiello, B
   Zuvekas, SH
   Norquist, GS
TI National estimates of antidepressant medication use among US children,
   1997-2002
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE antidepressants; children; adolescents; use; pharmacoepidemiology
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER;
   CONSENSUS CONFERENCE PANEL; MAJOR DEPRESSIVE DISORDER; OUTPATIENT
   TREATMENT; ALGORITHM PROJECT; CONTROLLED-TRIAL; ADOLESCENTS; TRENDS;
   PREVALENCE
AB Objective: A threefold increase in the use of antidepressants has been reported among children (18 years old and younger) between 1987 (0.3%) and 1996 (1.0%). The aim of this study was to determine whether pediatric use of antidepressants continued to rise at a national level during the period 1997-2002. Method: The Medical Expenditure Panel Survey (MEPS) database for the years 1997-2002 was analyzed. The MEPS is a yearly survey of a nationally representative sample of civilian, noninstitutionalized U.S. households, conducted by the U.S. Agency for Healthcare Research and Quality. Overall response rate ranged between 64% and 68%. Results: An estimated 1.4 million (95% confidence interval [CI] 1.1-1.7) children received antidepressant medication in 2002 as compared to 0.9 million (95% CI 0.7-1.2) in 1997(p = .01). The percentage of users increased from 1.3% (95% CI 0.9-1.6) in 1997 to 1.8% (95% CI 1.5-2.1) in 2002 (p < .01). Adolescent use (2.1% in 1997 versus 3.9% in 2002 (p < .001) accounted for the increase, with no change among children younger than 13 years. Also among adolescents, the use rate remained stable during the 2000-2002 period. The increase was caused by use of selective serotonin reuptake inhibitors and other newer antidepressants, whereas use of TCAs remained stable in adolescents (p = .84) and declined in prepubertal children (p = .04). Antidepressant use was similar among males and females and higher among whites than blacks and Hispanics. Conclusions: Nationwide, the use of selective serotonin reuptake inhibitor antidepressant medications continued to increase in adolescents in the late 1990s and until the year 2000, with no further increase through 2002, and remained stable in prepubertal children.
C1 NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA.
   US Dept HHS, Agcy Hlth Care Policy & Res, Div Social & Econ Res, Ctr Financing Access & Cost Trends, Rockville, MD 20852 USA.
   Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA.
RP Vitiello, B (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA.
EM bvitiell@mail.nih.gov
NR 33
TC 52
Z9 52
U1 3
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD MAR
PY 2006
VL 45
IS 3
BP 271
EP 279
DI 10.1097/01.chi.0000192249.61271.81
PG 9
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 017VZ
UT WOS:000235722700002
PM 16540811
ER

PT J
AU Kratochvil, CJ
   Vitiello, B
   Brent, D
   Bostic, JQ
   Naylor, MW
AF Kratochvil, CJ
   Vitiello, B
   Brent, D
   Bostic, JQ
   Naylor, MW
TI Selecting an antidepressant for the treatment of pediatric depression
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
ID CONTROLLED-TRIAL; FLUOXETINE; ADOLESCENTS; CHILDREN
C1 Univ Nebraska, Med Ctr, Dept Psychiat, Omaha, NE 68198 USA.
   NIMH, Bethesda, MD 20892 USA.
   Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Univ Illinois, Chicago, IL USA.
RP Kratochvil, CJ (reprint author), Univ Nebraska, Med Ctr, Dept Psychiat, 985581 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM ckratoch@unmc.edu
NR 7
TC 4
Z9 4
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD MAR
PY 2006
VL 45
IS 3
BP 371
EP 373
DI 10.1097/01.chi.0000197029.87378.1c
PG 3
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 017VZ
UT WOS:000235722700014
PM 16540823
ER

PT J
AU Hyman, JJ
   Reid, BC
   Mongeau, SW
   York, AK
AF Hyman, JJ
   Reid, BC
   Mongeau, SW
   York, AK
TI The military oral health care system as a model for eliminating
   disparities in oral health
SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION
LA English
DT Article
DE race; access to care; oral health; military health care
ID UNITED-STATES; DENTAL-CARE; CARIES; CHILDREN; ACCESS; DENTITION; WHITE
AB Background. Healthy People (HP) 2010 is a national health promotion and disease prevention initiative of the U.S. Department of Health and Human Services. The HP 2010 report highlighted a range of racial/ethnic disparities in dental health. A substantial portion of these disparities appear to be explained by differences in access to care. Members of the U.S. military have universal access to care that also has a compulsory component. The authors conducted a study to investigate the extent to which disparities in progress toward achievement of HP 2010 objectives were lower among the military population and to compare the oral health of the military population with that of the civilian population.
   Methods. The participants in this study were non-Hispanic white and non-Hispanic black males aged 18 to 44 years. They were drawn from the Tri-Service Comprehensive Oral Health Survey (10,869 including 899 recruits who participated in the TSCOHS Recruit Study) and the Third National Health and Nutrition Examination Survey (4,779).
   Results. We found no disparities between black and white adults in untreated caries and recent dental visit rates in the military population. Disparities in missing teeth were much lower among military personnel than among civilians.
   Conclusions. A universal access-to-care system that incorporated an aspect of compulsory treatment displayed little to no racial disparity in relevant oral health outcomes. This demonstrates that it is possible for large, diverse populations to have much lower levels of disparities in oral health even when universal access to care is not provided until the patient is 18 or 19 years of age.
C1 Natl Inst Dent & Craniofacial Res, Off Sci Policy & Anal, Bethesda, MD 20892 USA.
   Univ Maryland, Sch Dent, Dept Hlth Promot & Policy, Baltimore, MD 21201 USA.
   Uniformed Serv Univ Hlth Sci, Tri Serv Ctr Oral Hlth Studies, Bethesda, MD 20814 USA.
RP Hyman, JJ (reprint author), Natl Inst Dent & Craniofacial Res, Off Sci Policy & Anal, 45 Ctr Dr,Room 4AS-37K,MSC 4601, Bethesda, MD 20892 USA.
EM jh393y@nih.gov
NR 21
TC 9
Z9 11
U1 0
U2 2
PU AMER DENTAL ASSN
PI CHICAGO
PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA
SN 0002-8177
J9 J AM DENT ASSOC
JI J. Am. Dent. Assoc.
PD MAR
PY 2006
VL 137
IS 3
BP 372
EP 378
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 022UO
UT WOS:000236081800029
PM 16570471
ER

PT J
AU Flood, A
   Subar, AF
   Hull, SG
   Zimmerman, TP
   Jenkins, DJA
   Schatzkin, A
AF Flood, A
   Subar, AF
   Hull, SG
   Zimmerman, TP
   Jenkins, DJA
   Schatzkin, A
TI Methodology for adding glycemic load values to the National Cancer
   Institute Diet History Questionnaire database
SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION
LA English
DT Article
ID DENSITY-LIPOPROTEIN CHOLESTEROL; BREAST-CANCER; POSTMENOPAUSAL WOMEN;
   INDEX; RISK; DISEASE; HEALTH; FIBER; CARBOHYDRATE; INSULIN
AB Background A growing interest exists in using glycemic index and glycemic load as potentially important exposures in investigations of risk for a variety of chronic diseases.
   Objective We added values for glycemic index and glycemic load to the nutrient database of a commonly used dietary assessment instrument, the Diet History Questionnaire (DHQ).
   Design The nutrient database for the DHQ is based on 4,200 individual foods reported by adults in the 1994-1996 US Department of Agriculture Continuing Survey of Food Intakes by Individuals (CSFII). This list was condensed into 225 nutritionally similar groupings of individual foods. Using published glycemic index values we assigned glycemic index values to each of the individual CSFII foods in these food groups. In cases where CSFII foods did not correspond tightly to foods with published glycemic index values, we used decision criteria to assign glycemic index values. We then calculated sex- and serving size-specific glycemic load for each of the 225 food groups using the weighted mean method. Quality assessments were made to help evaluate the success of this method for assigning glycemic load values.
   Results Seventy-one percent of the top carbohydrate-contributing food groups had in excess of 90% of the CSFII mentions linked directly to a published glycemic index value (ie, no imputation was required), and 100% of these food groups had at least 50% of total mentions linked directly.
   Conclusions Using this method, it is now possible to use DHQ responses to assess the associations between reported glycemic load and glycemic index and risk of many chronic diseases in epidemiologic studies.
C1 Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA.
   NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   WESTAT Corp, Rockville, MD 20850 USA.
   Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada.
   NCI, Nutr Epidemiol Branch, Bethesda, MD 20892 USA.
   NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Flood, A (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, 1300 S 2nd St,Suite 300, Minneapolis, MN 55454 USA.
EM flood@epi.umn.edu
RI Jenkins, David/A-1992-2009
NR 20
TC 64
Z9 65
U1 0
U2 2
PU AMER DIETETIC ASSOC
PI CHICAGO
PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA
SN 0002-8223
J9 J AM DIET ASSOC
JI J. Am. Diet. Assoc.
PD MAR
PY 2006
VL 106
IS 3
BP 393
EP 402
DI 10.1016/j.jada.2005.12.008
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 018VK
UT WOS:000235792700017
PM 16503230
ER

PT J
AU Trujillo, E
   Davis, C
   Milner, J
AF Trujillo, E
   Davis, C
   Milner, J
TI Nutrigenomics, proteomics, metabolomics, and the practice of dietetics
SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION
LA English
DT Review
ID DNA METHYLATION; VITAMIN-D; BLOOD-PRESSURE; BREAST-CANCER;
   COLORECTAL-CANCER; CONTROLLED TRIAL; DIETARY CALCIUM; UNITED-STATES;
   RISK; GENE
AB The human genome is estimated to encode over 30,000 genes, and to be responsible for generating more than 100,000 functionally distinct proteins. Understanding the interrelationships among genes, gene products, and dietary habits is fundamental to identifying those who will benefit most from or be placed at risk by intervention strategies. Unraveling the multitude of nutrigenomic, proteomic, and metabolomic patterns that arise from the ingestion of foods or their bioactive food components will not be simple but is likely to provide insights into a tailored approach to diet and health. The use of new and innovative technologies, such as microarrays, RNA interference, and nanotechnologies, will provide needed insights into molecular targets for specific bioactive food components and how they harmonize to influence individual phenotypes. Undeniably, to understand the interaction of food components and gene products, there is a need for additional research in the "omics" of nutrition. It is incumbent upon dietetics professionals to recognize that an individual's response to dietary intervention will depend on his or her genetic background and that this information may be used to promote human health and disease prevention. The objectives of this review are to acquaint nutritional professionals with terms relating to "omics," to convey the state of the science to date, to envision the possibilities for future research and technology, and to recognize the implications for clinical practice.
C1 NCI, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA.
RP Milner, J (reprint author), NCI, Nutr Sci Res Grp, NIH, 6130 Execut Blvd,Suite 3164, Bethesda, MD 20892 USA.
EM milnerj@mail.nih.gov
NR 47
TC 97
Z9 114
U1 0
U2 30
PU AMER DIETETIC ASSOC
PI CHICAGO
PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA
SN 0002-8223
J9 J AM DIET ASSOC
JI J. Am. Diet. Assoc.
PD MAR
PY 2006
VL 106
IS 3
BP 403
EP 413
DI 10.1016/j.jada.2005.12.002
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 018VK
UT WOS:000235792700018
PM 16503231
ER

PT J
AU Nicklas, BJ
   Cesari, M
   Penninx, BWJH
   Kritchevsky, SB
   Ding, JZ
   Newman, A
   Kitzman, DW
   Kanaya, AM
   Pahor, M
   Harris, TB
AF Nicklas, BJ
   Cesari, M
   Penninx, BWJH
   Kritchevsky, SB
   Ding, JZ
   Newman, A
   Kitzman, DW
   Kanaya, AM
   Pahor, M
   Harris, TB
TI Abdominal obesity is an independent risk factor for chronic heart
   failure in older people
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE chronic heart failure; obesity; waist circumference; elderly; body fat
   distribution
ID LEFT-VENTRICULAR HYPERTROPHY; CARDIOVASCULAR-DISEASE;
   INSULIN-RESISTANCE; SYSTOLIC FUNCTION; BODY-COMPOSITION; ADIPOSE-TISSUE;
   WOMEN; HEALTH; MEN; ASSOCIATION
AB OBJECTIVES: To examine whether total and abdominal adiposity are risk factors for the development of chronic heart failure (CHF) in older men and women.
   DESIGN: Prospective, longitudinal cohort: The Health, Aging and Body Composition study.
   SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania, metropolitan areas.
   PARTICIPANTS: Three thousand seventy-five well-functioning community-dwelling older adults aged 70 to 79.
   MEAUSREMENTS: Body composition using dual energy X-ray absorptiometry, visceral adipose tissue area using computed tomography, adjudicated CHF.
   RESULTS: Of the remaining (640 participants excluded from original group of 3,075) 2,435 participants (1,081 men, 1,354 women) without coronary heart disease or CHF at baseline, there were 166 confirmed diagnoses of CHF during the median +/- standard deviation (SD) follow-up of 6.1 +/- 1.4 years. After adjustment for age, race, sex, site, education, smoking, and chronic obstructive pulmonary disorder, all adiposity variables (body mass index (BMI), adipose tissue mass, percentage body fat, waist-to-thigh ratio, waist circumference, and visceral and subcutaneous abdominal adipose tissue) were significant predictors of the development of CHF. In a model that included waist circumference and BMI, waist circumference was associated with incident CHF (hazard ratio (HR) = 1.27, 95% confidence interval (CI) = 1.04-1.54 per SD increase, P =.02), but BMI was not (HR = 1.08, 95% CI = 0.86-1.35). When waist circumference and percentage fat were included together, both variables were significant predictors of CHF (waist: HR = 1.17, 95% CI = 1.00-1.36 per SD increase, P=.05; percentage fat: HR = 1.47, 95% CI = 1.16-1.87 per SD increase, P=.002). Stepwise adjustment for inflammation, hypertension, insulin resistance, and diabetes mellitus did not decrease the relative risk of a greater waist circumference for the development of CHF (all HR = 1.27-1.32, 95% CI = 1.02-1.61 per SD increase).
   CONCLUSION: Abdominal body fat distribution may be a stronger risk factor for CHF than overall obesity.
C1 Wake Forest Univ, Med Ctr, Ctr Human Genom, Sect Gerontol & Geriatr Med,J Paul Sticht Ctr Agi, Winston Salem, NC 27157 USA.
   Wake Forest Univ, Sch Med, Dept Internal Med, Cardiol Sect, Winston Salem, NC 27157 USA.
   Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA.
   Vrije Univ Amsterdam, Dept Psychiat, Amsterdam, Netherlands.
   Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
   Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
   NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA.
RP Nicklas, BJ (reprint author), Wake Forest Univ, Med Ctr, Ctr Human Genom, Sect Gerontol & Geriatr Med,J Paul Sticht Ctr Agi, Winston Salem, NC 27157 USA.
EM bnicklas@wfubmc.edu
RI Cesari, Matteo/A-4649-2008; Newman, Anne/C-6408-2013; 
OI Cesari, Matteo/0000-0002-0348-3664; Newman, Anne/0000-0002-0106-1150;
   Kritchevsky, Stephen/0000-0003-3336-6781
FU NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2102, N01-AG-6-2106, P30 AG21332,
   R01 AG018915, R37 AG018915]
NR 45
TC 93
Z9 97
U1 2
U2 5
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0002-8614
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD MAR
PY 2006
VL 54
IS 3
BP 413
EP 420
DI 10.1111/j.1532-5415.2005.00624.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 017ZB
UT WOS:000235731000004
PM 16551307
ER

PT J
AU Lindberg, DAB
AF Lindberg, DAB
TI Commentary on G. Octo Barnett's report to the Computer Research Study
   Section
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Editorial Material
C1 Natl Lib Med, Bethesda, MD 20894 USA.
RP Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM lindberg@nlm.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1067-5027
EI 1527-974X
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD MAR-APR
PY 2006
VL 13
IS 2
BP 136
EP 137
DI 10.1197/jamia.M2022
PG 2
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 023HQ
UT WOS:000236118000003
PM 16357346
ER

PT J
AU Corby, PM
   Schleyer, T
   Spallek, H
   Hart, TC
   Weyant, RJ
   Corby, AL
   Bretz, WA
AF Corby, PM
   Schleyer, T
   Spallek, H
   Hart, TC
   Weyant, RJ
   Corby, AL
   Bretz, WA
TI Using biometrics for participant identification in a research study: A
   case report
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
AB This paper illustrates the use of biometrics through the application of an iris-based biometrics system for identifying twins and their parents in a longitudinal research study. It explores the use of biometrics (science of measuring physical or anatomical characteristics of individuals) as a technology for correct identification of individuals during longitudinal studies to help ensure data fidelity. Examples of these circumstances include longitudinal epidemiological and genetic studies, clinical trials, and multicenter collaborative studies where accurate identification of subjects over time can be difficult when the subject may be young or an unreliable source of identification information. The use of technology can automate the process of subject identification thereby reducing the need to depend on subject recall during repeated visits thus helping to ensure data quality. This case report provides insights that may serve as useful hints for those responsible for planning system implementation that involves participants' authentication that would require a more secure form of identification.
C1 Univ Pittsburgh, Sch Dent Med, Div Pediat & Dev Dent Sci, Pittsburgh, PA 15261 USA.
   Univ Pittsburgh, Ctr Biomed Informat, Pittsburgh, PA 15261 USA.
   Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
   Univ Pittsburgh, Ctr Dent Informat, Pittsburgh, PA 15261 USA.
   Harvard Univ, Dept Oral Biol, Boston, MA 02115 USA.
   Natl Inst Dent & Craniofacial Res, Bethesda, MD USA.
   Div Intramural Res, Bethesda, MD USA.
   Twins Inst Genet Res, Montes Claros, Brazil.
RP Corby, PM (reprint author), Univ Pittsburgh, Sch Dent Med, Div Pediat & Dev Dent Sci, 3501 Terrace St, Pittsburgh, PA 15261 USA.
EM pcorby@pitt.edu
OI Spallek, Heiko/0000-0001-6865-4818
FU NIDCR NIH HHS [DE14528, DE15351]
NR 4
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 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD MAR-APR
PY 2006
VL 13
IS 2
BP 233
EP 235
DI 10.1197/jamia.M1793
PG 3
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 023HQ
UT WOS:000236118000014
PM 16357359
ER

PT J
AU Roychoudhury, S
   Kobayashi, M
AF Roychoudhury, S
   Kobayashi, M
TI New findings on the developmental process of Ascogregarina taiwanensis
   and Ascogregarina culicis in Aedes albopictus and Aedes aegypti
SO JOURNAL OF THE AMERICAN MOSQUITO CONTROL ASSOCIATION
LA English
DT Article
DE Ascogregarina taiwanensis; Ascogregarina culicis; Aedes aegypti; Aedes
   albopictus; sporozoite; oocyst resistance to drying; parasites
ID LECUDINIDAE; APICOMPLEXA; DIPTERA; MOSQUITOS; PATHOGENICITY;
   EUGREGARINIDA; PREVALENCE; PARASITE; FLORIDA
AB Infection in different stages of larvae of Aedes aegypti and Ae. albopictus with Ascogregarina taiwanensis and A. culicis, respectively, revealed that the oocysts of Ascogregarina spp. are able to infect any instar and can complete their life cycle within 9.5 +/- 1 days. When early instars ingested oocysts, parasite development was synchronized to larval-pupal eedysis and oocyst dissemination occurred at the time of adult emergence, oviposition, or both. The parasites also developed normally when infecting 2nd, 3rd, and early 401 instars and oocysts were released only during oviposition. The parasitic development stopped at the gamont stage when oocysts were ingested by late 4th instars (6 days old). The release of sporozoites in the midgut of any larval stage started within 45 min of oocyst ingestion. About 98% of oocysts of both A. taiwanensis and A. culicis were emptied within 2-3 h of their ingestion in their respective hosts. The oocysts of both species remained viable on desiccated filter paper stored at 27 degrees C and 65 +/- 5% relative humidity, indicating that the oocysts were resistant to dryness. The oocysts of A. culicis could survive up to 6 months, whereas those of A. taiwanensis survived LIP to 4 months. These biological characteristics relating to parasite development might enhance the distribution of Ascogregarina spp. widely in nature and facilitate the species to be considered for biological control of Aedes mosquitoes in the future.
C1 NIAID, Dept Med Entomol, Shinjuku Ku, Tokyo 1628640, Japan.
RP Roychoudhury, S (reprint author), NIAID, Dept Med Entomol, Shinjuku Ku, Toyama 1-23-1, Tokyo 1628640, Japan.
NR 23
TC 12
Z9 12
U1 1
U2 2
PU AMER MOSQUITO CONTROL ASSOC
PI EATONTOWN
PA P O BOX 234, EATONTOWN, NJ 07724-0234 USA
SN 8756-971X
J9 J AM MOSQUITO CONTR
JI J. Am. Mosq. Control Assoc.
PD MAR
PY 2006
VL 22
IS 1
BP 29
EP 36
DI 10.2987/8756-971X(2006)22[29:NFOTDP]2.0.CO;2
PG 8
WC Entomology
SC Entomology
GA 027PS
UT WOS:000236428100006
PM 16646318
ER

PT J
AU Rule, AD
   Torres, VE
   Chapman, AB
   Grantham, JJ
   Guay-Woodford, LM
   Bae, KT
   Klahr, S
   Bennett, WM
   Meyers, CM
   Thompson, PA
   Miller, JP
AF Rule, Andrew D.
   Torres, Vicente E.
   Chapman, Arlene B.
   Grantham, Jared J.
   Guay-Woodford, Lisa M.
   Bae, Kyongtae T.
   Klahr, Saulo
   Bennett, William M.
   Meyers, Catherine M.
   Thompson, Paul A.
   Miller, J. Philip
CA CRISP Consortium
TI Comparison of methods for determining renal function decline in early
   autosomal dominant polycystic kidney disease: The consortium of
   radiologic imaging studies of polycystic kidney disease cohort
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; BLOOD-PRESSURE; GFR;
   PREDICTION; NEPHROPATHY; PROGRESSION; CLEARANCE; EQUATIONS; OUTCOMES
AB A decline in renal function suggests progression of chronic kidney disease. This can be determined by measured GFR (e.g., iothalamate clearance), serum creatinine (scr)-based GFR estimates, or creatinine clearance. A cohort of 234 patients with autosomal dominant polycystic kidney disease and baseline creatinine clearance > 70 ml/min were followed annually for four visits. lothalamate clearance, SCr, and creatinine clearance were obtained at each visit. Estimated GFR (eGFR) was determined with the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault equations. Renal function slopes had a mean residual SD of 10.7% by iothalamate clearance, 8.2% by MDRD equation, 7.7% by Cockcroft-Gault equation, and 14.8% by creatinine clearance. By each method, a decline in renal function (lowest quintile slope) was compared among baseline predictors. Hypertension was associated with a decline in iothalamate clearance (odds ratio [OR] 5.8; 95% confidence interval [CI] 2.3 to 14), eGFR (OR [MDRD] 2.0 [95% CI 1.0 to 4.2] or OR [Cockcroft-Gault] 1.9 [95% CI 0.9 to 3.91), and creatinine clearance (OR 2.0; 95% Cl 1.0 to 4.2). Each doubling of kidney volume at baseline was associated with a decline in iothalamate clearance (OR 2.4; 95% CI 1.5 to 3.7), eGFR (OR 1.7 [95% CI 1.1 to 2.61 or 2.1 [95% CI 1.4 to 3.31), and creatinine clearance (OR 1.7; 95% CI 1.1 to 2.5). Predictor associations were strongest with measured GFR. Misclassification from changes in non-GFR factors (e.g., creatinine production, tubular secretion) conservatively biased associations with eGFR. Misclassification from method imprecision attenuated associations with creatinine clearance.
C1 Mayo Fdn, Div Nephrol, Rochester, MN USA.
   Mayo Fdn, Div Epidemiol, Rochester, MN USA.
   Mayo Fdn, Div Radiol, Rochester, MN USA.
   Mayo Fdn, Div Biostat, Rochester, MN USA.
   Univ Alabama, Birmingham, AL USA.
   Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
   Washington Univ, St Louis, MO USA.
   NW Renal Clin, Portland, OR USA.
   NIDDKD, NIH, Bethesda, MD 20892 USA.
RP Rule, AD (reprint author), Mayo Clin, Div Nephrol & Hypertens, 200 1st St SW, Rochester, MN 55905 USA.
EM rule.andrew@mayo.edu
OI Miller, J Philip/0000-0003-4568-6846
FU NCRR NIH HHS [M01-RR00039, MO1-RR00052, MO1-RR00585]; NIDDK NIH HHS
   [F32-DK68996, UO1 DK56943, UO1 DK56956, UO1 DK56957, UO1 DK56961]
NR 28
TC 48
Z9 49
U1 0
U2 1
PU AMERICAN SOCIETY NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAR
PY 2006
VL 17
IS 3
BP 854
EP 862
DI 10.1681/ASN.2005070697
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 106SF
UT WOS:000242120400032
PM 16452494
ER

PT J
AU Liu, YM
   Berthier-Schaad, Y
   Fallin, MD
   Fink, NE
   Tracy, RP
   Klag, MJ
   Smith, MW
   Coresh, J
AF Liu, Yongmei
   Berthier-Schaad, Yvette
   Fallin, Margaret D.
   Fink, Nancy E.
   Tracy, Russell P.
   Klag, Michael J.
   Smith, Michael W.
   Coresh, Josef
TI IL-6 haplotypes, inflammation, and risk for cardiovascular disease in a
   multiethnic dialysis cohort
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID C-REACTIVE PROTEIN; INTERLEUKIN-6 GENE; MYOCARDIAL-INFARCTION; PROMOTER
   POLYMORPHISM; PLASMA-LEVELS; ASSOCIATION; SUSCEPTIBILITY; STROMELYSIN-1;
   POPULATION; MECHANISM
AB It is unknown whether IL-6, a central regulator of inflammation, is a cause of or just a marker of atherosclerosis. Studies of genetic susceptibility to inflammation, however, avoid the potential for reverse causality. Variation in IL6 gene was studied as a predictor of cardiovascular disease (CVD) risk in a cohort of 775 incident dialysis patients, in whom IL-6 levels are elevated. On the basis of published resequencing data on the IL6 gene, a phylogenetic tree with three main branches (clades 1 to 3) was constructed. Two "clade tag" polymorphisms, -174G/C and 1888G/T, and two missense variants, Pro32Ser and Asp162Val, were genotyped. Circulating IL-6 and albumin were measured a median of 5 mo after the start of dialysis. CVD events were ascertained from medical records. During a median follow-up of 2.5 yr, 294 CVD events occurred. The two coding variants, Pro32Ser (present only in black patients, 10% Ser allele) and Asp162Val (present only in white patients, 1% Val), were associated with lower levels of IL-6 and higher levels of albumin. The common variant in the promoter region, -174G/C, was strongly associated with higher CVD risk and weakly with IL-6 levels. Clade 3 (-174C carriers in the absence of 162 Val allele) was associated with higher IL-6 levels (P = 0.03) and higher CVD risk (hazard ratio 1.44, P = 0.006) after adjustment for covariates. The IL6 gene has functional variants that affect inflammation and risk for CVD among dialysis patients, supporting a causal role for IL6 in CVD.
C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
   Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
   SAIC Frederick, NCI, Lab Genom Divers, Frederick, MD USA.
   SAIC Frederick, NCI, Basic Res Program, Frederick, MD USA.
   Univ Vermont, Burlington, VT USA.
RP Coresh, J (reprint author), Johns Hopkins Univ, 2024 E Monument St,Suite 2-600, Baltimore, MD 21205 USA.
EM coresh@jhu.edu
RI Smith, Michael/B-5341-2012
FU AHRQ HHS [R01-HS-08365]; Intramural NIH HHS; NCI NIH HHS [N01-CO-12400];
   NHLBI NIH HHS [R01-HL-62985, HL 58329, HL 46696]; NIDDK NIH HHS
   [R01-DK-59616, K24-DK-02856]
NR 39
TC 62
Z9 65
U1 0
U2 0
PU AMERICAN SOCIETY NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD MAR
PY 2006
VL 17
IS 3
BP 863
EP 870
DI 10.1681/ASN.2005050465
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 106SF
UT WOS:000242120400033
PM 16467451
ER

PT J
AU Chatterjee, N
   Spinka, C
   Chen, JB
   Carroll, RJ
AF Chatterjee, N
   Spinka, C
   Chen, JB
   Carroll, RJ
TI Likelihood-based inference on haplotype effects in genetic association
   studies - Comment
SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
LA English
DT Editorial Material
ID ENVIRONMENT INDEPENDENCE
C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
   Univ Missouri, Dept Stat, Columbia, MO 65211 USA.
   Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA.
RP Chatterjee, N (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
EM chattern@mail.nih.gov; spinkac@missouri.edu; chenjin@mail.nih.gov;
   carroll@stat.tamu.edu
NR 6
TC 3
Z9 3
U1 0
U2 0
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA
SN 0162-1459
J9 J AM STAT ASSOC
JI J. Am. Stat. Assoc.
PD MAR
PY 2006
VL 101
IS 473
BP 108
EP 111
DI 10.1198/016214505000000835
PG 4
WC Statistics & Probability
SC Mathematics
GA 021BU
UT WOS:000235958400012
ER

PT J
AU Hildesheim, A
   de Gonzalez, AB
AF Hildesheim, A
   de Gonzalez, AB
TI Etiology and prevention of cervical adenocarcinomas
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID SQUAMOUS-CELL CARCINOMA; 13 EUROPEAN COUNTRIES; HUMAN-PAPILLOMAVIRUS;
   UNITED-STATES; PARTICLE VACCINE; INCIDENCE TRENDS; UTERINE CERVIX;
   YOUNG-WOMEN; CANCER; EFFICACY
C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
   Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
RP Hildesheim, A (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 7062,MSC 7234, Rockville, MD 20852 USA.
EM hildesha@mail.nih.gov
NR 15
TC 11
Z9 12
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAR 1
PY 2006
VL 98
IS 5
BP 292
EP 293
DI 10.1093/jnci/djj098
PG 2
WC Oncology
SC Oncology
GA 024EN
UT WOS:000236178400001
PM 16507820
ER

PT J
AU Narazaki, M
   Tosato, G
AF Narazaki, M
   Tosato, G
TI Tumor cell populations differ in angiogenic activity: A model system for
   spontaneous angiogenic switch can tell us why
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID CANCER STEM-CELLS; GROWTH; TUMORIGENESIS; MECHANISMS; THERAPY; VESSELS;
   TARGET
C1 NCI, Basic Res Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Tosato, G (reprint author), Bldg 10,12C205,10 Ctr Dr, Bethesda, MD 20892 USA.
EM togatog@mail.nih.gov
OI narazaki, masashi/0000-0002-5613-4409
NR 29
TC 8
Z9 9
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAR 1
PY 2006
VL 98
IS 5
BP 294
EP 295
DI 10.1093/jnci/djj099
PG 2
WC Oncology
SC Oncology
GA 024EN
UT WOS:000236178400002
PM 16507821
ER

PT J
AU Shavers, VL
   Shavers, BS
AF Shavers, VL
   Shavers, BS
TI Racism and health inequity among Americans
SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION
LA English
DT Review
DE racism; healthcare; race/ethnicity; minorities; disparities
ID INNER-CITY CHILDREN; AFRICAN-AMERICAN; SOCIOECONOMIC-STATUS;
   CARDIOVASCULAR-DISEASE; RISK-FACTORS; PERCEIVED DISCRIMINATION;
   EDUCATIONAL-LEVEL; AIR-POLLUTION; UNITED-STATES; MENTAL-HEALTH
AB Research reports often cite socioeconomic status as an underlying factor in the pervasive disparities in health observed for racial/ethnic minority populations. However, often little information or consideration is given to the social history and prevailing social climate that is responsible for racial/ethnic socioeconomic disparities, namely, the role of racism/racial discrimination. Much of the epidemiologic research on health disparities has focused on the relationship between demographic/clinical characteristics and health outcomes in main-effects multivariate models. This approach, however, does not examine the relationship between covariate levels and the processes that create them. It is important to understand the synergistic nature of these relationships to fully understand the impact they have on health status.
   Purpose: A review of the literature was conducted on the role that discrimination in education, housing, employment, the judicial system and the healthcare system plays in the origination, maintenance and perpetuation of racial/ethnic health disparities to serve as background information for funding Program Announcement, PA-05-006, The Effect of Racial/ Ethnic Discrimination/Bias on Healthcare Delivery (http:// grants.nih.gov/grants/guide/pa-files/PA-05-006.html). The effect of targeted marketing of harmful products and environmental justice are also discussed as they relate to racial/ethnic disparities in health.
   Conclusion: Racial/ethnic disparities in health are the result of a combination of social factors that influence exposure to risk factors, health behavior and access to and receipt of appropriate care. Addressing these disparities will require a system that promotes equity and mandates accountability both in the social environment and within health delivery systems.
C1 NCI, Hlth & Serv Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
   Dept Housing & Urban Dev, Off Assistant Secretary, Off Fair Housing & Equal Opportun, Washington, DC USA.
RP Shavers, VL (reprint author), NCI, Hlth & Serv Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 4005,MSC 7344, Bethesda, MD 20892 USA.
EM shaversv@mail.nih.gov
NR 149
TC 51
Z9 51
U1 5
U2 21
PU NATL MED ASSOC
PI WASHINGON
PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA
SN 0027-9684
J9 J NATL MED ASSOC
JI J. Natl. Med. Assoc.
PD MAR
PY 2006
VL 98
IS 3
BP 386
EP 396
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 020RP
UT WOS:000235928300010
PM 16573303
ER

PT J
AU Guccione, JM
   Walker, JC
   Beitler, JR
   Moonly, SM
   Zhang, P
   Guttman, MA
   Ozturk, C
   McVeigh, ER
   Wallace, AW
   Saloner, DA
   Ratcliffe, MB
AF Guccione, JM
   Walker, JC
   Beitler, JR
   Moonly, SM
   Zhang, P
   Guttman, MA
   Ozturk, C
   McVeigh, ER
   Wallace, AW
   Saloner, DA
   Ratcliffe, MB
TI The effect of anteroapical aneurysm plication on end-systolic
   three-dimensional strain in the sheep: A magnetic resonance imaging
   tagging study
SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
LA English
DT Article
ID LEFT-VENTRICULAR ANEURYSM; FINITE-ELEMENT MODEL; MECHANICAL DYSFUNCTION;
   WALL STRESS; BORDER ZONE; MR-IMAGES; VOLUME
AB Objectives: Although repair of left ventricular aneurysm has been extensively studied, its effect on regional ventricular function remains unclear. The primary goal of this study was to quantify the effect of anteroapical aneurysm plication on systolic deformation in noninfarcted adjacent (border zone) and remote left ventricular regions in sheep.
   Methods: Eight sheep underwent anteroapical myocardial infarction (25% of left ventricular mass). Ten weeks later, animals underwent aneurysm plication. Two and 6 weeks after this operation, animals underwent magnetic resonance imaging with tissue tagging in multiple short-axis and long-axis slices. Fully 3-dimensional strain analyses were performed. All 6 end-systolic strain components were compared at midwall in the border zone of the aneurysm or repair and in regions 1 cm, 2 cm, and 3 cm below the valves.
   Results: Circumferential shortening progressively increases from before plication to 2 weeks after plication to 6 weeks after plication toward the border zone. The effect on circumferential shortening is most pronounced in the anterior wall and septum. The biggest change is from 2 to 6 weeks after plication (from 4.3% to 11.3% in anterior wall, P<.0001; from 3.5% to 6.5% in septum, P<.0007). Longitudinal shortening is decreased at 2 weeks after plication but then returns to baseline (with slight improvement in the border zone) at 6 weeks after plication.
   Conclusions: Repair of left ventricular aneurysm significantly increases systolic circumferential shortening at the border zone in sheep.
C1 Univ Calif San Francisco, Dept Vet Affairs Med Ctr, Div Surg Serv, Dept Surg, San Francisco, CA 94121 USA.
   Univ Calif San Francisco, Dept Vet Affairs Med Ctr, Dept Bioengn, San Francisco, CA 94121 USA.
   Univ Calif San Francisco, Dept Vet Affairs Med Ctr, Dept Anesthesia, San Francisco, CA 94121 USA.
   Univ Calif San Francisco, Dept Vet Affairs Med Ctr, Dept Radiol, San Francisco, CA 94121 USA.
   NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
RP Guccione, JM (reprint author), Univ Calif San Francisco, Dept Vet Affairs Med Ctr, Div Surg Serv, Dept Surg, 112D,4150 Clement St, San Francisco, CA 94121 USA.
EM Julius.Guccione@med.va.gov
RI Ozturk, Cengizhan/A-6177-2016
OI Ozturk, Cengizhan/0000-0002-6966-0774
FU Intramural NIH HHS [Z01 HL004608-08]; NHLBI NIH HHS [R01-HL58759, R01
   HL063348, R01 HL077921, R01-HL-63348]
NR 20
TC 19
Z9 19
U1 0
U2 0
PU MOSBY, INC
PI ST LOUIS
PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA
SN 0022-5223
J9 J THORAC CARDIOV SUR
JI J. Thorac. Cardiovasc. Surg.
PD MAR
PY 2006
VL 131
IS 3
BP 579
EP U54
DI 10.1016/j.jtcvs.2005.07.065
PG 11
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 020VI
UT WOS:000235940600012
PM 16515908
ER

PT J
AU McKenzie, FE
   Smith, DL
AF McKenzie, FE
   Smith, DL
TI Mixed-species malaria infections in travelers
SO JOURNAL OF TRAVEL MEDICINE
LA English
DT Letter
ID IMPORTED MALARIA
C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP McKenzie, FE (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RI Smith, David/L-8850-2013
OI Smith, David/0000-0003-4367-3849
FU Intramural NIH HHS [Z99 TW999999]
NR 10
TC 0
Z9 0
U1 0
U2 1
PU B C DECKER INC
PI HAMILTON
PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7,
   CANADA
SN 1195-1982
J9 J TRAVEL MED
JI J. Travel Med.
PD MAR-APR
PY 2006
VL 13
IS 2
BP 123
EP 123
DI 10.1111/j.1708-8305.2006.00025.x
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 025HA
UT WOS:000236254800012
PM 16553602
ER

PT J
AU Hadjianastassiou, VG
   Franco, L
   Jerez, JM
   Evangelou, IE
   Goldhill, DR
   Tekkis, PP
   Hands, LJ
AF Hadjianastassiou, VG
   Franco, L
   Jerez, JM
   Evangelou, IE
   Goldhill, DR
   Tekkis, PP
   Hands, LJ
TI Optimal prediction of mortality after abdominal aortic aneurysm repair
   with statistical models
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT 5th Meeting of the Society-of-Academic-and-Research-Surgery
CY JAN, 2005
CL Newcastle, ENGLAND
SP Soc Acad & Res Surg
ID ARTIFICIAL NEURAL-NETWORKS; ILL HOSPITALIZED ADULTS; APACHE-II; OUTCOME
   PREDICTION; INTENSIVE-CARE; PORTSMOUTH POSSUM; VASCULAR-SURGERY; RISK;
   SYSTEM; AUDIT
AB Objective: To identify the best method for the prediction of postoperative mortality in individual abdominal aortic aneurysm surgery (AAA) patients by comparing statistical modelling with artificial neural networks' (ANN) and clinicians' estimates.
   Methods. An observational multicenter study was conducted of prospectively collected postoperative Acute Physiology and Chronic Health Evaluation 11 data for a 9-year period from 24 intensive care units (ICU) in the Thames region of the United Kingdom. The study cohort consisted of 1205 elective and 546 emergency AAA patients. Four independent physiologic variables-age, acute physiology score, emergency operation, and chronic health evaluation-were used to develop multiple regression and ANN models to predict in-hospital mortality. The models were developed on 75% of the patient population and their validity tested on the remaining 25%. The results from these two models were compared with the observed outcome and clinicians' estimates by using measures of calibration, discrimination, and subgroup analysis.
   Results. Observed in-hospital mortality for elective surgery was 9.3% (95% confidence interval [CI], 7.7% to 11.1%) and for emergency surgery, 46.7% (95% CI, 42.5 to 51.0%). The ANN and the statistical models were both more accurate than the clinicians' predictions. Only the statistical model was internally valid, however, when applied to the validation set of observations, as evidenced by calibration (Hosmer-Lemeshow C statistic, 14.97; P = .060), discrimination properties (area under receiver operating characteristic curve, 0.869; 95% CI, 0.824 to 0.913), and subgroup analysis.
   Conclusions. The prediction of in-hospital mortality in AAA patients by multiple regression is more accurate than clinicians' estimates or ANN modelling. Clinicians can use this statistical model as an objective adjunct to generate informed prognosis.
C1 John Radcliffe Hosp, Nuffield Dept Surg, Oxford OX3 9DU, England.
   Univ Oxford, Oxford OX1 2JD, England.
   Univ Malaga, Escuela Tecn Super Ingn Informat, Dept Lenguajes & Ciencias Computac, E-29071 Malaga, Spain.
   NIH, Oral Pharyngeal Funct Lab, OMF, Phys Disabil Branch,Clin Ctr, Bethesda, MD 20892 USA.
   Royal Natl Orthopaed Hosp, Dept Anaesthesia, London W1N 6AD, England.
   St Marys Hosp, Acad Surg Unit, London W2 1NY, England.
RP Hadjianastassiou, VG (reprint author), John Radcliffe Hosp, Nuffield Dept Surg, Headley Way, Oxford OX3 9DU, England.
EM vassilis@doctors.org.uk
RI Franco, Leonardo/C-3929-2008; Jerez, Jose Manuel/L-1801-2014
OI Franco, Leonardo/0000-0003-0012-5914; Jerez, Jose
   Manuel/0000-0002-7858-2966
NR 41
TC 20
Z9 20
U1 0
U2 3
PU MOSBY, INC
PI ST LOUIS
PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD MAR
PY 2006
VL 43
IS 3
BP 467
EP 473
DI 10.1016/j.jvs.2005.11.022
PG 7
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 019PI
UT WOS:000235848800008
PM 16520157
ER

PT J
AU Cohrs, RJ
   Gilden, DH
   Gomi, Y
   Yamanishi, K
   Cohen, JI
AF Cohrs, RJ
   Gilden, DH
   Gomi, Y
   Yamanishi, K
   Cohen, JI
TI Comparison of virus transcription during lytic infection of the Oka
   parental and vaccine strains of varicella-zoster virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID OPEN READING FRAME-62; TRANS-GOLGI NETWORK; GLYCOPROTEIN-I; REGULATORY
   PROTEIN; VIRAL REPLICATION; TRANSACTIVATION ACTIVITY; MUTATIONAL
   ANALYSIS; SKIN XENOGRAFTS; TERMINAL DOMAIN; DNA-SEQUENCE
AB The attenuated Oka vaccine (V-Oka) strain of varicella-zoster virus (VZV) effectively reduces disease produced by primary infection and virus reactivation. V-Oka was developed by propagation of the Oka parental (P-Oka) strain of VZV in guinea pig and human embryo fibroblasts. Complete DNA sequencing of both viruses has revealed 63 sites that differ between P-Oka and V-Oka, 37 of which are located within 21 unique open reading frames (ORFs). Of the ORFs that differ, ORF 62 contains the greatest number (10) of mutated sites. ORF 62 encodes IE 62, the major immediate-early transactivator of virus genes, and is essential for lytic virus replication. To determine whether a disproportionate number of mutations in ORF 62 might account for virus attenuation, we compared the global pattern of V-Oka gene expression to that of P-Oka. Transcription of ORFs 62, 65, 66, and 67 was suppressed, whereas ORF 41 was elevated in V-Oka-infected cells compared to P-Oka-infected cells (P < 0.01; z test). Suppression of ORF 62, 65, and 66 transcription was confirmed by quantitative dot blot and Western blot analyses. Transient-transfection assays to determine whether mutations within V-Oka-derived IE 62 affected its ability to transactivate VZV gene promoters revealed similar IE 62 transactivation of VZV gene 20, 21, 28, 29, 65, and 66 promoters in both P-Oka and V-Oka. Together, our results indicate that mutations in V-Oka IE 62 alone are unlikely to account for vaccine virus attenuation.
C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA.
   Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA.
   Osaka Univ, Grad Sch Med, Kanonji Inst, Dept Microbiol,Res Fdn Microbial Dis, Kagawa, Japan.
   Natl Inst Biomed Innovat, Ibaraki, Osaka 5670085, Japan.
   NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
RP Cohrs, RJ (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, Campus Mail Stop B182,4200 E 9th Ave, Denver, CO 80262 USA.
EM randall.cohrs@uchsc.edu
FU Intramural NIH HHS; NIA NIH HHS [R01 AG006127, R37 AG006127, AG06127];
   NINDS NIH HHS [NS 32623, P01 NS032623]
NR 34
TC 23
Z9 25
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2006
VL 80
IS 5
BP 2076
EP 2082
DI 10.1128/JVI.80.5.2076-2082.2006
PG 7
WC Virology
SC Virology
GA 013CY
UT WOS:000235388400001
PM 16474115
ER

PT J
AU Khurana, S
   Needham, J
   Mathieson, B
   Rodriguez-Chavez, IR
   Catanzaro, AT
   Bailer, RT
   Kim, J
   Polonis, V
   Cooper, DA
   Guerin, J
   Peterson, ML
   Gurwith, M
   Nguyen, N
   Graham, BS
   Golding, H
AF Khurana, S
   Needham, J
   Mathieson, B
   Rodriguez-Chavez, IR
   Catanzaro, AT
   Bailer, RT
   Kim, J
   Polonis, V
   Cooper, DA
   Guerin, J
   Peterson, ML
   Gurwith, M
   Nguyen, N
   Graham, BS
   Golding, H
CA HIV Vaccine Trial Network
TI Human immunodeficiency virus (HIV) vaccine trials: a novel assay for
   differential diagnosis of HIV infections in the face of
   vaccine-generated antibodies
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID EFFICACY TRIALS; CLINICAL-TRIALS; LESSONS; DISCRIMINATION; VOLUNTEERS;
   RESPONSES
AB All current human immunodeficiency virus (HfV) vaccine candidates contain multiple viral components and elicit antibodies that react positively in licensed HIV diagnostic tests, which contain similar viral products. Thus, vaccine trial participants could be falsely diagnosed as infected with HIV. Additionally, uninfected, seropositive vaccinees may encounter long-term social and economic harms. Moreover, this also interferes with early detection of true HIV infections during preventive HIV vaccine trials. An HIV-seropositive test result among uninfected vaccine trial participants is a major public health concern for volunteers who want to participate in future HIV vaccine trials. Based on the increased number of HIV vaccines being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Using a whole-HIV-genome phage display library, we identified conserved sequences in Env-gp41 and Gag-p6 which are recognized soon after infection, do not contain protective epitopes, and are not part of most current HIV vaccines. We established a new HIV serodetection assay based on these peptides. To date, this assay, termed HIV-SELECTEST, demonstrates > 99% specificity and sensitivity. Importantly, in testing of plasma samples from multiple HIV vaccine trials, uninfected trial participants scored negative, while all intercurrent infections were detected within I to 3 months of HIV infection. The new HIV-SELECTEST is a simple but robust diagnostic tool for easy implementation in HIV vaccine trials and blood banks worldwide.
C1 Ctr Biol Evaluat & Res, Div Viral Prod, FDA, Bethesda, MD 20892 USA.
   Ctr Biol Evaluat & Res, Core Facil, FDA, Bethesda, MD 20892 USA.
   NIH, Off AIDS Res, Bethesda, MD 20892 USA.
   NIAID, Vaccine Clin Res Branch, Div AIDS, NIH, Bethesda, MD 20892 USA.
   NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
   USAMC, Armed Forces Res Inst Med Sci, APO, AP 96546 USA.
   US Mil HIV Res Program, Rockville, MD 20850 USA.
   Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW 2010, Australia.
   VaxGen Inc, Brisbane, CA 94005 USA.
RP Golding, H (reprint author), Ctr Biol Evaluat & Res, Div Viral Prod, FDA, Bethesda, MD 20892 USA.
EM goldingh@cber.FDA.gov
NR 13
TC 21
Z9 25
U1 0
U2 4
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 MAR
PY 2006
VL 80
IS 5
BP 2092
EP 2099
DI 10.1128/JVI.80.5.2092-2099.2006
PG 8
WC Virology
SC Virology
GA 013CY
UT WOS:000235388400003
PM 16474117
ER

PT J
AU Baron, GS
   Magalhaes, AC
   Prado, MAM
   Caughey, B
AF Baron, GS
   Magalhaes, AC
   Prado, MAM
   Caughey, B
TI Mouse-adapted scrapie infection of SN56 cells: Greater efficiency with
   microsome-associated versus purified PrP-res
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PROTEASE-RESISTANT STATE; CELLULAR PRION PROTEIN; STEEL-SURFACE;
   IN-VITRO; CONVERSION; EXOSOMES; LINES; TRANSMISSION; PROPAGATION;
   EXPRESSION
AB The process by which transmissible spongiform encephalopathy agents, or prions, infect cells is unknown. We employed a new differentiable cell line (SN56) susceptible to infection with three mouse-adapted scrapie strains to gain insight into the cellular infection process. The effect of disease-associated PrP (PrP-res) association with microsomal membranes on infection efficiency was examined by comparing sustained PrP-res production in cells treated with either scrapie brain microsomes or purified, detergent-extracted PrP-res. When normalized for quantity of input PrP-res, scrapie brain microsomes induced dramatically enhanced persistent PrP-res formation compared to purified PrP-res. Infected SN56 cells released low levels of PrP-res into the culture supernatant, which also efficiently initiated infection in recipient cells. Interestingly, microsomes labeled with a fluorescent marker were internalized by SN56 cells in small vesicles, which were subsequently found in neuritic processes. When bound to culture wells to reduce internalization during the infection process, scrapie microsomes induced less long-term PrP-res production than suspended microsomes. Long-term differentiation of infected SN56 cells was accompanied by a decrease in PrP-res formation. Our observations provide evidence that infection of cells is aided by the association of PrP-res with membranes and/or other microsomal constituents.
C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA.
   Univ Fed Minas Gerais, Dept Pharmacol, ICB, Program Mol & Biochem Pharmacol, BR-31270901 Belo Horizonte, MG, Brazil.
RP Baron, GS (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM gbaron@niaid.nih.gov
RI Prado, Marco/K-7638-2013
OI Prado, Marco/0000-0002-3028-5778
FU Intramural NIH HHS
NR 58
TC 48
Z9 51
U1 1
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2006
VL 80
IS 5
BP 2106
EP 2117
DI 10.1128/JVI.80.5.2106-2117.2006
PG 12
WC Virology
SC Virology
GA 013CY
UT WOS:000235388400005
PM 16474119
ER

PT J
AU Bukreyev, A
   Bukreyev, A
   Yang, LJ
   Zaki, SR
   Shieh, WJ
   Rollin, PE
   Murphy, BR
   Collins, PL
   Sanchez, A
AF Bukreyev, A
   Bukreyev, A
   Yang, LJ
   Zaki, SR
   Shieh, WJ
   Rollin, PE
   Murphy, BR
   Collins, PL
   Sanchez, A
TI A single intranasal inoculation with a paramyxovirus-vectored vaccine
   protects guinea pigs against a lethal-dose Ebola virus challenge
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESPIRATORY SYNCYTIAL VIRUS; NEWCASTLE-DISEASE VIRUS; HEMORRHAGIC-FEVER;
   NONHUMAN-PRIMATES; DENDRITIC CELLS; MARBURG VIRUSES; MESSENGER-RNA; M2-2
   PROTEIN; INFECTION; PATHOGENESIS
AB To determine whether intranasal inoculation with a paramyxovirus-vectored vaccine can induce protective immunity against Ebola virus (EV), recombinant human parainfluenza virus type 3 (HPIV3) was modified to express either the EV structural glycoprotein (GP) by itself (HPIV3/EboGP) or together with the EV nucleoprotein (NP) (HPIV3/EboGP-NP). Expression of EV GP by these recombinant viruses resulted in its efficient incorporation into virus particles and increased cytopathic effect in Vero cells. HPIV3/EboGP was 100-fold more efficiently neutralized by antibodies to EV than by antibodies to HPIV3. Guinea pigs infected with a single intranasal inoculation of 10(5.3) PFU of HPIV3/EboGP or HPIV3/EboGP-NP showed no apparent signs of disease yet developed a strong Immoral response specific to the EV proteins. When these animals were challenged with an intraperitoneal injection of 10(3) PFU of EV, there were no outward signs of disease, no viremia or detectable EV antigen in the blood, and no evidence of infection in the spleen, liver, and lungs. In contrast, all of the control animals died or developed severe EV disease following challenge. The highly effective immunity achieved with a single vaccine dose suggests that intranasal immunization with live vectored vaccines based on recombinant respiratory viruses may be an advantageous approach to inducing protective responses against severe systemic infections, such as those caused by hemorrhagic fever agents.
C1 NIAID, NIH, LID, Bethesda, MD 20892 USA.
   Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA.
RP Bukreyev, A (reprint author), NIAID, NIH, LID, 50 S Dr,Rm 6505, Bethesda, MD 20892 USA.
EM abukreyev@niaid.nih.gov
FU Intramural NIH HHS
NR 56
TC 59
Z9 67
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 MAR
PY 2006
VL 80
IS 5
BP 2267
EP 2279
DI 10.1128/JVI.80.5.2267-2279.2006
PG 13
WC Virology
SC Virology
GA 013CY
UT WOS:000235388400020
PM 16474134
ER

PT J
AU Davis, MR
   Jiang, JY
   Zhou, J
   Freed, EO
   Aiken, C
AF Davis, MR
   Jiang, JY
   Zhou, J
   Freed, EO
   Aiken, C
TI A mutation in the human immunodeficiency virus type 1 gag protein
   destabilizes the interaction of the envelope protein subunits gp120 and
   gp41
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIV-1 MATRIX PROTEIN; NUCLEAR-LOCALIZATION SIGNAL; EARLY POSTENTRY STEP;
   CYTOPLASMIC DOMAIN; ENV INCORPORATION; GLYCOPROTEIN INCORPORATION;
   SOLUBLE CD4; LIFE-CYCLE; INTRACYTOPLASMIC DOMAIN; DEPENDENT REQUIREMENT
AB The Gag protein of human immunodeficiency virus type I (HIV-1) associates with the envelope protein complex during virus assembly. The available evidence indicates that this interaction involves recognition of the gp41 cytoplasmic tail (CT) by the matrix protein (MA) region of Pr55(Gag). Here we show that substitution of Asp for Leu at position 49 (L49D) in MA results in a specific reduction in particle-associated gp120 without affecting the levels of gp41. Mutant virions were markedly reduced in single-cycle infectivity despite a relatively modest defect in fusion with target cells. Studies with HIV-1 particles containing decreased levels of envelope proteins suggested that the L49D mutation also inhibits a postentry step in infection. Truncation of the gp41 tail, or pseudotyping by vesicular stomatitis virus glycoprotein, restored both the fusion and infectivity of L49D mutant virions to wild-type levels. Truncation of gp41 also resulted in equivalent levels of gp120 on particles with and without the MA mutation and enhanced the replication of the L49D mutant virus in T cells. The impaired fusion and infectivity of L49D mutant particles were also complemented by a single point mutation in the gp41 CT that disrupted the tyrosine-containing endocytic motif. Our results suggest that an altered interaction between the MA domain of Gag and the gp41 cytoplasmic tail leads to dissociation of gp120 from gp41 during HTV-1 particle assembly, thus resulting in impaired fusion and infectivity.
C1 Vanderbilt Univ, Dept Microbiol & Immunol, Sch Med, Nashville, TN 37232 USA.
   NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Aiken, C (reprint author), Vanderbilt Univ, Dept Microbiol & Immunol, Sch Med, A-5301 Med Ctr N, Nashville, TN 37232 USA.
EM chris.aiken@vanderbilt.edu
FU NIAID NIH HHS [AI47056, R01 AI047056]
NR 88
TC 45
Z9 48
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2006
VL 80
IS 5
BP 2405
EP 2417
DI 10.1128/JVI.80.5.2405-2417.2006
PG 13
WC Virology
SC Virology
GA 013CY
UT WOS:000235388400033
PM 16474147
ER

PT J
AU Ou, W
   Lu, N
   Yu, SS
   Silver, J
AF Ou, W
   Lu, N
   Yu, SS
   Silver, J
TI Effect of epitope position on neutralization by anti-human
   immunodeficiency virus monoclonal antibody 2F5
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MURINE LEUKEMIA-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEIN; MEDIATED
   MEMBRANE-FUSION; CELL-FUSION; NONNEUTRALIZING ANTIBODIES; CONFORMATIONAL
   CONSTRAINTS; SYNCYTIUM FORMATION; GP41 EPITOPE; HIV FUSION; PROTEIN
AB The membrane-proximal region of the human immunodeficiency virus type 1 (HIV-1) transmembrane protein (TM) is critical for envelope (Env)-mediated membrane fusion and contains the target for broadly reactive neutralizing antibody 2F5. It has been proposed that 2F5 neutralization might involve interaction of its long, hydrophobic, complementarity-determining region (CDR) 113, with adjacent viral membrane. Using Moloney murine leukemia virus (MLV) as a tool, we examined the effect of epitope position on 2F5 neutralization. When the 2175 epitope was inserted in the proline-rich region of MLV Env surface protein (SU), 2F5 blocked cell fusion and virus infection, whereas MLV with a hemagglutinin (HA) epitope at the same position was not neutralized by anti-HA, even though the antibodies bound their respective Envs on the surface of infected cells and viruses equally well. When the 2175 epitope was inserted in the MLV Env TM at a position comparable to its natural position in HIV-1 TM, 2F5 antibody blocked Env-mediated cell fusion. Epitope position had subtle effects on neutralization by 2F5: the antibody concentration for 50% inhibition of cell fusion was more than 10-fold lower when the 2175 epitope was in SU than in TM, and inhibition was less complete at high concentrations of antibody; we discuss possible explanations for these effects of epitope position. Since membrane proximity was not required for neutralization by 2F5 antibody, we speculate that the CDR H3 of 2F5 contributes to neutralization by destabilizing an adjacent protein rather than by inserting into an adjacent membrane.
C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Silver, J (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 336, Bethesda, MD 20892 USA.
EM jsilver@nih.gov
NR 63
TC 17
Z9 17
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2006
VL 80
IS 5
BP 2539
EP 2547
DI 10.1128/JVI.80.5.2539-2547.2006
PG 9
WC Virology
SC Virology
GA 013CY
UT WOS:000235388400046
PM 16474160
ER

PT J
AU Ambrose, Z
   Julias, JG
   Boyer, PL
   KewalRamani, VN
   Hughes, SH
AF Ambrose, Z
   Julias, JG
   Boyer, PL
   KewalRamani, VN
   Hughes, SH
TI The level of reverse transcriptase (RT) in human immunodeficiency virus
   type 1 particles affects susceptibility to nonnucleoside RT inhibitors
   but not to lamivudine
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RESISTANCE; HIV-1; HYPERSUSCEPTIBILITY; SENSITIVITY; MECHANISM;
   PRECURSOR; PROTEIN; AZT
AB We investigated the relationship between the level of reverse transcriptase (RT) in human immunodeficiency virus type 1 (HIV-1) particles and susceptibility to normucleoside reverse transcriptase inhibitors (NNRTIs). HIV-1 virions containing different active levels of RT were generated. Susceptibility to the NNRT1s efavirenz and nevirapine was inversely proportional to the level of enzymatically active RT. However, the sensitivity of HIV-1 to the nucleoside analog 3TC was not affected by the level of RT per particle. These data indicate that the susceptibility of HIV-1 to NNRT1s is influenced by RT activity.
C1 NCI, Frederick, MD 21702 USA.
   SAIC Frederick, HIV Drug Resistance Program, Frederick, MD 21702 USA.
   SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA.
RP Hughes, SH (reprint author), NCI, Bldg 539,Room 130A, Frederick, MD 21702 USA.
EM hughes@ncifcrf.gov
FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01-CO-12400]
NR 19
TC 11
Z9 11
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2006
VL 80
IS 5
BP 2578
EP 2581
DI 10.1128/JVI.80.5.2578-2581.2006
PG 4
WC Virology
SC Virology
GA 013CY
UT WOS:000235388400050
PM 16474164
ER

PT J
AU Di Mascio, M
   Sereti, I
   Matthews, LT
   Natarajan, V
   Adelsberger, J
   Lempicki, R
   Yoder, C
   Jones, E
   Chow, C
   Metcalf, JA
   Sidorov, IA
   Dimitrov, DS
   Polis, MA
   Kovacs, JA
AF Di Mascio, M
   Sereti, I
   Matthews, LT
   Natarajan, V
   Adelsberger, J
   Lempicki, R
   Yoder, C
   Jones, E
   Chow, C
   Metcalf, JA
   Sidorov, IA
   Dimitrov, DS
   Polis, MA
   Kovacs, JA
TI Naive T-cell dynamics in human immunodeficiency virus type 1 infection:
   Effects of highly active antiretroviral therapy provide insights into
   the mechanisms of naive T-cell depletion
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIV-1 INFECTION; IMMUNE ACTIVATION; LYMPHOID-TISSUES; RHESUS MACAQUES;
   CD4(+); TURNOVER; PROLIFERATION; LYMPHOCYTES; ANTIGEN; INTERLEUKIN-2
AB Both naive CD4(+) and naive CD8(+) T cells are depleted in individuals with human immunodeficiency virus type 1 (HIV-1) infection by unknown mechanisms. Analysis of their dynamics prior to and after highly active antiretroviral therapy (HAART) could reveal possible mechanisms of depletion. Twenty patients were evaluated with immunophenotyping, intracellular Ki67 staining, T-cell receptor excision circle (TREC) quantitation in sorted CD4 and CD8 cells, and thymic computed tomography scans prior to and similar to 6 and similar to 18 months after initiation of HAART. Naive T-cell proliferation decreased significantly during the first 6 months of therapy (P < 0.01) followed by a slower decline. Thymic indices did not change significantly over time. At baseline, naive CD4(+) T-cell numbers were lower than naive CD8(+) T-cell numbers; after HAART, a greater increase in naive CD4(+) T cells than naive CD8(+) T cells was observed. A greater relative change (it-fold) in the number of TREC+ T cells/mu l than in naive T-cell counts was observed at 6 months for both CD4(+) (median relative change [n-fold] of 2.2 and 1.7, respectively; P < 0.01) and CD8(+) T cell pools (1.4 and 1.2; P < 0.01). A more pronounced decrease in the proliferation than the disappearance rate of naive T cells after HAART was observed in a second group of six HIV-1-infected patients studied by in vivo pulse labeling with bromodeoxyuridine. These observations are consistent with a mathematical model where the HIV-1-induced increase in proliferation of naive T cells is mostly explained by a faster recruitment into memory cells.
C1 NIAID, NIH, Bethesda, MD 20892 USA.
   SAIC, Frederick, MD USA.
   NIH, Ctr Clin, Bethesda, MD 20892 USA.
   NCI, NIH, Frederick, MD 21701 USA.
RP Di Mascio, M (reprint author), NIAID, NIH, 6700 B Rockledge Dr,MSC 7609, Bethesda, MD 20892 USA.
EM mdimascio@niaid.nih.gov
RI Lempicki, Richard/E-1844-2012; 
OI Lempicki, Richard/0000-0002-7059-409X; Polis,
   Michael/0000-0002-9151-2268; Sidorov, Igor/0000-0001-6519-4983
FU Intramural NIH HHS
NR 48
TC 41
Z9 42
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2006
VL 80
IS 6
BP 2665
EP 2674
DI 10.1128/JVI.80.6.2665-2674.2006
PG 10
WC Virology
SC Virology
GA 023MS
UT WOS:000236131400008
PM 16501076
ER

PT J
AU Oliveira, NM
   Farrell, KB
   Eiden, MV
AF Oliveira, NM
   Farrell, KB
   Eiden, MV
TI In vitro characterization of a koala retrovirus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID APE LEUKEMIA-VIRUS; ENDOGENOUS RETROVIRUSES; RECEPTORS; DIVERSITY;
   PROTEINS
AB Recently, a new endogenous koala gammaretrovirus, designated KoRV, was isolated from koalas. The KoRV genome shares 78% nucleotide identity with another gammaretrovirus, gibbon ape leukemia virus (GALV). KoRV is endogenous in koalas, while GALV is exogenous, suggesting that KoRV predates GALV and that gibbons and koalas acquired the virus at different times from a common source. We have determined that subtle adaptive differences between the KoRV and GALV envelope genes account for differences in their receptor utilization properties. KoRV represents a unique example of a gammaretrovirus whose envelope has evolved to allow for its expanded host range and zoonotic potential.
C1 NIMH, Sect Mol Virol, NIH, Bethesda, MD 20892 USA.
RP Eiden, MV (reprint author), NIMH, Sect Mol Virol, NIH, 49 Convent Dr,MSC 4483, Bethesda, MD 20892 USA.
EM eidenm@mail.nih.gov
NR 15
TC 32
Z9 33
U1 2
U2 17
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 MAR
PY 2006
VL 80
IS 6
BP 3104
EP 3107
DI 10.1128/JVI.80.6.3104-3107.2006
PG 4
WC Virology
SC Virology
GA 023MS
UT WOS:000236131400054
PM 16501122
ER

PT J
AU Bandeen-Roche, K
   Xue, QL
   Ferrucci, L
   Walston, J
   Guralnik, JM
   Chaves, P
   Zeger, SL
   Fried, LP
AF Bandeen-Roche, K
   Xue, QL
   Ferrucci, L
   Walston, J
   Guralnik, JM
   Chaves, P
   Zeger, SL
   Fried, LP
TI Phenotype of frailty: Characterization in the women's health and aging
   studies
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
ID CARDIOVASCULAR HEALTH; ELDERLY WOMEN; OLDER; DISABILITY; EXERCISE;
   DISEASE; PEOPLE; MODEL
AB Background. "Frailty" is an adverse, primarily gerontologic. health condition regarded its frequent with aging and having severe consequences. Although clinicians claim that the extremes of frailty can be easily recognized, a standardized definition of frailty has proved elusive until recently. This article evaluates the cross-validity, criterion validity, and internal validity in the Women's Health and Aging Studies (WHAS) of a discrete measure, of frailty recently validated in the Cardiovascular Health Study (CHS).
   Methods. The frailty measure developed in CHS was delineated in the WHAS data sets. Using latent class analysis, we evaluated whether criteria composing the measure aggregate into a syndrome. We verified the criterion validity of the measure by testing whether participants defined as frail were more likely than others to develop adverse geriatric outcomes or to die.
   Results. The distributions of frailty in the WHAS and CHS were comparable. In latent class analyses, the measures demonstrated strong internal validity vis a vis stated theory characterizing frailty as a medical syndrome. In proportional hazards models, frail women had a higher risk of developing activities of daily living (ADL) and/or instrumental ADL disability, institutionalization, and death independently of multiple potentially confounding factors. , Conclusions. The findings of this study are consistent with the widely held theory that conceptualizes frailty its a syndrome. The frailty definition developed in the CHS is applicable across diverse population samples and identifies a profile of high risk of multiple adverse outcomes.
C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA.
   Johns Hopkins Med Inst, Dept Med, Ctr Aging & Hlth, Baltimore, MD 21205 USA.
   Johns Hopkins Med Inst, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA.
   NIA, Clin Res Branch, Intramural Res Program, Baltimore, MD 21224 USA.
   NIA, Div Epidemiol Demog & Biometry, Baltimore, MD 21224 USA.
RP Bandeen-Roche, K (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM kbandeen@jhsph.edu
FU NIA NIH HHS [1P50AG 021334-01, 1R37AG199502, R01 AG11703]
NR 33
TC 418
Z9 427
U1 4
U2 22
PU GERONTOLOGICAL SOCIETY AMER
PI WASHINGTON
PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAR
PY 2006
VL 61
IS 3
BP 262
EP 266
PG 5
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 039KC
UT WOS:000237303400008
PM 16567375
ER

PT J
AU Ble, A
   Cherubini, A
   Volpato, S
   Bartali, B
   Walston, LD
   Windham, BG
   Bandinelli, S
   Lauretani, F
   Guralnik, JM
   Ferrucci, L
AF Ble, A
   Cherubini, A
   Volpato, S
   Bartali, B
   Walston, LD
   Windham, BG
   Bandinelli, S
   Lauretani, F
   Guralnik, JM
   Ferrucci, L
TI Lower plasma vitamin e levels are associated with the frailty syndrome:
   The InCHIANTI study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
ID OLDER-ADULTS; HEALTH; INTERLEUKIN-6; SARCOPENIA; COMMUNITY; STRESS;
   CELLS
AB Background. The primary biologic mechanism that causes frailty in older persons has never been adequately explained. According to recent views, oxidative stress may be the driving force of this condition. We tested the hypothesis that, independent of confounders, low plasma levels of vitamin E (alpha-locopherol), the main fat-soluble human antioxidant, are associated with the frailty syndrome in older persons free from dementia and disability.
   Methods. The study sample included 827 older (>= 65 years) persons (women, 54%) who participated in a population based epidemiological study. Frail participants were identified based on the presence of at least three of live of the following features: self-reported weight loss, low energy, slow gait speed, low grip strength, and low physical activity. Participants with none of these features were considered nonfrail, while participants with one or two were considered intermediate frail. Plasma vitamin E levels were determined using reverse-phase high-performance liquid chromatography. Measured confounders included lower extremity muscle strength, cognitive function, diseases, and factors related to vitamin E metabolism.
   Results. Age- and gender-adjusted levels of vitamin E decreased gradually from the nonfrail to the frail group (p for trend=.015). In the logistic model adjusted for multiple potential confounders, participants in the highest vitamin E tertile were less likely to be frail than were participants in the lowest vitamin E tertile (odds ratio, 0.30; 95% confidence interval, 0.10-0.91).
   Conclusions. Our findings show an association between low circulating levels of one of the most important components of the human antioxidant system and the presence of frailty.
C1 Harbor Hosp, NIA, Longitudinal Studies Sect, Clin Res Branch,Natl Inst Hlth, Baltimore, MD 21225 USA.
   Univ Perugia, Inst Gerontol & Geriatr, I-06100 Perugia, Italy.
   Univ Ferrara, Sect Internal Med & Geriatr, Dept Clin & Expt Med, I-44100 Ferrara, Italy.
   Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
   Johns Hopkins Univ, Div Geriatr Med & Gerontol, Baltimore, MD USA.
   Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy.
   Tuscany Reg Hlth Agcy, Florence, Italy.
   NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
RP Ferrucci, L (reprint author), Harbor Hosp, NIA, Longitudinal Studies Sect, Clin Res Branch,Natl Inst Hlth, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA.
EM ferruccilu@grc.nia.nih.gov
RI VOLPATO, STEFANO/H-2977-2014; Lauretani, Fulvio/K-5115-2016; 
OI VOLPATO, STEFANO/0000-0003-4335-6034; Lauretani,
   Fulvio/0000-0002-5287-9972; Cherubini, Antonio/0000-0003-0261-9897
FU NIMHD NIH HHS [263 MD 821336, 263 MD 9164 13]
NR 29
TC 64
Z9 67
U1 0
U2 8
PU GERONTOLOGICAL SOCIETY AMER
PI WASHINGTON
PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAR
PY 2006
VL 61
IS 3
BP 278
EP 283
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 039KC
UT WOS:000237303400011
PM 16567378
ER

PT J
AU Koster, A
   Bosma, H
   Penninx, BWJH
   Newman, AB
   Harris, TB
   van Eijk, JTM
   Kempen, GIJM
   Simonsick, EM
   Johnson, KC
   Rooks, RN
   Ayonayon, HN
   Rubin, SM
   Kritchevsky, SB
AF Koster, A
   Bosma, H
   Penninx, BWJH
   Newman, AB
   Harris, TB
   van Eijk, JTM
   Kempen, GIJM
   Simonsick, EM
   Johnson, KC
   Rooks, RN
   Ayonayon, HN
   Rubin, SM
   Kritchevsky, SB
CA Hlth ABC Study
TI Association of inflammatory markers with socioeconomic status
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
ID C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; BODY-COMPOSITION; OLDER
   PERSONS; SYSTEMIC INFLAMMATION; WHITEHALL-II; RISK-FACTORS; HEALTH;
   INTERLEUKIN-6; CYTOKINES
AB Background. This Study examines the association between socioeconomic status (SES) and inflammatory markers in well-functioning older adults and seeks to determine whether my association remains after adjusting for biomedical and behavioral factors typically related to elevated serum levels of inflammatory markers.
   Methods. Data were obtained from 3044 men and women, aged 70-79 from Pittsburgh, Pennsylvania and Memphis, Tennessee participating in the Health, Aging and Body Composition Study. Three indicators of SES were used: education, income, and ownership of financial assets. Serum levels of interleukin-6, C-reactive protein, and tumor necrosis factor-alpha were measured.
   Results. Low SES was associated with significantly elevated levels of interleukin-6. C-reactive protein, and tumor necrosis factor-alpha compared to high SES. Behavioral factors (including smoking, drinking, obesity) explained a substantial part of'the inverse association between SES and inflammatory markers. Adjustment for prevalent diseases (including heart diseases, lung disease, and diabetes) associated with inflammation explained less of the association.
   Conclusions. This study suggests that intervention,,; to improve health behaviors, even in old age and especially in low SES groups, may be useful in reducing risks associated with inflammation.
C1 Univ Maastricht, Dept Hlth Care Studies, Sect Med Sociol, NL-6200 MD Maastricht, Netherlands.
   Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, NL-1081 HV Amsterdam, Netherlands.
   Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
   NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
   NIA, Clin Res Branch, Baltimore, MD 21224 USA.
   Johns Hopkins Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD USA.
   Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
   Kent State Univ, Dept Sociol, Kent, OH 44242 USA.
   Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   Wake Forest Univ, Sch Med, Sticht Ctr Aging Gerontol & Geriatr Med, Winston Salem, NC 27109 USA.
RP Koster, A (reprint author), Univ Maastricht, Dept Hlth Care Studies, Sect Med Sociol, POB 616, NL-6200 MD Maastricht, Netherlands.
EM a.koster@zw.unimaas.nl
RI Koster, Annemarie/E-7438-2010; Bosma, Hans/A-6184-2013; Newman,
   Anne/C-6408-2013; Kempen, Gertrudis/H-5978-2016
OI Newman, Anne/0000-0002-0106-1150; Kempen, Gertrudis/0000-0002-7053-2198
FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103,
   N01-AG-6-2106]
NR 36
TC 71
Z9 71
U1 1
U2 3
PU GERONTOLOGICAL SOCIETY AMER
PI WASHINGTON
PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD MAR
PY 2006
VL 61
IS 3
BP 284
EP 290
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 039KC
UT WOS:000237303400012
PM 16567379
ER

PT J
AU Terracciano, A
   McCrae, RR
   Costa, PT
AF Terracciano, Antonio
   McCrae, Robert R.
   Costa, Paul T., Jr.
TI Longitudinal trajectories in guilford-zimmerman temperament survey data:
   Results from the Baltimore longitudinal study of aging
SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL
   SCIENCES
LA English
DT Article
AB We examined developmental trends in personality traits over a 42-year time period by using data from the Baltimore Longitudinal Study on Aging (N = 2,359; individuals aged 17-98), collected from 1958 to 2002. Hierarchical linear modeling analyses revealed cumulative mean-level changes averaging about 0.5 SD across adulthood. Scales related to extraversion showed distinct developmental patterns: General Activity declined from age 60 to 90; Restraint increased; Ascendance peaked around age 60; and Sociability declined slightly. Scales related to neuroticism showed curvilinear declines up to age 70 and increases thereafter. Scales related to agreeableness and openness changed little; Masculinity declined linearly. We found significant individual variability in change. Although intercepts differed, trajectories were similar for men and women. Attrition and death had no effect on slopes. This study highlights the use of lower order traits in providing a more nuanced picture of developmental change.
C1 NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA.
RP Terracciano, A (reprint author), 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM terraccianoa@grc.nia.nih.gov
RI terracciano, antonio/B-1884-2008
FU Intramural NIH HHS [Z99 AG999999, ZIA AG000183-22, ZIA AG000183-23, ZIA
   AG000197-03, ZIA AG000197-04]
NR 42
TC 17
Z9 17
U1 0
U2 6
PU GERONTOLOGICAL SOC AMER
PI WASHINGTON
PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA
SN 1079-5014
J9 J GERONTOL B-PSYCHOL
JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci.
PD MAR
PY 2006
VL 61
IS 2
BP P108
EP P116
PG 9
WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology,
   Multidisciplinary
SC Geriatrics & Gerontology; Psychology
GA V44GZ
UT WOS:000202992500007
PM 16497954
ER

PT J
AU Dear, JW
   Yasuda, H
   Hu, X
   Hieny, S
   Yuen, PST
   Hewitt, SM
   Sher, A
   Star, RA
AF Dear, JW
   Yasuda, H
   Hu, X
   Hieny, S
   Yuen, PST
   Hewitt, SM
   Sher, A
   Star, RA
TI Sepsis-induced organ failure is mediated by different pathways in the
   kidney and liver: Acute renal failure is dependent on MyD88 but not
   renal cell apoptosis
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE acute renal failure; sepsis; MyD88; innate immunity; toll-like receptor
   4
ID TUMOR-NECROSIS-FACTOR; CAUTIONARY NOTE; CECAL LIGATION; AGED MICE;
   ENDOTOXIN; ACTIVATION; MUTATIONS; PUNCTURE; SPLEEN; DEATH
AB Toll-like receptors (TLRs) are important in sepsis. Myeloid differentiation factor 88 (MyD88) is a key molecule involved in signal transduction by multiple TLRs. The objective of this study was to investigate the contribution of TLR4 and MyD88 to acute renal failure (ARF) induced by polymicrobial sepsis. Liver dysfunction and apoptosis in the spleen contribute to sepsis severity after cecal ligation and puncture (CLP). Therefore, we also investigated liver injury and splenic apoptosis. We used a mouse model of sepsis-induced ARF using CLP to generate polymicrobial sepsis. Despite fluid and antibiotic resuscitation the mice developed multi-organ failure, including ARF, which resembles human sepsis. We investigated the role of the TLR4 receptor by comparing C3H/ HeJ mice ( which lack TLR4) with C3H/He0UJ normal controls. The role of MyD88 was investigated by comparing MyD88 knockout mice (MyD88(-/-)) with wild-type controls. Following CLP, mice lacking TLR4 and wild-type mice both developed comparable ARF. However, MyD88(-/-) mice did not develop ARF compared to wild-type controls. In contrast, MyD88(-/-) mice developed liver injury comparable to wild type. After CLP, MyD88(-/-) mice had significantly reduced apoptosis in the spleen compared with wild type. Apoptosis was not detected in the kidney of wild-type or MyD88(-/-) mice after CLP. In summary, ARF induced by polymicrobial sepsis is dependent on MyD88, but not TLR4. The absence of MyD88 dissociates ARF from liver injury; liver injury is MyD88-independent. There was MyD88-dependent apoptosis in the spleen, but no apoptosis in the kidney. MyD88 may be a good drug target for some, but not all, organ dysfunctions following sepsis.
C1 NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA.
   NIAID, Parasit Dis Lab, Immunobiol Sect, Bethesda, MD 20892 USA.
   NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Star, RA (reprint author), NIDDK, Renal Diagnost & Therapeut Unit, NIH, 10 Ctr Dr,Bldg 10,Room 3N108, Bethesda, MD 20892 USA.
EM Robert_Star@nih.gov
RI Yuen, Peter/B-1954-2008; 
OI Yuen, Peter/0000-0001-9557-3909; Hewitt, Stephen/0000-0001-8283-1788
FU Intramural NIH HHS [Z01 DK043403-08]
NR 28
TC 69
Z9 73
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
J9 KIDNEY INT
JI Kidney Int.
PD MAR
PY 2006
VL 69
IS 5
BP 832
EP 836
DI 10.1038/sj.ki.5000165
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 017YT
UT WOS:000235730000012
PM 16518342
ER

PT J
AU Friedman, B
   Berman, JJ
AF Friedman, B
   Berman, JJ
TI Reinventing pathology: The hemathopathologist as a model for the
   pathologist of the Future
SO LABMEDICINE
LA English
DT Editorial Material
C1 Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
   NCI, Canc Diag Program, Bethesda, MD 20892 USA.
RP Friedman, B (reprint author), Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0007-5027
J9 LABMEDICINE
JI Labmedicine
PD MAR
PY 2006
VL 37
IS 3
BP 182
EP 183
PG 2
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 017ES
UT WOS:000235677500015
ER

PT J
AU Bussey, TJ
   Saksida, LM
   Murray, EA
AF Bussey, TJ
   Saksida, LM
   Murray, EA
TI Perirhinal cortex and feature-ambiguous discriminations
SO LEARNING & MEMORY
LA English
DT Letter
ID MEDIAL TEMPORAL-LOBE; VISUAL-DISCRIMINATION; LESIONS; MEMORY;
   IMPAIRMENTS; ABLATION; COMPLEX; INTACT; VIEWS
C1 Univ Cambridge, Dept Expt Psychol, Cambridge CB1 3EB, England.
   NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Bussey, TJ (reprint author), Univ Cambridge, Dept Expt Psychol, Cambridge CB1 3EB, England.
EM tjb1000@cam.ac.uk
RI Bussey, Timothy/M-2758-2016; Saksida, Lisa/M-2753-2016
OI Bussey, Timothy/0000-0001-7518-4041; Saksida, Lisa/0000-0002-8416-8171
FU NIMH NIH HHS [MH24600]
NR 18
TC 21
Z9 21
U1 1
U2 5
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 1072-0502
J9 LEARN MEMORY
JI Learn. Mem.
PD MAR-APR
PY 2006
VL 13
IS 2
BP 103
EP 105
DI 10.1101/lm.163606
PG 3
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 029IQ
UT WOS:000236556200001
PM 16585785
ER

PT J
AU Lacroix, EM
   Backus, JEB
AF Lacroix, Eve-Marie
   Backus, Joyce E. B.
TI Organizing electronic information to serve the needs of health
   practitioners and consumers
SO LIBRARY TRENDS
LA English
DT Article
AB From its beginnings as the Library of the Army Surgeon General to today's Internet-driven information environment, the U.S. National Library of Medicine (NLM) has served a variety of audiences. As NLM strives to provide the best possible service to health scientists and consumers, the form of that service has changed depending on resources available and the state of technology. Throughout its history, NLM has adopted innovative programs and technology at the earliest sensible moment that would serve its patron needs. Today, NLM is a leader in providing electronic biomedical information to health professionals, researchers, the public, and anyone else with access to the Internet. These services have evolved in response to available technology and the demands of the various audiences, from clinicians to consumers. To serve the needs of this variety of patrons, NLM connects health information resources in ways that enable each audience to find the information appropriate to its need. NLM continues to improve this organization as the demand and technology and resources allow.
C1 Natl Lib Med, Publ Serv Div, Bethesda, MD 20894 USA.
   Natl Lib Med, Reference & Web Serv Sect, Bethesda, MD 20894 USA.
RP Lacroix, EM (reprint author), Natl Lib Med, Publ Serv Div, Bethesda, MD 20894 USA.
NR 21
TC 2
Z9 2
U1 0
U2 3
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
   21218-4363 USA
SN 0024-2594
J9 LIBR TRENDS
JI Libr. Trends
PD SPR
PY 2006
VL 54
IS 4
BP 607
EP 619
DI 10.1353/lib.2006.0038
PG 13
WC Information Science & Library Science
SC Information Science & Library Science
GA 085UJ
UT WOS:000240629600010
ER

PT J
AU Mayo, MJ
   Mosby, JM
   Jeyarajah, R
   Combes, B
   Khilnani, S
   Al-halimi, M
   Handem, I
   Grammer, AC
   Lipsky, PE
AF Mayo, MJ
   Mosby, JM
   Jeyarajah, R
   Combes, B
   Khilnani, S
   Al-halimi, M
   Handem, I
   Grammer, AC
   Lipsky, PE
TI The relationship between hepatic immunoglobulin production and CD154
   expression in chronic liver diseases
SO LIVER INTERNATIONAL
LA English
DT Article
DE CD154; CD40; CD40 ligand; hyperglobulinemia; immunoglobulin gamma;
   immunoglobulin mu
ID PRIMARY BILIARY-CIRRHOSIS; CD40 LIGAND; INVITRO
AB Background: CD40-CD154 is a receptor-ligand pair that provides key communication signals between cells of the adaptive immune system in states of inflammation and autoimmunity. The CD40 receptor is expressed constitutively on B lymphocytes, for which it provides important signals regulating clonal expansion and antibody production. CD154 is a member of the tumor necrosis factor superfamily, which is primarily expressed by activated T cells. Methods: Because many chronic liver diseases are characterized by lymphocytic infiltration of the liver and several have increased immunoglobulin (Ig) production, the role of CD40-CD154 in hepatic Ig production was investigated in patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis, autoimmune hepatitis (AIH), hepatitis C, hepatitis B, alcoholic and non-alcoholic steatohepatitis, as well as normal controls. Results: Soluble CD154 levels in the serum were found to be no different in chronic liver diseases vs normal controls. Likewise, CD154 mRNA levels in peripheral blood mononuclear cells did not differ. However, mRNA for CD154 was significantly increased in the liver of individuals with PBC and AIH as compared with the other groups. The quantity of CD154 mRNA in the liver correlated positively with the quantity of mRNA for secretory Ig. Conclusion: These findings suggest that CD40-CD154 signals may be involved in Ig production within the liver of autoimmune liver diseases.
C1 Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dept Internal Med, Dallas, TX 75390 USA.
   Univ Texas, SW Med Ctr, Dept Surg, Dallas, TX 75390 USA.
   NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
RP Mayo, MJ (reprint author), Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dept Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM marlyn.mayo@utsouthwestern.edu
FU NCRR NIH HHS [M1-RR00663]; NIDDK NIH HHS [K23DK02687, R01-DK46602]
NR 15
TC 8
Z9 9
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1478-3223
J9 LIVER INT
JI Liver Int.
PD MAR
PY 2006
VL 26
IS 2
BP 187
EP 196
DI 10.1111/j.1478-3231.2005.01211.x
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 008MP
UT WOS:000235045200006
PM 16448457
ER

PT J
AU Ying, JF
   Grishaev, AE
   Bax, A
AF Ying, JF
   Grishaev, AE
   Bax, A
TI Carbon-13 chemical shift anisotropy in DNA bases from field dependence
   of solution NMR relaxation rates
SO MAGNETIC RESONANCE IN CHEMISTRY
LA English
DT Article
DE NMR; C-13; H-1; base; chemical shift anisotropy; nucleic acid;
   relaxation
ID SPIN RELAXATION; NUCLEIC-ACIDS; ROTATIONAL DIFFUSION; DYNAMICS; RNA;
   PROTEIN; SENSITIVITY; RESOLUTION; EXCHANGE; RIBOSE
AB Knowledge of C-13 chemical shift anisotropy (CSA) in nucleotide bases is important for the interpretation of solution-state NMR relaxation data in terms of local dynamic properties of DNA and RNA. Accurate knowledge of the CSA becomes particularly important at high magnetic fields, prerequisite for adequate spectral resolution in larger oligonucleotides. Measurement of C-13 relaxation rates of protonated carbons in the bases of the so-called Dickerson dodecamer, d(CGCGAATTCGCG)(2), at 500 and 800 MHz H-1 frequency, together with the previously characterized structure and diffusion tensor yields CSA values for C5 in C, C6 in C and T, C8 in A and G, and C2 in A that are closest to values previously reported on the basis of solid-state FIREMAT NMR measurements, and mostly larger than values obtained by in vacuo DFT calculations. Owing to the noncollinearity of dipolar and CSA interactions, interpretation of the NMR relaxation rates is particularly sensitive to anisotropy of rotational diffusion, and use of isotropic diffusion models can result in considerable errors.
C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 126, Bethesda, MD 20892 USA.
EM bax@nih.gov
FU Intramural NIH HHS
NR 30
TC 11
Z9 11
U1 1
U2 6
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0749-1581
J9 MAGN RESON CHEM
JI Magn. Reson. Chem.
PD MAR
PY 2006
VL 44
IS 3
BP 302
EP 310
DI 10.1002/mrc.1762
PG 9
WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy
SC Chemistry; Spectroscopy
GA 021VK
UT WOS:000236013800014
PM 16477676
ER

PT J
AU Rodriguez, I
   Ennis, DB
   Wen, H
AF Rodriguez, I
   Ennis, DB
   Wen, H
TI Noninvasive measurement of myocardial tissue volume change during
   systolic contraction and diastolic relaxation in the canine left
   ventricle
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE coronary blood flow; microcirculation; capillary permeability; magnetic
   resonance imaging; DENSE
ID CORONARY BLOOD-FLOW; STIMULATED ECHOES; HUMAN HEART; IN-VIVO; MRI; MASS;
   PRESSURE; STRAIN; DENSE; QUANTIFICATION
AB In coronary circulation the flow in epicardial arteries and veins is observed to be pulsatile and out of phase with each other. Theoretical considerations predict that this phenomenon extends to all levels of the vascular tree and leads to a cyclic fluctuation of regional tissue volume. Intramyocardial tissue volume change between end-systole and end-diastole was measured noninvasively with MRI in 10 closed-chest beagles. The displacement encoding with stimulated-echo technique was used to obtain pixel-by-pixel tissue displacement field between end-diastole and end-systole and vice versa in the midlevel left ventricle, from which the 3D strain matrix and volume changes were calculated. The volume change was between 0.8 +/- 0.5% (mean +/- STD) in the epicardial layer and 1.5 0.6% in the subendocardial layer of the left ventricle. Tissue volume fluctuation reflects the amount of arterial inflow in a heartbeat under the assumption that regional arterial inflow and venous outflow have little time overlap. The corresponding perfusion level was estimated to be from (1.0 +/- 0.6) ml/min/g in the epicardial layer to (1.7 +/- 0.6) ml/min/g in the subendocardial layer, in good agreement with microsphere measurements in the same dog model. The result supports the notion of high arterial resistance at the microvascular level from intramyocardial pressure during systole.
C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
   Stanford Univ, Dept Radiol, Palo Alto, CA USA.
RP Wen, H (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
EM wenh@nhlbi.nih.gov
RI Rodriguez, Ignacio/B-1006-2015; Wen, Han/G-3081-2010
OI Rodriguez, Ignacio/0000-0002-4262-2516; Wen, Han/0000-0001-6844-2997
FU Intramural NIH HHS [ZIA HL004606-13]
NR 38
TC 16
Z9 16
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD MAR
PY 2006
VL 55
IS 3
BP 484
EP 490
DI 10.1002/mrm.20786
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 019TA
UT WOS:000235858400004
PM 16408273
ER

PT J
AU Chuang, KH
   Koretsky, A
AF Chuang, KH
   Koretsky, A
TI Improved neuronal tract tracing using manganese enhanced magnetic
   resonance imaging with fast T-1 mapping
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE manganese enhanced MRI; T-1 map; neuronal tract tracing; molecular
   imaging; olfactory pathways
ID BRAIN IN-VIVO; RAT-BRAIN; MOUSE-BRAIN; BASAL GANGLIA; ONE-SHOT; MRI;
   CONTRAST; MEMRI; OPTIMIZATION; SEQUENCE
AB There has been growing interest in using manganese-enhanced MRI (MEMRI) to detect neuronal activation, neural architecture, and neuronal connections. Usually Mn2+ produces a very wide range of T-1 change. In particular, in neuronal tract tracing experiments the site of Mn2+ injection can have very short T-1 while distant regions have small T-1 reductions, primarily due to dilution of Mn2+. Most MEMRI studies use T-1-weighted sequences, which can only give optimal contrast for a narrow range of T-1 changes. To improve sensitivity to the full extent of Mn2+ concentrations and to optimize detection of low concentrations of Mn2+, a fast T-1 mapping sequence based on the Look and Locker technique was implemented. Phantom studies demonstrated less than 6.5% error in T-1 compared to more conventional T-1 measurements. Using center-out segmented EPI, whole-brain 3D T-1 maps with 200-mu m isotropic resolution were obtained in 2 h from rat brain. Mn2+ transport from the rat olfactory bulb through appropriate brain structures could be detected to the amygdala in individual animals. The method reliably detected less than 7% reductions in T-1. With this quantitative imaging it should be possible to study more extensive pathways using MEMRI and decrease the dose of Mn2+ used. Magn Reson Med 55:604-611, 2006. Published 2006 Wiley-Liss, Inc.
C1 NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Koretsky, A (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,10-B1D728, Bethesda, MD 20892 USA.
EM KoretskyA@ninds.nih.gov
RI Koretsky, Alan/C-7940-2015; 
OI Koretsky, Alan/0000-0002-8085-4756; Chuang,
   Kai-Hsiang/0000-0002-8356-0657
FU Intramural NIH HHS [Z01 NS002989-08]
NR 56
TC 60
Z9 64
U1 1
U2 7
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD MAR
PY 2006
VL 55
IS 3
BP 604
EP 611
DI 10.1002/mrm.20797
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 019TA
UT WOS:000235858400019
PM 16470592
ER

PT J
AU Gomez, CR
   Acuna-Castillo, C
   Nishimura, S
   Perez, V
   Escobar, A
   Salazar-Onfray, F
   Sabaj, V
   Torres, C
   Walter, R
   Sierra, F
AF Gomez, CR
   Acuna-Castillo, C
   Nishimura, S
   Perez, V
   Escobar, A
   Salazar-Onfray, F
   Sabaj, V
   Torres, C
   Walter, R
   Sierra, F
TI Serum from aged F344 rats conditions the activation of young macrophages
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Article
DE aging; macrophages; cytokines; lipopolysaccharide; TNF-alpha; IL-6
ID GLYCOSYLATION END-PRODUCTS; CYTOKINE PRODUCTION; HUMAN-MONOCYTES;
   CALORIC RESTRICTION; DENDRITIC CELLS; IL-6 PRODUCTION; OLD-AGE; MICE;
   INFLUENZA; IMMUNITY
AB There is considerable controversy about the molecular mechanisms responsible for the variations in innate immunity associated with age. While in vivo, aged animals and humans react to an inflammatory signal with ail excessive production of pro-inflammatory cytokines, studies in vitro generally show that this response is attenuated in macrophages from old individuals. In ail effort to examine possible extrinsic factors that might affect the response of macrophages to lipopolysaccharide (LPS), we have challenged peritoneal macrophages obtained from young rats with sera obtained from rats of different ages. Our results indicate that the serum from aged rats significantly impairs the capacity of young macrophages to induce tumor necrosis factor-alpha (TNF-alpha) production, while at the same time it increases the basal levels of interleukin-6 (IL-6). The effect of serum from aged donors oil TNF-alpha secretion requires pre-incubation and is sensitive to heat inactivation. In contrast, the stimulating effect on IL-6 is resistant to heat, and thus should not be due to a protein factor. Therefore, our results indicate that the age-related changes in macrophage activity are not only the consequence of intrinsic changes, but there also appears to be a modulatory effect imparted by the external milieu. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
C1 Univ Chile, Fac Med, Ctr FONDAP Estudio Mol Celula, Santiago, Chile.
   Univ Chile, Fac Med, Inst Ciencias Biomed, Program Biol Celular & Mol, Santiago, Chile.
   Univ Chile, Fac Med, Inst Ciencias Biomed, Program Immunol, Santiago, Chile.
   Lankenau Inst Med Res, Wynnewood, PA 19096 USA.
RP Sierra, F (reprint author), NIA, Biol Aging Program, Gateway Bldg,Suite 2C231,7201 Wisconsin Ave, Rockville, MD 20850 USA.
EM sierraf@nia.nih.gov
FU NIA NIH HHS [AG13902]
NR 41
TC 17
Z9 18
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD MAR
PY 2006
VL 127
IS 3
BP 257
EP 263
DI 10.1016/j.mad.2005.10.002
PG 7
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 019TU
UT WOS:000235860400005
PM 16343598
ER

PT J
AU Perez, V
   Leiva-Salcedo, E
   Acuna-Castillo, C
   Aravena, M
   Gomez, C
   Sabaj, V
   Colombo, A
   Nishimura, S
   Perez, C
   Walter, R
   Sierra, F
AF Perez, V
   Leiva-Salcedo, E
   Acuna-Castillo, C
   Aravena, M
   Gomez, C
   Sabaj, V
   Colombo, A
   Nishimura, S
   Perez, C
   Walter, R
   Sierra, F
TI T-kininogen induces endothelial cell proliferation
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Article
DE endothelial cells; T-KG; kinin receptors; ERK; cell proliferation; aging
ID MOLECULAR-WEIGHT KININOGEN; SIGNAL-TRANSDUCTION; PROTEIN-KINASE;
   GENE-EXPRESSION; EGF RECEPTOR; NITRIC-OXIDE; AGE; ANGIOGENESIS;
   BRADYKININ; RATS
AB Basal proliferation of endothelial cells increases with age, and this might play a role in the etiology of age-related vascular diseases, as well as angiogenesis. Serum kininogen levels increase during aging in rats and humans, and T-kininogen (T-KG) can affect proliferative homeostasis in several cell models. Both kinins and kininogens have been shown previously to be angiogenic through activation of endothelial cell proliferation, and here we show that exposure of endothelial cells to T-KG results in vigorous cell proliferation, accompanied by ERK/AKT activation. In our experiments, the proliferative response requires B1 and B2 kinin receptors, even though kinins are not released from the precursor. We hypothesize that the age-related increase in T-KG could play a significant role in the age-related dysregulation of vascular physiology and function. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
C1 Univ Chile, Inst Ciencias Biomed, Programa Biol Celular & Mol, Santiago, Chile.
   Univ Chile, Fac Med, Ctr FONDAP Estudios Mol Celula, Santiago, Chile.
   Lankenau Inst Med Res, Wynnewood, PA 19096 USA.
RP Sierra, F (reprint author), NIA, Biol & Aging Program, NIH, 7201 Wisconsin Ave,Suite 2C231, Bethesda, MD 20892 USA.
EM Sierraf@nia.nih.gov
RI Colombo , Alicia /I-3329-2013
FU NIA NIH HHS [R01 AG13902]
NR 44
TC 6
Z9 9
U1 0
U2 1
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD MAR
PY 2006
VL 127
IS 3
BP 282
EP 289
DI 10.1016/j.mad.2005.11.002
PG 8
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 019TU
UT WOS:000235860400008
PM 16378635
ER

PT J
AU Narbonne-Reveau, K
   Besse, F
   Lamour-Isnard, C
   Busson, D
   Pret, AM
AF Narbonne-Reveau, K
   Besse, F
   Lamour-Isnard, C
   Busson, D
   Pret, AM
TI fused regulates germline cyst mitosis and differentiation during
   Drosophila oogpnesis
SO MECHANISMS OF DEVELOPMENT
LA English
DT Article
DE Drosophila melanogaster; ovarian tumor mutants; fused; oogenesis;
   germiline stem cell; germline cyst; cystoblast; Dpp/TGF beta; bag of
   marbles; cell cycle arrest
ID BAG-OF-MARBLES; SERINE-THREONINE KINASE; LINE SEX DETERMINATION; EGG
   CHAMBER FORMATION; GENIAL-CELL-NEOPLASM; WING IMAGINAL DISCS;
   STEM-CELLS; OVARIAN-TUMOR; ASYMMETRIC DIVISION; GENETIC-ANALYSIS
AB The fused gene encodes a serine-threonine kinase that functions as a positive regulator of Hedgehog signal transduction in Drosophila embryogenesis, wing morphogenesis, and somatic cell development during oogenesis. Here, we have characterized the germline ovarian tumors present in adult ovaries of fused mutant females, a phenotype not observed upon deregulation of any other component of Hedgehog signaling. In the strongest fused mutant contexts, we found that tumorous ovarian follicles accumulate early spectrosome-containing germ cells corresponding to germline stem cells and/or early cystoblasts as evidenced by activated Dpp signal transduction and transcriptional repression of bag-of-marbles, encoding the cystoblast determination factor. These early germ cells are maintained far from their usual position in a specialized niche of somatic cells in the apical part of the germarium, which appears normal in size in fused mutant ovarioles. Therefore, these results indicate a novel function for fused in down regulation of Dpp signaling which is necessary for de-repression of bag-of-marbles and consequent cystoblast determination. The abnormal accumulation of these early germ cells seems to be due primarily to defects in differentiation since we show that germline stem cell proliferation in the germarium is not affected. A later block in germline development, at the 16-cell cyst stage before significant nurse cell and oocyte differentiation, was also observed in tumorous follicles when fused function was only partially lowered. Finally, fused mutant ovaries exhibit some germline cysts having undergone a supernumerary fifth mitotic division. Through clonal analysis, we provide evidence that fused regulates these cystocyte divisions cell autonomously, while the tumorous phenotype probably reflects both a somatic and germline requirement for fused for cyst and follicle development. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA.
   EMBL, Dev Biol Programme, D-69117 Heidelberg, Germany.
   Univ Paris 06, Univ Denis Diderot, CNRS, UMR 7592,Inst J Monod,Lab Genet Dev & Evolut, F-75251 Paris, France.
RP Pret, AM (reprint author), Univ Paris 06, CNRS UPR 2167, Ctr Genet Mol, Dept Dev, F-91198 Gif Sur Yvette, France.
EM pret@cgm.cnrs-gif.fr
NR 58
TC 9
Z9 10
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4773
J9 MECH DEVELOP
JI Mech. Dev.
PD MAR
PY 2006
VL 123
IS 3
BP 197
EP 209
DI 10.1016/j.mod.2006.01.001
PG 13
WC Developmental Biology
SC Developmental Biology
GA 036UU
UT WOS:000237102200001
PM 16516445
ER

PT J
AU La Via, WV
   Lambert, JL
   Pelletier, MJ
   Morookian, JM
   Sirk, SJ
   Mickiene, D
   Walsh, TJ
   Borchert, MS
AF La Via, WV
   Lambert, JL
   Pelletier, MJ
   Morookian, JM
   Sirk, SJ
   Mickiene, D
   Walsh, TJ
   Borchert, MS
TI Measurement of Amphotericin B concentration by Resonant Raman
   Spectroscopy - a novel technique that may be useful for non-invasive
   monitoring
SO MEDICAL MYCOLOGY
LA English
DT Article
DE Resonant Raman Spectroscopy (RRS); amphotericin B (AmB)
ID LIPID FORMULATIONS; ENDOPHTHALMITIS; PENETRATION; GLUCOSE; RABBITS;
   MODEL
AB We wished to determine whether Resonant Raman Spectroscopy (RRS) could be used to measure Amphotericin B (AmB) at therapeutic and subtherapeutic concentrations in a model system mimicking the anterior chamber of the eye. The goal was to develop a technique for non-invasive measurement of AmB levels in the aqueous humor (AH) of the eye. A krypton-ion laser source (406.7 nm) was used for excitation and Resonant Raman Spectra were captured with a confocal system in an anterior chamber (AC) model. These spectra were used to develop a correlation curve for prediction of AmB levels. Subsequently, one rabbit was evaluated with this system after 5 days of intravenous AmB administration (1 mg/kg/day) and AmB concentrations measured by RRS were compared to those measured by high-performance liquid chromatography (HPLC). AmB exhibited a unique spectral peak at 1557 cm(-1). Integrated area of this peak linearly correlated with AmB concentration in our model AC. When integrated peak area from multiple in vivo measurements in one animal at steady-state was plotted on this correlation curve, we were able to predict AmB levels. These closely approximated those measured by HPLC. These measurements were not significantly affected by photobleaching or depth profile at acquisition. RRS at 406.7 ran is a method that may be useful for non-invasive monitoring of intraocular AmB levels. This instrument can help physicians decide when repeat, invasive delivery of this drug is warranted based on Measurement of actual drug levels in the AH. Also, there is the potential to measure the ocular concentrations of other pharmaceutical agents with similar instruments.
C1 Univ So Calif, Keck Sch Med, Div Infect Dis, Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
   CALTECH, Jet Prop Lab, Pasadena, CA USA.
   Univ So Calif, Keck Sch Med, Div Ophthalmol, Childrens Hosp Los Angeles, Los Angeles, CA USA.
   NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA.
RP La Via, WV (reprint author), Univ So Calif, Keck Sch Med, Div Infect Dis, Childrens Hosp Los Angeles, 4650 W Sunset Blvd,MS 51, Los Angeles, CA 90027 USA.
EM wlavia@chla.usc.edu
NR 15
TC 12
Z9 12
U1 1
U2 5
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1369-3786
J9 MED MYCOL
JI Med. Mycol.
PD MAR
PY 2006
VL 44
IS 2
BP 169
EP 174
DI 10.1080/13693780500338761
PG 6
WC Infectious Diseases; Mycology; Veterinary Sciences
SC Infectious Diseases; Mycology; Veterinary Sciences
GA 013VQ
UT WOS:000235438500009
PM 16519020
ER

PT J
AU Marcu, MG
   Jung, YJ
   Lee, S
   Chung, EJ
   Lee, MJ
   Trepel, J
   Neckers, L
AF Marcu, Monica G.
   Jung, Yun-Jin
   Lee, Sunmin
   Chung, Eun-Joo
   Lee, Min-Jung
   Trepel, Jane
   Neckers, Len
TI Curcumin is an Inhibitor of p300 Histone Acetylatransferase
SO MEDICINAL CHEMISTRY
LA English
DT Article
DE Curcumin; p300/CBP; acetylation; Michael reaction acceptor
AB Histone acetyltransferases (HATs), and p300/CBP in particular, have been implicated in cancer cell growth and survival, and as such, HATs represent novel, therapeutically relevant molecular targets for drug development. In this study, we demonstrate that the small molecule natural product curcumin, whose medicinal properties have long been recognized in India and Southeast Asia, is a selective HAT inhibitor. Furthermore the data indicate that alpha, beta unsaturated carbonyl groups in the curcumin side chain function as Michael reaction sites and that the Michael reaction acceptor functionality of curcumin is required for its HAT-inhibitory activity. In cells, curcumin promoted proteasome-dependent degradation of p300 and the closely related CBP protein without affecting the HATs PCAF or GCN5. In addition to inducing p300 degradation curcumin inhibited the acetyltransferase activity of purified p300 as assessed using either histone H3 or p53 as substrate. Radiolabeled curcumin formed a covalent association with p300, and tetrahydrocurcumin displayed no p300 inhibitory activity, consistent with a Michael reaction-dependent mechanism. Finally, curcumin was able to effectively block histone hyperacetylation in both PC3-M prostate cancer cells and peripheral blood lymphocytes induced by the histone deacetylase inhibitor MS-275. These data thus identify the medicinal natural product curcumin as a novel lead compound for development of possibly therapeutic, p300/CBP-specific HAT inhibitors.
C1 [Marcu, Monica G.; Jung, Yun-Jin; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
   [Lee, Sunmin; Chung, Eun-Joo; Lee, Min-Jung; Trepel, Jane; Neckers, Len] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM neckers@nih.gov
NR 17
TC 153
Z9 163
U1 2
U2 10
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
   EMIRATES
SN 1573-4064
J9 MED CHEM
JI Med. Chem.
PD MAR
PY 2006
VL 2
IS 2
BP 169
EP 174
DI 10.2174/157340606776056133
PG 6
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA V22GM
UT WOS:000208263700006
PM 16787365
ER

PT J
AU Moro, S
   Gao, ZG
   Jacobson, KA
   Spalluto, G
AF Moro, S
   Gao, ZG
   Jacobson, KA
   Spalluto, G
TI Progress in the pursuit of therapeutic adenosine receptor antagonists
SO MEDICINAL RESEARCH REVIEWS
LA English
DT Review
DE G protein-coupled receptor; adenosine receptor; antagonists
ID PROTEIN-COUPLED RECEPTORS; SITE-DIRECTED MUTAGENESIS; STRUCTURE-AFFINITY
   PROFILE; A(3) RECEPTOR; HIGHLY POTENT; A(1) RECEPTOR; HUMAN A(2B);
   LIGAND RECOGNITION; BIOLOGICAL EVALUATION; MEDICINAL CHEMISTRY
AB Ever since the discovery of the hypotensive and bradycardiac effects of adenosine, adenosine receptors continue to represent promising drug targets. First, this is due to the fact that the receptors are expressed in a large variety of tissues. In particular, the actions of adenosine (or methylxanthine antagonists) in the central nervous system, in the circulation, on immune cells. and on other tissues can be beneficial in certain disorders. Second, there exists a large number of ligands, which have been generated by introducing several modifications in the structure of the lead compounds (adenosine and methylxanthine), some of them highly specific. Four adenosine receptor subtypes (A(1), A(2A), A(2B), and A(3)) have been cloned and pharmacologically characterized. all of which are G protein-coupled receptors. Adenosine receptors can be distinguished according to their preferred mechanism of signal transduction: A(1) and A(3) receptors interact with pertussis toxin-sensitive G proteins of the G(i) and G(o) family; the canonical signaling mechanism of the A(2A) and of the A(2B) receptors is stimulation of adenylyl cyclase via G, proteins. In addition to the coupling to adenylyl cyclase, all four subtypes may Positively Couple to phospholipase C via different G protein subunits. The development of new ligands, in particular, potent and selective antagonists, for all subtypes of adenosine receptors has so far been directed by traditional medicinal chemistry. The availability of genetic information promises to facilitate understanding of the drug-receptor interaction leading to the rational design of a potentially therapeutically important class of drugs. Moreover, molecular modeling may further rationalize observed interactions between the receptors and their ligands. In this review, we Will summarize the most relevant progress in developing new therapeutic adenosine receptor antagonists. (c) 2005 Wiley Periodicals, Inc.
C1 Univ Padua, Dipartimento Sci Farmaceut, Mol Modeling Sect, I-35131 Padua, Italy.
   NIDDKD, Mol Recognit Sect, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA.
   Univ Trieste, Dipartimento Sci Farmaceut, I-34127 Trieste, Italy.
RP Moro, S (reprint author), Univ Padua, Dipartimento Sci Farmaceut, Mol Modeling Sect, Via Marzolo 5, I-35131 Padua, Italy.
EM stefano.moro@unipd.it
RI Jacobson, Kenneth/A-1530-2009; Moro, Stefano/A-2979-2012
OI Jacobson, Kenneth/0000-0001-8104-1493; Moro, Stefano/0000-0002-7514-3802
FU Intramural NIH HHS [Z01 DK031117-20]
NR 150
TC 113
Z9 115
U1 0
U2 6
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0198-6325
J9 MED RES REV
JI Med. Res. Rev.
PD MAR
PY 2006
VL 26
IS 2
BP 131
EP 159
DI 10.1002/med.20048
PG 29
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 016SO
UT WOS:000235640700001
PM 16380972
ER

PT J
AU Bondy, CA
   Van, PL
   Bakalov, VK
   Sachdev, V
   Malone, CA
   Vincent, BH
   Rosing, DR
AF Bondy, CA
   Van, PL
   Bakalov, VK
   Sachdev, V
   Malone, CA
   Vincent, BH
   Rosing, DR
TI Prolongation of the cardiac QTc interval in Turner syndrome
SO MEDICINE
LA English
DT Article
ID LEFT-VENTRICULAR HYPERTROPHY; CONGENITAL HEART-DISEASE; BLOOD-PRESSURE;
   RISK-FACTORS; REPOLARIZATION; ASSOCIATION; WOMEN; MALFORMATIONS;
   PREVALENCE; COMPLEXITY
AB Anatomic anomalies of the cardiovascular system Occur in similar to 50% of individuals with Turner syndrome (TS), with the specific genetic cause(s) for the heart defects still unknown. Because congenital heart disease may be associated with conduction system abnormalities, We compared electrocardiograms (ECGs) in 100 women with TS and 100 age-matched female controls. Women with TS were significantly more likely to demonstrate left posterior fascicular block (p < 0.005), accelerated AV conduction (p < 0.006), and T wave abnormalities (p < 0.006). The PR interval was significantly shorter (137 +/- 17 vs. 158 18 ms, p < 0.0001) and the rate-corrected QT interval (QTc) significantly longer in women with TS than in controls (423 +/- 19 ms vs. 397 +/- 18 ms; p < 0.0001). Twenty-one women with TS but no controls had a QTc greater than 440 ms. We found no statistically significant relation between body habitus, cardiac dimensions, evidence of congenital heart disease, or metabolic parameters and the incidence of ECG abnormalities or QTc duration in TS. Cardiac conduction and repolarization abnormalities appear to be intrinsic features of TS, suggesting that deletion of the second sex chromosome has more profound effects oil the cardiovascular system than previously recognized, and that ECG analysis should be included in evaluating and monitoring patients with Turner syndrome.
C1 NICHD, NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA.
   NHLBI, NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA.
   NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
   Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA.
RP Bondy, CA (reprint author), NICHD, NIH, Dev Endocrinol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM bondyc@mail.nih.gov
NR 36
TC 22
Z9 23
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7974
J9 MEDICINE
JI Medicine (Baltimore)
PD MAR
PY 2006
VL 85
IS 2
BP 75
EP 81
DI 10.1097/01.md.0000205629.16302.bc
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 032XG
UT WOS:000236809100001
PM 16609345
ER

PT J
AU O'Hanlon, TP
   Carrick, DM
   Targoff, IN
   Arnett, FC
   Reveille, JD
   Carrington, M
   Gao, AJ
   Oddis, CV
   Morel, PA
   Malley, JD
   Malley, K
   Shamim, EA
   Rider, LG
   Chanock, SJ
   Foster, CB
   Bunch, T
   Blackshear, PJ
   Plotz, PH
   Love, LA
   Miller, FW
AF O'Hanlon, TP
   Carrick, DM
   Targoff, IN
   Arnett, FC
   Reveille, JD
   Carrington, M
   Gao, AJ
   Oddis, CV
   Morel, PA
   Malley, JD
   Malley, K
   Shamim, EA
   Rider, LG
   Chanock, SJ
   Foster, CB
   Bunch, T
   Blackshear, PJ
   Plotz, PH
   Love, LA
   Miller, FW
TI Immunogenetic risk and protective factors for the idiopathic
   inflammatory myopathies - Distinct HLA-A -B, -Cw,-DRB1, and-DQA1 allelic
   profiles distinguish European American patients with different myositis
   autoantibodies
SO MEDICINE
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRANSFER RNA-SYNTHETASES; INCLUSION-BODY
   MYOSITIS; GENE-EXPRESSION DATA; CLASS-II ALLELES; AUTOIMMUNE-DISEASES;
   RHEUMATOID-ARTHRITIS; ANTI-JO-1 ANTIBODIES; CLASSIFICATION; ASSOCIATION
AB The idiopathic inflammatory myopathies (IIM) are systemic connective tissue diseases defined by chronic muscle inflammation and weakness associated with autoimmunity. We have performed low to high resolution Molecular typing to assess the genetic variability of major histocompatibility complex loci (HLA-A. -B, -Cw, -DRB1, and -DQA1) in a large population of European American patients with IIM (n = 571) representing the major myositis autoantibody groups. We established that alleles of the 8.1 ancestral haplotype (8.1 AH) are important risk factors for the development of IIM in patients producing anti-synthetase/anti-Jo-1, -La, -PM/Scl, and -Ro autoantibodies. Moreover, a random forests classification analysis suggested that 8.1 AH-associated alleles B*0801 and DRB1*0301 are the principal HLA risk markers. In addition, we have identified several novel HLA susceptibility factors associated distinctively with particular myositis-specific (MSA) and myositis-associated autoantibody (MAA) groups of the IIM. IIM patients with anti-PL-7 (anti-threonyl-tRNA synthetase) autoantibodies have a unique HLA Class 1 risk allele, Cw*0304 (pcorr = 0.046), and lack the 8.1 AH markers associated with other anti-synthetase autoantibodies (for example, anti-Jo-1 and anti-PL-12). In addition, HLA-B*5001 and DQA1*0104 are novel potential risk factors among anti-signal recognition particle autoantibody-positive IIM patients (pcorr = 0.024 and p 0.010, respectively). Among those patients with MAA, HLA DRB1*11 and DQA1*06 alleles were identified as risk factors for myositis patients with anti-Ku (pcorr = 0.041) and anti-La (pcorr = 0.023) autoantibodies, respectively. Amino acid sequence analysis of the FILA DRB1 third hypervariable region identified a consensus motif, D-70 (hydrophilic)/R-71 (basic)/(14)A (hydrophobic), conferring protection among patients producing ailti-synthetase/anti-Jo-1 and -PM/Scl autoantibodies. Together, these data demonstrate that HLA signatures, comprising both risk and protective alleles or motifs, distinguish IIM patients with different myositis autoantibodies and may have diagnostic and pathogenic implications. Variations in associated polymorphisims for these immune response genes may reflect divergent pathogenic mechanisms and/or responses to unique environmental triggers in different groups of subjects resulting in the heterogeneous syndromes of the IIM.
C1 Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   NIH, Dept Hlth & Human Serv, Ctr Informat Technol, Bethesda, MD 20892 USA.
   NCI, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
   Natl Inst Arthritis & Musculoskeletal Dis, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
   Univ Oklahoma, Hlth Sci Ctr, Vet Affairs Med Ctr, Norman, OK 73019 USA.
   Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA.
   Univ Texas, Hlth Sci Ctr, Houston, TX USA.
   SAIC Frederick Natl Canc Inst, Basic Res Program, Frederick, MD USA.
   Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
   Malley Res Programming Inc, Rockville, MD USA.
   Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
   Mayo Clin, Rochester, MN USA.
   US FDA, Rockville, MD 20857 USA.
RP O'Hanlon, TP (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, 9 Mem Dr,Room 1W101,MSC 0958, Bethesda, MD 20892 USA.
EM ohanlont@niehs.nih.gov
OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593;
   Morel, Penelope/0000-0002-1743-3676
FU Intramural NIH HHS
NR 55
TC 73
Z9 73
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7974
J9 MEDICINE
JI Medicine (Baltimore)
PD MAR
PY 2006
VL 85
IS 2
BP 111
EP 127
DI 10.1097/01.md.0000217525.82287.eb
PG 17
WC Medicine, General & Internal
SC General & Internal Medicine
GA 032XG
UT WOS:000236809100006
PM 16609350
ER

PT J
AU Pettee, KK
   Brach, JS
   Kriska, AM
   Boudreau, R
   Richardson, CR
   Colbert, LH
   Satterfield, S
   Visser, M
   Harris, TB
   Ayonayon, HN
   Newman, AB
AF Pettee, KK
   Brach, JS
   Kriska, AM
   Boudreau, R
   Richardson, CR
   Colbert, LH
   Satterfield, S
   Visser, M
   Harris, TB
   Ayonayon, HN
   Newman, AB
TI Influence of marital status on physical activity levels among older
   adults
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE exercise; marriage; spousal pairs; aging
ID HEALTH; POPULATION; LIMITATION; EXERCISE; LIFE
AB Purpose: The purpose of these analyses was to describe the levels and types of activity in relationship to current marital status among older adults and determine if the physical activity level of the husband was related to the physical activity level of his wife. Methods: Participants included 3075 well-functioning white and black men and women aged 70-79 yr with further examination of 345 spousal pairs. Marital status was self-reported and participants were grouped as married versus not married. Based on responses to a leisure-time questionnaire, total physical activity was calculated and participants were classified as low or high active. Descriptive statistics were used to describe level and proportions of type of activity by marital status. Logistic regression was used to determine if marital status was an important determinant of physical activity participation. Regression models were adjusted for demographics, body mass index (BMI), and chronic disease conditions. Results: When compared with their single counterparts, married men reported higher median levels of exercise participation (P = 0.008) and married women reported higher levels of total (P < 0.0001) and nonexercise activity (P < 0.0001) with a trend toward higher exercise participation (P = 0.05). In spousal pairs, compared with men in the low active group, highly active men were almost three times as likely (OR = 2.97; 95% Cl = 1.73, 5.10) to have a similarly active spouse. The model only modestly attenuated when adjusted for age, BMI, and health status of the husband [OR = 2.49 (1.41, 4.42)]. Conclusions: Marital status and spousal physical activity (PA) levels are important determinants for PA participation among older adults.
C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA.
   Univ Michigan, Ann Arbor, MI 48109 USA.
   Univ Wisconsin, Madison, WI USA.
   Univ Tennessee, Memphis, TN USA.
   Vrije Univ Amsterdam, Amsterdam, Netherlands.
   Univ Calif San Francisco, San Francisco, CA 94143 USA.
   NIA, NIH, San Francisco, CA USA.
RP Pettee, KK (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St, Pittsburgh, PA 15261 USA.
EM kkp1@pitt.edu
RI Newman, Anne/C-6408-2013; 
OI Newman, Anne/0000-0002-0106-1150; Kriska, Andrea/0000-0002-3522-0869;
   Boudreau, Robert/0000-0003-0162-5187
FU NIA NIH HHS [N01-AG-20-2103, N01-AG-20-2101, N01-AG-20-2106]
NR 16
TC 53
Z9 53
U1 3
U2 17
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 MAR
PY 2006
VL 38
IS 3
BP 541
EP 546
DI 10.1249/01.mss.0000191346.95244.f7
PG 6
WC Sport Sciences
SC Sport Sciences
GA 023OJ
UT WOS:000236135800020
PM 16540843
ER

PT J
AU Henrich, JB
   Hughes, JP
   Kaufman, SC
   Brody, DJ
   Curtin, LR
AF Henrich, JB
   Hughes, JP
   Kaufman, SC
   Brody, DJ
   Curtin, LR
TI Limitations of follicle-stimulating hormone in assessing menopause
   status: findings from the National Health and Nutrition Examination
   Survey (NHANES 1999-2000)
SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
LA English
DT Article; Proceedings Paper
CT 27th Annual Meeting of the Society-of-General-Internal-Medicine
CY MAY 12-15, 2004
CL Chicago, IL
SP Soc Gen Internal Med
DE gonadotropins; follicle-stimulating hormone; menopause; reproductive
   stage
ID TRANSITION; WOMEN; PERIMENOPAUSAL; POPULATION; ESTRADIOL; GONADOTROPINS;
   DETERMINANTS; PREVALENCE; ETHNICITY; SMOKING
AB Objective: We used data from the National Health and Nutrition Examination Survey (NHANES 1999-2000) to: establish new population-based estimates for follicle-stimulating hormone (FSH) and luteinizing hormone (LH); identify factors associated with FSH; and assess its efficacy in distinguishing among women in the reproductive, menopause transition, and postmenopausal stages.
   Design: Nationally representative sample of 576 women aged 35 to 60 years examined during NHANES 1999-2000.
   Results: Levels of FSH and LH increased significantly with reproductive stage. (Geometric mean FSH levels for successive stages: reproductive, 7.0 mIU/mL, SE 0.4; menopause transition, 21.9 mIU/mL, SE 3.7; and postmenopause, 45.7 mIU/mL, SE 4.3.) There was considerable overlap, however, among distributions of FSH by stage. Only age and reproductive stage were significantly associated with FSH in multivariable analysis. FSH cutoff points between the reproductive and menopause transition stages [FSH = 13 mIU/mL, sensitivity 67.4% (95% Cl 50.0-81.1), specificity 88.1% (95% Cl 81.1-92.8)] and between the menopause transition and postmenopause stages [FSH = 45 mIU/mL, sensitivity 73.6% (95% Cl 60.1-83.7), specificity 70.6% (95% Cl 52.4-84.0)] were neither sensitive nor very specific.
   Conclusions: Age and reproductive stage are the most important determinants of FSH levels in US women; however, FSH by itself has limited utility in distinguishing among women in different reproductive stages.
C1 Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA.
   Orkand Corp, Falls Church, VA USA.
   NICHHD, Contracept & Reprod Hlth Branch, Populat Res Ctr, NIH, Bethesda, MD 20892 USA.
   Ctr Dis Control & Prevent, Div Hlth & Nutr Examinat Stat, Natl Ctr Hlth Stat, Atlanta, GA USA.
RP Henrich, JB (reprint author), Yale Univ, Sch Med, Dept Internal Med, POB 208025, New Haven, CT 06520 USA.
EM janet.henrich@yale.edu
NR 27
TC 23
Z9 24
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-3714
J9 MENOPAUSE
JI Menopause-J. N. Am. Menopause Soc.
PD MAR-APR
PY 2006
VL 13
IS 2
BP 171
EP 177
DI 10.1097/01.gme.0000198489.49618.96
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 031NQ
UT WOS:000236711700006
PM 16645530
ER

PT J
AU Huang, JB
   Espinoza, J
   Romero, R
   Petty, HR
AF Huang, JB
   Espinoza, J
   Romero, R
   Petty, HR
TI Apparent role of dynein in glucose-6-phosphate dehydrogenase trafficking
   in neutrophils from pregnant women
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Article
ID UNDERGOES RETROGRADE TRAFFICKING; SUPRAMOLECULAR COMPLEX; MICROTUBULES
   INVITRO; INHIBITORS; TRANSPORT; PROTEIN; ATPASE
AB To better understand the mechanisms of metabolic microcompartmentalization associated with neutrophil hexose monophosphate shunt activity dining pregnancy, we have studied the intracellular trafficking of glucose-6-phosphate dehydrogenase (G6PDase). Microtubule motor proteins colocalize with G6PDase. Dynein inhibitors block G6PDase accumulation at the microtubule-organizing center in pregnancy cells. On this basis, we conclude that microtubule motor proteins participate in hexose monophosphate shunt enzyme transport within leukocytes. (c) 2006 Elsevier Inc. All rights reserved.
C1 Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
   Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48105 USA.
   NICHHD, Perinatol Res Branch, Bethesda, MD USA.
   Hutzel Hosp, Detroit, MI 48201 USA.
RP Petty, HR (reprint author), Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA.
EM hpetty@umich.edu
FU Intramural NIH HHS
NR 11
TC 3
Z9 3
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399 USA
SN 0026-0495
J9 METABOLISM
JI Metab.-Clin. Exp.
PD MAR
PY 2006
VL 55
IS 3
BP 279
EP 281
DI 10.1016/j.metabol.2005.09.002
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 018UQ
UT WOS:000235790700001
PM 16483869
ER

PT J
AU Flory, GS
   Chen, SA
   Woltz, LA
   Magleby, S
   Higley, JD
AF Flory, GS
   Chen, SA
   Woltz, LA
   Magleby, S
   Higley, JD
TI A computerized apparatus designed to automatically dispense, measure,
   and record alcohol consumption by individual members of a rhesus macaque
   social group: Trait-like drinking across social- and single-cage
   conditions
SO METHODS
LA English
DT Article
DE alcohol; self-administration; rhesus monkey; social; individual
   differences
ID NONHUMAN PRIMATE MODEL; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS;
   COMPETENCE; MONKEYS
AB Background: The present study tested the validity of an automated ethanol dispensing apparatus that is capable of identifying individual monkeys and precisely measuring their levels of ethanol consumption while living in a social group, and assessed individual subjects' level of consumption when alone and in social groups.
   Methods: In Experiment 1, 21 rhesus macaques (Macaca mulatta) were given access for 1-h each day to the dispensing apparatus, which contained an aspartame-sweetened 8.4% (v/v) ethanol solution. Measurements of blood ethanol concentrations were taken for each subject and compared with the level of consumption recorded by the apparatus for those subjects. To examine the possibility that competition among the animals limited their access to the dispensing unit, in Experiment 2, 10 of the subjects used in Experiment 1 were singly housed to allow them to drink without interference from other monkeys. A correlation was then performed to assess the interindividual relationship between the amount of ethanol consumed in these two housing conditions.
   Results: In Experiment 1, the volume of solution measured and recorded by the apparatus correlated positively with the true volume dispensed. Furthermore, the volume of solution reported by the computer to have been consumed by an individual subject correlated positively with blood ethanol concentrations. In Experiment 2, the volume of ethanol consumed by individual subjects in single cages correlated positively with their consumption in the social group.
   Conclusions: The apparatus accurately identified and measured individual patterns of ethanol consumption among socially housed animals. Additionally, individual differences in ethanol consumption remained stable across settings, as shown by the strong positive correlation between drinking in a social setting versus drinking alone. This finding may thus reflect an individual's constitutional proclivity to consume alcohol. (c) 2005 Elsevier Inc. All rights reserved.
C1 NIAAA, DICBR, LCTS, Anim Ctr,Sect Study Primate Models Psychopathol,N, Poolesville, MD 20837 USA.
   Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
   Synergy Res Inc, Monrovia, MD 21770 USA.
   Brigham Young Univ, Dept Engn Mech, Provo, UT 84602 USA.
RP Chen, SA (reprint author), NIAAA, DICBR, LCTS, Anim Ctr,Sect Study Primate Models Psychopathol,N, POB 529,Bldg 112, Poolesville, MD 20837 USA.
EM scott.chen@mail.nih.gov
NR 7
TC 2
Z9 2
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 1046-2023
J9 METHODS
JI Methods
PD MAR
PY 2006
VL 38
IS 3
BP 178
EP 184
DI 10.1016/j.ymeth.2005.12.002
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 027XX
UT WOS:000236450700003
PM 16458017
ER

PT J
AU Gil-da-Costa, R
   Braun, A
   Martin, A
AF Gil-da-Costa, R
   Braun, A
   Martin, A
TI Using PET H2O15 brain imaging to study the functional-anatomical
   correlates of non-human primate communication
SO METHODS
LA English
DT Article
DE PET; functional brain imaging; rhesus macaque; species-specific calls;
   communication; auditory processing; neurophysiology
ID MACACA-MULATTA VOCALIZATIONS; AUDITORY-CORTEX; RHESUS-MONKEYS; MACAQUE;
   RESPONSES; HUMANS
AB In this article, we describe methods for using oxygen-15 water (H2O15) positron emission tomography (PET) to explore the functional neuroanatomy of cognition in awake, non-human primates. The discussion is based on a recent study designed to identify regions in the monkey brain associated with perceiving auditory stimuli, and species-specific calls, in particular [Gil-da-Costa et al., Proc. Natl. Acad. Sci. USA 101 (2004) 17516-17521]. Details are provided concerning critical aspects of the experimental paradigm, including pre-scanning habituation sessions to acclimate the animals to the PET scanner environment, and details of a pilot study to determine the auditory stimulus parameters necessary to produce robust activity in brain regions known to process auditory information (belt and parabelt regions of monkey auditory cortex). Methods for acquiring and analyzing PET data to identify significant regions of brain activity in single animals are also presented. Published by Elsevier Inc.
C1 NIMH, NIH, Bethesda, MD 20892 USA.
   Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA.
   Harvard Univ, Cambridge, MA USA.
   Gulbenkian Inst Sci, Program Biol & Med, Lisbon, Portugal.
RP Martin, A (reprint author), NIMH, NIH, Bethesda, MD 20892 USA.
EM alexmartin@mail.nih.gov
RI martin, alex/B-6176-2009
FU Intramural NIH HHS; NIMH NIH HHS [Z01 MH002588-15]
NR 24
TC 1
Z9 1
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
J9 METHODS
JI Methods
PD MAR
PY 2006
VL 38
IS 3
BP 221
EP 226
DI 10.1016/j.ymeth.2005.08.003
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 027XX
UT WOS:000236450700008
PM 16466931
ER

PT J
AU Collazo, CM
   Sher, A
   Meierovics, AI
   Elkins, KL
AF Collazo, CM
   Sher, A
   Meierovics, AI
   Elkins, KL
TI Myeloid differentiation factor-88 (MyD88) is essential for control of
   primary in vivo Francisella tularensis LVS infection, but not for
   control of intramacrophage bacterial replication
SO MICROBES AND INFECTION
LA English
DT Article
DE Francisella tularensis; immunology; bacterial infections; toll-like
   receptors
ID TOLL-LIKE RECEPTORS; CELL-MEDIATED-IMMUNITY; LIVE VACCINE STRAIN;
   INTERFERON-GAMMA; LISTERIA-MONOCYTOGENES; CUTTING EDGE; PROTECTIVE
   IMMUNITY; INTRACELLULAR BACTERIA; STAPHYLOCOCCUS-AUREUS; MYD88-DEFICIENT
   MICE
AB The means by which Francisella turlarensis, the causative agent of tularemia, are recognized by mammalian immune systems are poorly understood. Here we wished to explore the contribution of the MyD88/Toll-like receptor signaling pathway in initiating murine responses to F. tularensis Live Vaccine Strain (LVS). MyD88 knockout (KO) mice, but not TLR2-, TLR4- or TLR9-deficient mice, rapidly succumbed following in vivo bacterial infection via the intradermal route even with a very low dose of LVS (5 x 10) that was 100,000-fold less than the LD50 of normal wild-type (WT) mice. By day 5 after LVS infection, bacterial organ burdens were 5-6 logs higher in MyD88 knockout mice; further, unlike infected WT mice, levels of interferon-y in the sera of LVS-infected MyD88 KO were undetectable. An in vitro culture system was used to assess the ability of bone marrow macrophages derived from either KO or WT mice to support bacterial growth, or to control intracellular bacterial replication when co-cultured with immune lymphocytes. In this assay, bacterial replication was similar in macrophages derived from either WT or any of the TLR KO mice. Bacterial growth was controlled in co-cultures containing macrophages from MyD88 KO mice or TLR KO mice as well as in co-cultures containing immune WT splenic lymphocytes and WT macrophages. Further, MyD88-deficient LVS-immune splenocytes controlled intracellular growth comparably to those from normal mice. Thus MyD88 is essential for innate host resistance to LVS infection, but is not required for macrophage control of intracellular bacterial growth. Published by Elsevier SAS.
C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Lab Mycobacterial Dis & Cellular Immunol, Rockville, MD 20852 USA.
   NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Elkins, KL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Lab Mycobacterial Dis & Cellular Immunol, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA.
EM karen.elkins@fda.hhs.gov
NR 55
TC 50
Z9 51
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
J9 MICROBES INFECT
JI Microbes Infect.
PD MAR
PY 2006
VL 8
IS 3
BP 779
EP 790
DI 10.1016/j.micinf.2005.09.014
PG 12
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 045PL
UT WOS:000237754000023
PM 16513388
ER

PT J
AU Hu, L
   McDaniel, JP
   Kopecko, DJ
AF Hu, L
   McDaniel, JP
   Kopecko, DJ
TI Signal transduction events involved in human epithelial cell invasion by
   Campylobacter jejuni 81-176
SO MICROBIAL PATHOGENESIS
LA English
DT Article
DE signal transduction; invasion; Campylobacter jejuni; epithelial cells;
   phosphorylation; G protein
ID HUMAN INTESTINAL-CELLS; CAMPYLOBACTER-JEJUNI; CYTOKINE PRODUCTION;
   INT-407 CELLS; SALMONELLA-TYPHIMURIUM; LISTERIA-MONOCYTOGENES;
   ADENYLATE-CYCLASE; PERTUSSIS TOXIN; PROTEIN; KINASE
AB Analyses of invasive enteric bacteria (e.g. Shigella, Salmonella, Listeria, and Campylobacter) have shown that these pathogens initiate orchestrated signal transduction cascades in host cells leading to host cytoskeletal rearrangements that result in bacterial uptake. This current study was specifically aimed at examining the involvement of host membrane caveolae and certain protein kinases in epithelial cell invasion by C jejuni strain 81-176, for which we have previously characterized the kinetics of entry and a unique microtubule-dependent mechanism of internalization. Utilizing in vitro cultured cell invasion assays with a gentamicin-kill step, disruption of membrane caveolae, by pretreatment of INT407 cell monolayers with filipin III reduced C jejuni 81-176 entry by >95%. Strain 81-176 uptake into INT407 cells was markedly inhibited by monolayer pretreatment with the protein kinase inhibitors genistein and staurosporine, or specific inhibitors of PI 3-kinase, wortmannin and LY294002. Western blot analysis using monoclonal anti-protein tyrosine phosphorylation antibody revealed distinctive changes during invasion in phosphorylation of at least nine proteins. Further inhibitor studies indicated that heterotrimeric G proteins, plus ERK and p38 MAP kinase activation are also involved in C jejuni 81-176 invasion. These results suggest that C. jejuni 81-176 interact at host cell surface membrane caveolae with G protein-coupled receptors, which presumably trigger G-proteins and kinases to activate host proteins including PI 3-kinase and MAP kinases, that appear to be intimately involved in the events controlling 81-176 internalization.
C1 US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20892 USA.
RP Kopecko, DJ (reprint author), US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, NIH, Campus Bldg 29-420,29 Lincoln Dr, Bethesda, MD 20892 USA.
EM kopecko@cber.fda.gov
NR 37
TC 44
Z9 46
U1 2
U2 5
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0882-4010
J9 MICROB PATHOGENESIS
JI Microb. Pathog.
PD MAR
PY 2006
VL 40
IS 3
BP 91
EP 100
DI 10.1016/j.micpath.2005.11.004
PG 10
WC Immunology; Microbiology
SC Immunology; Microbiology
GA 019FL
UT WOS:000235820900001
PM 16426812
ER

PT J
AU Chen, Y
   MacDonald, PJ
   Skinner, JP
   Patterson, GH
   Muller, JD
AF Chen, Y
   MacDonald, PJ
   Skinner, JP
   Patterson, GH
   Muller, JD
TI Probing nucleocytoplasmic transport by two-photon activation of PA-GFP
SO MICROSCOPY RESEARCH AND TECHNIQUE
LA English
DT Article
DE nuclear pore complex; green fluorescent protein; two-photon microscopy;
   restricted diffusion; photoactivation
ID GREEN FLUORESCENT PROTEIN; NUCLEAR-PORE COMPLEX; IN-VIVO; MICROSCOPY;
   TRANSLOCATION; PERMEABILITY; EXCITATION; CELLS; EGFP
AB Two-photon activation of photoactivatable green fluorescent protein (PA-GFP) provides a unique tool for probing cellular transport processes, because activation is strictly limited to the subfemtoliter optical volume of the two-photon spot. We demonstrate two-photon activation of PA-GFP immobilized in a gel and freely diffusing within cells and recover a quadratic power dependence. Illumination at 820 nm allows simultaneous activation and fluorescence monitoring by two-photon excitation. Alternatively, we activate PA-GFP using two-photon excitation and monitor the fluorescence of the photoconverted product with one-photon excitation. We probe nucleocytoplasmic transport through the nuclear pore complex of COS-1 cells, by observing the timedependent fluorescence at various locations within the cell after two-photon activation of PA-GFP in the nucleus and in the cytoplasm. Two-photon activation of a tandem construct of two PA-GFPs showed a markedly slower rate of crossing through the nuclear pore. Analysis based on a restricted diffusion model yields a nuclear pore radius of 4.5 nm, which is in good agreement with previously reported values. This application demonstrates the attractive features of two-photon photoactivation over traditional techniques, such as photobleaching, for studying transport processes in cells.
C1 Univ Minnesota, Sch Phys & Astron, Minneapolis, MN 55455 USA.
   NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA.
RP Chen, Y (reprint author), Univ Minnesota, Sch Phys & Astron, Minneapolis, MN 55455 USA.
EM Chen@physics.umn.edu
FU NIGMS NIH HHS [GM64589]
NR 21
TC 18
Z9 18
U1 0
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1059-910X
J9 MICROSC RES TECHNIQ
JI Microsc. Res. Tech.
PD MAR
PY 2006
VL 69
IS 3
BP 220
EP 226
DI 10.1002/jemt.20252
PG 7
WC Anatomy & Morphology; Biology; Microscopy
SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics;
   Microscopy
GA 028RT
UT WOS:000236506900010
PM 16538629
ER

PT J
AU Patterson, AD
   Hollander, MC
   Miller, GF
   Fornace, AJ
AF Patterson, AD
   Hollander, MC
   Miller, GF
   Fornace, AJ
TI Gadd34 requirement for normal hemoglobin synthesis
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID EUKARYOTIC TRANSLATION INITIATION-FACTOR-2; EIF2-ALPHA KINASE;
   ALPHA-SUBUNIT; ENDOPLASMIC-RETICULUM; PROTEIN-KINASE; MICE; SURVIVAL;
   MOUSE; GENE; AUTOPHOSPHORYLATION
AB The protein encoded by growth arrest and DNA damage-inducible transcript 34 (Gadd34) is associated with translation initiation regulation following certain stress responses. Through interaction with the protein phosphatase 1 catalytic subunit (PP1c), Gadd34 recruits PP1c for the removal of an inhibitory phosphate group on the alpha subunit of elongation initiation factor 2, thereby reversing the shutoff of protein synthesis initiated by stress-inducible kinases. In the absence of stress, the physiologic consequences of Gadd34 function are not known. Initial analysis of Gadd-34-null mice revealed several significant findings, including hypersplenism, decreased erythrocyte volume, increased numbers of circulating erythrocytes, and decreased hemoglobin content, resembling some thalassemia syndromes. Biochemical analysis of the hemoglobin-producing reticulocyte (an erythrocyte precursor) revealed that the decreased hemoglobin content in the Gadd34-nuil erythrocyte is due to the reduced initiation of the globin translation machinery. We propose that an equilibrium state exists between Gadd34/PP1c and the opposing heme-regulated inhibitor kinase during hemoglobin synthesis in the reticulocyte.
C1 NIH, GWU, Grad Partnerships Program Genet, Bethesda, MD 20892 USA.
   NCI, Gene Response Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
   NIH, Div Vet Resources, Bethesda, MD 20892 USA.
RP Fornace, AJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA.
EM afornace@hsph.harvard.edu
RI Fornace, Albert/A-7407-2008; Patterson, Andrew/G-3852-2012
OI Fornace, Albert/0000-0001-9695-085X; Patterson,
   Andrew/0000-0003-2073-0070
NR 33
TC 20
Z9 21
U1 0
U2 0
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 MAR
PY 2006
VL 26
IS 5
BP 1644
EP 1653
DI 10.1128/MCB.26.5.1644-1653.2006
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 016EE
UT WOS:000235602700007
PM 16478986
ER

PT J
AU Chiang, YJ
   Nguyen, ML
   Gurunathan, S
   Kaminker, P
   Tessarollo, L
   Campisi, J
   Hodes, RJ
AF Chiang, YJ
   Nguyen, ML
   Gurunathan, S
   Kaminker, P
   Tessarollo, L
   Campisi, J
   Hodes, RJ
TI Generation and characterization of telomere length maintenance in
   tankyrase 2-deficient mice
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID IN-VIVO; BINDING PROTEIN; REGULATOR TRF1; HUMAN-CELLS; IDENTIFICATION;
   IRAP; TIN2; DNA; CHROMOSOMES; EXPRESSION
AB Telomere length and function are crucial factors that determine the capacity for cell proliferation and survival, mediate cellular senescence, and play a role in malignant transformation in eukaryotic systems. The telomere length of a specific mammalian species is maintained within a given range by the action of telomerase and telomerea-associated proteins. TRF1 is a telomere-associated protein that inhibits telomere elongation by its binding to telomere repeats, preventing access to telomerase. Human TRF1 interacts with tankyrase 1 and tankyrase 2 proteins, two related members of the tankyrase family shown to have poly(ADP-ribose) polymerase activity. Human tankyrase 1 is reported to ADP-ribosylate TRF1 and to down-regulate the telomeric repeat binding activity of TRF1, resulting in telomerase-dependent telomere elongation. Human tankyrase 2 is proposed to have activity similar to that of tankyrase 1, although tankyrase 2 function has been less extensively characterized. In the present study, we have assessed the in vivo function of mouse tankyrase 2 by germ line gene inactivation and show that inactivation of tankyrase 2 does not result in detectable alteration in telomere length when monitored through multiple generations of breeding. This finding suggests that either mouse tankyrases 1 and 2 have redundant functions in telomere length maintenance or that mouse tankyrase 2 differs from human tankyrase 2 in its role in telomere length maintenance. Tankyrase 2 deficiency did result in a significant decrease in body weight sustained through at least the first year of life, most marked in male mice, suggesting that tankyrase 2 functions in potentially telomerase-independent pathways to affect overall development and/or metabolism.
C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
   Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA.
   NCI, Canc Res Ctr, Mouse Canc Genet Program, Frederick, MD 21702 USA.
   NIA, NIH, Bethesda, MD 20892 USA.
RP Chiang, YJ (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,4B36,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM chiangj@mail.nih.gov
FU Intramural NIH HHS
NR 36
TC 35
Z9 35
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 MAR
PY 2006
VL 26
IS 6
BP 2037
EP 2043
DI 10.1128/MCB.26.6.2037-2043.2006
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 020NE
UT WOS:000235915400003
PM 16507984
ER

PT J
AU Ueyama, T
   Geiszt, M
   Leto, TL
AF Ueyama, T
   Geiszt, M
   Leto, TL
TI Involvement of Rac1 in activation of multicomponent Nox1- and Nox3-based
   NADPH oxidases
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID COLON EPITHELIAL-CELLS; CHRONIC GRANULOMATOUS-DISEASE; SRC HOMOLOGY-3
   DOMAINS; SMOOTH-MUSCLE-CELLS; SUPEROXIDE-PRODUCTION; NAD(P)H OXIDASE-1;
   REACTIVE OXYGEN; FLAVOCYTOCHROME B(558); HUMAN-NEUTROPHILS; HOST-DEFENSE
AB Several Nox family NADPH oxidases function as multicomponent enzyme systems. We explored determinants of assembly of the multicomponent oxidases Nox1 and Nox3 and examined the involvement of Rac1 in their regulation. Both enzymes are supported by p47(phox) and p67(phox) or homologous regulators called Noxo1 and Noxal, although Nox3 is less dependent on these cofactors for activity. Plasma membrane targeting of Noxal depends on Noxo1, through tail-to-tail interactions between these proteins. Noxal can support Nox1 without Noxo1, when targeted to the plasma membrane by fusing membrane-binding sequences from Rac1 (amino acids 183 to 192) to the C terminus of Noxal. However, membrane targeting of Noxal is not sufficient for activation of Nox1. Both the Noxo1-independent and -dependent Nox1 systems involve Rac1, since they are affected by Rac1 mutants or Noxal mutants defective in Rac binding or short interfering RNA-mediated Rac1 silencing. Nox1 or Nox3 expression promotes p22(phox) transport to the plasma membrane, and both oxidases are inhibited by mutations in the p22(phox) binding sites (SH3 domains) of the Nox organizers (p47(phox) or Noxo1). Regulation of Nox3 by Rac1 was also evident from the effects of mutant Rac1 or mutant Nox3 activators (p67(phox) or Noxa1) or Rac1 silencing. In the absence of Nox organizers, the Nox activators (p67(phox) or Noxa1) colocalize with Rac1 within ruffling membranes, independently of their ability to bind Rac1. Thus, Rac1 regulates both oxidases through the Nox activators, although it does not appear to direct the subcellular localization of these activators.
C1 NIAID, Mol Def Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
   Semmelweis Univ, Dept Physiol, Fac Med, H-1444 Budapest, Hungary.
RP Ueyama, T (reprint author), NIAID, Mol Def Sect, Host Def Lab, NIH, Twinbrook 2,Room 203,12441 Parklawn Dr, Bethesda, MD 20892 USA.
EM tueyama@kobe-u.ac.jp
FU Wellcome Trust
NR 60
TC 132
Z9 133
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAR
PY 2006
VL 26
IS 6
BP 2160
EP 2174
DI 10.1128/MCB.26.6.2160-2174.2006
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 020NE
UT WOS:000235915400013
PM 16507994
ER

PT J
AU Menendez, D
   Inga, A
   Resnick, MA
AF Menendez, D
   Inga, A
   Resnick, MA
TI The biological impact of the human master regulator p53 can be altered
   by mutations that change the spectrum and expression of its target genes
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; BASE EXCISION-REPAIR; LI-FRAUMENI-SYNDROME;
   CELL-CYCLE ARREST; DNA-DAMAGE; APOPTOTIC RESPONSE; MISMATCH REPAIR;
   P53-DEPENDENT APOPTOSIS; MUTANT P53; IN-VIVO
AB Human tumor suppressor p53 is a sequence-specific master regulatory transcription factor that targets response elements (REs) in many genes. p53 missense mutations in the DNA-binding domain are often cancer associated. As shown with systems based on the yeast Saccharomyces cerevisiae, p53 mutants can alter the spectra and intensities of transactivation from individual RE's. We address directly in human cells the relationship between changes in the p53 master regulatory network and biological outcomes. Expression of integrated, tightly regulated DNA-binding domain p53 mutants resulted in many patterns of apoptosis and survival following UV or ionizing radiation, or spontaneously. These patterns reflected changes in the spectra and activities of target genes, as demonstrated for P21, MDM2, BAX, and MSH2. Thus,as originally proposed for "master genes of diversity," p53 mutations in human cells can differentially influence target gene transactivation, resulting in a variety of biological consequences which, in turn, might be expected to influence tumor development and therapeutic efficacy.
C1 NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Resnick, MA (reprint author), NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, POB 12233,111 Alexander Dr,Room D342,Maildrop D3-, Res Triangle Pk, NC 27709 USA.
EM resnick@niehs.nih.gov
NR 65
TC 54
Z9 56
U1 0
U2 0
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 MAR
PY 2006
VL 26
IS 6
BP 2297
EP 2308
DI 10.1128/MCB.26.6..2297-2308.2006
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 020NE
UT WOS:000235915400024
PM 16508005
ER

PT J
AU Barrantes, ID
   Montero-Pedrazuela, A
   Guadano-Ferraz, A
   Obregon, MJ
   de Mena, RM
   Gailus-Durner, V
   Fuchs, H
   Franz, TJ
   Kalaydjiev, S
   Klempt, M
   Holter, S
   Rathkolb, B
   Reinhard, C
   de Escobar, GM
   Bernal, J
   Busch, DH
   Wurst, W
   Wolf, E
   Schulz, H
   Shtrom, S
   Greiner, E
   de Angelis, MH
   Westphal, H
   Niehrs, C
AF Barrantes, ID
   Montero-Pedrazuela, A
   Guadano-Ferraz, A
   Obregon, MJ
   de Mena, RM
   Gailus-Durner, V
   Fuchs, H
   Franz, TJ
   Kalaydjiev, S
   Klempt, M
   Holter, S
   Rathkolb, B
   Reinhard, C
   de Escobar, GM
   Bernal, J
   Busch, DH
   Wurst, W
   Wolf, E
   Schulz, H
   Shtrom, S
   Greiner, E
   de Angelis, MH
   Westphal, H
   Niehrs, C
TI Generation and characterization of dickkopf3 mutant mice
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID TYPE-2 IODOTHYRONINE DEIODINASE; BROWN ADIPOSE-TISSUE; MODIFIED HOLE
   BOARD; THYROID-HORMONE; RAT-BRAIN; REDUCED EXPRESSION; PRECHORDAL PLATE;
   CEREBRAL-CORTEX; DOWN-REGULATION; ZEBRAFISH DKK1
AB dickkopf (dkk) genes encode a small family of secreted Wnt antagonists, except for dkk3, which is divergent and whose function is poorly understood. Here, we describe the generation and characterization of dkk3 mutant mice. dkk3-deficient mice are viable and fertile. Phenotypic analysis shows no major alterations in organ morphology, physiology, and most clinical chemistry parameters. Since Dkk3 was proposed to function as thyroid hormone binding protein, we have analyzed deiodinase activities, as well as thyroid hormone levels. Mutant mice are euthyroid, and the data do not support a relationship of dkk3 with thyroid hormone metabolism. Altered phenotypes in dkk3 mutant mice were observed in the frequency of NK cells, immunoglobulin M, hemoglobin, and hematocrit levels, as well as lung ventilation. Furthermore, dkk3-deficient mice display hyperactivity.
C1 Deutsch Krebsforschungszentrum, Div Mol Embryol, D-69120 Heidelberg, Germany.
   Univ Autonoma Madrid, CSIC, Inst Invest Biomed Alberto Sols, Dept Mol Endocrinol, E-28049 Madrid, Spain.
   GSF, Natl Res Ctr Environm & Hlth, Inst Expt Genet, D-85758 Neuherberg, Germany.
   GSF, Natl Res Ctr Environm & Hlth, Inst Dev Genet, D-85758 Neuherberg, Germany.
   GSF, Natl Res Ctr Environm & Hlth, Inst Inhalat Biol, D-85758 Neuherberg, Germany.
   Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-81675 Munich, Germany.
   Univ Munich, Inst Mol Anim Breeding & Biotechnol, Gene Ctr, D-81377 Munich, Germany.
   NIH, Bethesda, MD 20892 USA.
RP Niehrs, C (reprint author), Deutsch Krebsforschungszentrum, Div Mol Embryol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
EM niehrs@dkfz-Heidelberg.de
RI OBREGON, Maria Jesus/E-2946-2010; Hrabe de Angelis, Martin/F-5531-2012;
   Holter, Sabine/N-5868-2014; Rathkolb, Birgit/F-7041-2013; Montero
   Pedrazuela, Ana/J-7723-2013; Guadano-Ferraz, Ana/J-7870-2013; Bernal,
   Juan/J-6086-2014; Gailus-Durner, Valerie/M-7337-2014; Fuchs,
   Helmut/M-7347-2014; Schulz, Holger/J-5643-2015
OI Wolf, Eckhard/0000-0002-0430-9510; Hrabe de Angelis,
   Martin/0000-0002-7898-2353; Holter, Sabine/0000-0003-4878-5241; Montero
   Pedrazuela, Ana/0000-0003-2308-0894; Guadano-Ferraz,
   Ana/0000-0002-0666-935X; Bernal, Juan/0000-0002-5867-4951; Fuchs,
   Helmut/0000-0002-5143-2677; Schulz, Holger/0000-0002-1157-200X
NR 56
TC 46
Z9 46
U1 0
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAR
PY 2006
VL 26
IS 6
BP 2317
EP 2326
DI 10.1128/MCB.26.6.2317-2326.2006
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 020NE
UT WOS:000235915400026
ER

PT J
AU Small-Howard, A
   Morozova, N
   Stoytcheva, Z
   Forry, EP
   Mansell, JB
   Harney, JW
   Carlson, BA
   Xu, XM
   Hatfield, DL
   Berry, MJ
AF Small-Howard, A
   Morozova, N
   Stoytcheva, Z
   Forry, EP
   Mansell, JB
   Harney, JW
   Carlson, BA
   Xu, XM
   Hatfield, DL
   Berry, MJ
TI Supramolecular complexes mediate selenocysteine incorporation in vivo
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID SELENOPROTEIN MESSENGER-RNAS; MAMMALIAN-CELLS; TRANSFER RNA<SER>SEC;
   DECODING APPARATUS; ELONGATION-FACTOR; NONSENSE CODON; UGA; SELENIUM;
   PROTEIN; TRANSLATION
AB Selenocysteine incorporation in eukaryotes occurs cotranslationally at UGA codons via the interactions of RNA-protein complexes, one comprised of selenocysteyl (Sec)-tRNA([Ser]Sec) and its specific elongation factor, EFsec, and another consisting of the SECIS element and SECIS binding protein, SBP2. Other factors implicated in this pathway include two selenophosphate synthetases, SPS1 and SPS2, ribosomal protein L30, Sec and two factors identified as binding IRNA([Ser]Sec), termed soluble liver antigen/liver protein (SLA/LP) and SECp43. We report that SLA/LP :and SPS1 interact in vitro and in vivo and that SECp43 cotransfection increases this interaction and redistributes all three proteins to a predominantly nuclear localization. We further show that SECp43 interacts with the selenocysteyl-tRNA([Ser]Sec)-EFsec complex in vitro, and SECp43 coexpression promotes interaction between EFsec and SBP2 in vivo. Additionally, SECp43 increases selenocysteine incorporation and selenoprotein mRNA levels, the latter presumably due to circumvention of nonsense-mediated decay. Thus, SECp43 emerges as a key player in orchestrating the interactions and localization of the other factors involved in selenoprotein biosynthesis. Finally, our studies delineating the multiple, coordinated protein-nucleic acid interactions between SECp43 and the previously described selenoprotein cotranslational factors resulted in a model of selenocysteine biosynthesis and incorporation dependent upon both cytoplasmic and nuclear supramolecular complexes.
C1 Univ Hawaii Manoa, Dept Cell & Mol Biol, John A Burns Sch Med, Honolulu, HI 96822 USA.
   Brigham & Womens Hosp, Div Thyroid, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   NCI, Lab Canc Prevent, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Berry, MJ (reprint author), Univ Hawaii Manoa, Dept Cell & Mol Biol, John A Burns Sch Med, Honolulu, HI 96822 USA.
EM mberry@hawaii.edu
FU NIDDK NIH HHS [DK47320, DK52963, R01 DK047320, R01 DK052963, R56
   DK047320]
NR 29
TC 94
Z9 101
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAR
PY 2006
VL 26
IS 6
BP 2337
EP 2346
DI 10.1128/MCB.26.6.2337-2346.2006
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 020NE
UT WOS:000235915400028
PM 16508009
ER

PT J
AU Hitti, E
   Iakovleva, T
   Brook, M
   Deppenmeier, S
   Gruber, AD
   Radzioch, D
   Clark, AR
   Blackshear, PJ
   Kotlyarov, A
   Gaestel, M
AF Hitti, E
   Iakovleva, T
   Brook, M
   Deppenmeier, S
   Gruber, AD
   Radzioch, D
   Clark, AR
   Blackshear, PJ
   Kotlyarov, A
   Gaestel, M
TI Mitogen-activated protein kinase-activated protein kinase 2 regulates
   tumor necrosis factor mRNA stability and translation mainly by altering
   tristetraprolin expression, stability, and binding to
   adenine/uridine-rich element
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID TNF-ALPHA BIOSYNTHESIS; P38; PATHWAY; DECAY; INVOLVEMENT; TURNOVER;
   GENE; STABILIZATION; ARTHRITIS; DATABASE
AB The mitogen-activated protein kinase (MAPK) p38/MAPK-activated protein kinase 2 (MK2) signaling pathway plays an important role in the posttranscriptional regulation of tumor necrosis factor (TNF), which is dependent on the adenine/uridine-rich element (ARE) in the 3' untranslated region of TNF mRNA. After lipopolysaccharide (LPS) stimulation, MK2-deficient macrophages show a 90% reduction in TNF production compared to the wild type. Tristetraprolin (TTP), a protein induced by LPS, binds ARE and destabilizes TNF mRNA. Accordingly, macrophages lacking TTP produce large amounts of TNF. Here, we generated MK2/TTP double knockout mice and show that, after LPS stimulation, bone marrow-derived macrophages produce TNF mRNA and protein levels comparable to those of TTP knockout cells, indicating that in the regulation of TNF biosynthesis TTP is genetically downstream of MK2. In addition, we show that MK2 is essential for the stabilization of TTP mRNA, and phosphoryllation by MK2 leads to increased TTP protein stability but reduced A-RE affinity. These data suggest that MK2 inhibits the mRNA destabilizing activity of TTP and, in parallel, codegradation of TTP together, with the target mRNA resulting in increased cellular levels of TTP.
C1 Hannover Med Sch, Inst Biochem, D-30625 Hannover, Germany.
   Univ London Imperial Coll Sci Technol & Med, Kennedy Inst, Div Rheumatol, Fac Med, London SW7 2AZ, England.
   Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada.
   Free Univ Berlin, Dept Vet Pathol, D-1000 Berlin, Germany.
   NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA.
RP Gaestel, M (reprint author), Hannover Med Sch, Inst Biochem, Carl Neuberg Str 1, D-30625 Hannover, Germany.
EM gaestel.matthias@mh-hannover.de
OI Brook, Matthew/0000-0003-1245-7385; Clark, Andy/0000-0003-4996-8322;
   Gaestel, Matthias/0000-0002-4944-4652
NR 35
TC 253
Z9 265
U1 2
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD MAR
PY 2006
VL 26
IS 6
BP 2399
EP 2407
DI 10.1128/MCB.26.6.2399-2407.2006
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 020NE
UT WOS:000235915400033
PM 16508014
ER

PT J
AU Swanwick, CC
   Murthy, NR
   Kapur, J
AF Swanwick, CC
   Murthy, NR
   Kapur, J
TI Activity-dependent scaling of GABAergic synapse strength is regulated by
   brain-derived neurotrophic factor
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
DE inhibitory; homeostatic plasticity; mIPSC; TrkB; NMDA receptor; AMPA
   receptor
ID CULTURED HIPPOCAMPAL-NEURONS; GABA MINI AMPLITUDE; HOMEOSTATIC
   PLASTICITY; QUANTAL AMPLITUDE; FACTOR BDNF; INHIBITORY SYNAPTOGENESIS;
   SURFACE EXPRESSION; NERVOUS-SYSTEM; CELL-CULTURES; VISUAL-CORTEX
AB The homeostatic plasticity hypothesis suggests that neuronal activity scales synaptic strength. This study analyzed effects of activity deprivation on GABAergic synapses in cultured hippocampal neurons using patch clamp electrophysiology to record mIPSCs and immunocytochemistry to visualize presynaptic GAD-65 and the gamma 2 subunit of the GABA(A) receptor. When neural activity was blocked for 48 h with tetrodotoxin (TTX, 1 mu M), the amplitude of mIPSCs was reduced, corresponding with diminished sizes of GAD-65 puncta and gamma 2 clusters. Treatment with the NMDA receptor antagonist APV (50 mu M) or the AMPA receptor antagonist DNQX (20 mu M) mimicked these effects, and co-application of brain-derived neurotrophic factor (BDNF, 100 ng/mL) overcame them. Moreover, when neurons were treated with BDNF alone for 48 h, these effects were reversed via the TrkB receptor. Overall, these results suggest that activity-dependent scaling of inhibitory synaptic strength can be modulated by BDNF/TrkB-mediated signaling. (c) 2005 Elsevier Inc. All rights reserved.
C1 Univ Virginia, Grad Program Neurosci, Charlottesville, VA 22908 USA.
   Univ Virginia, Coll Arts & Sci, Charlottesville, VA 22908 USA.
   Univ Virginia, Dept Neurol, Charlottesville, VA 22908 USA.
RP Swanwick, CC (reprint author), NIDCD, Bldg 50,Room 4146,50 S Dr, Bethesda, MD 20892 USA.
EM swanwickc@nidcd.nih.gov
FU NINDS NIH HHS [R01 NS 040337, R01 NS040337, F31 NS043831-01, R01
   NS040337-06, F31 NS 43831, R01 NS044370, F31 NS043831, R01 NS044370-03,
   R01 NS 44370]
NR 52
TC 59
Z9 61
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 1044-7431
J9 MOL CELL NEUROSCI
JI Mol. Cell. Neurosci.
PD MAR
PY 2006
VL 31
IS 3
BP 481
EP 492
DI 10.1016/j.mcn.2005.11.002
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 026XF
UT WOS:000236375700010
PM 16330218
ER

PT J
AU Sissung, TM
   Price, DK
   Sparreboom, A
   Figg, WD
AF Sissung, TM
   Price, DK
   Sparreboom, A
   Figg, WD
TI Pharmacogenetics and regulation of human cytochrome P450 1B1:
   Implications in hormone-mediated tumor metabolism and a novel target for
   therapeutic intervention
SO MOLECULAR CANCER RESEARCH
LA English
DT Review
ID BREAST-CANCER RISK; ARYL-HYDROCARBON RECEPTOR; HUMAN CYP1B1 GENE;
   CATECHOL-O-METHYLTRANSFERASE; UTERINE ENDOMETRIAL CANCER; SINGLE
   NUCLEOTIDE POLYMORPHISMS; HEAT-SHOCK PROTEIN; AH RECEPTOR;
   PROSTATE-CANCER; ESTROGEN-RECEPTOR
AB Several of the hormone-mediated cancers (breast, endometrial, ovarian, and prostate) represent major cancers in both incidence and mortality rates. The etiology of these cancers is in large part modulated by the hormones estrogen and testosterone. As advanced disease develops, the common treatment for these cancers is chemotherapy. Thus, genes that can alter tissue response to hormones and alter clinical response to chemotherapy are of major interest. The cytochrome P450 1B1 (CYP1B1) may be involved in disease progression and modulate the treatment in the above hormone-mediated cancers. This review will focus on the pharmacogenetics of CYP1B1 in relation to hormone-mediated cancers and provide an assessment of cancer risk based on CYP1B1 polymorphisms and expression. In addition, it will provide a summary of CYP1B1 gene regulation and expression in normal and neoplastic tissue.
C1 NCI, Med Oncol Clin Res Unit, Clin Pharmacol Res Core, Bethesda, MD 20892 USA.
   NCI, Canc Therapeut Branch, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Med Oncol Clin Res Unit, Clin Pharmacol Res Core, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016
NR 156
TC 94
Z9 96
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD MAR
PY 2006
VL 4
IS 3
BP 135
EP 150
DI 10.1158/1541-7786.MCR-05-0101
PG 16
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 027XQ
UT WOS:000236449900001
PM 16547151
ER

PT J
AU Innes, CL
   Heinloth, AN
   Flores, KG
   Sieber, SO
   Deming, PB
   Bushel, PR
   Kaufmann, WK
   Paules, RS
AF Innes, CL
   Heinloth, AN
   Flores, KG
   Sieber, SO
   Deming, PB
   Bushel, PR
   Kaufmann, WK
   Paules, RS
TI ATM requirement in gene expression responses to ionizing radiation in
   human lymphoblasts and fibroblasts
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID G(2) CHECKPOINT FUNCTION; EPSTEIN-BARR-VIRUS; ATAXIA-TELANGIECTASIA;
   DNA-DAMAGE; OXIDATIVE STRESS; IDENTIFICATION; KINASE; PHOSPHORYLATION;
   CELLS; INSTABILITY
AB The heritable disorder ataxia telangiectasia (AT) is caused by mutations in the AT-mutated (ATM) gene with manifestations that include predisposition to lymphoproliferative cancers and hypersensitivity to ionizing radiation (IR). We investigated gene expression changes in response to IR in human lymphoblasts and fibroblasts from seven normal and seven AT-affected individuals. Both cell types displayed ATM-dependent gene expression changes after IR, with some responses shared and some responses varying with cell type and dose. Interestingly, after 5 Gy IR, lymphoblasts displayed ATM-independent responses not seen in the fibroblasts at this dose, which likely reflect signaling through ATM-related kinases, e.g., ATR, in the absence of ATM function.
C1 NIEHS, Growth Control & Canc Grp, Res Triangle Pk, NC 27709 USA.
   NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA.
   Univ N Carolina, Dept Pathol & Lab Med, Sch Med, Chapel Hill, NC USA.
RP Paules, RS (reprint author), NIEHS, Growth Control & Canc Grp, POB 12233,MD D2-03, Res Triangle Pk, NC 27709 USA.
EM paules@nichs.nih.gov
FU Intramural NIH HHS; NCI NIH HHS [CA81343]; NIEHS NIH HHS [ES011391]
NR 37
TC 12
Z9 12
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD MAR
PY 2006
VL 4
IS 3
BP 197
EP 207
DI 10.1158/1541-7786.MCR-05-0154
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 027XQ
UT WOS:000236449900007
PM 16547157
ER

PT J
AU Gills, JJ
   Holbeck, S
   Hollingshead, M
   Hewitt, SM
   Kozikowski, AP
   Dennis, PA
AF Gills, JJ
   Holbeck, S
   Hollingshead, M
   Hewitt, SM
   Kozikowski, AP
   Dennis, PA
TI Spectrum of activity and molecular correlates of response to
   phosphatidylinositol ether lipid analogues, novel lipid-based inhibitors
   of Akt
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID ANTICANCER DRUG SCREEN; TUMOR-CELL-LINES; CANCER-CELLS; ACTIVATION;
   PATTERNS
AB The serine/threonine kinase Akt is a promising target in cancer. We previously identified five phosphatidylinositol ether lipid analogues (PIA) that inhibited Akt activation and selectively killed lung and breast cancer cells with high levels of Akt activity. To assess the spectrum of activity in other cell types and to compare PIAs with other inhibitors of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway, we compared growth inhibition by PIAs against the PI3K inhibitors LY294002 and wortmannin and the mTOR inhibitor rapamycin in the NC160 cell line panel. Although each of these compounds inhibited the growth of all the cell lines, distinct patterns were observed. The PIAs were the least potent but the most cytotoxic. The broad spectrum of activity of PIAs was confirmed in vivo in hollow fiber assays. The response to PIAs was significantly correlated with levels of active but not total Akt in the NC160, as assessed using COMPARE analysis. However, a number of molecular targets were identified whose expression was more highly correlated with sensitivity to PIAs than active Akt. Expression of these molecular targets did not overlap with those that correlated with sensitivity to LY294002, wortmannin, or rapamycin. A COMPARE analysis of the National Cancer Institute chemical screening database revealed that the patterns of activity of PIAs correlated best with patterns of activity of other lipid-based compounds. These studies show that although PIAs are widely active in cancer cells, which correlates with the presence of its intended target, active Akt, PIAs are biologically distinct from other known inhibitors of the PI3K/Akt/mTOR pathway.
C1 NCI, Canc Therapeut Branch, Ctr Canc Res, Bethesda, MD 20889 USA.
   NCI, Canc Res Ctr, Med Oncol Branch, Pathol Lab, Bethesda, MD 20889 USA.
   NCI, Canc Res Ctr, Tissue Array Res Program, Pathol Lab, Bethesda, MD 20889 USA.
   NCI, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Frederick, MD 21701 USA.
   Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL USA.
RP Dennis, PA (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA.
EM pdennis@nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788
FU NCI NIH HHS [N01-CO-12400]
NR 12
TC 37
Z9 39
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD MAR
PY 2006
VL 5
IS 3
BP 713
EP 722
DI 10.1158/1535-7163.MCT-05-0484
PG 10
WC Oncology
SC Oncology
GA 027VS
UT WOS:000236444500027
PM 16546986
ER

PT J
AU Liu, Y
   Xia, XM
   Fondell, JD
   Yen, PM
AF Liu, Y
   Xia, XM
   Fondell, JD
   Yen, PM
TI Thyroid hormone-regulated target genes have distinct patterns of
   coactivator recruitment and histone acetylation
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID ESTROGEN-RECEPTOR; LIVING CELLS; GLUCOCORTICOID-RECEPTOR; RESPONSIVE
   PROMOTERS; IN-VIVO; TRANSCRIPTION; COMPLEXES; EXPRESSION; ACTIVATION;
   PROTEASOME
AB Thyroid hormone receptors (TRs) are ligand-regulated transcription factors that bind to thyroid hormone response elements of target genes. Upon ligand binding, they recruit coactivator complexes that increase histone acetylation and recruit RNA polymerase II (Pol II) to activate transcription. Recent studies suggest that nuclear receptors and coactivators may have temporal recruitment patterns on hormone response elements, yet little is known about the nature of the patterns at multiple endogenous target genes. We thus performed chromatin immunoprecipitation assays to investigate coactivator recruitment and histone acetylation patterns on the thyroid hormone response elements of four endogenous target genes (GH, sarcoplasmic endoplasmic reticulum calciumadenosine triphosphatase, phosphoenolpyruvate carboxykinase, and cholesterol 7 alpha- hydroxylase) in a rat pituitary cell line that expresses TRs. We found that TR beta\, several associated coactivators ( steroid receptor coactivator-1, glucocorticoid receptor interacting protein-1, and TR-associated protein 220), and RNA Pol II were rapidly recruited to thyroid hormone response elements as early as 15 min after T 3 addition. When the four target genes were compared, we observed differences in the types and temporal patterns of recruited coactivators and histone acetylation. Interestingly, the temporal pattern of RNA Pol II was similar for three genes studied. Our findings suggest that thyroid hormone-regulated target genes may have distinct patterns of coactivator recruitment and histone acetylation that may enable highly specific regulation.
C1 Johns Hopkins Bayview Med Ctr, Dept Med, Div Endocrinol, Baltimore, MD 21224 USA.
   NIDDKD, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
   Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ 08854 USA.
RP Liu, Y (reprint author), Johns Hopkins Bayview Med Ctr, Dept Med, Div Endocrinol, 4940 Eastern Ave,Room B114, Baltimore, MD 21224 USA.
NR 32
TC 41
Z9 43
U1 0
U2 1
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 MAR
PY 2006
VL 20
IS 3
BP 483
EP 490
DI 10.1210/me.2005-0101
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 014SW
UT WOS:000235501300002
PM 16254015
ER

PT J
AU Gahl, WA
AF Gahl, WA
TI Engulfed
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Editorial Material
DE SIMD; metabolic disorders; rare diseases; biochemical genetics
C1 NHGRI, SHBG, MGB, NIH, Bethesda, MD 20892 USA.
RP Gahl, WA (reprint author), NHGRI, SHBG, MGB, NIH, 10 Ctr Dr,MSC 1851, Bethesda, MD 20892 USA.
EM bgahl@helix.nih.gov
FU Intramural NIH HHS
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2006
VL 87
IS 3
BP 190
EP 193
DI 10.1016/j.ymgme.2005.10.005
PG 4
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 025JH
UT WOS:000236261200004
PM 16330232
ER

PT J
AU Hansson, SR
   Chen, Y
   Brodszki, J
   Chen, M
   Hernandez-Andrade, E
   Inman, JM
   Kozhich, OA
   Larsson, I
   Marsal, K
   Medstrand, P
   Xiang, CC
   Brownstein, MJ
AF Hansson, SR
   Chen, Y
   Brodszki, J
   Chen, M
   Hernandez-Andrade, E
   Inman, JM
   Kozhich, OA
   Larsson, I
   Marsal, K
   Medstrand, P
   Xiang, CC
   Brownstein, MJ
TI Gene expression profiling of human placentas from preeclamptic and
   normotensive pregnancies
SO MOLECULAR HUMAN REPRODUCTION
LA English
DT Article
DE Doppler ultrasound; hypertension; microarray; placenta; pregnancy
ID ENDOTHELIAL-CELLS; TROPHOBLAST INVASION; DIASTOLIC NOTCH; BREAST-CANCER;
   UP-REGULATION; PATHOGENESIS; GROWTH; HYPOXIA; CLASSIFICATION;
   DEHYDROGENASE
AB The aim of this study was to investigate patterns of gene expression in placental samples from patients with preeclampsia (PE), persistent bilateral uterine artery notching (without PE), and normal controls. This study included placental tissue from nine women with PE, seven with uncomplicated pregnancies and five with bilateral uterine artery notching in Doppler velocimetry tracings. Human cDNA microarrays with 6500 transcripts/genes were used and the results verified with real-time PCR and in-situ hybridization. Multidimensional scaling method and random permutation technique demonstrated significant differences among the three groups examined. Within the 6.5K arrays, 6198 elements were unique cDNA clones representing 5952 unique UniGenes and 5695 unique LocusLinks. Multidimensional scaling plots showed 5000 genes that met our quality criteria; among these, 366 genes were significantly different in at least one comparison. Differences in three genes of interest were confirmed with real-time PCR and in-situ hybridization; acid phosphatase 5 was shown to be overexpressed in PE samples and calmodulin 2 and v-rel reticuloendotheliosis viral oncogene homolog A (RELA) were downregulated in PE and uterine artery notch placentas. In conclusion downregulation of RELA and calmodulin 2 might represent an attempt by the placenta to compensate for elevations in intracellular calcium, possibly caused by hypoxia and/or apoptosis, in both pregnancies with uterine artery notching and preeclampsia.
C1 Lund Univ, Univ Lund Hosp, Dept Obstet & Gynecol, S-22185 Lund, Sweden.
   NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
   NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA.
   NCI, SAIC Frederick, Frederick, MD 21701 USA.
   Lund Univ, Dept Cell & Mol Biol, Lund, Sweden.
RP Hansson, SR (reprint author), Lund Univ, Univ Lund Hosp, Dept Obstet & Gynecol, BMC-C14, S-22185 Lund, Sweden.
EM stefan.hansson@med.lu.se
RI Brownstein, Michael/B-8609-2009
FU NCI NIH HHS [N01-CO-12400]
NR 50
TC 26
Z9 26
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1360-9947
J9 MOL HUM REPROD
JI Mol. Hum. Reprod.
PD MAR
PY 2006
VL 12
IS 3
BP 169
EP 179
DI 10.1093/molehr/gal011
PG 11
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 032XF
UT WOS:000236809000005
PM 16556680
ER

PT J
AU Duchesnes, UE
   Murphy, PM
   Williams, TJ
   Pease, JE
AF Duchesnes, UE
   Murphy, PM
   Williams, TJ
   Pease, JE
TI Alanine scanning mutagenesis of the chemokine receptor CCR3 reveals
   distinct extracellular residues involved in recognition of the eotaxin
   family of chemokines
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE chemokine; chemokine receptors; GPCR; inflammation; allergy
ID EOSINOPHIL CHEMOATTRACTANT CYTOKINE; LIGAND-INDUCED INTERNALIZATION; NMR
   SOLUTION STRUCTURE; GUINEA-PIG MODEL; AIRWAY HYPERRESPONSIVENESS;
   INTERNATIONAL UNION; ALLERGEN CHALLENGE; ENDOTHELIAL-CELLS;
   MOLECULAR-CLONING; MESSENGER-RNA
AB Despite considerable differences in primary structure, the chemokines eotaxin-1/CC11, eotaxin-2/CCL24 and eotaxin-3/CCL26 signal via a single receptor, CCR3. but exhibit different potencies and efficacies. To examine receptor/ligand interactions in more detail, we performed alanine scanning mutagenesis of 21 charged residues within the extracellular loops (ECLs) of CCR3. Following transient expression in the L1.2 cell line, CCR3 Mutants were assessed for their ability to be expressed at the cell surface, bind CCL11 and induce chemotactic responses to CCL11. CCL24 and CCL26.
   The majority of constructs were well expressed at the cell surface and bound CCL11 with low nanomolar affinity. Exceptions to this rule included the mutants E175A and E176A (ECL2) which were poorly expressed and responded weakly to all three ligands in chemotaxis assays. In contrast. the mutants K26 (amino-terminus) E179 and E180 (ECL2) responded in chemotaxis assays to CCL11 and CCL24, but not to CCL26. Mutation of residues in ECL3 was informative, with the D272A, K277A and D280A mutants exhibiting reduced chemotactic responses to two or more of the three ligands examined, despite being expressed on the cell surface at levels similar to WT CCR3. This suggests a major role for ECL3 in the recognition of all three eotaxins.
   In summary. distinct acidic and basic residues within CCR3 determine both receptor expression and activation by the eotaxins. Determining how these chemokines interact with their receptor at the molecular level should increase our understanding of the process of chemokine receptor activation. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Univ London Imperial Coll Sci Technol & Med, Fac Med, Leukocyte Biol & Sect, London SW7 2AZ, England.
   Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London SW7 2AZ, England.
   NIAID, Mol Signaling Sect, Lab Host Defenses, NIH, Bethesda, MD 20892 USA.
RP Pease, JE (reprint author), Univ London Imperial Coll Sci Technol & Med, Fac Med, Leukocyte Biol & Sect, Sir Alexander Fleming Bldg,S Kensington Campus, London SW7 2AZ, England.
EM j.pease@imperial.ac.uk
NR 50
TC 2
Z9 2
U1 1
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD MAR
PY 2006
VL 43
IS 8
BP 1221
EP 1231
DI 10.1016/j.molimm.2005.07.015
PG 11
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 017XP
UT WOS:000235726900016
ER

PT J
AU Rogozin, IB
   Pavlov, YI
AF Rogozin, IB
   Pavlov, YI
TI The cytidine deaminase AID exhibits similar functional properties in
   yeast and mammals
SO MOLECULAR IMMUNOLOGY
LA English
DT Article
DE somatic hypermutation; DNA context polynucleotide (deoxy)cytidine
   deaminase; mutation hotspots; mutation frequency
ID SOMATIC HYPERMUTATION; DNA DEAMINATION; MUTATION; MECHANISM; IMMUNITY;
   HOTSPOTS
AB A recent work published in Molecular Immunology examined the editing activity of activation-induced deaminase (AID) in yeast (Krause, K., Marcu, K.B., Greeve, J., 2006. The cytidine deaminases AID and APOBEC-1 exhibit distinct functional properties in a novel yeast selectable system. Mol. Immunol.). It was proposed that expression of AID in yeast is not sufficient for the generation of point mutations in a highly transcribed gene due to the lack of cofactors for AID-induced somatic hypermutation, which are unique to B cells. It was suggested that, on its own, AID does not have an intrinsic specificity for its target sequences. However, it has been shown previously that expression of the human AID gene in yeast was moderately mutagenic in a wild-type strain and highly mutagenic in an ung1 uracil-DNA glycosylase-deficient strain (Mayorov, V.I., Rogozin, I.B., Adkison, L.R., Frahm, C.R., Kunkel T.A., Pavlov Y.I., 2005. Expression of human AID in yeast induces mutations in context similar to the context of somatic hypermutation at G-C pairs in immunoglobulin genes. BMC Immunol. 6, 10; Poltoratsky, V.P., Wilson, S.H., Kunkel, T.A., Pavlov, Y.I., 2004. Recombinogenic phenotype of human activation-induced cytosine deaminase. J. Immunol. 172, 4308-4313). The vast majority of mutations were at G-C pairs. Mutations showed a clear DNA sequence context specificity which resembled the specificity of somatic hypermutation at G-C pairs in immunoglobulin genes and AID mutation specificity in vitro. The inability to detect mutator effects of AID by Krause et al. is likely to be caused by the use of the wild-type yeast strain and a small sample of clones examined for the presence of mutations. In addition, we show that non-uniformity of the mutation hotspot distribution is a factor potentially decreasing the chances of detecting mutations. (c) 2005 Elsevier Ltd. All rights reserved.
C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
   Univ Nebraska, Med Ctr, Eppley Inst Res Canc, Omaha, NE 68198 USA.
   Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA.
   Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA.
RP Rogozin, IB (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike,Bldg 38A,Room 5N505A, Bethesda, MD 20894 USA.
EM rogozin@ncbi.nlm.nih.gov
NR 21
TC 8
Z9 8
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD MAR
PY 2006
VL 43
IS 9
BP 1481
EP 1484
DI 10.1016/j.molimm.2005.09.002
PG 4
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA 022JT
UT WOS:000236052500021
PM 16219354
ER

PT J
AU Carlson, JH
   Wood, H
   Roshick, C
   Caldwell, HD
   McClarty, G
AF Carlson, JH
   Wood, H
   Roshick, C
   Caldwell, HD
   McClarty, G
TI In vivo and in vitro studies of Chlamydia trachomatis TrpR : DNA
   interactions
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID OBLIGATE INTRACELLULAR PATHOGEN; REPRESSOR-OPERATOR COMPLEX;
   ESCHERICHIA-COLI K-12; TRYPTOPHAN SYNTHASE; RNA-POLYMERASE;
   NUCLEOTIDE-SEQUENCE; GENE-EXPRESSION; STRUCTURAL GENE; HOST-CELLS;
   RESISTANCE
AB We previously reported that Chlamydia trachomatis expresses the genes encoding tryptophan synthase (trpBA) and the tryptophan repressor (trpR). Here we employ primer extension analysis to identify the transcriptional origins of both trpR and trpBA, allowing for the identification of the putative operator sequences for both trpR and trpBA. Moreover we demonstrate that native recombinant chlamydial TrpR binds to the predicted operator sequence upstream of trpR. A restriction endonuclease protection assay was designed and used to demonstrate that 5-fluorotryptophan was the only tryptophan analogue capable of activating binding of native recombinant chlamydial TrpR to its operator. Additionally, 5-fluorotryptophan was the only analogue that repressed expression of trpBA at a level analogous to L-tryptophan itself. Based on these findings, a mutant selection protocol was designed and a C. trachomatis isolate containing a frameshift mutation in trpR was isolated. This chlamydial mutant synthesizes a truncated TrpR protein that cannot regulate expression of trpBA and trpR in response to changes in tryptophan levels. These findings provide the first genetic proof that TrpR acts as a negative regulator of transcription in C. trachomatis.
C1 Hlth Canada, Natl Microbiol Lab, Winnipeg, MB R3E 3R2, Canada.
   NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
   Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 0W3, Canada.
RP McClarty, G (reprint author), Hlth Canada, Natl Microbiol Lab, 1015 Arlington St, Winnipeg, MB R3E 3R2, Canada.
EM grant_mcclarty@phac-aspc.gc.ca
NR 51
TC 15
Z9 15
U1 0
U2 2
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0950-382X
J9 MOL MICROBIOL
JI Mol. Microbiol.
PD MAR
PY 2006
VL 59
IS 6
BP 1678
EP 1691
DI 10.1111/j.1365-2958.2006.05045.x
PG 14
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 019NB
UT WOS:000235842600004
PM 16553875
ER

PT J
AU Wallqvist, A
   Connelly, J
   Sausville, EA
   Covell, DG
   Monks, A
AF Wallqvist, A
   Connelly, J
   Sausville, EA
   Covell, DG
   Monks, A
TI Differential gene expression as a potential classifier of
   2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole-sensitive
   and-insensitive cell lines
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID BREAST-CANCER CELLS; ANTITUMOR AGENT; SERIAL ANALYSIS; TUMOR-CELLS;
   IN-VITRO; RECEPTOR; DATABASE; CYP1A1; GROWTH; INDUCTION
AB 2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole (5F-203) is a candidate antitumor agent empirically discovered with the aid of the National Cancer Institute (NCI) Anticancer Drug Screen. In an effort to determine whether basal expression of genes could be used to classify cell sensitivity to this agent, serial analysis of gene expression (SAGE) libraries were generated for three sensitive and two insensitive human tumor cell lines. When the SAGE tags expressed within these cell line libraries were compared and evaluated for differences, several genes seemed more highly expressed in 5F-203-sensitive cell lines than in the insensitive cell lines. Constitutive expressions of 15 genes identified by the analysis were then measured by quantitative reverse-transcription polymerase chain reaction in the 60 cell lines of the NCI Anticancer Drug Screen. This generated a pattern of relative basal gene expression across the cell lines and also confirmed the differential expression of SAGE-discovered genes within the initial set of five cell lines. Further analyses of these expression data in 60 cell lines suggested that a smaller subset of genes could be used to classify tumor cell sensitivity to 5F-203. In contrast, the same set of genes did not predict with equivalent precision sensitivity to unrelated active drugs, and another set of genes could not better classify the cell lines in terms of 5F-203 sensitivity. These results suggest that constitutive gene expression profiles, in which the genes are not necessarily known to be related to the mechanism of action of a given drug, may be viewed as a general tool to extend and improve the concept of a single predictive gene to groups of predictive genes.
C1 NCI Frederick, Sci Applicat Int Corp, Ft Detrick, MD 21702 USA.
   NCI Frederick, Dev Therapeut Program, Ft Detrick, MD USA.
RP Wallqvist, A (reprint author), NCI Frederick, Sci Applicat Int Corp, POB B, Ft Detrick, MD 21702 USA.
EM wallqvis@ncifcrf.gov
OI wallqvist, anders/0000-0002-9775-7469
FU NCI NIH HHS [N01-CA12400]
NR 40
TC 2
Z9 3
U1 0
U2 0
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD MAR
PY 2006
VL 69
IS 3
BP 737
EP 748
DI 10.1124/mol.105.017061
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 012SN
UT WOS:000235359900009
PM 16332985
ER

PT J
AU Rankin, ML
   Marinec, PS
   Cabrera, DM
   Wang, Z
   Jose, PA
   Sibley, DR
AF Rankin, ML
   Marinec, PS
   Cabrera, DM
   Wang, Z
   Jose, PA
   Sibley, DR
TI The D-1 dopamine receptor is constitutively phosphorylated by G
   protein-coupled receptor kinase 4
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID AGONIST-INDUCED DESENSITIZATION; RHODOPSIN KINASE; BETA(2)-ADRENERGIC
   RECEPTOR; CELLS; GRK4; RESPONSIVENESS; IDENTIFICATION; HYPERTENSION;
   ACTIVATION; MECHANISMS
AB G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate agonist-activated GPCRs, initiating their homologous desensitization. In this article, we present data showing that GRK4 constitutively phosphorylates the D-1 receptor in the absence of agonist activation. This constitutive phosphorylation is mediated exclusively by the alpha isoform of GRK4; the beta, gamma, and delta isoforms are ineffective in this regard. Mutational analysis reveals that the constitutive phosphorylation mediated by GRK4 alpha is restricted to the distal region of the carboxyl terminus of the receptor, specifically to residues Thr428 and Ser431. Phosphorylation of the D-1 receptor by GRK4 alpha results in a decrease in cAMP accumulation, an increase in receptor internalization, and a decrease in total receptor number - all of which are abolished in a D-1 receptor mutant containing T428V and S431A. The increase in internalized D-1 receptors induced by GRK4 alpha phosphorylation is due to enhanced receptor internalization rather than retarded trafficking of newly synthesized receptors to the cell surface. The constitutive phosphorylation of the D-1 receptor by GRK4 alpha does not alter agonist-induced desensitization of the receptor because dopamine pretreatment produced a similar decrease in cAMP accumulation in control cells versus cells expressing GRK4 alpha. These observations shift the attenuation of D-1 receptor signaling from a purely agonist-driven process to one that is additionally modulated by the complement of kinases that are coexpressed in the same cell. Furthermore, our data provide direct evidence that, in contrast to current dogma, GRKs can (at least in some instances) constitutively phosphorylate GPCRs in the absence of agonist activation resulting in constitutive desensitization.
C1 NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA.
   Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA.
RP Sibley, DR (reprint author), NINDS, Mol Neuropharmacol Sect, NIH, 5625 Fishers Lane,Room 4S-04,MSC 9405, Bethesda, MD 20892 USA.
EM sibley@helix.nih.gov
RI Cabrera, David/I-1013-2014
FU Intramural NIH HHS
NR 35
TC 47
Z9 49
U1 0
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD MAR
PY 2006
VL 69
IS 3
BP 759
EP 769
DI 10.1124/mol.105.019901
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 012SN
UT WOS:000235359900011
PM 16338988
ER

PT J
AU Ohtani, M
   Oka, T
   Badyuk, M
   Xiao, YX
   Kellar, KJ
   Daly, JW
AF Ohtani, M
   Oka, T
   Badyuk, M
   Xiao, YX
   Kellar, KJ
   Daly, JW
TI Mouse beta-TC6 insulinoma cells: High expression of functional alpha 3
   beta 4 nicotinic receptors mediating membrane potential, intracellular
   calcium, and insulin release
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID ACETYLCHOLINE-RECEPTORS; PANCREATIC-ISLETS; SUBTYPE; BINDING; LINE;
   PHARMACOLOGY; ANTAGONISTS; SUBUNITS; AGONISTS; MICE
AB Nicotine elicited membrane depolarization, elevation of intracellular calcium, rubidium efflux, and release of insulin from mouse beta-TC6 insulinoma cells. Such responses were blocked by the nicotinic antagonist mecamylamine but not by the muscarinic antagonist atropine. Neither the selective alpha(4)beta(2) antagonist dihydro-beta-erythroidine nor the selective alpha(7) antagonist methyllycaconitine significantly blocked the nicotine-elicited depolarization or the calcium response. The elevation of intracellular calcium did not occur in calcium-free media, indicating that the increase in intracellular calcium was due to the influx of calcium. The rank order of potency for nicotinic agonists was as follows: epibatidine > nicotine = 3-(azetidinylmethoxy) pyridine (A-85380), cytisine, dimethylphenylpiperazinium (DMPP). Cytisine and DMPP seemed to be partial agonists. The density of nicotinic receptors measured by [H-3] epibatidine binding was 7-fold higher in membranes from beta-TC6 cells than in rat brain membranes. No binding of I-125-A-85380 was detected, indicating the absence of beta 2-containing receptors. Reverse transcription-polymerase chain reaction analyses indicated the presence of mRNA for alpha 3 and alpha 4 subunits and beta 2 and beta 4 subunits in beta-TC6 cells. The binding and functional data suggest that the major nicotinic receptor is composed of alpha 3 and beta 4 subunits. The beta-TC6 cells thus provide a model system for pharmacological study of such nicotinic receptors.
C1 NIDDKD, Bioorgan Chem Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA.
   Musashino Univ, Fac Pharm, Pharmaceut Sci Res Inst, Tokyo, Japan.
   Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20057 USA.
RP Daly, JW (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, US Dept HHS, Bldg 8,Room 1A17, Bethesda, MD 20892 USA.
EM jdaly@nih.gov
FU Intramural NIH HHS
NR 29
TC 14
Z9 15
U1 0
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD MAR
PY 2006
VL 69
IS 3
BP 899
EP 907
DI 10.1124/mol.105.014902
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 012SN
UT WOS:000235359900025
PM 16332988
ER

PT J
AU Hejazi, N
   Zhou, CY
   Oz, M
   Sun, H
   Ye, JH
   Zhang, L
AF Hejazi, N
   Zhou, CY
   Oz, M
   Sun, H
   Ye, JH
   Zhang, L
TI Delta(9)-Tetrahydrocannabinol and endogenous cannabinoid anandamide
   directly potentiate the function of glycine receptors
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID VENTRAL TEGMENTAL AREA; RAT SPINAL-CORD; XENOPUS OOCYTES; MEDIATED
   RESPONSES; K+ CHANNELS; SYNAPTIC-TRANSMISSION; KNOCKOUT MICE; ETHANOL;
   ALCOHOL; NEURONS
AB Anandamide (AEA) and Delta(9)-tetrahydrocannabinol (THC) are endogenous and exogenous ligands, respectively, for cannabinoid receptors. Whereas most of the pharmacological actions of cannabinoids are mediated by CB1 receptors, there is also evidence that these compounds can produce effects that are not mediated by the activation of identified cannabinoid receptors. Here, we report that THC and AEA, in a CB1 receptor-independent manner, cause a significant potentiation of the amplitudes of glycine-activated currents (I-Gly) in acutely isolated neurons from rat ventral tegmental area (VTA) and in Xenopus laevis oocytes expressing human homomeric (alpha 1) and heteromeric (alpha 1 beta 1) subunits of glycine receptors (GlyRs). The potentiation of I-Gly by THC and AEA is concentration-dependent, with respective EC 50 values of 86 +/- 9 and 319 +/- 31 nM for alpha 1 homomeric receptors, 73 +/- 8 and 318 +/- 24 nM for alpha 1 beta 1 heteromeric receptors, and 115 +/- 13 and 230 +/- 29 nM for native GlyRs in VTA neurons. The effects of THC and AEA are selective for I-Gly, because GABA-activated current in VTA neurons or in X. laevis oocytes expressing alpha 2 beta 3 gamma 2 GABA(A) receptor subunits were unaffected by these compounds. The maximal potentiation by THC and AEA was observed at the lowest concentration of glycine; with increasing concentrations of glycine, the potentiation significantly decreased. The site for THC and AEA seems to be distinct from that of the alcohol and volatile anesthetics. The results indicate that THC and AEA, in pharmacologically relevant concentrations, directly potentiate the function of GlyRs through an allosteric mechanism.
C1 NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA.
   Univ Med & Dent New Jersey, Sch Med, Dept Anesthesiol, Newark, NJ 07103 USA.
   Univ Med & Dent New Jersey, Sch Med, Dept Pharmacol & Physiol, Newark, NJ 07103 USA.
   NIDA, Cellular Neurobiol Branch, NIH, Washington, DC USA.
RP Zhang, L (reprint author), NIAAA, Lab Integrat Neurosci, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM lzhang@mail.nih.gov
RI Oz, Murat/E-2148-2012
FU Intramural NIH HHS
NR 51
TC 67
Z9 71
U1 0
U2 0
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD MAR
PY 2006
VL 69
IS 3
BP 991
EP 997
DI 10.1124/mol.105.019174
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 012SN
UT WOS:000235359900035
PM 16332990
ER

PT J
AU Lizanecz, E
   Bagi, Z
   Pasztor, ET
   Papp, Z
   Edes, I
   Kedei, N
   Blumberg, PM
   Toth, A
AF Lizanecz, E
   Bagi, Z
   Pasztor, ET
   Papp, Z
   Edes, I
   Kedei, N
   Blumberg, PM
   Toth, A
TI Phosphorylation-dependent desensitization by anandamide of vanilloid
   receptor-1 (TRPV1) function in rat skeletal muscle arterioles and in
   Chinese hamster ovary cells expressing TRPV1
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID PROTEIN-KINASE-C; ROOT GANGLION NEURONS; CAPSAICIN RECEPTORS;
   MESENTERIC-ARTERIES; CALCIUM RESPONSE; VR1 RECEPTORS; IN-VIVO;
   ACTIVATION; RELEASE; RECOMBINANT
AB It has been proposed that activation of vanilloid receptor-1 (TRPV1) affects the vasotone of resistance arteries. One of the endogenous activators of TRPV1 is anandamide. The effects of anandamide on TRPV1 responsiveness were tested on isolated, pressurized (80 mm Hg) skeletal muscle (m. gracilis) arterioles (179 +/- 33 mu m in diameter). We found that the TRPV1 agonist capsaicin (1 mu M) elicited a substantial constriction in isolated arterioles (51 +/- 12%). In contrast, anandamide (0 - 100 mu M) did not affect arteriolar diameter significantly (3 +/- 5%). Isolated vessels were also preincubated with anandamide (30 mu M for 20 min). This anandamide pretreatment completely blocked capsaicin-induced arteriolar constriction (response decreased to 1 +/- 0.6%), and this inhibition was reversed by a protein phosphatase-2B inhibitor (cyclosporin-A; 100 nM, 5 min) treatment (constriction, 31 +/- 1%). An exogenous TRPV1-expressing cell line [Chinese hamster ovary (CHO)-TRPV1] was used to specifically evaluate TRPV1-mediated effects of anandamide. The efficacy of anandamide in this system, as determined by Ca-45(2+) uptake, was 65 +/- 8% of that of capsaicin. Upon treatment of the cells with cyclosporin-A or the protein kinase C activator phorbol 12-myristate 13-acetate (PMA), anandamide was transformed to a full agonist. Anandamide treatment caused an acute desensitization in these cells as measured by intracellular Ca2+ imaging. Application of cyclosporin-A or PMA reversed this desensitization. Our data suggest that anandamide may cause a complete (albeit phosphorylation-dependent) desensitization of TRPV1 in skeletal muscle arterioles and in CHO-TRPV1 cells, which apparently transforms the ligand-gated TRPV1 into a phosphorylationgated channel. This property of anandamide may provide a new therapeutic strategy to manipulate TRPV1 activity.
C1 Univ Debrecen, Div Clin Physiol, Inst Cardiol, H-4004 Debrecen, Hungary.
   NCI, Mol Mechanisms Tumor Promot Sect, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA.
RP Toth, A (reprint author), Univ Debrecen, Div Clin Physiol, Inst Cardiol, POB 1, H-4004 Debrecen, Hungary.
EM atitoth@jaguar.unideb.hu
RI Edes, Istvan/B-8795-2011; Toth, Attila/F-4859-2010
OI Toth, Attila/0000-0001-6503-3653
FU Intramural NIH HHS
NR 40
TC 37
Z9 37
U1 0
U2 1
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD MAR
PY 2006
VL 69
IS 3
BP 1015
EP 1023
DI 10.1124/mol.105.015644
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 012SN
UT WOS:000235359900038
PM 16338989
ER

PT J
AU Zhang, HM
   Chen, SR
   Matsui, M
   Gautam, D
   Wess, J
   Pan, HL
AF Zhang, HM
   Chen, SR
   Matsui, M
   Gautam, D
   Wess, J
   Pan, HL
TI Opposing functions of spinal M-2, M-3, and M-4 receptor subtypes in
   regulation of GABAergic inputs to dorsal horn neurons revealed by
   muscarinic receptor knockout mice
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID ACETYLCHOLINE-RECEPTORS; CHOLINERGIC RECEPTORS; AUTORADIOGRAPHIC
   LOCALIZATION; CHOLINESTERASE INHIBITION; GABA(B) RECEPTORS; CORD;
   ANALGESIA; BINDING; M2; ANTINOCICEPTION
AB Spinal muscarinic acetylcholine receptors (mAChRs) play an important role in the regulation of nociception. To determine the role of individual mAChR subtypes in control of synaptic GABA release, spontaneous inhibitory postsynaptic currents (sIPSCs) and miniature IPSCs (mIPSCs) were recorded in lamina II neurons using whole-cell recordings in spinal cord slices of wildtype and mAChR subtype knockout (KO) mice. The mAChR agonist oxotremorine-M (3 - 10 mu M) dose-dependently decreased the frequency of GABAergic sIPSCs and mIPSCs in wild-type mice. However, in the presence of the M-2 and M-4 subtype-preferring antagonist himbacine, oxotremorine-M caused a large increase in the sIPSC frequency. In M-3 KO and M-1/M-3 double-KO mice, oxotremorine-M produced a consistent decrease in the frequency of sIPSCs, and this effect was abolished by himbacine. We were surprised to find that in M-2/M-4 double-KO mice, oxotremorine-M consistently increased the frequency of sIPSCs and mIPSCs in all neurons tested, and this effect was completely abolished by 4-diphenylacetoxy-N- methylpiperidine methiodide, an M 3 subtype-preferring antagonist. In M-2 or M-4 single-KO mice, oxotremorine-M produced a variable effect on sIPSCs; it increased the frequency of sIPSCs in some cells but decreased the sIPSC frequency in other neurons. Taken together, these data strongly suggest that activation of the M 3 subtype increases synaptic GABA release in the spinal dorsal horn of mice. In contrast, stimulation of presynaptic M 2 and M 4 subtypes predominantly attenuates GABAergic inputs to dorsal horn neurons in mice, an action that is opposite to the role of M 2 and M 4 subtypes in the spinal cord of rats.
C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Anesthesiol, Hershey, PA 17033 USA.
   Univ Tokyo, Inst Med Sci, Div Neuronal Network, Tokyo, Japan.
   NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Pan, HL (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Anesthesiol & Pain Med, Unit 409, 1400 Holcombe Blvd, Houston, TX 77030 USA.
FU NIGMS NIH HHS [GM64830]; NINDS NIH HHS [NS45602]
NR 33
TC 19
Z9 21
U1 0
U2 2
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD MAR
PY 2006
VL 69
IS 3
BP 1048
EP 1055
DI 10.1124/mol.105.018069
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 012SN
UT WOS:000235359900042
PM 16365281
ER

PT J
AU Wendland, JR
   Martin, BJ
   Kruse, MR
   Lesch, KP
   Murphy, DL
AF Wendland, JR
   Martin, BJ
   Kruse, MR
   Lesch, KP
   Murphy, DL
TI Simultaneous genotyping of four functional loci of human SLC6A4, with a
   reappraisal of 5-HTTLPR and rs25531
SO MOLECULAR PSYCHIATRY
LA English
DT Letter
ID SEROTONIN TRANSPORTER GENE
C1 NIMH, Clin Sci Lab, Bethesda, MD 20892 USA.
   Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany.
RP Wendland, JR (reprint author), NIMH, Clin Sci Lab, Bldg 10, Bethesda, MD 20892 USA.
EM wendlandj@mail.nih.gov
RI Wendland, Jens/A-1809-2012; Lesch, Klaus-Peter/J-4906-2013
OI Lesch, Klaus-Peter/0000-0001-8348-153X
FU Intramural NIH HHS
NR 11
TC 340
Z9 345
U1 1
U2 9
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 MAR
PY 2006
VL 11
IS 3
BP 224
EP 226
DI 10.1038/sj.mp.4001789
PG 3
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 017BF
UT WOS:000235668400001
PM 16402131
ER

PT J
AU Belfer, I
   Hipp, H
   McKnight, C
   Evans, C
   Buzas, B
   Bollettino, A
   Albaugh, B
   Virkkunen, M
   Yuan, Q
   Max, MB
   Goldman, D
   Enoch, MA
AF Belfer, I
   Hipp, H
   McKnight, C
   Evans, C
   Buzas, B
   Bollettino, A
   Albaugh, B
   Virkkunen, M
   Yuan, Q
   Max, MB
   Goldman, D
   Enoch, MA
TI Association of galanin haplotypes with alcoholism and anxiety in two
   ethnically distinct populations
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE single-nucleotide polymorphism; linkage disequilibrium; haplotype;
   galanin; alcoholism; anxiety
ID STRUCTURED CLINICAL INTERVIEW; ETHANOL INTAKE; HUMAN PREPROGALANIN;
   GENE-EXPRESSION; TRANSGENIC MICE; STRESS; NORADRENALINE; SEROTONIN;
   NUCLEUS; HISTORY
AB The neuropeptide galanin (GAL) is widely expressed in the central nervous system. Animal studies have implicated GAL in alcohol abuse and anxiety: chronic ethanol intake increases hypothalamic GAL mRNA; high levels of stress increase GAL release in the central amygdala. The coding sequence of the galanin gene, GAL, is highly conserved and a functional polymorphism has not yet been found. The aim of our study was, for the first time, to identify GAL haplotypes and investigate associations with alcoholism and anxiety. Seven single-nucleotide polymorphisms (SNPs) spanning GAL were genotyped in 65 controls from five populations: US and Finnish Caucasians, African Americans, Plains and Southwestern Indians. A single haplotype block with little evidence of historical recombination was observed for each population. Four tag SNPs were then genotyped in DSM-III-R lifetime alcoholics and nonalcoholics from two population isolates: 514 Finnish Caucasian men and 331 Plains Indian men and women. Tridimensional Personality Questionnaire harm avoidance (HA) scores, a dimensional measure of anxiety, were obtained. There was a haplotype association with alcoholism in both the Finnish (P = 0.001) and Plains Indian (P = 0.004) men. The SNPs were also significantly associated. Alcoholics were divided into high and low HA groups (X and < mean HA of population). In the Finns, haplotype (P < 0.0001) and diplotype (P < 0.0001) distributions differed between high HA alcoholics, low HA alcoholics and nonalcoholics. Our results from two independent populations suggest that GAL may contribute to vulnerability to alcoholism, perhaps mediated by dimensional anxiety.
C1 NIAAA, Neurogenet Lab, NIH, DHHS, Bethesda, MD 20892 USA.
   Natl Inst Dent & Craniofacial Res, Pain & Neurosurg Mechanisms Branch, Bethesda, MD USA.
   Ctr Human Behav Studies Inc, Weatherford, OK USA.
   Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland.
RP Belfer, I (reprint author), NIAAA, Neurogenet Lab, NIH, DHHS, 5625 Fishers Lane,Suite 3S32,MSC 9412, Bethesda, MD 20892 USA.
EM ibelfer@mail.nih.gov
RI Goldman, David/F-9772-2010; 
OI Goldman, David/0000-0002-1724-5405; Hipp, Heather/0000-0002-1089-3928
FU Intramural NIH HHS [Z99 AA999999]
NR 44
TC 49
Z9 51
U1 0
U2 0
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 MAR
PY 2006
VL 11
IS 3
BP 301
EP 311
DI 10.1038/sj.mp.4001768
PG 11
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 017BF
UT WOS:000235668400009
PM 16314872
ER

PT J
AU Di Pasquale, G
   Chiorini, JA
AF Di Pasquale, G
   Chiorini, JA
TI AAV transcytosis through barrier epithelia and endothelium
SO MOLECULAR THERAPY
LA English
DT Article
DE adeno-associated virus; transcytosis; virus entry; virus trafficking
ID ADENOASSOCIATED VIRUS TYPE-2; BLOOD-BRAIN-BARRIER; RECEPTOR-MEDIATED
   TRANSCYTOSIS; HUMAN-IMMUNODEFICIENCY-VIRUS; ESCHERICHIA-COLI K1; CANINE
   KIDNEY-CELLS; AIRWAY EPITHELIA; GENE-TRANSFER; POLARIZED MONOLAYER;
   SIALIC-ACID
AB To transduce efficiently barrier epithelia such as the lung is the goal of several gene therapy applications. However, experiments with AAV-2 suggest that transduction is limited in this type of barrier epithelia. In contrast, other serotypes of AAV transduce barrier epithelia and exhibit broad dissemination throughout the tissue. Transcytosis is a process by which proteins and pathogens overcome barrier layers to reach the opposite cell surface. To understand better the entry pathway of AAV particles and their ability to penetrate barrier epithelia, we tested the hypothesis that the limited transduction of some barrier epithelia in vitro or the spread of some AAV serotypes through tissue in vivo is due to transcytosis. Our experiments demonstrate that dependoviruses can penetrate barrier cells by transcytosis. The process is rapid as well as serotype and cell-type specific and can be blocked by neutralizing antibodies, temperature, or chemical inhibitors of transcytosis. The particles isolated following apical-to-basolateral transport are still encapsulated and they can transcluce permissive cell lines in vitro. Furthermore, the entry pathway used by AAV-5 for transcytosis appears to be independent of the one used for transduction. Importantly, inhibition of virus transcytosis results in a dramatic increase in intracellular vector and transduction.
C1 NIH, Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA.
RP Chiorini, JA (reprint author), NIH, 10 1N113,10 Ctr Dr,MSC1190, Bethesda, MD 20892 USA.
EM jchiorini@dir.nidcr.nih.gov
NR 56
TC 52
Z9 52
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 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAR
PY 2006
VL 13
IS 3
BP 506
EP 516
DI 10.1016/j.ymthe.2005.11.007
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA 027VX
UT WOS:000236445000006
PM 16368273
ER

PT J
AU Lomarev, MP
   Kanchana, S
   Bara-Jimenez, W
   Iyer, M
   Wassermann, EM
   Hallett, M
AF Lomarev, MP
   Kanchana, S
   Bara-Jimenez, W
   Iyer, M
   Wassermann, EM
   Hallett, M
TI Placebo-controlled study of rTMS for the treatment of Parkinson's
   disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; rTMS; motor cortex
ID TRANSCRANIAL MAGNETIC STIMULATION; SUBTHALAMIC NUCLEUS STIMULATION;
   LONG-TERM POTENTIATION; DEEP-BRAIN-STIMULATION; CEREBRAL BLOOD-FLOW;
   HUMAN MOTOR CORTEX; DOPAMINE RELEASE; CORTICAL EXCITABILITY; MOVEMENT;
   INCREASES
AB The objective of this study is to assess the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) for gait and bradykinesia in patients with Parkinson's disease (PD). In a double-blind placebo-controlled Study, we evaluated the effects of 25 Hz rTMS in 18 PD patients. Eight rTMS sessions were performed over a 4-week period. Four cortical targets (left and right motor and dorsolateral prefrontal cortex) were Stimulated in each session, with 300 Pulses each, 100% of motor threshold intensity. Left motor cortex (MC) excitability was assessed using motor evoked potentials (MEPs) from the abductor pollicis brevis. During the 4 weeks, times for executing walking and complex hand movements tests gradually decreased. The therapeutic rTMS effect lasted for at least 1 month after treatment ended. Right-hand bradykinesia improvement correlated with increased MEP amplitude evoked by left MC rTMS after individual sessions, but improvement overall did not correlate with MC excitability. rTMS sessions appear to have a cumulative benefit for improving gait, as well as reducing upper limb bradykinesia in PD patients. Although short-term benefit may be due to MC excitability enhancement, the mechanism of Cumulative benefit must have another explanation. (c) 2005 Movement Disorder Society.
C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
   NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA.
   NINDS, Brain Stimulat Unit & Cognit Neurosci, NIH, Bethesda, MD 20892 USA.
RP Lomarev, MP (reprint author), NIH Bldg 10,Room 5N240,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA.
EM lomarevm@ninds.nih.gov
NR 37
TC 99
Z9 105
U1 2
U2 5
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD MAR
PY 2006
VL 21
IS 3
BP 325
EP 331
DI 10.1002/mds.20713
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 027IS
UT WOS:000236409500007
PM 16211618
ER

PT J
AU Hardy, J
AF Hardy, J
TI Progress in deciding a therapeutic approach to PSP
SO MOVEMENT DISORDERS
LA English
DT Meeting Abstract
CT 5th international Medical Workshop of the
   Progressive-Supranuclear-Palsy-Association
CY JUL 08, 2005
CL London, ENGLAND
SP Progressive Supranuclear Palsy Assoc
C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   NINDS, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
   UCL, Reta Lila Weston Inst Neurol Studies, London, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD MAR
PY 2006
VL 21
IS 3
BP 437
EP 438
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 027IS
UT WOS:000236409500043
ER

PT J
AU Roilides, E
   Lyman, CA
   Armstrong, D
   Stergiopoulou, T
   Petraitiene, R
   Walsh, TJ
AF Roilides, E
   Lyman, CA
   Armstrong, D
   Stergiopoulou, T
   Petraitiene, R
   Walsh, TJ
TI Deoxycholate amphotericin B and amphotericin B lipid complex exert
   additive antifungal activity in combination with pulmonary alveolar
   macrophages against Fusarium solani
SO MYCOSES
LA English
DT Article
DE Fusarium solani; pulmonary alveolar macrophages; amphotericin B
   formulations
ID ASPERGILLUS-FUMIGATUS; HUMAN NEUTROPHILS; POLYMORPHONUCLEAR LEUKOCYTES;
   ACTIVATION; INVITRO; PHAGOCYTES; SUSCEPTIBILITY; MONONUCLEAR; MONOCYTES;
   CYTOKINES
AB Fusarium spp. have emerged as important causes of invasive fungal infections in immunocompromised patients. Rabbit pulmonary alveolar macrophages (PAMs) exhibited fungicidal activity against conidia of Fusarium solani and achieved a time-dependent increase in killing. Neither deoxycholate amphotericin B (DAMB) nor amphotericin B lipid complex (ABLC) exerted a suppressive effect on PAMs by decreasing their conidiocidal activity against F. solani. On the contrary, at a concentration of 0.125 mu g ml(-1), ABLC and, to a lesser degree. DAMB additively augmented the fungicidal activity of pulmonary alveolar macrophages against conidia of Fusarium solani.
C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
   Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, GR-54006 Thessaloniki, Greece.
RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA.
EM walsht@mail.nih.gov
NR 32
TC 1
Z9 1
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0933-7407
J9 MYCOSES
JI Mycoses
PD MAR
PY 2006
VL 49
IS 2
BP 109
EP 113
DI 10.1111/j.1439-0507.2006.01202.x
PG 5
WC Dermatology; Mycology
SC Dermatology; Mycology
GA 018PX
UT WOS:000235778400007
PM 16466443
ER

PT J
AU Smith, FJD
   Irvine, AD
   Terron-Kwiatkowski, A
   Sandilands, A
   Campbell, LE
   Zhao, YW
   Liao, HH
   Evans, AT
   Goudie, DR
   Lewis-Jones, S
   Arseculeratne, G
   Munro, CS
   Sergeant, A
   O'Regan, G
   Bale, SJ
   Compton, JG
   DiGiovanna, JJ
   Presland, RB
   Fleckman, P
   McLean, WHI
AF Smith, FJD
   Irvine, AD
   Terron-Kwiatkowski, A
   Sandilands, A
   Campbell, LE
   Zhao, YW
   Liao, HH
   Evans, AT
   Goudie, DR
   Lewis-Jones, S
   Arseculeratne, G
   Munro, CS
   Sergeant, A
   O'Regan, G
   Bale, SJ
   Compton, JG
   DiGiovanna, JJ
   Presland, RB
   Fleckman, P
   McLean, WHI
TI Loss-of-function mutations in the gene encoding filaggrin cause
   ichthyosis vulgaris
SO NATURE GENETICS
LA English
DT Article
ID EPIDERMAL DIFFERENTIATION COMPLEX; N-TERMINAL DOMAIN; FLAKY TAIL;
   GENOMIC ORGANIZATION; LAMELLAR ICHTHYOSIS; HUMAN PROFILAGGRIN; SKIN;
   IDENTIFICATION; EXPRESSION; PROTEINS
AB Ichthyosis vulgaris (OMIM 146700) is the most common inherited disorder of keratinization and one of the most frequent single-gene disorders in humans. The most widely cited incidence figure is 1 in 250 based on a survey of 6,051 healthy English schoolchildren(1). We have identified homozygous or compound heterozygous mutations R501X and 2282del4 in the gene encoding filaggrin (FLG) as the cause of moderate or severe ichthyosis vulgaris in 15 kindreds. In addition, these mutations are semidominant; heterozygotes show a very mild phenotype with incomplete penetrance. The mutations show a combined allele frequency of similar to 4% in populations of European ancestry, explaining the high incidence of ichthyosis vulgaris. Profilaggrin is the major protein of keratohyalin granules in the epidermis. During terminal differentiation, it is cleaved into multiple filaggrin peptides that aggregate keratin filaments. The resultant matrix is cross-linked to form a major component of the cornified cell envelope. We find that loss or reduction of this major structural protein leads to varying degrees of impaired keratinization.
C1 Univ Dundee, Ninewells Hosp & Med Sch, Div Pathol & Neurosci, Human Genet Unit,Epithelial Genet Grp, Dundee DD1 9SY, Scotland.
   Univ Dundee, Ninewells Hosp & Med Sch, Tayside Univ Hosp NHS Trust, Dundee DD1 9SY, Scotland.
   Our Ladys Hosp Sick Children, Dept Paediat Dermatol, Dublin 12, Ireland.
   S Glasgow Univ Hosp NHS Trust, Dept Dermatol, Glasgow G51 4TF, Lanark, Scotland.
   Gene Dx, Gaithersburg, MD 20877 USA.
   Rhode Isl Hosp, Providence, RI 02903 USA.
   Brown Univ, Sch Med, Dept Dermatol, Div Dermatopharmacol, Providence, RI 02903 USA.
   NCI, Basic Res Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
   Univ Washington, Sch Dent, Seattle, WA 98195 USA.
   Univ Washington, Dept Med, Div Dermatol, Seattle, WA 98195 USA.
RP McLean, WHI (reprint author), Univ Dundee, Ninewells Hosp & Med Sch, Div Pathol & Neurosci, Human Genet Unit,Epithelial Genet Grp, Dundee DD1 9SY, Scotland.
EM w.h.i.mclean@dundee.ac.uk
RI McLean, William/C-6352-2009; 
OI Presland, Richard/0000-0003-1440-7402; Irvine, Alan/0000-0002-9048-2044;
   McLean, William Henry Irwin/0000-0001-5539-5757
FU Medical Research Council [G0700314]; Wellcome Trust
NR 30
TC 495
Z9 521
U1 7
U2 38
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD MAR
PY 2006
VL 38
IS 3
BP 337
EP 342
DI 10.1038/ng1743
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA 015ZG
UT WOS:000235589600016
PM 16444271
ER

PT J
AU Brenchley, JM
   Price, DA
   Douek, DC
AF Brenchley, JM
   Price, DA
   Douek, DC
TI HIV disease: fallout from a mucosal catastrophe?
SO NATURE IMMUNOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL DEPLETION; ACTIVE ANTIRETROVIRAL
   THERAPY; VERSUS-HOST-DISEASE; GASTROINTESTINAL-TRACT; TYPE-1 INFECTION;
   IMMUNE-RESPONSES; CD4 LYMPHOCYTES; LYMPHOID-TISSUE; SIV INFECTION
AB The pathogenesis of human immunodeficiency virus has long been thought to center on a gradual depletion of CD4(+) T cells, with an average of 100 cells lost per microliter of blood per year. However, studies of macaques infected with simian immunodeficiency virus and humans infected with human immunodeficiency virus have shown that the infection rapidly kills most CD4(+) T cells at mucosal surfaces. Although most CD4(+) T cells reside at these sites, the magnitude of this assault on the immune system is not reflected in the peripheral blood. Here we consider models of human immunodeficiency virus disease pathogenesis given those findings and propose a hypothesis to account for particular aspects of the disease during the chronic phase of infection that can be directly attributed to early depletion of mucosal CD4(+) T cells.
C1 NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Brenchley, JM (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
EM ddouek@nih.gov
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
FU Medical Research Council [G108/441]
NR 38
TC 347
Z9 365
U1 3
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
J9 NAT IMMUNOL
JI Nat. Immunol.
PD MAR
PY 2006
VL 7
IS 3
BP 235
EP 239
DI 10.1038/ni1316
PG 5
WC Immunology
SC Immunology
GA 012SR
UT WOS:000235360400007
PM 16482171
ER

PT J
AU Shin, EC
   Rehermann, B
AF Shin, EC
   Rehermann, B
TI Taking the brake off T cells in chronic viral infection
SO NATURE MEDICINE
LA English
DT Editorial Material
ID HIV-1 INFECTION; PD-1; BLOCKADE; IMMUNITY; CTLA-4; MICE
C1 NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Shin, EC (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
EM rehermann@nih.gov
RI Shin, Eui-Cheol/C-1690-2011
NR 14
TC 6
Z9 7
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD MAR
PY 2006
VL 12
IS 3
BP 276
EP 277
DI 10.1038/nm0306-276
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 018ZA
UT WOS:000235802900019
PM 16520769
ER

PT J
AU Grossman, Z
   Meier-Schellersheim, M
   Paul, WE
   Picker, LJ
AF Grossman, Z
   Meier-Schellersheim, M
   Paul, WE
   Picker, LJ
TI Pathogenesis of HIV infection: what the virus spares is as important as
   what it destroys
SO NATURE MEDICINE
LA English
DT Review
ID CD4(+) T-CELLS; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNE-SYSTEM ACTIVATION;
   AFRICAN-GREEN MONKEYS; NECROSIS-FACTOR-ALPHA; IN-VIVO ACTIVATION; TYPE-1
   INFECTION; SIV INFECTION; GASTROINTESTINAL-TRACT; MACROPHAGE ACTIVATION
AB Upon transmission to a new host, HIV targets CCR5(+)CD4(+) effector memory T cells, resulting in acute, massive depletion of these cells from mucosal effector sites. This depletion does not initially compromise the regenerative capacity of the immune system because naive and most central memory T cells are spared. Here, we discuss evidence suggesting that frequent activation of these spared cells during the chronic phase of HIV infection supplies mucosal tissues with short-lived CCR5(+)CD4(+) effector cells that prevent life-threatening infections. This immune activation also facilitates continued viral replication, but infection and killing of target T cells by HIV are selective and the impact on effector-cell lifespan is limited. We propose, however, that persistent activation progressively disrupts the functional organization of the immune system, reducing its regenerative capacity and facilitating viral evolution that leads to loss of the exquisite target cell-sparing selectivity of viral replication, ultimately resulting in AIDS.
C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
   Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel.
   Oregon Hlth & Sci Univ, Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA.
   Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA.
RP Grossman, Z (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
EM grossman@helix.nih.gov
RI Grossman, Zvi/A-9643-2008
FU Intramural NIH HHS; NIAID NIH HHS [AI054292]
NR 101
TC 262
Z9 282
U1 1
U2 27
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD MAR
PY 2006
VL 12
IS 3
BP 289
EP 295
DI 10.1038/nm1380
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 018ZA
UT WOS:000235802900025
PM 16520776
ER

PT J
AU Machado, FS
   Johndrow, JE
   Esper, L
   Dias, A
   Bafica, A
   Serhan, CN
   Aliberti, J
AF Machado, FS
   Johndrow, JE
   Esper, L
   Dias, A
   Bafica, A
   Serhan, CN
   Aliberti, J
TI Anti-inflammatory actions of lipoxin A(4) and aspirin-triggered lipoxin
   are SOCS-2 dependent
SO NATURE MEDICINE
LA English
DT Article
ID IL-12 PRODUCTION; NEUTROPHIL RECRUITMENT; INFLAMMATION; RECEPTOR;
   IMMUNOPATHOLOGY; TRAFFICKING; RESOLUTION; MEDIATORS; INFECTION; ANALOG
AB Control of inflammation is crucial to prevent damage to the host during infection. Lipoxins and aspirin-triggered lipoxins are crucial modulators of proinflammatory responses; however, their intracellular mechanisms have not been completely elucidated. We previously showed that lipoxin A(4) (LXA(4)) controls migration of dendritic cells (DCs) and production of interleukin (IL)-12 in vivo(1). In the absence of LXA(4) biosynthetic pathways, the resulting uncontrolled inflammation during infection is lethal, despite pathogen clearance(2). Here we show that lipoxins activate two receptors in DCs, AhR and LXAR, and that this activation triggers expression of suppressor of cytokine signaling (SOCS)-2. SOCS-2-deficient DCs are hyper-responsive to microbial stimuli, as well as refractory to the inhibitory actions of LXA(4), but not to IL-10. Upon infection with an intracellular pathogen, SOCS-2-deficient mice had uncontrolled production of proinflammatory cytokines, decreased microbial proliferation, aberrant leukocyte infiltration and elevated mortality. We also show that SOCS-2 is a crucial intracellular mediator of the anti-inflammatory actions of aspirin-induced lipoxins in vivo.
C1 Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27705 USA.
   NIAID, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA.
   Fred Hutchinson Canc Res Inst, Seattle, WA 98109 USA.
   Fd Osvaldo Cruz, Lab Imunorregulacao, BR-40295 Salvador, BA, Brazil.
   Harvard Univ, Brigham & Womens Hosp, Ctr Expt Therapeut, Boston, MA 02115 USA.
RP Aliberti, J (reprint author), Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27705 USA.
EM fabiana.machado@duke.edu; julio.aliberti@duke.edu
RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013
OI Aliberti, Julio/0000-0003-3420-8478
FU NIDCR NIH HHS [P50-DE0161912]; NIGMS NIH HHS [GM38765]
NR 23
TC 176
Z9 185
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD MAR
PY 2006
VL 12
IS 3
BP 330
EP 334
DI 10.1038/nm1355
PG 5
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 018ZA
UT WOS:000235802900033
PM 16415877
ER

PT J
AU Bosselut, R
AF Bosselut, R
TI Retroviral TCR gene transduction: 2A for two
SO NATURE METHODS
LA English
DT Editorial Material
ID RECEPTOR TRANSGENIC MICE; T-CELLS; POLYPROTEIN; SELECTION; CLEAVAGE
AB A recently developed multigene viral expression system is put to work to generate mice carrying a single T-cell receptor (TCR) specificity. Complementing the transgenic-mice technique, this method offers new practical options to researchers studying T-cell development.
C1 NCI, Ctr Canc Res, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
RP Bosselut, R (reprint author), NCI, Ctr Canc Res, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
EM remy@helix.nih.gov
NR 11
TC 2
Z9 2
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD MAR
PY 2006
VL 3
IS 3
BP 162
EP 164
DI 10.1038/nmeth0306-162
PG 3
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 017LT
UT WOS:000235695800010
PM 16489331
ER

PT J
AU Lorenz, H
   Hailey, DW
   Lippincott-Schwartz, J
AF Lorenz, H
   Hailey, DW
   Lippincott-Schwartz, J
TI Fluorescence protease protection of GFP chimeras to reveal protein
   topology and subcellular localization
SO NATURE METHODS
LA English
DT Article
ID DIGITONIN PERMEABILIZATION; TRANSMEMBRANE TOPOLOGY; MEMBRANE-PROTEINS;
   GLOBAL ANALYSIS; PRION DISEASES; LIVING CELLS; YEAST; TRANSLOCATION;
   ORGANIZATION; DEGRADATION
AB Understanding the cell biology of many proteins requires knowledge of their in vivo topological distribution. Here we describe a new fluorescence-based technique, fluorescence protease protection (FPP), for investigating the topology of proteins and for localizing protein subpopulations within the complex environment of the Living cell. In the FPP assay, adapted from biochemical protease protection assays, GFP fusion proteins are used as noninvasive tools to obtain details of protein topology and localization within Living cells in a rapid and straightforward manner. To demonstrate the broad applicability of FPP, we used the technique to define the topology of proteins localized to a wide range of organelles including the endoplasmic reticulum (ER), Golgi apparatus, mitochondria, peroxisomes and autophagosomes. The success of the FPP assay in characterizing the topology of the tested proteins within their appropriate compartments suggests this technique has wide applicability in studying protein topology and localization within the cell.
C1 Natl Inst Child Hlth & Human Dev, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Lippincott-Schwartz, J (reprint author), Natl Inst Child Hlth & Human Dev, Cell Biol & Metab Branch, NIH, Bldg 18T Lib Dr, Bethesda, MD 20892 USA.
EM jlippin@helix.nih.gov
FU Intramural NIH HHS
NR 32
TC 88
Z9 90
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD MAR
PY 2006
VL 3
IS 3
BP 205
EP 210
DI 10.1038/nmeth857
PG 6
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 017LT
UT WOS:000235695800017
PM 16489338
ER

PT J
AU Paton, JFR
   Abdala, APL
   Koizumi, H
   Smith, JC
   St John, WM
AF Paton, JFR
   Abdala, APL
   Koizumi, H
   Smith, JC
   St John, WM
TI Respiratory rhythm generation during gasping depends on persistent
   sodium current
SO NATURE NEUROSCIENCE
LA English
DT Article
ID PRE-BOTZINGER COMPLEX; PACEMAKER NEURONS; IN-VITRO; MODELS; PATTERNS;
   MAMMALS; EUPNEA
AB In severe hypoxia, homeostatic mechanisms maintain function of the brainstem respiratory network. We hypothesized that hypoxia involves a transition from neuronal mechanisms of normal breathing (eupnea) to a rudimentary pattern of inspiratory movements (gasping). We provide evidence for hypoxia-driven transformation within the central respiratory oscillator, in which gasping relies on persistent sodium current, whereas eupnea does not depend on this cellular mechanism.
C1 Univ Bristol, Sch Med Sci, Bristol Heart Inst, Dept Physiol, Bristol BS8 1TH, Avon, England.
   NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
   Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Physiol, Lebanon, NH 03756 USA.
RP Paton, JFR (reprint author), Univ Bristol, Sch Med Sci, Bristol Heart Inst, Dept Physiol, Bristol BS8 1TH, Avon, England.
EM Julian.F.R.Paton@Bristol.ac.uk
RI Abdala, Ana Paula/G-9104-2014; 
OI Abdala, Ana Paula/0000-0001-6051-2591; Paton, Julian/0000-0001-7410-2913
FU Intramural NIH HHS
NR 15
TC 134
Z9 134
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD MAR
PY 2006
VL 9
IS 3
BP 311
EP 313
DI 10.1038/nn1650
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA 016UI
UT WOS:000235645600009
PM 16474390
ER

PT J
AU Antoni, MH
   Lutgendorf, SK
   Cole, SW
   Dhabhar, FS
   Sephton, SE
   McDonald, PG
   Stefanek, M
   Sood, AK
AF Antoni, MH
   Lutgendorf, SK
   Cole, SW
   Dhabhar, FS
   Sephton, SE
   McDonald, PG
   Stefanek, M
   Sood, AK
TI Opinion - The influence of bio-behavioural factors on tumour biology:
   pathways and mechanisms
SO NATURE REVIEWS CANCER
LA English
DT Review
ID ENDOTHELIAL GROWTH-FACTOR; EPSTEIN-BARR-VIRUS; BETA-ADRENERGIC
   RECEPTORS; QUALITY-OF-LIFE; STRUCTURED PSYCHIATRIC INTERVENTION;
   METASTATIC COLORECTAL-CANCER; CERVICAL-CARCINOMA CELLS; BREAST-CANCER;
   HEPATITIS-B; HUMAN-PAPILLOMAVIRUS
AB Epidemiological studies indicate that stress, chronic depression and lack of social support might serve as risk factors for cancer development and progression. Recent cellular and molecular studies have identified biological processes that could potentially mediate such effects. This review integrates clinical, cellular and molecular studies to provide a mechanistic understanding of the interface between biological and behavioural influences in cancer, and identifies novel behavioural or pharmacological interventions that might help improve cancer outcomes.
C1 NCI, Basic & Biobehav Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA.
   Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA.
   Univ Miami, Dept Psychiat, Coral Gables, FL 33124 USA.
   Univ Miami, Dept Behav Sci, Coral Gables, FL 33124 USA.
   Univ Miami, Sylvestor Canc Ctr, Coral Gables, FL 33124 USA.
   Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA.
   Univ Iowa, Dept Obstet & Gynecol, Iowa City, IA 52242 USA.
   Univ Iowa, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA.
   Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Los Angeles, CA 90095 USA.
   Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Off 2325, Stanford, CA 94305 USA.
   Univ Louisville, Dept Psychol & Brain Sci, James Graham Brown Canc Ctr, Louisville, KY 40202 USA.
   Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Unit 1362, Houston, TX 77230 USA.
   Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Unit 1362, Houston, TX 77230 USA.
RP McDonald, PG (reprint author), NCI, Basic & Biobehav Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, 6130 Execut Blvd,MSC 7363, Bethesda, MD 20892 USA.
EM pm252v@nih.gov
FU NCI NIH HHS [R01 CA109298-01A1, P50 CA083639, P50 CA083639-02, R01
   CA109298, R01 CA110793, R01 CA110793-01]
NR 146
TC 389
Z9 404
U1 3
U2 43
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD MAR
PY 2006
VL 6
IS 3
BP 240
EP 248
DI 10.1038/nrc1820
PG 9
WC Oncology
SC Oncology
GA 016AC
UT WOS:000235591900018
PM 16498446
ER

PT J
AU Szakacs, G
   Paterson, JK
   Ludwig, JA
   Booth-Genthe, C
   Gottesman, MM
AF Szakacs, G
   Paterson, JK
   Ludwig, JA
   Booth-Genthe, C
   Gottesman, MM
TI Targeting multidrug resistance in cancer
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Review
ID ACUTE MYELOID-LEUKEMIA; ORGANIC ANION TRANSPORTER; MDR1 P-GLYCOPROTEIN;
   CELL LUNG-CANCER; MEDIATED DRUG-RESISTANCE; SOUTHWEST-ONCOLOGY-GROUP;
   BLOOD-BRAIN-BARRIER; PEGYLATED LIPOSOMAL DOXORUBICIN; BASOLATERAL
   HEPATOCYTE MEMBRANE; ATP-DEPENDENT TRANSPORTERS
AB Effective treatment of metastatic cancers usually requires the use of toxic chemotherapy. In most cases, multiple drugs are used, as resistance to single agents occurs almost universally. For this reason, elucidation of mechanisms that confer simultaneous resistance to different drugs with different targets and chemical structures-multidrug resistance-has been a major goal of cancer biologists during the past 35 years. Here, we review the most common of these mechanisms, one that relies on drug efflux from cancer cells mediated by ATP-binding cassette (ABC) transporters. We describe various approaches to combating multidrug-resistant cancer, including the development of drugs that engage, evade or exploit efflux by ABC transporters.
C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   Hungarian Acad Sci, Inst Enzymol, Biol Res Ctr, H-1518 Budapest, Hungary.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA.
EM MGottesman@nih.gov
RI Szakacs, Gergely/A-2580-2009; 木子, 瑞/N-8882-2015
OI Szakacs, Gergely/0000-0002-9311-7827; 
NR 263
TC 1646
Z9 1716
U1 53
U2 394
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD MAR
PY 2006
VL 5
IS 3
BP 219
EP 234
DI 10.1038/nrd1984
PG 16
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA 019LD
UT WOS:000235836300018
PM 16518375
ER

PT J
AU Jacobson, KA
   Gao, ZG
AF Jacobson, KA
   Gao, ZG
TI Adenosine receptors as therapeutic targets
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Review
ID AFFINITY ANTAGONIST RADIOLIGAND; SIGNAL-REGULATED KINASE-1/2;
   ISCHEMIA-REPERFUSION INJURY; MOUSE INTRAOCULAR-PRESSURE; ACTIVATED
   PROTEIN-KINASE; HUMAN-MELANOMA CELLS; SMOOTH-MUSCLE-CELLS; A(2A)
   RECEPTORS; A(3) RECEPTORS; A(1) RECEPTOR
AB Adenosine receptors are major targets of caffeine, the most commonly consumed drug in the world. There is growing evidence that they could also be promising therapeutic targets in a wide range of conditions, including cerebral and cardiac ischaemic diseases, sleep disorders, immune and inflammatory disorders and cancer. After more than three decades of medicinal chemistry research, a considerable number of selective agonists and antagonists of adenosine receptors have been discovered, and some have been clinically evaluated, although none has yet received regulatory approval. However, recent advances in the understanding of the roles of the various adenosine receptor subtypes, and in the development of selective and potent ligands, as discussed in this review, have brought the goal of therapeutic application of adenosine receptor modulators considerably closer.
C1 NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, 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 Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU Intramural NIH HHS [Z01 DK031117-20]
NR 209
TC 739
Z9 766
U1 13
U2 84
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD MAR
PY 2006
VL 5
IS 3
BP 247
EP 264
DI 10.1038/nrd1983
PG 18
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA 019LD
UT WOS:000235836300020
PM 16518376
ER

PT J
AU Ting, JPY
   Kastner, DL
   Hoffman, HM
AF Ting, JPY
   Kastner, DL
   Hoffman, HM
TI CATERPILLERs, pyrin and hereditary immunological disorders
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID FAMILIAL MEDITERRANEAN FEVER; CLASS-II TRANSACTIVATOR; NF-KAPPA-B;
   MHC-CLASS-II; BARE LYMPHOCYTE SYNDROME; COMPLEX CLASS-II; COLD
   AUTOINFLAMMATORY SYNDROME; MUCKLE-WELLS-SYNDROME; LEUCINE-RICH REPEATS;
   MULTISYSTEM INFLAMMATORY DISEASE
AB The newly described CATERPILLER family (also known as NOD-LRR or NACHT-LRR) is comprised of proteins with a nucleotide-binding domain and a leucine-rich region. This family has gained rapid prominence because of its demonstrated and anticipated roles in immunity, cell death and growth, and diseases. CATERPILLER proteins are structurally similar to a subgroup of plant-disease-resistance (R) proteins and to the apoptotic protease activating factor 1 (APAF1). They provide positive and negative signals for the control of immune and inflammatory responses, and might represent intracellular sensors of pathogen products. Most importantly, they are genetically linked to several human immunological disorders.
C1 Univ N Carolina, Dept Immunol Microbiol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
   NIH, Genet & Gen Branch NIAMS, Bethesda, MD 20892 USA.
   Univ Calif San Diego, Div Rheumatol Allergy & Immunol, La Jolla, CA 92093 USA.
   Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
RP Ting, JPY (reprint author), Univ N Carolina, Dept Immunol Microbiol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
EM panyun@med.unc.edu
RI Osborne, Nicholas/N-4915-2015
OI Osborne, Nicholas/0000-0002-6700-2284
NR 138
TC 213
Z9 224
U1 0
U2 3
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 MAR
PY 2006
VL 6
IS 3
BP 183
EP 195
DI 10.1038/nri1788
PG 13
WC Immunology
SC Immunology
GA 015ZY
UT WOS:000235591500011
PM 16498449
ER

PT J
AU Gilfillan, AM
   Tkaczyk, C
AF Gilfillan, AM
   Tkaczyk, C
TI Integrated signalling pathways for mast-cell activation
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID FC-EPSILON-RI; HIGH-AFFINITY RECEPTOR; NECROSIS-FACTOR-ALPHA; DEPENDENT
   CYTOKINE PRODUCTION; BRUTONS TYROSINE KINASE; C-KIT RECEPTOR;
   PROTEIN-KINASE; T-CELLS; IGE RECEPTOR; ANTIGEN RECEPTOR
AB Mast-cell activation mediated by the high-affinity receptor for IgE (Fc epsilon Rl) is considered to be a key event in the allergic inflammatory response. However, in a physiological setting, other receptors, such as KIT, might also markedly influence the release of mediators by mast cells. Recent studies have provided evidence that Fc epsilon Rl-dependent degranulation is regulated by two complementary signalling pathways, one of which activates phospholipase C. and the other of which activates phosphatidylinositol 3-kinase, using specific transmembrane and cytosolic adaptor molecules. In this Review, we discuss the evidence for these interacting pathways and describe how the capacity of KIT, and other receptors, to influence Fc epsilon Rl-dependent mast-cell-mediator release might be a function of the relative abilities of these receptors to activate these alternative pathways.
C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C206,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA.
EM agilfillan@niaid.nih.gov
FU Intramural NIH HHS
NR 125
TC 477
Z9 489
U1 5
U2 39
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 MAR
PY 2006
VL 6
IS 3
BP 218
EP 230
DI 10.1038/nri1782
PG 13
WC Immunology
SC Immunology
GA 015ZY
UT WOS:000235591500014
PM 16470226
ER

PT J
AU Haldar, D
   Kamakaka, RT
AF Haldar, D
   Kamakaka, RT
TI tRNA genes as chromatin barriers
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Editorial Material
ID FISSION YEAST CENTROMERE; SCHIZOSACCHAROMYCES-POMBE;
   SACCHAROMYCES-CEREVISIAE; HETEROCHROMATIN; INSULATORS; BOUNDARIES;
   EXPRESSION; SEQUENCE; ELEMENT; DOMAINS
AB Chromatin barriers restrict silenced chromatin domains from invading active domains. A recent study shows that a tRNA gene functions as a barrier in Schizosaccharomyces pombe. These results, similar to previous observations in Saccharomyces cerevisiae, point toward a novel function for tRNA genes and a common mechanism of compartmentalizing and organizing eukaryotic chromatin.
C1 NICHHD, Unit Chromatin & Transcript, US Natl Inst Hlth, Bethesda, MD 20892 USA.
   Univ Calif Santa Cruz, Dept MCD Biol, Santa Cruz, CA 95064 USA.
RP Haldar, D (reprint author), NICHHD, Unit Chromatin & Transcript, US Natl Inst Hlth, 18 Library Dr, Bethesda, MD 20892 USA.
EM rohinton@biology.ucsc.edu
NR 16
TC 12
Z9 12
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD MAR
PY 2006
VL 13
IS 3
BP 192
EP 193
DI 10.1038/nsmb0306-192
PG 3
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 018PI
UT WOS:000235776900008
PM 16518388
ER

PT J
AU Brown, DT
   Izard, T
   Misteli, T
AF Brown, DT
   Izard, T
   Misteli, T
TI Mapping the interaction surface of linker histone H1(0) with the
   nucleosome of native chromatin in vivo
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID DNA-BINDING SITES; GLOBULAR DOMAIN; CRYSTAL-STRUCTURE; GENE-EXPRESSION;
   H1; LOCATION; H5; PARTICLE; H-1; IDENTIFICATION
AB H1 linker histones stabilize the nucleosome, limit nucleosome mobility and facilitate the condensation of metazoan chromatin. Here, we have combined systematic mutagenesis, measurement of in vivo binding by photobleaching microscopy, and structural modeling to determine the binding geometry of the globular domain of the H1(0) linker histone variant within the nucleosome in unperturbed, native chromatin in vivo. We demonstrate the existence of two distinct DNA-binding sites within the globular domain that are formed by spatial clustering of multiple residues. The globular domain is positioned via interaction of one binding site with the major groove near the nucleosome dyad. The second site interacts with linker DNA adjacent to the nucleosome core. Multiple residues bind cooperatively to form a highly specific chromatosome structure that provides a mechanism by which individual domains of linker histones interact to facilitate chromatin condensation.
C1 Univ Mississippi, Med Ctr, Dept Biochem, Jackson, MS 39216 USA.
   St Jude Childrens Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA.
   NCI, NIH, Bethesda, MD 20892 USA.
RP Brown, DT (reprint author), Univ Mississippi, Med Ctr, Dept Biochem, Jackson, MS 39216 USA.
EM dbrown@biochem.umsmed.edu; misteli@mail.nih.gov
FU Intramural NIH HHS; NCI NIH HHS [Z01 BC010309-07]; NCRR NIH HHS [P20
   RR016476, RR016476]
NR 41
TC 108
Z9 110
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD MAR
PY 2006
VL 13
IS 3
BP 250
EP 255
DI 10.1038/nsmb1050
PG 6
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 018PI
UT WOS:000235776900016
PM 16462749
ER

PT J
AU Lee, S
   Tsai, YC
   Mattera, R
   Smith, WJ
   Kostelansky, MS
   Weissman, AM
   Bonifacino, JS
   Hurley, JH
AF Lee, S
   Tsai, YC
   Mattera, R
   Smith, WJ
   Kostelansky, MS
   Weissman, AM
   Bonifacino, JS
   Hurley, JH
TI Structural basis for ubiquitin recognition and autoubiquitination by
   Rabex-5
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID RECEPTOR DOWN-REGULATION; CUE DOMAIN; MEMBRANE-FUSION; RAB GTPASES;
   MOLECULAR REPLACEMENT; ENDOPLASMIC-RETICULUM; INTERACTING MOTIF; BINDING
   DOMAINS; PROTEIN; COMPLEX
AB Rabex-5 is an exchange factor for Rab5, a master regulator of endosomal trafficking. Rabex-5 binds monoubiquitin, undergoes covalent ubiquitination and contains an intrinsic ubiquitin ligase activity, all of which require an N-terminal A20 zinc finger followed immediately by a helix. The structure of the N-terminal portion of Rabex-5 bound to ubiquitin at 2.5-angstrom resolution shows that Rabex-5-ubiquitin interactions occur at two sites. The first site is a new type of ubiquitin-binding domain, an inverted ubiquitin-interacting motif, which binds with similar to 29-mu M affinity to the canonical IIe44 hydrophobic patch on ubiquitin. The second is a diaromatic patch on the A20 zinc finger, which binds with similar to 22-mu M affinity to a polar region centered on Asp58 of ubiquitin. The A20 zinc-finger diaromatic patch mediates ubiquitin-ligase activity by directly recruiting a ubiquitin-loaded ubiquitin-conjugating enzyme.
C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   NCI, Lab Prot Dynam & Signaling, NIH, Ft Detrick, MD 21702 USA.
   NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM hurley@helix.nih.gov
OI Bonifacino, Juan S./0000-0002-5673-6370; Tsai, Yien
   Che/0000-0001-9624-1092
FU Intramural NIH HHS; NIDDK NIH HHS [Z01 DK036118-12]
NR 49
TC 129
Z9 130
U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD MAR
PY 2006
VL 13
IS 3
BP 264
EP 271
DI 10.1038/nsmb1064
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 018PI
UT WOS:000235776900018
PM 16462746
ER

PT J
AU Tegeder, I
   Costigan, M
   Griffin, RS
   Abele, A
   Belfer, I
   Schmidt, H
   Ehnert, C
   Scholz, J
   Wu, T
   Allchorne, A
   Diatchenko, L
   Sama, S
   Atlas, SJ
   Fillingim, RB
   Maixner, W
   Geisslinger, G
   Max, MB
   Woolf, CJ
AF Tegeder, I
   Costigan, M
   Griffin, RS
   Abele, A
   Belfer, I
   Schmidt, H
   Ehnert, C
   Scholz, J
   Wu, T
   Allchorne, A
   Diatchenko, L
   Sama, S
   Atlas, SJ
   Fillingim, RB
   Maixner, W
   Geisslinger, G
   Max, MB
   Woolf, CJ
TI GTP-cyclohydrolase, the rate-limiting enzyme in tetrahydrobiopterin
   biosynthesis, regulates pain sensitivity and persistence
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 47th Spring Meeting of the
   Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
   -Toxikologie
CY APR 04-06, 2006
CL Mainz, GERMANY
SP Deutsch Gesell Expt & Klin Pharmakol & Toxikol
C1 Massachusetts Gen Hosp, Neural Plast Res Grp, Charlestown, MA USA.
   Harvard Univ, Sch Med, Charlestown, MA USA.
   Univ Frankfurt, Pharmazentrum Frankfurt, D-6000 Frankfurt, Germany.
   NIH, Neurogenet Lab, Rockville, MD USA.
   Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
   Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC USA.
   Univ Florida, Coll Dent, Gainesville, FL USA.
   Gainesville VA Med Ctr, Gainesville, FL USA.
   Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0028-1298
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD MAR
PY 2006
VL 372
SU 1
MA S2
BP 13
EP 13
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 037DL
UT WOS:000237126800003
ER

PT J
AU Reichel, V
   Miller, DS
   DiPasquale, K
   Fricker, G
AF Reichel, V
   Miller, DS
   DiPasquale, K
   Fricker, G
TI Texas red transport in rat and shark choroid plexus
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 47th Spring Meeting of the
   Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
   -Toxikologie
CY APR 04-06, 2006
CL Mainz, GERMANY
SP Deutsch Gesell Expt & Klin Pharmakol & Toxikol
C1 Univ Heidelberg, Inst Pharm & Mol Biotechnol, Heidelberg, Germany.
   Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
   Vassar Coll, Poughkeepsie, NY 12604 USA.
   Mt Desert Isl Biol Lab, Saslisbury Cove, ME USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0028-1298
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD MAR
PY 2006
VL 372
SU 1
MA 19
BP 18
EP 19
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 037DL
UT WOS:000237126800025
ER

PT J
AU Schonfelder, G
   Menendez, D
   Krysiak, O
   Inga, A
   Krysiak, B
   Resnick, MA
AF Schonfelder, G
   Menendez, D
   Krysiak, O
   Inga, A
   Krysiak, B
   Resnick, MA
TI A single nucleotide promoter polymorphism places the human VEGF-receptor
   1 (flt-1) in the p53 stress-response transcriptional network
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 47th Spring Meeting of the
   Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
   -Toxikologie
CY APR 04-06, 2006
CL Mainz, GERMANY
SP Deutsch Gesell Expt & Klin Pharmakol & Toxikol
C1 Charite Univ Med Berlin, Inst Clin Pharmacol & Toxicol, Berlin, Germany.
   NIEHS, Mol Genet Lab, Chromosome Stabil Sect, NIH, Res Triangle Pk, NC 27709 USA.
   IST, ABC, Natl Inst Canc Res, Lab Expt Oncol B, Genoa, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0028-1298
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD MAR
PY 2006
VL 372
SU 1
BP 116
EP 116
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 037DL
UT WOS:000237126800450
ER

PT J
AU Rummel, A
   Eichner, T
   Weil, T
   Sandhoff, K
   Proia, R
   Binz, T
   Bigalke, H
AF Rummel, A
   Eichner, T
   Weil, T
   Sandhoff, K
   Proia, R
   Binz, T
   Bigalke, H
TI Interaction with one ganglioside and one protein receptor mediates the
   neurotoxicity of botulinum neurotoxins
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 47th Spring Meeting of the
   Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
   -Toxikologie
CY APR 04-06, 2006
CL Mainz, GERMANY
SP Deutsch Gesell Expt & Klin Pharmakol & Toxikol
C1 Hannover Med Sch, Hannover, Germany.
   Merz Pharmaceut GmbH, Frankfurt, Germany.
   Kekule Inst, Bonn, Germany.
   NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0028-1298
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD MAR
PY 2006
VL 372
SU 1
BP 123
EP 124
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 037DL
UT WOS:000237126800480
ER

PT J
AU Nakahara, H
   Amari, SI
   Richmond, BJ
AF Nakahara, H
   Amari, SI
   Richmond, BJ
TI A comparison of descriptive models of a single spike train by
   information-geometric measure
SO NEURAL COMPUTATION
LA English
DT Article
ID CAT STRIATE CORTEX; NEURONAL RESPONSES; CORTICAL-NEURONS; VISUAL-CORTEX;
   PATTERNS; MOTOR; VARIABILITY; INTEGRATION; STATISTICS; SYNCHRONY
AB In examining spike trains, different models are used to describe their structure. The different models often seem quite similar, but because they are cast in different formalisms, it is often difficult to compare their predictions. Here we use the information-geometric measure, an orthogonal coordinate representation of point processes, to express different models of stochastic point processes in a common coordinate system. Within such a framework, it becomes straightforward to visualize higher-order correlations of different models and thereby assess the differences between models. We apply the information-geometric measure to compare two similar but not identical models of neuronal spike trains: the inhomogeneous Markov and the mixture of Poisson models. It is shown that they differ in the second- and higher-order interaction terms. In the mixture of Poisson model, the second- and higher-order interactions are of comparable magnitude within each order, whereas in the inhomogeneous Markov model, they have alternating signs over different orders. This provides guidance about what measurements would effectively separate the two models. As newer models are proposed, they also can be compared to these models using information geometry.
C1 RIKEN, Brain Sci Inst, Lab Math Neurosci, Wako, Saitama 3510198, Japan.
   NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Nakahara, H (reprint author), RIKEN, Brain Sci Inst, Lab Math Neurosci, Wako, Saitama 3510198, Japan.
EM hiro@brain.riken.jp; amari@brain.riken.go.jp; bjr@ln.nimh.nih.gov
RI Nakahara, Hiroyuki/N-5411-2015; Amari, Shun-ichi/A-5901-2016
OI Nakahara, Hiroyuki/0000-0001-6891-1175; 
NR 41
TC 11
Z9 11
U1 0
U2 2
PU M I T PRESS
PI CAMBRIDGE
PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA
SN 0899-7667
J9 NEURAL COMPUT
JI Neural Comput.
PD MAR
PY 2006
VL 18
IS 3
BP 545
EP 568
DI 10.1162/089976606775623289
PG 24
WC Computer Science, Artificial Intelligence
SC Computer Science
GA 014MU
UT WOS:000235485100003
PM 16483407
ER

PT J
AU Lerchner, A
   Ursta, C
   Hertz, J
   Ahmadi, M
   Ruffiot, P
   Enemark, S
AF Lerchner, A
   Ursta, C
   Hertz, J
   Ahmadi, M
   Ruffiot, P
   Enemark, S
TI Response variability in balanced cortical networks
SO NEURAL COMPUTATION
LA English
DT Article
ID SPIKING NEURONS; VISUAL-CORTEX; STRIATE CORTEX; MODEL; DYNAMICS; MONKEY;
   CAT; DISCHARGE; PATTERNS; DISCRIMINATION
AB We study the spike statistics of neurons in a network with dynamically balanced excitation and inhibition. Our model, intended to represent a generic cortical column, comprises randomly connected excitatory and inhibitory leaky integrate-and-fire neurons, driven by excitatory input from an external population. The high connectivity permits a mean field description in which synaptic currents can be treated as gaussian noise, the mean and autocorrelation function of which are calculated self-consistently from the firing statistics of single model neurons. Within this description, a wide range of Fano factors is possible. We find that the irregularity of spike trains is controlled mainly by the strength of the synapses relative to the difference between the firing threshold and the postfiring reset level of the membrane potential. For moderately strong synapses, we find spike statistics very similar to those observed in primary visual cortex.
C1 Tech Univ Denmark, Lyngby 2800, Denmark.
   Niels Bohr Inst, Copenhagen 2100 0, Denmark.
   Nordita, Copenhagen 2100 0, Denmark.
   Univ Grenoble 1, Grenoble, France.
RP Lerchner, A (reprint author), NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20893 USA.
EM LerchnerA@mail.nih.gov; cristina@nordita.dk; hertz@nordita.dk;
   ahmadi@nordita.dk; pruffiot@ujf-grenoble.fr; enemark@nbi.dk
NR 29
TC 20
Z9 20
U1 0
U2 3
PU M I T PRESS
PI CAMBRIDGE
PA 238 MAIN STREET, STE 500, CAMBRIDGE, MA 02142-1046 USA
SN 0899-7667
J9 NEURAL COMPUT
JI Neural Comput.
PD MAR
PY 2006
VL 18
IS 3
BP 634
EP 659
DI 10.1162/089976606775623261
PG 26
WC Computer Science, Artificial Intelligence
SC Computer Science
GA 014MU
UT WOS:000235485100007
PM 16483411
ER

PT J
AU Corleto, VD
   Severi, C
   Romano, G
   Tattoli, I
   Weber, HC
   Stridsberg, M
   Rindi, G
   Campanini, N
   Tomassoni, F
   Pagotto, U
   Coy, DH
   Jensen, RT
   Delle Fave, G
AF Corleto, VD
   Severi, C
   Romano, G
   Tattoli, I
   Weber, HC
   Stridsberg, M
   Rindi, G
   Campanini, N
   Tomassoni, F
   Pagotto, U
   Coy, DH
   Jensen, RT
   Delle Fave, G
TI Somatostatin receptor subtypes mediate contractility on human colonic
   smooth muscle cells
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Article
DE contraction; relaxation; smooth muscle cell; somatostatin receptor
ID GASTROINTESTINAL-TRACT; CHOLECYSTOKININ-OCTAPEPTIDE; INTESTINAL TRANSIT;
   DISTAL COLON; OCTREOTIDE; INHIBITION; MOTILITY; ANALOG; PATHOGENESIS;
   RELAXATION
AB This study demonstrates the expression of functional somatostatin receptor (sstr) subtypes in human circular and longitudinal colonic smooth muscle cells (SMC). Native somatostatin (SS) and sstr subtype-specific analogues were used to characterize the sstr subtypes present in both cell types by contraction/relaxation studies. Qualitative and quantitative mRNA analysis and immunohistochemistry of sstr subtypes were also carried out. sstr subtype 2 mRNA was expressed in circular SMC, and various levels of subtypes 1, 2 and 3 mRNA were expressed in longitudinal colonic SMC. Native SS and each subtype-specific analogue exerted a modest, but significant, contraction, although inhibition of carbachol-induced contraction (relaxation) was the main effect on SMC from both layers. CH-288, a sstr subtype 1-specific analogue, and octreotide, a sstr subtype 2-specific analogue, were the most effective relaxant analogues on longitudinal and circular SMC, respectively. sstr subtypes display a distinct expression pattern on human colonic SMC; on circular SMC, subtype 2 is the only sstr, whereas sstr subtypes 1, 2 and 3 are expressed on human SMC isolated from the longitudinal layer. The contractile effects of SS are mediated through sstr subtype 2 and sstr subtype 1 on circular and longitudinal human colonic SMC, respectively.
C1 Univ Roma La Sapienza, Dept Digest & Liver Dis, Sch Med 1, Rome, Italy.
   Univ Roma La Sapienza, Dept Digest & Liver Dis, Sch Med 2, Rome, Italy.
   Boston Univ, Sch Med, Boston, MA 02118 USA.
   Univ Uppsala Hosp, Dept Med Sci Clin Chem, Uppsala, Sweden.
   Univ Parma, Dept Pathol, I-43100 Parma, Italy.
   S Orsola M Malpighi Hosp, Dept Internal Med, Bologna, Italy.
   S Orsola M Malpighi Hosp, Ctr Appl Biomed Res, Bologna, Italy.
   Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA.
   NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA.
RP Corleto, VD (reprint author), Univ Roma La Sapienza, Dept Digest & Liver Dis, Sch Med 2, Sant Andrea Hosp, Via Grottarossa 1035-1037, I-00189 Rome, Italy.
EM corleto@bce.uniroma1.it
OI RINDI, Guido/0000-0003-2996-4404
NR 43
TC 15
Z9 16
U1 0
U2 1
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1350-1925
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD MAR
PY 2006
VL 18
IS 3
BP 217
EP 225
DI 10.1111/j.1365-2982.2005.00752.x
PG 9
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA 012WI
UT WOS:000235371200007
PM 16487413
ER

PT J
AU Combes, P
   Bonnet-Dupeyron, MN
   Gauthier-Barichard, F
   Schiffmann, R
   Bertini, E
   Rodriguez, D
   Armour, JAL
   Boespflug-Tanguy, O
   Vaurs-Barriere, C
AF Combes, P
   Bonnet-Dupeyron, MN
   Gauthier-Barichard, F
   Schiffmann, R
   Bertini, E
   Rodriguez, D
   Armour, JAL
   Boespflug-Tanguy, O
   Vaurs-Barriere, C
TI PLP1 and GPM6B intragenic copy number analysis by MAPH in 262 patients
   with hypomyelinating leukodystrophies: identification of one partial
   triplication and two partial deletions of PLP1
SO NEUROGENETICS
LA English
DT Article
DE PMD; PLP1; GPM6B; gene quantification; MAPH
ID PELIZAEUS-MERZBACHER-DISEASE; PROTEOLIPID PROTEIN GENE; MAJOR CAUSE;
   MENTAL-RETARDATION; DUPLICATIONS; MUTATIONS; OLIGODENDROCYTES;
   REARRANGEMENTS; HYBRIDIZATION; EXPRESSION
AB The proteolipid protein 1 (PLP1) gene is known to be mutated in the X-linked disorders of myelin formation Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2. The most commonly found PLP1 mutations are gene duplications (60-70%) and point mutations (20%). About 20% of patients with a PMD phenotype do not present identified PLP1 mutation, thus suggesting genetic heterogeneity and/or undetected PLP1 abnormalities. Except the recently described MLPA screening the seven exonic regions, the currently used techniques to quantify PLP1 gene copy number do not investigate small intragenic PLP1 rearrangements. Using the multiplex amplifiable probe hybridization (MAPH) technique, we looked simultaneously for intragenic rearrangements along the PLP1 gene (exonic and regulatory regions) and for rearrangements in the GPM6B candidate gene (a member of the proteolipid protein family). We tested 262 hypomyelinating patients: 56 PLP1 duplicated patients, 1 PLP1 triplicated patient, and 205 patients presenting a leukodystrophy of undetermined origin with brain MRI suggesting a defect in myelin formation. Our results show that MAPH is an alternative reliable technique for diagnosis of PLP1 gene copy number. It allows us (1) to demonstrate that all PLP1 duplications previously found encompass the whole gene, (2) to establish that copy number changes in GPM6B and intragenic duplications of PLP1 are very unlikely to be involved in the etiology of UHL, and (3) to identify one partial triplication and two partial deletions of PLP1 in patients presenting with a PMD phenotype.
C1 INSERM, U384, Fac Med, F-63000 Clermont Ferrand, France.
   NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA.
   IRCCS, Inst Sci, Osped Pediat Bambino Gesu, Dept Mol Med, Rome, Italy.
   Fac Pitie Salpetriere, INSERM, U546, F-75013 Paris, France.
   Univ Nottingham, Queens Med Ctr, Inst Genet, Nottingham NG7 2UH, England.
RP Boespflug-Tanguy, O (reprint author), INSERM, U384, Fac Med, Pl Henri Dunant, F-63000 Clermont Ferrand, France.
EM Odile.Boespflug@inserm.u-clermont1.fr
OI Bertini, Enrico/0000-0001-9276-4590
NR 32
TC 15
Z9 15
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 1364-6745
J9 NEUROGENETICS
JI Neurogenetics
PD MAR
PY 2006
VL 7
IS 1
BP 31
EP 37
DI 10.1007/s10048-005-0021-1
PG 7
WC Genetics & Heredity; Clinical Neurology
SC Genetics & Heredity; Neurosciences & Neurology
GA 018IU
UT WOS:000235758500005
PM 16416265
ER

PT J
AU Blair, KS
   Newman, C
   Mitchell, DGV
   Richell, RA
   Leonard, A
   Morton, J
   Blair, RJR
AF Blair, KS
   Newman, C
   Mitchell, DGV
   Richell, RA
   Leonard, A
   Morton, J
   Blair, RJR
TI Differentiating among prefrontal substrates in psychopathy:
   Neuropsychological test findings
SO NEUROPSYCHOLOGY
LA English
DT Article
DE psychopathy; orbitofrontal cortex (OFC); dorsolateral prefrontal cortex
   (DLPFC); anterior cingulate cortex (ACC)
ID ANTERIOR CINGULATE CORTEX; POSITRON-EMISSION-TOMOGRAPHY; BORDERLINE
   PERSONALITY-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; FRONTAL-LOBE
   DYSFUNCTION; ANTISOCIAL-BEHAVIOR; OBJECT ALTERNATION; HYPERACTIVITY
   DISORDER; CRIMINAL PSYCHOPATHS; PSYCHIATRIC-PATIENTS
AB Frontal lobe and consequent executive dysfunction have long been related to psychopathy. More recently, there have been suggestions that specific regions of frontal cortex, rather than all of frontal cortex, may be implicated in psychopathy. To examine this issue, the authors presented 25 individuals with psychopathy and 30 comparison individuals with measures preferentially indexing the orbitofrontal cortex (OFC; object alternation task), dorsolateral prefrontal cortex (DLPFC; spatial alternation task), and anterior cingulate cortex (ACC; number-Stroop reading and counting tasks). The individuals with psychopathy showed significant impairment on the measure preferentially sensitive to OFC functioning. In contrast, the 2 groups did not show impairment on the measures preferentially sensitive to the functioning of the DLPFC or ACC. These results are interpreted with reference to executive dysfunction accounts of the disorder.
C1 NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
   UCL, Inst Cognit Neurosci, London, England.
RP Blair, KS (reprint author), NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, NIH, 15K N Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA.
EM blairj@intra.nimh.nih.gov
NR 88
TC 64
Z9 66
U1 5
U2 22
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0894-4105
J9 NEUROPSYCHOLOGY
JI Neuropsychology
PD MAR
PY 2006
VL 20
IS 2
BP 153
EP 165
DI 10.1037/0894-4105.20.2.153
PG 13
WC Psychology, Clinical; Neurosciences; Psychology
SC Psychology; Neurosciences & Neurology
GA 031IW
UT WOS:000236699000003
PM 16594776
ER

PT J
AU Ishiguro, H
   Liu, QR
   Gong, JP
   Hall, FS
   Ujike, H
   Morales, M
   Sakurai, T
   Grumet, M
   Uhl, GR
AF Ishiguro, H
   Liu, QR
   Gong, JP
   Hall, FS
   Ujike, H
   Morales, M
   Sakurai, T
   Grumet, M
   Uhl, GR
TI NrCAM in addiction vulnerability: Positional cloning, drug-regulation,
   haplotype-specific expression, and altered drug reward in knockout mice
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE neuronal adhesion; gene regulation; addiction; association; morphine
ID SUBSTANCE-ABUSE VULNERABILITY; CELL-ADHESION MOLECULE; POPULATION-BASED
   SAMPLE; ALCOHOL DEPENDENCE; GENE-EXPRESSION; ENVIRONMENTAL-INFLUENCES;
   NEURITE OUTGROWTH; PLACE PREFERENCE; MOUSE-BRAIN; NR-CAM
AB Several lines of evidence support roles for the cell adhesion molecule NrCAM in addictions. Fine mapping within a chromosome 7 region that contains previously linked and associated genomic markers identifies NrCAM haplotypes that are associated with substance abuse vulnerabilities in four samples of abusers and controls. Differential display identifies NrCAM as a drug regulated gene. NrCAM is expressed in neurons linked to reward and memory. NrCAM displays haplotype-specific gene expression in human post-mortem brain samples. Knockout mice display reduced opiate- and stimulant-conditioned place preferences. These observations support NrCAM as a positionally cloned and drug-regulated gene whose variants are likely to change expression and alter substance abuse vulnerabilities in human addictions and animal models of drug reward.
C1 NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD 21224 USA.
   Okayama Univ, Sch Med, Dept Neuropsychiat, Okayama 700, Japan.
   NIDA, Cellular Neurosci Branch, IRP, Baltimore, MD 21224 USA.
   Mt Sinai Sch Med, Dept Neurobiol, New York, NY USA.
   Rutgers State Univ, Keck Ctr Collab Neurosci, Piscataway, NJ USA.
RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, IRP, NIH, Box 5180, Baltimore, MD 21224 USA.
EM guhl@intra.nida.nih.gov
RI Liu, Qing-Rong/A-3059-2012; Hall, Frank/C-3036-2013
OI Liu, Qing-Rong/0000-0001-8477-6452; Hall, Frank/0000-0002-0822-4063
FU NICHD NIH HHS [N01-HD-1-3138]
NR 49
TC 41
Z9 42
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAR
PY 2006
VL 31
IS 3
BP 572
EP 584
DI 10.1038/sj.npp.1300855
PG 13
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 023QP
UT WOS:000236141600010
PM 16123759
ER

PT J
AU Lotze, M
   Grodd, W
   Rodden, FA
   Gut, E
   Schonle, PW
   Kardatzki, B
   Cohen, LG
AF Lotze, M
   Grodd, W
   Rodden, FA
   Gut, E
   Schonle, PW
   Kardatzki, B
   Cohen, LG
TI Neuroimaging patterns associated with motor control in traumatic brain
   injury
SO NEUROREHABILITATION AND NEURAL REPAIR
LA English
DT Article
DE TBI; fMRI; primary motor cortex; outcome
ID HEAD-INJURY; STROKE; RECOVERY; FMRI; METABOLISM; ACTIVATION; MODERATE;
   ARM
AB Objective. To determine if patients with traumatic brain injury (TBI) and motor deficits show differences in functional activation maps during repetitive hand movements relative to healthy controls. Are there predictors for motor Outcome in the functional maps of these patients? Methods. In an exploratory.. cross-sectional study, functional magnetic resonance imaging (fMRI) was used to study the blood-oxygenation-level-dependent (BOLD) response in cortical motor areas of 34 patients suffering from moderate motor deficits after TBI as they performed unilateral fist-clenching motions. Twelve of these patients with unilateral motor deficits were studied 3 months after TBI and a 2nd time approximately 4 months later. Results. Compared to age-matched, healthy controls performing the same task, TB patients showed diminished fMRI-signal change in the primary sensorimotor cortex contralateral to the moving hand (cSM1), the contralateral dorsal premotor cortex, and bilaterally in the supplementary motor areas (SMAs). Clinical impairment and the magnitude of the fMRI-signal change in cSM1 and SMA were negatively correlated. Patients with poor and good motor recovery showed comparable motor impairment at baseline. Only patients who evolved to "poor clinical outcome's had decreased fMRI-signal change in the cSM1 during baseline. Conclusions. These observations raise the hypothesis that the magnitude of the fMRI-signal change in the cSM1 region could have prognostic value in the evaluation of patients with TBI.
C1 Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany.
   Univ Tubingen, Dept Neuroradiol, CNS, Sect MR, D-7400 Tubingen, Germany.
   Univ Konstanz, Kliniken Schmieder, Lurija Inst Rehabil Sci & Hlth Res, Allenbach, Germany.
   NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA.
RP Lotze, M (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Gartenstr 29, D-72074 Tubingen, Germany.
EM martin.lotze@uni-tuebingen.de
NR 27
TC 19
Z9 19
U1 1
U2 7
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1545-9683
J9 NEUROREHAB NEURAL RE
JI Neurorehabil. Neural Repair
PD MAR
PY 2006
VL 20
IS 1
BP 14
EP 23
DI 10.1177/1545968305282919
PG 10
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 011PG
UT WOS:000235280000003
PM 16467275
ER

PT J
AU Kong, L
   Saavedra, JE
   Buzard, GS
   Xu, X
   Hood, BL
   Conrads, TP
   Veenstra, TD
   Keefer, LK
AF Kong, L
   Saavedra, JE
   Buzard, GS
   Xu, X
   Hood, BL
   Conrads, TP
   Veenstra, TD
   Keefer, LK
TI Deamidation of peptides in aerobic nitric oxide solution by a
   nitrosative pathway
SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY
LA English
DT Article
DE nitric oxide; deamidation; amide nitrosation
ID PROTEIN DEAMIDATION; MOLECULAR CLOCKS; MACROPHAGES; ASPARAGINYL;
   RESIDUES; KINETICS; DAMAGE; DNA
AB Hydrolytic deamidation of asparagine (Asn) and glutarnine (Gln) residues to aspartate (Asp) and glutamate (Glu), respectively.. can have significant biological consequences. We hypothesize that a wholly different mechanism of deamidation might occur in the presence of aerobic nitric oxide (NO). Accordingly.. we examined the deamidating ability of aerobic NO toward three model peptides, 2,4-dinitrophenyl (DNP)-Pro-Gln-Gly, Lys-Trp-Asp-Asn-Gln, and Ser-Glu-Asn-Tyr-Pro-Ile-Val, incubating them with the NO-generating compound, Et2N[N(O)NO]Na (DEA/NO, 30-48 mM), in aerobic, pH 7.4, buffer at 37 degrees C. DNP-Pro-Glu-Gly was detected after 2 h, while LysTrp-Asp-Asp-Gln, Lys-Trp-Asp-Asn-Glu, and Ser-Glu-Asp-Tyr-Pi-o-Ile-Val were detected within 10 min, accumulating in apparent yields of up to similar to 10%. In the latter case, tyrosine nitration was also observed, producing the expected nitrotyrosine residue. DEA/NO solutions preincubated to exhaust the NO before the peptides were added did not induce detectable deamidation. The data demonstrate that aerobic NO exposures can lead to nitrosative deamidation of peptides, a pathway that differs from the established hydrolytic deamidation mechanism in several key respects: the by-products of the former are molecular nitrogen and an acid (HONO) while that of the latter is a base (NH3); the nitrosative path can in principle proceed in the absence of water molecules; Asn is much more easily deamidated than Gln in the hydrolytic pathway, while the two amino acid residues were deamidated to a similar extent by exposure to NO in the presence of oxygen. (c) 2005 Elsevier Inc. All rights reserved.
C1 NCI, Chem Sect, Lab Comparat Carcinogeneis, Frederick, MD 21702 USA.
   NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
   NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Keefer, LK (reprint author), NCI, Chem Sect, Lab Comparat Carcinogeneis, Frederick, MD 21702 USA.
EM keefer@ncifcrf.gov
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]
NR 22
TC 4
Z9 4
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 1089-8603
J9 NITRIC OXIDE-BIOL CH
JI Nitric Oxide-Biol. Chem.
PD MAR
PY 2006
VL 14
IS 2
SI SI
BP 144
EP 151
DI 10.1016/j.niox.2005.09.003
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 014HE
UT WOS:000235469500008
PM 16249103
ER

PT J
AU Anderson, LM
   Riffle, L
   Wilson, R
   Travlos, GS
   Lubomirski, MS
   Alvord, WG
AF Anderson, LM
   Riffle, L
   Wilson, R
   Travlos, GS
   Lubomirski, MS
   Alvord, WG
TI Preconceptional fasting of fathers alters serum glucose in offspring of
   mice
SO NUTRITION
LA English
DT Article
DE paternal fasting; offspring; glucose; corticosterone; insulin-like
   growth factor-1
ID METABOLIC SYNDROME; RATS
AB Objective: Maternal nutrition has long-term effects on offspring characteristics. Similar effects mediated through fathers have not been tested.
   Methods: Outbred Swiss male mice were fasted one or six times 1 to 4 wk before mating. Offspring were killed at age intervals of 4 to 10 wk and their sera were analyzed for glucose, corticosterone, and insulin-like growth factor-1. Statistical linear mixed effects models were used to determine treatment (paternal diet restriction versus control) differences and possible effects of covariates, including sex, litter membership, and litter size.
   Results: Paternal food deprivation resulted in a consistent decrease in average serum glucose in male and female offspring. Significant changes in corticosterone and insulin-like growth factor-1 were found for some groups. The results indicated a male-mediated transgenerational effect on metabolism- and growth-related parameters, in particular glucose.
   Conclusions: Effects of paternal nutritional experiences on offspring metabolism, if confirmed, would be novel and could have far-reaching implications in the context of transgenerational effects on chronic diseases. (c) 2006 Elsevier Inc. All rights reserved.
C1 NCI, Lab Comparat Carcinogenesis, Frederick, MD 21701 USA.
   SAIC Frederick, Frederick, MD USA.
   NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA.
   Data Management Inc, Frederick, MD USA.
RP Anderson, LM (reprint author), NCI, Lab Comparat Carcinogenesis, Frederick, MD 21701 USA.
EM anderso1@mail.ncifcrf.gov
NR 22
TC 75
Z9 78
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0899-9007
J9 NUTRITION
JI Nutrition
PD MAR
PY 2006
VL 22
IS 3
BP 327
EP 331
DI 10.1016/j.nut.2005.09.006
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 020GZ
UT WOS:000235898000015
PM 16500559
ER

PT J
AU Kolotkin, RL
   Zeller, M
   Modi, AC
   Samsa, GP
   Quinlan, NP
   Yanovski, JA
   Bell, SK
   Maahs, DM
   de Serna, DG
   Roehrig, HR
AF Kolotkin, Ronette L.
   Zeller, Meg
   Modi, Avani C.
   Samsa, Gregory P.
   Quinlan, Nicole Polanichka
   Yanovski, Jack A.
   Bell, Stephen K.
   Maahs, David M.
   de Serna, Daniela Gonzales
   Roehrig, Helmut R.
TI Assessing weight-related quality of life in adolescents
SO OBESITY
LA English
DT Article
DE health-related quality of life; Impact of Weight on Quality of
   Life-Kids; weight loss; pediatric; adolescent
ID GASTRIC BYPASS-SURGERY; OVERWEIGHT CHILDREN; CHRONIC ILLNESS; OBESE
   CHILDREN; HEALTH-STATUS; US CHILDREN; COMMUNITY SAMPLE; IMPACT;
   QUESTIONNAIRE; PREVALENCE
AB Objective: The development of a new weight-related measure to assess quality of life in adolescents [impact of Weight oil Quality of Life (IWQOL)-Kids] is described.
   Research Methods and Procedures: Using a literature search, clinical experience. and consultation with pediatric clinicians, 73 items were developed. pilot tested, and administered to 642 participants. I I to 19 years old, recruited from weight loss programs/studies and community samples (mean z-BMI, 1.5; range, - 1.2 to 3.4; mean age, 14.0; 60% female; 56% white). Participants completed the 73 items and the Pediatric Quality of Life Inventory and were weighed and measured.
   Results: Four factors (27 items) were identified (physical comfort. body esteem, social life, and family relations), accounting for 71% of the variance. The IWQOL-Kids demonstrated excellent psychometric properties. Internal consistency coefficients ranged from 0.88 to 0.95 for scales and equaled 0.96 for total score. Convergent validity was demonstrated with strong correlations between IWQOL-Kids total score and the Pediatric Quality of Life Inventory (r=0.76, p < 0.0001). Significant differences were found across BMI groups and between clinical and community samples, supporting the sensitivity of this measure. Participant in a weight loss camp demonstrated improved IWQOL-Kids scores, suggesting responsiveness of the IWQOL-Kids to weight loss/social support intervention.
   Discussion: The present study provides preliminary evidence regarding the psychometric properties of the IWQOL-Kids, a weight-related quality of life measure for adolescents. Given the rise of obesity ill youth, the development of a reliable and valid weight-related measure of quality of life is timely.
C1 Obes & Qual Life Consulting, Durham, NC 27707 USA.
   Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA.
   Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
   Duke Univ, Med Ctr, Ctr Clin Hlth Policy Res, Durham, NC 27710 USA.
   Univ Cincinnati, Coll Med, Div Psychol, Cincinnati, OH USA.
   Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
   Duke Univ, Dept Psychol Social & Hlth Sci, Durham, NC USA.
   NICHHD, Unit Growth & Obes, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   Childrens Syst Childrens Behav Hlth, Birmingham, AL USA.
   Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Diabet, Denver, CO USA.
   Univ New Mexico Hosp, Dept Internal Med, Albuquerque, NM USA.
RP Kolotkin, RL (reprint author), Obes & Qual Life Consulting, 1004 Norwood Ave, Durham, NC 27707 USA.
EM rkolotkin@qualityoflifeconsulting.com
FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NCRR NIH HHS [M01
   RR000997, M01-RR00997]; NICHD NIH HHS [Z01 HD000641, HD00641]; NIDDK NIH
   HHS [DK600301]
NR 79
TC 89
Z9 91
U1 1
U2 12
PU NORTH AMER ASSOC STUDY OBESITY
PI SILVER SPRING
PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA
SN 1930-7381
J9 OBESITY
JI Obesity
PD MAR
PY 2006
VL 14
IS 3
BP 448
EP 457
DI 10.1038/oby.2006.59
PG 10
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 226DG
UT WOS:000250566800015
PM 16648616
ER

PT J
AU Payson, M
   Leppert, P
   Segars, J
AF Payson, M
   Leppert, P
   Segars, J
TI Epidemiology of myomas
SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
ID BLACK WOMENS HEALTH; UTERINE LEIOMYOMA; RISK-FACTORS; CELL-CANCER;
   FIBROIDS; HISTORY; AGE; PREVALENCE; MYOMECTOMY; MANAGEMENT
AB About one in four American women experience symptoms from fibroids in their lifetime. Half of American women have ultrasound evidence of fibroids by the time of menopause. The prevalence of fibroid disease varies by race and geography. Fibroids are associated with hypertension and factors that cause Uterine irritation, Such as infection. There may be different types of fibroid disease.
C1 NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA.
   Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
RP Segars, J (reprint author), NICHD, Reprod Biol & Med Branch, NIH, Bldg 10,CRC,1E-3140,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 34
TC 54
Z9 58
U1 1
U2 9
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399 USA
SN 0889-8545
J9 OBSTET GYN CLIN N AM
JI Obstet. Gynecol. Clin. N. Am.
PD MAR
PY 2006
VL 33
IS 1
BP 1
EP +
DI 10.1016/j.ogc.2005.12.004
PG 12
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 028QB
UT WOS:000236501800003
PM 16504803
ER

PT J
AU He, YY
   Huang, JL
   Chignell, CF
AF He, YY
   Huang, JL
   Chignell, CF
TI Cleavage of epidermal growth factor receptor by caspase during apoptosis
   is independent of its internalization
SO ONCOGENE
LA English
DT Article
DE EGFR; caspase; apoptosis; internalization
ID DOWN-REGULATION; HUMAN KERATINOCYTES; KINASE-ACTIVITY; CELL-DEATH;
   ACTIVATION; CANCER; UVA; CHOLESTEROL
AB Epidermal growth factor receptor ( EGFR) plays a critical role in cell proliferation, differentiation, and transformation. EGFR downregulation attenuates its signaling intensity and duration to maintain cellular homeostasis. Here, we report that during apoptosis EGFR is cleaved by activated caspase-3 or related proteases at its C-terminus domain. EGFR downregulation by activation of caspases is neither stimulus- nor cell type-specific. EGFR internalization during apoptosis required dynamin and cholesterol since dominant-negative dynamin (K44A) or cholesterol depletion by methyl-beta-cyclodextrin prevented EGFR internalization. However, EGFR downregulation did not require its internalization. The EGFR cleavage fragment was detected in the membrane blebs in addition to the cell pellets. Mutations at the consensus sequence (DXXD) at the C-terminus domain revealed that DVVD1012 and to a lesser extent DNPD1172 may be target sites for active recombinant caspase-3 in vitro and activated caspase-3 or related proteases in vivo. We have detected the N-terminus and C-terminus fragments in vitro and in vivo. A cleavage-deficient EGFR mutant delayed apoptosis process. We conclude that the evolutionarily conserved C-terminus domain of EGFR is the target of caspases and subjected to degradation during apoptosis to shut down its signaling.
C1 NIEHS, Chem Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP He, YY (reprint author), NIEHS, Chem Pharmacol Lab, NIH, MD F0-06,111 Alexander Dr,PO 12233, Res Triangle Pk, NC 27709 USA.
EM he3@niehs.nih.gov
FU Intramural NIH HHS
NR 29
TC 29
Z9 30
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR
PY 2006
VL 25
IS 10
BP 1521
EP 1531
DI 10.1038/sj.onc.1209184
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 020EE
UT WOS:000235890400009
PM 16247443
ER

PT J
AU Tang, S
   Tao, M
   McCoy, J
   Zheng, ZM
AF Tang, S
   Tao, M
   McCoy, J
   Zheng, ZM
TI Short-term induction and long-term suppression of HPV16 oncogene
   silencing by RNA interference in cervical cancer cells
SO ONCOGENE
LA English
DT Article
DE HPV16; E6; E7; oncogene; siRNA; cervical cancer
ID HUMAN-PAPILLOMAVIRUS TYPE-16; MAMMALIAN-CELLS; VIRAL SUPPRESSOR;
   GENE-EXPRESSION; CARCINOMA CELLS; ENZYME COMPLEX; MESSENGER-RNA; HUMAN
   DICER; IN-VITRO; E6
AB RNA interference-mediated gene silencing has the potential to block gene expression. A synthetic double-stranded small interfering RNA (siRNA) based on a sequence motif of 21 nucleotides from human papillomavirus 16 (HPV16) E6E7 bicistronic RNA was found to be a potent siRNA that suppresses expression of both the E6 and E7 oncogenes in HPV16(+) CaSki and SiHa cells. When stably expressed as a short hairpin RNA in these cells, however, siRNA silencing of E6 and E7 expression was efficient only at early cell passages, but became inefficient with increased cell passages despite the continued expression of the siRNA at the same level. The loss of the siRNA function was duplicable in stable p53 siRNA cells, but not in stable lamin A/C siRNA cells, suggesting that it is gene selective. The cells resistant to siRNA function retained normal siRNA processing, duplex unwinding and degradation of the unwound sense strand and RNA-induced silencing complex formation, suggesting that loss of the siRNA function occurred at a later step. Surprisingly, the siRNA-resistant cells were found to express notably a cytoplasmic protein of similar to 50 kDa that specifically and characteristically interacted with the unwound, antisense strand E7 siRNA. Altogether, our data indicate that a potent siRNA targeting to an essential or regulatory gene might induce a cell to develop siRNA-suppressive function.
C1 NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD USA.
RP Zheng, ZM (reprint author), NCI, HIV & AIDS Malignancy Branch, Ctr Canc Res, NIH, Bldg 10,Room10S255,MSC 1868,10 Ctr Dr, Bethesda, MD 20892 USA.
EM zhengt@exchange.nih.gov
RI Tang, Shuang/F-9115-2014
OI Tang, Shuang/0000-0002-3084-0903
FU Intramural NIH HHS; NCI NIH HHS [Z01 SC010357-06]
NR 51
TC 37
Z9 39
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR
PY 2006
VL 25
IS 14
BP 2094
EP 2104
DI 10.1038/sj.onc.1209244
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 026RL
UT WOS:000236359700012
PM 16369495
ER

PT J
AU Spillare, EA
   Wang, XW
   von Kobbe, C
   Bohr, VA
   Hickson, ID
   Harris, CC
AF Spillare, EA
   Wang, XW
   von Kobbe, C
   Bohr, VA
   Hickson, ID
   Harris, CC
TI Redundancy of DNA helicases in p53-mediated apoptosis
SO ONCOGENE
LA English
DT Article
DE helicases; apoptosis; microinjection
ID BLOOMS-SYNDROME PROTEIN; WERNERS-SYNDROME GENES;
   SACCHAROMYCES-CEREVISIAE; GENOMIC INSTABILITY; XERODERMA-PIGMENTOSUM;
   HOMOLOGOUS RECOMBINATION; FUNCTIONAL INTERACTION; RECQ HELICASES;
   SYNDROME CELLS; SGS1 MUTANT
AB A subset of DNA helicases, the RecQ family, has been found to be associated with the p53-mediated apoptotic pathway and is involved in maintaining genomic integrity. This family contains the BLM and WRN helicases, in which germline mutations are responsible for Bloom and Werner syndromes, respectively. TFIIH DNA helicases, XPB and XPD, are also components in this apoptotic pathway. We hypothesized that there may be some redundancy between helicases in their ability to complement the attenuated p53-mediated apoptotic levels seen in cells from individuals with diseases associated with these defective helicase genes. The attenuated apoptotic phenotype in Bloom syndrome cells was rescued not only by ectopic expression of BLM, but also by WRN or XPB, both 30-50 helicases, but not expression of the 50-30 helicase XPD. Overexpression of Sgs1, a WRN/BLM yeast homolog, corrected the reduction in BS cells only, which is consistent with Sgs1 being evolutionarily most homologous to BLM. A restoration of apoptotic levels in cells from WS, XPB or XPD patients was attained only by overexpression of the specific helicase. Our data suggest a limited redundancy in the pathways of these RecQ helicases in p53-induced apoptosis.
C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
   NIA, Lab Mol Gerontol, DHHS, NIH, Baltimore, MD USA.
   Univ Oxford, John Radcliffe Hosp, Canc Res UK, Weatherall Inst Mol Med, Oxford, England.
RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, 37 Convent Dr,Bldg 37,Room 3068, Bethesda, MD 20892 USA.
EM curtis_harris@nih.gov
RI Wang, Xin/B-6162-2009
FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005795-11]
NR 40
TC 20
Z9 20
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAR
PY 2006
VL 25
IS 14
BP 2119
EP 2123
DI 10.1038/sj.onc.1209242
PG 5
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 026RL
UT WOS:000236359700015
PM 16288211
ER

PT J
AU Carroll, E
   Blacklock-Schuver, B
AF Carroll, E
   Blacklock-Schuver, B
TI A video is worth a thousand words.
SO ONCOLOGY NURSING FORUM
LA English
DT Meeting Abstract
C1 NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ONCOLOGY NURSING SOCIETY
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD MAR
PY 2006
VL 33
IS 2
MA 3
BP 394
EP 395
PG 2
WC Oncology; Nursing
SC Oncology; Nursing
GA 031II
UT WOS:000236697600025
ER

PT J
AU Castro, K
   Babb, R
AF Castro, K
   Babb, R
TI Implementing a phase I trial at a clinical research center: Defining
   oncology nursing roles.
SO ONCOLOGY NURSING FORUM
LA English
DT Meeting Abstract
C1 NIH, AOCN, Ctr Clin, Bethesda, MD 20892 USA.
   NCI, OCN, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ONCOLOGY NURSING SOCIETY
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD MAR
PY 2006
VL 33
IS 2
MA 60
BP 411
EP 411
PG 1
WC Oncology; Nursing
SC Oncology; Nursing
GA 031II
UT WOS:000236697600082
ER

PT J
AU Muehlbauer, P
   Castro, K
   Shelburne, N
   Cusack, G
   Phelps, S
   Woolery, M
AF Muehlbauer, P
   Castro, K
   Shelburne, N
   Cusack, G
   Phelps, S
   Woolery, M
TI Novice to expert: Guiding new oncology nurses on the journey
SO ONCOLOGY NURSING FORUM
LA English
DT Meeting Abstract
C1 NIH, OCN, Bethesda, MD 20892 USA.
   NIH, AOCN, Bethesda, MD 20892 USA.
   NIH, CPON, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ONCOLOGY NURSING SOCIETY
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD MAR
PY 2006
VL 33
IS 2
MA 77
BP 416
EP 416
PG 1
WC Oncology; Nursing
SC Oncology; Nursing
GA 031II
UT WOS:000236697600099
ER

PT J
AU Calzone, K
   Jenkins, J
   Badzek, L
   Constantin, C
   Debisette, A
   Feetham, S
   Geolot, D
   Hagan, P
   Hess, M
   Lea, D
   Lewis, J
   Nesseler, K
   Potempa, K
   Prows, C
   Thomson, E
   Tinkle, M
   Williams, J
AF Calzone, K
   Jenkins, J
   Badzek, L
   Constantin, C
   Debisette, A
   Feetham, S
   Geolot, D
   Hagan, P
   Hess, M
   Lea, D
   Lewis, J
   Nesseler, K
   Potempa, K
   Prows, C
   Thomson, E
   Tinkle, M
   Williams, J
TI Establishing essential nursing competencies and curricula guidelines for
   genetics and genomics.
SO ONCOLOGY NURSING FORUM
LA English
DT Meeting Abstract
C1 NCI, CCR, Genet Branch, Bethesda, MD 20892 USA.
   NHGRI, Bethesda, MD 20892 USA.
   Amer Nurses Assoc, Silver Spring, MD USA.
   Ctr Dis Control & Prevent, Atlanta, GA USA.
   US Hlth Resources & Serv Adm, Rockville, MD 20857 USA.
   Virginia Commonwealth Univ, Richmond, VA USA.
   Oregon Hlth & Sci Univ, Portland, OR USA.
   Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
   NINR, Bethesda, MD 20892 USA.
   Univ Iowa, Iowa City, IA USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU ONCOLOGY NURSING SOCIETY
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD MAR
PY 2006
VL 33
IS 2
MA 88
BP 419
EP 419
PG 1
WC Oncology; Nursing
SC Oncology; Nursing
GA 031II
UT WOS:000236697600110
ER

PT J
AU Marin, K
   Loving, N
   Muehlbauer, P
AF Marin, K
   Loving, N
   Muehlbauer, P
TI Nursing care and management of patients receiving intraperitoneal
   chemotherapy.
SO ONCOLOGY NURSING FORUM
LA English
DT Meeting Abstract
C1 NIH, OCN, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ONCOLOGY NURSING SOCIETY
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD MAR
PY 2006
VL 33
IS 2
MA 145
BP 435
EP 436
PG 2
WC Oncology; Nursing
SC Oncology; Nursing
GA 031II
UT WOS:000236697600167
ER

PT J
AU Cusack, G
   Decarvalho, M
   Al Khateib, A
   Aleco, M
AF Cusack, G
   Decarvalho, M
   Al Khateib, A
   Aleco, M
TI National Cancer Institute forms partnership with hospital in Amman
   Jordan to establish premiere cancer center in Middle East
SO ONCOLOGY NURSING FORUM
LA English
DT Meeting Abstract
C1 NIH, DHHS, AOCN, Bethesda, MD 20892 USA.
   Genentech Inc, AOCN, San Francisco, CA 94080 USA.
   King Hussein Canc Ctr, Amman, Jordan.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ONCOLOGY NURSING SOCIETY
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD MAR
PY 2006
VL 33
IS 2
MA 185
BP 447
EP 447
PG 1
WC Oncology; Nursing
SC Oncology; Nursing
GA 031II
UT WOS:000236697600207
ER

PT J
AU Steakley, C
   Ness, E
   Bennett, LM
   Roland, G
AF Steakley, C
   Ness, E
   Bennett, LM
   Roland, G
TI Patient Navigator Academy
SO ONCOLOGY NURSING FORUM
LA English
DT Meeting Abstract
C1 NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ONCOLOGY NURSING SOCIETY
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD MAR
PY 2006
VL 33
IS 2
MA 186
BP 447
EP 447
PG 1
WC Oncology; Nursing
SC Oncology; Nursing
GA 031II
UT WOS:000236697600208
ER

PT J
AU Krebs, L
   Burhansstipanov, L
   Gamito, E
   Bradley, A
AF Krebs, L
   Burhansstipanov, L
   Gamito, E
   Bradley, A
TI Enhancing clinical trials education following evaluation of ongoing
   programs.
SO ONCOLOGY NURSING FORUM
LA English
DT Meeting Abstract
C1 Univ Colorado, Sch Nursing, AOCN, Denver, CO 80202 USA.
   Native Amer Canc Res, Pine, CO USA.
   Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
   NCI, Canc Informat Serv, Colorado Springs, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ONCOLOGY NURSING SOCIETY
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD MAR
PY 2006
VL 33
IS 2
MA 222
BP 457
EP 457
PG 1
WC Oncology; Nursing
SC Oncology; Nursing
GA 031II
UT WOS:000236697600244
ER

PT J
AU Knobf, MT
   Fennie, K
   Avila, D
   Woodward, P
   Thompson, AS
   Diepietro, L
AF Knobf, MT
   Fennie, K
   Avila, D
   Woodward, P
   Thompson, AS
   Diepietro, L
TI The effect of an exercise intervention on QOL and symptoms in breast
   cancer survivors.
SO ONCOLOGY NURSING FORUM
LA English
DT Meeting Abstract
C1 Yale Univ, Sch Nursing, AOCN, New Haven, CT 06536 USA.
   NIH, Bethesda, MD 20892 USA.
   Yale New Haven Med Ctr, New Haven, CT 06504 USA.
   Yale Univ, Sch Med, New Haven, CT USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU ONCOLOGY NURSING SOCIETY
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD MAR
PY 2006
VL 33
IS 2
MA 243
BP 463
EP 463
PG 1
WC Oncology; Nursing
SC Oncology; Nursing
GA 031II
UT WOS:000236697600265
ER

PT J
AU Tanner, E
AF Tanner, E
TI Lions and tigers and tracheostomies, oh my!!!
SO ONCOLOGY NURSING FORUM
LA English
DT Meeting Abstract
C1 NIH, OCN, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ONCOLOGY NURSING SOCIETY
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD MAR
PY 2006
VL 33
IS 2
MA 314
BP 483
EP 483
PG 1
WC Oncology; Nursing
SC Oncology; Nursing
GA 031II
UT WOS:000236697600336
ER

PT J
AU Singh, AS
   MacPherson, GR
   Price, DK
   Schimel, D
   Figg, WD
AF Singh, AS
   MacPherson, GR
   Price, DK
   Schimel, D
   Figg, WD
TI Evaluation of human fetal bone implants in SCID mice as a model of
   prostate cancer bone metastasis
SO ONCOLOGY REPORTS
LA English
DT Article
DE prostate; cancer; metastasis; bone; imaging; luminescence; PC3
ID ZOLEDRONIC ACID; ANIMAL-MODEL; CARCINOMA; MITOXANTRONE; PREDNISONE;
   MECHANISMS; DOCETAXEL; DISEASE; MOUSE; CELLS
AB The metastasis of prostate cancer cells to the bone marrow constitutes the major source of morbidity and mortality in prostate cancer. Studying this process has been hampered by the lack of preclinical models to evaluate novel therapeutics and to study the biology of the disease. One proposed model utilizes human fetal bone implants to serve as the target for prostate cancer cells injected via the tail vein. We employed this model to test the ability of zoledronic acid to prophylax and to treat bone metastases. To improve the rate of bone metastasis, we used two bone implants instead of one to evaluate the cell lines PC3 and PC3M, a more metastatic subline. For this purpose we generated the novel cell line PC3EGFPLuc, which can be used for luminescence and/or fluorescence imaging in vivo. We did not observe bone implant metastases in 52 mice, with 90 bone implants following tail vein injection of 1x10(6) PC3 or PC3M cells. Soft tissue lesions in the buttocks and hind limbs as well as cellular growth in the hindlimbs were observed via bioluminescence imaging. This evidence together with literature findings suggests that this model produces artifactual 'bone metastasis' lesions.
C1 NCI, Med Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA.
   Howard Hughes Med Inst, Chevy Chase, MD USA.
   NCI, Mouse Imaging Facil, Canc Res Ctr, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Med Oncol Branch, Canc Res Ctr, Bldg 10-Room 5A01 MSC 1910,900 Rockville Pike, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
NR 19
TC 6
Z9 6
U1 1
U2 4
PU PROFESSOR D A SPANDIDOS
PI ATHENS
PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE
SN 1021-335X
J9 ONCOL REP
JI Oncol. Rep.
PD MAR
PY 2006
VL 15
IS 3
BP 519
EP 524
PG 6
WC Oncology
SC Oncology
GA 012DF
UT WOS:000235317700001
PM 16465406
ER

PT J
AU Okano, T
   Gemma, A
   Hosoya, Y
   Hosomi, Y
   Nara, M
   Kokubo, Y
   Yoshimura, A
   Shibuya, M
   Nagashima, M
   Harris, CC
   Kudoh, S
AF Okano, T
   Gemma, A
   Hosoya, Y
   Hosomi, Y
   Nara, M
   Kokubo, Y
   Yoshimura, A
   Shibuya, M
   Nagashima, M
   Harris, CC
   Kudoh, S
TI Alterations in novel candidate tumor suppressor genes, ING1 and ING2 in
   human lung cancer
SO ONCOLOGY REPORTS
LA English
DT Article
DE ING1; ING2; lung cancer; polymorphism; mRNA expression
ID ALTERNATIVE TRANSCRIPTS; HISTONE ACETYLATION; GENOMIC STRUCTURE;
   GASTRIC-CANCER; P33(ING1); EXPRESSION; COMPLEX; P53; MUTATIONS; DNA
AB The ING1 gene is involved in the regulation of the cell cycle, senescence, and apoptosis and is a novel candidate tumor suppressor gene. ING2, another gene in the ING family, was identified and cloned. The functions of ING1 and ING2 largely depend on the activity of p53. To determine whether an alteration in these genes plays a role in carcinogenesis and tumor progression in lung cancer, we screened 30 human lung cancer cell lines and 31 primary lung cancer tumors for mutations in these genes using polymerase chain reaction-single strand conformation polymorphism (PCRSSCP) and direct sequencing. Our findings failed to uncover any mutations in these genes. We also examined the expression of ING1 and ING2 in lung cancer cell lines that either had or lacked a p53 mutation, and in a control bronchial epithelium cell line, using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). ING1 expression was up-regulated in all 7 lung cancer cell lines that had a p53 mutation, while the expression of ING2 was down-regulated in 6 of 7 lung cancer cell lines that had a p53 mutation. These results suggest that the ING1 and ING2 genes have different roles in lung carcinogenesis and progression, and the ING2 gene may be an independent tumor suppressor candidate on p53.
C1 Nippon Med Coll, Dept Internal Med 4, Bunkyo Ku, Tokyo 1138602, Japan.
   NCI, Lab Human Carcinogenesis, NIH, Bethesda, MD 20892 USA.
RP Gemma, A (reprint author), Nippon Med Coll, Dept Internal Med 4, Bunkyo Ku, 1-1-5,Sendagi, Tokyo 1138602, Japan.
EM agemma@nms.ac.jp
NR 33
TC 31
Z9 33
U1 0
U2 2
PU PROFESSOR D A SPANDIDOS
PI ATHENS
PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE
SN 1021-335X
J9 ONCOL REP
JI Oncol. Rep.
PD MAR
PY 2006
VL 15
IS 3
BP 545
EP 549
PG 5
WC Oncology
SC Oncology
GA 012DF
UT WOS:000235317700005
PM 16465410
ER

PT J
AU Klein, R
   Klein, BEK
   Knudtson, MD
   Wong, TY
   Cotch, MF
   Liu, K
   Burke, G
   Saad, MF
   Jacobs, DR
AF Klein, R
   Klein, BEK
   Knudtson, MD
   Wong, TY
   Cotch, MF
   Liu, K
   Burke, G
   Saad, MF
   Jacobs, DR
TI Prevalence of age-related macular degeneration in 4 racial/ethnic groups
   in the multi-ethnic study of atherosclerosis
SO OPHTHALMOLOGY
LA English
DT Article
ID POLYPOIDAL CHOROIDAL VASCULOPATHY; NUTRITION EXAMINATION SURVEY; BEAVER
   DAM EYE; GEOGRAPHIC REGION; NATIONAL-HEALTH; UNITED-STATES; MACULOPATHY;
   POPULATION; WISCONSIN; ETHNICITY
AB Objective: To describe the prevalence of age-related macular degeneration (AMD) in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) that participated in the second examination of the Multi-ethnic Study of Atherosclerosis (MESA).
   Design: Prospective cohort study.
   Participants: Six thousand one hundred seventy-six 45- to 85-year-old subjects selected from 6 United States communities.
   Methods: Fundus images were taken using a 450 digital camera through dark-adapted pupils and were graded for drusen size, type, area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System.
   Main Outcome Measure: Age-related macular degeneration.
   Results: Prevalences of AMD were 2.4% (black), 4.2% (Hispanic), 4.6% (Chinese), to 5.4% (white) (P < 0.001 for any differences among groups). The highest prevalence of any AMD occurred in those 75 to 84 years old, varying from 7.4% in blacks to 15.8% in whites and Chinese (P = 0.03). Estimated prevalences of late AMD were 0.3% (black), 0.2% (Hispanic), 0.6% (white), and 1.0% (Chinese). These differences were marginally significant (age and gender adjusted, P = 0.08). The frequency of exudative AMD was highest in Chinese (age- and gender-adjusted odds ratio, 4.30; 95% confidence interval, 1.30-14.27) compared with whites. Differences in age, gender, pupil size, body mass index, smoking, alcohol drinking history, diabetes, and hypertension status did not explain the variability among the 4 racial/ethnic groups.
   Conclusions: Low prevalences of AMD were found in the MESA cohort in all groups. A lower prevalence of AMD was found in blacks compared with whites. The higher prevalence of exudative AMD in Chinese needs further study.
C1 UW Madison, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA.
   Univ Melbourne, Ctr Eye Res, Melbourne, Vic, Australia.
   NEI, NIH, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA.
   Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
   Wake Forest Univ, Dept Publ Hlth Sci, Wake Forest, NC USA.
   Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
   Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
RP Klein, R (reprint author), UW Madison, Dept Ophthalmol & Visual Sci, 4th Floor WARF,610 N Walnut St, Madison, WI 53726 USA.
EM kleinr@epi.ophth.wisc.edu
OI Cotch, Mary Frances/0000-0002-2046-4350
FU Intramural NIH HHS [ZIA EY000403-08, Z01 EY000403-06, Z01 EY000403-07,
   Z99 EY999999, ZIA EY000403-09, ZIA EY000403-10]; NHLBI NIH HHS
   [HL69979-03, R01 HL069979]
NR 27
TC 189
Z9 192
U1 3
U2 16
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 MAR
PY 2006
VL 113
IS 3
BP 373
EP 380
DI 10.1016/j.ophtha.2005.12.013
PG 8
WC Ophthalmology
SC Ophthalmology
GA 017LD
UT WOS:000235694200003
PM 16513455
ER

PT J
AU Zheng, C
   Voutetakis, A
   Kok, MR
   Goldsmith, CM
   Smith, GBJ
   Elmore, S
   Nyska, A
   Vallant, M
   Irwin, RD
   Baum, BJ
AF Zheng, C
   Voutetakis, A
   Kok, MR
   Goldsmith, CM
   Smith, GBJ
   Elmore, S
   Nyska, A
   Vallant, M
   Irwin, RD
   Baum, BJ
TI Toxicity and biodistribution of a first-generation recombinant
   adenoviral vector, in the presence of hydroxychloroquine, following
   retroductal delivery to a single rat submandibular gland
SO ORAL DISEASES
LA English
DT Article
DE adenovirus; salivary gland; hydroxychloroquine; gene therapy; safety
ID MEDIATED GENE-TRANSFER; SALIVARY-GLANDS; ENDOCRINE SECRETION;
   LOCAL-DELIVERY; GROWTH-HORMONE; IN-VIVO; INDIVIDUALS; SPECTRUM
AB OBJECTIVE: We examined the toxicity and biodistribution associated with a single administration of a first-generation, serotype 5, adenoviral vector encoding human growth hormone (hGH; AdCMVhGH) to a single rat submandibular gland in the presence of hydroxychloroquine (HCQ). Previously, we showed that hGH is primarily secreted into saliva (approximately ninefold serum level) when expressed as a transgene in salivary glands (e.g. Baum et al, 1999), but administration of HCQ substantially increases the hGH levels secreted into the bloodstream (Hoque et al, 2001). A potential application of this observation is for patients with adult hGH deficiency.
   METHODS: Six groups of male and female adult rats (n = 12 each) were studied, with zero to 1.5 x 10(11) particles of AdCMVhGH, +/- HCQ, administered retroductally. Multiple clinical and pathological parameters, as well as vector tissue distribution, were assessed.
   RESULTS: All animals survived until the scheduled day of sacrifice, and essentially no untoward events were observed clinically or at gross necropsy. We observed no vector-related effects on clinical hematology evaluations and a single, transient significant change on clinical chemistry evaluations (increased serum globulin levels). Three days after AdCMVhGH administration, the vector distributed to all tissues analyzed with the exception of gonads and heart. By day 29, most organs, other than the targeted and contralateral submandibular glands, were negative for the presence of vector. On day 3, none of the animals tested positive for the presence of replication competent adenovirus in either their blood or saliva.
   CONCLUSION: Salivary gland delivery of AdCMVhGH +/- HCQ appears associated with limited toxicity in rats.
C1 NIDCR, GTTB, NIH, DHHS, Bethesda, MD 20892 USA.
   AMC, Dept Clin Immunol & Rheumatol, Amsterdam, Netherlands.
   BioReliance Inc, Rockville, MD USA.
   Integrated Lab Syst, Res Triangle Pk, NC USA.
   NIEHS, Natl Toxicol Program, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Baum, BJ (reprint author), NIDCR, GTTB, NIH, DHHS, Bldg 10,Room 1N113,MSC-1190, Bethesda, MD 20892 USA.
EM bbaum@dir.nidcr.nih.gov
NR 20
TC 12
Z9 12
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1354-523X
J9 ORAL DIS
JI Oral Dis.
PD MAR
PY 2006
VL 12
IS 2
BP 137
EP 144
DI 10.1111/j.1601-0825.2005.01170.x
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 012IX
UT WOS:000235333200009
PM 16476034
ER

PT J
AU Miyazaki, H
   Patel, V
   Wang, HX
   Ensley, JF
   Gutkind, JS
   Yeudall, WA
AF Miyazaki, H
   Patel, V
   Wang, HX
   Ensley, JF
   Gutkind, JS
   Yeudall, WA
TI Growth factor-sensitive molecular targets identified in primary and
   metastatic head and neck squamous cell carcinoma using microarray
   analysis
SO ORAL ONCOLOGY
LA English
DT Article
DE squamous cell carcinoma; oral cancer; metastasis; invasion; growth
   factor; EGF; TGF beta
ID VISININ-LIKE PROTEIN-1; FACTOR RECEPTOR; CANCER-CELLS; IN-VIVO;
   CHEMOKINE RECEPTORS; GENE-EXPRESSION; P63 EXPRESSION; POOR-PROGNOSIS;
   ORAL-CAVITY; EPIREGULIN
AB Polypeptide growth factors play key roles in the processes of cell migration and invasion. In this study, we have used cDNA microarrays to identify target genes whose expression is differentially modulated by the growth factors TGF beta and EGF. HN4 and HN12 cell lines, established from primary tumor and a lymph node metastasis arising in one patient with head and neck squamous cell carcinoma, were treated with 2 nM EGF or 50 pM TGF beta for 24 h and extracted RNA was used to prepare labeled cDNAs which were hybridized to NCI UniGem 2.0 cDNA microarrays containing 9128 features. Results revealed constitutive overexpression of 41 genes and underexpression of 109 genes in metastatic HN12 compared to HN4 under conditions of serum withdrawal. Furthermore, TGF beta treatment resulted in relative up-regulation of 53 genes and downregulation of 91 genes in HN12 compared with HN4, whereas cells treated with EGF showed relative upregulation of 67 genes and downregulation of 113 genes. Partial overlap was found between TGF beta and EGF-modulated gene sets. Results were verified for a subset of each category using quantitative PCR, western blotting and zymography. The data indicate that TGF beta and EGF differentially affect gene expression in primary and metastatic HNSCC cells, and likely contribute to the invasive properties of metastatic cells through regulation of both common and specific mediators for each growth factor. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Virginia Commonwealth Univ, Sch Dent, Philips Inst Oral & Craniofacial Mol Biol, Richmond, VA 23298 USA.
   Virginia Commonwealth Univ, Dept Biochem, Richmond, VA 23298 USA.
   Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA.
   Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA.
   Wayne State Univ, Karmanos Canc Inst, Div Hematol Oncol, Detroit, MI 48201 USA.
RP Yeudall, WA (reprint author), Virginia Commonwealth Univ, Sch Dent, Philips Inst Oral & Craniofacial Mol Biol, POB 980566,Room 424,521 N 11th St, Richmond, VA 23298 USA.
EM wayeudall@vcu.edu
RI Gutkind, J. Silvio/A-1053-2009
NR 61
TC 24
Z9 25
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
EI 1879-0593
J9 ORAL ONCOL
JI Oral Oncol.
PD MAR
PY 2006
VL 42
IS 3
BP 240
EP 256
DI 10.1016/j.oraloncology.2005.07.006
PG 17
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA 025UH
UT WOS:000236291900003
PM 16266819
ER

PT J
AU Martin, AM
AF Martin, AM
TI How to argue for the value of humanity
SO PACIFIC PHILOSOPHICAL QUARTERLY
LA English
DT Article
AB Significant effort has been devoted to locating a good argument for Kant's Formula of Humanity. In this paper, I contrast two arguments, based on Kant's text, for the Formula of Humanity. The first, which I call the 'Valued Ends' argument, is an influential and appealing argument developed most notably by Christine Korsgaard and Allen Wood. Notwithstanding the appeal and influence of this argument, it ultimately fails on several counts. I therefore present as an alternative the 'Autonomy' argument, which is largely inspired by the failings of the Valued Ends argument.
C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA.
RP Martin, AM (reprint author), NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA.
NR 13
TC 3
Z9 3
U1 1
U2 2
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0279-0750
J9 PAC PHILOS QUART
JI Pac. Philos. Q.
PD MAR
PY 2006
VL 87
IS 1
BP 96
EP 125
DI 10.1111/j.1468-0114.2006.00249.x
PG 30
WC Philosophy
SC Philosophy
GA 022QY
UT WOS:000236072000006
ER

PT J
AU Moody, TW
AF Moody, TW
TI Peptide hormones and lung cancer
SO PANMINERVA MEDICA
LA English
DT Article
DE lung neoplasms; gastrin releasing peptide; neurotensin; adremedullin
ID GASTRIN-RELEASING-PEPTIDE; EPIDERMAL-GROWTH-FACTOR; FOCAL ADHESION
   KINASE; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; BOMBESIN-LIKE PEPTIDES;
   TUMOR-CELL LINES; POSSIBLE PROMOTION MECHANISM; ELEVATES CYCLIC-AMP;
   STIMULATES C-FOS; INTESTINAL-PEPTIDE
AB Several peptide hormones have been identified which alter the proliferation of lung cancer. Small cell lung cancer (SCLC), which is a neuroendocrine cancer, produces and secretes gastrin releasing peptide (GRP), neurotensin (NT) and adrenomedullin (AM) as autocrine growth factors. GRP, NT and AM bind to G-protein coupled receptors causing phosphatidylinositol turnover or elevated cAMP in SCLC cells. Addition of GRP, NT or AM to SCLC cells causes altered expression of nuclear oncogenes, such as c-fos, and stimulation of growth. Antagonists have been developed for GRP, NT and AM receptors which function as cytostatic agents and inhibit SCLC growth. Growth factor antagonists, such as the NT1 receptor antagonist SR48692, facilitate the ability of chemotherapeutic drugs to kill lung cancer cells. It remains to be determined if GRP, NT and AM receptors will served as molecular targets, for development of new therapies for the treatment of SCLC patients. Non-small cell lung cancer (NSCLC) cells also have a high density of GRP, NT, AM and epidermal growth factor (EGF) receptors. Several NSCLC patients with EGF receptor mutations respond to gefitinib, a tyrosine kinase inhibitor. Gefitinib relieves NSCLC symptoms, maintaining stable disease in patients who are not eligible for systemic chemotherapy. It is important to develop new therapeutic approaches using translational research techniques for the treatment of lung cancer patients.
C1 NCI, Canc Res Ctr, Off Director, Bethesda, MD 20892 USA.
RP Moody, TW (reprint author), NCI, Canc Res Ctr, Off Director, Bldg 31,Rm 4A48,31 Ctr Dr, Bethesda, MD 20892 USA.
EM moodyt@mail.nih.gov
NR 91
TC 9
Z9 9
U1 0
U2 2
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 0031-0808
J9 PANMINERVA MED
JI Panminerva Medica
PD MAR
PY 2006
VL 48
IS 1
BP 19
EP 26
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 051HA
UT WOS:000238151000004
PM 16633328
ER

PT J
AU Tabak, LA
AF Tabak, LA
TI In Defense of the oral cavity: The protective role of the salivary
   secretions
SO PEDIATRIC DENTISTRY
LA English
DT Article; Proceedings Paper
CT 58th Annual Session of the American-Academy-of-Pediatric-Dentistry
CY MAY 26-29, 2005
CL Orlando, FL
SP Amer Acad Pediat Dent
DE saliva; mucins; salivary proteins; caries; statherin
ID HUMAN-PAROTID-SALIVA; CALCIUM-PHOSPHATE PRECIPITATION; PROLINE-RICH
   PROTEINS; LOW-MOLECULAR-WEIGHT; 2-DIMENSIONAL GEL-ELECTROPHORESIS;
   SECRETORY IMMUNOGLOBULIN-A; MASS-SPECTROMETRY; CARIES EXPERIENCE; MUCIN
   MG1; STREPTOCOCCUS-MUTANS
AB Saliva performs important protective roles in the oral cavity. Debate in the 1970s over the "specific" or "non-specific" action of salivary components has given way to current attempts to identify the full complement of all proteins in saliva that are now considered to act in concert. At the same time, more fundamental protective qualities of saliva*water and pH control*are receiving less attention. These qualities may be among saliva's most important. This presentation will review recent advances in the genomics and proteomics of saliva, as well as saliva's roles in tissue coating, alimentation, and regulation of the oral flora.
C1 Natl Inst Dent & Craniofacial Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
RP Tabak, LA (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
EM tabakl@mail.nih.gov
NR 108
TC 32
Z9 33
U1 0
U2 8
PU AMER ACAD PEDIATRIC DENTISTRY
PI CHICAGO
PA 211 E CHICAGO AVENUE SUITE 1036, CHICAGO, IL 60611-2616 USA
SN 0164-1263
J9 PEDIATR DENT
JI Pediatr. Dent.
PD MAR-APR
PY 2006
VL 28
IS 2
BP 110
EP 117
PG 8
WC Dentistry, Oral Surgery & Medicine; Pediatrics
SC Dentistry, Oral Surgery & Medicine; Pediatrics
GA 036VP
UT WOS:000237104600006
PM 16708785
ER

PT J
AU Lotan, D
   Eisenkraft, A
   Jacobsson, JM
   Bar-Yosef, O
   Kleta, R
   Gal, N
   Raviv-Zilka, L
   Gore, H
   Anikster, Y
AF Lotan, D
   Eisenkraft, A
   Jacobsson, JM
   Bar-Yosef, O
   Kleta, R
   Gal, N
   Raviv-Zilka, L
   Gore, H
   Anikster, Y
TI Clinical and molecular findings in a family with the carbonic anhydrase
   II deficiency syndrome
SO PEDIATRIC NEPHROLOGY
LA English
DT Article
DE carbonic anhydrase II deficiency syndrome; CA2; growth failure; primary
   pulmonary hypertension; osteopetrosis; renal tubular acidosis
ID PRIMARY PULMONARY-HYPERTENSION; MALIGNANT INFANTILE OSTEOPETROSIS; RENAL
   TUBULAR-ACIDOSIS; OSTEOPROTEGERIN; TRANSPLANTATION; CALCIFICATION;
   PATHOGENESIS
AB Carbonic anhydrase II (CA2) deficiency syndrome is an autosomal recessive disorder leading to osteopetrosis, renal tubular acidosis, and cerebral calcifications. Affected members of an Arab family with the CA2 deficiency syndrome carried the "Egyptian mutation" in CA2, i.e., c.191 del A, H64fsX90. One affected member, homozygote for the mutation, developed primary pulmonary hypertension. Primary pulmonary hypertension was never described before in patients with this unique syndrome. The likelihood of both occurring randomly in a single individual is very low. We therefore speculate that there might be a possibility of an etiologic link between these entities.
C1 Chaim Sheba Med Ctr, Edmond & Lily Safra Childrens Hosp, Metab Dis Unit, IL-52621 Tel Hashomer, Israel.
   Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
   NHGRI, Bethesda, MD 20892 USA.
   Chaim Sheba Med Ctr, Edmond & Lily Safra Childrens Hosp, Dept Pediat Radiol, IL-52621 Tel Hashomer, Israel.
   Chaim Sheba Med Ctr, Edmond & Lily Safra Childrens Hosp, Dept Pediat Nephrol, IL-52621 Tel Hashomer, Israel.
   Chaim Sheba Med Ctr, Edmond & Lily Safra Childrens Hosp, Dept Pediat, IL-52621 Tel Hashomer, Israel.
RP Anikster, Y (reprint author), Chaim Sheba Med Ctr, Edmond & Lily Safra Childrens Hosp, Metab Dis Unit, IL-52621 Tel Hashomer, Israel.
EM yair.anikster@sheba.health.gov.il
NR 16
TC 9
Z9 9
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0931-041X
J9 PEDIATR NEPHROL
JI Pediatr. Nephrol.
PD MAR
PY 2006
VL 21
IS 3
BP 423
EP 426
DI 10.1007/s00467-005-2125-0
PG 4
WC Pediatrics; Urology & Nephrology
SC Pediatrics; Urology & Nephrology
GA 013ZN
UT WOS:000235448600022
PM 16382316
ER

PT J
AU Choi, EH
   Ehrmantraut, M
   Foster, CB
   Moss, J
   Chanock, SJ
AF Choi, EH
   Ehrmantraut, M
   Foster, CB
   Moss, J
   Chanock, SJ
TI Association of common haplotypes of surfactant protein A1 and A2 (SFTPA1
   and SFTPA2) genes with severity of lung disease in cystic fibrosis
SO PEDIATRIC PULMONOLOGY
LA English
DT Article
DE surfactant protein A1; surfactant protein A2; mannose-binding lectin;
   genetic association study; cystic fibrosis; polymorphisms
ID MANNOSE-BINDING LECTIN; PULMONARY SURFACTANT; DEFICIENT MICE; MODIFIER
   GENES; PHENOTYPE; GENOTYPE; DECLINE; CHROMOSOME-10; POLYMORPHISMS;
   PANCREATITIS
AB Most individual cystic fibrosis transmembrane conductance regulator (CFTR) mutations appear not to correlate directly with severity of lung damage in cystic fibrosis (CF). Components of innate immunity, namely, mannose-binding lectin (MBL2), and surfactant protein A1 and A2 genes (SFTPA1 and SFTPA2), were shown to be critical in pulmonary host defenses. A pilot association study was conducted to identify genetic modifiers of lung disease in adult patients with CF. The structural and promoter (-221 x/y) variants of MBL2, variants at codons 19,50, 62, and 219 of SFTPA1, and at codons 9, 91, and 223 for SFTPA2 were studied in 135 adults with CF and compared to their forced expired volume in 1 sec (FEV1), diffusion of CO (DLCO), and other pulmonary scores. Predicted FEV1 was significantly lower in adults with the SFTPA 1 6A(3) allele and SFTPA2 1A(1) allele (P = 0.01 and 0.009, respectively). The extended haplotype 6A(3)1 1A(1), which includes SFTPA1 and SFTPA2, was associated with lower pulmonary function, using FEV1 (P = 0.005) and poor pulmonary scores which were determined by American Medical Association, American Thoracic Society, and modified Shwachman-Kulczycki scores. Lower FEV1 and DLCO values were associated with MBL2 coding variants in those who had the Delta F508 CFTR mutation (P = 0.03 and 0.004, respectively). These results support the current hypothesis that variants in pulmonary host defense molecules are potentially genetic modifiers of pulmonary disease in CF Further work in larger populations is required to provide important new insights into the pathogenesis of CF.
C1 NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, Bethesda, MD 20892 USA.
   Seoul Natl Univ, Coll Med, Dept Pediat, Seoul, South Korea.
   NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA.
   Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
RP Chanock, SJ (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, 8717 Grovemont Circle, Bethesda, MD 20892 USA.
EM sc83a@nih.gov
RI Choi, Eun Hwa/J-5691-2012
NR 40
TC 15
Z9 15
U1 0
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 8755-6863
J9 PEDIATR PULM
JI Pediatr. Pulmonol.
PD MAR
PY 2006
VL 41
IS 3
BP 255
EP 262
DI 10.1002/ppul.20361
PG 8
WC Pediatrics; Respiratory System
SC Pediatrics; Respiratory System
GA 018HT
UT WOS:000235755800008
PM 16429424
ER

PT J
AU Chen, A
   Schwarz, D
   Radcliffe, J
   Rogan, WJ
AF Chen, A
   Schwarz, D
   Radcliffe, J
   Rogan, WJ
TI Maternal IQ, child IQ, behavior, and achievement in urban 5-7 year olds
SO PEDIATRIC RESEARCH
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the Pediatric-Academic-Societies
CY MAY 14-17, 2005
CL Washington, DC
SP Pediat Acad Soc
ID MENTALLY-RETARDED PARENTS; LEAD-EXPOSURE; ENVIRONMENTAL LEAD;
   PRESCHOOL-CHILDREN; CHELATION-THERAPY; HERITABILITY; INTELLIGENCE;
   PREDICTORS; AGREEMENT; DISORDER
AB In one study of children in 27 families with maternal retardation, those children with higher intelligence quotient (IQ) were more likely to have multiple behavior problems than those with lower IQ. If true, this result would affect clinical practice, but it has not been replicated. Because the setting of the initial observation is similar to the setting of childhood lead poisoning, we attempted a replication using data from the Treatment of Lead-Exposed Children (TLC) study, in which 780 children aged 12-33 mo with blood lead levels 20-44 mu g/dL were randomized to either succimer treatment or placebo and then followed up to 5 y. Of 656 mothers of TLC children with IQ measured, 113 demonstrated mental retardation (IQ < 70). Whether maternal IQ was < 70 or >= 70, children with IQ >= 85 were rated more favorably on cognitive tests and behavioral questionnaires than children with IQ < 85; these measures included Conners' Parent Rating Scale-Revised at age 5, the Developmental Neuropsychological Assessment at ages 5 and 7, and the Behavioral Assessment System for Children at age 7. Among children of mothers With IQ < 70, those with IQ >= 85 did not show more severe clinical behavioral problems, nor were they more likely to show multiple behavior problems. Children with higher IQ have fewer behavior problems, irrespective of the mother's IQ. In the special setting of mothers with IQ < 70, children with higher IQ are not at greater risk of behavior problems.
C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
   Childrens Hosp Philadelphia, Dept Adolescent Med, Philadelphia, PA 19104 USA.
   Childrens Hosp Philadelphia, Dept Psychol, Philadelphia, PA 19104 USA.
   Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA.
EM rogan@niehs.mh.gov
RI Rogan, Walter/I-6034-2012
OI Rogan, Walter/0000-0002-9302-0160
NR 40
TC 4
Z9 4
U1 3
U2 7
PU INT PEDIATRIC RESEARCH FOUNDATION, INC
PI BALTIMORE
PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA
SN 0031-3998
J9 PEDIATR RES
JI Pediatr. Res.
PD MAR
PY 2006
VL 59
IS 3
BP 471
EP 477
DI 10.1203/01.pdr.0000199910.16681.f0
PG 7
WC Pediatrics
SC Pediatrics
GA 016NK
UT WOS:000235626700024
PM 16492992
ER

PT J
AU Nozyce, ML
   Lee, SS
   Wiznia, A
   Nachman, S
   Mofenson, LM
   Smith, ME
   Yogev, R
   McIntosh, K
   Stanley, K
   Pelton, S
AF Nozyce, ML
   Lee, SS
   Wiznia, A
   Nachman, S
   Mofenson, LM
   Smith, ME
   Yogev, R
   McIntosh, K
   Stanley, K
   Pelton, S
TI A behavioral and cognitive profile of clinically stable HIV-infected
   children
SO PEDIATRICS
LA English
DT Article
DE HIV; child; cognition; behavioral symptoms; attention-deficit disorder
   with; hyperactivity; neuropsychological tests; antiretroviral agents
ID HUMAN-IMMUNODEFICIENCY-VIRUS; DEVELOPMENTAL ABNORMALITIES; SYNDROME
   AIDS; BRAIN-SCAN; DISEASE; DEMENTIA; INFANTS; COMPLEX; GROWTH; CARE
AB OBJECTIVE. The purpose of this research was to characterize behavioral and cognitive profiles of clinically and immunologically stable antiretroviral-experienced HIV-infected children.
   METHODS. Two hundred seventy-four previously treated HIV-infected children aged 2 to 17 years were assessed for behavioral, developmental, and cognitive functioning. Correlations between neuropsychological measures, age, and CD4 lymphocyte count were investigated.
   RESULTS. The most common behavioral problems, as measured by the Conners' Parent Rating Scale, were psychosomatic (28%), learning (25%), hyperactivity (20%), impulsive-hyperactive (19%), conduct (16%), and anxiety (8%) problems. Mean Wechsler Intelligence Scale for Children-III scores were less than established population norms; the mean verbal IQ was 85, the mean performance IQ was 90, and the mean full-scale score was 86. Hyperactivity was more frequent in children with a Wechsler Intelligence Scale for Children-III performance IQ of < 90. Anxiety problems were more likely in children >= 9 years of age. Children with CD4 counts of < 660 cells per mm(3) were more likely to be identified as having a conduct disorder. No association was noted between behavioral problems and neuroimaging.
   CONCLUSIONS. Clinically and immunologically stable HIV-infected children had more frequent behavioral problems and lower developmental and cognitive scores than established childhood norms.
C1 Jacob Med Ctr, Neurodev Serv, Dept Pediat, Bronx, NY 10461 USA.
   Bronx Lebanon Hosp Ctr, Dept Pediat, Bronx, NY 10456 USA.
   Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   Albert Einstein Coll Med, Bronx, NY 10467 USA.
   SUNY Hlth Sci Ctr, Dept Pediat, Stony Brook, NY USA.
   NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA.
   NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA.
   Childrens Mem Hosp, Div Infect Dis, Chicago, IL 60614 USA.
   Northwestern Univ, Sch Med, Chicago, IL 60611 USA.
   Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   Boston Med Ctr, Dept Pediat, Boston, MA USA.
RP Nozyce, ML (reprint author), Jacob Med Ctr, Neurodev Serv, Dept Pediat, 1400 Pelham Pkwy S, Bronx, NY 10461 USA.
EM molly.nozyce@nbhn.net
OI Mofenson, Lynne/0000-0002-2818-9808
FU NIAID NIH HHS [AI-41110]
NR 47
TC 85
Z9 88
U1 1
U2 1
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2006
VL 117
IS 3
BP 763
EP 770
DI 10.1542/peds.2005-0451
PG 8
WC Pediatrics
SC Pediatrics
GA 017QV
UT WOS:000235709000047
PM 16510656
ER

PT J
AU Grosse, SD
   Boyle, CA
   Kenneson, A
   Khoury, MJ
   Wilfond, BS
AF Grosse, SD
   Boyle, CA
   Kenneson, A
   Khoury, MJ
   Wilfond, BS
TI From public health emergency to public health service: The implications
   of evolving criteria for newborn screening panels
SO PEDIATRICS
LA English
DT Editorial Material
ID TANDEM MASS-SPECTROMETRY; CYSTIC-FIBROSIS; PREVENTIVE-SERVICES;
   UNITED-STATES; FOLLOW-UP; CHILDREN; DIAGNOSIS; LESSONS; PROGRAM;
   MALNUTRITION
C1 Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA.
   Ctr Dis Control & Prevent, Off Genom & Dis Prevent, Atlanta, GA 30333 USA.
   NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
   NIH, Warren Grant Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA.
RP Grosse, SD (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, 1600 Clifton Rd, Atlanta, GA 30333 USA.
EM sgrosse@cdc.gov
NR 62
TC 73
Z9 73
U1 0
U2 0
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2006
VL 117
IS 3
BP 923
EP 929
DI 10.1542/peds.2005-0553
PG 7
WC Pediatrics
SC Pediatrics
GA 017QV
UT WOS:000235709000066
PM 16510675
ER

PT J
AU De Ravin, SS
   Naumann, N
   Robinson, MR
   Barron, KS
   Kleiner, DE
   Ulrick, J
   Friend, J
   Anderson, VL
   Darnell, D
   Kang, EM
   Malech, HL
AF De Ravin, SS
   Naumann, N
   Robinson, MR
   Barron, KS
   Kleiner, DE
   Ulrick, J
   Friend, J
   Anderson, VL
   Darnell, D
   Kang, EM
   Malech, HL
TI Sarcoidosis in chronic granulomatous disease
SO PEDIATRICS
LA English
DT Article
DE chronic granulomatous disease; sarcoidosis; neurosarcoidosis;
   angiotensin-converting enzyme
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TUMOR-NECROSIS-FACTOR; PULMONARY
   SARCOIDOSIS; CHORIORETINAL LESIONS; NEUROSARCOIDOSIS; COMPLICATIONS;
   STIMULATION; RELEASE
AB In addition to increased susceptibility to infections in patients with chronic granulomatous disease (CGD), a higher incidence of sterile inflammatory disorders in these patients has been noted. However, sarcoidosis has not been reported previously in CGD. In this report, we describe two patients who have CGD and a disorder consistent with sarcoidosis on the basis of unequivocal clinical-radiographic presentations, their responses to treatment, and serum angiotensin-converting enzyme levels. Serum angiotensin-converting enzyme levels were measured in 26 other patients with CGD to establish an appropriate reference range. A possible relationship between CGD and sarcoidosis is discussed.
C1 Natl Inst Allergy & Infect Dis, Lab Host Def, NIH, Bethesda, MD 20892 USA.
   NEI, Bethesda, MD 20892 USA.
RP Malech, HL (reprint author), Natl Inst Allergy & Infect Dis, Lab Host Def, NIH, Bldg 10-CRC,Room 4-3750, Bethesda, MD 20892 USA.
EM hmalech@niaid.nih.gov
OI Malech, Harry/0000-0001-5874-5775; Kleiner, David/0000-0003-3442-4453
FU Intramural NIH HHS
NR 29
TC 19
Z9 19
U1 0
U2 0
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2006
VL 117
IS 3
BP E590
EP E595
DI 10.1542/peds.2005-1349
PG 6
WC Pediatrics
SC Pediatrics
GA 017QV
UT WOS:000235709000025
PM 16452321
ER

PT J
AU Anand, KJS
   Aranda, JV
   Berde, CB
   Buckman, S
   Capparelli, EV
   Carlo, W
   Hummel, P
   Johnston, CC
   Lantos, J
   Tutag-Lehr, V
   Lynn, AM
   Maxwell, LG
   Oberlander, TF
   Raju, TNK
   Soriano, SG
   Taddio, A
   Walco, GA
AF Anand, KJS
   Aranda, JV
   Berde, CB
   Buckman, S
   Capparelli, EV
   Carlo, W
   Hummel, P
   Johnston, CC
   Lantos, J
   Tutag-Lehr, V
   Lynn, AM
   Maxwell, LG
   Oberlander, TF
   Raju, TNK
   Soriano, SG
   Taddio, A
   Walco, GA
TI Summary proceedings from the neonatal pain-control group
SO PEDIATRICS
LA English
DT Article; Proceedings Paper
CT Newborn Drug Development Initiative Workshop
CY MAR 29-30, 2004
CL Baltimore, MD
SP NICHD, FDA
DE pain; neonate; Newborn Drug Development Initiative; analgesia;
   anesthesia
ID LOW-BIRTH-WEIGHT; SYSTEMIC CLEARANCE PATHWAYS; RANDOMIZED
   CONTROLLED-TRIAL; INTENSIVE-CARE-UNIT; BLOOD-FLOW VELOCITY;
   POSTOPERATIVE PAIN; NEWBORN-INFANTS; PRETERM INFANTS; PREMATURE-INFANTS;
   PROCEDURAL PAIN
AB Recent advances in neurobiology and clinical medicine have established that the fetus and newborn may experience acute, established, and chronic pain. They respond to such noxious stimuli by a series of complex biochemical, physiologic, and behavioral alterations. Studies have concluded that controlling pain experience is beneficial with respect to short-term and perhaps long-term outcomes. Yet, pain-control measures are adopted infrequently because of unresolved scientific issues and lack of appreciation for the need for control of pain and its long-term sequelae during the critical phases of neurologic maturation in the preterm and term newborn. The neonatal pain-control group, as part of the Newborn Drug Development Initiative (NDDI) Workshop I, addressed these concerns. The specific issues addressed were (1) management of pain associated with invasive procedures, (2) provision of sedation and analgesia during mechanical ventilation, and (3) mitigation of pain and stress responses during and after surgery in the newborn infant. The cross-cutting themes addressed within each category included (1) clinical-trial designs, (2) drug prioritization, (3) ethical constraints, (4) gaps in our knowledge, and (5) future research needs. This article provides a summary of the discussions and deliberations. Full-length articles on procedural pain, sedation and analgesia for ventilated infants, perioperative pain, and study designs for neonatal pain research were published in Clinical Therapeutics (June 2005).
C1 Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA.
   Univ Arkansas Med Sci, Dept Anesthesiol, Little Rock, AR 72205 USA.
   Univ Arkansas Med Sci, Dept Neurobiol, Little Rock, AR 72205 USA.
   Univ Arkansas Med Sci, Dept Pharmacol, Little Rock, AR 72205 USA.
   Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Pharmacol & Pharmaceut Sci, Detroit, MI USA.
   Wayne State Univ, Childrens Hosp Michigan, Eugene Applebaum Sch Pharm & Hlth Sci, Dept Pharmaceut, Detroit, MI USA.
   Harvard Univ, Sch Med, Dept Anaesthesia, Div Pain Med, Boston, MA USA.
   Harvard Univ, Sch Med, Dept Pediat, Div Pain Med, Boston, MA USA.
   Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Anesthesiol, Boston, MA USA.
   US FDA, Ctr Drug Evaluat & Res, Off Counter Terrorism & Pediat Drug Dev, Rockville, MD 20857 USA.
   Univ Calif San Diego, Dept Pediat, Pediat Pharmacol Res Unit, La Jolla, CA 92093 USA.
   Univ Alabama, Dept Pediat, Birmingham, AL USA.
   Loyola Univ, Med Ctr, Dev Follow Up Program, Maywood, IL 60153 USA.
   McGill Univ, Sch Nursing, Montreal, PQ, Canada.
   Univ Chicago, Dept Pediat, MacLean Ctr Clin Med Eth, Robert Wood Johnson Clin Scholars Program, Chicago, IL 60637 USA.
   Univ Chicago, Dept Med, MacLean Ctr Clin Med Eth, Robert Wood Johnson Clin Scholars Program, Chicago, IL 60637 USA.
   Univ Washington, Sch Med, Childrens Hosp & Reg Med Ctr, Dept Anesthesiol & Pediat, Seattle, WA USA.
   Univ Penn, Childrens Hosp Philadelphia, Dept Anesthesiol, Philadelphia, PA 19104 USA.
   Univ British Columbia, BC Childrens Hosp, Div Dev Pediat, Vancouver, BC V5Z 1M9, Canada.
   NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, Rockville, MD USA.
   Hosp Sick Children, Dept Pharm, Toronto, ON M5G 1X8, Canada.
   Hosp Sick Children, Populat Hlth Sci Res Inst, Toronto, ON M5G 1X8, Canada.
   Univ Med & Dent New Jersey, Hackensack Univ Med Ctr, Dept Pediat, Newark, NJ USA.
RP Anand, KJS (reprint author), Arkansas Childrens Hosp, Slot 900,800 Marshall St, Little Rock, AR 72202 USA.
EM anandsunny@uams.edu
OI Anand, Kanwaljeet/0000-0001-6498-1483
FU NICHD NIH HHS [R01 HD36484]
NR 169
TC 104
Z9 112
U1 2
U2 9
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 MAR
PY 2006
VL 117
IS 3
SU S
BP S9
EP S22
DI 10.1542/peds.2005-0620C
PG 14
WC Pediatrics
SC Pediatrics
GA 017XT
UT WOS:000235727300002
PM 16777824
ER

PT J
AU Finer, NN
   Higgins, R
   Kattwinkel, J
   Martin, RJ
AF Finer, NN
   Higgins, R
   Kattwinkel, J
   Martin, RJ
TI Summary proceedings from the apnea-of-prematurity group
SO PEDIATRICS
LA English
DT Article; Proceedings Paper
CT Newborn Drug Development Initiative Workshop
CY MAR 29-30, 2004
CL Baltimore, MD
DE apnea of prematurity; gastroesophageal reflux disease; pulse oximetry;
   bradycardia; neurodevelopmental follow-up; xanthines; doxapram
ID GASTROESOPHAGEAL REFLUX; INFANTS
AB Apnea of prematurity (AOP) is found in >50% of premature infants and is almost universal in infants who are <1000 g at birth. The literature clearly defines clinically significant apnea in infants (breathing pauses that last for >20 seconds or for >10 seconds if associated with bradycardia or oxygen desaturation), but there is no consensus about the duration of apnea, the degree of change in oxygen saturation, or severity of bradycardia that should be considered pathologic. Although caregivers are able to respond successfully to apnea events with drugs (as well as physical and mechanical interventions) in the NICU, it remains unproven whether such interventions have any long-term effects. One of the most effective drugs, caffeine citrate, is currently labeled for short-term use only and within a limited gestational-age population. Clinicians often use off-label drugs that have been approved for gastroesophageal reflux disease, which is common in premature infants, with the belief that such treatments also have an impact on AOP, although this link has never been demonstrated. Key treatment issues include (1) lack of standardization for definition, diagnosis, and treatment of AOP, (2) unproven benefit of intervention, (3) lack of real-time data documenting AOP events, (4) unevaluated sustained treatment improvement at 7 days or later, (5) failure to address confounding conditions, (6) unsubstantiated AOP-gastroesophageal reflux disease relationship, and (7) undetermined role of AOP affecting long-term neurodevelopmental outcomes. In addressing study-design issues, the pulmonary group identified (1) key questions about neonatal apnea, (2) methodologic requirements for study, (3) appropriate outcome measures, and (4) ethical considerations for future studies. This article describes a sample framework for the study of apnea in neonates and identifies future research needs. Plenary-session discussion points are also listed.
C1 Univ Calif San Diego, Dept Pediat, Div Neonatol, San Diego, CA 92103 USA.
   NICHHD, Neonatal Res Network,Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   Univ Virginia Hlth Syst, Dept Pediat, Div Neonatol, Charlottesville, VA USA.
   Rainbow Babies & Childrens Hosp, Case Med Sch, Div Neonatol, Cleveland, OH 44106 USA.
RP Finer, NN (reprint author), Univ Calif San Diego, Dept Pediat, Div Neonatol, 200 W Arbor Dr,8774, San Diego, CA 92103 USA.
EM nfiner@ucsd.edu
NR 9
TC 79
Z9 82
U1 2
U2 8
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 MAR
PY 2006
VL 117
IS 3
SU S
BP S47
EP S51
DI 10.1542/peds.2005-0620H
PG 5
WC Pediatrics
SC Pediatrics
GA 017XT
UT WOS:000235727300007
PM 16777822
ER

PT J
AU Giacoia, GP
   Birenbaum, DL
   Sachs, HC
   Mattison, DR
AF Giacoia, GP
   Birenbaum, DL
   Sachs, HC
   Mattison, DR
TI The Newborn Drug Development Initiative - Introduction
SO PEDIATRICS
LA English
DT Editorial Material
DE clinical research/trials; neonatology; clinical-trial design
ID NEONATAL INTENSIVE-CARE; METABOLIZING-ENZYMES; PRETERM INFANTS;
   ANESTHETIC AGENTS; RENAL-FUNCTION; DELIVERY; PHARMACOKINETICS; ONTOGENY;
   BRAIN; SERUM
AB The Best Pharmaceuticals for Children Act (BPCA; Pub L 107-109) was enacted in January 2002 and will sunset in October 2007. The BPCA established processes for studying off-patent and on-patent drugs that are used in pediatric population. Although some drugs have been successfully developed for the neonate (eg, surfactant, nitric oxide), drug development for the youngest, least mature, and most vulnerable pediatric patients is generally lacking. Most drugs are empirically administered to newborns once efficacy has been demonstrated in adults and usefulness is suspected or demonstrated in the older pediatric population. Unfortunately, this process undermines the ability to perform the appropriate studies necessary to demonstrate a drug's short- and long-term safety and efficacy and establish appropriate dosing in neonates. The Newborn Drug Development Initiative Workshop I (held March 29-30, 2004) specifically addressed scientific, clinical, and ethical concerns in the development of trials of pediatric therapeutic agents for neonates. Implementation of the BPCA for all pediatric populations will foster collaboration among federal agencies and academic institutions on scientific investigation, clinical-study design, and consideration of the weight of evidence and address ethical issues related to the performance of drug studies.
C1 NICHHD, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   US FDA, Dept Hlth & Human Serv, Ctr Drug Evaluat & Res, Div Pediat Drug Dev,Off Counter Terrorism & Pedia, Silver Spring, MD USA.
RP Giacoia, GP (reprint author), NICHHD, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH,Dept Hlth & Human Serv, 6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA.
EM gg65m@nih.gov
RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013
OI Mattison, Donald/0000-0001-5623-0874
NR 39
TC 19
Z9 19
U1 0
U2 0
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2006
VL 117
IS 3
SU S
BP S1
EP S8
DI 10.1542/peds.2005-0620B
PG 8
WC Pediatrics
SC Pediatrics
GA 017XT
UT WOS:000235727300001
PM 16777817
ER

PT J
AU Roth, SJ
   Adatia, I
   Pearson, GD
AF Roth, SJ
   Adatia, I
   Pearson, GD
CA Members Cardiology Grp
TI Summary proceedings from the cardiology group on postoperative cardiac
   dysfunction
SO PEDIATRICS
LA English
DT Article; Proceedings Paper
CT Newborn Drug Development Initiative Workshop
CY MAR 29-30, 2004
CL Baltimore, MD
DE neonates; congenital heart disease; cardiopulmonary bypass surgery;
   postoperative myocardial dysfunction; vasoactive agents
ID ARTERIAL SWITCH OPERATION; CARDIOPULMONARY BYPASS; INTRACARDIAC SURGERY;
   RANDOMIZED-TRIAL; SEPTIC SHOCK; DOUBLE-BLIND; INFANTS; CHILDREN; REPAIR;
   PERFORMANCE
AB As many as one third of the 35 000 to 40 000 infants born in the United States each year with significant congenital heart defects require surgery before the first year of life. Intraoperative support techniques, including cardiopulmonary bypass, can precipitate a complex, systemic inflammatory response that impairs the function of multiple organs and results in more hemodynamic instability and early morbidity in newborns than in older infants and children. Vasoactive agents are routinely used in the postoperative management of these patients either to treat or prevent hemodynamic instability and low cardiac output. However, the effectiveness of vasoactive agents used either individually or in combination in achieving specific therapeutic goals such as maintenance of a minimum cardiac index or arteriovenous oxygen saturation difference has not been systematically evaluated in preterm and term neonates. In addition, there are insufficient safety data for these agents in preterm and term neonates, both as individual agents and in combination. This article proposes a framework for developing prospective clinical studies to determine the efficacy of different vasoactive agents to promote adequate cardiac output and hemodynamic stability after neonatal cardiac surgery. The framework provides an overview of the issues relevant to the design of prospective clinical studies of vasoactive agents in the newborn patient population undergoing cardiac surgery. The issues identified by the cardiology group illustrate the difficulty of designing and executing clinical trials in vulnerable pediatric populations with limited numbers of patients, especially when standard practice is widely believed to be beneficial despite the lack of rigorous data to support such practice.
C1 Stanford Univ, Sch Med, Dept Pediat, Div Pediat Cardiol, Palo Alto, CA 94304 USA.
   Univ Calif San Francisco, San Francisco Childrens Hosp, Sch Med, Dept Pediat, San Francisco, CA 94143 USA.
   NHLBI, Div Heart & Vasc Dis, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Roth, SJ (reprint author), Stanford Univ, Lucile Packard Childrens Hosp,Sch Med, Dept Pediat, Div Pediat Cardiol,Cardiovasc Intens Care Unit, 750 Welch Rd,Suite 325, Palo Alto, CA 94304 USA.
NR 35
TC 12
Z9 13
U1 0
U2 0
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD MAR
PY 2006
VL 117
IS 3
SU S
BP S40
EP S46
DI 10.1542/peds.2005-0620G
PG 7
WC Pediatrics
SC Pediatrics
GA 017XT
UT WOS:000235727300006
PM 16777821
ER

PT J
AU Hardin, MG
   Perez-Edgar, K
   Guyer, AE
   Pine, DS
   Fox, NA
   Ernst, M
AF Hardin, MG
   Perez-Edgar, K
   Guyer, AE
   Pine, DS
   Fox, NA
   Ernst, M
TI Reward and punishment sensitivity in shy and non-shy adults: Relations
   between social and motivated behavior
SO PERSONALITY AND INDIVIDUAL DIFFERENCES
LA English
DT Article
DE motivation; reward; punishment; social behavior; shyness; anxiety;
   behavioral inhibition
ID AUTONOMIC ACTIVITY; PERSONALITY; DEPRESSION; SHYNESS; PHOBIA;
   ANTICIPATION; TEMPERAMENT; DISORDERS; ANXIETY; BRAIN
AB Few studies have examined underlying mechanisms linking social behavior, motivated behavior, and reward and punishment systems. The current study was designed to investigate these mechanisms by examining responses to both rewarding and punishing non-social stimuli in shy and non-shy adults. Ninety-three participants, comprising three social behavior groups (Shy, Non-shy, Control) completed the Monetary Incentive Delay task. Consistent with previous research, all participants were sensitive to incentive manipulations. There were also significant individual differences in response. Non-shy participants demonstrated sensitivity to both reward and punishment stimuli, and behavior indicative of high levels of arousal in approach motivation. Shy individuals demonstrated a large discrepancy in sensitivity to reward compared to punishment, with this discrepancy being driven by enhanced sensitivity to reward. Their behavior suggested conflict generated by increased arousal in both approach and withdrawal motivation systems. Current findings contribute to theoretical accounts of relations between social behavior and behavior modulated by reward and punishment. These findings carry implications for the study of psychopathology and neuroimaging research designed to examine relationships between social behavior, motivated behavior, and underlying reward and punishment systems. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Natl Inst Mental Hlth, Sect Dev Affect Neurosci, NIH DHHS, Bethesda, MD 20892 USA.
   Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
RP Hardin, MG (reprint author), Natl Inst Mental Hlth, Sect Dev Affect Neurosci, NIH DHHS, 15K North Dr,Rm 208, Bethesda, MD 20892 USA.
EM hardinm@mail.nih.gov
RI Perez-Edgar, Koraly/B-8463-2008; 
OI Perez-Edgar, Koraly/0000-0003-4051-9563
FU Intramural NIH HHS [Z99 MH999999]
NR 41
TC 23
Z9 26
U1 1
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0191-8869
J9 PERS INDIV DIFFER
JI Pers. Individ. Differ.
PD MAR
PY 2006
VL 40
IS 4
BP 699
EP 711
DI 10.1016/j.paid.2005.08.010
PG 13
WC Psychology, Social
SC Psychology
GA 024XJ
UT WOS:000236229500007
PM 19718273
ER

PT J
AU Baird, AE
AF Baird, AE
TI The blood option: transcriptional profiling in clinical trials
SO PHARMACOGENOMICS
LA English
DT Editorial Material
ID MESSENGER-RNA EXPRESSION; GENE-EXPRESSION; MICROARRAY PLATFORMS; DNA
   MICROARRAY; BREAST-CANCER; CELL; CLASSIFICATION; CARCINOMAS; PREDICTION;
   DISEASE
C1 NINDS, Stroke Neurosci Unit, NIH, Bethesda, MD 20892 USA.
RP Baird, AE (reprint author), NINDS, Stroke Neurosci Unit, NIH, 10 Ctr Dr,MSC 1294,Room 3N258, Bethesda, MD 20892 USA.
EM bairda@ninds.nih.gov
NR 29
TC 11
Z9 12
U1 0
U2 0
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
   1QB, ENGLAND
SN 1462-2416
J9 PHARMACOGENOMICS
JI Pharmacogenomics
PD MAR
PY 2006
VL 7
IS 2
BP 141
EP 144
DI 10.2217/14622416.7.2.141
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 018GO
UT WOS:000235752500001
PM 16515391
ER

PT J
AU Trepicchio, WL
   Essayan, D
   Hall, ST
   Schechter, G
   Tezak, Z
   Wang, SJ
   Weinreich, D
   Simon, R
AF Trepicchio, WL
   Essayan, D
   Hall, ST
   Schechter, G
   Tezak, Z
   Wang, SJ
   Weinreich, D
   Simon, R
TI Designing prospective clinical pharmacogenomic (PG) trials: meeting
   report on drug development strategies to enhance therapeutic decision
   making
SO PHARMACOGENOMICS JOURNAL
LA English
DT Editorial Material
ID MICROARRAY DATA; LUNG-CANCER; MUTATIONS; GEFITINIB; FDA
C1 Millennium Pharmaceut Inc, Div Mol Med, Cambridge, MA 02139 USA.
   NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
   GeneLog Inc, Gaithersburg, MD USA.
   US FDA, Off Biostat, Off Pharmacoepidemiol & Stat Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA.
   US FDA, Ctr Devices & Radiol Hlth, OIVD, Rockville, MD 20857 USA.
   US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
   GlaxoSmithKline Inc, Us Regulatory Affairs, Res Triangle Pk, NC USA.
   Amgen Inc, Regulatory Affairs, Thousand Oaks, CA USA.
RP Trepicchio, WL (reprint author), Millennium Pharmaceut Inc, Div Mol Med, 40 Landsdowne St, Cambridge, MA 02139 USA.
EM wtrepicchio@mpi.com
NR 11
TC 4
Z9 7
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1470-269X
J9 PHARMACOGENOMICS J
JI Pharmacogenomics J.
PD MAR-APR
PY 2006
VL 6
IS 2
BP 89
EP 94
DI 10.1038/sj.tpj.6500344
PG 6
WC Genetics & Heredity; Pharmacology & Pharmacy
SC Genetics & Heredity; Pharmacology & Pharmacy
GA 033XV
UT WOS:000236889200003
PM 16402088
ER

PT J
AU Pacher, P
   Nivorozhkin, A
   Szabo, C
AF Pacher, P
   Nivorozhkin, A
   Szabo, C
TI Therapeutic effects of xanthine oxidase inhibitors: Renaissance half a
   century after the discovery of allopurinol
SO PHARMACOLOGICAL REVIEWS
LA English
DT Review
ID CHRONIC HEART-FAILURE; OF-WISCONSIN SOLUTION; SPONTANEOUSLY
   HYPERTENSIVE-RATS; INTESTINAL ISCHEMIA-REPERFUSION; FOCAL
   CEREBRAL-ISCHEMIA; MYOCARDIAL INFARCT SIZE; FREE-RADICAL GENERATION;
   OXYGEN-FREE-RADICALS; ACUTE LUNG INJURY; POLY(ADP-RIBOSE) POLYMERASE
   ACTIVATION
AB The prototypical xanthine oxidase ( XO) inhibitor allopurinol, has been the cornerstone of the clinical management of gout and conditions associated with hyperuricemia for several decades. More recent data indicate that XO also plays an important role in various forms of ischemic and other types of tissue and vascular injuries, inflammatory diseases, and chronic heart failure. Allopurinol and its active metabolite oxypurinol showed considerable promise in the treatment of these conditions both in experimental animals and in small-scale human clinical trials. Although some of the beneficial effects of these compounds may be unrelated to the inhibition of the XO, the encouraging findings rekindled significant interest in the development of additional, novel series of XO inhibitors for various therapeutic indications. Here we present a critical overview of the effects of XO inhibitors in various pathophysiological conditions and also review the various emerging therapeutic strategies offered by this approach.
C1 NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
   Ctr Integrat Med & Innovat Technol, Cambridge, MA USA.
   Univ Med & Dent New Jersey, Dept Surg, Newark, NJ USA.
   Semmelweis Univ, Med Sch, Dept Human Physiol & Clin Expt Res, Budapest, Hungary.
RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413,Room 2N-17, Bethesda, MD 20892 USA.
EM pacher@mail.nih.gov
RI Pacher, Pal/B-6378-2008
OI Pacher, Pal/0000-0001-7036-8108
FU Intramural NIH HHS [Z01 AA000375-02]
NR 428
TC 461
Z9 471
U1 9
U2 77
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0031-6997
J9 PHARMACOL REV
JI Pharmacol. Rev.
PD MAR
PY 2006
VL 58
IS 1
BP 87
EP 114
DI 10.1124/pr.58.1.6
PG 28
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 017GZ
UT WOS:000235683400008
PM 16507884
ER

PT J
AU Wrenn, CC
   Turchi, JN
   Schlosser, S
   Dreiling, JL
   Stephenson, DA
   Crawley, JN
AF Wrenn, CC
   Turchi, JN
   Schlosser, S
   Dreiling, JL
   Stephenson, DA
   Crawley, JN
TI Performance of galanin transgenic mice in the 5-choice serial reaction
   time attentional task
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE galanin; attention; mice; five-choice; operant; transgenic;
   neuropeptide; acetylcholine
ID FOREBRAIN CHOLINERGIC NEURONS; RAT VENTRAL HIPPOCAMPUS; INHIBITS
   ACETYLCHOLINE-RELEASE; NONMATCHING-TO-SAMPLE; BASAL FOREBRAIN;
   ALZHEIMERS-DISEASE; PHOSPHOINOSITIDE TURNOVER; PREFRONTAL CORTEX;
   IN-VIVO; VISUAL-DISCRIMINATION
AB The neuropeptide galanin impairs learning and memory in rodents. The mechanism underlying the cognitive effects of galanin may be related to inhibitory effects of galanin on cholinergic transmission. As cholinergic function is thought to modulate sustained attention, the present study examined whether galanin-overexpressing transgenic mice have impairments in sustained attention. Galanin transgenic (GAL-tg) mice and wildtype (WT) littermate controls were trained in a 5-choice serial reaction time task, modified to assess sustained attention. GAL-tg and WT mice performed similarly during acquisition with respect to accuracy, total omissions, and response speed. Attentional mechanisms were challenged by parametric changes including increased event rate, event asynchrony, or decreased stimulus duration. Singly, these challenges did not differentially affect performance between genotypes. Concurrent administration of these challenges, which represents an optimal test of sustained attention, also had similar effects on GAL-tg and WT mice. When stimulus discriminability was reduced by constant illumination of the house light, GAL-tg mice omitted more trials than WT mice, but other measures of performance did not differ by genotype. Moreover, intraventricular injection of galanin in WT mice did not affect sustained attention. These data indicate that previously reported learning and memory effects of galanin are not secondary to attentional dysfunction. (c) 2006 Elsevier Inc. All rights reserved.
C1 NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA.
   NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA.
RP Wrenn, CC (reprint author), Drake Univ, Coll Pharm & Hlth Sci, 118 Fitch Hall, Des Moines, IA 50311 USA.
EM craige.wrenn@drake.edu
FU Intramural NIH HHS
NR 79
TC 22
Z9 22
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD MAR
PY 2006
VL 83
IS 3
BP 428
EP 440
DI 10.1016/j.pbb.2006.03.003
PG 13
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 053IM
UT WOS:000238298800010
PM 16626795
ER

PT J
AU Aleman, C
   Zanuy, D
   Jimenez, AI
   Cativiela, C
   Haspel, N
   Zheng, J
   Casanovas, J
   Wolfson, H
   Nussinov, R
AF Aleman, C
   Zanuy, D
   Jimenez, AI
   Cativiela, C
   Haspel, N
   Zheng, J
   Casanovas, J
   Wolfson, H
   Nussinov, R
TI Concepts and schemes for the re-engineering of physical protein modules:
   generating nanodevices via targeted replacements with constrained amino
   acids
SO PHYSICAL BIOLOGY
LA English
DT Article
ID ALPHA-HELICAL PEPTIDE; SIDE-CHAIN; CONFORMATIONAL PREFERENCES;
   MOLECULAR-SURFACE; HUMAN CALCITONIN; ANALOGS; DESIGN; PHENYLALANINE;
   SIMULATIONS; DIPEPTIDES
AB Physically building complex multi-molecular structures from naturally occurring biological macromolecules has aroused a great deal of interest. Here we focus on nanostructures composed of re-engineered, natural 'foldamer' building blocks. Our aim is to provide some of the underlying concepts and schemes for crafting structures utilizing such conformationally relatively stable molecular components. We describe how, via chemical biology strategies, it is further possible to chemically manipulate the foldamer building blocks toward specific shape-driven structures, which in turn could be used toward potential-designed functions. We outline the criteria in choosing candidate foldamers from the vast biological repertoire, and how to enhance their stability through selected targeted replacements by non-proteinogenic conformationally constrained amino acids. These approaches combine bioinformatics, high performance computations and mathematics with synthetic organic chemistry. The resulting artificially engineered self-organizing molecular scale structures take advantage of nature's nanobiology toolkit and at the same time improve on it, since their new targeted function differs from that optimized by evolution. The major challenge facing nanobiology is to be able to exercise fine control over the performance of these target-specific molecular machines.
C1 Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, E-08028 Barcelona, Spain.
   Univ Zaragoza, Dept Quim Organ, Inst Ciencia Mat Aragon, CSIC, E-50009 Zaragoza, Spain.
   Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel.
   NCI, SAIC Frederick, Ctr Canc Res, Nanobiol Program, Ft Detrick, MD 21702 USA.
   Univ Lleida, Dept Quim, Escola Univ Politecn, E-25001 Lleida, Spain.
   Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel.
RP Univ Politecn Cataluna, Dept Engn Quim, ETS Engn Ind Barcelona, Diagonal 647, E-08028 Barcelona, Spain.
EM carlos.aleman@upc.edu; ruthn@ncifcrf.gov
RI Wolfson, Haim/A-1837-2011; Casanovas, Jordi/B-5435-2013; Zanuy,
   David/G-3930-2014; Zheng, Jie/B-5057-2013; Haspel, Nurit/D-1961-2017
OI Casanovas, Jordi/0000-0002-4914-9194; Zanuy, David/0000-0001-7704-2178;
   Zheng, Jie/0000-0003-1547-3612; 
FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]
NR 64
TC 20
Z9 21
U1 0
U2 3
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 1478-3967
EI 1478-3975
J9 PHYS BIOL
JI Phys. Biol.
PD MAR
PY 2006
VL 3
IS 1
BP S54
EP S62
DI 10.1088/1478-3975/3/1/S06
PG 9
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 029DZ
UT WOS:000236540400007
PM 16582465
ER

PT J
AU Zanuy, D
   Nussinov, R
   Aleman, C
AF Zanuy, D
   Nussinov, R
   Aleman, C
TI From peptide-based material science to protein fibrils: discipline
   convergence in nanobiology
SO PHYSICAL BIOLOGY
LA English
DT Article
ID MOLECULAR-DYNAMICS SIMULATIONS; ISLET AMYLOID POLYPEPTIDE; SOLID-STATE
   NMR; POLY(GAMMA-GLUTAMIC ACID); SUPRAMOLECULAR STRUCTURE; SECONDARY
   STRUCTURES; CHLOROFORM SOLUTION; SURFACE CALCULATION; CHAIN
   CONFORMATION; CRYSTAL-STRUCTURE
AB This paper illustrates the merits of convergence in nanobiology of two seemingly disparate fields, material science and computational biology. Traditionally, material science has been a discipline involving design and fabrication of synthetic polymers consisting of repeating units. Collaboration with synthetic organic chemists allowed design of new polymers, with a range of altered conformations. Yet, naturally occurring proteins are also materials. Their varied sequences and structures should enrich material science providing more complex shapes, scaffolds and chemical properties. For material scientists, the enhanced coverage of chemical space obtained by integrating proteins and synthetic organic chemistry through the introduction of non-natural residues allows a range of new useful potential applications.
C1 Univ Politecn Catalunya, Dept Engn Quim, ETS Engn Ind Barcelona, E-08028 Barcelona, Spain.
   NCI, SAIC Frederick, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
   Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel.
RP Zanuy, D (reprint author), Univ Politecn Catalunya, Dept Engn Quim, ETS Engn Ind Barcelona, Diagonal 647, E-08028 Barcelona, Spain.
EM ruthn@ncifcrf.gov; carlos.aleman@upc.edu
RI Zanuy, David/G-3930-2014
OI Zanuy, David/0000-0001-7704-2178
FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]
NR 66
TC 13
Z9 14
U1 0
U2 4
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 1478-3967
J9 PHYS BIOL
JI Phys. Biol.
PD MAR
PY 2006
VL 3
IS 1
BP S80
EP S90
DI 10.1088/1478-3975/3/1/S08
PG 11
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 029DZ
UT WOS:000236540400009
PM 16582467
ER

PT J
AU Nussinov, R
   Aleman, C
AF Nussinov, R
   Aleman, C
TI Nanobiology: from physics and engineering to biology - Preface
SO PHYSICAL BIOLOGY
LA English
DT Editorial Material
C1 NCI, SAIC Frederick, Ctr Canc Res, Nanobiol Program, Ft Detrick, MD 21702 USA.
   Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel.
   Univ Politecn Catalunya, Dept Engn Quim, ETS Engn Ind Barcelona, E-08028 Barcelona, Spain.
RP Nussinov, R (reprint author), NCI, SAIC Frederick, Ctr Canc Res, Nanobiol Program, Ft Detrick, MD 21702 USA.
EM ruthn@ncifcrf.gov; carlos.aleman@upc.edu
NR 0
TC 0
Z9 1
U1 0
U2 2
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 1478-3967
J9 PHYS BIOL
JI Phys. Biol.
PD MAR
PY 2006
VL 3
IS 1
DI 10.1088/1478-3967/3/1/E01
PG 2
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 029DZ
UT WOS:000236540400001
ER

PT J
AU Strunnikov, AV
AF Strunnikov, AV
TI SMC complexes in bacterial chromosome condensation and segregation
SO PLASMID
LA English
DT Article
DE SMC; condensin; chromosome condensation; chromosome segregation
ID BACILLUS-SUBTILIS SMC; STRAND-BREAK REPAIR; STRUCTURAL MAINTENANCE;
   SACCHAROMYCES-CEREVISIAE; DNA-REPAIR; SUBCELLULAR-LOCALIZATION;
   CHROMATID SEGREGATION; MITOTIC CHROMOSOME; PROTEIN COMPLEX; DUAL ROLES
AB Bacterial chromosomes segregate via a partition apparatus that employs a score of specialized proteins. The SMC complexes play a crucial role in the chromosome partitioning process by organizing bacterial chromosomes through their ATP-dependent chromatin-compacting activity. Recent progress in the composition of these complexes and elucidation of their structural and enzymatic properties has advanced our comprehension of chromosome condensation and segregation mechanics in bacteria. (c) 2005 Elsevier Inc. All rights reserved.
C1 NICHD, NIH, Bethesda, MD 20892 USA.
RP Strunnikov, AV (reprint author), NICHD, NIH, Bethesda, MD 20892 USA.
EM strunnik@mail.nih.gov
OI Strunnikov, Alexander/0000-0002-9058-2256
FU Intramural NIH HHS [Z01 HD001903-11, Z99 AI999999]
NR 77
TC 13
Z9 14
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0147-619X
J9 PLASMID
JI Plasmid
PD MAR
PY 2006
VL 55
IS 2
BP 135
EP 144
DI 10.1016/j.plasmid.2005.08.004
PG 10
WC Genetics & Heredity; Microbiology
SC Genetics & Heredity; Microbiology
GA 018RC
UT WOS:000235781500005
PM 16229890
ER

PT J
AU Murphy, WJ
   Wilkerson, AJP
   Raudsepp, T
   Agarwala, R
   Schaffer, AA
   Stanyon, R
   Chowdhary, BP
AF Murphy, William J.
   Wilkerson, Alison J. Pearks
   Raudsepp, Terje
   Agarwala, Richa
   Schaffer, Alejandro A.
   Stanyon, Roscoe
   Chowdhary, Bhanu P.
TI Novel gene acquisition on carnivore Y chromosomes
SO PLOS GENETICS
LA English
DT Article
ID RADIATION HYBRID MAP; HUMAN X-CHROMOSOME; SEX-DETERMINING GENES;
   MALE-SPECIFIC REGION; DIRECT SELECTION; PSEUDOAUTOSOMAL REGION;
   EVOLUTIONARY STRATA; GENOMIC REGIONS; DOMESTIC CAT; PHYSICAL MAP
AB Despite its importance in harboring genes critical for spermatogenesis and male-specific functions, the Y chromosome has been largely excluded as a priority in recent mammalian genome sequencing projects. Only the human and chimpanzee Y chromosomes have been well characterized at the sequence level. This is primarily due to the presumed low overall gene content and highly repetitive nature of the Y chromosome and the ensuing difficulties using a shotgun sequence approach for assembly. Here we used direct cDNA selection to isolate and evaluate the extent of novel Y chromosome gene acquisition in the genome of the domestic cat, a species from a different mammalian superorder than human, chimpanzee, and mouse (currently being sequenced). We discovered four novel Y chromosome genes that do not have functional copies in the finished human male-specific region of the Y or on other mammalian Y chromosomes explored thus far. Two genes are derived from putative autosomal progenitors, and the other two have X chromosome homologs from different evolutionary strata. All four genes were shown to be multicopy and expressed predominantly or exclusively in testes, suggesting that their duplication and specialization for testis function were selected for because they enhance spermatogenesis. Two of these genes have testis-expressed, Y-borne copies in the dog genome as well. The absence of the four newly described genes on other characterized mammalian Y chromosomes demonstrates the gene novelty on this chromosome between mammalian orders, suggesting it harbors many lineage-specific genes that may go undetected by traditional comparative genomic approaches. Specific plans to identify the male-specific genes encoded in the Y chromosome of mammals should be a priority.
C1 Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA.
   Natl Lib Med, Informat Engn Branch, Natl Ctr Biotechnol Informat, NIH,Dept Hlth & Human Serv, Bethesda, MD USA.
   Natl Lib Med, Computat Biol Branch, Natl Ctr Biotechnol Informat, NIH,Dept Hlth & Human Serv, Bethesda, MD USA.
   Univ Florence, Dept Anim Breeding & Genet, Florence, Italy.
RP Murphy, WJ (reprint author), Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA.
EM wmurphy@cvm.tamu.edu
RI Schaffer, Alejandro/F-2902-2012; 
OI Stanyon, Roscoe/0000-0002-7229-1092
FU Intramural NIH HHS
NR 52
TC 41
Z9 42
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD MAR
PY 2006
VL 2
IS 3
BP 353
EP 363
AR e43
DI 10.1371/journal.pgen.0020043
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 070BD
UT WOS:000239494400013
PM 16596168
ER

PT J
AU Fee, E
   Parry, M
AF Fee, Elizabeth
   Parry, Manon
TI David Bodian - 15 May 1910-18 September 1992
SO PROCEEDINGS OF THE AMERICAN PHILOSOPHICAL SOCIETY
LA English
DT Biographical-Item
C1 Natl Lib Med, Hist Med Div, NIH, Bethesda, MD 20894 USA.
RP Fee, E (reprint author), Natl Lib Med, Hist Med Div, NIH, Bethesda, MD 20894 USA.
NR 1
TC 1
Z9 1
U1 0
U2 0
PU AMER PHILOSOPHICAL SOC
PI PHILADELPHIA
PA 104 SOUTH FIFTH ST, PHILADELPHIA, PA 19106-3387 USA
SN 0003-049X
J9 P AM PHILOS SOC
JI Proc. Amer. Philos. Soc.
PD MAR
PY 2006
VL 150
IS 1
BP 167
EP 172
PG 6
WC Humanities, Multidisciplinary
SC Arts & Humanities - Other Topics
GA 086JJ
UT WOS:000240669300009
PM 17526159
ER

PT J
AU Eling, T
AF Eling, T
TI Alternation in gene expression by Cox inhibitors
SO PROSTAGLANDINS & OTHER LIPID MEDIATORS
LA English
DT Meeting Abstract
CT 9th International Conference Eicosanoids
CY SEP 11-14, 2005
CL San Francisco, CA
C1 NIEHS, NIH, Lab Mol Carcinogenesis Res, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-8823
J9 PROSTAG OTH LIPID M
JI Prostaglandins Other Lipid Mediat.
PD MAR
PY 2006
VL 79
IS 1-2
BP 150
EP 150
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 027NS
UT WOS:000236422900035
ER

PT J
AU Arita, M
   Bianchini, F
   Aliberti, J
   Sher, A
   Yoshida, M
   Blumberg, RS
   Chiang, N
   Hong, S
   Petasis, NA
   Serhan, CN
AF Arita, M
   Bianchini, F
   Aliberti, J
   Sher, A
   Yoshida, M
   Blumberg, RS
   Chiang, N
   Hong, S
   Petasis, NA
   Serhan, CN
TI Omega-3 derived lipid mediator resolvin E1: Stereochemistry, receptor,
   and anti-inflammatory and protective actions in colitis
SO PROSTAGLANDINS & OTHER LIPID MEDIATORS
LA English
DT Meeting Abstract
CT 9th International Conference Eicosanoids
CY SEP 11-14, 2005
CL San Francisco, CA
C1 Brigham & Womens Hosp, Div Gastroenterol, Dept Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
   Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
   Univ So Calif, Loker Hydrocarbon Res Inst, Los Angeles, CA 90089 USA.
RI Aliberti, Julio/I-7354-2013
OI Aliberti, Julio/0000-0003-3420-8478
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-8823
J9 PROSTAG OTH LIPID M
JI Prostaglandins Other Lipid Mediat.
PD MAR
PY 2006
VL 79
IS 1-2
BP 154
EP 154
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 027NS
UT WOS:000236422900050
ER

PT J
AU Gray, T
   Lao, HC
   Lee, C
   Langenbach, R
AF Gray, T
   Lao, HC
   Lee, C
   Langenbach, R
TI The EP2 receptor plays a prominent role in the regulation of papilloma
   formation during mouse skin tumorigenesis
SO PROSTAGLANDINS & OTHER LIPID MEDIATORS
LA English
DT Meeting Abstract
CT 9th International Conference Eicosanoids
CY SEP 11-14, 2005
CL San Francisco, CA
C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-8823
J9 PROSTAG OTH LIPID M
JI Prostaglandins Other Lipid Mediat.
PD MAR
PY 2006
VL 79
IS 1-2
BP 161
EP 162
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 027NS
UT WOS:000236422900079
ER

PT J
AU Mcentee, M
   Ziegler, C
   Ray, M
   Tomer, K
   Whelan, J
AF Mcentee, M
   Ziegler, C
   Ray, M
   Tomer, K
   Whelan, J
TI Modification of prostate cancer progression by dietary polyunsaturated
   fatty acids
SO PROSTAGLANDINS & OTHER LIPID MEDIATORS
LA English
DT Meeting Abstract
CT 9th International Conference Eicosanoids
CY SEP 11-14, 2005
CL San Francisco, CA
C1 Univ Tennessee, Dept Pathobiol, Knoxville, TN 37996 USA.
   NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
   Univ Tennessee, Dept Nutr, Knoxville, TN 37996 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-8823
J9 PROSTAG OTH LIPID M
JI Prostaglandins Other Lipid Mediat.
PD MAR
PY 2006
VL 79
IS 1-2
BP 162
EP 162
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 027NS
UT WOS:000236422900081
ER

PT J
AU Chun, KS
   Akunda, JK
   Lee, CA
   Langenbach, R
AF Chun, KS
   Akunda, JK
   Lee, CA
   Langenbach, R
TI Cyclooxygenase-2 inhibits UVB-induced apoptosis in mouse skin through
   activation of EP2 receptor
SO PROSTAGLANDINS & OTHER LIPID MEDIATORS
LA English
DT Meeting Abstract
CT 9th International Conference Eicosanoids
CY SEP 11-14, 2005
CL San Francisco, CA
C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-8823
J9 PROSTAG OTH LIPID M
JI Prostaglandins Other Lipid Mediat.
PD MAR
PY 2006
VL 79
IS 1-2
BP 173
EP 173
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 027NS
UT WOS:000236422900123
ER

PT J
AU Kambe, A
   Moon, Y
   Iguchi, G
   Kamitani, H
   Watanabe, T
   Eling, TE
AF Kambe, A
   Moon, Y
   Iguchi, G
   Kamitani, H
   Watanabe, T
   Eling, TE
TI Troglitazone suppresses the expression of prostaglandin E2 receptor
   subtype EP4 via MEK/Erk pathway
SO PROSTAGLANDINS & OTHER LIPID MEDIATORS
LA English
DT Meeting Abstract
CT 9th International Conference Eicosanoids
CY SEP 11-14, 2005
CL San Francisco, CA
C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
   Pusan Natl Univ, Dept Microbiol & Immunol, Sch Med, Pusan 602739, South Korea.
   Tottori Univ, Fac Med, Div Neurosurg, Inst Neurol Sci, Yonago, Tottori 6838504, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-8823
J9 PROSTAG OTH LIPID M
JI Prostaglandins Other Lipid Mediat.
PD MAR
PY 2006
VL 79
IS 1-2
BP 191
EP 191
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 027NS
UT WOS:000236422900191
ER

PT J
AU Chatterjee, DK
   Esposito, D
AF Chatterjee, DK
   Esposito, D
TI Enhanced soluble protein expression using two new fusion tags
SO PROTEIN EXPRESSION AND PURIFICATION
LA English
DT Article
DE solubility tag; protein expression; inclusion bodies; fusion proteins
ID MALTOSE-BINDING PROTEIN; INCLUSION-BODY FORMATION; OUTER-MEMBRANE
   PROTEIN; ESCHERICHIA-COLI; MOLECULAR CHAPERONES; MESSENGER-RNA; GENE;
   PURIFICATION; BACTERIOPHAGE-T7; POLYPEPTIDES
AB Production of soluble recombinant proteins is vital for structure-function analysis and therapeutic applications. Unfortunately, when expressed in a heterologous host, such as Escherichia coli, most proteins are expressed as insoluble aggregates. Two new fusion partners have been identified to address these solubility problems. One of the tags was derived from a bacteriophage T7 protein kinase and the other one from a small E coli chaperone, Skp. We have expressed a panel of insoluble human proteins including Hif1 alpha, IL13, and folliculin as fusion proteins using these tags. Most of these fusion proteins were able to be expressed in a soluble form and could be purified by virtue of a Strep-tag It installed at the amino-terminal end of the fusion partners. In addition, we show that some of these proteins remained soluble after removal of the fusion tags by a site-specific protease. The results with these tags compare favorably to results with the most commonly used solubility tags described in the literature. Therefore, these two new fusion tags have the potential to express soluble proteins when fused with many recalcitrant proteins. (c) 2005 Elsevier Inc. All rights reserved.
C1 SAIC Frederick Inc, Natl Canc Inst Frederick, Prot Express Lab, Frederick, MD 21702 USA.
RP Chatterjee, DK (reprint author), SAIC Frederick Inc, Natl Canc Inst Frederick, Prot Express Lab, 1050 Boyles St,Bldg 327, Frederick, MD 21702 USA.
EM chatterjee@ncifcrf.gov
FU NCI NIH HHS [N01-CO-12400]
NR 29
TC 38
Z9 44
U1 1
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-5928
J9 PROTEIN EXPRES PURIF
JI Protein Expr. Purif.
PD MAR
PY 2006
VL 46
IS 1
BP 122
EP 129
DI 10.1016/j.pep.2005.07.028
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
   Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 020IR
UT WOS:000235902700015
PM 16146696
ER

PT J
AU Moore, RA
   Herzog, C
   Errett, J
   Kocisko, DA
   Arnold, KM
   Hayes, SF
   Priola, SA
AF Moore, RA
   Herzog, C
   Errett, J
   Kocisko, DA
   Arnold, KM
   Hayes, SF
   Priola, SA
TI Octapeptide repeat insertions increase the rate of protease-resistant
   prion protein formation
SO PROTEIN SCIENCE
LA English
DT Article
DE prion; fibril; amyloid; kinetics; octapeptide repeat; insertional
   mutations
ID CREUTZFELDT-JAKOB-DISEASE; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES;
   AMYLOID FIBRIL; LIMITED PROTEOLYSIS; IN-VITRO; BIOCHEMICAL-PROPERTIES;
   CULTURED-CELLS; PRNP GENE; MUTATION; SCRAPIE
AB A central feature of transmissible spongiform encephalopathies (TSE or prion diseases) involves the conversion of a normal, protease-sensitive glycoprotein termed prion protein (PrP-sen) into a protease-resistant form, termed PrP-res. The N terminus of PrP-sen has five copies of a repeating eight amino acid sequence (octapeptide repeat). The presence of one to nine extra copies of this motif is associated with a heritable form of Creutzfeld-Jakob disease (CJD) in humans. An increasing number of octapeptide repeats correlates with earlier CJD onset, suggesting that the rate at which PrP-sen misfolds into PrP-res may be influenced by these mutations. In order to determine if octapeptide repeat insertions influence the rate at which PrP-res is formed, we used a hamster PrP amyloid-forming peptide (residues 23-144) into which two to 10 extra octapeptide repeats were inserted. The spontaneous formation of protease-resistant PrP amyloid from these peptides was more rapid in response to an increased number of octapeptide repeats. Furthermore, experiments using full-length glycosylated hamster PrP-sen demonstrated that PrP-res formation a ISO occurred more rapidly from PrP-sen molecules expressing 10 extra copies of the octapeptide repeat. The rate increase for PrP-res formation did not appear to be due to any influence of the octapeptide repeat region on PrP structure, but rather to more rapid binding between PrP molecules. Our data from both models support the hypothesis that extra octapeptide repeats in PrP increase the rate at which protease resistant PrP is formed which in turn may affect the rate of disease onset in familial forms of CJD.
C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA.
   NIAID, Rocky Mt Labs, Electron Microscopy Branch, NIH, Hamilton, MT 59840 USA.
   Commissariat Energie Atom, Dept Rech Med, Fontenay Aux Roses, France.
RP Priola, SA (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM spriola@nih.gov
NR 64
TC 38
Z9 40
U1 0
U2 1
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD MAR
PY 2006
VL 15
IS 3
BP 609
EP 619
DI 10.1110/ps.051822606
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 021AS
UT WOS:000235955400021
PM 16452616
ER

PT J
AU Marino-Ramirez, L
   Hsu, B
   Baxevanis, AD
   Landsman, D
AF Marino-Ramirez, L
   Hsu, B
   Baxevanis, AD
   Landsman, D
TI The histone database: A comprehensive resource for histones and histone
   fold-containing proteins
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE histones; histone-like proteins; multiple sequence alignments; histone
   database
ID MULTIPLE SEQUENCE ALIGNMENT; NUCLEOSOMES; PROGRAMS; PROMOTER; MOTIF
AB TheThe Histone Database is a curated and searchable collection of full-length sequences and structures of histones and nonhistone proteins containing histone-like folds, compiled from major public databases. Several new histone fold-containing proteins have been identified, including the huntingtin-interacting protein HYPM. Additionally, based on the recent crystal structure of the Son of Sevenless protein, an interpretation of the sequence analysis of the histone fold domain is presented. The database contains an updated collection of multiple sequence alignments for the four core histones (H2A, H2B, H3, and H4) and the linker histones (H1/H5) from a total of 975 organisms. The database also contains information on the human histone gene complement and provides links to three-dimensional structures of histone and histone fold-containing proteins. The Histone Database is a comprehensive bioinformatics resource for the study of structure and function of histones and histone fold-containing proteins. The database is available at http://research.nhgri.nih.gov/histones/.
C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Computat Biol Branch, Bethesda, MD 20894 USA.
   NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Landsman, D (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Computat Biol Branch, 8600 Rockville Pike,MSC 6075, Bethesda, MD 20894 USA.
EM landsman@ncbi.nlm.nih.gov
RI Landsman, David/C-5923-2009; Marino-Ramirez, Leonardo/I-5759-2013; 
OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman,
   David/0000-0002-9819-6675
FU Intramural NIH HHS [Z99 LM999999]
NR 20
TC 36
Z9 39
U1 1
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0887-3585
J9 PROTEINS
JI Proteins
PD MAR 1
PY 2006
VL 62
IS 4
BP 838
EP 842
DI 10.1002/prot.20814
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 019XV
UT WOS:000235872700002
PM 16345076
ER

PT J
AU Ernst, M
   Pine, DS
   Hardin, M
AF Ernst, M
   Pine, DS
   Hardin, M
TI Triadic model of the neurobiology of motivated behavior in adolescence
SO PSYCHOLOGICAL MEDICINE
LA English
DT Review
ID NUCLEUS-ACCUMBENS DOPAMINE; ANTERIOR CINGULATE CORTEX; EVENT-RELATED
   POTENTIALS; PREFRONTAL CORTEX; DECISION-MAKING; ORBITOFRONTAL CORTEX;
   HUMAN AMYGDALA; FACIAL EXPRESSIONS; BRAIN-DEVELOPMENT; MAJOR DEPRESSION
AB Background. Risk-taking behavior is a major cause of morbidity and mortality in adolescence. In the context of decision theory and motivated (goal-directed) behavior, risk-taking reflects a pattern of decision-making that favors the selection of courses of action with uncertain and possibly harmful consequences. We present a triadic, neuroscience systems-based model of adolescent decision-making.
   Method. We review the functional role and neurodevelopmental findings of three key structures in the control of motivated behavior, i.e. amygdala, nucleus accumbens, and medial/ventral prefrontal cortex. We adopt a cognitive neuroscience approach to motivated behavior that uses a temporal fragmentation of a generic motivated action. Predictions about the relative contributions of the triadic nodes to the three stages of a motivated action during adolescence are proposed.
   Results. The propensity during adolescence for reward/novelty seeking in the face of uncertainty or potential harm might be explained by a strong reward system (nucleus accumbens), a weak harm-avoidant system (amygdala), and/or an inefficient supervisory system (medial/ventral prefrontal cortex). Perturbations in these systems may contribute to the expression of psychopathology, illustrated here with depression and anxiety.
   Conclusions. A triadic model, integrated in a temporally organized map of motivated behavior, can provide a helpful framework that suggests specific hypotheses of neural bases of typical and atypical adolescent behavior.
C1 NIMH, Sect Dev & Affect Neurosc, Mood & Anxiety Disorders Program, NIH,HHS, Bethesda, MD 20892 USA.
RP Ernst, M (reprint author), NIMH, Sect Dev & Affect Neurosc, Mood & Anxiety Disorders Program, NIH,HHS, 15K North Dr, Bethesda, MD 20892 USA.
EM ernstm@mail.nih.gov
FU Intramural NIH HHS [Z99 MH999999]
NR 150
TC 305
Z9 308
U1 17
U2 41
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD MAR
PY 2006
VL 36
IS 3
BP 299
EP 312
DI 10.1017/S0033291705005891
PG 14
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 019CE
UT WOS:000235812400002
PM 16472412
ER

PT J
AU Nguyen, HT
   Zonderman, AB
AF Nguyen, HT
   Zonderman, AB
TI Relationship between age and aspects of depression: Consistency and
   reliability across two longitudinal studies
SO PSYCHOLOGY AND AGING
LA English
DT Article
DE age; depression; CES-D; subscales
ID SCALE CES-D; GENDER DIFFERENCES; MAJOR DEPRESSION; OLDER-ADULTS; LATER
   LIFE; SYMPTOMS; SAMPLE; MIDDLE; WOMEN; SEX
AB In this study, the authors examined cross-sectional and longitudinal age and gender differences in each of the Center for Epidemiological Studies Depression Scale's 4 subscales of depressive symptomatology. Two independent studies (Sample 1 = 2,076; Sample 2 = 943) were used for purposes of establishing stability of findings. Results indicate a reasonable degree of stability among adults under 70 years of age. However, there were significant age-related increases in somatic symptoms and lack of well-being after approximately 70 years of age, whereas symptoms related to depressed affect and interpersonal problems remained stable. Notably, depressive affect symptoms remained stable given significant age-related somatic changes. The addition of comorbid physical illness to the analysis did not reduce the association between age and depressive symptoms, indicating that part of the association was not substantially accounted for by physical health.
C1 NIA, Gerontol Res Ctr, Cognit Sect, Lab Personal & Cognit,NIH, Baltimore, MD 21224 USA.
RP Nguyen, HT (reprint author), NIA, Gerontol Res Ctr, Cognit Sect, Lab Personal & Cognit,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM nguyenha@grc.nia.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
NR 46
TC 24
Z9 26
U1 1
U2 7
PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0882-7974
J9 PSYCHOL AGING
JI Psychol. Aging
PD MAR
PY 2006
VL 21
IS 1
BP 119
EP 126
DI 10.1037/0882-7974.21.1.119
PG 8
WC Gerontology; Psychology, Developmental
SC Geriatrics & Gerontology; Psychology
GA 031RR
UT WOS:000236722200012
PM 16594797
ER

PT J
AU Wang, JS
   Fang, Q
   Liu, ZH
   Lu, L
AF Wang, JS
   Fang, Q
   Liu, ZH
   Lu, L
TI Region-specific effects of brain corticotropin-releasing factor receptor
   type 1 blockade on footshock-stress- or drug-priming-induced
   reinstatement of morphine conditioned place preference in rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE amygdala; bed nucleus of the stria terminalis; corticotropin-releasing
   factor; conditioned place preference; nucleus accumbens; opiate;
   reinstatement; relapse
ID COCAINE-INDUCED REINSTATEMENT; INDUCED RELAPSE; STRIA TERMINALIS; BED
   NUCLEUS; SEEKING BEHAVIOR; NONPEPTIDE ANTAGONIST; INDUCED REACTIVATION;
   OPIATE WITHDRAWAL; HEROIN-SEEKING; DOPAMINE
AB Rationale: Systemic injections of the selective corticotropin-releasing factor 1 (CRF1) receptor antagonist CP-154,526 attenuate footshock-stress-induced reinstatement of heroin and cocaine seeking and morphine conditioned place preference (CPP). Intracranial injections of the nonselective CRF receptor antagonist D-Phe-CRF into the bed nucleus of the stria terminalis (BNST), but not the amygdala, attenuate footshock-induced reinstatement of cocaine seeking. However, the brain sites involved in the effect of CP-154,526 on footshock-induced reinstatement of opiate seeking are unknown. Objective: We used a CPP version of the reinstatement model to examine the role of CRF1 receptors in the BNST, amygdala, and nucleus accumbens (NAc) in footshock- or drug-priming-induced reinstatement of extinguished morphine CPP. Methods: Rats acquired morphine CPP over a period of 8 days during which they were given four morphine (10 mg/kg s.c.) and four saline injections and were subsequently confined to distinct chambers for 50 min. Subsequently, the morphine CPP was extinguished in 14 daily sessions during which rats were given saline injections and given access to both the saline- and morphine-paired chambers. The rats were then tested for reinstatement of morphine CPP induced by priming injections of morphine (0 or 3.0 mg/ kg s.c.) or by exposure to intermittent footshock (15 min, 0.5 mA). Prior to the test sessions, the rats were given intracranial injections of CP-154,526 (1.0 mu g) or vehicle into the BNST, amygdala, or NAc. Results: CP-154,526 injections into the BNST, but not the amygdala or NAc, attenuated footshock-stress-induced reinstatement of morphine CPP. In contrast, CP-154,526 injections into the amygdala or NAc, but not the BNST, attenuated morphine-priming-induced reinstatement of morphine CPP. Conclusion: The present results demonstrate dissociable roles of CRF1 receptors in the BNST, amygdala, and NAc in footshock-stress- vs morphine-priming-induced reinstatement of drug CPP.
C1 NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA.
   Guiyang Med Coll, Affiliated Hosp, Dept Pharmacol, Guiyang 550004, Peoples R China.
   New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA.
   Fudan Univ, Shanghai Med Sch, Natl Lab Med Neurobiol, Shanghai 200032, Peoples R China.
   Peking Univ, Natl Inst Drug Dependence, Beijing 100083, Peoples R China.
RP Lu, L (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM LLu@intra.nida.nih.gov
NR 66
TC 78
Z9 83
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAR
PY 2006
VL 185
IS 1
BP 19
EP 28
DI 10.1007/s00213-005-0262-6
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 015JL
UT WOS:000235547600003
PM 16374599
ER

PT J
AU Rutledge, T
   Reis, SE
   Olson, M
   Owens, J
   Kelsey, SF
   Pepine, CJ
   Mankad, S
   Rogers, WJ
   Sopko, G
   Cornell, CE
   Sharaf, B
   Mfrz, CNBY
AF Rutledge, T
   Reis, SE
   Olson, M
   Owens, J
   Kelsey, SF
   Pepine, CJ
   Mankad, S
   Rogers, WJ
   Sopko, G
   Cornell, CE
   Sharaf, B
   Mfrz, CNBY
TI Depression is associated with cardiac symptoms, mortality risk, and
   hospitalization among women with suspected coronary disease: The
   NHLBI-sponsored WISE study
SO PSYCHOSOMATIC MEDICINE
LA English
DT Article
DE women; CAD; depression; mortality; ischemia
ID ACUTE MYOCARDIAL-INFARCTION; HEART-DISEASE; CARDIOVASCULAR-DISEASE;
   GENDER-DIFFERENCES; CHEST-PAIN; ARTERY DISEASE; FAILURE; RECOVERY;
   SUPPORT; EVENTS
AB Objective: Depression is a robust predictor of cardiovascular risk. In this Study, we examined the association between depression measured in terms of symptom severity and treatment history, cardiac symptom presentation, and clinical outcomes among a sample of women with suspected myocardial ischemia. Methods: Seven hundred fifty women with chest pain, mean age 53.4, completed a diagnostic protocol including depression measures, coronary angiogram, ischemia testing, and coronary disease risk factor assessment. Five hundred five participants also completed the Beck Depression Inventory. We further tracked participants over a mean 2.3-year period to evaluate subsequent cardiac events, hospitalization, and mortality. Results: Depression treatment history and Current symptom severity were differentially associated with cardiac symptoms and outcomes. Both measures were reliably associated with coronary artery disease (CAD) risk factors and more severe cardiac symptoms. Depression symptom severity was linked to an increased mortality risk over follow-up (RR. = 1.05; 95% CI, 1.01-1.09), whereas depression treatment history predicted an increased risk of hospitalization (RR 1.3; 95% CI, 1.02-1.6), less severe CAD from angiogram, and a reduced likelihood of a positive ischemia test. Conclusion: Among a sample of women with suspected myocardial ischemia, depression was associated with cardiac symptoms and health Outcomes over follow-up. The findings extend the range of depression effects by demonstrating relationships within a sample of women experiencing symptoms of myocardial ischemia but showing a relative absence of flow limiting coronary stenoses. Depression measurements can assist the clinician in evaluating cardiac symptom presentation and cardiovascular risk status in women.
C1 Univ Calif San Diego, San Diego, CA 92103 USA.
   Univ Pittsburgh, Pittsburgh, PA USA.
   Univ Florida, Gainesville, FL USA.
   Allegheny Gen Hosp, Pittsburgh, PA USA.
   Univ Alabama, Birmingham, AL USA.
   Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   NHLBI, Bethesda, MD 20892 USA.
   Rhode Isl Hosp, Providence, RI USA.
RP Rutledge, T (reprint author), VA San Diego Healthcare Syst, Psychol Serv 116B, Med Ctr, 3350 La Jolla Village Dr, La Jolla, CA 92161 USA.
EM Thomas.Rutledge@med.va.gov
RI Reis, Steven/J-3957-2014
FU NCRR NIH HHS [M01-RR00425]; NHLBI NIH HHS [N01-HV-68164, N01-HV-68163,
   N01-HV-68161, N01-HV-68162]
NR 31
TC 20
Z9 22
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0033-3174
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD MAR-APR
PY 2006
VL 68
IS 2
BP 217
EP 223
DI 10.1097/01.psy.0000195751.94998.c3
PG 7
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA 029VB
UT WOS:000236591400007
PM 16554386
ER

PT J
AU Cammack, R
   Fann, Y
   Lancashire, RJ
   Maher, JP
   McIntyre, PS
   Morse, R
AF Cammack, R
   Fann, Y
   Lancashire, RJ
   Maher, JP
   McIntyre, PS
   Morse, R
TI JCAMP-DX for electron magnetic resonance(EMR)
SO PURE AND APPLIED CHEMISTRY
LA English
DT Article
DE recommendations; JCAMP-DX; data standard; spectroscopy; EMR; EPR; ESR;
   IUPAC Committee on Printed and Electronic Publications
ID IUPAC RECOMMENDATIONS 2001; COMPUTER-READABLE FORM; SPECTROMETRY;
   EXCHANGE
AB In this document, we define a data exchange format initially formulated from discussions of an International Union of Pure and Applied Chemistry (IUPAC) limited-term task group at the 35(th) Royal Society of Chemistry-ESR conference in Aberdeen 2002. The definition of this format is based on the IUPAC Joint Committee on Atomic and Molecular Physical Data Exchange (JCAMP-DX) protocols, which were developed for the exchange of infrared spectra and extended to chemical structures, nuclear magnetic resonance data, mass spectra, and ion mobility spectra. This standard of the JCAMP-DX was further extended to cover year 2000 compatible date strings and good laboratory practice, and the next release will cover the information needed for storing n-dimensional data sets. The aim of this paper is to adapt JCAMP-DX to the special requirements for electron magnetic resonance (EMR).
C1 Univ W Indies, Dept Chem, Kingston JMAAW15, Jamaica.
   Kings Coll London, Pharmaceut Sci Res Div, London SE1 9NH, England.
   NINDS, Intramural IT Program, NIH, Bethesda, MD 20892 USA.
   Univ Bristol, Sch Chem, Bristol BS8 1TS, Avon, England.
   Univ Glamorgan, Sch Appl Sci, Pontypridd CF37 1DL, M Glam, Wales.
   Illinois State Univ, Dept Chem, Normal, IL 61790 USA.
RP Lancashire, RJ (reprint author), Univ W Indies, Dept Chem, Kingston JMAAW15, Jamaica.
EM robert.lancashire@uwimona.edu.jm
RI Cammack, Richard/B-7841-2008; Lancashire, Robert/B-1049-2008
OI Lancashire, Robert/0000-0002-6780-3903
NR 15
TC 6
Z9 7
U1 0
U2 3
PU INT UNION PURE APPLIED CHEMISTRY
PI RES TRIANGLE PK
PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA
SN 0033-4545
J9 PURE APPL CHEM
JI Pure Appl. Chem.
PD MAR
PY 2006
VL 78
IS 3
BP 613
EP 631
DI 10.1351/pac200678030613
PG 19
WC Chemistry, Multidisciplinary
SC Chemistry
GA 025FH
UT WOS:000236250200003
ER

PT J
AU Brechbie, MW
   Milenic, DE
   Garmestani, K
   Brady, ED
   Abdulla, A
   Overstreet, T
   Flynn, J
AF Brechbie, MW
   Milenic, DE
   Garmestani, K
   Brady, ED
   Abdulla, A
   Overstreet, T
   Flynn, J
TI Modeling clinical applications or radioimmunotherapy: Targeting the HER2
   antigen
SO RADIOTHERAPY AND ONCOLOGY
LA English
DT Meeting Abstract
CT 3rd International Conference on Translational Research and Pre-Clinical
   Strategies in Radiation Oncology
CY MAR 12-15, 2006
CL Lugano, SWITZERLAND
SP European Sch Oncol, European Soc Radiotherapeut Radiol & Oncol, European Org Res & Treatment Canc, Amer Med Assoc, EACCME
C1 NCI, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA.
   Walter Reed Army Med Ctr, Washington, DC 20307 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0167-8140
J9 RADIOTHER ONCOL
JI Radiother. Oncol.
PD MAR
PY 2006
VL 78
SU 1
MA 67
BP S23
EP S23
DI 10.1016/S0167-8140(06)80561-X
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 043KD
UT WOS:000237599000065
ER

PT J
AU Coleman, CN
AF Coleman, CN
TI Normal tissue countermeasures
SO RADIOTHERAPY AND ONCOLOGY
LA English
DT Meeting Abstract
CT 3rd International Conference on Translational Research and Pre-Clinical
   Strategies in Radiation Oncology
CY MAR 12-15, 2006
CL Lugano, SWITZERLAND
SP European Sch Oncol, European Soc Radiotherapeut Radiol & Oncol, European Org Res & Treatment Canc, Amer Med Assoc, EACCME
C1 NCI, Radiat Oncol Sci Program, NIH, Bethesda, MD 20892 USA.
   Dept Hlth & Human Serv, Off Publ Hlth Emergency Preparedness, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0167-8140
J9 RADIOTHER ONCOL
JI Radiother. Oncol.
PD MAR
PY 2006
VL 78
SU 1
MA 39
BP S14
EP S14
DI 10.1016/S0167-8140(06)80533-5
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 043KD
UT WOS:000237599000039
ER

PT J
AU Raben, D
   Chen, C
   Kane, M
   Song, J
   Eckhardt, G
   Meyers, A
   McCoy, K
   Raben, A
   Quon, H
   Hu, K
   Dancey, J
AF Raben, D
   Chen, C
   Kane, M
   Song, J
   Eckhardt, G
   Meyers, A
   McCoy, K
   Raben, A
   Quon, H
   Hu, K
   Dancey, J
TI Discussion of toxicity and biomarkers in a phase I trial of gefitinib
   (iressatm) in combination with radiation or chemo-radiation for patients
   with locally advanced head and neck cancer (LAHNC)
SO RADIOTHERAPY AND ONCOLOGY
LA English
DT Meeting Abstract
CT 3rd International Conference on Translational Research and Pre-Clinical
   Strategies in Radiation Oncology
CY MAR 12-15, 2006
CL Lugano, SWITZERLAND
SP European Sch Oncol, European Soc Radiotherapeut Radiol & Oncol, European Org Res & Treatment Canc, Amer Med Assoc, EACCME
C1 Univ Colorado, Boulder, CO 80309 USA.
   Univ Penn, Philadelphia, PA 19104 USA.
   Beth Israel Hosp, Boston, MA 02215 USA.
   NCI, Clin Trials Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0167-8140
J9 RADIOTHER ONCOL
JI Radiother. Oncol.
PD MAR
PY 2006
VL 78
SU 1
MA 123
BP S39
EP S39
DI 10.1016/S0167-8140(06)80602-X
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 043KD
UT WOS:000237599000106
ER

PT J
AU Celli, J
AF Celli, J
TI Surviving inside a macrophage: The many ways of Brucella
SO RESEARCH IN MICROBIOLOGY
LA English
DT Review
DE Brucella; replication; macrophage; virulence factors; permissivity
ID CELLULAR PRION PROTEIN; IV SECRETION SYSTEMS; ENDOPLASMIC-RETICULUM;
   INTRACELLULAR REPLICATION; MURINE MACROPHAGES; CYCLIC BETA-1,2-GLUCAN;
   VIRULENCE FACTOR; SUIS; ABORTUS; INFECTION
AB Bacteria of the genus Brucella are intracellular pathogens capable of survival and replication within macrophages of mammalian hosts. Recent advances have shed fight on virulence factors and host functions involved at various stages of: the Brucella intracellular life cycle. This review focuses on how this pathogen uses multiple strategies to circumvent macrophage defense mechanisms and generate an organelle permissive for replication. (c) 2005 Elsevier SAS. All rights reserved.
C1 NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Celli, J (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA.
EM jcelli@niaid.nih.gov
NR 32
TC 81
Z9 93
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0923-2508
J9 RES MICROBIOL
JI Res. Microbiol.
PD MAR
PY 2006
VL 157
IS 2
BP 93
EP 98
DI 10.1016/j.resmic.2005.10.002
PG 6
WC Microbiology
SC Microbiology
GA 019VE
UT WOS:000235864000001
PM 16364608
ER

PT J
AU Mruthyunjaya, P
   Wirostko, WJ
   Chandrashekhar, R
   Stinnett, S
   Lai, JC
   Deramo, V
   Tang, J
   Dev, S
   Postel, EA
   Connor, TB
   Fekrat, S
AF Mruthyunjaya, Prithvi
   Wirostko, William J.
   Chandrashekhar, Ravindra
   Stinnett, Sandra
   Lai, James C.
   Deramo, Vincent
   Tang, Johnny
   Dev, Sundeep
   Postel, Eric A.
   Connor, Thomas B.
   Fekrat, Sharon
TI Central retinal vein occlusion in patients treated with long-term
   warfarin sodium (Coumadin) for anticoagulation
SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the
   Association-for-Research-in-Vision-and-Ophthalmology
CY MAY 05-10, 2002
CL Ft Lauderdale, FL
SP Assoc Res Vis & Ophthalmol
DE anticoagulation; central retinal vein occlusion; Coumadin; international
   normalization ratio; retinal vein occlusion; systemic; therapeutic
ID TISSUE-PLASMINOGEN ACTIVATOR; HYPERCOAGULABLE STATES; RISK-FACTORS;
   THROMBOSIS; INJECTION; DISEASES
AB Purpose: To describe the clinical features of persons who developed central retinal vein occlusion (CVO) while being treated with Coumadin for chronic anticoagulation.
   Methods: In a retrospective, comparative, noninterventional case series of patients diagnosed with CVO while being treated with Coumadin as a systemic anticoagulant, visual and anatomical outcomes were compared with those for a cohort of patients diagnosed with CVO who were not treated with any systemic anticoagulation.
   Results: Fourteen eyes of 14 patients treated with Coumadin were identified. At presentation, the median international normalization ratio (INR) was 2.20 (range, 1.3-5.0). Eight patients (57%) had a therapeutic INR at the time of CVO. Their visual acuity and perfusion status were similar to those of patients with subtherapeutic INR. At the last follow-up (median, 16 months), visual acuity and perfusion status of the group of 14 eyes were similar to baseline findings (P = 0.62). Clinical features and outcomes were similar to those for a cohort of patients with CVO who were not being treated with systemic anticoagulation.
   Conclusion: CVO can occur in patients being treated with Coumadin for systemic anticoagulation. Final visual acuity and perfusion status were similar to those in a cohort of patients with CVO who were not treated with Coumadin. Although visual acuity is unaffected, ensuring that the INR for these patients remains in the therapeutic range may be important to help prevent secondary systemic thrombotic and embolic disease.
C1 Duke Univ, Ctr Eye, Durham, NC 27710 USA.
   Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA.
   Wilson Mem Reg Med Ctr, New York, NY USA.
   Long Isl Vitreoretinal Consultants, Great Neck, NY USA.
   N Shore Univ Hosp, Dept Ophthalmol, Manhasset, NY 11030 USA.
   NEI, NIH, Bethesda, MD 20892 USA.
   VitreoRetinal Surg PA, Minneapolis, MN USA.
RP Fekrat, S (reprint author), Duke Univ, Ctr Eye, Box 3802,Erwin Rd, Durham, NC 27710 USA.
EM fekra001@mc.duke.edu
NR 28
TC 15
Z9 15
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0275-004X
J9 RETINA-J RET VIT DIS
JI Retin.-J. Retin. Vitr. Dis.
PD MAR
PY 2006
VL 26
IS 3
BP 285
EP 291
DI 10.1097/00006982-200603000-00006
PG 7
WC Ophthalmology
SC Ophthalmology
GA 100QW
UT WOS:000241684700006
PM 16508428
ER

PT J
AU Bindewald, E
   Shapiro, BA
AF Bindewald, E
   Shapiro, BA
TI RNA secondary structure prediction from sequence alignments using a
   network of k-nearest neighbor classifiers
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE RNA; secondary structure; mutual information; machine learning;
   alignment
ID DYNAMIC-PROGRAMMING ALGORITHM; PARALLEL GENETIC ALGORITHM; CONTEXT-FREE
   GRAMMARS; WEB SERVER; P RNA; INFORMATION; PSEUDOKNOTS; BINDING;
   THERMODYNAMICS; IMPLEMENTATION
AB We present a machine learning method (a hierarchical network of k-nearest neighbor classifiers) that uses an RNA sequence alignment in order to predict a consensus RNA secondary structure. The input to the network is the mutual information, the fraction of complementary nucleotides, and a novel consensus RNAfold secondary structure prediction of a pair of alignment columns and its nearest neighbors. Given this input, the network computes a prediction as to whether a particular pair of alignment columns corresponds to a base pair. By using a comprehensive test set of 49 RFAM alignments, the program KNetFold achieves an average Matthews correlation coefficient of 0.81. This is a significant improvement compared with the secondary structure prediction methods PFOLD and RNAalifold. By using the example of archaeal RNase P, we show that the program can also predict pseudoknot interactions.
C1 NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA.
   SAIC Frederick Inc, Basic Res Program, Frederick, MD USA.
RP Shapiro, BA (reprint author), NCI, Ctr Canc Res, Nanobiol Program, Bldg 469,Room 150, Frederick, MD 21702 USA.
EM bshapiro@ncifcrf.gov
FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400]
NR 45
TC 47
Z9 52
U1 0
U2 5
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 1355-8382
J9 RNA
JI RNA-Publ. RNA Soc.
PD MAR
PY 2006
VL 12
IS 3
BP 342
EP 352
DI 10.1261/rna.2164906
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 018VN
UT WOS:000235793000004
PM 16495232
ER

PT J
AU Huang, AY
AF Huang, AY
TI Dynamic high-resolution imaging of immune cell behavior using intravital
   2-photon microscopy
SO SCANNING
LA English
DT Meeting Abstract
C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU FAMS INC
PI MAHWAH
PA BOX 832, MAHWAH, NJ 07430-0832 USA
SN 0161-0457
J9 SCANNING
JI Scanning
PD MAR-APR
PY 2006
VL 28
IS 2
BP 58
EP 58
PG 1
WC Instruments & Instrumentation; Microscopy
SC Instruments & Instrumentation; Microscopy
GA 035OZ
UT WOS:000237012500004
ER

PT J
AU Bassett, JHD
   O'Shea, PJ
   Chassande, O
   Samarut, J
   Cheng, SY
   Vennstrom, B
   Howell, PGT
   Boyde, A
   Williams, GR
AF Bassett, JHD
   O'Shea, PJ
   Chassande, O
   Samarut, J
   Cheng, SY
   Vennstrom, B
   Howell, PGT
   Boyde, A
   Williams, GR
TI Analysis of skeletal phenotypes in thyroid hormone receptor mutant mice
SO SCANNING
LA English
DT Meeting Abstract
C1 Univ London Imperial Coll Sci & Technol, Mol Endocrinol Grp, MRC, Ctr Clin Sci, London, England.
   Univ Victor Segalen, INSERM, Bordeaux, France.
   ENS, CNRS, UMR, Lyon, France.
   NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
   Karolinska Inst, Dept Mol Biol, Stockholm, Sweden.
   UCL, Eastman Dent Inst, London, England.
   QMUL, Barts & London Sch Med & Dent, Biophys Sect, London, England.
FU Medical Research Council [G108/502]; Wellcome Trust [076584]
NR 0
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0161-0457
J9 SCANNING
JI Scanning
PD MAR-APR
PY 2006
VL 28
IS 2
BP 91
EP 93
PG 3
WC Instruments & Instrumentation; Microscopy
SC Instruments & Instrumentation; Microscopy
GA 035OZ
UT WOS:000237012500047
PM 19584945
ER

PT J
AU Dennis, JU
AF Dennis, JU
TI Defending animal research
SO SCIENTIST
LA English
DT Letter
C1 NCI, SAIC Frederick LASP, NIH, Bethesda, MD 20892 USA.
RP Dennis, JU (reprint author), NCI, SAIC Frederick LASP, NIH, Bethesda, MD 20892 USA.
EM dennisj@mail.nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SCIENTIST INC
PI PHILADELPHIA
PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA
SN 0890-3670
J9 SCIENTIST
JI Scientist
PD MAR
PY 2006
VL 20
IS 3
BP 14
EP 14
PG 1
WC Information Science & Library Science; Multidisciplinary Sciences
SC Information Science & Library Science; Science & Technology - Other
   Topics
GA 016QE
UT WOS:000235634200004
ER

PT J
AU Ness, RB
   Smith, KJ
   Chang, CCH
   Schisterman, EF
   Bass, DC
AF Ness, RB
   Smith, KJ
   Chang, CCH
   Schisterman, EF
   Bass, DC
CA Gynecologic Infection Follow-Throu
TI Prediction of pelvic inflammatory disease among young, single, sexually
   active women
SO SEXUALLY TRANSMITTED DISEASES
LA English
DT Article
ID RISK-FACTORS; BACTERIAL VAGINOSIS; CIGARETTE-SMOKING; INFECTION;
   CONTRACEPTION; ENDOMETRITIS; POPULATION; DIAGNOSIS; HEALTH; CANCER
AB Objectives: To assess prediction strategies for pelvic inflammatory disease (PID).
   Study Design: One thousand one hundred seventy women were enrolled based on a high chlamydial risk score. Incident PID over a median of 3 years was diagnosed by either histologic endometritis or Centers for Disease Control and Prevention criteria. A multivariable prediction model for PID was assessed.
   Results: Women enrolled using the risk score were young, single, sexually active, and often had prior sexually transmitted infections. Incident PID was common (8.6%). From 24 potential predictors, significant factors included age at first sex, gonococcal/chiamydial cervicitis, history of PID, family income, smoking, medroxyprogesterone acetate use, and sex with menses. The model correctly predicted 74% of incident PID; in validation models, correct prediction was only 69%.
   Conclusions: Our data validate a modified chlamydial risk factor scoring system for prediction of PID. Additional multivariable modeling contributed little to prediction. Women identified by a threshold value on the chlamydial risk score should undergo intensive education and screening.
C1 Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
   Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15261 USA.
   NICHD, Bethesda, MD USA.
RP Ness, RB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Room A548,Crabtree Hall,130 DeSoto St, Pittsburgh, PA 15261 USA.
EM repro@pitt.edu
OI Smith, Kenneth J/0000-0001-8088-566X; Schisterman,
   Enrique/0000-0003-3757-641X
FU NIAID NIH HHS [AI44151-01]
NR 38
TC 20
Z9 20
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0148-5717
J9 SEX TRANSM DIS
JI Sex. Transm. Dis.
PD MAR
PY 2006
VL 33
IS 3
BP 137
EP 142
DI 10.1097/01.olq.0000187205.67390.d1
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA 021AR
UT WOS:000235955300003
PM 16505735
ER

PT J
AU Knutson, KM
   Wood, JN
   Spampinato, MV
   Grafman, J
AF Knutson, Kristine M.
   Wood, Jacqueline N.
   Spampinato, Maria V.
   Grafman, Jordan
TI Politics on the brain: An MRI investigation
SO SOCIAL NEUROSCIENCE
LA English
DT Article
ID INFERIOR PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; IMPLICIT
   ASSOCIATION TEST; FALSE DISCOVERY RATE; FUSIFORM FACE AREA; FUNCTIONAL
   MRI; ORBITOFRONTAL CORTEX; COGNITIVE CONTROL; HUMAN AMYGDALA; FMRI
AB We assessed political attitudes using the Implicit Association Test (IAT) in which participants were presented with faces and names of well-known Democrat and Republican politicians along with positive and negative words while undergoing functional MRI. We found a significant behavioral IAT effect for the face, but not the name, condition. The fMRI face condition results indicated that ventromedial and anterior prefrontal cortices were activated during political attitude inducement. Amygdala and fusiform gyrus were activated during perceptual processing of familiar faces. Amygdala activation was also associated with measures of strength of emotion. Frontopolar activation was positively correlated with an implicit measure of bias and valence strength (how strongly the participants felt about the politicians), while strength of affiliation with political party was negatively correlated with lateral PFC, lending support to the idea that two distinct but interacting networks-one emphasizing rapid, stereotypic, and emotional associative knowledge and the other emphasizing more deliberative and factual knowledge-co-operate in the processing of politicians. Our findings of ventromedial PFC activation suggests that when processing the associative knowledge concerned with politicians, stereotypic knowledge is activated, but, in addition, the anterior prefrontal activations indicate that more elaborative, reflective knowledge about the politician is activated.
C1 [Knutson, Kristine M.; Wood, Jacqueline N.; Grafman, Jordan] Natl Inst Hlth, Bethesda, MD USA.
   [Spampinato, Maria V.] Med Univ S Carolina, Charleston, SC USA.
RP Grafman, J (reprint author), Natl Inst Hlth, NINDS, Cognit Neurosci Sect, Bldg 10, Room 5C205, MSC 1440, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM grafmanj@ninds.nih.gov
OI Knutson, Kristine/0000-0003-4626-4514
FU Intramural NIH HHS [Z01 NS002792-17]
NR 64
TC 47
Z9 47
U1 2
U2 11
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1747-0919
EI 1747-0927
J9 SOC NEUROSCI-UK
JI Soc. Neurosci.
PD MAR
PY 2006
VL 1
IS 1
BP 25
EP 40
DI 10.1080/17470910600670603
PG 16
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA 242ZL
UT WOS:000251764600004
PM 17372621
ER

PT J
AU Cai, JL
   Chen, J
   Liu, Y
   Miura, T
   Luo, YQ
   Loring, JF
   Freed, WJ
   Rao, MS
   Zeng, XM
AF Cai, Jingli
   Chen, Jia
   Liu, Ying
   Miura, Takumi
   Luo, Yongquan
   Loring, Jeanne F.
   Freed, William J.
   Rao, Mahendra S.
   Zeng, Xianmin
TI Assessing self-renewal and differentiation in human embryonic stem cell
   lines
SO STEM CELLS
LA English
DT Review
DE human embryonic stem cell; embryoid body; differentiation
ID GENE-EXPRESSION; GROWTH-FACTOR; ES CELLS; TRANSCRIPTION FACTORS;
   MOLECULAR SIGNATURE; NEURAL PRECURSORS; PROGENITOR CELLS;
   BINDING-PROTEIN; NERVOUS-SYSTEM; MESSENGER-RNA
AB Like other cell populations, undifferentiated human embryonic stem cells (hESCs) express a characteristic set of proteins and mRNA that is unique to the cells regardless of culture conditions, number of passages, and methods of propagation. We sought to identify a small set of markers that would serve as a reliable indicator of the balance of undifferentiated and differentiated cells in hESC populations. Markers of undifferentiated cells should be rapidly downregulated as the cells differentiate to form embryoid bodies (EBs), whereas markers that are absent or low during the undifferentiated state but that are induced as hESCs differentiate could be used to assess the presence of differentiated cells in the cultures. In this paper, we describe a list of markers that reliably distinguish undifferentiated and differentiated cells. An initial list of approximately 150 genes was generated by scanning published massively parallel signature sequencing, expressed sequence tag scan, and microarray datasets. From this list, a subset of 109 genes was selected that included 55 candidate markers of undifferentiated cells, 46 markers of hESC derivatives, four germ cell markers, and four trophoblast markers. Expression of these candidate marker genes was analyzed in undifferentiated hESCs and differentiating EB populations in four different lines by immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR), microarray analysis, and quantitative RT-PCR (qPCR). We show that qPCR, with as few as 12 selected genes, can reliably distinguish differentiated cells from undifferentiated hESC populations.
C1 Buck Inst Age Res, Program Stem Cells & Regenerat, Novato, CA 94945 USA.
   NIA, Neurosci Lab, US Dept HHS, Baltimore, MD 21224 USA.
   NIDA, Cellular Neurobiol Branch, US Dept HHS, Baltimore, MD 21224 USA.
   Burnham Inst, Program Stem Cells & Regenerat, La Jolla, CA 92037 USA.
   Invitrogen, Carlsbad, CA 92008 USA.
   Buck Inst, Novato, CA USA.
RP Zeng, XM (reprint author), Buck Inst Age Res, Program Stem Cells & Regenerat, 8001 Redwood Blvd, Novato, CA 94945 USA.
EM xzeng@buckinstitute.org
FU NIDA NIH HHS [Z01 DA000472-02]
NR 105
TC 96
Z9 96
U1 0
U2 17
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD MAR
PY 2006
VL 24
IS 3
BP 516
EP 530
DI 10.1634/stemcells.2005-0143
PG 15
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
   Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 085WX
UT WOS:000240636200007
PM 16293578
ER

PT J
AU Plaia, TW
   Josephson, R
   Liu, Y
   Zeng, XM
   Ording, C
   Toumadje, A
   Brimble, SN
   Sherrer, ES
   Uhl, EW
   Freed, WJ
   Schulz, TC
   Maitra, A
   Rao, MS
   Auerbach, JM
AF Plaia, Todd W.
   Josephson, Richard
   Liu, Ying
   Zeng, Xianmin
   Ording, Carol
   Toumadje, Arazdordi
   Brimble, Sandii N.
   Sherrer, Eric S.
   Uhl, Elizabeth W.
   Freed, William J.
   Schulz, Thomas C.
   Maitra, Anirban
   Rao, Mahendra S.
   Auerbach, Jonathan M.
TI Characterization of a new NIH-Registered variant human embryonic stem
   cell line, BG01V: A tool for human embryonic stem cell research
SO STEM CELLS
LA English
DT Article
DE embryonic stem cell; hESC karyotype; characterization; BG01V; NTERA-2
ID METHYLATION-SPECIFIC PCR; DOPAMINERGIC DIFFERENTIATION; HUMAN
   BLASTOCYSTS; GENE-EXPRESSION; RETINOIC ACID; INACTIVATION; ANTIGENS;
   TUMORS; TERATOCARCINOMA; IDENTIFICATION
AB Human embryonic stem cells (hESCs) offer a renewable source of a wide range of cell types for use in research and cell-based therapies. Characterizing these cells provides important information about their current state and affords relevant details for subsequent manipulations. For example, identifying genes expressed during culture, as well as their temporal expression order after passaging and conditions influencing the formation of all three germ layers may be helpful for the production of functional beta islet cells used in treating type I diabetes. Although several hESC lines have demonstrated karyotypic instability during extended time in culture, select variant lines exhibit characteristics similar to their normal parental lines. Such variant lines may be excellent tools and abundant sources of cells for pilot studies and in vitro differentiation research in which chromosome number is not a concern, similar to the role currently played by embryonal carcinoma cell lines. It is crucial that the cells be surveyed at a genetic and proteomic level during extensive propagation, expansion, and manipulation in vitro. Here we describe a comprehensive characterization of the variant hESC line BG01V, which was derived from the karyotypically normal, parental hESC line BG01. Our characterization process employs cytogenetic analysis, short tandem repeat and HLA typing, mitochondrial DNA sequencing, gene expression analysis using quantitative reverse transcription-polymerase chain reaction and microarray, assessment of telomerase activity, methylation analysis, and immunophenotyping and teratoma formation, in addition to screening for bacterial, fungal, mycoplasma, and human pathogen contamination.
C1 Amer Type Culture Collect, Stem Cell Ctr, Manassas, VA 20110 USA.
   NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
   NIDA, Cellular Neurobiol Branch, NIH, Baltimore, MD 21224 USA.
   BresaGen, Athens, GA USA.
   Univ Georgia, Coll Vet Med, Dept Vet Pathol, Athens, GA USA.
   Johns Hopkins Univ, Sch Med, Dept Pathol Oncol & Genet Med, Baltimore, MD USA.
RP Auerbach, JM (reprint author), Amer Type Culture Collect, Stem Cell Ctr, 10801 Univ Blvd, Manassas, VA 20110 USA.
EM jauerbach@atcc.org
FU NCRR NIH HHS [9R24RR021313-04]; NIA NIH HHS [N01AG40002]
NR 41
TC 50
Z9 52
U1 2
U2 3
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 MAR
PY 2006
VL 24
IS 3
BP 531
EP 546
DI 10.1634/stemcells.2005-0315
PG 16
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
   Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 085WX
UT WOS:000240636200008
PM 16293579
ER

PT J
AU Kim, DW
   Chung, S
   Hwang, M
   Ferree, A
   Tsai, HC
   Park, JJ
   Chung, S
   Nam, TS
   Kang, UJ
   Isacson, O
   Kim, KS
AF Kim, Dong-Wook
   Chung, Sangmi
   Hwang, Mikyeong
   Ferree, Andrew
   Tsai, Hsing-Chen
   Park, Jae-Joon
   Chung, Seungsoo
   Nam, Taick Sang
   Kang, Un Jung
   Isacson, Ole
   Kim, Kwang-Soo
TI Stromal cell-derived inducing activity, Nurr1, and signaling molecules
   synergistically induce dopaminergic neurons from mouse embryonic stem
   cells
SO STEM CELLS
LA English
DT Article
DE embryonic stem cells; stromal cell-derived inducing activity; Nurr1;
   dopaminergic neurons; Parkinson's disease
ID JAN 20 2006; SUBSTANTIA-NIGRA; PARKINSONS-DISEASE; SEROTONERGIC NEURONS;
   NEURAL PRECURSORS; PROGENITOR CELLS; RETRACTED SEE; IN-VITRO; ES CELLS;
   PG 335
AB To induce differentiation of embryonic stem cells (ESCs) into specialized cell types for therapeutic purposes, it may be desirable to combine genetic manipulation and appropriate differentiation signals. We studied the induction of dopaminergic (DA) neurons from mouse ESCs by overexpressing the transcription factor Nurr1 and coculturing with PA6 stromal cells. Nurr1-expressing ESCs (N2 and N5) differentiated into a higher number of neurons (similar to twofold) than the naive ESCs (D3). In addition, N2/N5-derived cells contained a significantly higher proportion (> 50%) of tyrosine hydroxylase (TH)(+) neurons than D3 (< 30%) and an even greater proportion of TH+ neurons (similar to 90%) when treated with the signaling molecules sonic hedgehog, fibroblast growth factor 8, and ascorbic acid. N2/N5-derived cells express much higher levels of DA markers (e.g., TH, dopamine transporter, aromatic amino acid decarboxylase, and G protein-regulated inwardly rectifying K+ channel 2) and produce and release a higher level of dopamine, compared with D3-derived cells. Furthermore, the majority of generated neurons exhibited electrophysiological properties' characteristic of midbrain DA neurons. Finally, transplantation experiments showed efficient in vivo integration/generation of TH+ neurons after implantation into mouse striatum. Taken together, our results show that the combination of genetic manipulation(s) and in vitro cell differentiation conditions offers a reliable and effective induction of DA neurons from ESCs and may pave the way for future cell transplantation therapy in Parkinson's disease.
C1 Harvard Univ, McLean Hosp, Sch Med, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02178 USA.
   Harvard Univ, McLean Hosp, Sch Med, Mol Neurobiol Labs, Belmont, MA 02178 USA.
   Yonsei Univ, Coll Med, Dept Physiol, Seoul 120749, South Korea.
   Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Labs, Belmont, MA 02178 USA.
   Univ Chicago, Dept Neurol & Pharmacol, Chicago, IL 60637 USA.
   Univ Chicago, Dept Physiol, Chicago, IL 60637 USA.
   Univ Chicago, Dept Neurobiol, Chicago, IL 60637 USA.
RP Kim, KS (reprint author), Harvard Univ, McLean Hosp, Sch Med, Udall Parkinsons Dis Res Ctr Excellence, MRC 216,115 Mill St, Belmont, MA 02178 USA.
EM kskim@mclean.harvard.edu
FU NIMH NIH HHS [R29 MH048866, R01 MH048866, MH48866]; NINDS NIH HHS [P50
   NS039793, NS044439, P50 NS039793-07, P50NS39793, R01 NS032080, R21
   NS044439, NS32080]
NR 46
TC 58
Z9 64
U1 1
U2 5
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD MAR
PY 2006
VL 24
IS 3
BP 557
EP 567
DI 10.1634/stemcells.2005-0233
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
   Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 085WX
UT WOS:000240636200010
PM 16123386
ER

PT J
AU Arbab, AS
   Frenkel, V
   Pandit, SD
   Anderson, SA
   Yocum, GT
   Bur, M
   Khuu, HM
   Read, EJ
   Frank, JA
AF Arbab, Ali S.
   Frenkel, Victor
   Pandit, Sunil D.
   Anderson, Stasia A.
   Yocum, Gene T.
   Bur, Monica
   Khuu, Hanh M.
   Read, Elizabeth J.
   Frank, Joseph A.
TI Magnetic resonance imaging and confocal microscopy studies of
   magnetically labeled endothelial progenitor cells trafficking to sites
   of tumor angiogenesis
SO STEM CELLS
LA English
DT Article
DE ferumoxides; protamine sulfate; neovasculature; quantum dots;
   hematopoietic stem cells; magnetic resonance imaging; vasculogenesis
ID MESENCHYMAL STEM-CELLS; BONE-MARROW; IN-VIVO; PRECURSOR CELLS; CANCER;
   VASCULATURE; MOBILIZATION; FERUMOXIDES; IDENTIFY; BREAST
AB AC133 cells, a subpopulation of CD34(+) hematopoietic stem cells, can transform into endothelial cells that may integrate into the neovasculature of tumors or ischemic tissue. Most current imaging modalities do not allow monitoring of early migration and incorporation of endothelial progenitor cells (EPCs) into tumor neovasculature. The goals of this study were to use magnetic resonance imaging (MRI) to track the migration and incorporation of intravenously injected, magnetically labeled EPCs into the blood vessels in a rapidly growing flank tumor model and to determine whether the pattern of EPC incorporation is related to the time of injection or tumor size. Materials and Methods: EPCs labeled with ferumoxide-protamine sulfate (FePro) complexes were injected into mice bearing xenografted glioma, and MRI was obtained at different stages of tumor development and size. Results: Migration and incorporation of labeled EPCs into tumor neovasculature were detected as low signal intensity on MRI at the tumor periphery as early as 3 days after EPC administration in preformed tumors. However, low signal intensities were not observed in tumors implanted at the time of EPC administration until tumor size reached I cm at 12 to 14 days. Prussian blue staining showed iron-positive cells at the sites corresponding to low signal intensity on MRI. Confocal microcopy showed incorporation into the neovasculature, and immunohistochemistry clearly demonstrated the transformation of the administered EPCs into endothelial cells. Conclusion: MRI demonstrated the incorporation of FePro-labeled human CD34(+)/AC133(+) EPCs into the neovasculature of implanted flank tumors.
C1 Henry Ford Hlth Syst, Detroit, MI 48202 USA.
   NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Dept Transfus Med, Bethesda, MD USA.
   NIH, Mol Imaging Lab, Ctr Clin, Dept Transfus Med, Bethesda, MD USA.
   NIH, NINDS, Dept Transfus Med, Bethesda, MD USA.
   NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD USA.
RP Arbab, AS (reprint author), Henry Ford Hlth Syst, 1 Ford Pl,2F,Mailbox 82, Detroit, MI 48202 USA.
EM saali@rad.hfh.edu
FU Intramural NIH HHS
NR 33
TC 130
Z9 151
U1 1
U2 7
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD MAR
PY 2006
VL 24
IS 3
BP 671
EP 678
DI 10.1634/stemcells.2005-0017
PG 8
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
   Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 085WX
UT WOS:000240636200022
PM 16179427
ER

PT J
AU Weiss, ML
   Medicetty, S
   Bledsoe, AR
   Rachakatla, RS
   Choi, M
   Merchav, S
   Luo, YQ
   Rao, MS
   Velagaleti, G
   Troyer, D
AF Weiss, Mark L.
   Medicetty, Satish
   Bledsoe, Amber R.
   Rachakatla, Raja Shekar
   Choi, Michael
   Merchav, Shosh
   Luo, Yongquan
   Rao, Mahendra S.
   Velagaleti, Gopalrao
   Troyer, Deryl
TI Human umbilical cord matrix stem cells: Preliminary characterization and
   effect of transplantation in a rodent model of Parkinson's disease
SO STEM CELLS
LA English
DT Article
DE Wharton's jelly; flow cytometry; regenerative medicine; in vitro
   expansion; noncontroversial source of stem cells
ID MESENCHYMAL PROGENITOR CELLS; BONE-MARROW; DOPAMINERGIC-NEURONS;
   AMNIOTIC-FLUID; HUMAN PLACENTA; LESION MODEL; RAT-BRAIN; IN-VITRO;
   BLOOD; CULTURE
AB The umbilical cord contains an inexhaustible, noncontroversial source of stem cells for therapy. In the U.S., stem cells found in the umbilical cord are routinely placed into biohazardous waste after birth. Here, stem cells derived from human umbilical cord Wharton's Jelly, called umbilical cord matrix stem (UCMS) cells, are characterized. UCMS cells have several properties that make them of interest as a source of cells for therapeutic use. For example, they 1) can be isolated in large numbers, 2) are negative for CD34 and CD45, 3) grow robustly and can be frozen/thawed, 4) can be clonally expanded, and 5) can easily be engineered to express exogenous proteins. UCMS cells have genetic and surface markers of mesenchymal stem cells (positive for CD10, CD13, CD29, CD44, and CD90 and negative for CD14, CD33, CD56, CD31, CD34, CD45, and HLA-DR) and appear to be stable in terms of their surface marker expression in early passage (passages 4-8). Unlike traditional mesenchymal stem cells derived from adult bone marrow stromal cells, small populations of UCMS cells express endoglin (SH2, CD105) and CD49e at passage 8. UCMS cells express growth factors and angiogenic factors, suggesting that they may be used to treat neurodegenerative disease. To test the therapeutic value of UCMS cells, undifferentiated human UCMS cells were transplanted into the brains of hemiparkinsonian rats that were not immune-suppressed. UCMS cells ameliorated apomorphine-induced rotations in the pilot test. UCMS cells transplanted into normal rats did not produce brain tumors, rotational behavior, or a frank host immune rejection response. In summary, the umbilical cord matrix appears to be a rich, noncontroversial, and inexhaustible source of primitive mesenchymal stem cells.
C1 Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA.
   ViaCell Singapore Res Ctr, Singapore, Singapore.
   NIA, Neurosci Lab, Bethesda, MD 20892 USA.
   Childrens Hosp, Galveston, TX USA.
RP Weiss, ML (reprint author), Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA.
EM weiss@vet.ksu.edu
FU NINDS NIH HHS [NS034160]
NR 63
TC 363
Z9 434
U1 1
U2 26
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD MAR
PY 2006
VL 24
IS 3
BP 781
EP 792
DI 10.1634/stemcells.2005-0330
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
   Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 085WX
UT WOS:000240636200034
PM 16223852
ER

PT J
AU Crowell, JA
   Page, JG
   Levine, BS
   Tomlinson, MJ
   Hebert, CD
AF Crowell, JA
   Page, JG
   Levine, BS
   Tomlinson, MJ
   Hebert, CD
TI Indole-3-carbinol, but not its major digestive product
   3,3'-diindolylmethane, induces reversible hepatocyte hypertrophy and
   cytochromes P450
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE indole-3-carbinol; 3,3'-diindolylmethane; cancer prevention; cytochromes
   P450
ID RECURRENT RESPIRATORY PAPILLOMATOSIS; DIETARY INDOLE-3-CARBINOL;
   ESTROGEN METABOLISM; PROSTATE-CANCER; MAMMARY-TUMOR; LIVER; RATS;
   3,3'-DIINDOLYLMETHANE; CARCINOGENESIS; INDUCTION
AB Indole-3-carbinol (I-3-C) and 3,3'-diindolylmethane (DIM) have been shown to reduce the incidence and multiplicity of cancers in laboratory animal models. Based on the observation that I-3-C induced hepatocyte hypertrophy when administered orally for 13 weeks to rats, a treatment and recovery study was undertaken to test the hypothesis that the induction of hepatocyte hypertrophy and cytochrome P450 (CYP) activity by I-3-C are adaptive, reversible responses. Additionally, we directly compared the effects of I-3-C to those of its principle metabolite DIM. Rats were treated orally for 28 days with 2 doses of I-3-C (5 and 50 mg I-3-C/kg body weight/day) and DIM (7.5 and 75 mg DIM/kg body weight/day) and then one-half of the animals were not treated for an additional 28 days. Organ weights, histopathology, and the CYP enzyme activities of 1A1/2, 2B1/2, 2C9, 2D6, 2E1, 3A4, and 19 A were measured both after treatment and after recovery. Oral administration of 50 mg I-3-C/kg body weight/day to rats for 28 days significantly increased liver weights and CYP enzyme activities. The effects in males were more pronounced and persistent after recovery than the effects in females. The increased organ weights returned to control values after treatment. Conversely, DIM did not alter liver weights and had no effect on CYP activities after the 28-day treatment. Some changes in CYP activities were measured after the DIM recovery period but the magnitudes of the changes were considered biologically insignificant. The results show that I-3-C, but not DIM, induces reversible adaptive responses in the liver. Published by Elsevier Inc.
C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA.
   So Res Inst, Birmingham, AL 35205 USA.
   Univ Illinois, Dept Pharmacol, Chicago, IL 60612 USA.
   Pathol Associates Inc, Chicago, IL 60612 USA.
RP NCI, Div Canc Prevent, 6130 Execut Blvd,MSC 7322 Bldg,EpN,Rm 2118, Bethesda, MD 20892 USA.
EM jc94h@nih.gov
FU NCI NIH HHS [N01-CN-95133, N01-CN-15352-02]
NR 46
TC 20
Z9 20
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 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD MAR 1
PY 2006
VL 211
IS 2
BP 115
EP 123
DI 10.1016/j.taap.2005.06.011
PG 9
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 018LR
UT WOS:000235766300004
PM 16043203
ER

PT J
AU Smith, NF
   Figg, WD
   Sparreboom, A
AF Smith, NF
   Figg, WD
   Sparreboom, A
TI Pharmacogenetics of irinotecan metabolism and transport: An update
SO TOXICOLOGY IN VITRO
LA English
DT Review
DE CPT-11; SN-38; CYP3A; CES; UGT1A; ABCB1; ABCC1; ABCC2; ABCG2
ID CANCER RESISTANCE PROTEIN; SINGLE-NUCLEOTIDE POLYMORPHISMS; HUMAN
   HEPATIC MICROSOMES; DNA TOPOISOMERASE-I; UDP-GLUCURONOSYLTRANSFERASE;
   ACTIVE METABOLITE; HUMAN CARBOXYLESTERASE-2;
   7-ETHYL-10-HYDROXYCAMPTOTHECIN SN-38; HAPLOTYPE STRUCTURE;
   COLORECTAL-CANCER
AB The anticancer agent irinotecan (CPT- 11) is converted to SN-38, which is approximately 100 to 1000-fold more cytotoxic than the parent drug. The pharmacokinetics of irinotecan are extremely complex and have been the subject of intensive investigation in recent years. Irinotecan is subject to extensive metabolism by various polymorphic enzymes, including CES2 to form SN-38, members of the UGT1A subfamily, and CYP3A4 and CYP3A5, which form several pharmacologically inactive oxidation products. Elimination of irinotecan is also dependent on drug-tran sporting proteins, notably ABCB1 (P-glycoprotein), ABCC2 (cMOAT) and ABCG2 (BCRP), present on the bile canalicular membrane. The various processes mediating drug elimination, either through metabolic breakdown or excretion, likely impact substantially on interindividual variability in drug handling. This report provides an update on current strategies to individualize irinotecan chemotherapy based on each patient's genetic constitution, which may ultimately lead to more selective use of this agent. Published by Elsevier Ltd.
C1 NCI, Clin Pharmacol Res Core, Med Oncol Branch, Bethesda, MD 20892 USA.
   NCI, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Res Core, Med Oncol Branch, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016
NR 76
TC 85
Z9 89
U1 3
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0887-2333
J9 TOXICOL IN VITRO
JI Toxicol. Vitro
PD MAR
PY 2006
VL 20
IS 2
BP 163
EP 175
DI 10.1016/j.tiv.2005.06.045
PG 13
WC Toxicology
SC Toxicology
GA 023YE
UT WOS:000236161300004
PM 16271446
ER

PT J
AU Vergarajauregui, S
   Puertollano, R
AF Vergarajauregui, S
   Puertollano, R
TI Two di-leucine motifs regulate trafficking of mucolipin-1 to lysosomes
SO TRAFFIC
LA English
DT Editorial Material
DE di-leucine; lysosomes; MLIV; mucolipin-1; sorting
ID PROTEIN PALMITOYLATION; MEMBRANE-PROTEINS; CYTOPLASMIC TAIL;
   PLASMA-MEMBRANE; IV; GENE; RECEPTOR; CHANNEL; IDENTIFICATION; MUTATIONS
AB Mutations in the mucolipin-1 gene have been linked to mucolipidosis type IV, a lysosomal storage disorder characterized by severe neurological and ophthalmologic abnormalities. Mucolipin-1 is a membrane protein containing six putative transmembrane domains with both its N- and C-termini localized facing the cytosol. To gain information on the sorting motifs that mediate the trafficking of this protein to lysosomes, we have generated chimeras in which the N- and C- terminal tail portions of mucolipin-1 were fused to a reporter gene. In this article, we report the identification of two separate di-leucine-type motifs that co-operate to regulate the transport of mucolipin-1 to lysosomes. One di-leucine motif is positioned at the N-terminal cytosolic tail and mediates direct transport to lysosomes, whereas the other di-leucine motif is found at the C-terminal tail and functions as an adaptor protein 2-dependent internalization motif. We have also found that the C-terminal tail of mucolipin-1 is palmitoylated and that this modification might regulate the efficiency of endocytosis. Finally, the mutagenesis of both di-leucine motifs abrogated lysosomal accumulation and resulted in cell-surface redistribution of mucolipin-1. Taken together, these results reveal novel information regarding the motifs that regulate mucolipin-1 trafficking and suggest a role for palmitoylation in protein sorting.
C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Puertollano, R (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM puertolr@mail.nih.gov
FU Intramural NIH HHS
NR 43
TC 93
Z9 93
U1 0
U2 4
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD MAR
PY 2006
VL 7
IS 3
BP 337
EP 353
DI 10.1111/j.1600-0854.2006.00387.x
PG 17
WC Cell Biology
SC Cell Biology
GA 016AK
UT WOS:000235592700009
PM 16497227
ER

PT J
AU Caruccio, L
   Bettinotti, M
   Director-Myska, AE
   Arthur, DC
   Stroncek, D
AF Caruccio, L
   Bettinotti, M
   Director-Myska, AE
   Arthur, DC
   Stroncek, D
TI The gene overexpressed in polycythemia rubra vera, PRV-1, and the gene
   encoding a neutrophil alloantigen, NB1, are alleles of a single gene,
   CD177, in chromosome band 19q13.31
SO TRANSFUSION
LA English
DT Article
ID ESSENTIAL THROMBOCYTHEMIA; EXPRESSION; POLYMORPHISMS; ASSOCIATION
AB BACKGROUND: PRV-1 mRNA is overexpressed by neutrophils from polycythemia vera patients and is homologous to NB1 a gene overexpressed in reactive neutrophilia.
   STUDY DESIGN AND METHODS:These investigations were designed to confirm searches of genome databases suggesting that PRV-1 and NB1 are alleles of the same gene, CD177, and confirm a pseudogene adjacent to CD177. Methods included polymerase chain reaction (PCR), cloning, sequencing, and fluorescent hybridization studies.
   RESULTS: The coding region of PRV-1 was PCR-amplified from human fetal RNA, cloned, and used to screen the RPCI-11 bacterial artificial chromosome (BAC) library. Five BACs were reactive with the PRV-1 probe. PCR analysis of the BACs with primers encompassing PRV-1 exons, containing four known single-nucleotide polymorphisms, followed by sequencing rendered amplicons identical to PRV-1 in all five BACs. Analysis of all five by restriction digestion yielded fragments possible only if both the gene and the pseudogene are present. End sequencing of the BACs localized them to the same chromosome region. G-banding and fluorescence in situ hybridization at the 400- and 850-band levels of resolution mapped one BAC to chromosome band 19q13.2 and sublocalized the BAC to band 19q13.31, respectively.
   CONCLUSION: PRV-1 and NB1 are alleles of the same gene now referred to as CD177. Changes in CD177 expression may be a marker of increased or decreased myelopoiesis and are therefore an effect of, rather than a cause of, myeloproliferative disorders.
C1 NCI, Dept Transfus Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA.
   NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Caruccio, L (reprint author), NCI, Dept Transfus Med, Warren G Magnuson Clin Ctr, NIH, Bldg 10,Room 1C711,10 Ctr Dr MSC 1184, Bethesda, MD 20892 USA.
EM lcaruccio@mail.cc.nih.gov
NR 11
TC 13
Z9 14
U1 0
U2 0
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD MAR
PY 2006
VL 46
IS 3
BP 441
EP 447
DI 10.1111/j.1537-2995.2006.00741.x
PG 7
WC Hematology
SC Hematology
GA 016ZA
UT WOS:000235662500021
PM 16533288
ER

PT J
AU de Pauw, BE
   Sable, CA
   Walsh, TJ
   Lupinacci, RJ
   Bourque, MR
   Wise, BA
   Nguyen, BY
   DiNubile, MJ
   Teppler, H
AF de Pauw, BE
   Sable, CA
   Walsh, TJ
   Lupinacci, RJ
   Bourque, MR
   Wise, BA
   Nguyen, BY
   DiNubile, MJ
   Teppler, H
TI Impact of alternate definitions of fever resolution on the composite
   endpoint in clinical trials of empirical antifungal therapy for
   neutropenic patients with persistent fever: analysis of results from the
   Caspofungin Empirical Therapy Study
SO TRANSPLANT INFECTIOUS DISEASE
LA English
DT Article
DE fever; neutropenia; caspofungin; liposomal amphotericin B; endpoints
ID LIPOSOMAL AMPHOTERICIN-B; CANCER-PATIENTS; FEBRILE
AB Background. Sensitivity analyses were incorporated in a Phase III study of caspofungin vs. liposomal amphotericin B as empirical antifungal therapy for febrile neutropenic patients to determine the impact of varying definitions of fever resolution on response rates. Methods. The primary analysis used a 5-part composite endpoint: resolution of any baseline invasive fungal infection, no breakthrough invasive fungal infection, survival, no premature discontinuation of study drug, and fever resolution for 48 h during the period of neutropenia. Pre-specified analyses used 3 other definitions for fever resolution: afebrile for 24 h during the period of neutropenia, afebrile at 7 days post therapy, and eliminating fever resolution altogether from the composite endpoint. Patients were stratified on entry by use of antifungal prophylaxis and risk of infection. Allogeneic hematopoietic stern cell transplants or relapsed acute leukemia defined high-risk patients. Results. In the primary analysis, 41% of patients in each treatment group met the fever-resolution criteria. Low-risk patients had shorter durations of neutropenia but failed fever-resolution criteria more often than high-risk patients. In each exploratory analysis, response rates increased in both treatment groups compared to the primary analysis, particularly in low-risk patients. Conclusions. Response rates for the primary composite endpoint for both treatment groups in this study were driven by low rates of fever resolution. Requiring fever resolution during neutropenia in a composite endpoint can mask more clinically relevant outcomes.
C1 Univ Hosp St Radboud, Nijmegen, Netherlands.
   Merck Res Labs, West Point, PA USA.
   NCI, Bethesda, MD 20892 USA.
RP de Pauw, BE (reprint author), 603 Univ Med Ctr St Radboud, Dept Blood Transfus Transplant Immunol, Geert Grootepl Zuid 6,POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM B.dePauw@abti.umcn.nl
NR 19
TC 25
Z9 25
U1 0
U2 3
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1398-2273
J9 TRANSPL INFECT DIS
JI Transpl. Infect. Dis.
PD MAR
PY 2006
VL 8
IS 1
BP 31
EP 37
DI 10.1111/j.1399-3062.2006.00127.x
PG 7
WC Immunology; Infectious Diseases; Transplantation
SC Immunology; Infectious Diseases; Transplantation
GA 039WX
UT WOS:000237340000005
PM 16623818
ER

PT J
AU Horowits, R
AF Horowits, R
TI Nebulin regulation of actin filament lengths: new angles
SO TRENDS IN CELL BIOLOGY
LA English
DT Article
ID STRIATED-MUSCLE; THIN-FILAMENTS; SKELETAL-MUSCLES; TROPOMODULIN; GIANT;
   END; EXPRESSION; PROTEINS; RULERS
AB The highly organized arrays of thick and thin filaments found in striated muscles continue to be the subject of studies that yield groundbreaking concepts regarding cell motility. One example is the idea that massive, linearly extended polypeptides function as molecular rulers that set the length of polymeric filaments. Actin filaments that are polymerized in vitro exhibit wide variations in length, but many cells can assemble structures that contain actin filaments that are remarkably uniform. In striated muscles, the giant nebulin polypeptide extends the length of the actin filaments, and nebulin size has been correlated with actin filament lengths in muscles from different species. Here, I discuss a recent study by Gregorio and colleagues that demonstrates that nebulin knockdown leads to loss of actin filament-length regulation in cardiomyocytes, providing functional evidence that is consistent with the molecular ruler concept.
C1 NIAMSD, Muscle Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Horowits, R (reprint author), NIAMSD, Muscle Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM horowits@helix.nih.gov
FU Intramural NIH HHS
NR 18
TC 17
Z9 17
U1 0
U2 2
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD MAR
PY 2006
VL 16
IS 3
BP 121
EP 124
DI 10.1016/j.tcb.2006.01.003
PG 4
WC Cell Biology
SC Cell Biology
GA 028JR
UT WOS:000236484000001
PM 16480876
ER

PT J
AU Wu, XF
   Xiang, X
   Hammer, JA
AF Wu, XF
   Xiang, X
   Hammer, JA
TI Motor proteins at the microtubule plus-end
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
ID DYNEIN-DEPENDENT INTERACTIONS; CYTOPLASMIC DYNEIN; MITOTIC SPINDLE;
   ASPERGILLUS-NIDULANS; BUDDING YEAST; SACCHAROMYCES-CEREVISIAE; TRACKING
   PROTEINS; CELL CORTEX; INTERMEDIATE CHAIN; NEURONAL POLARITY
AB The plus-end of the microtubule has a central role in the interactions that occur between the microtubule and actin cytoskeletons. The recent identification of a family of proteins that congregate at the plus-end is enabling an increased mechanistic understanding of how this cross talk is accomplished. These proteins, termed plus-end tracking proteins because they appear to associate with the plus-end as it grows, have already been shown to regulate microtubule dynamics and to facilitate the formation of connections between the plus-end and the actin-rich cortex. Several motor proteins, including an actin-based motor, microtubule-based motors that move towards either end of the microtubule and microtubule motors that depolymerize microtubule ends, can now be added to the list of plus-end tracking proteins. Here, we discuss how the presence of these motors at the plus-end seems to drive several fundamental cellular processes involving force generation at the interface between microtubule ends and the cortex, vesicle translocation following search and capture, microtubule disassembly and the delivery of signals to the cortex that govern actin assembly and cell polarity.
C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
   Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA.
RP Hammer, JA (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM hammerj@nhlbi.nih.gov
NR 78
TC 65
Z9 66
U1 0
U2 9
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD MAR
PY 2006
VL 16
IS 3
BP 135
EP 143
DI 10.1016/j.tcb.2006.01.004
PG 9
WC Cell Biology
SC Cell Biology
GA 028JR
UT WOS:000236484000003
PM 16469495
ER

PT J
AU Goncalves, LF
   Lee, W
   Espinoza, J
   Romero, R
AF Goncalves, LF
   Lee, W
   Espinoza, J
   Romero, R
TI Examination of the fetal heart by four-dimensional (4D) ultrasound with
   spatio-temporal image correlation (STIC)
SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY
LA English
DT Article
DE 3D; 4D; congenital heart disease; fetus; four-dimensional; heart; STIC;
   three-dimensional; ultrasound
ID COLOR DOPPLER ULTRASOUND; STANDARD CARDIAC VIEWS; PRENATAL-DIAGNOSIS;
   3-DIMENSIONAL ULTRASOUND; B-FLOW; ECHOCARDIOGRAPHIC ANALYSIS; NORMAL
   FETUSES; GREAT-VESSELS; BLOOD-FLOW; DISEASE
C1 NICHHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA.
   Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA.
   William Beaumont Hosp, Div Fetal Imaging, Royal Oak, MI 48072 USA.
RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, NICHD, NIH,DHHS, Box 4,3990 John R,, Detroit, MI 48201 USA.
EM warfiela@mail.nih.gov
FU Intramural NIH HHS
NR 80
TC 62
Z9 74
U1 0
U2 5
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0960-7692
J9 ULTRASOUND OBST GYN
JI Ultrasound Obstet. Gynecol.
PD MAR
PY 2006
VL 27
IS 3
BP 336
EP 348
DI 10.1002/uog.2724
PG 13
WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
   Medical Imaging
SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine &
   Medical Imaging
GA 020ZI
UT WOS:000235951600023
PM 16482611
ER

PT J
AU Looper, JS
   Malarkey, DE
   Ruslander, D
   Proulx, D
   Thrall, DE
AF Looper, J. S.
   Malarkey, D. E.
   Ruslander, D.
   Proulx, D.
   Thrall, D. E.
TI Epidermal growth factor receptor expression in feline oral squamous cell
   carcinomas
SO VETERINARY AND COMPARATIVE ONCOLOGY
LA English
DT Article
DE epidermal growth factor receptor; feline; immunohistochemistry; oral
   squamous cell carcinoma; tyrosine kinase inhibitors
ID FACTOR-ALPHA; RADIATION RESPONSE; MESSENGER-RNA; BRAIN-TUMORS; HEAD;
   NECK; NEOPLASMS; THERAPY; PROTEIN; TARGET
AB Feline oral squamous cell carcinomas (SCC) have a poor prognosis despite aggressive treatment with surgery, radiation and anticancer drugs. Overexpression of the epidermal growth factor receptor (EGFR), a membrane-bound tyrosine kinase receptor, has been found in many human epithelial neoplasms, including oral SCC. EGFR overexpression has been associated with advanced disease and a poor prognosis. The purpose of this study was to determine whether feline oral SCC express EGFR. Thirteen formalin-fixed paraffin wax-embedded biopsy samples from feline oral SCC were analysed for EGFR expression using immunohistochemistry. Nine of 13 tumours (69%) were positive for EGFR expression, suggesting that altered EGFR expression plays a role in feline oral SCC and provides a rationale for a potential clinical benefit using EGFR inhibitors in combination with conventional treatments.
C1 N Carolina State Univ, Dept Mol Biomed Sci, Coll Vet Med, Raleigh, NC 27695 USA.
   Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
   N Carolina State Univ, Dept Clin Sci, Coll Vet Med, Raleigh, NC 27695 USA.
RP Looper, JS (reprint author), 2600 W Galena Blvd, Aurora, IL 60506 USA.
EM jayme.looper@vcamail.com
NR 41
TC 19
Z9 19
U1 1
U2 4
PU BLACKWELL PUBLISHING
PI OXFORD
PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
SN 1476-5810
J9 VET COMP ONCOL
JI Vet. Comp. Oncol.
PD MAR
PY 2006
VL 4
IS 1
BP 33
EP 40
DI 10.1111/j.1476-5810.2006.00091.x
PG 8
WC Veterinary Sciences
SC Veterinary Sciences
GA 172AA
UT WOS:000246775300005
PM 19754827
ER

PT J
AU Blaney, JE
   Durbin, AP
   Murphy, BR
   Whitehead, SS
AF Blaney, JE
   Durbin, AP
   Murphy, BR
   Whitehead, SS
TI Development of a live attenuated dengue virus vaccine using reverse
   genetics
SO VIRAL IMMUNOLOGY
LA English
DT Review
ID ANTIBODY-DEPENDENT ENHANCEMENT; GLYCOPROTEIN PROTECT MICE;
   HEMORRHAGIC-FEVER; RHESUS-MONKEYS; MONOCLONAL-ANTIBODIES;
   NONHUMAN-PRIMATES; TYPE-4 VIRUS; VERO CELLS; UNTRANSLATED REGION;
   MOLECULAR EVOLUTION
AB There are four serotypes of dengue (DEN1-DEN4) virus that are endemic in most areas of Southeast Asia, Central and South America, and other subtropical regions. The number of cases of severe disease associated with DEN virus infection is growing because of the continued spread of the mosquito vector, Aedes aegypti, which transmits the virus to humans. Infection with DEN virus can result in an asymptomatic infection, a febrile illness called dengue fever (DF), and the very severe disease called dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Currently, a licensed vaccine is not available. However, a tetravalent vaccine is urgently needed to prevent DF and DHF/DSS, the latter of which occurs predominantly in partially immune individuals. A live attenuated, tetravalent DEN virus vaccine candidate has been generated using reverse genetics that is able to provide immunity to each of the four serotypes of DEN. Attenuation has been achieved by generating recombinant DEN (rDEN) viruses which are modified by deletion or, alternatively, by antigenic chimerization between two related DEN viruses using the following two strategies: 1) introduction of an attenuating 30 nucleotide deletion (Delta 30) mutation into the 3 ' untranslated region of DEN1 and DEN4; and 2) replacement of structural proteins of the attenuated rDEN4 Delta 30 vaccine candidate with those from DEN2 or DEN3. Attenuation of the four monovalent vaccine candidates has been achieved for rhesus monkeys or humans and an immunogenic tetravalent vaccine candidate has been formulated. The level of attenuation of each dengue vaccine component can be increased, if needed, by introduction of additional attenuating mutations that have been well characterized.
C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
   Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD USA.
RP Blaney, JE (reprint author), NIAID, Infect Dis Lab, NIH, Twinbrook 3,Room 3W-13,12735 Twinbrook Pkwy,MSC 8, Bethesda, MD 20892 USA.
EM jblaney@niaid.nih.gov
FU Intramural NIH HHS
NR 98
TC 57
Z9 62
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0882-8245
J9 VIRAL IMMUNOL
JI Viral Immunol.
PD SPR
PY 2006
VL 19
IS 1
BP 10
EP 32
DI 10.1089/vim.2006.19.10
PG 23
WC Immunology; Virology
SC Immunology; Virology
GA 027DK
UT WOS:000236393700003
PM 16553547
ER

PT J
AU Schiffmann, R
   Rapkiewicz, A
   Abu-Asab, M
   Ries, M
   Askari, H
   Tsokos, M
   Quezado, M
AF Schiffmann, R
   Rapkiewicz, A
   Abu-Asab, M
   Ries, M
   Askari, H
   Tsokos, M
   Quezado, M
TI Pathological findings in a patient with Fabry disease who died after 2.5
   years of enzyme replacement
SO VIRCHOWS ARCHIV
LA English
DT Article
DE Fabry disease; lysosomes; atherosclerosis; myocardial infarction; enzyme
   replacement therapy; glycolipids
ID CEREBRAL HYPERPERFUSION; CARDIAC MANIFESTATIONS; ALPHA-GALACTOSIDASE;
   THERAPY; INVOLVEMENT; DEFICIENCY; EFFICACY; SAFETY
AB We describe the postmortem findings of a 47-year-old man with Fabry disease, an X-linked glycolipid storage disorder, who was on enzyme replacement therapy with recombinant alpha-galactosidase A for more than 2 years. The patient had widespread atherosclerotic coronary artery disease that culminated in a massive acute myocardial infarction. Atherosclerotic lesions were seen in the right and left coronary systems, aorta, and the basilar artery. Typical Fabry cardiomyopathy and glomerular nephropathy were found. With the exception of vascular endothelial cells, extensive glycolipid storage deposits were seen in all vascular and nonvascular cells and organ systems. We conclude that, at least in this patient, repeated infusions with alpha-galactosidase A over a prolonged period did not appreciably clear storage material in cells other than vascular endothelial cells. These findings also illustrate accelerated atherosclerosis in susceptible patients with Fabry disease.
C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA.
   NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Room 3D03,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM RS4e@nih.gov
OI Abu-Asab, Mones/0000-0002-4047-1232; Ries, Markus/0000-0002-5054-5741
FU Intramural NIH HHS [Z99 CA999999]
NR 22
TC 45
Z9 46
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING STREET, NEW YORK, NY 10013 USA
SN 0945-6317
J9 VIRCHOWS ARCH
JI Virchows Arch.
PD MAR
PY 2006
VL 448
IS 3
BP 337
EP 343
DI 10.1007/s00428-005-0089-x
PG 7
WC Pathology
SC Pathology
GA 020JN
UT WOS:000235905000015
PM 16315019
ER

PT J
AU Bhattacharjee, RN
   Archer, TK
AF Bhattacharjee, RN
   Archer, TK
TI Transcriptional silencing of the mouse mammary tumor virus promoter
   through chromatin remodeling is concomitant with histone H1
   phosphorylation and histone H3 hyperphosphorylation at M phase
SO VIROLOGY
LA English
DT Article
DE histone H1 phosphorylation; H3 hyperphosphorylation; cell cycle; MMTV;
   GR; chromatin remodeling
ID MMTV PROMOTER; IN-VIVO; NUCLEOSOME; CONDENSATION; RESOLUTION; RECEPTORS
AB We examined histone phosphorylation and their effects on glucocorticoid receptor (GR)-mediated activation of the mouse mammary tumor virus promoter (MMTV) in synchronized cells. In vivo protein expression studies suggest that both histones H1 and H3 are highly phosphorylated in mitotic-arrested cells in which GR is unable to remodel chromatin and recruit transcription factor NF1 to the promoter. Postmitotic cells show an open chromatin structure and efficient binding of NFI to the promoter accompanied by reversing histone H1 and H3 phosphorylation level. In contrast, the acetylation status of histone H3 and H4 did not change in either condition. These results Suggest that hyperphosphorylation of histone H1 and H3 leads to inhibition of GR-mediated chromatin remodeling and inactivation of MMTV by preventing the association of transcription factors to the promoter in vivo. (c) 2005 Elsevier Inc. All rights reserved.
C1 Osaka Univ, ERATO, Akira Innate Immun Project, Japan Sci & Technol Agcy, Suita, Osaka 5650871, Japan.
   Univ Western Ontario, Dept Obstet & Gynaecol, London, ON N6A 4L6, Canada.
   NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
RP Bhattacharjee, RN (reprint author), Osaka Univ, ERATO, Akira Innate Immun Project, Japan Sci & Technol Agcy, 3-1 Yamadaoka, Suita, Osaka 5650871, Japan.
EM rabin@biken.osaka-u.ac.jp
NR 26
TC 9
Z9 10
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD MAR 1
PY 2006
VL 346
IS 1
BP 1
EP 6
DI 10.1016/j.virol.2005.10.034
PG 6
WC Virology
SC Virology
GA 020SJ
UT WOS:000235930400001
PM 16458342
ER

PT J
AU Chiba, M
   Reed, JC
   Prokhnevsky, AI
   Chapman, EJ
   Mawassi, M
   Koonin, EV
   Carrington, JC
   Dolja, VV
AF Chiba, M
   Reed, JC
   Prokhnevsky, AI
   Chapman, EJ
   Mawassi, M
   Koonin, EV
   Carrington, JC
   Dolja, VV
TI Diverse suppressors of RNA silencing enhance agroinfection by a viral
   replicon
SO VIROLOGY
LA English
DT Article
DE RNA silencing; viral suppressors; agroinfection
ID BEET-YELLOWS-VIRUS; TO-CELL MOVEMENT; TRANSIENT EXPRESSION; PLANT
   CLOSTEROVIRUS; HSP70 HOMOLOG; PROTEIN; REPLICATION; GENOME; INSERTION;
   SIGNAL
AB Launching the Beet yellows virus (BYV) minireplicon by agrobacterial delivery resulted in an unexpectedly low number of infected cells per inoculated leaf. This effect was due to a strong RNA silencing response in the agroinfiltrated leaves. Strikingly, ectopic co-expression of p21, a BYV RNA silencing suppressor, increased minireplicon infectivity by three orders of magnitude. Mutational analysis demonstrated that this effect correlates with suppressor activity of p21. Five diverse, heterologous viral suppressors were also active in this system, providing a useful approach for a dramatic, Lip to 10,000-fold, increase of the efficiency of agroinfection. The minireplicon agroinfection assay was also used to identify a new Suppressor, a homolog of BYV p21, derived from Grapevine leafroll-associated virus-2. In addition, we report preliminary data on the suppressor activity of the p10 protein of Grapevine virus A and show that this protein belongs to a family of Zn-ribbon-containing proteins encoded by filamentous plant RNA viruses from three genera. The members of this family are predicted to have RNA silencing suppressor activity. (c) 2005 Elsevier Inc. All rights reserved.
C1 Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA.
   Oregon State Univ, Ctr Gene Res & Biotechnol, Corvallis, OR 97331 USA.
   Agr Res Org, Dept Virol, IL-50250 Bet Dagan, Israel.
   NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Dolja, VV (reprint author), Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA.
EM doljav@science.oregonstate.edu
RI Carrington, James/A-4656-2012
OI Carrington, James/0000-0003-3572-129X
FU NCRR NIH HHS [1S10RR107903-01]; NIAID NIH HHS [AI43288]; NIGMS NIH HHS
   [GM053190]
NR 39
TC 79
Z9 85
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD MAR 1
PY 2006
VL 346
IS 1
BP 7
EP 14
DI 10.1016/j.virol.2005.09.068
PG 8
WC Virology
SC Virology
GA 020SJ
UT WOS:000235930400002
PM 16300814
ER

PT J
AU Pierson, TC
   Sanchez, MD
   Puffer, BA
   Ahmed, AA
   Geiss, BJ
   Valentine, LE
   Altamura, LA
   Diamond, MS
   Doms, RW
AF Pierson, TC
   Sanchez, MD
   Puffer, BA
   Ahmed, AA
   Geiss, BJ
   Valentine, LE
   Altamura, LA
   Diamond, MS
   Doms, RW
TI A rapid and quantitative assay for measuring antibody-mediated
   neutralization of West Nile virus infection
SO VIROLOGY
LA English
DT Article
DE West Nile viris; flavivirus; antibody-ruediated neutralization; reporter
   virus particle; pseudotype
ID TICK-BORNE ENCEPHALITIS; PLAQUE REDUCTION NEUTRALIZATION; PACKAGING
   CELL-LINE; DENGUE VIRUS; ENVELOPE GLYCOPROTEIN; IN-VITRO; DEPENDENT
   ENHANCEMENT; STRUCTURAL PROTEINS; REPLICON PARTICLES; SUBVIRAL PARTICLES
AB West Nile virus (WNV) is a neurotropic flavivirus within the Japanese encephalitis antigenic complex that is responsible for causing West Nile encephalitis in humans. The surface of WNV virions is covered by a highly ordered icosahedral array of envelope proteins that is responsible for mediating attachment and fusion with target cells. These envelope proteins are also primary targets for the generation of neutralizing antibodies in vivo. In this study, we describe a novel approach for measuring antibody-mediated neutralization of WNV infection using Virus-like particles that measure infection as a function of reporter gene expression. These reporter virus particles (RVPs) are produced by complementation of a subgenomic replicon with WNV structural proteins provided in trans using conventional DNA expression vectors. The precision and accuracy of this approach stern from an ability to measure the Outcome of the interaction between antibody and viral antigens under conditions that satisfy the assumptions of the law of mass action as applied to virus neutralization. In addition to its quantitative strengths, this approach allows the production of WNV RVPs bearing the prM-E proteins of different WNV strains and mutants, offering considerable flexibility for the study of the humoral immune response to WNV in vitro. WNV RVPs are capable of only a Single round of infection, can be used under BSL-2 conditions, and offer a rapid and quantitative approach for detecting Virus entry and its inhibition by neutralizing antibody. Published by Elsevier Inc.
C1 NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA.
   Univ Penn, Dept Microbiol, Sch Med, Philadelphia, PA 19104 USA.
   Washington Univ, Sch Med, Dept Med Mol Microbiol Pathol & Immunol, St Louis, MO 63110 USA.
RP Doms, RW (reprint author), NIH, Viral Pathogenesis Sect, Viral Dis Lab, 4 Ctr Dr,Room 216, Bethesda, MD 20892 USA.
EM piersontc@mail.nih.gov; doms@mail.med.upenn.edu
RI Altamura, Louis/B-5668-2008
FU Intramural NIH HHS; NCRR NIH HHS [F31 RR05074]; NIAID NIH HHS [U01
   AI061373, U54 AI57173]
NR 72
TC 95
Z9 100
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 0042-6822
J9 VIROLOGY
JI Virology
PD MAR 1
PY 2006
VL 346
IS 1
BP 53
EP 65
DI 10.1016/j.virol.2005.10.030
PG 13
WC Virology
SC Virology
GA 020SJ
UT WOS:000235930400006
PM 16325883
ER

PT J
AU Gemeniano, M
   Mpanju, O
   Salomon, DR
   Elden, MV
   Wilson, CA
AF Gemeniano, M
   Mpanju, O
   Salomon, DR
   Elden, MV
   Wilson, CA
TI The infectivity and host range of the ecotropic porcine endogenous
   retrovirus, PERV-C, is modulated by residues in the C-terminal region of
   its surface envelope protein
SO VIROLOGY
LA English
DT Article
DE porcine endogenous retrovirus; receptor binding domain; envelope; virus
   entry
ID MURINE LEUKEMIA-VIRUS; RECEPTOR-BINDING DOMAIN; MINIATURE SWINE;
   SUBGROUP-B; IDENTIFICATION; CELLS; GLYCOPROTEIN; ACTIVATION; ENTRY;
   DETERMINANTS
AB Endogenous retroviral genetic material serves as a reservoir for the generation of retroviral pathogens by recombination between activated endogenous or exogenous infectious agents. Some porcine tissues actively express infectious porcine endogenous retroviruses (PERVs). Of the three classes of PERV characterized to date, two, PERV-A and B, are capable of infecting human cells in vitro, whereas PERV-C cannot. Here, we demonstrate that the PERV-C envelope Surface protein (SU) when disassociated from its C-terminus binds human cells. Further, we show that PERV-C binding to human cells is not inhibited in 293 cells productively infected with PERV-A, confirming that the molecule PERV-C interacts with on human cells is distinct from that used by PERV-A. Moreover, we demonstrate that the envelope region encompassing the proline-rich region is required for binding to cells in addition to the putative variable region A (VRA) and B (VRB). The region in the C-terminus of the SU that alters the binding and infectivity properties of PERV-C differs by only nine residues from the analogous region of PERV-A. Caution may be warranted even when a xenotransplantation product is from source pigs that do not express human-tropic viruses, as minimal mutations within PERV-C combined with selection in a human recipient Could render PERV-C infectious in humans. Published by Elsevier Inc.
C1 US FDA, Ctr Biol Evaluat & Res, Lab Immunol & Virol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA.
   Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA.
   NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA.
RP Wilson, CA (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Immunol & Virol, Div Cellular & Gene Therapies, 8000 Rockville Pike,HFM-725,Bldg 29B,Room 2NN12, Bethesda, MD 20892 USA.
EM wilsonc@cber.fda.gov
RI Salomon, Daniel/E-9380-2012
FU NIAID NIH HHS [R0A AI52349]
NR 32
TC 34
Z9 36
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD MAR 1
PY 2006
VL 346
IS 1
BP 108
EP 117
DI 10.1016/j.virol.2005.10.021
PG 10
WC Virology
SC Virology
GA 020SJ
UT WOS:000235930400011
PM 16309725
ER

PT J
AU Mazurov, D
   Heidecker, G
   Derse, D
AF Mazurov, D
   Heidecker, G
   Derse, D
TI HTLV-1 Gag protein associates with CD82 tetraspanin microdomains at the
   plasma membrane
SO VIROLOGY
LA English
DT Article
DE HTLV-1; retrovirus; HIV-1; T cells; immune synapse; tetraspanins; CD82
ID LEUKEMIA-VIRUS TYPE-1; T-CELL-ACTIVATION; LIPID RAFTS; METASTASIS
   SUPPRESSOR; SIGNALING COMPLEXES; MATRIX PROTEIN; MAJOR CD9; LYMPHOCYTES;
   CHOLESTEROL; INTEGRINS
AB We examined the association of HTLV-1 Gag with tetraspanin-enriched microdomains in the plasma membrane. Immunofluorescent staining and confocal image analysis showed that HTLV-1 Gag protein colocalized with CD82 and other tetraspanins at the plasma membrane of T cells. HTLV-1 Gag, which is associated with the inner surface of the plasma membrane, was concentrated to the patches formed by antibody-mediated cross-linking of CD82 oil the cell Surface. Also, CD82 and HTLV-1 Gag rapidly segregated to the immune synapse that is formed between Raji B cells and Jurkat T cells in the presence of bacterial superantigen. CD82, which was immunoprecipitated from cell extracts prepared in Brij97 detergent conditions, was associated with the matrix (MA) protein. Stable interaction of MA and CD82 in Brij97-disrupted cell extracts required Gag multimerization and proteolytic processing. The form of MA that coimmunoprecipitated with CD82 was a cysteine-linked homodimer. The viral envelope glycoprotein was not required for the association of Gag with CD82-enriched membrane regions. in contrast to HTLV-1, HIV-1 Gag did not colocalize, cosegregate, or coimmunoprecipitate with CD82. Our data suggest that once at the plasma membrane, HTLV-1 virion components associate with CD82-containing microdomains, which may facilitate the mobilization of nascent virions to sites of intercellular adhesion. Published by Elsevier Inc.
C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Derse, D (reprint author), NCI, HIV Drug Resistance Program, Bld 535,Rm 110, Frederick, MD 21702 USA.
EM derse@ncifcrf.gov
FU Intramural NIH HHS
NR 46
TC 31
Z9 33
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD MAR 1
PY 2006
VL 346
IS 1
BP 194
EP 204
DI 10.1016/j.virol.2005.10.033
PG 11
WC Virology
SC Virology
GA 020SJ
UT WOS:000235930400018
PM 16325219
ER

PT J
AU Lodmell, DL
   Dimcheff, DE
   Ewalt, LC
AF Lodmell, DL
   Dimcheff, DE
   Ewalt, LC
TI Viral RNA in the bloodstream suggests viremia occurs in clinically ill
   rabies-infected mice
SO VIRUS RESEARCH
LA English
DT Article
DE rabies; rabies virus; viremia; TaqMan PCR; mice
ID VIRUS; PATHOGENESIS; CORTISONE; RISK
AB Data regarding the Occurrence of a viremia during rabies virus infections are contradictory. Here, we attempted to clarify the dissimilar results using a qualitative TaqMan PCR assay to detect viral RNA in blood of mice that had been injected intramuscularly with rabies virus. Viral RNA was detected at two different intervals. Initially, RNA was present in blood of 30/32 (94%) mice, from I It to 2 days after injection of virus. The RNA in the blood at this time most likely resulted from trauma to blood vessels at the injection site and leakage of the inoculated virus into the circulation. Thereafter, from 3 to 30 days, viral RNA Was undetectable in the blood of 37 mice that remained free of clinical disease. However, and more importantly, viral RNA was detected again in 21/25 (84%) mice that became clinically ill and were emanguinated 2-4 days after the onset of paralysis. The presence of viral RNA in blood of the clinically ill mice might have been due to an escape of virus into the bloodstream as a result of viral replication induced injury in the central nervous system and other tissues. Anti-rabies virus neutralizing antibody was detected in sera of 11/21 (52%) clinically ill mice whose blood was positive for rabies viral RNA. The presence of viral RNA in the bloodstream of mice that developed clinical rabies suggested that a viremia might occur in rabies-infected mice. Thus, the Current opinion that a viremia does not occur in experimental or natural rabies infections of other species might need to be re-evaluated. Published by Elsevier B.V.
C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
RP Lodmell, DL (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA.
EM djrabid@aol.com
NR 29
TC 4
Z9 5
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD MAR
PY 2006
VL 116
IS 1-2
BP 114
EP 118
DI 10.1016/j.virusres.2005.09.004
PG 5
WC Virology
SC Virology
GA 019VI
UT WOS:000235864400014
PM 16242805
ER

PT J
AU Miura, K
   Matsuura, K
   Taki, M
   Tabata, H
   Inaba, N
   Kawano, K
   Miles, FA
AF Miura, K
   Matsuura, K
   Taki, M
   Tabata, H
   Inaba, N
   Kawano, K
   Miles, FA
TI The visual motion detectors underlying ocular following responses in
   monkeys
SO VISION RESEARCH
LA English
DT Article
DE missing fundamental; spatio-temporal filtering; energy-based mechanisms;
   eye movements
ID SHORT-LATENCY; 2ND-ORDER MOTION; BINOCULAR DISPARITY; VIEWING DISTANCE;
   MACAQUE MONKEY; EYE-MOVEMENTS; AREA MT; PERCEPTION; CONTRAST; HUMANS
AB Psychophysical evidence indicates that visual motion can be sensed by low-level (energy-based) and high-level (feature-based) mechanisms. The present experiments were undertaken to determine which of these mechanisms mediates the initial ocular following response (OFR) that can be elicited at ultra-short latencies by sudden motion of large-field images. We used the methodology of Sheliga, Chen, Fitzgibbon, and Miles (Initial ocular following in humans: A response to first-order motion energy. Vision Research, 2005a), who studied the initial OFRs of humans, to study the initial OFRs of monkeys. Accordingly, we applied horizontal motion to: (1) vertical square-wave gratings lacking the fundamental ("missing fundamental stimulus") and (2) vertical grating patterns consisting of the sum of two sinusoids of frequency 3f and 4f, which created a repeating pattern with beat frequency, f. Both visual stimuli share a critical property: when subject to 1/4-wavelength steps, their overall pattern (feature) shifts in the direction of the steps, whereas their major Fourier component shifts in the reverse direction (because of spatial aliasing). We found that the initial OFRs of monkeys to these stimuli, like those of humans, were always in the opposite direction to the 1/4-wavelength shifts, i.e., in the direction of the major Fourier component, consistent with detection by (low-level) oriented spatio-temporal filters as in the well-known energy model of motion analysis. Our data indicate that the motion detectors mediating the initial OFR have quantitatively similar properties in monkeys and humans, suggesting that monkeys provide a good animal model for the human OFR. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Kyoto Univ, Grad Sch Med, Horizontal Med Res Org, Kyoto, Japan.
   Kyoto Univ, Grad Sch Med, Dept Integrat Brain Sci, Kyoto, Japan.
   Kyoto Prefectural Univ Med, Dept Otolaryngol, Kyoto, Japan.
   NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA.
RP Miura, K (reprint author), Kyoto Univ, Grad Sch Med, Horizontal Med Res Org, Kyoto, Japan.
EM kmiura@brain.med.kyoto-u.ac.jp
OI Inaba, Naoko/0000-0002-0073-275X
FU Intramural NIH HHS [Z01 EY000153-24]
NR 46
TC 24
Z9 24
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD MAR
PY 2006
VL 46
IS 6-7
BP 869
EP 878
DI 10.1016/j.visres.2005.10.021
PG 10
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 022RM
UT WOS:000236073400012
PM 16356529
ER

PT J
AU Sheliga, BM
   Chen, KJ
   FitzGibbon, EJ
   Miles, FA
AF Sheliga, BM
   Chen, KJ
   FitzGibbon, EJ
   Miles, FA
TI The initial ocular following responses elicited by apparent-motion
   stimuli: Reversal by inter-stimulus intervals
SO VISION RESEARCH
LA English
DT Article
DE temporal impulse response; energy-based mechanisms; missing fundamental;
   scotopic vision
ID LATERAL GENICULATE-NUCLEUS; TEMPORAL IMPULSE-RESPONSE; VERGENCE
   EYE-MOVEMENTS; SHORT-LATENCY; VISUAL-MOTION; 2ND-ORDER MOTION;
   INTERMITTENT DISPLAY; BINOCULAR DISPARITY; TRANSIENT RESPONSES; DYNAMIC
   PROPERTIES
AB Transient apparent-motion stimuli, consisting of single 1/4-wavelength steps applied to square-wave gratings lacking the fundamental ("missing fundamental stimulus") and to sinusoidal gratings, were used to elicit ocular following responses (OFRs) in humans. As previously reported [Sheliga, B. M., Chen, K. J., FitzGibbon, E. J., & Miles, F. A. (2005). Initial ocular following in humans: a response to first-order motion energy. Vision Research, in press], the earliest OFRs were strongly dependent on the motion of the major Fourier component, consistent with early spatio-temporal filtering prior to motion detection, as in the well-known energy model of motion analysis. Introducing inter-stimulus intervals (ISIs) of 10-200 ms, during which the screen was gray with the same mean luminance, reversed the initial direction of the OFR, the peak reversed responses (with ISIs of 20-40 ms) being substantially greater than the non-reversed responses (with an ISI of 20-40 ms). When the mean luminance was reduced to scotopic levels, reversals now occurred only with ISIs >= 60 ms and the peak reversed responses (with ISIs of 60-100 ms) were substantially smaller than the non-reversed responses (with an ISI of 0 ms). These findings are consistent with the idea that initial OFRs are mediated by first-order motion-energy-sensing mechanisms that receive a visual input whose temporal impulse response function is strongly biphasic in photopic conditions and almost monophasic in scotopic conditions. Published by Elsevier Ltd.
C1 NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA.
RP Sheliga, BM (reprint author), NEI, Lab Sensorimotor Res, NIH, Bethesda, MD 20892 USA.
EM bms@lsr.nei.nih.gov
FU Intramural NIH HHS [Z01 EY000153-24]
NR 72
TC 28
Z9 28
U1 1
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0042-6989
J9 VISION RES
JI Vision Res.
PD MAR
PY 2006
VL 46
IS 6-7
BP 979
EP 992
DI 10.1016/j.visres.2005.09.001
PG 14
WC Neurosciences; Ophthalmology
SC Neurosciences & Neurology; Ophthalmology
GA 022RM
UT WOS:000236073400023
PM 16242168
ER

PT J
AU Brust, D
   Polis, M
   Davey, R
   Hahn, B
   Bacharach, S
   Whatley, M
   Fauci, AS
   Carrasquillo, JA
AF Brust, D
   Polis, M
   Davey, R
   Hahn, B
   Bacharach, S
   Whatley, M
   Fauci, AS
   Carrasquillo, JA
TI Fluorodeoxyglucose imaging in healthy subjects with HIV infection:
   impact of disease stage and therapy on pattern of nodal activation
SO AIDS
LA English
DT Article
DE fluorodeoxyglucose; F-18; positron emission tomography; PET; HIV; HAART
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY;
   POSITRON-EMISSION-TOMOGRAPHY; VIRAL SUPPRESSION; LYMPHOID ORGANS;
   T-CELLS; DYNAMICS; PLASMA; LYMPHOCYTES; TURNOVER
AB Objectives: Nodal uptake in areas of lymphocyte activation can be visualized using fluorodeoxyglucose (FDG). Various patterns of FDG accumulation in HIV-positive subjects have been described previously and hypothesized to potentially represent regions of active HIV replication and or nodal activation. We evaluated the utility of FDG scanning as a tool to study HIV pathogenesis.
   Design: We evaluated FDG biodistribution visually and quantitatively in HIV-negative individuals and various groups of HIV-infected subjects to determine the impact on pattern of nodal activation of: HIV infection; stage of HIV infection and degree of viremia; and HAART. In addition, we attempted to image anatomical site(s) of on-going HIV replication in subjects with suppressed HIV viremia on ART, but who subsequently discontinued ART.
   Method: We performed FDG imaging on five groups: HIV-negative, HIV-positive with early infection, HIV-positive with advanced disease, HIV-positive with suppressed viral loads, and HIV-positive who stopped ART.
   Results: Healthy HIV subjects with suppressed viral loads and HIV-negative individuals had no or little FDG nodal accumulation or any other hypermetabolic areas, whereas viremic subjects with early and advanced HIV had increased FDG in peripheral nodes, indicating that FDG potentially identifies areas of HIV replication. FDG biodistribution was similar between early and advanced-stage. Four of five subjects taken off ART had negative baseline scans but developed nodal uptake and increases in viral load.
   Conclusions: Abnormal FDG accumulation occurs in nodes of subjects with detectable viral loads. Interruption of effective ART results in activation of previously quiescent nodal areas. (C) 2006 Lippincott Williams & Wilkins.
C1 NIAID, NIH, Bethesda, MD USA.
   NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD USA.
RP Carrasquillo, JA (reprint author), 10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA.
EM jcarrasquillo@mail.nih.gov
OI Polis, Michael/0000-0002-9151-2268; Carrasquillo,
   Jorge/0000-0002-8513-5734
NR 37
TC 16
Z9 16
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD FEB 28
PY 2006
VL 20
IS 4
BP 495
EP 503
DI 10.1097/01.aids.0000210603.40267.29
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 019XY
UT WOS:000235873000002
PM 16470113
ER

PT J
AU Mayer, KH
   Maslankowski, LA
   Gai, F
   El-Sadr, WM
   Justman, J
   Kwiecien, A
   Masse, B
   Eshleman, SH
   Hendrix, C
   Morrow, K
   Rooney, JF
   Soto-Torres, L
AF Mayer, KH
   Maslankowski, LA
   Gai, F
   El-Sadr, WM
   Justman, J
   Kwiecien, A
   Masse, B
   Eshleman, SH
   Hendrix, C
   Morrow, K
   Rooney, JF
   Soto-Torres, L
CA HPTN 050 Protocol Team
TI Safety and tolerability of tenofovir vaginal gel in abstinent and
   sexually active HIV-infected and uninfected women
SO AIDS
LA English
DT Article
DE microbicide; women; HIV prevention; clinical trial; antiretroviral
ID SIMIAN IMMUNODEFICIENCY VIRUS; TOPICAL MICROBICIDES; NEWBORN MACAQUES;
   TRIAL; 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE; ACCEPTABILITY; COLPOSCOPY;
   METABOLISM; PREVENTION; IRRITATION
AB Objectives: To establish the highest practical dose and frequency (HPDF) of 0.3% or 1% tenofovir vaginal gel applied once or twice daily by sexually abstinent HIV-uninfected women, and to evaluate the safety, tolerability and systemic pharmacokinetics of the HPDF in abstinent and sexually active HIV-negative and HIV-infected women.
   Methods: Eighty-four women, enrolled in sequential cohorts, used the study product for 14 consecutive intermenstrual days. Safety laboratory assessments and pelvic examinations were carried out during five study visits, with colposcopy at enrollment and on day 14. Samples for pharmacokinetics were collected before and after the initial tenofovir gel use and at day 13.
   Results: The 1% tenofovir gel used twice daily was as well tolerated as other regimens used by the 48 HIV-negative sexually abstinent women, establishing the HPDF. Although 92% of the women reported at least one adverse event, the majority were mild (87%) and involved the genitourinary tract (70%). One possibly product-related severe adverse event involving lower abdominal cramping was reported by a sexually abstinent woman who used 0.3% gel twice daily. Serum tenofovir levels were low but detectable in 14 of the 25 women. No new HIV RNA resistance mutations were detected after 2 weeks of tenofovir gel in the 24 HIV-infected participants. No significant systemic toxicity was detected.
   Conclusion: A 2-week course of 1% tenofovir vaginal gel used twice daily was well tolerated in sexually abstinent and sexually active HIV-negative and HIV-positive women. Systemic tenofovir absorption occurred. Expanded safety and effectiveness testing is warranted. (C) 2006 Lippincott Williams & Wilkins.
C1 Brown Univ, Miriam Hosp, Providence, RI 02906 USA.
   NIAID, Bethesda, MD 20892 USA.
   Gilead Sci Inc, Foster City, CA 94404 USA.
   Johns Hopkins Univ, Baltimore, MD USA.
   Family Hlth Int, Arlington, VA USA.
   Bronx Lebanon Hosp Ctr, New York, NY USA.
   Columbia Univ, New York, NY USA.
   Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, New York, NY 10032 USA.
   Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   Univ Penn, Philadelphia, PA 19104 USA.
   Fenway Community Hlth, Boston, MA USA.
RP Mayer, KH (reprint author), Brown Univ, Miriam Hosp, 164 Summit Ave, Providence, RI 02906 USA.
EM Kenneth_Mayer@brown.edu
OI Masse, Benoit/0000-0002-4944-8098
FU NIAID NIH HHS [U01-AI-48016, U01-AI-46702, U01-AI-46745, U01-AI-48014,
   U01-AI-48040]
NR 36
TC 118
Z9 120
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD FEB 28
PY 2006
VL 20
IS 4
BP 543
EP 551
DI 10.1097/01.aids.0000210608.70762.c3
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 019XY
UT WOS:000235873000007
PM 16470118
ER

PT J
AU Best, BM
   Mirochnick, M
   Capparelli, EV
   Stek, A
   Burchett, SK
   Holland, DT
   Read, JS
   Smith, E
   Hu, CC
   Spector, SA
   Connor, JD
AF Best, BM
   Mirochnick, M
   Capparelli, EV
   Stek, A
   Burchett, SK
   Holland, DT
   Read, JS
   Smith, E
   Hu, CC
   Spector, SA
   Connor, JD
CA PACTG P1026s Study Team
TI Impact of pregnancy on abacavir pharmacokinetics
SO AIDS
LA English
DT Article; Proceedings Paper
CT 33rd Annual Meeting of the American-College-of-Clinical-Pharmacology
CY OCT 03-05, 2004
CL Phoenix, AZ
SP Amer Coll Clin Pharmacol
DE reverse transcriptase inhibitors; pharmacokinetics; pregnancy;
   antiretroviral agents; HIV; AIDS; drug monitoring
ID HUMAN-IMMUNODEFICIENCY-VIRUS; DOSE PHARMACOKINETICS; INFECTED SUBJECTS;
   ZIDOVUDINE; WOMEN; SAFETY; LAMIVUDINE; 1592U89; ADULTS; COMBINATION
AB Objective: To describe abacavir pharmacokinetics during pregnancy and postpartum; physiological changes during pregnancy are known to affect antiretroviral drug disposition.
   Design: The Pediatric AIDS Clinical Trials Group P1026s study is an on-going, prospective, non-blinded pharmacokinetic study of pregnant women receiving one or more antiretroviral drugs for routine clinical care, including a cohort receiving abacavir 300 mg twice daily.
   Methods: Serial plasma samples (predose, 1, 2, 4, and 6 h postdose) obtained antepartum (30-36 weeks of gestation) and again postpartum (6-12 weeks after delivery) were assayed for abacavir concentration by reversed-phase high-performance liquid chromatography.
   Results: Antepartum evaluations were available for 25 women [mean age, 28.6 years (SD, 6); mean third-trimester weight 92 kg (SD, 35.4); and race/ethnicity 52% black, 28% Hispanic, 16% white, 4% Asian], with geometric mean abacavir area under the concentration-time curve (AUC) of 5.9 mg.h/l [90% confidence interval (CI), 5.2-6.8] and maximum plasma concentration (C-max) of 1.9 mg/l (90% CI, 1.6-2.2). Seventeen women completed postpartum sampling, and the ratios of antepartum to postpartum AUC and C-max were 1.04 (90% CI, 0.91-1.18) and 0.79 (90% CI, 0.65-0.98), respectively.
   Conclusions: Abacavir AUC during pregnancy was similar to that at 6-12 weeks postpartum and to that for non-pregnant historical controls (5.8 mg.h/l). Consequently, pregnancy does not appear to affect overall abacavir exposure significantly or to necessitate dose adjustments. (C) 2006 Lippincott Williams & Wilkins.
C1 Univ Calif San Diego, San Diego, CA 92103 USA.
   NIAID, Bethesda, MD 20892 USA.
   NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, DHHS, Bethesda, MD USA.
   Univ So Calif, Los Angeles, CA USA.
   Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
   Childrens Hosp, Boston, MA 02115 USA.
   Boston Univ, Boston, MA 02215 USA.
RP Best, BM (reprint author), Univ Calif San Diego, 200 W Arbor Dr,MC 8214, San Diego, CA 92103 USA.
EM brookie@ucsd.edu
RI Hu, Chengcheng/A-8391-2017
FU NIAID NIH HHS [U01 AI04189, U01 AI41089]; NICHD NIH HHS
   [N01-HD-031318-11, N01-HD-3-3365]
NR 21
TC 29
Z9 29
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD FEB 28
PY 2006
VL 20
IS 4
BP 553
EP 560
DI 10.1097/01.aids.0000210609.52836.d1
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 019XY
UT WOS:000235873000008
PM 16470119
ER

PT J
AU Liang, MC
   Bardhan, S
   Pace, EA
   Rosman, D
   Beutler, JA
   Porco, JA
   Gilmore, TD
AF Liang, MC
   Bardhan, S
   Pace, EA
   Rosman, D
   Beutler, JA
   Porco, JA
   Gilmore, TD
TI Inhibition of transcription factor NF-kappa B signaling proteins IKK
   beta and p65 through specific cysteine residues by epoxyquinone A
   monomer: Correlation with its anti-cancer cell growth activity
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE NF-kappaB; IkappaB; IkappaB kinase; epoxyquinone A monomer; fungal
   metabolite; epoxyquinoid
ID SESQUITERPENE LACTONES; INDUCED APOPTOSIS; NATURAL-PRODUCTS; COVALENT
   MODIFICATION; BIOLOGICAL-ACTIVITY; MEDIATED APOPTOSIS; MULTIPLE-MYELOMA;
   CANCER CELLS; DNA-BINDING; IN-VIVO
AB Transcription factor NF-kappa B is constitutively active in many human chronic inflammatory diseases and cancers. Epoxyquinone A monomer (EqM), a synthetic derivative of the natural product epoxyquinol A, has previously been shown to be a potent inhibitor of tumor necrosis factor-a (TNF-alpha)-induced activation of NF-kappa B, but the mechanism by which EqM inhibits NF-kappa B activation was not known. In this report, we show that EqM blocks activation of NF-kappa B by inhibiting two molecular targets: I kappa B kinase IKK beta and NF-kappa B subunit p65. EqM inhibits TNF-alpha-induced I kappa B alpha phosphorylation and degradation by targeting IKK beta, and an alanine substitution for Cys179 in the activation loop of IKK beta makes it resistant to EqM-mediated inhibition. EqM also directly inhibits DNA binding by p65, but not p50; moreover, replacement of Cys38 in p65 with Ser abolishes EqM-mediated inhibition of DNA binding. Pretreatment of cells with reducing agent dithiothreitol close-dependently reduces EqM-mediated inhibition of NF-kappa B, further suggesting that EqM directly modifies the thiol group of Cys residues in protein targets. Modifications of the exocyclic alkene of EqM substantially reduce EqM's ability to inhibit NF-kappa B activation. In the human SUDHL-4 lymphoma cell line, EqM inhibits both proliferation and NF-kappa B DNA binding, and activates caspase-3 activity. EqM also effectively inhibits the growth of human leukemia, kidney, and colon cancer cell lines in the NCI's tumor cell panel. Among six colon cancer cell lines, those with low amounts of constitutive NF-kappa B DNA-binding activity are generally more sensitive to growth inhibition by EqM. Taken together, these results suggest that EqM inhibits growth and induces cell death in tumor cells through a mechanism that involves inhibition of NF-kappa B activity at multiple steps in the signaling pathway. (c) 2005 Elsevier Inc. All rights reserved.
C1 Boston Univ, Dept Biol, Boston, MA 02215 USA.
   Boston Univ, Dept Chem, Boston, MA 02215 USA.
   Boston Univ, Ctr Chem Methodol & Lib Dev, Boston, MA 02215 USA.
   NCI, Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21702 USA.
RP Gilmore, TD (reprint author), Boston Univ, Dept Biol, 5 Cummington St, Boston, MA 02215 USA.
EM gilmore@bu.edu
RI Beutler, John/B-1141-2009
OI Beutler, John/0000-0002-4646-1924
FU NCI NIH HHS [CA 47763]
NR 59
TC 59
Z9 59
U1 1
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD FEB 28
PY 2006
VL 71
IS 5
BP 634
EP 645
DI 10.1016/j.bcp.2005.11.013
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 011VT
UT WOS:000235297300009
PM 16360644
ER

PT J
AU Hopper, RK
   Carroll, S
   Aponte, AM
   Johnson, DT
   French, S
   Shen, RF
   Witzmann, FA
   Harris, RA
   Balaban, RS
AF Hopper, RK
   Carroll, S
   Aponte, AM
   Johnson, DT
   French, S
   Shen, RF
   Witzmann, FA
   Harris, RA
   Balaban, RS
TI Mitochondrial matrix phosphoproteome: Effect of extra mitochondrial
   calcium
SO BIOCHEMISTRY
LA English
DT Article
ID MANGANESE-SUPEROXIDE-DISMUTASE; PYRUVATE-DEHYDROGENASE COMPLEX; STATE
   PROTEIN-PHOSPHORYLATION; PERMEABILITY TRANSITION PORE; BOVINE
   HEART-MITOCHONDRIA; RAT CARDIAC-MUSCLE; OXIDATIVE-PHOSPHORYLATION; GEL
   STAIN; KINASE; APOPTOSIS
AB Post-translational modification of mitochondrial proteins by phosphorylation or dephosphorylation plays an essential role in numerous cell signaling pathways involved in regulating energy metabolism and in mitochondrion-induced apoptosis. Here we present a phosphoproteomic screen of the mitochondrial matrix proteins and begin to establish the protein phosphorylations acutely associated with calcium ions (Ca2+) signaling in porcine heart mitochondria. Forty-five phosphorylated proteins were detected by gel electrophoresis-mass spectrometry of Pro-Q Diamond staining, while many more Pro-Q Diamond-stained proteins evaded mass spectrometry detection. Time-dependent P-32 incorporation in intact mitochondria confirmed the extensive matrix protein phosphoryation and revealed the dynamic nature of this process. Classes of proteins that were detected included all of the mitochondrial respiratory chain complexes, as well as enzymes involved in intermediary metabolism, such as pyruvate dehydrogenase (PDH), citrate synthase, and acyl-CoA dehydrogenases. These data demonstrate that the phosphoproteome of the mitochondrial matrix is extensive and dynamic. Ca2+ has previously been shown to activate various dehydrogenases, promote the generation of reactive oxygen species (ROS), and initiate apoptosis via cytochrome c release. To evaluate the Ca2+ signaling network, the effects of a Ca2+ challenge sufficient to release cytochrome c were evaluated on the mitochondrial phosphoproteome. Novel Ca2+-induced dephosphorylation was observed in manganese superoxide dismutase (MnSOD) as well as the previously characterized PDH. A Ca2+ dose-dependent dephosphorylation of MnSOD was associated with an similar to 2-fold maximum increase in activity; neither the dephosphorylation nor activity changes were induced by ROS production in the absence of Ca2+. These data demonstrate the use of a phosphoproteome screen in determining mitochondrial signaling pathways and reveal new pathways for Ca2+ modification of mitochondrial function at the level of MnSOD.
C1 NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   NHLBI, Proteom Core Facil, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, 10 Ctr Dr,Room B1D416, Bethesda, MD 20892 USA.
EM rsb@nih.gov
RI Balaban, Robert/A-7459-2009
OI Balaban, Robert/0000-0003-4086-0948
FU Intramural NIH HHS; NHLBI NIH HHS [Z01 HL004601-18]; NIDDK NIH HHS
   [DK47844, R01 DK047844]
NR 52
TC 168
Z9 168
U1 2
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD FEB 28
PY 2006
VL 45
IS 8
BP 2524
EP 2536
DI 10.1021/bi052475e
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 018VG
UT WOS:000235792300008
PM 16489745
ER

PT J
AU Raval, AN
   Karmarkar, PV
   Guttman, MA
   Ozturk, C
   Sampath, S
   DeSilva, R
   Aviles, RJ
   Xu, MN
   Wright, VJ
   Schenke, WH
   Kocaturk, O
   Dick, AJ
   Raman, VK
   Atalar, E
   McVeigh, ER
   Lederman, RJ
AF Raval, AN
   Karmarkar, PV
   Guttman, MA
   Ozturk, C
   Sampath, S
   DeSilva, R
   Aviles, RJ
   Xu, MN
   Wright, VJ
   Schenke, WH
   Kocaturk, O
   Dick, AJ
   Raman, VK
   Atalar, E
   McVeigh, ER
   Lederman, RJ
TI Real-time magnetic resonance imaging-guided endovascular recanalization
   of chronic total arterial occlusion in a swine model
SO CIRCULATION
LA English
DT Article
DE angioplasty; catheterization; magnetic resonance imaging; occlusion;
   peripheral vascular disease
ID SUPERFICIAL FEMORAL-ARTERY; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY;
   PRIMARY STENT PLACEMENT; ATRIAL SEPTAL-DEFECTS; BALLOON ANGIOPLASTY;
   CARDIAC-CATHETERIZATION; TRANSCATHETER CLOSURE; INTERVENTIONAL MRI;
   ILIAC ARTERIES; ANIMAL-MODEL
AB Background - Endovascular recanalization (guidewire traversal) of peripheral artery chronic total occlusion (CTO) can be challenging. X-ray angiography resolves CTO poorly. Virtually "blind" device advancement during x-ray - guided interventions can lead to procedure failure, perforation, and hemorrhage. Alternatively, MRI may delineate the artery within the occluded segment to enhance procedural safety and success. We hypothesized that real-time MRI (rtMRI) - guided CTO recanalization can be accomplished in an animal model.
   Methods and Results - Carotid artery CTO was created by balloon injury in 19 lipid-overfed swine. After 6 to 8 weeks, 2 underwent direct necropsy analysis for histology, 3 underwent primary x-ray - guided CTO recanalization attempts, and the remaining 14 underwent rtMRI-guided recanalization attempts in a 1.5-T interventional MRI system. Real-time MRI intervention used custom CTO catheters and guidewires that incorporated MRI receiver antennae to enhance device visibility. The mean length of the occluded segments was 13.3 +/- 1.6 cm. The rtMRI- guided CTO recanalization was successful in 11 of 14 swine and in only 1 of 3 swine with the use of x-ray alone. After unsuccessful rtMRI (n = 3), x-ray - guided attempts were also unsuccessful.
   Conclusions - Recanalization of long CTO is entirely feasible with the use of rtMRI guidance. Low-profile clinical-grade devices will be required to translate this experience to humans.
C1 NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
   NHLBI, Lab Cardiac Energet, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
   Univ Wisconsin, Dept Med, Cardiovasc Sect, Madison, WI USA.
   Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
RP Lederman, RJ (reprint author), NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bldg 10,Room 2c713,MSC 1538, Bethesda, MD 20892 USA.
EM lederman@nih.gov
RI Atalar, Ergin/D-3184-2012; Kocaturk, Ozgur/A-1419-2016; Ozturk,
   Cengizhan/A-6177-2016
OI Atalar, Ergin/0000-0002-6874-6103; Ozturk, Cengizhan/0000-0002-6966-0774
FU Intramural NIH HHS [Z01 HL004608-08]; NHLBI NIH HHS [Z01 HL005062,
   Z01-HL005062-03]
NR 45
TC 36
Z9 36
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
BP 1101
EP 1107
DI 10.1161/CIRCULATIONAHA.105.586727
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100011
PM 16490819
ER

PT J
AU Avery, CL
   Mohlke, KL
   Freedman, BI
   Kraja, AT
   Arnett, D
   Miller, MB
   Pankow, JS
   Lewis, CE
   Myers, RH
   Baird, L
   Leppert, M
   Hunt, SC
   Bergman, RN
   Tuomilehto, J
   Collins, FS
   Scott, LJ
   Boehnke, M
   North, KE
AF Avery, CL
   Mohlke, KL
   Freedman, BI
   Kraja, AT
   Arnett, D
   Miller, MB
   Pankow, JS
   Lewis, CE
   Myers, RH
   Baird, L
   Leppert, M
   Hunt, SC
   Bergman, RN
   Tuomilehto, J
   Collins, FS
   Scott, LJ
   Boehnke, M
   North, KE
TI Evidence for association between TNRC6B and type 2 diabetes under a
   chromosome 22 linkage peak: The HyperGEN study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Univ N Carolina, Chapel Hill, NC USA.
   Wake Forest Univ, Winston Salem, NC 27109 USA.
   Washington Univ, Sch Med, St Louis, MO USA.
   Univ Alabama, Sch Med, Birmingham, AL USA.
   Univ Minnesota, Minneapolis, MN USA.
   Boston Univ, Boston, MA 02215 USA.
   Univ Utah, Salt Lake City, UT USA.
   Univ So Calif, Los Angeles, CA USA.
   Univ Helsinki, Helsinki, Finland.
   Natl Publ Hlth Inst, Helsinki, Finland.
   NHGRI, Bethesda, MD 20892 USA.
   Univ Michigan, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA 30
BP E308
EP E308
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100055
ER

PT J
AU Bahrami, H
   Sadatsafavi, M
   Pourshams, A
   Kamangar, F
   Malekzadeh, R
AF Bahrami, H
   Sadatsafavi, M
   Pourshams, A
   Kamangar, F
   Malekzadeh, R
TI Iranian women experience higher rates of obesity and hypertension than
   American women
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Johns Hopkins Univ, Baltimore, MD USA.
   Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
   Univ Tehran Med Sci, Tehran, Iran.
   NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P195
BP E350
EP E350
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100251
ER

PT J
AU Becker, DM
   Yanek, LR
   Yoho, AC
   White, LW
   Moy, TF
   Hasan, AA
   Becker, LC
   Faraday, N
AF Becker, DM
   Yanek, LR
   Yoho, AC
   White, LW
   Moy, TF
   Hasan, AA
   Becker, LC
   Faraday, N
TI Patient adherence influences platelet reactivity in response to low-dose
   daily aspirin
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
   NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P80
BP E327
EP E327
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100142
ER

PT J
AU Bleys, J
   Miller, ER
   Ange, BA
   Appel, LJ
AF Bleys, J
   Miller, ER
   Ange, BA
   Appel, LJ
TI Effects of dietary sodium intake and the dietary approaches to stop
   hypertension diet on renal excretion of water: Results from the
   DASH-sodium trial
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Johns Hopkins Univ, Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
   NIA, NIH, Baltimore, MD 21224 USA.
   Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P34
BP E317
EP E317
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100096
ER

PT J
AU Carty, CL
   Carlson, CS
   Rice, K
   Fornage, M
   Boerwinkle, E
   Jacquish, C
   Lewis, CE
   Williams, OD
   Nickerson, DA
   Siscovick, DS
   Reiner, AP
AF Carty, CL
   Carlson, CS
   Rice, K
   Fornage, M
   Boerwinkle, E
   Jacquish, C
   Lewis, CE
   Williams, OD
   Nickerson, DA
   Siscovick, DS
   Reiner, AP
TI Association between plasma fibrinogen and polymorphisms in the alpha,
   beta, and gamma-fibrinogen genes
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Univ Washington, Seattle, WA 98195 USA.
   Univ Texas, Houston, TX USA.
   NIH, Bethesda, MD 20892 USA.
   Univ Alabama, Birmingham, AL USA.
RI Rice, Kenneth/A-4150-2013; Carty, Cara/B-8683-2013
OI Rice, Kenneth/0000-0001-5779-4495; 
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P43
BP E319
EP E319
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100105
ER

PT J
AU Durda, JP
   Carlson, C
   Psaty, BM
   Reiner, A
   Olson, JL
   Taylor, C
   Tracy, RP
AF Durda, JP
   Carlson, C
   Psaty, BM
   Reiner, A
   Olson, JL
   Taylor, C
   Tracy, RP
TI Evaluating whole genome amplification as a means of replenishing a DNA
   repository: Results for the cardiovascular health study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   Univ Vermont, Colchester, VT USA.
   Univ Washington, Seattle, WA 98195 USA.
   NHLBI, Bethesda, MD 20892 USA.
   Illumina, San Diego, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P61
BP E323
EP E323
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100123
ER

PT J
AU Espeland, MA
   Regensteiner, JG
   Hiatt, WR
   Wagenknecht, LE
   Bahnson, J
   Chiu, KC
   Gregg, E
   Haffner, S
   Hill, J
   Jaramillo, SA
   Knowler, W
AF Espeland, MA
   Regensteiner, JG
   Hiatt, WR
   Wagenknecht, LE
   Bahnson, J
   Chiu, KC
   Gregg, E
   Haffner, S
   Hill, J
   Jaramillo, SA
   Knowler, W
TI A model-based approach to analyzing ankle-brachial index: Results from
   the action for health in diabetes study group
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
   Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
   City Hope Natl Med Ctr, Duarte, CA 91010 USA.
   Ctr Dis Control & Prevent, Atlanta, GA USA.
   Univ Texas, Hlth Sci Ctr, San Antonio, TX USA.
   NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P229
BP E357
EP E357
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100283
ER

PT J
AU Fox, CS
   Massaro, JM
   Hoffmann, U
   Maurovich-Horvat, P
   Vasan, RS
   Meigs, JB
   O'Donnell, CJ
AF Fox, CS
   Massaro, JM
   Hoffmann, U
   Maurovich-Horvat, P
   Vasan, RS
   Meigs, JB
   O'Donnell, CJ
TI Subcutaneous and visceral adipose tissue compartments and association
   with metabolic risk factors: The Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 NHLBI Framingham Heart Study, Framingham, MA USA.
   Boston Univ, Sch Med, Boston, MA 02118 USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 4
Z9 4
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA 21
BP E306
EP E306
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100046
ER

PT J
AU Franceschini, N
   MacCluer, JW
   Goring, HH
   Cole, S
   Rose, KM
   Almasy, L
   Diego, VP
   Laston, S
   Howard, BV
   Kaufman, DJ
   Lee, ET
   Best, LG
   Fabsitz, RR
   North, KE
AF Franceschini, N
   MacCluer, JW
   Goring, HH
   Cole, S
   Rose, KM
   Almasy, L
   Diego, VP
   Laston, S
   Howard, BV
   Kaufman, DJ
   Lee, ET
   Best, LG
   Fabsitz, RR
   North, KE
TI QTL-specific genotype-by-sex interaction on systolic blood pressure
   variation in American Indians: The Strong Heart family Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Univ N Carolina, Chapel Hill, NC USA.
   SW Fdn Biomed Res, San Antonio, TX 78284 USA.
   NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA.
   Univ Oklahoma, Hlth Sci Ctr, Sch Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA.
   Missouri Breaks Ind Res Inc, Timber Lake, SD USA.
   NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P53
BP E321
EP E321
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100115
ER

PT J
AU Fyr, CLW
   Kanaya, AM
   Cummings, SR
   Harris, TB
   Hsueh, WC
   Reich, D
   Moffett, S
   Ding, JZ
   Li, RL
   Miljkovic-Gacic, I
   Ziv, E
AF Fyr, CLW
   Kanaya, AM
   Cummings, SR
   Harris, TB
   Hsueh, WC
   Reich, D
   Moffett, S
   Ding, JZ
   Li, RL
   Miljkovic-Gacic, I
   Ziv, E
TI The association of genetic ancestry, C-reactive protein levels, and
   cardiovascular disease in black Americans
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Univ Calif San Francisco, San Francisco, CA 94143 USA.
   Calif Pacific Med Ctr, San Francisco, CA USA.
   NIH, Bethesda, MD 20892 USA.
   Harvard Univ, Boston, MA 02115 USA.
   Univ Pittsburgh, Pittsburgh, PA USA.
   Wake Forest Univ, Winston Salem, NC 27109 USA.
   Univ Tennessee, Memphis, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P49
BP E320
EP E320
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100111
ER

PT J
AU Goring, HH
   Cole, SA
   Laston, S
   Dyer, TD
   Diego, VP
   Almasy, L
   Fabsitz, RR
   Howard, BV
   Ebbesson, SO
   Comuzzie, AG
   MacCluer, JW
AF Goring, HH
   Cole, SA
   Laston, S
   Dyer, TD
   Diego, VP
   Almasy, L
   Fabsitz, RR
   Howard, BV
   Ebbesson, SO
   Comuzzie, AG
   MacCluer, JW
TI Linkage analysis of glycosylated hemoglobin in the GOCADAN study:
   Evidence for a major locus on chromosome 19q
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 SW Fdn Biomed Res, San Antonio, TX 78284 USA.
   NHLBI, Bethesda, MD 20892 USA.
   MedStar Res Inst, Hyattsville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
BP E320
EP E320
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100109
ER

PT J
AU He, K
   Liu, K
   Daviglus, ML
   Mayer-Davis, E
   Jenny, N
   Jiang, R
   Ouyang, P
   Steffen, L
   Siscovick, D
   Wu, C
   Burke, G
AF He, K
   Liu, K
   Daviglus, ML
   Mayer-Davis, E
   Jenny, N
   Jiang, R
   Ouyang, P
   Steffen, L
   Siscovick, D
   Wu, C
   Burke, G
TI Intakes of long-chain N-3 polyunsaturated fatty acids and fish in
   relation to biomarkers of subclinical atherosclerosis: The Multi-Ethnic
   Study of Atherosclerosis (MESA)
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Northwestern Univ, Chicago, IL 60611 USA.
   Univ S Carolina, Columbia, SC 29208 USA.
   Univ Vermont, Colchester, VT USA.
   Columbia Univ, New York, NY USA.
   Johns Hopkins Univ, Baltimore, MD USA.
   Univ Minnesota, St Paul, MN 55108 USA.
   Cardiovasc Hlth Res Unit, Seattle, WA USA.
   NHLBI, EBP, DECA, NIH, Bethesda, MD 20892 USA.
   Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P238
BP E359
EP E359
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100292
ER

PT J
AU Howard, G
   Cushman, M
   Prineas, RJ
   Howard, VJ
   Moy, CS
   McVlure, LA
   Pulley, L
   Cantrell, RA
   Tabereaux, P
   Safford, MM
AF Howard, G
   Cushman, M
   Prineas, RJ
   Howard, VJ
   Moy, CS
   McVlure, LA
   Pulley, L
   Cantrell, RA
   Tabereaux, P
   Safford, MM
TI Relationship for stroke and heart disease between the average Framingham
   Risk Scores with cause-specific mortality at the state level
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Univ Alabama, Birmingham, AL USA.
   Univ Vermont, Burlington, VT USA.
   Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
   NINDS, Bethesda, MD 20892 USA.
   Univ Arkansas, Little Rock, AR 72204 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P7
BP E312
EP E312
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100071
ER

PT J
AU Jerome, GJ
   Young, DR
   Brantley, PJ
   Coughlin, JW
   Erlinger, TP
   Cooper, LS
   Appel, LJ
AF Jerome, GJ
   Young, DR
   Brantley, PJ
   Coughlin, JW
   Erlinger, TP
   Cooper, LS
   Appel, LJ
TI Effects of lifestyle modification interventions on social support:
   Results from the PREMIER trial
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
   Univ Maryland, College Pk, MD 20742 USA.
   Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
   Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
   Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA.
   NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P292
BP E370
EP E370
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100345
ER

PT J
AU Kanaya, AM
   Fyr, CW
   Cummings, SR
   Harris, TB
   Hsueh, WC
   Reich, D
   Li, RL
   Miljkovic-Gacic, I
   Ziv, E
AF Kanaya, AM
   Fyr, CW
   Cummings, SR
   Harris, TB
   Hsueh, WC
   Reich, D
   Li, RL
   Miljkovic-Gacic, I
   Ziv, E
TI The effect of genetic ancestry on the association between adiponectin
   and coronary heart disease in black Americans
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Univ Calif San Francisco, San Francisco, CA 94143 USA.
   Univ Minnesota, Minneapolis, MN USA.
   Calif Pacific Med Ctr, San Francisco, CA USA.
   NIA, Bethesda, MD 20892 USA.
   Harvard Univ, Cambridge, MA 02138 USA.
   Univ Tennessee, Memphis, TN USA.
   Univ Pittsburgh, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P116
BP E334
EP E334
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100177
ER

PT J
AU Kaplan, RC
   Tirschwell, DL
   Longstreth, WT
   Manolio, TA
   Heckbert, SR
   LeValley, AJ
   Lefkowitz, D
   El-Saed, A
   Psaty, BM
AF Kaplan, RC
   Tirschwell, DL
   Longstreth, WT
   Manolio, TA
   Heckbert, SR
   LeValley, AJ
   Lefkowitz, D
   El-Saed, A
   Psaty, BM
TI Blood pressure level and outcomes among older adults with prior ischemic
   stroke
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Albert Einstein Coll Med, Bronx, NY 10467 USA.
   Univ Washington, Seattle, WA 98195 USA.
   NHLBI, NIH, Bethesda, MD 20892 USA.
   Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
   Univ Pittsburgh, Pittsburgh, PA USA.
RI Kaplan, Robert/A-2526-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA 2
BP E302
EP E302
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100027
ER

PT J
AU Kuller, LH
   Arnold, AM
   Longstreth, WL
   Manolio, TA
   O'Leary, DH
   Burke, GL
   Fried, LP
   Newman, AB
AF Kuller, LH
   Arnold, AM
   Longstreth, WL
   Manolio, TA
   O'Leary, DH
   Burke, GL
   Fried, LP
   Newman, AB
TI Longevity and probable vascular disease in the brain: The Cardiovascular
   Health Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Univ Pittsburgh, Pittsburgh, PA USA.
   Univ Washington, Seattle, WA 98195 USA.
   NHLBI, Bethesda, MD 20892 USA.
   Tufts New England Med Ctr, Boston, MA USA.
   Wake Forest Univ, Winston Salem, NC 27109 USA.
   Johns Hopkins Univ, Baltimore, MD USA.
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA 1
BP E302
EP E302
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100026
ER

PT J
AU Levitzky, YS
   Cupples, LA
   Murabito, JM
   Wilson, PW
   Kiel, DP
   Kannel, W
   O'Donnell, CJ
AF Levitzky, YS
   Cupples, LA
   Murabito, JM
   Wilson, PW
   Kiel, DP
   Kannel, W
   O'Donnell, CJ
TI Abdominal aortic calcium as a risk factor for development of
   intermittent claudication: The Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 NHLBI Framingham Heart Study, Framingham, MA USA.
   Boston Univ, Sch Publ Hlth, Boston, MA USA.
   Boston Med Ctr, Boston, MA USA.
   Med Univ S Carolina, Charleston, SC 29425 USA.
   Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
NR 0
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P237
BP E359
EP E359
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100291
ER

PT J
AU Lin, JP
   O'Donnell, CJ
   Schwaiger, JP
   Cupples, A
   Lingenhel, A
   Hunt, SC
   Yang, S
   Kronenberg, F
AF Lin, JP
   O'Donnell, CJ
   Schwaiger, JP
   Cupples, A
   Lingenhel, A
   Hunt, SC
   Yang, S
   Kronenberg, F
TI Association between the UGT1A1*28 allele, bilirubin levels and coronary
   heart disease
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 NHLBI, Framingham, MA USA.
   NHLBI, Bethesda, MD 20892 USA.
   Innsbruck Med Univ, Schoepfstr, Austria.
   Boston Univ, Sch Publ Hlth, Boston, MA USA.
   Univ Utah, Salt Lake City, UT USA.
NR 0
TC 0
Z9 0
U1 6
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P51
BP E321
EP E321
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100113
ER

PT J
AU Loehr, LR
   Rosamond, W
   Chang, PP
   Sorlie, PD
   Folsom, AR
   Chambless, L
AF Loehr, LR
   Rosamond, W
   Chang, PP
   Sorlie, PD
   Folsom, AR
   Chambless, L
TI Hospitalized heart failure incidence and survival: 13-year follow-up of
   the ARIC cohort
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Univ N Carolina, Chapel Hill, NC USA.
   NHLBI, Bethesda, MD 20892 USA.
   Univ Minnesota, Minneapolis, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P205
BP E352
EP E352
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100261
ER

PT J
AU Lynch, EB
   Liu, K
   Spring, B
   Wei, GS
   Greenland, P
AF Lynch, EB
   Liu, K
   Spring, B
   Wei, GS
   Greenland, P
TI The influence of body-size discrepancy on weight change: The CARDIA
   study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Northwestern Univ, Chicago, IL 60611 USA.
   NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P284
BP E368
EP E368
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100337
ER

PT J
AU Murabito, JM
   Guo, CY
   Fox, CS
   D'Agostino, RB
AF Murabito, JM
   Guo, CY
   Fox, CS
   D'Agostino, RB
TI Borderline low ankle-brachial index level predicts incident
   cardiovascular disease events: The Framingham Offspring Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Boston Univ, Sch Med, Framingham, MA USA.
   Boston Univ, Boston, MA 02215 USA.
   NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P242
BP E360
EP E360
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100296
ER

PT J
AU Murabito, JM
   Guo, CY
   Fox, CS
   Polak, JF
   D'Agostino, RB
AF Murabito, JM
   Guo, CY
   Fox, CS
   Polak, JF
   D'Agostino, RB
TI Predictive value of noninvasive measures of peripheral atherosclerosis
   for incident cardiovascular disease events: The Framingham Offspring
   Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Boston Univ, Sch Med, Framingham, MA USA.
   Boston Univ, Boston, MA 02215 USA.
   NHLBI, Bethesda, MD 20892 USA.
   Tufts Univ, Sch Med, Boston, MA 02111 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P241
BP E359
EP E360
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100295
ER

PT J
AU Murabito, JM
   Guo, CY
   Fox, CS
   D'Agostino, RB
AF Murabito, JM
   Guo, CY
   Fox, CS
   D'Agostino, RB
TI Genetic contributions to peripheral arterial disease: Heritability of
   the ankle-brachial blood pressure index in the Framingham Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Boston Univ, Sch Med, Framingham, MA USA.
   Boston Univ, Boston, MA 02215 USA.
   NHLBI, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P68
BP E325
EP E325
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100130
ER

PT J
AU Parikh, NI
   Hwang, SJ
   Larson, MG
   Meigs, JB
   Levy, D
   Fox, CS
AF Parikh, NI
   Hwang, SJ
   Larson, MG
   Meigs, JB
   Levy, D
   Fox, CS
TI Cardiovascular disease risk factors in chronic kidney disease: Overall
   burden and rates of treatment and control
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Boston Univ, Sch Med, Boston, MA 02118 USA.
   NHLBI Framingham Heart Study, Framingham, MA USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P83
BP E328
EP E328
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100145
ER

PT J
AU Rodeheffer, RJ
   Jacobsen, SJ
   Best, LG
   Lee, E
   Fabsitz, RR
   Welty, TK
   Howard, BV
   Devereux, RB
AF Rodeheffer, RJ
   Jacobsen, SJ
   Best, LG
   Lee, E
   Fabsitz, RR
   Welty, TK
   Howard, BV
   Devereux, RB
TI Cardiovascular disease prevalence in American Indian and white community
   populations
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Mayo Clin, Rochester, MN USA.
   Missouri Breaks Ind, Timber Falls, SD USA.
   Univ Oklahoma, Oklahoma City, OK USA.
   Natl Inst Hlth, Bethesda, MD USA.
   MedStar Res Inst, Washington, DC USA.
   New York Presbyterian Hosp, Weill Cornell Med Ctr, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P336
BP E379
EP E379
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100387
ER

PT J
AU Rosamond, WD
   Folsom, A
   Sorlie, P
   Wang, CH
AF Rosamond, WD
   Folsom, A
   Sorlie, P
   Wang, CH
TI Trends in the incidence of myocardial infarction: Separating natural
   history from improved biomarker sensitivity
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Univ N Carolina, Chapel Hill, NC USA.
   Univ Minnesota, Minneapolis, MN USA.
   NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P204
BP E352
EP E352
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100260
ER

PT J
AU Ruttmann, E
   Ulmer, H
   Brant, LJ
   Concin, H
   Diem, G
   Rapp, K
AF Ruttmann, E
   Ulmer, H
   Brant, LJ
   Concin, H
   Diem, G
   Rapp, K
TI Letter regarding article by Ruttmann et al, "gamma-glutamyltransferase
   as a risk factor for cardiovascular disease mortality: An
   epidemiological investigation in a cohort of 163 944 Austrian adults" -
   Response
SO CIRCULATION
LA English
DT Letter
C1 Innsbruck Med Univ, Dept Med Stat Informat & Hlth, Innsbruck, Austria.
   NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA.
   Agcy Prevent & Social Med, Bregenz, Austria.
   Univ Ulm, Dept Epidemiol, Ulm, Germany.
RP Ruttmann, E (reprint author), Innsbruck Med Univ, Dept Med Stat Informat & Hlth, Innsbruck, Austria.
EM hanno.ulmer@i-med.ac.at
RI Ruttmann, Elfriede/D-6501-2011; vhmpp, aks/F-9756-2012; Ulmer,
   Hanno/C-3488-2011
OI Ulmer, Hanno/0000-0001-5911-1002
NR 4
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
BP E299
EP E300
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100024
ER

PT J
AU Sarpong, DF
   Steffes, M
   Akylbekova, E
   Walker, E
   Taylor, H
AF Sarpong, DF
   Steffes, M
   Akylbekova, E
   Walker, E
   Taylor, H
TI Diabetes prevalence, awareness, and control at baseline in African
   Americans in the Jackson Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Jackson State Univ, Jackson, MS USA.
   Univ Minnesota, Minneapolis, MN USA.
   NHLBI, Bethesda, MD 20892 USA.
   Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P166
BP E344
EP E344
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100223
ER

PT J
AU Schreiner, PJ
   Fornage, M
   Boerwinkle, E
   Daviglus, M
   Siscovick, D
   Loria, C
AF Schreiner, PJ
   Fornage, M
   Boerwinkle, E
   Daviglus, M
   Siscovick, D
   Loria, C
TI Fatty acid binding protein 2 polymorphism and dietary fat intake affect
   lipid levels: The CARDIA study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Univ Minnesota, Minneapolis, MN USA.
   Univ Texas, Houston, TX USA.
   Northwestern Univ, Chicago, IL 60611 USA.
   Univ Washington, Seattle, WA 98195 USA.
   NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P41
BP E319
EP E319
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100103
ER

PT J
AU Vaidya, D
   Yanek, LR
   Moy, TF
   Faraday, N
   Hasan, AA
   Becker, LC
   Becker, DM
AF Vaidya, D
   Yanek, LR
   Moy, TF
   Faraday, N
   Hasan, AA
   Becker, LC
   Becker, DM
TI Common subclinical symptoms in apparently healthy people without active
   infections are associated with high-sensitivity C-reactive protein
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Johns Hopkins Univ, Baltimore, MD USA.
   NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P125
BP E336
EP E336
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100186
ER

PT J
AU Vaidya, D
   Yanek, LR
   Moy, TF
   Hasan, AA
   Becker, DM
   Becker, LC
AF Vaidya, D
   Yanek, LR
   Moy, TF
   Hasan, AA
   Becker, DM
   Becker, LC
TI Statin use prevents increases in serum CRP levels related to aging
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Johns Hopkins Univ, Baltimore, MD USA.
   NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P124
BP E336
EP E336
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100185
ER

PT J
AU Wyatt, SB
   Wofford, MR
   Akylbekova, M
   Keahy, W
   Walker, ER
   Andrew, ME
   Taylor, HA
   Jones, DW
AF Wyatt, SB
   Wofford, MR
   Akylbekova, M
   Keahy, W
   Walker, ER
   Andrew, ME
   Taylor, HA
   Jones, DW
TI Prevalence, awareness, and control of hypertension at baseline in the
   Jackson Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
   Jackson State Univ, Jackson, MS USA.
   NHLBI, Jackson, MS USA.
   Ctr Dis Control & Prevent, NIOSH, Morgantown, WV USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA 34
BP E309
EP E309
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100059
ER

PT J
AU Xu, JQ
   Yeh, JL
   Devereux, R
   Knowler, WC
   Umans, JG
   Begum, M
   Fabsitz, RR
   Lee, ET
AF Xu, JQ
   Yeh, JL
   Devereux, R
   Knowler, WC
   Umans, JG
   Begum, M
   Fabsitz, RR
   Lee, ET
TI Low-grade albuminuria and risk of cardiovascular disease and death in
   American Indians: The Strong Heart Study
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA.
   Cornell Univ, Med Ctr, New York, NY 10021 USA.
   NIDDKD, NIH, Phoenix, AZ USA.
   MedStar Res Inst, Penn Med Lab, Washington, DC USA.
   NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P1
BP E311
EP E311
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100065
ER

PT J
AU Yanek, LR
   Vaidya, D
   Moy, TF
   Hasan, AA
   Becker, DM
   Becker, LC
AF Yanek, LR
   Vaidya, D
   Moy, TF
   Hasan, AA
   Becker, DM
   Becker, LC
TI Heritability of pulse pressure in white and black American families with
   a history of premature coronary artery disease
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
   NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P67
BP E324
EP E324
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100129
ER

PT J
AU Zhang, L
   Kao, L
   Berthier-Schaad, Y
   Plantinga, L
   Fink, N
   Smith, MW
   Coresh, J
AF Zhang, L
   Kao, L
   Berthier-Schaad, Y
   Plantinga, L
   Fink, N
   Smith, MW
   Coresh, J
TI C-reactive protein (CRP) haplotype found in African Americans is
   associated with lower serum CRP in a dialysis cohort
SO CIRCULATION
LA English
DT Meeting Abstract
CT 46th Annual Conference on Cardiovascular Disease Epidemiology and
   Prevention
CY MAR 02-05, 2006
CL Phoenix, AZ
SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst
C1 Johns Hopkins Univ, Baltimore, MD USA.
   NCI, Frederick, MD 21701 USA.
RI Smith, Michael/B-5341-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 28
PY 2006
VL 113
IS 8
MA P48
BP E320
EP E320
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 016KW
UT WOS:000235620100110
ER

PT J
AU Ahn, BH
   Min, G
   Bae, YS
   Bae, YS
   Min, DS
AF Ahn, BH
   Min, G
   Bae, YS
   Bae, YS
   Min, DS
TI Phospholipase D is activated and phosphorylated by casein kinase-II in
   human U87 astroglioma cells
SO EXPERIMENTAL AND MOLECULAR MEDICINE
LA English
DT Article
DE casin kinase II; cell proliferation; phospholipase D; phosphorylation
ID TYROSINE PHOSPHORYLATION; PROTEIN; PROLIFERATION; CK2; ALPHA; SUBUNIT;
   SYSTEM; ENZYME; MICE
AB Elevated expression of protein casein kinase II (CKII) stimulated basal phospholipase D (PLD) activity as well as PMA-induced PLD activation in human U87 astroglioma cells. Moreover, CKIII-selective inhibitor, emodin and apigenin suppressed PMA-induced PLD activation in a dose-dependent manner as well as basal PLD activity, suggesting the involvement of CKII in the activation of both PLD1 and PLD2. CKII was associated with PLD1 and PLD2 in co-transfection experiments. Furthermore, CKII induced serine/threonine phosphorylation of PLD2 in vivo, and the multiple regions of PLD2 were phosphorylated by CKII in vitro kinase assay using glutathione S-transferase-PILD2 fusion protein fragments. Elevated expression of CKII or PLD increased cell proliferation but pretreatment of cells with 1-butanol suppressed CKII-induced cell proliferation. These results suggest that CKII is involved in proliferation of U87 cells at least in part, through stimulation of PLD activity.
C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA.
   Jinju Natl Univ, Dept Microbiol Engn, Jinju 660758, South Korea.
   Dong A Univ, Coll Med, Med Res Ctr Canc Mol Therapy, Pusan 602714, South Korea.
   Dong A Univ, Coll Med, Dept Biochem, Pusan 602714, South Korea.
   Kyungpook Natl Univ, Coll Nat Sci, Dept Biochem, Taegu 702701, South Korea.
   Pusan Natl Univ, Coll Nat Sci, Dept Mol Biol, Pusan 609735, South Korea.
RP Min, DS (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10-CRC 5-3288,10 Ctr Dr, Bethesda, MD 20892 USA.
EM minds@pusan.ac.kr; minds@pusan.ac.kr
NR 32
TC 13
Z9 13
U1 0
U2 1
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 FEB 28
PY 2006
VL 38
IS 1
BP 55
EP 62
PG 8
WC Biochemistry & Molecular Biology; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Research & Experimental Medicine
GA 019ZI
UT WOS:000235877100007
PM 16520553
ER

PT J
AU Ponomarenko, NA
   Durova, OM
   Vorobiev, II
   Belogurov, AA
   Telegin, GB
   Suchkov, SV
   Misikov, VK
   Morse, HC
   Gabibov, AG
AF Ponomarenko, NA
   Durova, OM
   Vorobiev, II
   Belogurov, AA
   Telegin, GB
   Suchkov, SV
   Misikov, VK
   Morse, HC
   Gabibov, AG
TI Catalytic activity of autoantibodies toward myelin basic protein
   correlates with the scores on the multiple sclerosis expanded disability
   status scale
SO IMMUNOLOGY LETTERS
LA English
DT Article
DE autoantibody to myclin basic protein; multiple sclerosis; catalytic
   antibodies; EDSS
ID OLIGODENDROCYTE GLYCOPROTEIN; HEMOPHILIA-A; FACTOR-VIII; ANTIBODIES;
   PREVALENCE; PEPTIDE; EPITOPE; ELISA; MICE
AB Autoantibodies toward myelin basic protein (MBP) evidently emerge in sera and cerebrospinal fluid of the patients with multiple sclerosis (MS), as well as in a MS rodent model, i.e., experimental autoimmune encephalomyelitis (EAE). The studies of the last two decades have unveiled somewhat controversial data on the diagnostic applicability of anti-MBP autoantibodies as a disease' marker. Here, we present the results of new functional analysis of the anti-MBP autoantibodies isolated from MS (in patients) and EAE (in mice) sera, based on their proteolytic activity against the targeted autoantigen. The activity was shown to be the intrinsic property of the IgG molecule. No activity was found in the sera-derived antibody fraction of healthy donors and control mice. Sera of 24 patients with clinically proven MS at different stages of the disease, and 20 healthy controls were screened for the anti-MBP antibody-mediated proteolytic activity. The activity correlated with the scores on the MS expanded disability status scale (EDSS) (r(2) =0.85, P < 0.001). Thus, the anti-MBP autoantibody-mediated proteolysis may be regarded as an additional marker of the disease progression. (c) 2005 Elsevier B.V. All rights reserved.
C1 RAS, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia.
   Vladimirsky Moscow Reg Clin Inst, Moscow, Russia.
   Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119899, Russia.
   RAS, Pushchino Branch Shemyakin, Pushchino 142290, Russia.
   RAS, Ovchinnikov Inst Bioorgan Chem, Pushchino 142290, Russia.
   Natl Inst Allergy & Infect Dis, Lab Immunopathol, NIH, Rockville, MD 20852 USA.
RP Gabibov, AG (reprint author), Russian Federat, Miklukho Maklaya 16-10, Moscow 117971, Russia.
EM gabibov@ibch.ru
OI Morse, Herbert/0000-0002-9331-3705; Ponomarenko,
   Natalia/0000-0003-3129-3515
NR 22
TC 24
Z9 27
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2478
J9 IMMUNOL LETT
JI Immunol. Lett.
PD FEB 28
PY 2006
VL 103
IS 1
BP 45
EP 50
DI 10.1016/j.imlet.2005.10.006
PG 6
WC Immunology
SC Immunology
GA 015MF
UT WOS:000235554800008
PM 16297986
ER

PT J
AU Hagiwara, M
   Watanabe, E
   Barrett, JC
   Tsutsui, T
AF Hagiwara, M
   Watanabe, E
   Barrett, JC
   Tsutsui, T
TI Assessment of genotoxicity of 14 chemical agents used in dental
   practice: Ability to induce chromosome aberrations in Syrian hamster
   embryo cells
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article
DE chromosome aberrations; chemical agents used in dentistry; Syrian
   hamster embryo cells
ID UNSCHEDULED DNA-SYNTHESIS; ASSAY; TRANSFORMATION; MUTAGENICITY;
   DIETHYLSTILBESTROL; SALMONELLA; TOXICITY; CULTURES; PHENOL; ACID
AB To assess the genotoxicity of 14 chemical agents used as locally applied agents in dental practice, the ability of these agents to elicit chromosome aberrations was examined using Syrian hamster embryo (SHE) cells. Chromosome aberrations in SHE cells were induced by treatment with three of eight chemical agents used as endodontic medicaments, i.e. ethylenediaminetetraacetic acid (EDTA), formocresol (a mixture of formalin and tricresol), and sodium arsenite. The other five chemical agents, i.e. chloramphenicol, p-chlorophenol, p-phenolsulfonic acid, sodium hypochlorite, and tetracycline hydrochloride exhibited a negative response for chromosome aberrations. Assessment of three dyes used for disclosing dental plaque showed chromosome aberrations induced by basic fuchsin but not by acid fuchsin and erythrosine B. Three local anesthetics, lidocaine hydrochloride, prilocaine hydrochloride, and procaine hydrochloride, were negative for chromosome aberrations. Among the ten chemical agents that exhibited a negative response in the assay, p-chlorophenol, sodium hypochlorite, and erythrosine B induced chromosome aberrations in SHE cells when treated in the presence of exogenous metabolic activation. The percentages of cells with polyploidy or endoreduplication were enhanced by formocresol, sodium arsenite, p-chlorophenol, p-phenolsulfonic acid, sodium hypochlorite, erythrosine B, prilocaine hydrochloride, and procaine hydrochloride in the absence or presence of exogenous metabolic activation. Our results indicate that the chemical agents that had a positive response in the present study are potentially genotoxic to mammalian cells. (C) 2005 Elsevier B.V. All rights reserved.
C1 Nippon Dent Univ Tokyo, Dept Pharmacol, Sch Dent, Chiyoda Ku, Tokyo 1028159, Japan.
   NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA.
RP Tsutsui, T (reprint author), Nippon Dent Univ Tokyo, Dept Pharmacol, Sch Dent, Chiyoda Ku, 1-9-20 Fujimi, Tokyo 1028159, Japan.
EM takeki@tokyo.ndu.ac.jp
NR 35
TC 39
Z9 44
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5718
J9 MUTAT RES-GEN TOX EN
JI Mutat. Res. Genet. Toxicol. Environ. Mutagen.
PD FEB 28
PY 2006
VL 603
IS 2
BP 111
EP 120
DI 10.1016/j.mrgentox.2005.08.011
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 018CQ
UT WOS:000235741700001
PM 16406784
ER

PT J
AU van der Knaap, MS
   Ramesh, V
   Schiffmann, R
   Blaser, S
   Kyllerman, M
   Gholkar, A
   Ellison, DW
   van der Voorn, JP
   van Dooren, SJM
   Jakobs, C
   Barkhof, F
   Salomons, GS
AF van der Knaap, MS
   Ramesh, V
   Schiffmann, R
   Blaser, S
   Kyllerman, M
   Gholkar, A
   Ellison, DW
   van der Voorn, JP
   van Dooren, SJM
   Jakobs, C
   Barkhof, F
   Salomons, GS
TI Alexander disease - Ventricular garlands and abnormalities of the
   medulla and spinal cord
SO NEUROLOGY
LA English
DT Article
ID FIBRILLARY ACIDIC PROTEIN; MUTATION; GFAP; GENE; JUVENILE
AB Background: Alexander disease is most commonly associated with macrocephaly and, on MRI, a leukoencephalopathy with frontal preponderance. The disease is caused by mutation of the GFAP gene. Clinical and MRI phenotypic variation have been increasingly recognized. Methods: The authors studied seven patients with Alexander disease, diagnosed based on mutations in the GFAP gene, who presented unusual MRI findings. The authors reviewed clinical history, MRI abnormalities, and GFAP mutations. Results: All patients had juvenile disease onset with signs of brainstem or spinal cord dysfunction. None of the patients had a macrocephaly. The MRI abnormalities were dominated by medulla and spinal cord abnormalities, either signal abnormalities or atrophy. One patient had only minor cerebral white matter abnormalities. A peculiar finding was the presence of a kind of garland along the ventricular wall in four patients. Three patients had an unusual GFAP mutation, one of which was a duplication mutation of two amino acids, and one an insertion deletion. Conclusion: Signal abnormalities or atrophy of the medulla or spinal cord on MRI are sufficient to warrant DNA analysis for Alexander disease. Ventricular garlands constitute a new sign of the disease. Unusual phenotypes of Alexander disease are found among patients with late onset and protracted disease course.
C1 VU Univ Med Ctr, Dept Child Neurol, NL-1081 HV Amsterdam, Netherlands.
   VU Univ Med Ctr, Dept Pathol, NL-1081 HV Amsterdam, Netherlands.
   VU Univ Med Ctr, Dept Radiol, NL-1081 HV Amsterdam, Netherlands.
   VU Univ Med Ctr, Dept Clin Chem, Metab Unit, NL-1081 HV Amsterdam, Netherlands.
   Newcastle Gen Hosp, Dept Pediat Neurol, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England.
   Newcastle Gen Hosp, Dept Neuroradiol, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England.
   Newcastle Gen Hosp, Dept Neuropathol, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England.
   NIH, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA.
   Hosp Sick Children, Dept Radiol, Toronto, ON M5G 1X8, Canada.
   Univ Gothenburg, Queen Silvia Childrens Hosp, Dept Pediat Neurol, Gothenburg, Sweden.
RP van der Knaap, MS (reprint author), VU Univ Med Ctr, Dept Child Neurol, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands.
EM ms.vanderknaap@vumc.nl
NR 14
TC 62
Z9 63
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD FEB 28
PY 2006
VL 66
IS 4
BP 494
EP 498
DI 10.1212/01.wnl.0000198770.80743.37
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 016UF
UT WOS:000235645200012
PM 16505300
ER

PT J
AU Richert, ND
   Howard, T
   Frank, JA
   Stone, R
   Ostuni, J
   Ohayon, J
   Bash, C
   McFarland, HF
AF Richert, ND
   Howard, T
   Frank, JA
   Stone, R
   Ostuni, J
   Ohayon, J
   Bash, C
   McFarland, HF
TI Relationship between inflammatory lesions and cerebral atrophy in
   multiple sclerosis
SO NEUROLOGY
LA English
DT Article
ID RELAPSING-REMITTING MS; BRAIN VOLUME CHANGES; FOLLOW-UP; INTERFERON
   BETA-1B; VENTRICULAR VOLUME; ENHANCING LESIONS; SERIAL MRI; DISABILITY;
   CONSEQUENCES; PROGRESSION
AB Objective: To investigate the temporal relationship between inflammation and cerebral atrophy in a longitudinal study of 19 patients with relapsing-remitting multiple sclerosis (RRMS) using serial monthly contrast enhanced MRI examinations and monthly measurements of brain fractional volume (BFV) for an average of 4 (range 2.4 to 10) years. Methods: In this retrospective study, all patients had an active MRI scan at entry with a minimum of two new contrast enhancing lesions (CEL) on baseline MRI examinations. Patients were followed for a minimum of 3 months during a baseline (pretreatment) phase and subsequently followed during treatment with recombinant interferon beta (IFN) and various other immunomodulatory agents. Pre- and post contrast axial images were obtained using 3-mm slice thickness and a gadolinium contrast dose of 0.1 mmol/kg. Monthly CEL were sequentially numbered on hardcopy films and monthly BFV was determined on precontrast T1W images using a semiautomated program. For BFV measurements, all T1W scans were registered to the entry examination, which served as a mask image. Cerebral atrophy was measured as percent brain fractional volume change (PBVC) compared to the entry baseline scan. Results: The results demonstrate that cerebral atrophy paralleled that of contrast enhancing lesion accumulation. The correlation between cumulative CEL and PBVC ranged from R-2 = 0.47 to 0.81. Immunomodulatory agents that effectively reduced CEL accumulation also slowed the rate of atrophy. Conclusions: The correlation between contrast enhancing lesions (CEL) and atrophy suggests that patients who are not responding to therapy with a decrease in CEL may also be at risk for developing increased atrophy.
C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
   NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA.
   Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA.
RP Richert, ND (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B16,10 Ctr Dr, Bethesda, MD 20892 USA.
EM richertn@helix.nih.gov
FU Intramural NIH HHS
NR 41
TC 22
Z9 22
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD FEB 28
PY 2006
VL 66
IS 4
BP 551
EP 556
DI 10.1212/01.wnl.0000197982.78063.06
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 016UF
UT WOS:000235645200023
PM 16505310
ER

PT J
AU Wildman, DE
   Chen, CY
   Erez, O
   Grossman, LI
   Goodman, M
   Romero, R
AF Wildman, DE
   Chen, CY
   Erez, O
   Grossman, LI
   Goodman, M
   Romero, R
TI Evolution of the mammalian placenta revealed by phylogenetic analysis
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE discoid shape; Eutheria; hemochorial; maternofetal interdigitation;
   villous type
ID GROWTH-HORMONE; 2 FORMS; LACTOGEN; PREGNANCY; METABOLISM; SECRETION;
   PROLACTIN; SEQUENCES; WOMEN
AB The placenta is essential for the success of therian mammalian reproduction. Intense selective pressure has shaped changes in placental anatomy and function during mammalian claclogenesis. Here we challenge the view that the hemochorial placenta is a derived feature in haplorhine primates. Using phylogenetic and statistical analyses of molecular and morphological data, we demonstrate that the ancestral eutherian mammalian placenta had the distinctive features of (i) hemochorial placental interface, ii a discoid shape, and (iii) a labyrinthine maternofetal interdigitation. These results reveal that the first eutherians had a deeply invasive placenta and imply that the major role of the placenta in sustaining pregnancy and promoting gestational development existed throughout the eutherian lineage that descended to humans from the last common ancestor of placental mammals. The ancestral state reconstructions demonstrate both clade-specific patterns of placentation and specific cases of convergent evolution within individual eutherian clades. Determining the mammalian pattern of change in placental morphology is important for understanding the evolutionary pressures faced by these lineages. The effects of selection pressures on the efficiency of placentation may stem from changes in nutritional demand, gestational length, number of embryos per pregnancy, uterine shape, and maternal body constitution. The influence of these factors on placental development needs further investigation.
C1 Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
   NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA.
   Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA.
   Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
   Hutzel Womens Hosp, Detroit, MI 48201 USA.
RP Goodman, M (reprint author), Wayne State Univ, Sch Med, Ctr Mol Med & Genet, 540 E Canfield Ave, Detroit, MI 48201 USA.
EM mgoodwayne@aol.com
FU Intramural NIH HHS
NR 48
TC 154
Z9 164
U1 4
U2 34
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 FEB 28
PY 2006
VL 103
IS 9
BP 3203
EP 3208
DI 10.1073/pnas.0511344103
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 018QU
UT WOS:000235780700038
PM 16492730
ER

PT J
AU Varga, R
   Eriksson, M
   Erdos, MR
   Olive, M
   Harten, I
   Koldgie, F
   Capell, BC
   Cheng, J
   Faddah, D
   Perkins, S
   Avallone, H
   San, H
   Qu, X
   Ganesh, S
   Gordon, LB
   Virmani, R
   Wight, TN
   Nabel, EG
   Collins, FS
AF Varga, R
   Eriksson, M
   Erdos, MR
   Olive, M
   Harten, I
   Koldgie, F
   Capell, BC
   Cheng, J
   Faddah, D
   Perkins, S
   Avallone, H
   San, H
   Qu, X
   Ganesh, S
   Gordon, LB
   Virmani, R
   Wight, TN
   Nabel, EG
   Collins, FS
TI Progressive vascular smooth muscle cell defects in a mouse model of
   Hutchinson-Gilford progeria syndrome
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE lamin A; atherosclerosis; laminopathy
ID LAMIN-A; MUTATIONS; ABNORMALITIES; FARNESYLATION; FIBROBLASTS; ZMPSTE24;
   HUMANS
AB Children with Hutchinson-Gilford progeria syndrome (HGPS) suffer from dramatic acceleration of some symptoms associated with normal aging, most notably cardiovascular disease that eventually leads to death from myocardial infarction and/or stroke usually in their second decade of life. For the vast majority of cases, a de novo point mutation in the lamin A (LMNA) gene is the cause of HGPS. This missense mutation creates a cryptic splice donor site that produces a mutant lamin A protein, termed "progerin," which carries a 50-aa deletion near its C terminus. We have created a mouse model for progeria by generating transgenics carrying a human bacterial artificial chromosome that harbors the common HGPS mutation. These mice develop progressive loss of vascular smooth muscle cells in the medial layer of large arteries, in a pattern very similar to that seen in children with HGPS. This mouse model should prove valuable for testing experimental therapies for this devastating disorder and for exploring cardiovascular disease in general.
C1 NHGRI, NIH, Genome Technol Branch, Bethesda, MD 20892 USA.
   NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA.
   Karolinska Inst, Novum, Dept Med Nutr, S-14157 Huddinge, Sweden.
   Virginia Mason, Benaroya Res Inst, Hope Heart Program, Seattle, WA 98101 USA.
   Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA.
   CVPath Inc, Gaithersburg, MD 20878 USA.
   Brown Univ, Sch Med, Dept Pediat, Providence, RI 02912 USA.
   NHLBI, NIH, Bethesda, MD 20892 USA.
RP Collins, FS (reprint author), NHGRI, NIH, Genome Technol Branch, Bldg 31,Room 4B09,31 Ctr Dr,MSC2152,50 South Dr, Bethesda, MD 20892 USA.
EM fc23a@nih.gov
FU NHLBI NIH HHS [HL-18645, P01 HL018645]
NR 31
TC 122
Z9 124
U1 2
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 FEB 28
PY 2006
VL 103
IS 9
BP 3250
EP 3255
DI 10.1073/pnas.0600012103
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 018QU
UT WOS:000235780700046
PM 16492728
ER

PT J
AU Takikawa, S
   Engle, RE
   Emerson, SU
   Purcell, RH
   St Claire, M
   Bukh, J
AF Takikawa, S
   Engle, RE
   Emerson, SU
   Purcell, RH
   St Claire, M
   Bukh, J
TI Functional analyses of GB virus B p13 protein: Development of a
   recombinant GB virus B hepatitis virus with a p7 protein
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE animal model; chronicity; ion channel
ID SEMLIKI-FOREST-VIRUS; ION-CHANNEL ACTIVITY; C VIRUS; MEMBRANE
   PERMEABILIZATION; P7 POLYPEPTIDE; VPU PROTEIN; CDNA-CLONE; AGENT;
   IDENTIFICATION; INFECTION
AB GB virus B (GBV-B), which infects tamarins, is the virus most closely related to hepatitis C virus (HCV). HCV has a protein (p7) that is believed to form an ion channel. It is critical for viability. In vitro studies suggest that GBV-B has an analogous but larger protein (p13). We found that substitutions of the -1 and/or -3 residues of the putative cleavage sites (amino acid 613/614 and 732/733) abolished processing in vitro and rendered an infectious GBV-B clone nonviable in tamarins. Internal cleavage was predicted at two sites (amino acid 669/670 and 681/682), and in vitro analysis indicated processing at both sites, suggesting that p13 is processed into two components (p6 and p7). Mutants with substitution at amino acid 669 or 681 were viable in vivo, but the recovered viruses had changes at amino acid 669 and 681, respectively, which restored cleavage. A mutant lacking amino acid 614-681 (p6 plus part of p7) was nonviable. However, a mutant lacking amino acid 614-669 (p6) produced high titer viremia and acute resolving hepatitis; viruses recovered from both animals lacked the deleted sequence and had no other mutations. Thus, p6 was dispensable but p7 was essential for infectivity. The availability of a recombinant GBV-B virus containing a p7 protein with similarities to the HCV p7 will enhance the relevance of this model and will be of importance for identifying compounds that inhibit p7 function as additional therapeutic agents.
C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
   NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
   Bioqual Inc, Rockville, MD 20850 USA.
RP Purcell, RH (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
EM rpurcell@niaid.nih.gov; jbukh@niaid.nih.gov
FU Intramural NIH HHS
NR 29
TC 25
Z9 26
U1 0
U2 0
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 FEB 28
PY 2006
VL 103
IS 9
BP 3345
EP 3350
DI 10.1073/pnas.0511297103
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 018QU
UT WOS:000235780700062
PM 16492760
ER

PT J
AU Nanda, A
   Karim, B
   Peng, ZS
   Liu, GS
   Qiu, WP
   Gan, C
   Vogelstein, B
   St Croix, B
   Kinzler, KW
   Huso, DL
AF Nanda, A
   Karim, B
   Peng, ZS
   Liu, GS
   Qiu, WP
   Gan, C
   Vogelstein, B
   St Croix, B
   Kinzler, KW
   Huso, DL
TI Tumor endothelial marker 1 (Tem1) functions in the growth and
   progression of abdominal tumors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE endosialin; metastasis; stroma; tumor invasiveness; angiogenesis
ID ENDOTHELIAL MARKERS; STROMAL FIBROBLASTS; BREAST-CANCER; CELLS;
   ANGIOGENESIS; SURFACE; ENDOSIALIN; EXPRESSION; MICROENVIRONMENT;
   IDENTIFICATION
AB Tumor endothelial marker 1 (Tem1; endosialin) is the prototypical member of a family of genes expressed in the stroma of tumors. To assess the functional role of Tem1, we disrupted the Tem1 gene in mice by targeted homologous recombination. Tem1(-/-) mice were healthy, their wound healing was normal, and tumors grew normally when implanted in s.c. sites. However, there was a striking reduction in tumor growth, invasiveness, and metastasis after transplantation of tumors to abdominal sites in mice without functional Tem1 genes. These data indicate that the stroma can control tumor aggressiveness and that this control varies with anatomic site. Therefore, they have significant implications for the mechanisms underlying tumor invasiveness and for models that evaluate this process.
C1 Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
   Johns Hopkins Med Inst, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21205 USA.
   Johns Hopkins Med Inst, Dept Comparat Med, Baltimore, MD 21205 USA.
   Johns Hopkins Med Inst, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
   NCI, Tumor Angiogenesis Sect, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA.
RP Vogelstein, B (reprint author), Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
EM vogelbe@welch.jhu.edu; kinzlke@jhmi.edu; dhuso@jhmi.edu
FU NCI NIH HHS [CA57345, CA62924, P50 CA062924, R01 CA057345, R37
   CA057345]; NCRR NIH HHS [RR00171, K26 RR000171]; NIGMS NIH HHS [GM07184,
   GM07309, T32 GM007184, T32 GM007309]
NR 31
TC 76
Z9 77
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 28
PY 2006
VL 103
IS 9
BP 3351
EP 3356
DI 10.1073/pnas.0511306103
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 018QU
UT WOS:000235780700063
PM 16492758
ER

PT J
AU Sakai, K
   Dimas, J
   Lenardo, MJ
AF Sakai, K
   Dimas, J
   Lenardo, MJ
TI The Vif and Vpr accessory proteins independently cause HIV-1-induced T
   cell cytopathicity and cell cycle arrest
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE AIDS; apoptosis; lymphocytes; necrosis; NL4-3
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 VPR; VIRION INCORPORATION; VIRAL
   EXPRESSION; IN-VIVO; APOPTOSIS; INFECTION; MECHANISM; DYNAMICS; DEATH
AB HIV type I (HIV-1) can cause G(2) cell cycle arrest and death of CD4+ T lymphocytes in vitro and inexorable depletion of these cells in vivo. However, the molecular mechanism of viral cytoparthicity has not been satisfactorily elucidated. Previously, we showed that HIV-1 kills T cells by a necrotic form of cell death that requires high level expression of an integrated provirus but not the env or nef genes. To determine which viral protein(s) are required for cell death, we systematically mutated, alone and in combination, the ORFs of the NL4-3 strain of HIV-1. We found that the elimination of the viral functions encoded by gag-pol and vpu, tat, and rev did not mitigate cytopathicity. However, elimination of the vif and vpr accessory genes together, but not individually, renders the virus incapable of causing cell death and G(2) cell cycle blockade. We thus identify vif and vpr as necessary for T cell cytopathic effects induced by HIV-1. These findings may provide an important insight into the molecular mechanism of viral pathogenesis in AIDS.
C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM lenardo@nih.gov
RI sakai, Keiko/F-5807-2013
FU Intramural NIH HHS
NR 53
TC 75
Z9 78
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 28
PY 2006
VL 103
IS 9
BP 3369
EP 3374
DI 10.1073/pnas.0509417103
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 018QU
UT WOS:000235780700066
PM 16492778
ER

PT J
AU Lee, CH
   Olson, P
   Hevener, A
   Mehl, I
   Chong, LW
   Olefsky, JM
   Gonzalez, FJ
   Ham, J
   Kang, H
   Peters, JM
   Evans, RM
AF Lee, CH
   Olson, P
   Hevener, A
   Mehl, I
   Chong, LW
   Olefsky, JM
   Gonzalez, FJ
   Ham, J
   Kang, H
   Peters, JM
   Evans, RM
TI PPAR delta regulates glucose metabolism and insulin sensitivity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE fatty acid and glucose metabolism; insulin sensitivity
ID PROLIFERATOR-ACTIVATED RECEPTORS; FATTY-ACIDS; LIPID-METABOLISM; GAMMA;
   ALPHA; ADIPOSE; MUSCLE; EICOSANOIDS; RESISTANCE; OBESITY
AB The metabolic syndrome is a collection of obesity-related disorders. The peroxisome proliferator-activated receptors (PPARs) regulate transcription in response to fatty acids and, as such, are potential therapeutic targets for these diseases. We show that PPAR delta (NR1C2) knockout mice are metabolically less active and glucose-intolerant, whereas receptor activation in db/db mice improves insulin sensitivity. Euglycemic-hyperinsulinemic-clamp experiments further demonstrate that a PPAR delta-specific agonist suppresses hepatic glucose output, increases glucose disposal, and inhibits free fatty acid release from adipocytes. Unexpectedly, gene array and functional analyses suggest that PPAR delta ameliorates hyperglycemia by increasing glucose flux through the pentose phosphate pathway and enhancing fatty acid synthesis. Coupling increased hepatic carbohydrate catabolism with its ability to promote beta-oxidation in muscle allows PPAR delta to regulate metabolic homeostasis and enhance insulin action by complementary effects in distinct tissues. The combined hepatic and peripheral actions of PPAR delta suggest new therapeutic approaches to treat type II diabetes.
C1 Salk Inst Biol Studies, Howard Hughes Med Inst, Gene Express Lab, La Jolla, CA 92037 USA.
   Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA.
   Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA.
   Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
   NCI, Lab Metab, Div Basic Sci, Bethesda, MD 20892 USA.
   Seoul Natl Univ, Marine Biotechnol Lab, Sch Earth & Environm Sci, Seoul 151747, South Korea.
   Seoul Natl Univ, Ctr Marine Nat Prod Drug Discovery, Seoul 151747, South Korea.
   Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA.
   Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
RP Evans, RM (reprint author), Salk Inst Biol Studies, Howard Hughes Med Inst, Gene Express Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
EM evans@salk.edu
RI Peters, Jeffrey/D-8847-2011
FU NHLBI NIH HHS [5P50HL56989, P50 HL056989]; NIDDK NIH HHS [5R37DK057978,
   R37 DK057978, U19 DK062434, U19DK62434-01]
NR 34
TC 289
Z9 304
U1 2
U2 18
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 FEB 28
PY 2006
VL 103
IS 9
BP 3444
EP 3449
DI 10.1073/pnas.0511253103
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 018QU
UT WOS:000235780700079
PM 16492734
ER

PT J
AU Alpert, JE
   Biggs, MM
   Davis, L
   Shores-Wilson, K
   Harlan, WR
   Schneider, GW
   Ford, AL
   Farabaugh, A
   Stegman, D
   Ritz, AL
   Husain, MM
   Macleod, L
   Wisniewski, SR
   Rush, AJ
AF Alpert, JE
   Biggs, MM
   Davis, L
   Shores-Wilson, K
   Harlan, WR
   Schneider, GW
   Ford, AL
   Farabaugh, A
   Stegman, D
   Ritz, AL
   Husain, MM
   Macleod, L
   Wisniewski, SR
   Rush, AJ
CA STAR D investigators
TI Enrolling research subjects from clinical practice: Ethical and
   procedural issues in the Sequenced Treatment Alternatives to Relieve
   Depression (STAR*D) trial
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE recruitment; randomized clinical trial; major depressive disorder
ID THERAPEUTIC MISCONCEPTION; CONSENT; PARTICIPANTS
AB The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial is a multi-site effectiveness study funded by the National Institute of Mental Health (NIMH) with the aim of identifying successful, acceptable and cost-effective treatment strategies for outpatients with unremitted depression. With enrollment of 4041 adults with major depressive disorder (MDD), it is the largest controlled psychiatric treatment study ever undertaken. In the course of developing procedures to ensure that ambitious enrollment goals were met, a number of ethical and practical issues became apparent that underscore the conflicts between effectiveness research and human subject protections. These are delineated as they relate to study design; eligibility criteria; incentives to subjects; investigators and clinical sites; the complementary roles of clinical research coordinators (CRCs) and study clinicians; and recruitment and consent procedures. The STAR*D trial exemplifies the interplay and tension between those strategies that integrate research and clinical aims and roles in the service of enhancing external validity, site participation, and recruitment and retention versus those strategies that differentiate research and clinical treatment in the service of research integrity and human subject protections. We hope that a discussion of these key challenges and dilemmas and how they have been addressed will help inform future discussions concerning design and conduct of ethical effectiveness trials designed to optimize care in real world clinical settings. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA.
   Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA.
   Vet Adm Med Ctr, Dept Res, Tuscaloosa, AL 35404 USA.
   Univ Alabama, Birmingham, AL 35233 USA.
   NIMH, Bethesda, MD 20892 USA.
   Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA.
   Univ Pittsburgh, Epidemiol Data Coordinating Ctr, Pittsburgh, PA 15261 USA.
RP Alpert, JE (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St,4th Floor, Boston, MA 02114 USA.
EM jalpert@partners.org
RI Biggs, Dr. Melanie/C-1468-2010; 
OI Wisniewski, Stephen/0000-0002-3877-9860; Alpert,
   Jonathan/0000-0002-4332-908X; Rush, Augustus/0000-0003-2004-2382
FU NIMH NIH HHS [N01MH90003]
NR 26
TC 10
Z9 10
U1 1
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD FEB 28
PY 2006
VL 141
IS 2
BP 193
EP 200
DI 10.1016/j.psychres.2005.04.007
PG 8
WC Psychiatry
SC Psychiatry
GA 033BB
UT WOS:000236820000008
PM 16457894
ER

PT J
AU Schisterman, EF
   Reiser, B
   Faraggi, D
AF Schisterman, EF
   Reiser, B
   Faraggi, D
TI ROC analysis for markers with mass at zero
SO STATISTICS IN MEDICINE
LA English
DT Article
DE Box-Cox power transformations; coronary calcium score; diagnostic
   markers; Mann-Whitney statistic; mixture model
ID OPERATING CHARACTERISTIC CURVES; TRANSFORMATION MODELS;
   DIAGNOSTIC-TESTS; AREA
AB The receiver operating characteristic (ROC) curve and in particular the area under the curve (AUC) is commonly used to examine the discriminatory ability of diagnostic markers. Certain markers while basically continuous and non-negative have a positive probability mass (spike) at the value zero. We discuss a flexible modelling approach to such data and contrast it with the standard non-parametric approach. We show how the modelling approach can be extended to take account of the effect of explanatory variables. We motivate this problem and illustrate the modelling approach using data on the coronary calcium score, measured by electron beam tomography, which is a marker for atherosclerosis. Copyright (c) 2005 John Wiley & Sons, Ltd.
C1 Univ Haifa, Dept Stat, IL-31905 Haifa, Israel.
   NICHD, Div Epidemiol, NIH, Bethesda, MD 20892 USA.
RP Faraggi, D (reprint author), Univ Haifa, Dept Stat, Mt Carmel, IL-31905 Haifa, Israel.
EM faraggi@stat.haifa.ac.il
RI Reiser, Benjamin/G-6591-2012; 
OI Reiser, Benjamin/0000-0002-9797-9029; Schisterman,
   Enrique/0000-0003-3757-641X
NR 19
TC 14
Z9 15
U1 0
U2 1
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD FEB 28
PY 2006
VL 25
IS 4
BP 623
EP 638
DI 10.1002/sim.2301
PG 16
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 009EE
UT WOS:000235093300007
PM 16345033
ER

PT J
AU Levine, AM
   Karim, R
   Mack, W
   Gravink, DJ
   Anastos, K
   Young, M
   Cohen, M
   Newman, M
   Augenbraun, M
   Gange, S
   Watts, DH
AF Levine, AM
   Karim, R
   Mack, W
   Gravink, DJ
   Anastos, K
   Young, M
   Cohen, M
   Newman, M
   Augenbraun, M
   Gange, S
   Watts, DH
TI Neutropenia in human immunodeficiency virus infection - Data from the
   Women's Interagency HIV Study
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article; Proceedings Paper
CT 14th International AIDS Conference
CY JUL 07-12, 2002
CL BARCELONA, SPAIN
SP Univ N Carolina, Gen Clin Res Ctr, UNC Ctr AIDS Res, Natl Inst Hlth, Swiss Natl AIDS Res Program, Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoWellcome Res & Dev, HIV Antiviral Res
ID AIDS-RELATED COMPLEX; ANTIRETROVIRAL THERAPY; PROGENITOR CELLS;
   HEMATOPOIESIS; INDUCTION; DISEASE; GROWTH
AB Background: Neutropenia is well described in individuals infected with human immunodeficiency virus (HIV) and occurs in approximately 10% to 50% of cases. Neither the effect of highly active antiretroviral therapy ( HAART) on neutrophil counts nor the significance of neutropenia in terms of survival has previously been evaluated.
   Methods: The prevalence of neutropenia among 1729 HIV-infected women, followed up as part of the Women's Interagency HIV Study, was evaluated. The CD4 lymphocyte counts, HIV-1 RNA levels, and complete blood cell counts, including absolute neutrophil counts, were obtained at 6-month intervals.
   Results: Neutropenia was common among HIV-infected women; at baseline, 44% had neutrophil counts less than 2000/mu L, whereas 7% had counts less than 1000/ mu L. During 7.5 years of follow-up, neutrophil counts less than 2000/ mu L occurred on at least 1 occasion in 79%, whereas absolute neutrophil counts less than 1000/ mu L were documented in 31%. Worsening HIV disease parameters, such as lower CD4 cell counts ( P <. 001) and higher HIV-1 RNA levels ( P <. 001), were associated with development of neutropenia. Resolution of neutropenia was associated with higher CD4 cell counts ( P <. 001) and use of HAART ( P=. 007). We found that HAART, without zidovudine, was associated with protection against development of neutropenia. On multivariate analysis, neutropenia was not found to be associated with decreased survival among HIV-infected women.
   Conclusions: Worsening HIV disease parameters are associated with neutropenia in HIV-infected women. Treatment with HAART, without zidovudine in the regimen, protects against development of neutropenia, whereas HAART use and higher CD4 cell counts are associated with resolution of neutropenia. Neutropenia is not associated with decreased survival in HIV-infected women.
C1 Univ So Calif, Keck Sch Med, Norris Canc Ctr, Dept Med,Div Hematol, Los Angeles, CA 90033 USA.
   Univ So Calif, Keck Sch Med, Dept Prevent Med, Div Biostat, Los Angeles, CA 90033 USA.
   Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA.
   Georgetown Univ, Sch Med, Dept Med, Washington, DC USA.
   Rush Med Coll, Dept Med, Cook Cty Bur Hlth Serv, Care Ctr, Chicago, IL 60612 USA.
   Univ Calif San Francisco, Sch Med, San Francisco Gen Hosp, Dept Med,Div AIDS, San Francisco, CA USA.
   Maimonides Hosp, Dept Med, Brooklyn, NY 11219 USA.
   SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA.
   Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
   NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA.
RP Levine, AM (reprint author), Univ So Calif, Keck Sch Med, Norris Canc Ctr, Dept Med,Div Hematol, 1441 Eastlake Ave, Los Angeles, CA 90033 USA.
EM alevine@usc.edu
OI Gange, Stephen/0000-0001-7842-512X
FU NIAID NIH HHS [U01-AI-35004, U01-AI-45290, N01-AI-35161, U01-AI-31834,
   U01-AI-34989, U01-AI-34994]; NICHD NIH HHS [U01-HD-32632]
NR 24
TC 18
Z9 20
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD FEB 27
PY 2006
VL 166
IS 4
BP 405
EP 410
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 017YW
UT WOS:000235730400004
PM 16505259
ER

PT J
AU Goedert, JJ
   Rabkin, CS
   Ross, SR
AF Goedert, JJ
   Rabkin, CS
   Ross, SR
TI Prevalence of serologic reactivity against four strains of mouse mammary
   tumour virus among US women with breast cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE breast cancer; mouse mammary tumour virus (MMTV); seroprevalence;
   Western immunoblot; immunoprecipitation
ID PRIMARY BILIARY-CIRRHOSIS; VIRAL-INFECTION; T-CELLS; IN-VIVO;
   ANTIBODIES; RETROVIRUS; RESPONSES; SERUM; MICE
AB Mouse mammary tumour virus (MMTV) causes breast cancer in mice, and MMTV-specific antibodies develop to high titers among mice infected as adults. Whether MMTV or a related virus infects humans is uncertain, because MMTV DNA sequences have been detected inconsistently and because serologic methods have varied widely. The current study used immunoblot and immunoprecipitation with four strains of MMTV (RIII, FM, C3H, and LA) to detect specific antibodies in 92 sera from US women with breast cancer and in masked dilutions of monoclonal hybridoma and hyperimmunised goat positive-control reagents. In these positive controls, MMTV antibodies of the expected molecular weights were detected at high titer (1 : 100 in the monoclonal reagent, 1 : 10000 in the hyperimmunised goat serum). Nearly 30% of the sera from women with breast cancer had at least one faint band on an immunoblot, but none of these matched the molecular weight of bands revealed by probing the same blot strips with the goat serum. The goat serum readily immunoprecipitated MMTV antigens from all four strains of MMTV, but MMTV antigens were not immunoprecipitated by any of the six breast cancer sera that had four or more nonspecific immunoblot bands. Thus, among women with breast cancer, we found no MMTV-specific antibodies. The upper 95% confidence limit implies that MMTV seroprevalence among breast cancer patients does not exceed 3%.
C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
   Univ Penn, Sch Med, Dept Microbiol, Ctr Canc, Philadelphia, PA 19104 USA.
RP Goedert, JJ (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8012, Rockville, MD 20892 USA.
EM goedertj@mail.nih.gov
FU NCI NIH HHS [R01 CA073746, R01 CA73746]
NR 19
TC 15
Z9 16
U1 0
U2 0
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 FEB 27
PY 2006
VL 94
IS 4
BP 548
EP 551
DI 10.1038/sj.bjc.6602977
PG 4
WC Oncology
SC Oncology
GA 014JG
UT WOS:000235475300015
PM 16449994
ER

PT J
AU Levy, JR
   Sumner, CJ
   Caviston, JP
   Tokito, MK
   Ranganathan, S
   Ligon, LA
   Wallace, KE
   LaMonte, BH
   Harmison, GG
   Puls, L
   Fischbeck, KH
   Holzbaur, ELF
AF Levy, JR
   Sumner, CJ
   Caviston, JP
   Tokito, MK
   Ranganathan, S
   Ligon, LA
   Wallace, KE
   LaMonte, BH
   Harmison, GG
   Puls, L
   Fischbeck, KH
   Holzbaur, ELF
TI A motor neuron disease-associated mutation in p150(Glued) perturbs
   dynactin function and induces protein aggregation
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID BULBAR MUSCULAR-ATROPHY; CYTOPLASMIC DYNEIN; DROSOPHILA-MELANOGASTER;
   COMPLEX; CELLS; DEGENERATION; MICROTUBULES; TRANSPORT; COMPONENT; BINDS
AB The microtubule motor cytoplasmic dynein and its activator dynactin drive vesicular transport and mitotic spindle organization. Dynactin is ubiquitously expressed in eukaryotes, but a G59S mutation in the p150(Glued) subunit of dynactin results in the specific degeneration of motor neurons. This mutation in the conserved cytoskeleton-associated protein, glycine-rich (CAP-Gly) domain lowers the affinity of p150(Glued) for microtubules and EB1. Cell lines from patients are morphologically normal but show delayed recovery after nocodazole treatment, consistent with a subtle disruption of dynein/dynactin function. The G59S mutation disrupts the folding of the CAP-Gly domain, resulting in aggregation of the p150(Glued) protein both in vitro and in vivo, which is accompanied by an increase in cell death in a motor neuron cell line. Overexpression of the chaperone Hsp70 inhibits aggregate formation and prevents cell death. These data support a model in which a point mutation in p150(Glued) causes both loss of dynein/dynactin function and gain of toxic function, which together lead to motor neuron cell death.
C1 Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA.
   NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
RP Holzbaur, ELF (reprint author), Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA.
EM holzbaur@mail.med.upenn.edu
OI Ligon, Lee/0000-0002-5735-3654
FU Intramural NIH HHS; NIA NIH HHS [T32 AG000255, T32 AG00255]; NIGMS NIH
   HHS [GM48661, R01 GM048661]; NINDS NIH HHS [K22 NS048199,
   K22-NS0048199-01]
NR 38
TC 104
Z9 109
U1 1
U2 4
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 FEB 27
PY 2006
VL 172
IS 5
BP 733
EP 745
DI 10.1083/jcb.200511068
PG 13
WC Cell Biology
SC Cell Biology
GA 019NR
UT WOS:000235844500012
PM 16505168
ER

PT J
AU Yen, PM
   Ando, S
   Feng, X
   Liu, Y
   Maruvada, P
   Xia, XM
AF Yen, PM
   Ando, S
   Feng, X
   Liu, Y
   Maruvada, P
   Xia, XM
TI Thyroid hormone action at the cellular, genomic and target gene levels
SO MOLECULAR AND CELLULAR ENDOCRINOLOGY
LA English
DT Article; Proceedings Paper
CT International Symposium on Steroid Hormone Receptor Superfamily and
   Molecular Signaling
CY NOV 25-27, 2004
CL Trivandrum, INDIA
DE thyroid hormone receptor; transcription; green fluorescent protein;
   microarray; chromatin immunprecipitation assay
ID ESTROGEN-RECEPTOR-ALPHA; TRANSCRIPTION FACTOR TFIIH;
   GLUCOCORTICOID-RECEPTOR; RESPONSIVE PROMOTERS; LIVING CELLS; IN-VIVO;
   COACTIVATOR COMPLEXES; LIGAND; EXPRESSION; ACTIVATION
AB Thyroid hormone (TH) plays important roles in metabolism, growth and differentiation. Thyroid hormone receptors (TRs) are ligand-regulatable transcription factors that bind both TH and DNA enhancer sequences in the promoter region of target genes where they can interact with co-repressor and co-activator complexes. These interactons, in turn, have consequent effects on transcription. This review describes studies on TH action from our laboratory examining the cellular localization and motility of TRs using green fluorescent fusion proteins. gene expression profiles of TH in WT and TR alpha and TR beta KO mice, as well as general transcription factor and co-activator recruitment on the promoters of target genes by TH in chromatin immunoprecipitation assays. (c) 2006 Published by Elsevier Ireland Ltd.
C1 Johns Hopkins Bayview Med Ctr, Dept Med, Baltimore, MD 21224 USA.
   Natl Inst Diabet Digest & Kidney Dis, Clin Endocrinol Branch, NIH, Bethesda, MD USA.
RP Yen, PM (reprint author), Johns Hopkins Bayview Med Ctr, Dept Med, 4940 Eastern Ave Rm B114, Baltimore, MD 21224 USA.
EM pyen3@jhmi.edu
NR 33
TC 117
Z9 128
U1 0
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
   IRELAND
SN 0303-7207
J9 MOL CELL ENDOCRINOL
JI Mol. Cell. Endocrinol.
PD FEB 26
PY 2006
VL 246
IS 1-2
BP 121
EP 127
DI 10.1016/j.mce.2005.11.030
PG 7
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 021VN
UT WOS:000236014100016
PM 16442701
ER

PT J
AU Fauci, AS
AF Fauci, AS
TI Emerging and re-emerging infectious diseases: Influenza as a prototype
   of the host-pathogen balancing act
SO CELL
LA English
DT Editorial Material
AB To respond to emerging and re-emerging infections, it is necessary to understand the interactions between microbial pathogens and their hosts and the impact of environmental and social factors on these interactions. The importance of understanding host-pathogen interactions is underscored by the emergence of virulent H5N1 avian influenza viruses and their transmission to humans, and the potential pandemic threat they pose.
C1 NIAID, NIH, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM afauci@niaid.nih.gov
NR 7
TC 49
Z9 54
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA
SN 0092-8674
J9 CELL
JI Cell
PD FEB 24
PY 2006
VL 124
IS 4
BP 665
EP 670
DI 10.1016/j.cell.2006.02.010
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 038RO
UT WOS:000237240900008
PM 16497575
ER

PT J
AU Douek, DC
   Kwong, PD
   Nabell-, GJ
AF Douek, DC
   Kwong, PD
   Nabell-, GJ
TI The rational design of an AIDS vaccine
SO CELL
LA English
DT Editorial Material
ID EVOLUTIONARY
AB The extraordinary genetic diversity and immune evasion of human immunodeficiency virus (HIV) pose significant challenges for vaccine development. AIDS vaccine design requires a scientifically driven, rational approach that encompasses the latest advances in viral molecular genetics, structural biology, and immunology.
C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Nabell-, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Room 4502,Bldg 40,MSC-3005,40 Convent Dr, Bethesda, MD 20892 USA.
EM gnabel@nih.gov
FU Intramural NIH HHS
NR 5
TC 94
Z9 101
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA
SN 0092-8674
J9 CELL
JI Cell
PD FEB 24
PY 2006
VL 124
IS 4
BP 677
EP 681
DI 10.1016/j.cell.2006.02.005
PG 5
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 038RO
UT WOS:000237240900010
PM 16497577
ER

PT J
AU Vos, MD
   Dallol, A
   Eckfeld, K
   Allen, NPC
   Donninger, H
   Hesson, LB
   Calvisi, D
   Latif, F
   Clark, GJ
AF Vos, MD
   Dallol, A
   Eckfeld, K
   Allen, NPC
   Donninger, H
   Hesson, LB
   Calvisi, D
   Latif, F
   Clark, GJ
TI The RASSF1A tumor suppressor activates Bax via MOAP-1
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID EPIGENETIC INACTIVATION; BREAST CANCERS; RAS EFFECTOR; APOPTOSIS;
   FAMILY; GENE; PROTEIN; DOMAIN; NORE1; LUNG
AB The novel tumor suppressor RASSF1A is frequently inactivated during human tumorigenesis by promoter methylation. RASSF1A may serve as a node in the integration of signaling pathways controlling a range of critical cellular functions including cell cycle, genomic instability, and apoptosis. The mechanism of action of RASSF1A remains under investigation. We now identify a novel pathway connecting RASSF1A to Bax via the Bax binding protein MOAP-1. RASSF1A and MOAP-1 interact directly, and this interaction is enhanced by the presence of activated K-Ras. RASSF1A can activate Bax via MOAP-1. Moreover, activated K-Ras, RASSF1A, and MOAP-1 synergize to induce Bax activation and cell death. Analysis of a tumor-derived point mutant of RASSF1A showed that the mutant was defective for the MOAP-1 interaction and for Bax activation. Moreover, inhibition of RASSF1A by shRNA impaired the ability of K-Ras to activate Bax. Thus, we identify a novel pro-apoptotic pathway linking K-Ras, RASSF1A and Bax that is specifically impaired in some human tumors.
C1 NCI, Dept Cell & Canc Biol, Rockville, MD 20850 USA.
   Univ Sassari, Dept Biomed Sci, I-07110 Sassari, Italy.
   Univ Birmingham, Div Reprod & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England.
RP Clark, GJ (reprint author), NCI, Dept Cell & Canc Biol, 9610 Med Ctr Dr, Rockville, MD 20850 USA.
EM gclark@mail.nih.gov
RI Dallol, Ashraf/H-8661-2012
OI Dallol, Ashraf/0000-0002-8803-228X
NR 39
TC 72
Z9 75
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 FEB 24
PY 2006
VL 281
IS 8
BP 4557
EP 4563
DI 10.1074/jbc.M512128200
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 013RF
UT WOS:000235426200002
PM 16344548
ER

PT J
AU Fukumoto, S
   Miner, JH
   Ida, H
   Fukumoto, E
   Yuasa, K
   Miyazaki, H
   Hoffman, MP
   Yamada, Y
AF Fukumoto, S
   Miner, JH
   Ida, H
   Fukumoto, E
   Yuasa, K
   Miyazaki, H
   Hoffman, MP
   Yamada, Y
TI Laminin alpha 5 is required for dental epithelium growth and polarity
   and the development of tooth bud and shape
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PHOSPHOINOSITIDE 3-OH KINASE; EMBRYONIC SIGNALING CENTER; GLAND
   CELL-LINE; ALPHA-6-BETA-4 INTEGRIN; BASEMENT-MEMBRANE; ALPHA(6)BETA(4)
   INTEGRIN; DYSTROGLYCAN-BINDING; MOUSE TOOTH; ACTIN CYTOSKELETON;
   LAMELLAE FORMATION
AB In tooth development, the oral ectoderm and mesenchyme coordinately and reciprocally interact through the basement membrane for their growth and differentiation to form the proper shape and size of the tooth. Laminin alpha 5 subunit-containing laminin-10/11 ( LM-511/521) is the major laminin in the tooth germ basement membrane. Here, we have examined the role of laminin alpha 5 ( Lama5) in tooth development using laminin alpha 5-null mouse primary dental epithelium and tooth germ organ cultures. Lama5-null mice develop a small tooth germ with defective cusp formation and have reduced proliferation of dental epithelium. Also, cell polarity and formation of the monolayer of the inner dental epithelium are disturbed. The enamel knot, a signaling center for tooth germ development, is defective, and there is a significant reduction of Shh and Fgf4 expression in the dental epithelium. In the absence of laminin alpha 5, the basement membrane in the inner dental epithelium becomes discontinuous. In normal mice, integrin alpha 6 beta 4, a receptor for laminin alpha 5, is strongly localized at the basal layer of the epithelium, whereas in mutant mice, integrin alpha 6 beta 4 is expressed around the cell surface. In primary dental epithelium culture, laminin-10/11 promotes cell growth, spreading, and filopodia-like micro-spike formation. This promotion is inhibited by anti-integrin alpha 6 and beta 4 antibodies and by phosphatidylinositol 3-kinase inhibitors and dominant negative Rho-GTPase family proteins Cdc42 and Rac. In organ culture, anti-integrin alpha 6 antibody and wortmannin reduce tooth germ size and shape. Our studies demonstrate that laminin alpha 5 is required for the proliferation and polarity of basal epithelial cells and suggest that the interaction between laminin-10/11-integrin alpha 6 beta 4 and the phosphatidylinositol 3-kinase-Cdc42/Rac pathways play an important role in determining the size and shape of tooth germ.
C1 NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA.
   NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
   Washington Univ, Sch Med, Div Renal, St Louis, MO 63110 USA.
   Nagasaki Univ, Grad Sch Biomed Sci, Nagasaki 8528521, Japan.
   Kyushu Univ, Fac Dent Sci, Fukuoka 8128582, Japan.
RP Yamada, Y (reprint author), NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, 30 Convent Dr,Bldg 30,Rm 407, Bethesda, MD 20892 USA.
EM yoshi.yamada@nih.gov
FU Intramural NIH HHS
NR 72
TC 64
Z9 65
U1 2
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 FEB 24
PY 2006
VL 281
IS 8
BP 5008
EP 5016
DI 10.1074/jbc.M509295200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 013RF
UT WOS:000235426200053
PM 16365040
ER

PT J
AU Rey, O
   Papazyan, R
   Waldron, RT
   Young, SH
   Lippincott-Schwartz, J
   Jacamo, R
   Rozengurt, E
AF Rey, O
   Papazyan, R
   Waldron, RT
   Young, SH
   Lippincott-Schwartz, J
   Jacamo, R
   Rozengurt, E
TI The nuclear import of protein kinase D3 requires its catalytic activity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID COUPLED RECEPTOR ACTIVATION; PLECKSTRIN HOMOLOGY DOMAIN; CYSTEINE-RICH
   MOTIFS; INTRACELLULAR REDISTRIBUTION; MOLECULAR-CLONING; TYROSINE
   KINASE; PHORBOL ESTERS; EXPORT SIGNALS; C FAMILY; TRANSLOCATION
AB The protein kinase D (PKD) family consists of three serine/threonine protein kinases termed PKD, PKD2, and PKD3, which are similar in overall structure and primary amino acid sequence. However, each isozyme displays a distinctive intracellular localization. Taking advantage of the structural homology and opposite nuclear localization of PKD2 and PKD3, we generated an extensive set of chimeric proteins between both isozymes to determine which PKD3 domain(s) mediates its nuclear localization. We found that the C-terminal region of PKD3, which contains its catalytic domain, is necessary but not sufficient for its nuclear localization. Real time imaging of a photoactivatable green fluorescent protein fused to PKD3 revealed that point mutations that render PKD3 catalytically inactive completely prevented its nuclear import despite its interaction with importin alpha and beta. We also found that activation loop phosphorylation of PKD3 did not require its nuclear localization, and it was not sufficient to promote the nuclear import of PKD3. These results identify a novel function for the kinase activity of PKD3 in promoting its nuclear entry and suggest that the catalytic activity of PKD3 may regulate its nuclear import through autophosphorylation and/or interaction with another protein(s).
C1 Univ Calif Los Angeles, Dept Med, Unit Signal Transduct & Gastrointestinal Canc, Div Digest Dis,CURE Digest Dis Res Ctr,David Geff, Los Angeles, CA 90095 USA.
   Univ Calif Los Angeles, Inst Mol Biol, David Geffen Sch Med, Los Angeles, CA 90095 USA.
   NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Rey, O (reprint author), Univ Calif Los Angeles, Dept Med, Unit Signal Transduct & Gastrointestinal Canc, Div Digest Dis,CURE Digest Dis Res Ctr,David Geff, 900 Vet Ave,Warren Hall Rm 11-115, Los Angeles, CA 90095 USA.
EM orey@mednet.ucla.edu
FU NCI NIH HHS [K01CA097956]; NIDDK NIH HHS [DK 55003, DK 56930, 5 P30
   DK41301]
NR 46
TC 14
Z9 15
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 FEB 24
PY 2006
VL 281
IS 8
BP 5149
EP 5157
DI 10.1074/jbc.M508014200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 013RF
UT WOS:000235426200069
PM 16380377
ER

PT J
AU Sher, I
   Zisman-Rozen, S
   Eliahu, L
   Whitelock, JM
   Maas-Szabowski, N
   Yamada, Y
   Breitkreutz, D
   Fusenig, NE
   Arikawa-Hirasawa, E
   Iozzo, RV
   Bergman, R
   Ron, D
AF Sher, I
   Zisman-Rozen, S
   Eliahu, L
   Whitelock, JM
   Maas-Szabowski, N
   Yamada, Y
   Breitkreutz, D
   Fusenig, NE
   Arikawa-Hirasawa, E
   Iozzo, RV
   Bergman, R
   Ron, D
TI Targeting perlecan in human keratinocytes reveals novel roles for
   perlecan in epidermal formation
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HEPARAN-SULFATE PROTEOGLYCANS; FIBROBLAST-GROWTH-FACTOR;
   BASEMENT-MEMBRANE FORMATION; CULTURED HUMAN KERATINOCYTES; ORGANOTYPIC
   SKIN CULTURE; GENE-EXPRESSION; PROTEIN CORE; EXTRACELLULAR-MATRIX;
   BIOLOGICAL-ACTIVITY; RECEPTOR-BINDING
AB Heparin-binding growth factors are crucial for the formation of human epidermis, but little is known about the role of heparan sulfate proteoglycans in this process. Here we investigated the role of the heparan sulfate proteoglycan, perlecan, in the formation of human epidermis, by utilizing in vitro engineered human skin. By disrupting perlecan expression either in the dermis or the epidermis, we found that epidermally derived perlecan is essential for epidermal formation. Perlecan-deficient keratinocytes formed a strikingly thin and poorly organized epidermis because of premature apoptosis and failure to complete their stratification program. Exogenous perlecan fully restored epidermal formation. Perlecan deposition in the basement membrane zone correlated with formation of multilayered epidermis. Perlecan deficiency, however, had no effect on the lining and deposition of major basement membrane components as was evident by a continuous linear staining of laminin and collagen IV. Similarly, perlecan deficiency did not affect the distribution of beta 1 integrin. Addition of the perlecan ligand, fibroblast growth factor 7, protected perlecan-deficient keratinocytes from cell death and improved the thickness of the epidermis. Taken together, our results revealed novel roles for perlecan in epidermal formation. Perlecan regulates both the survival and terminal differentiation steps of keratinocytes. Our results suggested a model whereby perlecan regulates these processes via controlling the bioavailability of perlecan-binding soluble factors involved in epidermal morphogenesis.
C1 Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.
   CSIRO, N Ryde, NSW 2113, Australia.
   DKFZ, Div Differentiat & Carcinogenesis, D-69120 Heidelberg, Germany.
   NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA.
   Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
   Thomas Jefferson Univ, Kimmel Canc Ctr, Cellular Biol & Signaling Program, Philadelphia, PA 19107 USA.
   Rambam Med Ctr, Dept Dermatol, IL-31096 Haifa, Israel.
   Rambam Med Ctr, Lab Mol Dermatol, IL-31096 Haifa, Israel.
RP Ron, D (reprint author), Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.
EM dinar@tx.technion.ac.il
OI Iozzo, Renato/0000-0002-5908-5112
NR 76
TC 53
Z9 53
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 FEB 24
PY 2006
VL 281
IS 8
BP 5178
EP 5187
DI 10.1074/jbc.M509500200
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 013RF
UT WOS:000235426200072
PM 16269412
ER

PT J
AU Miura, A
   Yamagata, K
   Kakei, M
   Hatakeyama, H
   Takahashi, N
   Fukui, K
   Nammo, T
   Yoneda, K
   Inoue, Y
   Sladek, FM
   Magnuson, MA
   Kasai, H
   Miyagawa, J
   Gonzalez, FJ
   Shimomura, I
AF Miura, A
   Yamagata, K
   Kakei, M
   Hatakeyama, H
   Takahashi, N
   Fukui, K
   Nammo, T
   Yoneda, K
   Inoue, Y
   Sladek, FM
   Magnuson, MA
   Kasai, H
   Miyagawa, J
   Gonzalez, FJ
   Shimomura, I
TI Hepatocyte nuclear factor-4 alpha is essential for glucosestimulated
   insulin secretion by pancreatic beta-cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TRANSCRIPTION FACTOR HNF-4; SENSITIVE K+ CHANNELS; GLUCOSE-METABOLISM;
   GENE-EXPRESSION; ATP CHANNELS; YOUNG MODY1; ALPHA-GENE; MUTATIONS;
   RECEPTOR; MOUSE
AB Mutations in the hepatocyte nuclear factor (HNF)-4 alpha gene cause a form of maturity-onset diabetes of the young (MODY1) that is characterized by impairment of glucose- stimulated insulin secretion by pancreatic beta-cells. HNF-4 alpha, a transcription factor belonging to the nuclear receptor superfamily, is expressed in pancreatic islets as well as in the liver, kidney, and intestine. However, the role of HNF-4 alpha in pancreatic beta-cell is unclear. To clarify the role of HNF-4 alpha in beta-cells, we generated beta-cell-specific HNF-4 alpha knock-out (beta HNF-4 alpha KO) mice using the Cre-LoxP system. The beta HNF-4 alpha KO mice exhibited impairment of glucose- stimulated insulin secretion, which is a characteristic of MODY1. Pancreatic islet morphology, beta-cell mass, and insulin content were normal in the HNF-4 alpha mutant mice. Insulin secretion by beta HNF-4 alpha KO islets and the intracellular calcium response were impaired after stimulation by glucose or sulfonylurea but were normal after stimulation with KCl or arginine. Both NAD(P)H generation and ATP content at high glucose concentrations were normal in the beta HNF-4 alpha KO mice. Expression levels of Kir6.2 and SUR1 proteins in the beta HNF-4 alpha KO mice were unchanged as compared with control mice. Patch clamp experiments revealed that the current density was significantly increased in beta HNF-4 alpha KO mice compared with control mice. These results are suggestive of the dysfunction of K-ATP channel activity in the pancreatic beta-cells of HNF-4 alpha-deficient mice. Because the K-ATP channel is important for proper insulin secretion in beta-cells, altered K-ATP channel activity could be related to the impaired insulin secretion in the beta HNF-4 alpha KO mice.
C1 Osaka Univ, Grad Sch Med, Dept Metab Med, Suita, Osaka 5650871, Japan.
   Akita Univ, Sch Med, Dept Internal Med, Div Endocrinol Metab & Geriatr Med, Akita 0108543, Japan.
   Natl Inst Physiol Sci, Dept Cell Physiol, Okazaki, Aichi 4448787, Japan.
   Grad Univ Adv Studies, Okazaki, Aichi 4448787, Japan.
   Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Kawaguchi, Saitama 3320012, Japan.
   Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA.
   Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
   NCI, Lab Metab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Yamagata, K (reprint author), Osaka Univ, Grad Sch Med, Dept Metab Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan.
EM kazu@imed2.med.osaka-u.ac.jp
RI Magnuson, Mark/B-1335-2009
OI Magnuson, Mark/0000-0002-8824-6499
NR 45
TC 92
Z9 92
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 FEB 24
PY 2006
VL 281
IS 8
BP 5246
EP 5257
DI 10.1074/jbc.M507496200
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 013RF
UT WOS:000235426200079
PM 16377800
ER

PT J
AU Tsai, CW
   Duggan, PF
   Shimp, RL
   Miller, LH
   Narum, DL
AF Tsai, CW
   Duggan, PF
   Shimp, RL
   Miller, LH
   Narum, DL
TI Overproduction of Pichia pastoris or Plasmodium falciparum protein
   disulfide isomerase affects expression, folding and O-linked
   glycosylation of a malaria vaccine candidate expressed in P-pastoris
SO JOURNAL OF BIOTECHNOLOGY
LA English
DT Article
DE Pichia pastoris; Plasinodium falciparum; protein disulfide isornerase;
   O-linked glycosylation; heterologous protein expression; Malaria vaccine
ID TRANSMISSION-BLOCKING VACCINE; SACCHAROMYCES-CEREVISIAE;
   ENDOPLASMIC-RETICULUM; ESCHERICHIA-COLI; YEAST; PFS25; OVEREXPRESSION;
   PURIFICATION; PARASITE; ANTIGEN
AB Production of recombinant malaria proteins in the methylotrophic yeast Pichia pastoris has been difficult due to constraints in transcription, translation and/or post-translation controls. Use of codon-optimized genes has resolved many of the transcriptional controls; however, efforts to overcome translational and post-translational modifications involving disulfide bond formation and glycosylation have been mostly restricted to knocking-out putative N-linked glycosylation sites. We report now on the effect of overproduction of P pastoris protein disulfide isomerase (PpPDI) and Plasmodium falciparum (PfPDI) on production of a disulfide-rich P. falciparum transmission-blocking vaccine candidate, Pfs25. Pfs25 is expressed in P pastoris as two isoforms (A and 13); the A form has been selected for Phase I human studies. Overproduction of PpPDI in the R pastoris Pfs25 production clone markedly enhanced the expression level of Pfs25(A) and (B) by 3-fold, while overproduction of PfPDI increased the proportion of Pfs25(A) compared to (13). The resultant Pfs25 products were purified and fully characterized biochemically. In addition to differences in production levels, the mass spectra of PpPDI-Pfs25(A) compared to Pfs25(A) and PfPDI-Pfs25(A) were different due to the pattern and level of O-linked glycosylation. The overproduction of PpPDI or PfPDI provides new platforms for expression of disulfide-rich malaria proteins. (c) 2005 Elsevier B.V All rights reserved.
C1 NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA.
RP Narum, DL (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, 5640 Fishers Lane, Rockville, MD 20852 USA.
EM dnarum@niaid.nih.gov
RI Chiang, Vincent, Ming-Hsien/D-4312-2016
OI Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863
NR 30
TC 52
Z9 57
U1 1
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1656
J9 J BIOTECHNOL
JI J. Biotechnol.
PD FEB 24
PY 2006
VL 121
IS 4
BP 458
EP 470
DI 10.1016/j.jbiotec.2005.08.025
PG 13
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 017MG
UT WOS:000235697100004
PM 16274825
ER

PT J
AU Anantharaman, V
   Aravind, L
AF Anantharaman, V
   Aravind, L
TI Diversification of catalytic activities and ligand interactions in the
   protein fold shared by the sugar isomerases, elF2B, DeoR transcription
   factors Acyl-CoA transferases and methenyltetrahydrofolate synthetase
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE catalysis; Rossmann fold; small molecule binding; protein fold;
   DNA-binding
ID MULTIPLE SEQUENCE ALIGNMENT; PENTOSE-PHOSPHATE PATHWAY;
   ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; D-RIBOSE-5-PHOSPHATE ISOMERASE;
   SACCHAROMYCES-CEREVISIAE; GLUCOSAMINE-6-PHOSPHATE DEAMINASE;
   RIBOSE-5-PHOSPHATE ISOMERASE; KLEBSIELLA-PNEUMONIAE; ANGSTROM RESOLUTION
AB Evolution of diverse catalytic and ligand-binding activities in a given protein fold is a widely observed phenomenon in the protein-domain universe. However, the details of this evolutionary process, general principles, if any, and implications for origins of particular catalytic mechanisms are poorly understood in many common protein folds. Taking advantage of the wealth of Currently available protein structure and sequence data, we explore these issues in the context of a large assemblage of biochemically diverse protein domains sharing a common origin, namely the sugar isomerases, translation factor eIF2B, ligand-binding domains of the DeoR-family transcription factors, acetyl-CoA transferases and methenyltetrahydrofolate synthetase. We show that in at least three independent instances, including the sugar-binding domains of the DeoR family transcription factors, this domain has been used as small molecule sensor coupled to helix-turn-helix DNA-binding domains. In at least two of these instances the domain functions as a noncatalytic sensor of ligands. We provide evidence that the ancestral version of this fold was a distinct version of the Rosmann-like folds, which probably possessed two distinct ligwid-binding areas that were differentially utilized in different descendents. Analyzing the sequences and structures of proteins in this fold we show that there are two principal factors related to the origin of catalytic diversity in this fold. Firstly, specific inserts and extension added to the core domain on multiple occasions in evolution have affected the access to the active site regions, and thereby allowed for different substrates and allosteric regulators. The second major factor appears to be the emergence of considerable diversity of family-specific residues with important biochemical roles. Interestingly, proteins of this fold, which catalyze similar reactions on similar substrates, might possess very distinctive sets of active residues required for substrate binding catalysis. In particular, different sugar isomerases or acyl transferases in this fold might show distinct constellations of active site residues. These findings suggest that whereas ligand-binding, and even generic catalytic ability emerged early in the evolution of the fold, the specific catalytic mechanisms appear to have independently emerged on multiple occasions in the generic precursors of this fold. Published by Elsevier Ltd.
C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM aravind@mail.nih.gov
OI Anantharaman, Vivek/0000-0001-8395-0009
FU Intramural NIH HHS
NR 73
TC 17
Z9 17
U1 0
U2 4
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 FEB 24
PY 2006
VL 356
IS 3
BP 823
EP 842
DI 10.1016/j.jmb.2005.11.031
PG 20
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 013LK
UT WOS:000235410600023
PM 16376935
ER

PT J
AU Armakolas, A
   Klar, AJS
AF Armakolas, A
   Klar, AJS
TI Cell type regulates selective segregation of mouse chromosome 7 DNA
   strands in mitosis
SO SCIENCE
LA English
DT Article
ID STEM-CELLS; MITOTIC RECOMBINATION; COSEGREGATION; CHROMATIDS; DROSOPHILA
AB After chromosome replication, sister chromatid copies are generally thought to segregate randomly to daughter cells. However, sister chromatids differ in their DNA strands, with each chromatid inheriting one older strand that is paired to a newly synthesized strand. Genetic analysis with a homologous chromosome pair indicated nonrandom chromatid distribution in embryonic stem cells. Biased segregation pattern was also found in all 100 endoderm cells examined, but not in any of the 165 neuroectoderm cells. In contrast, the mesoderm, cardiomyocyte, and pancreatic cells exhibited a random mode of segregation. Strand distribution mechanisms regulated by cell, type may have consequences for cellular differentiation and for evolving strategies for developmental mechanisms.
C1 NCI, Ctr Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
RP Klar, AJS (reprint author), NCI, Ctr Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA.
EM klar@ncifcrf.gov
FU Intramural NIH HHS
NR 19
TC 71
Z9 73
U1 0
U2 3
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 FEB 24
PY 2006
VL 311
IS 5764
BP 1146
EP 1149
DI 10.1126/science.1120519
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 017IU
UT WOS:000235688100047
PM 16497932
ER

PT J
AU Liu, DL
   Peddada, SD
   Li, LP
   Weinberg, CR
AF Liu, DL
   Peddada, SD
   Li, LP
   Weinberg, CR
TI Phase analysis of circadian-related genes in two tissues
SO BMC BIOINFORMATICS
LA English
DT Article
ID CELL-CYCLE; EXPRESSION; CLOCK; IDENTIFICATION; TRANSCRIPTION; MAMMALS
AB Background: Recent circadian clock studies using gene expression microarray in two different tissues of mouse have revealed not all circadian-related genes are synchronized in phase or peak expression times across tissues in vivo. Instead, some circadian-related genes may be delayed by 4-8 hrs in peak expression in one tissue relative to the other. These interesting biological observations prompt a statistical question regarding how to distinguish the synchronized genes from genes that are systematically lagged in phase/peak expression time across two tissues.
   Results: We propose a set of techniques from circular statistics to analyze phase angles of circadian-related genes in two tissues. We first estimate the phases of a cycling gene separately in each tissue, which are then used to estimate the paired angular difference of the phase angles of the gene in the two tissues. These differences are modeled as a mixture of two von Mises distributions which enables us to cluster genes into two groups; one group having synchronized transcripts with the same phase in the two tissues, the other containing transcripts with a discrepancy in phase between the two tissues. For each cluster of genes we assess the association of phases across the tissue types using circular-circular regression. We also develop a bootstrap methodology based on a circular-circular regression model to evaluate the improvement in fit provided by allowing two components versus a one-component von-Mises model.
   Conclusion: We applied our proposed methodologies to the circadian-related genes common to heart and liver tissues in Storch et al. [2], and found that an estimated 80% of circadian-related transcripts common to heart and liver tissues were synchronized in phase, and the other 20% of transcripts were lagged about 8 hours in liver relative to heart. The bootstrap p-value for being one cluster is 0.063, which suggests the possibility of two clusters. Our methodologies can be extended to analyze peak expression times of circadian-related genes across more than two tissues, for example, kidney, heart, liver, and the suprachiasmatic nuclei (SCN) of the hypothalamus.
C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
   CIIT Ctr Hlth Res, Res Triangle Pk, NC 27709 USA.
RP Weinberg, CR (reprint author), NIEHS, Biostat Branch, MD A3-03,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM dliu@ciit.org; peddada@niehs.nih.gov; li3@niehs.nih.gov;
   weinberg@niehs.nih.gov
RI Peddada, Shyamal/D-1278-2012
NR 15
TC 17
Z9 17
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD FEB 23
PY 2006
VL 7
AR 87
DI 10.1186/1471-2105-7-87
PG 10
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
GA 022NN
UT WOS:000236062600001
PM 16504088
ER

PT J
AU Varma, S
   Simon, R
AF Varma, S
   Simon, R
TI Bias in error estimation when using cross-validation for model selection
SO BMC BIOINFORMATICS
LA English
DT Article
ID GENE-EXPRESSION; MICROARRAY DATA; CANCER TYPES; CLASSIFICATION
AB Background: Cross-validation (CV) is an effective method for estimating the prediction error of a classifier. Some recent articles have proposed methods for optimizing classifiers by choosing classifier parameter values that minimize the CV error estimate. We have evaluated the validity of using the CV error estimate of the optimized classifier as an estimate of the true error expected on independent data.
   Results: We used CV to optimize the classification parameters for two kinds of classifiers; Shrunken Centroids and Support Vector Machines (SVM). Random training datasets were created, with no difference in the distribution of the features between the two classes. Using these "null" datasets, we selected classifier parameter values that minimized the CV error estimate. 10-fold CV was used for Shrunken Centroids while Leave-One-Out-CV (LOOCV) was used for the SVM. Independent test data was created to estimate the true error. With "null" and "non null" (with differential expression between the classes) data, we also tested a nested CV procedure, where an inner CV loop is used to perform the tuning of the parameters while an outer CV is used to compute an estimate of the error.
   The CV error estimate for the classifier with the optimal parameters was found to be a substantially biased estimate of the true error that the classifier would incur on independent data. Even though there is no real difference between the two classes for the " null" datasets, the CV error estimate for the Shrunken Centroid with the optimal parameters was less than 30% on 18.5% of simulated training data-sets. For SVM with optimal parameters the estimated error rate was less than 30% on 38% of " null" data-sets. Performance of the optimized classifiers on the independent test set was no better than chance.
   The nested CV procedure reduces the bias considerably and gives an estimate of the error that is very close to that obtained on the independent testing set for both Shrunken Centroids and SVM classifiers for "null" and " non-null" data distributions.
   Conclusion: We show that using CV to compute an error estimate for a classifier that has itself been tuned using CV gives a significantly biased estimate of the true error. Proper use of CV for estimating true error of a classifier developed using a well defined algorithm requires that all steps of the algorithm, including classifier parameter tuning, be repeated in each CV loop. A nested CV procedure provides an almost unbiased estimate of the true error.
C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
RP Varma, S (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
EM varmas@mail.nih.gov; rsimon@mail.nih.gov
RI Varma, Sudhir/N-8763-2014
OI Varma, Sudhir/0000-0002-4096-4782
NR 12
TC 204
Z9 212
U1 3
U2 29
PU BIOMED CENTRAL LTD
PI LONDON
PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD FEB 23
PY 2006
VL 7
AR 91
DI 10.1186/1471-2105-7-91
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Mathematical & Computational Biology
GA 020GG
UT WOS:000235896100001
PM 16504092
ER

PT J
AU Xiao, XS
   Antony, S
   Pommier, Y
   Cushman, M
AF Xiao, XS
   Antony, S
   Pommier, Y
   Cushman, M
TI Total synthesis and biological evaluation of 22-hydroxyacuminatine
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID TOPOISOMERASE-I POISON; CURRENT PERSPECTIVES; CAMPTOTHECIN; INHIBITION;
   STABILITY; TOLUENES; COMPLEX; POTENT
AB A total synthesis of 22-hydroxyacuminatine, a cytotoxic alkaloid isolated from Camptotheca acuminata, is reported. The key step in the synthesis involves the reaction of 2,3-dihydro-1H-pyrrolo[3,4-b]quinoline with a brominated phthalide to generate a substituted pentacyclic 12H-5,11a-diazadibenzo[b,h]fluoren-11-one intermediate. Despite its structural resemblance to camptothecin and luotonin A, a biological evaluation of 22-hydroxyacuminatine in a topoisomerase I-deficient cell line P388/CPT45 has confirmed that the observed cytotoxicity is not due to topoisomerase I inhibition, even though 22-hydroxyacuminatine has a hydroxyl group that can theoretically hydrogen bond to Asp533. This result is consistent with the hypothesis that pi-pi stacking is more important than hydrogen-bonding interactions in determining topoisomerase I inhibitor binding in the ternary cleavage complex.
C1 Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA.
   Purdue Univ, Sch Pharm & Pharmaceut Sci, Purdue Canc Ctr, W Lafayette, IN 47907 USA.
   NCI, Mol Pharmacol Lab, Canc Res Ctr, Bethesda, MD 20892 USA.
RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA.
EM cushman@pharmacy.purdue.edu
FU NCI NIH HHS [U01 CA089566-02, UO1 CA89566, U01 CA089566-05, U01
   CA089566-04, U01 CA089566-01A1, U01 CA089566, U01 CA089566-03]; PHS HHS
   [C06-14499]
NR 27
TC 44
Z9 44
U1 1
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD FEB 23
PY 2006
VL 49
IS 4
BP 1408
EP 1412
DI 10.1021/jm051116e
PG 5
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 016MR
UT WOS:000235624800020
PM 16480276
ER

PT J
AU Clegg, DO
   Reda, DJ
   Harris, CL
   Klein, MA
   O'Dell Jr
   Hooper, MM
   Bradley, JD
   Bingham, CO
   Weisman, MH
   Jackson, CG
   Lane, NE
   Cush, JJ
   Moreland, LW
   Schumacher, HR
   Oddis, CV
   Wolfe, F
   Molitor, JA
   Yocum, DE
   Schnitzer, TJ
   Furst, DE
   Sawitzke, AD
   Shi, H
   Brandt, KD
   Moskowitz, RW
   Williams, HJ
AF Clegg, DO
   Reda, DJ
   Harris, CL
   Klein, MA
   O'Dell, JR
   Hooper, MM
   Bradley, JD
   Bingham, CO
   Weisman, MH
   Jackson, CG
   Lane, NE
   Cush, JJ
   Moreland, LW
   Schumacher, HR
   Oddis, CV
   Wolfe, F
   Molitor, JA
   Yocum, DE
   Schnitzer, TJ
   Furst, DE
   Sawitzke, AD
   Shi, H
   Brandt, KD
   Moskowitz, RW
   Williams, HJ
TI Glucosamine, chondroitin sulfate, and the two in combination for painful
   knee osteoarthritis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID DOUBLE-BLIND; CLINICAL-TRIAL; RHEUMATOID-ARTHRITIS; RESEARCH-SOCIETY;
   OSTEO-ARTHRITIS; EFFICACY; PLACEBO; ACETAMINOPHEN; ROFECOXIB; CELECOXIB
AB BACKGROUND:
   Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis.
   METHODS:
   We randomly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild [N=1229] vs. moderate to severe [N=354]). The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24.
   RESULTS:
   The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. As compared with the rate of response to placebo (60.1 percent), the rate of response to glucosamine was 3.9 percentage points higher (P=0.30), the rate of response to chondroitin sulfate was 5.3 percentage points higher (P=0.17), and the rate of response to combined treatment was 6.5 percentage points higher (P=0.09). The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P=0.008). For patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2 percent vs. 54.3 percent, P=0.002). Adverse events were mild, infrequent, and evenly distributed among the groups.
   CONCLUSIONS:
   Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee. Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain.
C1 Univ Utah, Sch Med, Salt Lake City, UT USA.
   Hines Vet Affairs Cooperat Studies Program Coordi, Hines, IL USA.
   Clin Res Pharm Coordinating Ctr, Albuquerque, NM USA.
   NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
   Univ Nebraska, Med Ctr, Omaha, NE USA.
   Case Western Reserve Univ, Cleveland, OH 44106 USA.
   Indiana Univ, Sch Med, Indianapolis, IN USA.
   Hosp Joint Dis & Med Ctr, New York, NY USA.
   Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
   Univ Calif San Francisco, San Francisco, CA 94143 USA.
   Presbyterian Med Ctr, Dallas, TX USA.
   Univ Alabama, Birmingham, AL USA.
   Hosp Univ Penn, Philadelphia, PA 19104 USA.
   Univ Pittsburgh, Pittsburgh, PA 15260 USA.
   Arthrit Res Ctr, Wichita, KS USA.
   Ctr Clin, Wichita, KS USA.
   Virginia Mason Med Ctr, Seattle, WA 98101 USA.
   Univ Arizona, Coll Med, Tucson, AZ USA.
   Northwestern Univ, Chicago, IL 60611 USA.
   Univ Calif Los Angeles, Los Angeles, CA USA.
RP Clegg, DO (reprint author), Univ Utah, Sch Med 4B200, Div Rheumatol, 50 N Med Dr, Salt Lake City, UT 84132 USA.
EM gait.study@hsc.utah.edu
FU NIAMS NIH HHS [N01AR92236]
NR 36
TC 551
Z9 597
U1 12
U2 93
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 FEB 23
PY 2006
VL 354
IS 8
BP 795
EP 808
DI 10.1056/NEJMoa052771
PG 14
WC Medicine, General & Internal
SC General & Internal Medicine
GA 014CL
UT WOS:000235456200004
PM 16495392
ER

PT J
AU Sterneck, E
   Zhu, S
   Ramirez, A
   Jorcano, JL
   Smart, RC
AF Sterneck, E
   Zhu, S
   Ramirez, A
   Jorcano, JL
   Smart, RC
TI Conditional ablation of C/EBP beta demonstrates its
   keratinocyte-specific requirement for cell survival and mouse skin
   tumorigenesis
SO ONCOGENE
LA English
DT Article
DE C/EBP; apoptosis; carcinogenesis
ID CCAAT/ENHANCER-BINDING-PROTEINS; GENE-EXPRESSION; DEFICIENT MICE;
   TRANSCRIPTION FACTORS; CARCINOMA-CELLS; ONCOGENIC RAS; DIFFERENTIATION;
   CANCER; PROLIFERATION; INACTIVATION
AB The CCAAT/enhancer binding protein beta(C/EBP beta) is implicated in the regulation of many different molecular and physiological processes. Mice with a germline deletion of C/EBP beta (C/EBP beta(-/-)) display phenotypes in a multitude of cell types and organ systems, including skin where C/EBP beta(-/-) mice exhibit increased apoptosis in epidermal keratinocytes in response to carcinogen treatment and are completely resistant to carcinogen-induced skin tumorigenesis. To determine the contribution of systemic versus cell autonomous functions of C/EBP beta to specific phenotypes, mice with a conditional 'floxed' C/EBP beta null allele were generated. Epidermal-specific deletion of C/EBP beta was achieved by Cre recombinase expression from a keratin 5 (K5) promoter. Similar to C/EBP beta(-/-) mice, K5-Cre; C/EBP beta(fl)/(fl) mice were completely refractory to 7,12 dimethylbenz[a] anthracene (DMBA)-induced skin tumorigenesis and these mice displayed increased DMBA-induced apoptosis in epidermal keratinocytes compared to wild-type mice. In contrast, mice lacking the related gene, C/ EBP delta, were not resistant to DMBA-induced skin tumorigenesis, indicating a unique role of C/EBP beta in skin tumor development. Our findings demonstrate that C/EBP beta exerts an essential, keratinocyte-intrinsic role in cell survival in response to carcinogen treatment and the elimination of C/EBP beta in keratinocytes is sufficient to confer complete resistance of the skin to chemical carcinogenesis.
C1 N Carolina State Univ, Dept Environm & Mol Toxicol, Cell Signaling & Canc Grp, Raleigh, NC 27695 USA.
   NCI, Mol Mech Dev Grp, Lab Prot Dynam & Signaling, Frederick, MD USA.
   CIEMAT, Repair & Tissue Engn Program, Madrid, Spain.
RP Smart, RC (reprint author), N Carolina State Univ, Dept Environm & Mol Toxicol, Cell Signaling & Canc Grp, Raleigh, NC 27695 USA.
EM rcsmart@unity.ncsu.edu
FU NCI NIH HHS [R01 CA046637, CA46637]
NR 31
TC 45
Z9 45
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD FEB 23
PY 2006
VL 25
IS 8
BP 1272
EP 1276
DI 10.1038/sj.onc.1209144
PG 5
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 015FO
UT WOS:000235537500014
PM 16205634
ER

PT J
AU Wang, Y
   Zhang, Z
   Lubet, RA
   You, M
AF Wang, Y
   Zhang, Z
   Lubet, RA
   You, M
TI A mouse model for tumor progression of lung cancer in ras and p53
   transgenic mice
SO ONCOGENE
LA English
DT Article
DE lung; cancer; progression; ras; p53; transgenic mice
ID ONCOGENE ACTIVATION; CIGARETTE-SMOKING; SUPPRESSOR GENES; LIVER-TUMORS;
   A/J MICE; MUTATIONS; CARCINOGENESIS; PROTOONCOGENE; ADENOCARCINOMAS;
   TUMORIGENESIS
AB Although ras and p53 are the most commonly found oncogene and tumor suppressor gene, respectively, in human cancers, their collective roles in tumor progression have yet to be defined in animal models. Here, we demonstrated the synergistic effect between ras and p53 in promoting tumor progression during lung tumorigenesis using bitransgenic mice. Mice with a heterozygous knockout of K-ras (K-ras(wt/ko)) were mated to p53 transgenic mice (p53(val135/wt)) in lung tumorigenesis ( K-ras(wt/ko) x p53(val135/wt)). F-1 mice exhibited a significant increase in lung tumor load (tumor multiplicity x tumor volume) when compared to those seen in either K-ras(wt/ko) mice or p53(val135/wt) mice alone. Furthermore, over 50% of the lung tumors were lung adenocarcinomas in bitransgenic mice compared to only 3% in wild-type mice. Alterations of ras and p53 appear to promote the development of lung adenocarcinomas. These results provide the in vivo experimental evidence of synergistic interactions of ras and p53 in lung tumor progression.
C1 Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
   Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA.
   NCI, Chemoprevent Branch, Bethesda, MD USA.
RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Euclid Ave, St Louis, MO 63110 USA.
EM youm@msnotes.wustl.edu
FU NCI NIH HHS [R01CA78797, R01CA58554]
NR 40
TC 11
Z9 12
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD FEB 23
PY 2006
VL 25
IS 8
BP 1277
EP 1280
DI 10.1038/sj.onc.1209182
PG 4
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 015FO
UT WOS:000235537500015
PM 16247444
ER

PT J
AU Porter, JD
   Israel, S
   Gong, BD
   Merriam, AP
   Feuerman, J
   Khanna, S
   Kaminski, HJ
AF Porter, JD
   Israel, S
   Gong, BD
   Merriam, AP
   Feuerman, J
   Khanna, S
   Kaminski, HJ
TI Distinctive morphological and gene/protein expression signatures during
   myogenesis in novel cell lines from extraocular and hindlimb muscle
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE allotype; cell line; DNA microarray; extraocular muscle; limb muscle;
   myoblast; proteomics
ID HEAVY-CHAIN ISOFORMS; SKELETAL-MUSCLE; GENE-EXPRESSION;
   MUSCULAR-DYSTROPHY; LIMB DEVELOPMENT; FIBER TYPES; PRECURSOR CELLS;
   MOUSE EMBRYO; MYOSIN EXPRESSION; TRANSGENIC MICE
AB Skeletal muscles are not created equal. The underutilized concept of muscle allotypes defines distinct muscle groups that differ in their intrinsic capacity to express novel traits when exposed to a facilitating extrinsic environment. Allotype-specific traits may have significance as determinants of the preferential involvement or sparing of muscle groups that is observed in a variety of neuromuscular diseases. Little is known, however, of the developmental mechanisms underlying the distinctive skeletal muscle allotypes. The lack of appropriate in vitro models, to dissociate the cell-autonomous and non-cell-autonomous mechanisms behind allotype diversity, has been a barrier to such studies. Here, we derived novel cell lines from the extraocular and hindlimb muscle allotypes and assessed their similarities and differences during early myogenesis using morphological and gene/protein expression profiling tools. Our data establish that there are fundamental differences in the transcriptional and cellular signaling pathways used by the two myoblast lineages. Taken together, these data show that myoblast lineage plays a significant role in the divergence of the distinctive muscle groups or allotypes.
C1 Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA.
   Case Western Reserve Univ, Dept Neurosci, Cleveland, OH 44106 USA.
   Univ Hosp Cleveland, Cleveland, OH 44106 USA.
RP Porter, JD (reprint author), NINDS, 6001 Execut Blvd,NSC 2142, Bethesda, MD 20892 USA.
EM porterjo@ninds.nih.gov
FU NCI NIH HHS [P30 CA43703]; NEI NIH HHS [R01 EY12779, R01 EY015306, P30
   EY11371, R01 EY09834]
NR 95
TC 29
Z9 29
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD FEB 23
PY 2006
VL 24
IS 3
BP 264
EP 275
DI 10.1152/physiolgenomics.00234.2004
PG 12
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 031RV
UT WOS:000236722600009
PM 16291736
ER

PT J
AU Lamason, R
   Zhao, P
   Rawat, R
   Davis, A
   Hall, JC
   Chae, JJ
   Agarwal, R
   Cohen, P
   Rosen, A
   Hoffman, EP
   Nagaraju, K
AF Lamason, R
   Zhao, P
   Rawat, R
   Davis, A
   Hall, JC
   Chae, JJ
   Agarwal, R
   Cohen, P
   Rosen, A
   Hoffman, EP
   Nagaraju, K
TI Sexual dimorphism in immune response genes as a function of puberty
SO BMC IMMUNOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTORS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; FAS LIGAND
   EXPRESSION; INTERFERON-GAMMA; INNATE IMMUNITY; C1Q DEFICIENCY; FACTOR-I;
   MICE; DISEASE; ESTROGEN
AB Background: Autoimmune diseases are more prevalent in females than in males, whereas males have higher mortality associated with infectious diseases. To increase our understanding of this sexual dimorphism in the immune system, we sought to identify and characterize inherent differences in immune response programs in the spleens of male and female mice before, during and after puberty.
   Results: After the onset of puberty, female mice showed a higher expression of adaptive immune response genes, while males had a higher expression of innate immune genes. This result suggested a requirement for sex hormones. Using in vivo and in vitro assays in normal and mutant mouse strains, we found that reverse signaling through FasL was directly influenced by estrogen, with downstream consequences of increased CD8(+) T cell-derived B cell help (via cytokines) and enhanced immunoglobulin production.
   Conclusion: These results demonstrate that sexual dimorphism in innate and adaptive immune genes is dependent on puberty. This study also revealed that estrogen influences immunoglobulin levels in post-pubertal female mice via the Fas-FasL pathway.
C1 Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA.
   Johns Hopkins Univ, Sch Med, Dept Med, Div Rheumatol, Baltimore, MD 21205 USA.
   NIH, Bethesda, MD 20892 USA.
   Univ Penn, Philadelphia, PA 19104 USA.
RP Nagaraju, K (reprint author), Childrens Natl Med Ctr, Res Ctr Genet Med, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM rlamaso1@jhmi.edu; pzhao@cnmcresearch.org; rrawat67@yahoo.com;
   daviesa@mskcc.org; jhall4@jhem.jhmi.edu; chaej@exchange.nih.gov;
   agarwalraj@nei.nih.gov; philipco@mail.med.upenn.edu; arosen@jhmi.edu;
   EHoffman@cnmcresearch.org; knagaraju@cnmcresearch.org
FU NHLBI NIH HHS [U01 HL66614-01, U01 HL066614]; NIAMS NIH HHS [AR050478];
   NINDS NIH HHS [N01-NS-1-2339]
NR 47
TC 43
Z9 44
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND
SN 1471-2172
J9 BMC IMMUNOL
JI BMC Immunol.
PD FEB 22
PY 2006
VL 7
AR UNSP 2
DI 10.1186/1471-2172-7-2
PG 14
WC Immunology
SC Immunology
GA 021ZS
UT WOS:000236025000001
PM 16504066
ER

PT J
AU Braiman, A
   Barda-Saad, M
   Sommers, CL
   Samelson, LE
AF Braiman, A
   Barda-Saad, M
   Sommers, CL
   Samelson, LE
TI Recruitment and activation of PLC gamma 1 in T cells: a new insight into
   old domains
SO EMBO JOURNAL
LA English
DT Article
DE calcium; confocal microscopy; FRET; protein-protein interaction; TCR
ID PHOSPHOLIPASE C-GAMMA-1 PLC-GAMMA-1; ANTIGEN RECEPTOR; TYROSINE
   PHOSPHORYLATION; SIGNAL-TRANSDUCTION; MEDIATED ACTIVATION; ACTIN
   CYTOSKELETON; ADAPTER PROTEINS; EXCHANGE FACTOR; BINDING-SITE; TEC
   KINASES
AB Engagement of the T- cell antigen receptor leads to recruitment of phospholipase C gamma 1 ( PLC gamma 1) to the LAT- nucleated signaling complex and to PLC gamma 1 activation in a tyrosine phosphorylation- dependent manner. The mechanism of PLC gamma 1 recruitment and the role of PLC gamma 1 Src homology ( SH) domains in this process remain incompletely understood. Using a combination of biochemical methods and real- time fluorescent imaging, we show here that the N- terminal SH2 domain of PLC gamma 1 is necessary but not sufficient for its recruitment. Either the SH3 or C- terminal SH2 domain of PLC gamma 1, with the participation of Vav1, c- Cbl and Slp76, are required to stabilize PLC gamma 1 recruitment. All three PLC gamma 1 SH domains are required for phosphorylation of PLC gamma 1 Y783, which is critical for enzyme activation. These novel findings entailed revision of the currently accepted model of PLC gamma 1 recruitment and activation in T lymphocytes.
C1 NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, NIH, Bldg 37,Room 2066, Bethesda, MD 20892 USA.
EM samelson@helix.nih.gov
RI Braiman, Alex/F-2179-2012
OI Braiman, Alex/0000-0003-2802-1148
FU Intramural NIH HHS
NR 47
TC 76
Z9 77
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD FEB 22
PY 2006
VL 25
IS 4
BP 774
EP 784
DI 10.1038/sj.emboj.7600978
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 024VS
UT WOS:000236225000012
PM 16467851
ER

PT J
AU Booth, NL
   Overk, CR
   Yao, P
   Totura, S
   Deng, Y
   Hedayat, AS
   Bolton, JL
   Pauli, GF
   Farnsworth, NR
AF Booth, NL
   Overk, CR
   Yao, P
   Totura, S
   Deng, Y
   Hedayat, AS
   Bolton, JL
   Pauli, GF
   Farnsworth, NR
TI Seasonal variation of red clover (Trifolium pratense L., fabaceae)
   isoflavones and estrogenic activity
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE botanical dietary supplement; estrogenic activity; HPLC; Ishikawa
   bioassay; isoflavone content; MCF-7 cell proliferation; red clover;
   seasonal variation; Trifolium pratense
ID OESTROGENIC ISOFLAVONES; PLANT ESTROGENS; BIOCHANIN; EQUOL;
   IDENTIFICATION; FORMONONETIN; METABOLISM; GENISTEIN; EXTRACTS; PARTS
AB Red clover (Trifolium pratense L., Fabaceae) dietary supplements are currently used to treat menopausal symptoms because of their high content of the mildly estrogenic isoflavones daidzein, genistein, formononetin, and biochanin A. These compounds are estrogenic in vitro and in vivo, but little information exists on the best time to harvest red clover fields to maximize content of the isoflavones and thus make an optimal product. Samples of cultivated red clover above-ground parts and flower heads were collected in parallel over one growing season in northeastern Illinois. Generally, autohydrolytic extracts of above-ground parts contained more isoflavones and had more estrogenic activity in Ishikawa endometrial cells as compared with extracts of flower heads. Daidzein and genistein contents peaked around June to July, while formononetin and biochanin A contents peaked in early September. Flower head and total above-ground parts extracts exhibited differential estrogenic activity in an Ishikawa (endometrial) cell-based alkaline phosphatase induction assay, whereas nondifferential activity was observed for most extracts tested in an MCF-7 (breast) cell proliferation assay when tested at the same final concentrations. Ishikawa assay results could be mapped onto the extracts' content of individual isoflavones, but MCF-7 results did not show such a pattern. These results suggest that significant metabolism of isoflavones may occur in MCF-7 cells but not in Ishikawa cells; therefore, caution is advised in the choice of bioassay used for the biological standardization of botanical dietary supplements.
C1 Univ Illinois, Coll Pharm, NIH, Ctr Bot Dietary Supplements Res,Program Collabora, Chicago, IL 60612 USA.
   Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA.
   Univ Illinois, Coll Arts & Sci, Dept Math Stat & Comp Sci, Chicago, IL 60607 USA.
RP Farnsworth, NR (reprint author), Univ Illinois, Coll Pharm, NIH, Ctr Bot Dietary Supplements Res,Program Collabora, MC 877,833 S Wood St, Chicago, IL 60612 USA.
EM norman@uic.edu
OI Pauli, Guido/0000-0003-1022-4326
FU NCCIH NIH HHS [F31 AT002423, F31 AT000804, P50 AT000155]
NR 27
TC 52
Z9 55
U1 1
U2 14
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD FEB 22
PY 2006
VL 54
IS 4
BP 1277
EP 1282
DI 10.1021/jf052927u
PG 6
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
   Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 016NV
UT WOS:000235627800042
PM 16478248
ER

PT J
AU Wang, CY
   Chang, K
   Petralia, RS
   Wang, YX
   Seabold, GK
   Wenthold, RJ
AF Wang, CY
   Chang, K
   Petralia, RS
   Wang, YX
   Seabold, GK
   Wenthold, RJ
TI A novel family of adhesion-like molecules that interacts with the NMDA
   receptor
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE adhesion; PDZ domains; NMDA receptors; synaptic plasticity; glutamate
   receptor; synapse
ID LEUCINE-RICH REPEAT; SODIUM-CHANNEL BETA-1; SYNAPSE FORMATION; EPHB
   RECEPTORS; CELL-SURFACE; PROTEIN; DOMAIN; TRAFFICKING; EXPRESSION;
   DROSOPHILA
AB We have identified a novel family of synaptic adhesion-like molecules (SALMs). The family members, SALM1-SALM4, have a single transmembrane (TM) domain and contain extracellular leucine-rich repeats, an Ig C2 type domain, a fibronectin type III domain, and an intracellular postsynaptic density-95 (PSD-95)/Discs large/ zona occludens-1 (PDZ) binding domain, which is present on all members except SALM4. SALM1 interacts with PSD-95, synapse-associated protein 102 (SAP102), and SAP97 based on coimmunoprecipitation of detergent-solubilized brain. Distribution studies show that SALM1 is present in synaptic membrane and postsynaptic density fractions but is also distributed in axons and dendrites. Transfection of hippocampal neurons for 4 d in vitro (DIV) with SALM1 more than doubles the dendritic lengths of neurons after 48 h, whereas transfection of neurons 14 DIV has no significant effect on neurite outgrowth. Overexpression of SALM1 in 14 DIV neurons recruits NMDA receptors (NR) and PSD-95 to dendritic puncta. This effect is dependent on the PDZ-binding domain of SALM1. SALM1 also enhances surface expression of transfected NR2A subunit. Immunoprecipitation of detergent-solubilized brain membranes with anti-SALM1 antibodies shows coimmunoprecipitation of NR1 and NR2 subunits. After transfection of heterologous cells with NR1 and NR2 cDNAs, through coimmunoprecipitation analyses, we find that SALM1 also interacts with the NMDA receptor NR1 subunit through its extracellular or TM1 domains.
C1 NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA.
RP Wenthold, RJ (reprint author), NIDCD, Neurochem Lab, NIH, Bldg 50,Room 4140, Bethesda, MD 20892 USA.
EM wenthold@nidcd.nih.gov
FU Intramural NIH HHS
NR 38
TC 67
Z9 79
U1 0
U2 3
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 22
PY 2006
VL 26
IS 8
BP 2174
EP 2183
DI 10.1523/JNEUROSCI.3799-05.2006
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 014YC
UT WOS:000235515800006
PM 16495444
ER

PT J
AU Gnanakaran, S
   Nussinov, R
   Garcia, AE
AF Gnanakaran, S
   Nussinov, R
   Garcia, AE
TI Atomic-level description of amyloid beta-dimer formation
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID MOLECULAR-DYNAMICS; A-BETA(16-22) PEPTIDE; FIBRIL FORMATION;
   HYDROGEN-BONDS; SIMULATIONS; OLIGOMERIZATION; FRAGMENT; SHEETS
C1 Los Alamos Natl Lab, Los Alamos, NM 87545 USA.
   NCI, Lab Expt & Computat Biol, SAIC, Frederick, MD 21702 USA.
   Tel Aviv Univ, Dept Human Genet, IL-69978 Tel Aviv, Israel.
   Rensselaer Polytech Inst, Dept Phys Appl Phys & Astron, Troy, NY 12180 USA.
RP Garcia, AE (reprint author), Los Alamos Natl Lab, T-10 MS K710, Los Alamos, NM 87545 USA.
EM angel@rpi.edu
OI Gnanakaran, S/0000-0002-9368-3044
FU NCI NIH HHS [N01 CO 12400]
NR 27
TC 110
Z9 114
U1 4
U2 22
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 FEB 22
PY 2006
VL 128
IS 7
BP 2158
EP 2159
DI 10.1021/ja0548337
PG 2
WC Chemistry, Multidisciplinary
SC Chemistry
GA 015PI
UT WOS:000235562900002
PM 16478138
ER

PT J
AU London, RE
   Gabel, SA
AF London, RE
   Gabel, SA
TI Photoactivated H/D exchange in tyrosine: Involvement of a radical anion
   intermediate
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID AROMATIC-AMINO-ACIDS; HYDROGEN-DEUTERIUM EXCHANGE; PHOTO-BIRCH
   REDUCTION; D ISOTOPE-EXCHANGE; AQUEOUS-SOLUTION; PROTON-TRANSFER;
   EXCITED-STATE; SODIUM-BOROHYDRIDE; ENHANCED BASICITY; PHOTOCHEMISTRY
AB The aromatic hydrogen nuclei of tyrosine are photochemically labile and exchange with deuterons in neutral D2O solution. The site meta to the ring hydroxyl substituent is preferentially deuterated, exhibiting a meta/ortho cleuteration rate of similar to 4:1. In contrast with acid-catalyzed H/D exchange and with nearly all of the reported photoactivated H/D exchange studies, the UV-induced H/D exchange of tyrosine is optimal at pH 9 and is effectively quenched at acid pH. Photochemical H/D exchange is strongly stimulated by the alpha-amino group (the aromatic hydrogens of p-cresol are far less subject to exchange) and by imidazole or phosphate buffers. On the basis of the results obtained here and on the previously identified cyclohexadienyl radical (Bussandri, A.; van Willigen, H. J. Phys. Chem. A 2002, 106, 1524-1532), we conclude that the exchange reaction involves a radical intermediate and results from two distinct roles of tyrosine: (1) as a phototransducer of light energy into solvated electrons (e(aq)(-)), and (2) as an acceptor of an electron to create a radical anion intermediate which is rapidly protonated, yielding a neutral cyclohexadienyl radical. Regeneration of the tyrosine can occur via a bimolecular redox reaction of the cyclohexadienyl and phenoxyl radicals to yield a carbocation/phenoxide pair, followed by deprotonation of the carbocation. The oxidation step is pH dependent, requiring the deprotonated form of the cyclohexadienyl radical. The H/D exchange thus results from a cyclic one-electron (Birch) reduction/protonation/reoxidation (by phenoxyl radical)/ deprotonation cycle. Consistent with these mechanistic conclusions, the aromatic hydrogens of tyrosine O-methyl ether are photochemically inert, but become labile in the presence of tyrosine at high pH. The deuteration rate of O-methyl tyrosine is lower than that of tyrosine and shows a preference for the ortho positions. This difference is proposed to result from a variation in the oxidation step, characterized by a preferential oxidation of a cyclohexadienyl resonance structure with the unpaired electron localized on the oxygen substituent.
C1 Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
RP London, RE (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA.
EM london@niehs.nih.gov
FU Intramural NIH HHS
NR 54
TC 5
Z9 5
U1 2
U2 13
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 FEB 22
PY 2006
VL 128
IS 7
BP 2268
EP 2275
DI 10.1021/ja055011c
PG 8
WC Chemistry, Multidisciplinary
SC Chemistry
GA 015PI
UT WOS:000235562900044
PM 16478180
ER

PT J
AU Zhang, H
   Rhee, C
   Bebenek, A
   Drake, JW
   Wang, JM
   Konigsberg, W
AF Zhang, H
   Rhee, C
   Bebenek, A
   Drake, JW
   Wang, JM
   Konigsberg, W
TI The L561A substitution in the nascent base-pair binding pocket of RB69
   DNA polymerase reduces base discrimination
SO BIOCHEMISTRY
LA English
DT Article
ID REPLICATION FIDELITY; CRYSTAL-STRUCTURE; ACTIVE-SITE; ERROR-PRONE;
   LESION-BYPASS; Y-FAMILY; ESCHERICHIA-COLI; DOMAIN MUTANTS; REPAIR;
   BACTERIOPHAGE-RB69
AB Several variants of RB69 DNA polymerase (RB69 pol) with single-site replacements in the nascent base-pair binding pocket are less discriminating with respect to noncomplementary dNMP incorporation than the wild-type enzyme. To quantify the loss in base selectivity, we determined the transient-state kinetic parameters for incorporation of correct and all combinations of incorrect dNMPs by the exonuclease-deficient form of one of these RB69 pol variants, L561A, using rapid chemical quench assays. The L561A variant did not significantly alter the k(pol) and K-D values for incorporation of correct dNMPs, but it showed increased incorporation efficiency (k(pol)/K-D) for mispaired bases relative to the wild-type enzyme. The incorporation efficiency for mispaired bases by the L561A variant ranged from 1.5 x 10(-5) mu M-1 s(-1) for dCMP opposite templating C to 2 x 10(-3) mu M-1 s(-1) for dAMP opposite templating C. These k(pol)/K-D values are 3-60-fold greater than those observed with the wild-type enzyme. The effect of the L561A replacement on the mutation frequency in vivo was determined by infecting Escherichia coli harboring a plasmid encoding the L561A variant of RB69 pol with T4 phage bearing a mutant rII locus, and the rates of reversions to rII(+) were scored. The exonuclease-proficient RB69 pol L561 A displayed a weak mutator phenotype. In contrast, no progeny phage were produced after infection of E. coli, expressing an exonuclease-deficient RB69 poi L561A, with either mutant or wild-type T4 phage. This dominant-lethal phenotype was attributed to error catastrophe caused by the high rate of mutation expected from combining the poi L561A and exo- mutator activities.
C1 Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
   Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland.
   NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
RP Konigsberg, W (reprint author), Yale Univ, Dept Mol Biophys & Biochem, 333 Cedar St, New Haven, CT 06520 USA.
EM William.Konigsberg@yale.edu
FU FIC NIH HHS [TW006626, R01 TW006626]; Intramural NIH HHS; NIGMS NIH HHS
   [R01 GM063276, GM63276]
NR 49
TC 26
Z9 26
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD FEB 21
PY 2006
VL 45
IS 7
BP 2211
EP 2220
DI 10.1021/bi052099y
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 014AR
UT WOS:000235451600023
PM 16475809
ER

PT J
AU Burton, RA
   Tsurupa, G
   Medved, L
   Tjandra, N
AF Burton, RA
   Tsurupa, G
   Medved, L
   Tjandra, N
TI Identification of an ordered compact structure within the recombinant
   bovine fibrinogen alpha C-domain fragment by NMRT
SO BIOCHEMISTRY
LA English
DT Article
ID PROTEIN SECONDARY STRUCTURE; CHEMICAL-SHIFT INDEX; CRYSTAL-STRUCTURE;
   CROSS-LINKING; ELECTRON-MICROSCOPY; CELL-ADHESION; BINDING; FIBRONECTIN;
   SEQUENCE; CHAINS
AB The NMR solution structure of the bovine fibrinogen alpha C-domain fragment, including residues A074-538, reveals a type-I' beta-hairpin, restricted at the base by a C423-C453 disulfide linkage and a short turn preceding C423. Although both faces of the hairpin are formed mainly by hydrophilic residues, one of them is uncharged while the other has a characteristic pattern of charged residues which are highly conserved among vertebrate species. Chemical shift indexing and relaxation data indicate the presence of a collapsed hydrophobic region next to the hairpin that includes approximately 30 residues with slower concerted motion and higher content of nonpolar residues and, according to a previous study (Tsurupa, G., Tsonev, L., and Medved, L. (2002) Biochemistry 41, 6449-6459), may cooperate with the hairpin to form a compact cooperative unit (domain). Structure and relaxation data show that the region between C423 and C453 is populated by both random coil and beta-structure, suggesting that the cooperative structure in the isolated alpha C-domain is intrinsically unstable. This observation is in agreement with a very low energy of stabilization of the A alpha 374-538 fragment determined in unfolding experiments. The low stability of the alpha C-domain suggests a possible explanation for the previously observed intra- and intermolecular interactions of these domains in fibrinogen and fibrin.
C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA.
   Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA.
   Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, NIH, 50 Ctr Dr, Bethesda, MD 20892 USA.
EM lmedved@som.umaryland.edu; tjandran@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999]; NHLBI NIH HHS [HL-56051, R01
   HL056051]
NR 61
TC 29
Z9 30
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD FEB 21
PY 2006
VL 45
IS 7
BP 2257
EP 2266
DI 10.1021/bi052380c
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 014AR
UT WOS:000235451600028
PM 16475814
ER

PT J
AU Kathiresan, S
   Gona, P
   Larson, MG
   Vita, JA
   Mitchell, GF
   Tofler, GH
   Levy, D
   Newton-Cheh, C
   Wang, TJ
   Benjamin, EJ
   Vasan, RS
AF Kathiresan, S
   Gona, P
   Larson, MG
   Vita, JA
   Mitchell, GF
   Tofler, GH
   Levy, D
   Newton-Cheh, C
   Wang, TJ
   Benjamin, EJ
   Vasan, RS
TI Cross-sectional relations of multiple biomarkers from distinct
   biological pathways to brachial artery endothelial function
SO CIRCULATION
LA English
DT Article
DE atrial natriuretic factor; endothelium; inflammation; natriuretic
   peptides; renin
ID FLOW-MEDIATED VASODILATION; BRAIN NATRIURETIC PEPTIDE;
   PLASMINOGEN-ACTIVATOR INHIBITOR; CORONARY-HEART-DISEASE; C-REACTIVE
   PROTEIN; URINARY ALBUMIN EXCRETION; NITRIC-OXIDE;
   ESSENTIAL-HYPERTENSION; CARDIOVASCULAR EVENTS; HEALTHY-SUBJECTS
AB Background - Endothelial dysfunction is a critical intermediate phenotype in the pathogenesis of cardiovascular disease. We evaluated the relative contributions of distinct biological pathways to interindividual variation in endothelial function by relating prototype biomarkers ( representing these pathways) to brachial artery vasodilator function.
   Methods and Results - We investigated the cross-sectional relations of a panel of 7 biomarkers measured at a routine examination to brachial artery vasodilator function (flow-mediated dilation [FMD] and reactive hyperemia) assessed at a subsequent examination (mean interval, 2.9 years) in 2113 Framingham Heart Study participants (mean age, 61 years; 54% women). We selected biomarkers from 4 biological domains: neurohormonal (N-terminal pro-atrial natriuretic peptide [N-ANP], B-type natriuretic peptide [BNP], renin, aldosterone), hemostatic factors (plasminogen activator inhibitor-1 [PAI-1]), inflammation (C-reactive protein [CRP]), and target organ damage (urine albumin-creatinine ratio). In age- and sex-adjusted models, several biomarkers were related to baseline brachial artery diameter (PAI-1, CRP, urine albumin-creatinine ratio), baseline mean flow (N-ANP, BNP, PAI-1, CRP, aldosterone), FMD (N-ANP, PAI-1, CRP, renin), and reactive hyperemia (BNP, PAI-1, CRP, renin, urine albumin-creatinine ratio). In multivariable analyses relating the 7 biomarkers conjointly to each vascular function measure (adjusting for known risk factors), N-ANP and renin were positively related to FMD (P = 0.001 and P = 0.04, respectively), and N-ANP was inversely related to baseline mean flow velocity (P = 0.01). None of the other biomarkers was significantly related to the vascular function measures studied.
   Conclusions - In our large community-based sample, a conservative strategy relating several biomarkers to vascular endothelial function identified plasma N-ANP as a key correlate of mean flow under basal conditions and of FMD in response to forearm cuff occlusion.
C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA.
   Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
   Boston Univ, Evans Dept Med, Boston, MA 02215 USA.
   Boston Univ, Whitaker Cardiovasc Inst, Boston, MA 02215 USA.
   Cardiovasc Engn Inc, Holliston, MA USA.
   Royal N Shore Hosp, Sydney, NSW, Australia.
   MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA.
   Harvard Univ, Cambridge, MA 02138 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA.
RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM vasan@bu.edu
OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254;
   Ramachandran, Vasan/0000-0001-7357-5970; Benjamin,
   Emelia/0000-0003-4076-2336
FU NHLBI NIH HHS [HL70100, HL60040, HL67288, K23-HL-074077, K24-HL04334,
   N01-HC-25195]
NR 49
TC 63
Z9 64
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD FEB 21
PY 2006
VL 113
IS 7
BP 938
EP 945
DI 10.1161/CIRCULATIONAHA.105.580233
PG 8
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 013IV
UT WOS:000235403900007
PM 16476848
ER

PT J
AU Koh, KK
   Quon, MJ
   Han, SH
   Chung, WJ
AF Koh, KK
   Quon, MJ
   Han, SH
   Chung, WJ
TI Comparative metabolic effects of ramipril and candesartan in the
   treatment of hypertensive patients
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 55th Annual Scientific Session of the American-College-of-Cardiology
CY MAR 11-14, 2006
CL Atlanta, GA
SP Amer Coll Cardiol
C1 NIH, Diabet Unit, Bethesda, MD 20892 USA.
   Gachon Med Sch, Inchon, South Korea.
RI Quon, Michael/B-1970-2008
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 21
PY 2006
VL 47
IS 4
SU A
BP 49A
EP 49A
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 015CV
UT WOS:000235530400213
ER

PT J
AU Arai, AE
   Cao, JJ
   Sigurdsson, S
   Jonasson, T
   Vincent, P
   Kellman, P
   Aletras, AH
   Aspelund, T
   Thorgeirsson, G
   Launer, L
   Eiriksdottir, G
   Harris, T
   Gudnason, V
AF Arai, AE
   Cao, JJ
   Sigurdsson, S
   Jonasson, T
   Vincent, P
   Kellman, P
   Aletras, AH
   Aspelund, T
   Thorgeirsson, G
   Launer, L
   Eiriksdottir, G
   Harris, T
   Gudnason, V
TI Prevalence of recognized and unrecognized myocardial infarction: The
   ICELAND MI substudy to the AGES-Reykjavik study
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 55th Annual Scientific Session of the American-College-of-Cardiology
CY MAR 11-14, 2006
CL Atlanta, GA
SP Amer Coll Cardiol
C1 NIH, Bethesda, MD 20892 USA.
   Iceland Heart Assoc, Reykjavik, Iceland.
RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason,
   Vilmundur/K-6885-2015
OI Aspelund, Thor/0000-0002-7998-5433; Gudnason,
   Vilmundur/0000-0001-5696-0084
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 21
PY 2006
VL 47
IS 4
SU A
BP 137A
EP 137A
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 015CV
UT WOS:000235530400589
ER

PT J
AU Arena, R
   Owens, DS
   Smith, K
   Mohiddin, SA
   McAreavey, D
   Ulisney, KL
   Fananapazir, L
   Plehn, JF
AF Arena, R
   Owens, DS
   Smith, K
   Mohiddin, SA
   McAreavey, D
   Ulisney, KL
   Fananapazir, L
   Plehn, JF
TI Relationship between cardiopulmonary exercise testing and pulmonary
   pressures in hypertrophic cardiomyopathy
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 55th Annual Scientific Session of the American-College-of-Cardiology
CY MAR 11-14, 2006
CL Atlanta, GA
SP Amer Coll Cardiol
C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA.
   Virginia Commonwealth Univ, Richmond, VA 23284 USA.
RI Arena, Ross/A-3141-2008
OI Arena, Ross/0000-0002-6675-1996
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 21
PY 2006
VL 47
IS 4
SU A
BP 156A
EP 156A
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 015CV
UT WOS:000235530400673
ER

PT J
AU McCrindle, BW
   Atz, AM
   Colan, SD
   Gersony, WM
   Li, JS
   Minich, LLA
   Mitchell, PD
   Takahashi, M
   Vetter, VL
   Newburger, JW
AF McCrindle, BW
   Atz, AM
   Colan, SD
   Gersony, WM
   Li, JS
   Minich, LLA
   Mitchell, PD
   Takahashi, M
   Vetter, VL
   Newburger, JW
TI Risk factors for coronary artery involvement in children after Kawasaki
   disease
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 55th Annual Scientific Session of the American-College-of-Cardiology
CY MAR 11-14, 2006
CL Atlanta, GA
SP Amer Coll Cardiol
C1 Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
   NHLBI, NIH, Pediatr Heart Network, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 21
PY 2006
VL 47
IS 4
SU A
BP 247A
EP 247A
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 015CV
UT WOS:000235530401381
ER

PT J
AU Cao, JJ
   Gudnason, V
   Pang, J
   Johannes, J
   Karlsdottir, G
   Sigurdson, S
   Bandettini, WP
   Eiriksdottir, G
   Launer, L
   Harris, T
   Arai, AE
AF Cao, JJ
   Gudnason, V
   Pang, J
   Johannes, J
   Karlsdottir, G
   Sigurdson, S
   Bandettini, WP
   Eiriksdottir, G
   Launer, L
   Harris, T
   Arai, AE
TI The relation between aortic distensibility and calcified aortic
   atherosclerosis: Cardiovascular MRI and CT correlations
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 55th Annual Scientific Session of the American-College-of-Cardiology
CY MAR 11-14, 2006
CL Atlanta, GA
SP Amer Coll Cardiol
C1 Natl Inst Hlth, Bethesda, MD USA.
   Iceland Heart Assoc, Reykjavik, Iceland.
RI Gudnason, Vilmundur/K-6885-2015
OI Gudnason, Vilmundur/0000-0001-5696-0084
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 21
PY 2006
VL 47
IS 4
SU A
BP 345A
EP 345A
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 015CV
UT WOS:000235530402299
ER

PT J
AU Koh, KK
   Quon, MJ
   Han, SH
   Shin, EK
AF Koh, KK
   Quon, MJ
   Han, SH
   Shin, EK
TI Additive beneficial effects of fenofibrate combined with candesartan in
   the treatment of hypertriglyceridemic, hypertensive patients
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Meeting Abstract
CT 55th Annual Scientific Session of the American-College-of-Cardiology
CY MAR 11-14, 2006
CL Atlanta, GA
SP Amer Coll Cardiol
C1 Gachon Med Sch, Inchon, South Korea.
   NIH, Diabet Unit, Bethesda, MD USA.
RI Quon, Michael/B-1970-2008
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 21
PY 2006
VL 47
IS 4
SU A
BP 359A
EP 359A
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 015CV
UT WOS:000235530402361
ER

PT J
AU Williams, RG
   Pearson, GD
   Barst, RJ
   Child, JS
   del Nido, P
   Gersony, WM
   Kuehl, KS
   Landzberg, MJ
   Myerson, M
   Nelsh, SR
   Sahn, DJ
   Verstappen, A
   Warnes, CA
   Webb, CL
AF Williams, RG
   Pearson, GD
   Barst, RJ
   Child, JS
   del Nido, P
   Gersony, WM
   Kuehl, KS
   Landzberg, MJ
   Myerson, M
   Nelsh, SR
   Sahn, DJ
   Verstappen, A
   Warnes, CA
   Webb, CL
TI Report of the National Heart, Lung, and Blood Institute Working Group on
   research in adult congenital heart disease
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
ID SUDDEN CARDIAC DEATH; GREAT-ARTERIES; FONTAN OPERATION; VENTRICULAR
   PERFORMANCE; CORRECTED TRANSPOSITION; SURGICAL REPAIR; PREGNANT-WOMEN;
   FALLOT REPAIR; RISK-FACTORS; TETRALOGY
AB The Working Group oil research in adult congenital heart disease (ACHD) was convened in September 2004 under the sponsorship of National Heart, Lung, and Blood Institute (NHLBI) and the Office of Rare Diseases, National Institutes of Health, Department of Health and Human Services, to make recommendations oil research needs. The Purpose Of the Working Group was to advise the NHLBI oil the current state of the science in ACHD and barriers to optimal clinical care, and to make specific recommendations for overcoming those barriers. The members of the Working Group were chosen to provide expert input oil a broad range of research issues from both scientific and lay perspectives. The Working Group reviewed data oil the epidemiology of ACHD, long-term outcomes of complex cardiovascular malformations, issues in assessing morphology and function with current imaging techniques, surgical and catheter-based interventions, management of related conditions including pregnancy and arrhythmias, quality of life, and informatics. After research and training barriers were discussed, the Working Group recommended Outreach and educational programs for adults with congenital heart disease, a network of specialized adult congenital heart disease regional centers, technology development to Support advances in imaging and modeling of abnormal structure and function, and a consensus oil appropriate training for physicians to provide care for adults with congenital heart disease.
C1 NHLBI, Div Heart & Vasc Dis, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   Univ So Calif, Dept Pediat, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
   Columbia Univ, Coll Phys & Surg, Dept Pediat Cardiol, Childrens Hosp New York,New York Presbyterian Col, New York, NY USA.
   Univ Calif Los Angeles, Adult Congenital Heart Dis Ctr, David Geffen Sch Med, Sch Med, Los Angeles, CA USA.
   Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA 02115 USA.
   George Washington Univ, Childrens Natl Med Ctr, Div Pediat Cardiol, Washington, DC USA.
   Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA.
   Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA.
   NHLBI, Div Epidemiol & Clin Applicat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
   Texas Childrens Hosp, Baylor Coll Med, Brown Fdn Heart Clin, Houston, TX 77030 USA.
   Oregon Hlth Sci Univ, Doernbecher Mem Hosp Children, Clin Care Ctr Congenital Heart Dis, Portland, OR 97201 USA.
   Adult Congenital Heart Assoc, Philadelphia, PA USA.
   Mayo Clin, Coll Med, Div Cardiovasc Dis & Pediat Cardiol, Rochester, MN USA.
   Northwestern Univ, Feinberg Sch Med, Childrens Mem Hosp, Div Pediat Cardiol, Chicago, IL 60611 USA.
RP Pearson, GD (reprint author), NHLBI, Div Heart & Vasc Dis, NIH, Dept Hlth & Human Serv, 6701 Rockledge Dr,Room 9202, Bethesda, MD 20892 USA.
EM pearsong@mail.nih.gov
NR 68
TC 78
Z9 84
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD FEB 21
PY 2006
VL 47
IS 4
BP 701
EP 707
DI 10.1016/j.jacc.2005.08.074
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 013QB
UT WOS:000235422900002
PM 16487831
ER

PT J
AU Pedersen, LG
   Bartolotti, L
   Li, LP
AF Pedersen, LG
   Bartolotti, L
   Li, LP
TI Deuterium and its role in the machinery of evolution
SO JOURNAL OF THEORETICAL BIOLOGY
LA English
DT Article
DE deuterium; evolution; zero-point; DNA; mutation
ID WATER; DYNAMICS; ELEGANS
AB An argument is presented that the spontaneous mutation rate, the core of evolution theory, may be dictated by the deuterium/ hydrogen (D/H) abundance ratio. This argument is supported by quantum mechanical calculations of the zero-point energy reduction for DNA base pairs upon deuterium substitution for hydrogen and recent experiments that show that the rate of catalytic dsDNA unwinding is dependent on the stability of the dsDNA. (c) 2005 Elsevier Ltd. All rights reserved.
C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA.
   E Carolina Univ, Dept Chem, Greenville, NC 27858 USA.
   Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA.
RP Pedersen, LG (reprint author), Univ N Carolina, Dept Chem, CB 3290, Chapel Hill, NC 27599 USA.
EM lee_pedersen@unc.edu
RI Pedersen, Lee/E-3405-2013
OI Pedersen, Lee/0000-0003-1262-9861
FU NHLBI NIH HHS [HL-06350]
NR 27
TC 2
Z9 3
U1 1
U2 5
PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-5193
J9 J THEOR BIOL
JI J. Theor. Biol.
PD FEB 21
PY 2006
VL 238
IS 4
BP 914
EP 918
DI 10.1016/j.jtbi.2005.07.002
PG 5
WC Biology; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology
GA 018RJ
UT WOS:000235782200014
PM 16098990
ER

PT J
AU Vanita, V
   Hejtmancik, JF
   Hennies, HC
   Guleria, K
   Nurnberg, P
   Singh, D
   Sperling, K
   Singh, JR
AF Vanita, V
   Hejtmancik, JF
   Hennies, HC
   Guleria, K
   Nurnberg, P
   Singh, D
   Sperling, K
   Singh, JR
TI Sutural cataract associated with a mutation in the ferritin light chain
   gene (FTL) in a family of Indian origin
SO MOLECULAR VISION
LA English
DT Article
ID IRON-RESPONSIVE ELEMENT; CONGENITAL CATARACT; MESSENGER-RNA;
   HYPERFERRITINEMIA; LENS; BINDING; PROTEIN; MORPHOLOGY; ANOMALIES;
   SPECTRUM
AB Purpose: The molecular characterization of 27 members of an Indian family, with 13 members in four generations, affected with Y-sutural congenital cataract.
   Methods: Detailed family history and clinical data were collected. A genome-wide scan by two-point linkage analysis using more than 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was performed. Mutation screening was carried out in the candidate gene by bi-directional sequencing of amplified products.
   Results: A maximum two-point lod score of 6.37 at theta=0.00 was obtained with marker D19S879. Haplotype analysis placed the cataract locus to a 5.0 cM region between D19S902 and D19S867, in close proximity to the L-ferritin light chain gene (FTL) on chromosome 19q13.3. Hematological tests in two affected individuals showed very high levels of serum ferritin without iron overload leading to the diagnosis of hyperferritinemia-cataract syndrome. Mutation screening in FTL identified a G>A change at position 32 (c.-168G>A) in a highly conserved 3 nucleotide motif that forms a loop structure in the iron responsive element (IRE) in the 5'-untranslated region (5'-UTR). This nucleotide alteration was neither seen in any unaffected member of the family nor found in 50 unrelated control subjects.
   Conclusions: The present study is the first report of a Y-sutural congenital cataract mapping to 19q13.3. The mutation observed in FTL in this family highlights the phenotypic heterogeneity of the disorder in relation to the genotype as the identical mutation (32 G>A) has previously been reported in two Italian families with entirely different phenotypes. It is also the first report of hereditary hyperferritinemia-cataract syndrome in a family of Indian origin.
C1 Guru Nanak Dev Univ, Ctr Genet Disorders, Amritsar 143005, Punjab, India.
   NEI, NIH, Bethesda, MD 20892 USA.
   Univ Cologne, Cologne Ctr Genom, D-5000 Cologne, Germany.
   Univ Cologne, Inst Genet, D-5000 Cologne 41, Germany.
   Max Delbruck Ctr Mol Med, Gene Mapping Ctr, Berlin, Germany.
   Dr Daljit Singh Eye Hosp, Amritsar, Punjab, India.
   Charite Humboldt Univ, Inst Human Genet, Berlin, Germany.
RP Vanita, V (reprint author), Guru Nanak Dev Univ, Ctr Genet Disorders, Amritsar 143005, Punjab, India.
EM vanita_kumar@yahoo.com
NR 42
TC 25
Z9 29
U1 0
U2 1
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
   ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD FEB 21
PY 2006
VL 12
IS 10
BP 93
EP 99
PG 7
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 018BA
UT WOS:000235736500001
PM 16518306
ER

PT J
AU Shen, XY
   Xu, KF
   Fan, QY
   Pacheco-Rodriguez, G
   Moss, J
   Vaughan, M
AF Shen, XY
   Xu, KF
   Fan, QY
   Pacheco-Rodriguez, G
   Moss, J
   Vaughan, M
TI Associaticon of brefeldin A-inhibited guanine nucleotide-exchange
   protein 2 (BIG2) with recycling endosomes during transferrin uptake
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE ADP-ribosylation factor; transferrin receptor; Exo70; Rab11
ID ADP-RIBOSYLATION FACTORS; TRANS-GOLGI NETWORK; CLATHRIN ADAPTER
   COMPLEXES; ENDOCYTIC PATHWAY; COATED VESICLES; PLASMA-MEMBRANE; CELLS;
   AP-1; LOCALIZATION; TRAFFICKING
AB ADP-ribosylation factors (ARFs) are critical in vesicular trafficking.Brefeldin A-inhibited guanine nucleotide-exchange protein (BIG)l and BIG2 activate ARFs toy accelerating replacement of bound GDP with GTP. Additional and differing functions of these approximate to 200-kDa proteins are now being recognized, as are their independent intracellular movement:;. Here, we describe the localization in COS7 cells by immunofluorescence microscopy of BIG2, but not BIG1, with structures that have characteristics of recycling endosomes during transferrin (Tfn) uptake and Tfn receptor (TfnR) recycling. Cell content of BIG2 and Rab11, but not TfnR, BIG1, Rab4, or Exo70, was increased after 60 min of Tfn uptake. BIG2, but not BIG1, appeared in density-gradient fractions containing TfnR, Rab11, and Exo70 after 60 min of Tfn uptake. Treatment of cells with BIG2 small interfering RNA (siRNA), but not BIG1 or control siRNAs, decreased BIG2 protein > 90% without affecting BIG1, ARF, or actin content, whereas TfnR was significantly increased as was its accumulation in perinuclear recycling endosomes. Tfn release appeared unaffected by BIG1 siRNA but was significantly slowed from cells treated with BIG2 siRNA alone or plus BIG1 siRNA. We suggest that BIG2 has an important role in Tfn uptake and TfnR recycling, perhaps through its demonstrated interaction with Exo70 and the exocyst complex.
C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA.
RP Vaughan, M (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room SN307,MSC 1434, Bethesda, MD 20892 USA.
EM vaughanm@nih.gov
FU Intramural NIH HHS
NR 36
TC 38
Z9 42
U1 2
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 21
PY 2006
VL 103
IS 8
BP 2635
EP 2640
DI 10.1073/pnas.0510599103
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015MG
UT WOS:000235554900030
PM 16477018
ER

PT J
AU Citterio, C
   Jones, HD
   Pacheco-Rodriguez, G
   Islam, A
   Moss, J
   Vaughan, M
AF Citterio, C
   Jones, HD
   Pacheco-Rodriguez, G
   Islam, A
   Moss, J
   Vaughan, M
TI Effect of protein kinase A on accumulation of brefeldin A-inhibited
   guanine nucleotide-exchange protein 1 (BIG1) in HepG2 cell nuclei
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE ADP-ribosylation factor; protein trafficking; A kinase-anchoring protein
ID ADP-RIBOSYLATION FACTORS; MEMBRANE-TRANSPORT; ARF; LOCALIZATION; IMPORT;
   SEC7; PHOSPHORYLATION; IDENTIFICATION; MICROTUBULES; ASSOCIATION
AB Brefeldin A-inhibited guanine nucleotide-exchange proteins, BIG1 and BIG2, are activators of ADP-ribosylation factor GTPases that are essential for regulating vesicular traffic among intracellular organelles. Biochemical analyses and immunofluorescence microscopy demonstrated BIG1 in nuclei as well as membranes and cytosol of serum-starved HepG2 cells. Within 20 min after addition of 8-Br-cAMP, BIG1 accumulated in nuclei, and this effect was blocked by protein kinase A (PKA) inhibitors H-89 and PKI, suggesting a dependence on PKA-catalyzed phosphorylation. BIG2 localization was notaltered by CAMP, nor did BIG2 small interfering RNA influence nuclear accumulation of BIG1 induced by cAMP. Mutant BIG1 (S883A) in which Ala replaced Ser-883, a putative PKA phosphorylation site, did not move to the nucleus with cAMP addition, whereas replacement with Asp (S883D) resulted in nuclear accumulation of BIG1 without or with CAMP exposure, consistent with the mechanistic importance of a negative charge at that site. Mutation (712KPK714) of the nuclear localization signal inhibited BIG1 accumulation in nuclei, and PKA-catalyzed phosphorylation of S883, although necessary, was not sufficient for nuclear accumulation, as shown by the double mutation S883D/ nuclear localization signal. A role for microtubules in cAMP-induced translocation of BIG1 is inferred from its inhibition by nocodazole. Thus, two more critical elements of BIG1 molecular structure were identified, as well as the potential function of microtubules in a novel PKA effect on BIG1 translocation.
C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA.
RP Vaughan, M (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room SN-307, Bethesda, MD 20892 USA.
EM citteric@nhlbi.nih.gov; vaughanm@nih.gov
FU Intramural NIH HHS
NR 32
TC 17
Z9 19
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 21
PY 2006
VL 103
IS 8
BP 2683
EP 2688
DI 10.1073/pnas.0510571103
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015MG
UT WOS:000235554900038
PM 16467138
ER

PT J
AU Martinat, C
   Bacci, JJ
   Leete, T
   Kim, J
   Vanti, WB
   Newman, AH
   Cha, JH
   Gether, U
   Wang, HG
   Abeliovich, A
AF Martinat, C
   Bacci, JJ
   Leete, T
   Kim, J
   Vanti, WB
   Newman, AH
   Cha, JH
   Gether, U
   Wang, HG
   Abeliovich, A
TI Cooperative transcription activation by Nurr1 and Pitx3 induces
   embryonic stem cell maturation to the midbrain dopamine neuron phenotype
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE differentiation; Parkinson; transplantation
ID HOMEODOMAIN PROTEIN FTZ; SUBSTANTIA-NIGRA; DIRECTED DIFFERENTIATION;
   NUCLEAR RECEPTOR; GENE-EXPRESSION; ENGRAILED GENES; IN-VITRO; MICE;
   TRANSPLANTATION; INDUCTION
AB Midbrain dopamine I neurons play a central role in the regulation of voluntary movement, and their degeneration is associated with Parkinson's disease. Cell replacement therapies, and in particular embryonic stem (ES) cell-derived DA neurons, offer a potential therapeutic venue for Parkinson's disease. We sought to identify genes that can potentiate maturation of ES cell cultures to the midbrain DA neuron phenotype. A number of transcription factors have been implicated in the development of midbrain DA neurons by expression analyses and loss-of-function knockout mouse studies, including Nurr1, Pitx3, Lmx1b, Engrailed-1, and Engrailed-2. However, none of these factors appear sufficient alone to induce the mature midbrain DA neuron phenotype in ES cell cultures in vitro, suggesting a more complex regulatory network. Here we show that Nurr1 and Pitx3 cooperatively promote terminal maturation to the midbrain DA neuron phenotype in murine and human ES cell cultures.
C1 Columbia Univ, Coll Phys & Surg, Dept Pathol, Ctr Neurobiol & Behav, New York, NY 10032 USA.
   Columbia Univ, Coll Phys & Surg, Dept Neurol, Ctr Neurobiol & Behav, New York, NY 10032 USA.
   Columbia Univ, Coll Phys & Surg, Taub Inst, New York, NY 10032 USA.
   Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   Univ Copenhagen, Panum Inst, Dept Pharmacol, Mol Pharmacol Grp, DK-2200 Copenhagen, Denmark.
RP Abeliovich, A (reprint author), Columbia Univ, Coll Phys & Surg, Dept Pathol, Ctr Neurobiol & Behav, 630 W 168th St,15-403, New York, NY 10032 USA.
EM aa900@columbia.edu
RI MARTINAT, Cecile/F-6777-2010; Vanti, William/E-6518-2016
OI Vanti, William/0000-0002-5591-5350
NR 46
TC 145
Z9 152
U1 4
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 FEB 21
PY 2006
VL 103
IS 8
BP 2874
EP 2879
DI 10.1073/pnas.0511153103
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015MG
UT WOS:000235554900071
PM 16477036
ER

PT J
AU Margolis, EB
   Lock, H
   Chefer, VI
   Shippenberg, TS
   Hjelmstad, GO
   Fields, HL
AF Margolis, EB
   Lock, H
   Chefer, VI
   Shippenberg, TS
   Hjelmstad, GO
   Fields, HL
TI kappa opioids selectively control dopaminergic neurons projecting to the
   prefrontal cortex
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
DE GABA; reward; motivation; nucleus accumbens; ventral tegmental area
ID VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; COCAINE; RECEPTORS; STIMULI;
   RATS; IMMUNOFLUORESCENCE; RESPONSIVENESS; SCHIZOPHRENIA; TRANSMISSION
AB Dopaminergic afferents arising from the ventral tegmental area (VTA) are crucial elements in the neural circuits that mediate arousal, motivation, and reinforcement. Two major targets of these afferents are the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc). Whereas dopamine (DA) in the mPFC has been implicated in working memory and attentional processes, DA in the NAc is required for responding to reward predictive cues. These distinct functions suggest a role for independent firing patterns of dopaminergic neurons projecting to these brain regions. In fact, DA release in mPFC and NAc can be differentially modulated. However, to date, electrophysiological studies have largely overlooked heterogeneity among VTA neurons. Here, we provide direct evidence for differential neurotransmitter control of DA neural activity and corresponding DA release based on projection target. kappa opioid receptor agonists inhibit VTA DA neurons that project to the mPFC but not those that project to the NAc. Moreover, DA levels in the mPFC, but not the NAc, are reduced after local infusion of kappa opioid receptor agonists into the VTA. These findings demonstrate that DA release in specific brain regions can be independently regulated by opioid targeting of a subpopulation of VTA DA neurons. Selective control of VTA DA neurons projecting to the mPFC has important implications for understanding addiction, attention disorders, and schizophrenia, all of which are associated with DA dysfunction in the mPFC.
C1 Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Emeryville, CA 94608 USA.
   Natl Inst Drug Abuse, Integrat Neurosci Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
   Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
   Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
   Univ Calif San Francisco, Wheeler Ctr Neurobiol Addict, San Francisco, CA 94143 USA.
RP Margolis, EB (reprint author), Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, 5858 Horton St,Suite 200, Emeryville, CA 94608 USA.
EM elyssam@egcrc.net
FU Intramural NIH HHS; NIAAA NIH HHS [U01 AA 13486]; NIDA NIH HHS
   [DA-15686, R01 DA015686]
NR 34
TC 169
Z9 172
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 FEB 21
PY 2006
VL 103
IS 8
BP 2938
EP 2942
DI 10.1073/pnas.0511159103
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 015MG
UT WOS:000235554900082
PM 16477003
ER

PT J
AU Harlan, LC
   Clegg, LX
   Abrams, J
   Stevens, JL
   Ballard-Barbash, R
AF Harlan, LC
   Clegg, LX
   Abrams, J
   Stevens, JL
   Ballard-Barbash, R
TI Community-based use of chemotherapy and hormonal therapy for early-stage
   breast cancer: 1987-2000
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID RANDOMIZED-TRIALS
AB Purpose We describe trends in the use of chemotherapy and hormonal therapy by nodal and estrogen receptor (ER) status in women with early-stage breast cancer.
   Methods Cases were randomly sampled from the population-based Surveillance, Epidemiology and End Results (SEER) program and physician verified treatment was examined. A total of 9,481 women, aged 20 years and older, diagnosed with early-stage breast cancer in 1987 to 1991, 1995, and 2000 were included in the study.
   Results The use of chemotherapy plus tamoxifen increased between 1995 and 2000 for women with node-negative, ER-positive breast cancer : 1 cm (8% to 21%). Nearly 23% of women with node-negative and ER-positive tumors >= 1 cm received no adjuvant therapy. The use of chemotherapy alone increased to nearly 60% in women with node-negative, ER-negative tumors >= 1 cm (48% to 59%). However, in 2000, 16% of women with node-positive and ER-negative tumors received no adjuvant therapy and an additional 6% received tamoxifen alone. The influence of age can clearly be seen. Chemotherapy is given much less often in women 70 years or older.
   Conclusion The results from SEER areas across the United States suggest that physicians quickly responded to publications and guidelines regarding breast cancer therapy. The lack of definitive findings from clinical trials on the use of adjuvant therapy in women 70 years and older may explain the lower use in this group of women.
C1 NCI, Appl Res Program, Bethesda, MD 20892 USA.
   NCI, Surveillance Res Program, Bethesda, MD 20892 USA.
   NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
   Informat Management Syst, Silver Spring, MD USA.
RP Harlan, LC (reprint author), NCI, Appl Res Program, 6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA.
EM lh50w@nih.gov
FU NCI NIH HHS [N01-PC-35143, N01-PC-35133, N01-PC-35135, N01-PC-35136,
   N01-PC-35137, N01-PC-35138, N01-PC-35139, N01-PC-35141, N01-PC-35142,
   N01-PC-35145]
NR 13
TC 57
Z9 57
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2006
VL 24
IS 6
BP 872
EP 877
DI 10.1200/JCO.2005.03.5840
PG 6
WC Oncology
SC Oncology
GA 014HF
UT WOS:000235469700009
PM 16484696
ER

PT J
AU Iqbal, J
   Neppalli, VT
   Wright, G
   Dave, LJ
   Horsman, DE
   Rosenwald, A
   Lynch, J
   Hans, CP
   Weisenburger, DD
   Greiner, TC
   Gascoyne, RD
   Campo, E
   Ott, G
   Muller-Hermelink, HK
   Delabie, J
   Jaffe, ES
   Grogan, TM
   Connors, JM
   Vose, JM
   Armitage, JO
   Staudt, LM
   Chan, WC
AF Iqbal, J
   Neppalli, VT
   Wright, G
   Dave, LJ
   Horsman, DE
   Rosenwald, A
   Lynch, J
   Hans, CP
   Weisenburger, DD
   Greiner, TC
   Gascoyne, RD
   Campo, E
   Ott, G
   Muller-Hermelink, HK
   Delabie, J
   Jaffe, ES
   Grogan, TM
   Connors, JM
   Vose, JM
   Armitage, JO
   Staudt, LM
   Chan, WC
TI BCL2 expression is a prognostic marker for the activated B-cell-like
   type of diffuse large B-cell lymphoma
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID NON-HODGKINS-LYMPHOMA; PROTEIN EXPRESSION; CLINICAL-SIGNIFICANCE; GENE
   REARRANGEMENT; TISSUE MICROARRAY; TRANSGENIC MICE; KAPPA-B; SURVIVAL;
   T(14/18); CLASSIFICATION
AB Background The role of BCL2 as a predictor of survival in diffuse large B-cell lymphoma (DLBCL) is controversial. DLBCL is heterogeneous, and the expression of BCL2 is variable within the two major subgroups of DLBCL, germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL, as well as primary mediastinal DLBCL.
   Patients and Methods In this study, we investigated the correlation of BCL2 expression with survival in the two major subgroups of DLBCL, as well as the mechanisms of BCL2 expression.
   Results There was no significant correlation between BCL2 protein expression and overall survival within the GCB subgroup, but BCL2 expression had a significant adverse effect on overall survival within the ABC subgroup (P = .008). This correlation was also observed at the mRNA level (P < .04). The difference remained significant when the analyses were performed at different cutoff values. The t(14;18) was frequently observed in the GCB subgroup and was highly associated with BCL2 expression. Patients with ABC DLBCL did not exhibit t(14,18) but had a markedly higher frequency of chromosome 18q21 amplification, on which BCL2 resides. Thus, alternative mechanisms such as 18q21 amplification or activation of the nuclear factor-kappa B pathway, as reported previously, seem to be mainly responsible for the upregulation of BCL2 expression in the ABC subgroup.
   Conclusion Treating all DLBCL as a single entity ignores the mechanistic differences in BCL2 upregulation and obscures the prognostic significance of BCL2 expression. Hence, the significance of BCL2 and other biomarkers should be assessed in the context of DLBCL subgroups in future studies.
C1 Univ Nebraska, Med Ctr, Leukemia Lymphoma Mol Profiling Project, Dept Pathol & Microbiol, Omaha, NE 68182 USA.
   Univ Nebraska, Med Ctr, Dept Genet, Omaha, NE 68182 USA.
   Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68182 USA.
   Univ Nebraska, Med Ctr, Dept Prevent & Societal Med, Omaha, NE 68182 USA.
   NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
   NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
   NCI, Biometr Res Branch, Dept Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
   Univ Arizona, Dept Pathol, Tucson, AZ USA.
   British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 4E6, Canada.
   British Columbia Canc Agcy, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada.
   Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany.
   Univ Barcelona, Hosp Clin Barcelona, Dept Pathol, Barcelona, Spain.
   Norwegian Radium Hosp, Dept Pathol, Oslo, Norway.
RP Chan, WC (reprint author), 983135 Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA.
EM jchan@unmc.edu
OI Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793
FU NCI NIH HHS [CA36727, CA84967]
NR 41
TC 151
Z9 167
U1 1
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 20
PY 2006
VL 24
IS 6
BP 961
EP 968
DI 10.1200/JCO.2005.03.4264
PG 8
WC Oncology
SC Oncology
GA 014HF
UT WOS:000235469700022
PM 16418494
ER

EF